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 Alternative medicine

A comprehensive examination of alternative medicine is beyond my capability. This area, though, is useful, as it highlights many of the controversies in statistical evidence. I have included some sites that take an evidence based or skeptical view of alternative medicine. The purpose is not to criticize alternative medicine but to use some of the controversies as teaching examples on how to do good research.

The original set of links for this page was produced by Badri Badrinath in an email he posted to the Evidence Based Health mailing list.

The Alternative Medicine Advisory Page. Robert Imrie and David Ramey. Accessed on 2002-11-27. "The mission of the NCRHI Veterinary Task Force is to promote animal health and welfare, to protect consumers from fraudulent, unsafe, and unproven veterinary practices, to promote science-based medicine and the critical examination of medical claims and to provide sound information and leadership to veterinary practitioners and their clients." www.seanet.com/~vettf/

Complementary and Alternative Medicine. Loyola University Health System. Accessed on 2002-12-31. "Complementary and alternative medicine (CAM) encompasses nonconventional approaches to healing, beyond traditional medicine. According to Dr. David Eisenberg (1993), complementary and alternative medicine is the modalities or interventions not taught widely at U.S. medical schools or are not generally available at U.S. hospitals." www.luhs.org/health/topics/cam/index.htm

Complementary and Alternative Medicine Researcher Network. Research Council for Complimentary Medicine. Accessed on 2002-12-31. "To facilitate research of the highest quality and to encourage collaboration, the RCCM has established a Complementary and Alternative Medicine Researcher Network (CAMRN). The purpose of the Network is to bring together researchers in CAM and conventional medicine in order to promote collaboration. The CAMRN web pages allow researchers to share details of the research they are involved in as well as news and information on events that they think others might be interested in." www.rccm.org.uk

Complementary and Alternative Therapies. Bandolier. Accessed on 2003-03-25. "This site is intended to gather the best evidence available about complementary and alternative therapies (CAT) for sufferers and professionals, to update it as more or better evidence becomes available, and to have it accessible over Internet. The principal mechanism will be by searching for systematic reviews and meta-analyses of complementary and alternative therapies, and providing abstracts of them. It contains stories from Bandolier, plus abstracts of systematic reviews, meta-analyses, or other studies about CAT. We are able to do this because of generous sponsorship from an unconditional educational grant from the BUPA Foundation. Lesley Smith, Anna Oldman and Jayne Edwards have all contributed by reading the reviews and preparing the abstracts for the Internet site." www.jr2.ox.ac.uk/bandolier/booth/booths/altmed.html

Complementary Medicine. British Medical Journal. Accessed on 2003-05-06. Collected Resources of the British Medical Journal. bmj.com/cgi/collection/complementary_medicine

Health Care Reality Check. Georgia Council Against Health Fraud. Accessed on 2002-12-31. "Founded in 1997, the Georgia Council Against Health Fraud, Inc. (GCAHF) is an autonomous local affiliate of the National Council Against Health Fraud, Inc. and is a non-profit, tax-exempt voluntary organization. The GCAHF shares the goals and purposes of NCAHF, and seeks to combat health quackery through public education. A particular focus of GCAHF is the linking of scientific and medical professionals via the Internet for greater distribution of anti-quackery information." www.hcrc.org/

The National Council Against Health Fraud. Enhancing Freedom of Choice through Reliable Health Information. Stephen Barrett. Accessed on 2002-11-27. "NCAHF is a private nonprofit, voluntary health agency that focuses upon health misinformation, fraud, and quackery as public health problems. Our positions are based upon the principles of science that underlie consumer protection law. We advocate: (a) adequate disclosure in labeling and other warranties to enable consumers to make truly informed choices; (b) premarketing proof of safety and effectiveness for products and services claimed to prevent, alleviate, or cure any health problem; and, (c) accountability for those who violate the law." www.ncahf.org/

Quackwatch. Your Guide to Health Fraud, Quackery, and Intelligent Decisions. Stephen Barrett. Accessed on 2003-05-06. "Quackwatch, Inc., a member of Consumer Federation of America, is a nonprofit corporation whose purpose is to combat health-related frauds, myths, fads, and fallacies. Its primary focus is on quackery-related information that is difficult or impossible to get elsewhere." www.quackwatch.org/

Science and Technology - Sixth Report. House of Lords United Kingdom Parliament. Accessed on 2002-12-31. "The use of complementary and alternative medicine (CAM) is widespread and increasing across the developed world. This raises significant issues of public health policy such as whether good structures of regulation to protect the public are in place; whether an evidence base has been accumulated and research is being carried out; whether there are adequate information sources on the subject; whether the practitioner's training is adequate and what the prospects are for NHS provision of these treatments. It was the need to consider these issues that prompted this Inquiry (Chapter 1)." www.parliament.the-stationery-office.co.uk/pa/ld199900/ldselect/ldsctech/123/12301.htm

Individual journals with some or all content online

Links to multiple journals with some or all content online

Anti-environmental myths. Jim Norton. Accessed on 2002-11-27. "A new web page devoted to exposing the propaganda of the anti-environmental lobby." http://members.aol.com/jimn469897/myths.htm

CenterWatch Clinical Trials Listing Service. Thomson Centerwatch. Accessed on 2002-11-27. "Welcome to the Centerwatch Clinical Trials Listing Service! You can use this site to find a wealth of information about clinical research, including listings of more than 41,000 active industry and government-sponsored clinical trials, as well as new drug therapies in research and those recently approved by the FDA. Our site is designed to be an open resource for patients interested in participating in clinical trials and for research professionals." www.centerwatch.com/

Electric and Magnetic Fields Research and Public Information Dissemination Program. National Institute of Environmental Health Sciences. Accessed on 2002-11-27. "The National Institute of Environmental Health Sciences (NIEHS) and the Department of Energy (DOE) coordinated the implementation of the Electric and Magnetic Fields (EMF) Research and Public Information Dissemination (RAPID) Program, established by the 1992 Energy Policy Act (Section 2118 for Public Law 102-486) which was signed in October 1992. This was a six year United States federally coordinated effort to evaluate developing technologies and research on the effects on biological systems of exposure to 60 Hz electric and magnetic fields produced by the generation, transmission and use of electric energy and to communicate these results to the public sector." www.niehs.nih.gov/emfrapid/home.htm

FORCES: Fight Ordinances & Restrictions to Control & Eliminate Smoking. FORCES International. Accessed on 2002-11-27. An organization for smokers rights. www.forces.org/index.htm

The Guide to Health Economics, Medical, and Pharmacy Resources. HealthEconomics.Com. Accessed on 2002-11-27. "The mission of HealthEconomics.Com is to be the premier web site devoted to internet resources focused on health care value. With resources ranging from job opportunities to journals reporting on the cost-effectiveness of a new pharmaceutical, HealthEconomics.Com is the Professional's Guide to Health Economics Resources on the 'Net. " www.healtheconomics.com/index.cfm

High Quality Internet Resources in Health and Medicine. OMNI: Organising Medical Networked Information. Accessed on 2002-11-27. "Welcome to OMNI. Your guide to quality Internet resources in health and medicine. OMNI offers free access to a searchable catalogue of Internet sites covering health and medicine. " omni.ac.uk/

MetaRegister of Controlled Clinical Trials. Current Controlled Trials Ltd. Accessed on 2002-11-27. "Welcome to Current Controlled Trials. The metaRegister of Controlled Trials is a searchable, international database of ongoing randomised controlled trials in all areas of healthcare. At present, the mRCT also contains some completed trials. Offering access to more than 12,500 records, the mRCT is free." www.controlled-trials.com/

The Patient Medical Information Center. Med Help International. Accessed on 2002-11-27. "Med Help International is dedicated to helping patients find the highest quality medical information in the world today. We offer patients the tools necessary to make informed treatment decisions within the short time lines dictated by their illness or disease." www.medhelp.org/

PDQ - NCI's Comprehensive Cancer Database. National Cancer Institute. Accessed on 2002-11-27. "PDQ (Physician Data Query) is NCI's comprehensive cancer database. It contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of approximately 1,800 open and 12,000 closed cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care." www.cancer.gov/cancer_information/

Show Me The Science! Corporate Polluters and the 'Junk Science' Strategy. Environmental Working Group. Accessed on 2002-11-27. "The battle over the Environmental Protection Agency's new proposed clean air standards is the latest example in a long line of similar efforts by environmental backlash groups to weaken, repeal or prevent passage of strong environmental protections." www.ewg.org/pub/home/CLEAR/By_Clear/ShowMe.html

Statistics. American Heart Association. Accessed on 2002-11-27. Information about various cardiovascular diseases and risk factors. www.americanheart.org/presenter.jhtml?identifier=1200026

UKMedW3. Adrian Midgley and Andrew Herd. Accessed on 2002-11-27. "Gateway to medicine on the net." www.schin.ncl.ac.uk/GPUK/UKMed3/index.htm

Welcome to Your Family Doctor. International Medical Journal. Accessed on 2002-11-27. "This is a place for everyone challenged by health problems who wants to know as much as possible about the ailment, from a basic understanding to the latest research and trials. Our services are far beyond general info! Your Family Doctor service provides you with tailored information, based on your specific scenario. www.consult.iperweb.com/

WHO Library & Information Networks for Knowledge. World Health Organization. Accessed on 2002-11-27. "The WHO Library and Information Networks for Knowledge (LNK) provides comprehensive library and information services on WHO-produced recorded information in print and other media. In addition, library services give access to worldwide health, medical and development information resources to WHO headquarters, regions and country offices, ministries of health and other government offices, health workers in Member States, other UN and international agencies, and diplomatic missions. The WHO library programmes help regions and developing countries achieve self-sufficiency in providing information services to the health sector." www.who.int/library/

WHO MONICA Project: preliminary analysis of final results. World Health Organization. Accessed on 2002-11-27. "The European Congress of Cardiology in Vienna this week is seeing preliminary analyses of the final ten-year results of the largest collaborative study of heart disease ever undertaken. These results - on the effects of treatments and risk factors in determining trends in coronary heart attack rates and mortality - which include some early surprises, will create considerable discussion and controversy amongst the world’s experts, although further analyses remain to be done. The near completion of this World Health Organization (Geneva) initiative is a remarkable feat of international research collaboration." www.ktl.fi/monica/public/vienna/press_release.htm

A biography of Carlo Emilio Bonferroni (Michael Dewey) www.nottingham.ac.uk/~mhzmd/bonf.html

Graduate programs in Statistics www-stat.ucdavis.edu/stat.html

Lloyd's Warehouse of Economic Indicators www.rt66.com/~llubet

Ozone Depletion, History and Politics. Brien Sparling. (Accessed on January 11, 2001)
www.nas.nasa.gov/About/Education/Ozone/history.html

This site explains how the ozone hole was first discovered. It mentions the (inaccurate) claim that a computer filter on a previous satellite had discarded outliers which masked the discovery of the ozone hole for eight years. Although this makes a wonderful teaching example, the actual story is not quite that good.

Resampling Stats. (Accessed on October 2, 2000)
www.resample.com/

This page offers a variety resources (some are free) for resampling, including software for resampling with a 30 day free trial period.

Statistics jokes. www.xs4all.nl/~jcdverha/scijokes/1_2.html

Second Moment. (Accessed on November 1, 2000)
www.secondmoment.org/

"Second Moment is a dynamic meeting place for academia and industry in the fields of applied statistics and analytics. It is a platform for showcasing cutting edge academic research and a resource for industry analysts and businesses interested in applying the latest statistical and analytical tools and technology."

New and undocumented

Businesses

Employee directories

Personal web pages

James A. Deddens. Accessed on 2002-11-27. math.uc.edu/~deddens/

David C. Howell. Accessed on 2002-11-27. www.uvm.edu/~dhowell/StatPages/StatHomePage.html

Dennis Roberts. Accessed on 2002-11-27. roberts.ed.psu.edu/users/droberts/drober~1.htm

Phil Wood. Accessed on 2002-11-27. web.missouri.edu/~wood/

Miscellaneous

Usenet Archive. (Accessed on October 10, 2002) groups.google.com "Post and read comments in Usenet discussion forums." 

http://www.xs4all.nl/~jcdverha/scijokes/1_2.html Science Jokes: Statistics and Statisticians, by Joachim Verhagen. Link last checked on June 30, 2000. Here's a sample: "Two statisticians were travelling in an airplane from LA to New York. About an hour into the flight, the pilot announced that they had lost an engine, but don't worry, there are three left. However, instead of 5 hours it would take 7 hours to get to New York. A little later, he announced that a second engine failed, and they still had two left, but it would take 10 hours to get to New York. Somewhat later, the pilot again came on the intercom and announced that a third engine had died. Never fear, he announced, because the plane could fly on a single engine. However, it would now take 18 hours to get to new York. At this point, one statistician turned to the other and said, 'Gee, I hope we don't lose that last engine, or we'll be up here forever!'"

Web writing and web design

Web and Internet information

Accumulated references as of December 23, 2002.

placebo.asp reference: The better-than-nothing idea: debating the use of placebo controls. Cmaj 2002:166(5);573, 575. [Medline]

chapter7asp. reference: Epidemiology on trial. Lancet 2002:360(9331);421. [Medline]

chapter1.asp reference: A controlled trial of immunotherapy for asthma in allergic children. Adkinson NF, Jr., Eggleston PA, Eney D, Goldstein EO, Schuberth KC, Bacon JR, Hamilton RG, Weiss ME, Arshad H, Meinert CL, Tonascia J and Wheeler B. New England Journal of Medicine 1997:336(5);324-31. BACKGROUND: Injections of allergens are widely prescribed for patients with asthma, but little is known about the effectiveness of immunotherapy. METHODS: We conducted a double-blind, placebo-controlled trial of multiple-allergen immunotherapy in 121 allergic children with moderate-to-severe, perennial asthma. The children, who required daily medication for their asthma, were randomly assigned to receive subcutaneous injections of either a mixture of up to seven aeroallergen extracts or a placebo. Maintenance injections were continued for 18 months or longer. Medications were adjusted every two to three weeks on the basis of peak flow rates and symptoms. The principal outcome was the daily medication score. Bronchial sensitivity to methacholine (the concentration provoking a 20 percent decrease in the forced expiratory volume in one second [PC20]) was measured twice yearly. RESULTS: The median medication score declined from 5.4 to 4.9 in the immunotherapy group (P<0.001) and from 5.2 to 5.0 in the placebo group (P<0.001), but there was no significant difference between the groups (P>0.6). The number of days on which oral corticosteroids were used was similar in the two groups. Partial or complete remission of asthma occurred in 31 percent of the immunotherapy group and in 28 percent of the placebo group (P>0.5). There was no difference between the groups in the use of medical care, symptoms, or peak flow rates. The median PC20 increased significantly in both groups, but again with no difference between the two groups. CONCLUSIONS: Immunotherapy with injections of allergens for over two years was of no discernible benefit in allergic children with perennial asthma who were receiving appropriate medical treatment. [Medline]

irb.asp reference intro.asp reference: Poor-quality medical research: what can journals do? Altman DG. Jama 2002:287(21);2765-7. The aim of medical research is to advance scientific knowledge and hence--directly or indirectly--lead to improvements in the treatment and prevention of disease. Each research project should continue systematically from previous research and feed into future research. Each project should contribute beneficially to a slowly evolving body of research. A study should not mislead; otherwise it could adversely affect clinical practice and future research. In 1994 I observed that research papers commonly contain methodological errors, report results selectively, and draw unjustified conclusions. Here I revisit the topic and suggest how journal editors can help. [Medline]

chapter2.asp reference: Dangers of using "optimal" cutpoints in the evaluation of prognostic factors. Altman DG, Lausen B, Sauerbrei W and Schumacher M. Journal of the National Cancer Institute 1994:86(11);829-35. Abstract not available yet. [Medline]

diagnostic.asp reference: Measurement of markers of tobacco smoking in patients with coronary heart disease. Archbold GP, Cupples ME, McKnight A and Linton T. Ann Clin Biochem 1995:32 ( Pt 2)(201-7. 591 patients with a history of coronary heart disease had one or more biochemical markers of tobacco smoking measured. 26% were self reported smokers and a further 4% were apparent 'smoking deceivers'. The urinary nicotine metabolite concentration is an excellent marker for tobacco smoking; breath CO would be a suitable alternative for busy clinics. Half the patients were subjected to regular advice on risk factor management but there was no evidence that this contributed effectively to smoking cessation. Overall smoking cessation rate was poor. [Medline]

chapter2.asp reference: Responsibilities of sponsors are limited in premature discontinuation of trials. Ashcroft R. BMJ 2001:323(7303);53-. Abstract not available yet.

diagnostic.asp reference: Prospective evaluation of criteria for microbiological diagnosis of prosthetic-joint infection at revision arthroplasty. The OSIRIS Collaborative Study Group. Atkins BL, Athanasou N, Deeks JJ, Crook DW, Simpson H, Peto TE, McLardy-Smith P and Berendt AR. J Clin Microbiol 1998:36(10);2932-9. A prospective study was performed to establish criteria for the microbiological diagnosis of prosthetic joint infection at elective revision arthroplasty. Patients were treated in a multidisciplinary unit dedicated to the management and study of musculoskeletal infection. Standard multiple samples of periprosthetic tissue were obtained at surgery, Gram stained, and cultured by direct and enrichment methods. With reference to histology as the criterion standard, sensitivities, specificities, and likelihood ratios (LRs) were calculated by using different cutoffs for the diagnosis of infection. We performed revisions on 334 patients over a 17-month period, of whom 297 were evaluable. The remaining 37 were excluded because histology results were unavailable or could not be interpreted due to underlying inflammatory joint disease. There were 41 infections, with only 65% of all samples sent from infected patients being culture positive, suggesting low numbers of bacteria in the samples taken. The isolation of an indistinguishable microorganism from three or more independent specimens was highly predictive of infection (sensitivity, 65%; specificity, 99.6%; LR, 168.6), while Gram staining was less useful (sensitivity, 12%; specificity, 98%; LR, 10). A simple mathematical model was developed to predict the performance of the diagnostic test. We recommend that five or six specimens be sent, that the cutoff for a definite diagnosis of infection be three or more operative specimens that yield an indistinguishable organism, and that because of its low level of sensitivity, Gram staining should be abandoned as a diagnostic tool at elective revision arthroplasty. [Medline]

diagnostic.asp reference: Can the clinical examination diagnose left-sided heart failure in adults? Badgett RG, Lucey CR and Mulrow CD. Jama 1997:277(21);1712-9. We systematically reviewed the literature to ascertain how well clinicians determine the probability and type of left-sided heart failure in their patients. Left-sided heart failure is characterized by decreased left ventricular ejection fraction or increased filling pressure. The type of heart failure determines optimal treatment. Systolic dysfunction exists when ejection fraction is reduced. Diastolic dysfunction is presumed to be present when filling pressure is increased with a normal ejection fraction and without another explanatory diagnosis. Many findings are associated with heart failure, and wide variation exists in clinicians' ability to detect these findings. The best findings for detecting increased filling pressure are jugular venous distention and radiographic redistribution. The best findings for detecting systolic dysfunction are abnormal apical impulse, radiographic cardiomegaly, and q waves or left bundle branch block on an electrocardiogram. Diastolic dysfunction is especially difficult to diagnose, but is associated with an elevated blood pressure during heart failure. [Medline]

chapter4.asp reference: Statistical issues in randomized trials of cancer screening. Baker SG, Kramer BS and Prorok PC. BMC Med Res Methodol 2002:2(1);11. BACKGROUND: The evaluation of randomized trials for cancer screening involves special statistical considerations not found in therapeutic trials. Although some of these issues have been discussed previously, we present important recent and new methodologies. METHODS: Our emphasis is on simple approaches. RESULTS: We make the following recommendations:(1) Use death from cancer as the primary endpoint, but review death records carefully and report all causes of death(2) Use a simple "causal" estimate to adjust for nonattendance and contamination occurring immediately after randomization(3) Use a simple adaptive estimate to adjust for dilution in follow-up after the last screen CONCLUSION: The proposed guidelines combine recent methodological work on screening endpoints and noncompliance/contamination with a new adaptive method to adjust for dilution in a study where follow-up continues after the last screen. These guidelines ensure good practice in the design and analysis of randomized trials of cancer screening. [Medline]

diagnostic.asp reference: Patterns of psychiatric morbidity in a genito-urinary clinic. A validation of the Hospital Anxiety Depression scale (HAD). Barczak P, Kane N, Andrews S, Congdon AM, Clay JC and Betts T. Br J Psychiatry 1988:152(698-700. The prevalence of psychiatric disorder (by DSM-III criteria) in a population attending a genito-urinary clinic was found to be 31%. The performance of the Hospital Anxiety Depression (HAD) scale as a screening questionnaire for psychiatric disorder was assessed. Case definition by a score of 8 or more on either of the anxiety or depressive subscales produced optimal results, giving sensitivities of 82% and 70%, and specificities of 94% and 68%, for depressive and anxiety disorders respectively. [Medline]

nnt.asp reference: Missing the point (estimate)? Confidence intervals for the number needed to treat. Barrowman NJ. Cmaj 2002:166(13);1676-7. [Medline]

diagnostic.asp reference: Biases in the assessment of diagnostic tests. Begg CB. Stat Med 1987:6(4);411-23. Diagnostic tests are traditionally characterized by simple measures of efficacy such as the sensitivity and the specificity. These measures, though widely recognized and easy to understand, are subject to definitional arbitrariness. Moreover, studies constructed to estimate the sensitivity and specificity are susceptible to a variety of biases. In this paper the various potential problems are described with reference to examples from the diagnostic literature. These difficulties have implications for the design of diagnostic test evaluations, and the choice of suitable measures of test efficacy.

ethics.asp reference: The quality improvement-research divide and the need for external oversight. Bellin E and Dubler NN. American Journal of Public Health 2001:91(9);1512-7. Historically, quality assurance studies have received scant ethical attention.The advent of information systems capable of supporting research-grade continuous quality improvement projects demands that we clearly define how these projects differ from research and when they require external review. The ethical obligation for the performance of quality assurance projects, with its emphasis on identifiable immediate action for a served population, is a critical distinction.The obligation to perform continuous quality improvement is a deliverable of the social contract entered into implicitly by patients and health care providers and systems. In this article, the authors review the ethical framework that requires these studies, evaluate the differences between quality assurance studies and classic research, and propose criteria for requiring external review. [Medline]

diagnostic.asp reference: Is C-reactive protein useful in the management of children with suspected bacterial meningitis? Benjamin DR, Opheim KE and Brewer L. Am J Clin Pathol 1984:81(6);779-82. C-reactive protein (CRP) was evaluated in both serum and cerebrospinal fluid in 119 patients to determine if either or both measurements were of clinical value in the diagnosis of bacterial meningitis. CSF C-reactive protein is too insensitive (sensitivity = 66%) to be useful, while serum CRP is too nonspecific for routine application. Serum CRP may have a role if used selectively in those patients with a low-grade CSF pleocytosis and a negative Gram's stain.

Why Bogus Therapies Seem to Work. Beyerstein BL 1997. chapter3.asp reference

diagnostic.asp reference: Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Bhutani VK, Johnson L and Sivieri EM. Pediatrics 1999:103(1);6-14. OBJECTIVE: To assess the predictive ability of a universal predischarge serum bilirubin measurement to screen for risk of subsequent significant hyperbilirubinemia in the direct Coombs negative healthy term and near-term newborn during the first postnatal week. METHODS: Total serum bilirubin (TSB) levels were obtained at the time of the routine metabolic screen in all term and near-term newborns cared for in the Pennsylvania Hospital Well Baby Nursery (n = 13 003). Postnatal age (in hours) at the time of TSB measurement was recorded. A percentile-based bilirubin nomogram for the first week was constructed from hour-specific predischarge and postdischarge TSB values of newborns (n = 2840; median BW = 3230 g and median gestational age = 39 weeks) who met classification criteria for healthy newborns (excluding those with a positive direct Coombs test or those requiring phototherapy before age 60 hours) and who were enrolled in a hospital supervised home or outpatient follow-up program. The accuracy of the predischarge TSB as a predictor of subsequent degree of hyperbilirubinemia was determined. RESULTS: The study patients in the nomogram were racially diverse. Nearly 60% were breastfed. Predischarge, 6.1% of the study population (172/2840) had TSB values in the high-risk zone (>/=95th percentile) at 18 to 72 hours; of these, 39.5% (68/172) remained in that zone (likelihood ratio [LR] = 14.08, sensitivity = 54%; specificity = 96.2%, probability = 39.5%). Predischarge, 32.1% of the population (912/2840) had TSB values in the intermediate-risk zone. In a clinically significant minority of these newborns (58/912 or 6.4%), the postdischarge TSB moved into the high-risk zone (LR of this move: 3.2 from the upper-intermediate zone and.48 from the lower-intermediate risk zone). The predischarge TSB in 61.8% of the newborns (1756/2840) was in the low-risk zone (<40th percentile) and there was no measurable risk for significant hyperbilirubinemia (LR = 0, sensitivity = 100%; specificity = 64.7%; probability = 0%). CONCLUSIONS: An hour-specific TSB before hospital discharge can predict which newborn is at high, intermediate or low risk for developing clinically significant hyperbilirubinemia (specifically defined as TSB levels >/=95th percentile for age in hours). Risk designation and subsequent increases or decreases of in TSB can be easily monitored on an hour-specific percentile based predictive bilirubin nomogram. A predischarge TSB measured as a universal policy would facilitate targeted intervention and follow-up in a safe, cost-effective manner. In conjunction with bilirubin practice parameter of the American Academy of Pediatrics, it could reduce the potential risk for bilirubin-induced neurologic dysfunction. [Medline]

diagnostic.asp reference: Comparing diagnostic tests: a simple graphic using likelihood ratios. Biggerstaff BJ. Statistics in Medicine 2000:19(5);649-63. The diagnostic abilities of two or more diagnostic tests are traditionally compared by their respective sensitivities and specificities, either separately or using a summary of them such as Youden's index. Several authors have argued that the likelihood ratios provide a more appropriate, if in practice a less intuitive, comparison. We present a simple graphic which incorporates all these measures and admits easily interpreted comparison of two or more diagnostic tests. We show, using likelihood ratios and this graphic, that a test can be superior to a competitor in terms of predictive values while having either sensitivity or specificity smaller. A decision theoretic basis for the interpretation of the graph is given by relating it to the tent graph of Hilden and Glasziou (Statistics in Medicine, 1996). Finally, a brief example comparing two serodiagnostic tests for Lyme disease is presented. Published in 2000 by John Wiley & Sons, Ltd. [Medline]

diagnostic.asp reference: The validity of the Hospital Anxiety and Depression Scale. An updated literature review. Bjelland I, Dahl AA, Haug TT and Neckelmann D. J Psychosom Res 2002:52(2);69-77. OBJECTIVE: To review the literature of the validity of the Hospital Anxiety and Depression Scale (HADS). METHOD: A review of the 747 identified papers that used HADS was performed to address the following questions: (I) How are the factor structure, discriminant validity and the internal consistency of HADS? (II) How does HADS perform as a case finder for anxiety disorders and depression? (III) How does HADS agree with other self-rating instruments used to rate anxiety and depression? RESULTS: Most factor analyses demonstrated a two-factor solution in good accordance with the HADS subscales for Anxiety (HADS-A) and Depression (HADS-D), respectively. The correlations between the two subscales varied from.40 to.74 (mean.56). Cronbach's alpha for HADS-A varied from.68 to.93 (mean.83) and for HADS-D from.67 to.90 (mean.82). In most studies an optimal balance between sensitivity and specificity was achieved when caseness was defined by a score of 8 or above on both HADS-A and HADS-D. The sensitivity and specificity for both HADS-A and HADS-D of approximately 0.80 were very similar to the sensitivity and specificity achieved by the General Health Questionnaire (GHQ). Correlations between HADS and other commonly used questionnaires were in the range.49 to.83. CONCLUSIONS: HADS was found to perform well in assessing the symptom severity and caseness of anxiety disorders and depression in both somatic, psychiatric and primary care patients and in the general population. [Medline]

diagnostic.asp reference: Mathematical tools for demonstrating the clinical usefulness of biochemical markers. Boyd JC. Scand J Clin Lab Invest Suppl 1997:227(46-63. Various approaches have been proposed for evaluating the diagnostic value of biochemical markers. Careful design of experimental protocol is key in carrying out any evaluation of clinical diagnostic value. A prospective cohort study is the best clinical trial design and should include an appropriate reference (gold) standard applied in every patient, the results of which are assessed blindly. The spectrum of patients evaluated should reflect the population in which the test will be used, be appropriately broad to avoid bias, and include both symptomatic and asymptomatic patients. The handling of indeterminate results and the eligibility criteria for inclusion in the study should be carefully defined. Although sensitivity, specificity, and predictive value have long been used as indices of test accuracy, newer methods such as receiver operating characteristic curve (ROC) analysis, logistic regression analysis and likelihood ratios are more robust indicators that overcome many limitations of the traditional indices. The area under the ROC curve (AUC) is the best global indicator of test accuracy, but comparisons of AUC for different tests must take correlation between the tests into account if they have been performed in the same patients. Logistic regression analysis allows the diagnostic information from several tests to be evaluated multivariately, provides a probability estimate for a given outcome, and requires few assumptions regarding the underlying distributions of test data. Logistic regression also provides a straightforward method for calculating likelihood ratios. Likelihood ratios are useful for interpreting test results in the individual patient because they provide a convenient means to directly determine predictive value without having to calculate sensitivity and specificity for a given decision limit. Application of these methods is demonstrated using specific examples.

chapter5.asp reference: Economic evaluation and clinical trials: size matters. Briggs A. Bmj 2000:321(7273);1362-3. [Medline]

diagnostic.asp reference: Screening for alcohol abuse using CAGE scores and likelihood ratios. Buchsbaum DG, Buchanan RG, Centor RM, Schnoll SH and Lawton MJ. Ann Intern Med 1991:115(10);774-7. OBJECTIVE: To assess the performance of the CAGE (acronym referring to four questions, see below) questionnaire in discriminating between medicine outpatients with and without an alcohol abuse or dependence disorder. DESIGN: A cross-sectional design of a sample of consecutive patients who received both the alcohol module of the diagnostic interview schedule and the CAGE (Cut down, Annoyed, Guilty, Eye-opener) screening questionnaire. SETTING: The outpatient medical practice of an urban university teaching hospital. PATIENTS: All patients 18 years or older who signed a consent form approved by the university's institutional review board. MEASUREMENT: Calculation of the sensitivity, specificity, receiver operating characteristic (ROC) curve, and likelihood ratio for CAGE scores of 0 to 4. RESULTS: Thirty-six percent of the sample group met criteria for a history of alcohol abuse or dependence. A CAGE score of 2 or more was associated with a sensitivity and specificity of 74% and 91%. The calculated area under the ROC curve was 0.89, whereas the likelihood ratios for CAGE scores of 0 to 4 were 0.14, 1.5, 4.5, 13, and 100, respectively. These ratios were associated with posterior probabilities for an abuse or dependence disorder of 7%, 46%, 72%, 88%, and 98%, respectively. CONCLUSION: Clinicians can improve their ability to estimate a patient's risk for an alcohol abuse or dependence disorder using likelihood ratios for CAGE scores. [Medline]

chapter1.asp reference chapter3.asp reference: Controlled trial of acupuncture for severe recidivist alcoholism. Bullock ML, Culliton PD and Olander RT. Lancet 1989:1(8652);1435-9. In a placebo-controlled study, 80 severe recidivist alcoholics received acupuncture either at points specific for the treatment of substance abuse (treatment group) or at nonspecific points (control group). 21 of 40 patients in the treatment group completed the programme compared with 1 of 40 controls. Significant treatment effects persisted at the end of the six-month follow-up: by comparison with treatment patients more control patients expressed a moderate to strong need for alcohol, and had more than twice the number of both drinking episodes and admissions to a detoxification centre. [Medline]

diagnostic.asp reference: Genetic test evaluation: information needs of clinicians, policy makers, and the public. Burke W, Atkins D, Gwinn M, Guttmacher A, Haddow J, Lau J, Palomaki G, Press N, Richards CS, Wideroff L and Wiesner GL. Am J Epidemiol 2002:156(4);311-8. Growing knowledge about gene-disease associations will lead to new opportunities for genetic testing. Many experts predict that genetic testing will become increasingly important as a guide to prevention, clinical management, and drug treatment based on genetic susceptibilities. As part of a Human Genetic Epidemiology workshop convened by the Centers for Disease Control and Prevention, a group of experts evaluated the evidence needed when considering the appropriate use of new genetic tests. Because new tests are likely to vary in their predictive value, their potential to direct prevention or treatment efforts, and their personal and social consequences, the task of determining appropriate use will require careful consideration of a variety of factors, including the analytic validity, clinical validity, clinical utility, and ethical, legal, and social implications of the test. Standardized formats are needed to summarize what is known and not known about new genetic tests with respect to each of these features. Following criteria for the objective assessment of test properties, reports should be structured to enable policy makers, clinicians, and the public to identify the available evidence, so that uncertainties can be taken into account when considering test use and planning future research. [Medline]

chapter1.asp reference: The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Cameron E and Campbell A. Chem Biol Interact 1974:9(4);285-315. Abstract not available yet. [Medline]

chapter1.asp reference: A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, Heptonstall J, Ippolito G, Lot F, McKibben PS and Bell DM. N Engl J Med 1997:337(21);1485-90. BACKGROUND: The average risk of human immunodeficiency virus (HIV) infection after percutaneous exposure to HIV-infected blood is 0.3 percent, but the factors that influence this risk are not well understood. METHODS: We conducted a case-control study of health care workers with occupational, percutaneous exposure to HIV-infected blood. The case patients were those who became seropositive after exposure to HIV, as reported by national surveillance systems in France, Italy, the United Kingdom, and the United States. The controls were health care workers in a prospective surveillance project who were exposed to HIV but did not seroconvert. RESULTS: Logistic-regression analysis based on 33 case patients and 665 controls showed that significant risk factors for seroconversion were deep injury (odds ratio= 15; 95 percent confidence interval, 6.0 to 41), injury with a device that was visibly contaminated with the source patient's blood (odds ratio= 6.2; 95 percent confidence interval, 2.2 to 21), a procedure involving a needle placed in the source patient's artery or vein (odds ratio=4.3; 95 percent confidence interval, 1.7 to 12), and exposure to a source patient who died of the acquired immunodeficiency syndrome within two months afterward (odds ratio=5.6; 95 percent confidence interval, 2.0 to 16). The case patients were significantly less likely than the controls to have taken zidovudine after the exposure (odds ratio=0.19; 95 percent confidence interval, 0.06 to 0.52). CONCLUSIONS: The risk of HIV infection after percutaneous exposure increases with a larger volume of blood and, probably, a higher titer of HIV in the source patient's blood. Postexposure prophylaxis with zidovudine appears to be protective.

diagnostic.asp reference: Percentage of free prostate-specific antigen in sera predicts aggressiveness of prostate cancer a decade before diagnosis. Carter HB, Partin AW, Luderer AA, Metter EJ, Landis P, Chan DW, Fozard JL and Pearson JD. Urology 1997:49(3);379-84. OBJECTIVES: To evaluate serial measurements of free and total prostate-specific antigen (PSA) as a predictor of prostate cancer aggressiveness. METHODS: Twenty men diagnosed with adenocarcinoma of the prostate in the pre-PSA era had serum PSA measurements made on multiple stored frozen sera samples available for up to 18 years prior to diagnosis. Subjects were categorized as having aggressive cancer (n = 12) based on the presence of clinical Stage T3, or nodal or bone metastases (N+, M+), or pathologic positive-margin disease, or a Gleason score of 7 or greater; nonaggressive cancer (n = 8) was identified by the absence of these criteria. RESULTS: There was no statistically significant difference in free PSA levels among men with aggressive and nonaggressive prostate cancers from 0 to 15 years before diagnosis. Total PSA levels were significantly different between the groups by 5 years before diagnosis (P = 0.04). At a time when total PSA levels were not different between groups (10 years before diagnosis), there was a statistically significant difference in the percentage of free PSA between aggressive and nonaggressive cancers (P = 0.008). Among 14 men who had sera available for analysis at 10 years before diagnosis, all 8 men with aggressive cancers had a percent free PSA of 0.14 or less; this compares with only 2 of 6 men (33%) with nonaggressive cancer. CONCLUSIONS: These data suggest that the percentage of free PSA in sera is predictive of tumor behavior at a time when total PSA levels provide no information on tumor aggressiveness. Evaluation of the percentage of free serum PSA may be helpful in making the decision between expectant management and treatment for those men who are diagnosed with early prostate cancers by PSA testing. [Medline]

diagnostic.asp reference: The role of clinical suspicion in evaluating a new diagnostic test for active tuberculosis: results of a multicenter prospective trial. Catanzaro A, Perry S, Clarridge JE, Dunbar S, Goodnight-White S, LoBue PA, Peter C, Pfyffer GE, Sierra MF, Weber R, Woods G, Mathews G, Jonas V, Smith K and Della-Latta P. Jama 2000:283(5);639-45. CONTEXT: In laboratory trials, nucleic acid amplification tests for the diagnosis of tuberculosis (TB) are more accurate than acid-fast bacilli (AFB) smear microscopy and are faster than culture. The impact of these tests on clinical diagnosis is not known. OBJECTIVE: To assess the performance of a nucleic acid amplification test, the enhanced Mycobacterium tuberculosis Direct (E-MTD) test, against a uniform clinical standard stratified by level of clinical suspicion. DESIGN: Prospective multicenter trial conducted between February and December 1996, documenting the clinical suspicion of TB at enrollment and using final comprehensive diagnosis as the criterion standard. SETTING: Six urban medical centers and 1 public health TB clinic. PATIENTS: A total of 338 patients with symptoms and signs consistent with active pulmonary TB and complete clinical diagnosis were stratified by the clinical investigators to be at low (< or =25%), intermediate (26%-75%), or high (>75%) relative risk of having TB. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of the E-MTD test in clinical suspicion of groups with low (n = 224); intermediate (n = 68); and high (n = 46) clinical suspicion of TB. RESULTS: Based on comprehensive clinical diagnosis, sensitivity of the E-MTD test was 83%, 75%, and 87% for low, intermediate, and high clinical suspicion of TB, respectively, and corresponding specificity was 97%, 100%, and 100% (P = .25). Positive predictive value of the E-MTD test was 59% (low), 100% (intermediate), and 100% (high) compared with 36% (low), 30% (intermediate), and 94% (high) for AFB smear. Corresponding negative predictive values were 99%, 91%, and 55% [corrected] (E-MTD test) vs 96%, 71%, and 37% (AFB smear). CONCLUSIONS: For complex diagnostic problems like TB, clinical risk assessments can provide important information regarding predictive values more likely to be experienced in clinical practice. For this series, a clinical suspicion of TB was helpful in targeting areas of the clinical spectrum in which nucleic acid amplification tests can make an important contribution. [Medline]

chapter5.asp reference: How well is the clinical importance of study results reported? An assessment of randomized controlled trials. Chan KB, Man-Son-Hing M, Molnar FJ and Laupacis A. Cmaj 2001:165(9);1197-202. BACKGROUND: The interpretation of the results of randomized controlled trials (RCTs) has traditionally emphasized statistical significance rather than clinical importance. Our aim was to assess the quality of reporting of factors related to clinical importance in a sample of published RCTs. METHODS: A random sample of 27 (of a total of 266) RCTs published in 5 major medical journals over a 1-year period were reviewed by 4 independent reviewers for factors considered important in the interpretation of the clinical importance of study results: identification of a clearly defined primary outcome, reporting of the expected difference between groups used in the calculation of sample size (the delta value) and whether it was based on the minimal clinically important difference of the intervention, the statistical significance of the results, presentation of pertinent confidence intervals, and the authors' interpretation of the clinical importance of the results. RESULTS: Twenty-two of 27 (81%) articles explicitly reported a single primary outcome. Of the 20 articles that included a sample size calculation, 18 (90%) reported a delta value. Two of the 18 (11%) articles explicitly stated that the delta value was chosen to reflect the minimal clinically important difference of the intervention. For the primary outcomes, confidence intervals surrounding the point estimates of the efficacy of the interventions were reported in 11 of 27 (41%) studies. The study results were interpreted from the perspective of clinical importance in 20 of 27 (74%) of the articles. Of these 20 reports, 5 (25%) provided justification for their clinical interpretation of the results. INTERPRETATION: Authors of RCTs published in major general medical and internal medicine journals do not consistently provide their own interpretation of the clinical importance of their results, and they often do not provide sufficient information to allow readers to make their own interpretation.

qualitative.asp reference: Why men with prostate cancer want wider access to prostate specific antigen testing: qualitative study. Chapple A, Ziebland S, Shepperd S, Miller R, Herxheimer A and McPherson A. Bmj 2002:325(7367);737. OBJECTIVES: To explore the attitudes of men with confirmed or suspected prostate cancer to testing for prostate specific antigen. DESIGN: Qualitative interview study with a purposive sample. SETTING: Great Britain. PARTICIPANTS: 52 men with suspected or confirmed prostate cancer, recruited through general practitioners, urologists, patient support groups, and charities. RESULTS: Almost all men remembered their prostate specific antigen test but recalled being given little information beforehand. Arguments in favour of increased access to testing included the belief that early diagnosis would reduce mortality, improve quality of life, and save the NHS money. Men also thought that a national screening programme should be available because symptoms can be ambiguous, screening for cancer is responsible health behaviour, and screening would encourage men to be tested. Four men who opposed a screening programme had gathered information alerting them to uncertainty about the benefits of treatment, and two regretted that they had been tested. Others thought that access to testing is restricted in the United Kingdom because of a lack of government backing, concerns about the accuracy of the test, and a lack of resources. CONCLUSIONS: The few men in this study who subscribed to the argument that evidence of the benefits of treatment is a prerequisite for a screening programme did not want to see screening introduced. Men who proposed an alternative set of principles for testing gave reasons that did not all relate to overoptimism about the benefits of early diagnosis. People who plan services and people who respond to requests for testing need to understand men's perspectives and concerns. [Medline]

diagnostic.asp reference: The diagnostic accuracy of cervico-vaginal fetal fibronectin in predicting preterm delivery: an overview. Chien PF, Khan KS, Ogston S and Owen P. British Journal of Obstetrics and Gynaecology 1997:104(4);436-44. OBJECTIVE: To determine the accuracy with which cervico-vaginal fetal fibronectin predicts preterm delivery using systematic quantitative overview of the available literature. DESIGN: Online searching of MEDLINE database (1966 to April 1996), scanning of bibliography of known primary and review articles and review of recent journal issues. Study selection, assessment of study quality and data extraction were performed in duplicate under masked conditions. Likelihood ratios were generated in subgroups of symptomatic and asymptomatic pregnant women by pooling data from different studies. An LR of > 10 or < 0.1 indicated conclusive changes in the pretest probability of preterm delivery while an LR of 5-10 or 0.2-0.1 indicated only moderate changes. PARTICIPANTS: Seven hundred and twenty-three symptomatic women with threatened preterm labour included in nine studies and 847 asymptomatic women (635 low risk and 212 high risk) included in six studies selected for meta-analyses. MAIN OUTCOME MEASURES: Likelihood ratios for positive and negative test results using delivery at < 37 and < 34 weeks of gestation, and within one week of testing as outcome measures. RESULTS: In symptomatic women a positive test predicted delivery < 37 weeks of gestation with a pooled likelihood ratio (LR) of 4.6 (95% CI 3.5-6.1) while a negative test had a pooled LR of 0.5 (95% CI 0.4-0.6). For delivery < 34 weeks of gestation, the pooled LR was 2.6 (95% CI 1.8-3.7) for a positive test and 0.2 (95% CI 0.1-0.5) for a negative test. For delivery within one week of testing, the pooled LR was 5.0 (95% CI 3.8-6.4) for a positive test and 0.2 (95% CI 0.1-0.4) for a negative test. In asymptomatic women at low risk of delivery < 37 weeks of gestation the pooled LR was 3.2 (95% CI 2.2-4.8) for a positive test and 0.8 (95% CI 0.7-0.9) for a negative test. In high risk asymptomatic women using delivery < 37 weeks of gestation as an outcome measure the pooled LR was 2.0 (95% CI 1.5-2.6) for a positive test and 0.4 (95% CI 0.2-0.8) for a negative test. For delivery < 34 weeks of gestation in high risk, asymptomatic women the pooled LR was 2.4 (95% CI 1.8-3.2) for a positive test and 0.6 (95% CI 0.4-0.9) for a negative test. CONCLUSION: The presence of fetal fibronectin in cervico-vaginal mucus has limited accuracy in predicting preterm delivery as the likelihood ratios for positive and negative test results generated only minimal to moderate changes in the pretest probability of preterm birth. [Medline]

diagnostic.asp reference: Slopes of a receiver operating characteristic curve and likelihood ratios for a diagnostic test. Choi B. AJE 1998:148(11);1127-32. ABSTRACT: This paper clarifies two important concepts in clinical epidemiology: the slope of a receiver operating characteristic (ROC) curve and the likelihood ratio. It points out that there are three types of slopes in an ROC curve--the tangent at a point on the curve, the slope between the origin and a point on the curve, and the slope between two points on the curve. It also points out that there are three types of likelihood ratios that can be defined for a diagnostic test that produces results on a continuous scale--the likelihood ratio for a particular single test value, the likelihood ratio for a positive test result, and the likelihood ratio for a test result in a particular level or category. It further illustrates mathematically and empirically the following three relations between these various definitions of slopes and likelihood ratios: 1) the tangent at a point on the ROC curve corresponds to the likelihood ratio for a single test value represented by that point; 2) the slope between the origin and a point on the curve corresponds to the positive likelihood ratio using the point as a criterion for positivity; and 3) the slope between two points on the curve corresponds to the likelihood ratio for a test result in a defined level bounded by the two points. The likelihood ratio for a single test value is considered an important parameter for evaluating diagnostic tests, but it is not easily estimable directly from laboratory data because of limited sample size. However, by using ROC analysis, the likelihood ratio for a single test value can be easily measured from the tangent. It is suggested that existing ROC analysis software be revised to provide estimates for tangents at various points on the ROC curve.

microarray.asp reference: Assessment of the relationship between signal intensities and transcript concentration for Affymetrix GeneChip arrays. Chudin E, Walker R, Kosaka A, Wu SX, Rabert D, Chang TK and Kreder DE. Genome Biol 2002:3(1);RESEARCH0005. BACKGROUND: Affymetrix microarrays have become increasingly popular in gene-expression studies; however, limitations of the technology have not been well established for commercially available arrays. The hybridization signal has been shown to be proportional to actual transcript concentration for specialized arrays containing hundreds of distinct probe pairs per gene. Additionally, the technology has been described as capable of distinguishing concentration levels within a factor of 2, and of detecting transcript frequencies as low as 1 in 2,000,000. Using commercially available arrays, we assessed these representations directly through a series of 'spike-in' hybridizations involving four prokaryotic transcripts in the absence and presence of fixed eukaryotic background. The contribution of probe-target interactions to the mismatch signal was quantified under various analyte concentrations. RESULTS: A linear relationship between transcript abundance and signal was consistently observed between 1 pM and 10 pM transcripts. The signal ceased to be linear above the 10 pM level and commenced saturating around the 100 pM level. The 0.1 pM transcripts were virtually undetectable in the presence of eukaryotic background. Our measurements show that preponderance of the signal for mismatch probes derives from interactions with the target transcripts. CONCLUSIONS: Landmark studies outlining an observed linear relationship between signal and transcript concentration were carried out under highly specialized conditions and may not extend to commercially available arrays under routine operating conditions. Additionally, alternative metrics that are not based on the difference in the signal of members of a probe pair may further improve the quantitative utility of the Affymetrix GeneChip array. [Medline] [Abstract] [Full text] [PDF]

chapter2.asp reference: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. Clark LC, Combs GF, Jr., Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL, Jr., Park HK, Sanders BB, Jr., Smith CL and Taylor JR. Jama 1996:276(24);1957-63. OBJECTIVE: To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. DESIGN: A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. SETTING: Seven dermatology clinics in the eastern United States. PATIENTS: A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. INTERVENTIONS: Oral administration of 200 microg of selenium per day or placebo. MAIN OUTCOME MEASURES: The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers. RESULTS: After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. CONCLUSIONS: Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made.

chapter3.asp reference: How study design affects outcomes in comparisons of therapy. I: Medical. Colditz G, Miller J and Mosteller F. Stat Med 1989:8(4);441-454. ABSTRACT: We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old. Overall we rated 87 per cent of new therapies as improvements over standard therapies. The mean gain (measured by the Mann-Whitney statistic) was relatively constant across study designs, except for non-randomized controlled trials with sequential assignment to therapy, which showed a significantly higher likelihood that a patient would do better on the innovation than on standard therapy (p = 0.004). Randomized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials (p = 0.02). Any evaluation of an innovation may include both bias and the true efficacy of the new therapy, therefore we may consider making adjustments for the average bias associated with a study design. When interpreting an evaluation of a new therapy, readers should consider the impact of the following average adjustments to the Mann-Whitney statistic: for trials with non-random sequential assignment a decrease of 0.15, for non-double-blind randomized controlled trials a decrease of 0.11.

diagnostic.asp reference: Does this patient have carpal tunnel syndrome? D' Arcy C and McGee S. Jama 2000:283(23);3110-7. CONTEXT: History taking and physical examination maneuvers, including Tinel and Phalen signs, are widely used for the diagnosis of carpal tunnel syndrome (CTS). OBJECTIVE: To systematically review the precision and accuracy of history taking and physical examination in diagnosing CTS in adults. DATA SOURCES: English-language literature was searched using MEDLINE (January 1966-February 2000) as well as bibliographies of relevant articles. STUDY SELECTION: Studies of patients presenting to clinicians with symptoms suggestive of CTS in which findings from clearly described physical examination maneuvers were independently compared with electrodiagnostic testing. Twelve of 42 initially identified articles met these criteria and were included in the review. DATA EXTRACTION: Two authors independently reviewed and abstracted data from all of the articles and reached consensus about any discrepancies. DATA SYNTHESIS: In patients presenting with hand dysesthesias, the findings that best distinguish between patients with electrodiagnostic evidence of CTS and patients without it are hypalgesia in the median nerve territory (likelihood ratio [LR], 3. 1; 95% confidence interval [CI], 2.0-5.1), classic or probable Katz hand diagram results (LR, 2.4; 95% CI, 1.6-3.5), and weak thumb abduction strength (LR, 1.8; 95% CI, 1.4-2.3). Findings that argue against the diagnosis of carpal tunnel syndrome are unlikely Katz hand diagram results (LR, 0.2; 95% CI, 0.0-0.7) and normal thumb abduction strength (LR, 0.5; 95% CI, 0.4-0.7). Several traditional findings of CTS have little or no diagnostic value, including nocturnal paresthesias; Phalen and Tinel signs; thenar atrophy; and 2-point, vibratory, and monofilament sensory testing. Other less commonly used maneuvers, including the square wrist sign, flick sign, and closed fist sign, require validation by other studies before they can be recommended. CONCLUSIONS: Hand symptom diagrams, hypalgesia, and thumb abduction strength testing are helpful in the establishing electrodiagnosis of CTS. The utility of these results is limited, however, by problems inherent in using nerve conduction studies as a criterion standard. JAMA. 2000.

diagnostic.asp reference: Sensitivity and specificity of QTc dispersion for identification of risk of cardiac death in patients with peripheral vascular disease. Darbar D, Luck J, Davidson N, Pringle T, Main G, McNeill G and Struthers AD. British Medical Journal 1996:312(7035);874-8; discussion 878-9. OBJECTIVE: To determine whether QTc dispersion, which is easily obtained from a standard electrocardiogram, can predict those patients with peripheral vascular disease who will subsequently suffer a cardiac death, despite having no cardiac symptoms or signs. DESIGN: Patients with peripheral vascular disease were followed up for five years after they had had coronary angiography, radionuclide ventriculography, and their QTc dispersion calculated from their 12 lead electrocardiogram. SUBJECTS: 49 such patients were then divided into three groups: survivors (34), cardiac death (12), and non-cardiac death (3). MAIN OUTCOME MEASURE: Survival. RESULTS: The mean (SD; range) ejection fractions were similar in all three groups: survivors 45.9 (11.0; 27.0-52.0), cardiac death 44.0 (7.90; 28.5-59.0), and non-cardiac death 45.3 (4.55; 39.0-50.0). QTc dispersion was significantly prolonged in the cardiac death group compared with in the survivors (86.3(23.9; 41.0-139) v 56.5 (25.4; 25.0-164); P = 0.002). A QTc dispersion > or = 60 ms had a 92% sensitivity and 81% specificity in predicting cardiac death, QTc dispersion in patients with diffuse coronary artery disease was significantly (P < 0.05) greater than in those with no disease or disease affecting one, two, or three vessels. CONCLUSIONS: There is a strong link between QTc dispersion and cardiac death in patients with peripheral vascular disease. QTc dispersion may therefore be a cheap and non-invasive way of assessing the risk of cardiac death in patients with peripheral vascular disease. [Medline]

oddsratio.asp reference: When can odds ratios mislead? Odds ratios should be used only in case-control studies and logistic regression analyses [letter]. Deeks J. British Medical Journal 1998:317(7166);1155-6; discussion 1156-7. Abstract not available.

diagnostic.asp reference: Evidence-based diagnostic radiology. Dixon AK. Lancet 1997:350(9076);509-12. The radiological community has a long track record of self-examination, starting well before evidence-based medicine came of age. It had to produce such evidence to prove the need for and win funds for its expensive gadgets. The assessment of new tests is easier than proving the value of well-established ones, and in scrutinising the evidence base for an imaging technique a balance must be struck between apparent (eg, diagnostic) benefit and real benefit to the patient. And even when there is a wealth of good evidence healthy debate continues. So radiology may be ahead of some other disciplines in considering the evidence for its daily practice. For example, where is the evidence for the routine clinical examination-and might the radiologist with a chest X-ray and abdominal ultrasound do better? [Medline]

diagnostic.asp reference: Computer program for the diagnosis and treatment of polycythemia rubra vera. Djulbegovic B and Hozo I. MD Comput 1999:16(1);83-9. Abstract not available yet. [Medline]

chapter5.asp reference: Dulcet tones of a surgeon's voice may have a hidden meaning. Dobson R. Bmj 2002:325(7359);297. [Medline]

qualitative.asp reference: Quality improvement report: Improving design and conduct of randomised trials by embedding them in qualitative research: ProtecT (prostate testing for cancer and treatment) study. Commentary: presenting unbiased information to patients can be difficult. Donovan J, Mills N, Smith M, Brindle L, Jacoby A, Peters T, Frankel S, Neal D and Hamdy F. Bmj 2002:325(7367);766-70. PROBLEM: Recruitment to randomised trials is often difficult, and many important trials are not mounted because recruitment is thought to be "impossible." DESIGN: Controversial ProtecT (prostate testing for cancer and treatment) trial embedded within qualitative research. BACKGROUND AND SETTING: Screening for prostate cancer is hotly debated, and evidence from trials about the effectiveness of treatments (surgery, radiotherapy, and monitoring) is lacking. Mounting a treatment trial is controversial because of past failures and concerns that differences in complications of treatment but not survival make randomisation unacceptable to patients and clinicians, particularly for a trial including monitoring. STRATEGY FOR CHANGE: In-depth interviews explored interpretation of study information. Audiotape recordings of recruitment appointments enabled scrutiny of content and presentation of study information by recruiters. Initial qualitative findings showed that recruiters had difficulty discussing equipoise and presenting treatments equally; they unknowingly used terminology that was misinterpreted by participants. Findings were used to determine changes to content and presentation of information. EFFECTS OF CHANGE: Changes to the order of presenting treatments encouraged emphasis on equivalence, misinterpreted terms were avoided, the non-radical arm was redefined, and randomisation and clinical equipoise were presented more convincingly. The randomisation rate increased from 40% to 70%, all treatments became acceptable, and the three arm trial became the preferred design. LESSONS LEARNT: Changes to information and presentation resulted in efficient recruitment acceptable to patients and clinicians. Embedding this controversial trial within qualitative research improved recruitment. Such methods probably have wider applicability and may enable even the most difficult evaluative questions to be tackled. [Medline]

diagnostic.asp reference: Problems in using the hospital anxiety and depression scale for screening patients in general practice. Dowell AC and Biran LA. Br J Gen Pract 1990:40(330);27-8. A study was made of the feasibility of screening general practice patients for anxiety and depression using the hospital anxiety and depression scale. A group of consecutive patients aged 18 years and over completed the questionnaire at the surgery and an age and sex matched sample were sent questionnaires by post; 94 patients (84%) returned the postal questionnaire. A further group of 170 consecutive patients coming for consultation were recruited. Using a threshold score of eight and over, 51% of patients screened by post were probable 'cases' of psychiatric disorder and using a score of 11 and over, 28% were 'cases'. These proportions were similar for patients screened when attending the surgery. The findings are discussed in the context of well-person screening, and a strategy for follow-up of probable cases is put forward. [Medline]

irb.asp reference: . Dresser R. Accessed on 2002.

diagnostic.asp reference: The ratio of free to total serum prostate specific antigen and its use in differential diagnosis of prostate carcinoma in Japan. Egawa S, Soh S, Ohori M, Uchida T, Gohji K, Fujii A, Kuwao S and Koshiba K. Cancer 1997:79(1);90-8. BACKGROUND: To improve the clinical usefulness of prostate specific antigen (PSA), unique methods have been proposed. The percentage of free PSA in serum facilitates the distinction between benign histologic conditions and prostate carcinoma while retaining high sensitivity. METHODS: Using monoclonal antibodies, an AIA total PSA assay system was established that recognized PSA equally in free or complex form. The clinical usefulness of the ratio of two different molecular forms of PSA was investigated using 268 archival serum samples. RESULTS: Men with prostate carcinoma had significantly lower ratios of free to total PSA than those with benign prostatic hyperplasia (BPH) (P = 0.0001). At total PSA levels between 2.1 and 10 ng/mL, medians of total PSA were not significantly different between men with prostate carcinoma and men with BPH. Differences in median percentages of free PSA for these two groups were statistically significant (P = 0.0001). The ratio of free to total PSA was useful for identifying prostate carcinoma in palpably benign glands with total PSA of 2.1-10 ng/mL (P = 0.0001), whereas total PSA was not useful for such identification. When calculated for low total PSA levels between 2.1 and 4 ng/mL, sensitivity and specificity were 91.7% and 72.2%, respectively, with a cutoff value of 17%. This ratio of free to total PSA was as useful as PSA density in receiver-operating curve analysis. CONCLUSIONS: The use of the ratio of free to total PSA renders total PSA of greater use of distinguishing prostate carcinoma and is applicable to patients with low total PSA. Elderly men with a clinical diagnosis of BPH who are scheduled for surgery may benefit from the determination of this ratio. [Medline]

chapter1.asp reference: Systematic reviews and lifelong diseases. Elphick HE, Tan A, Ashby D and Smyth RL. Bmj 2002:325(7360);381-4. [Medline]

placebo.asp reference: The ethics of placebo-controlled trials--a middle ground. Emanuel EJ and Miller FG. N Engl J Med 2001:345(12);915-9. Abstract not available.

chapter1.asp reference: Unconventional cancer therapies : what We need is rigorous research, not closed minds. Ernst E. Chest 2000:117(2);307-8. [Medline]

diagnostic.asp reference: Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate. Eskew LA, Bare RL and McCullough DL. J Urol 1997:157(1);199-202; discussion 202-3. PURPOSE: The number of patients undergoing prostate biopsy has dramatically increased due to prostate specific antigen screening. The low specificity of this screening tool requires prostate biopsy for diagnosis of prostate cancer. The sextant biopsy technique has been used widely with success in diagnosing carcinoma of the prostate. However, concern has arisen that the original sextant method may not include an adequate sampling of the prostate. For many years we have used a method of prostate biopsy that, in addition to sextant biopsies, takes additional biopsies in a systematic fashion, which we call the 5 region prostate biopsy. We conducted a prospective study to determine if our 5 region prostate biopsy technique significantly increases the chances of finding carcinoma of the prostate compared to the sextant biopsy technique. MATERIALS AND METHODS: A total of 119 patients underwent transrectal ultrasound guided needle biopsy of the prostate. In addition to sextant biopsies, cores were taken from the far lateral and mid regions of the gland. Pathological findings of the additional regions were compared to those of the sextant regions. RESULTS: Of the 48 patients with prostate cancer 17 (35%) had carcinomas only in the additional regions, which would have remained undetected had the sextant biopsy technique been used alone (p < 0.05). Of these additional cancers 83% had Gleason scores of 6 or more. CONCLUSIONS: We introduce the 5 region technique of prostate biopsy as a means of significantly increasing the diagnostic yield of prostate biopsy in finding carcinoma of the prostate. We have found this technique to be safe, efficacious and superior to the sextant method of biopsy in identifying prostate cancer at an early but significant stage. The greatest use of the 5 region biopsy technique is in patients who have prostate specific antigen levels between 4 and 10 ng./ml. [Medline]

oddsratio.asp reference: evidence-based purchasing: understanding results of clinical trials and systematic reviews. Fahey T, Griffiths S and Peters TJ. British Medical Journal 1995:311(7012);1056-9; discussion 1059-60. OBJECTIVE--To assess whether the way in which the results of a randomised controlled trial and a systematic review are presented influences health policy decisions. DESIGN--A postal questionnaire to all members of a health authority within one regional health authority. SETTING--Anglia and Oxford regional health authorities. SUBJECTS--182 executive and non-executive members of 13 health authorities, family health services authorities, or health commissions. MAIN OUTCOME MEASURES--The average score from all health authority members in terms of their willingness to fund a mammography programme or cardiac rehabilitation programme according to four different ways of presenting the same results of research evidence--namely, as a relative risk reduction, absolute risk reduction, proportion of event free patients, or as the number of patients needed to be treated to prevent an adverse event. RESULTS--The willingness to fund either programme was significantly influenced by the way in which data were presented. Results of both programmes when expressed as relative risk reductions produced significantly higher scores when compared with other methods (P < 0.05). The difference was more extreme for mammography, for which the outcome condition is rarer. CONCLUSIONS--The method of reporting trial results has a considerable influence on the health policy decisions made by health authority members.

bonferroni.asp reference: Do multiple outcome measures require p-value adjustment? Feise RJ. BMC Med Res Methodol 2002:2(1);8. BACKGROUND: Readers may question the interpretation of findings in clinical trials when multiple outcome measures are used without adjustment of the p-value. This question arises because of the increased risk of Type I errors (findings of false "significance") when multiple simultaneous hypotheses are tested at set p-values. The primary aim of this study was to estimate the need to make appropriate p-value adjustments in clinical trials to compensate for a possible increased risk in committing Type I errors when multiple outcome measures are used. DISCUSSION: The classicists believe that the chance of finding at least one test statistically significant due to chance and incorrectly declaring a difference increases as the number of comparisons increases. The rationalists have the following objections to that theory: 1) P-value adjustments are calculated based on how many tests are to be considered, and that number has been defined arbitrarily and variably; 2) P-value adjustments reduce the chance of making type I errors, but they increase the chance of making type II errors or needing to increase the sample size. SUMMARY: Readers should balance a study's statistical significance with the magnitude of effect, the quality of the study and with findings from other studies. Researchers facing multiple outcome measures might want to either select a primary outcome measure or use a global assessment measure, rather than adjusting the p-value. [Medline]

ethics.asp reference: Paying for children to participate in research: A slippery slope or an enlightened stairway? Fernhoff PM. The Journal of Pediatrics 2002:141(2);153-154. Abstract not available yet.

ethics.asp reference: Safeguarding patients in clinical trials with high mortality rates. Freeman BD, Danner RL, Banks SM and Natanson C. Am J Respir Crit Care Med 2001:164(2);190-192. Abstract not available yet.

chapter1.asp reference chapter3.asp reference: Statistics in Action. Gail MH. Journal of the American Statistical Association 1996:91(433);1-13. Abstract not available.

pilot.asp reference: The Carotene and Retinol Efficacy Trial (CARET) to Prevent Lung Cancer in High-Risk Populations: Pilot Study with Cigarette Smokers. Goodman G, Omenn G, Thornquist M, Lund B, Metch B and Gylys-Colwell I. Cancer Epidemilogy, Biomarkers & Prevention 1993:2(4);389-396. ABSTRACT: In preparation for a phase IV lung cancer chemoprevention trial, we conducted a pilot trial of beta-carotene and retinol in high-risk smokers. Eligibility criteria were ages of 50-69 years, a smoking history of at least 20 pack-years, and either being a current smoker or having quit within the past 6 years. Participants were recruited by mailing an interest survey to 29,928 age-selected members of King County Medical Blue Shield. We randomized 1,029 women and men to one of four intervention arms: placebo, retinol, 25,000 international units/day; beta-carotene, 30 mg/day; or retinol plus beta-carotene. Participants were followed for side effects and adherence every 2 months either by a telephone call or a clinic visit. Blood was sampled for retinoid, carotenoid, and liver function analyses annually. beta-carotene and retinol were well tolerated during the follow-up period, which had a median of 1.5 years and a maximum of 3.3 years. Yellowing of the skin was seen in both beta-carotene arms. No differences were seen among arms or over time in incidence or severity of the other 15 monitored symptoms and signs or in serum liver function tests. Adherence was good: 83% of participants remained active on study at 1 year and 75% at 2 years. Serum beta-carotene increased from a prerandomization median concentration of 170 to 2100 ng/ml after 4 months of supplementation, and retinyl palmitate median levels more than tripled.(ABSTRACT TRUNCATED AT 250 WORDS).

diagnostic.asp reference: How to read a paper. Papers that report diagnostic or screening tests. Greenhalgh T. Bmj 1997:315(7107);540-3. [Medline]

oddsratio.asp reference: Interpretation and Choice of Effect Measures in Epidemiologic Analyses. Greenland S. American Journal of Epidemiology 1987:125(5);761-767. Abstract not available.

diagnostic.asp reference: Accuracy of clinical diagnosis of cirrhosis among alcohol-abusing men. Hamberg KJ, Carstensen B, Sorensen TI and Eghoje K. J Clin Epidemiol 1996:49(11);1295-301. There is a considerable variation among specialists in the use of liver biopsy for the diagnosis of alcoholic cirrhosis, which is often based solely on clinical findings, sometimes supplemented with blood tests. To assess the diagnostic accuracy that may be achieved by this approach, we related items of the history, symptoms and signs, and routine blood tests to the presence/absence of cirrhosis in a unique, previously established, consecutive series of 303 alcohol-abusing men, in whom liver biopsy was performed irrespective of the clinical and biochemical findings. Using logistic regression analyses, we created a clinical, a combined clinical and biochemical, and a pure biochemical diagnostic model. The probability of cirrhosis in patients with the specified characteristics was estimated, the diagnostic accuracy was assessed as functions of diagnostic thresholds for cirrhosis defined by the probability of cirrhosis varying between 0 and 1,and confidence intervals were estimated by bootstrap sampling. The clinical model, including facial teleangiectasia, vascular spiders, white nails, abdominal veins, fatness, and peripheral edema, could be used with high diagnostic accuracy and it was clearly superior to the biochemical model. Adding biochemical findings to the clinical model improved the accuracy of the clinical model only slightly. We conclude that cirrhosis may be diagnosed in alcohol-abusing men with a high accuracy using selected, properly weighted clinical observations only. [Medline]

diagnostic.asp reference: Using the Hospital Anxiety and Depression Scale to screen for psychiatric disorders in people presenting with deliberate self-harm. Hamer D, Sanjeev D, Butterworth E and Barczak P. Br J Psychiatry 1991:158(782-4. In-patients referred to a deliberate self-harm team were asked to complete the HAD questionnaire and diagnoses were made using the SCID. The total prevalence of psychiatric disorder by DSM-III criteria was 54%. The HAD performed well as a screening instrument; a threshold score of eight gave a sensitivity of 88% and a positive predictive value of 80%; its use by non-psychiatrists to detect depressive disorder in patients presenting with deliberate self-harm is to be recommended. [Medline]

diagnostic.asp reference: Sensitivity and specificity of photography and direct ophthalmoscopy in screening for sight threatening eye disease: the Liverpool Diabetic Eye Study. Harding SP, Broadbent DM, Neoh C, White MC and Vora J. Bmj 1995:311(7013);1131-5. OBJECTIVE--To evaluate different methods for community based screening for sight threatening diabetic eye disease. DESIGN--Prospective study. SETTING--Mobile screening unit visiting inner city community clinics; hospital assessment clinic (tertiary centre). SUBJECTS--395 diabetic patients registered with four general practices in an inner city location. INTERVENTIONS--Community based photography with mydriasis and direct ophthalmoscopy through dilated pupils by an experienced ophthalmologist, both compared with reference standard of slit lamp biomicroscopy by a consultant specialist in medical retinal disease. MAIN OUTCOME MEASURES--Sensitivity and specificity of screening method and prevalence of sight threatening diabetic eye disease (moderate preproliferative retinopathy, circinate maculopathy, exudate within 1 disc diameter of fixation, other diabetes related eye disease). RESULTS--358 subjects underwent photography, 326 attended hospital clinic for ophthalmoscopy, and six were ungradable on photographs and biomicroscopy, leaving 320 for analysis. Of these 295 (91%) attended clinic within four months of photography. Sensitivity of detection of eye disease by photography was 89% (95% confidence interval 80% to 98%), significantly better than for direct ophthalmoscopy (65% (51% to 79%)). Analysis of patients with false negative results indicated possible improvement of photographic sensitivity to 93% by addition of stereoscopic macular pair photographs. Specificity of detection of sight threatening eye disease was 86% (82% to 90%) for photography and 97% (95% to 99%) for direct ophthalmoscopy. CONCLUSIONS--Since high sensitivity is essential for an effective screening programme, a photographic method should be considered as preferred option in national, community based screening programmes. Even in the hands of an experienced ophthalmologist, direct ophthalmoscopy is limited by weaknesses inherent to the instrument. [Medline]

diagnostic.asp reference: Screening for anxiety, depressive and somatoform disorders in rehabilitation--validity of HADS and GHQ-12 in patients with musculoskeletal disease. Harter M, Reuter K, Gross-Hardt K and Bengel J. Disabil Rehabil 2001:23(16);737-44. PURPOSE: The detection of patients with comorbid mental illness is of high clinical importance in orthopaedic rehabilitation. To simplify detection of cases, screening instruments are recommended. The study investigated the discriminant validity of the Hospital Anxiety and Depression Scale (HADS) and the General Health Questionnaire (GHQ-12) to identify patients with comorbid mental disorders, specifically anxiety, depressive and somatoform disorders. METHOD: Two hundred and six patients with musculoskeletal disease from four orthopaedic rehabilitation clinics participated in a two-stage survey: (1) patients were assessed with the GHQ-12 and HADS; and (2) they were examined for DSM-IV mental disorders by clinical standardized interview (CIDI). Validity of the two instruments regarding the detection of mental disorders was compared using ROC-analysis and CIDI-diagnoses as criteria. RESULTS: The HADS sumscale performed better in all analyses compared to the GHQ-12, specifically in detecting depressive and anxiety disorders. Best results are achieved for depressive disorders with an area under the curve (AUC) of 0.79, a sensitivity of 78% and a specificity of 71% (cut off point= 16). The positive predictive value (PPV) is best for the detection of any mental disorder with a cut-off point of 16 (46%). CONCLUSION: The HADS can be used as a screening instrument for the detection of comorbid depressive and anxiety disorders in patients with musculoskeletal disorders. Limitations in performance of screening instruments are due to: (1) different methodological approaches of tests (dimensional approach) and criterion (categorical approach); and (2) difficulties in diagnosing mental disorders in patients with prominent physical illness. [Medline]

diagnostic.asp reference: A survey of validity and utility of electronic patient records in a general practice. Hassey A, Gerrett D and Wilson A. British Medical Journal 2001:322(7299);p1401-5. OBJECTIVE: To develop methods of measuring the validity and utility of electronic patient records in general practice. DESIGN: A survey of the main functional areas of a practice and use of independent criteria to measure the validity of the practice database. SETTING: A fully computerised general practice in Skipton, north Yorkshire. SUBJECTS: The records of all registered practice patients. MAIN OUTCOME MEASURES: Validity of the main functional areas of the practice clinical system. Measures of the completeness, accuracy, validity, and utility of the morbidity data for 15 clinical diagnoses using recognised diagnostic standards to confirm diagnoses and identify further cases. Development of a method and statistical toolkit to validate clinical databases in general practice. RESULTS: The practice electronic patient records were valid, complete, and accurate for prescribed items (99.7%), consultations (98.1%), laboratory tests (100%), hospital episodes (100%), and childhood immunisations (97%). The morbidity data for 15 clinical diagnoses were complete (mean sensitivity=87%) and accurate (mean positive predictive value=96%). The presence of the Read codes for the 15 diagnoses was strongly indicative of the true presence of those conditions (mean likelihood ratio=3917). New interpretations of descriptive statistics are described that can be used to estimate both the number of true cases that are unrecorded and quantify the benefits of validating a clinical database for coded entries. CONCLUSION: This study has developed a method and toolkit for measuring the validity and utility of general practice electronic patient records.

chapter2.asp reference: Journals should see original protocols for clinical trials. Hawkey CJ. BMJ 2001:323(7324);1309-. Abstract not available yet.

chapter1.asp reference: Proof versus plausibility: rules of engagement for the struggle to evaluate alternative cancer therapies. Hoffer LJ. Cmaj 2001:164(3);351-3. [Medline]

chapter2.asp reference: Assessing cause and effect from trials: a cautionary note. Howel D and Bhopal R. Control Clin Trials 1994:15(5);331-4. Abstract not available.

chapter3.asp reference: Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. Hrobjartsson A and Gotzsche PC. N Engl J Med 2001:344(21);1594-602. BACKGROUND: Placebo treatments have been reported to help patients with many diseases, but the quality of the evidence supporting this finding has not been rigorously evaluated. METHODS: We conducted a systematic review of clinical trials in which patients were randomly assigned to either placebo or no treatment. A placebo could be pharmacologic (e.g., a tablet), physical (e.g., a manipulation), or psychological (e.g., a conversation). RESULTS: We identified 130 trials that met our inclusion criteria. After the exclusion of 16 trials without relevant data on outcomes, there were 32 with binary outcomes (involving 3795 patients, with a median of 51 patients per trial) and 82 with continuous outcomes (involving 4730 patients, with a median of 27 patients per trial). As compared with no treatment, placebo had no significant effect on binary outcomes (pooled relative risk of an unwanted outcome with placebo, 0.95; 95 percent confidence interval, 0.88 to 1.02), regardless of whether these outcomes were subjective or objective. For the trials with continuous outcomes, placebo had a beneficial effect (pooled standardized mean difference in the value for an unwanted outcome between the placebo and untreated groups, -0.28; 95 percent confidence interval, -0.38 to -0.19), but the effect decreased with increasing sample size, indicating a possible bias related to the effects of small trials. The pooled standardized mean difference was significant for the trials with subjective outcomes (-0.36; 95 percent confidence interval, -0.47 to -0.25) but not for those with objective outcomes. In 27 trials involving the treatment of pain, placebo had a beneficial effect (-0.27; 95 percent confidence interval, -0.40 to -0.15). This corresponded to a reduction in the intensity of pain of 6.5 mm on a 100-mm visual-analogue scale. CONCLUSIONS: We found little evidence in general that placebos had powerful clinical effects. Although placebos had no significant effects on objective or binary outcomes, they had possible small benefits in studies with continuous subjective outcomes and for the treatment of pain. Outside the setting of clinical trials, there is no justification for the use of placebos.

chapter1.asp reference: Dietary fat intake and the risk of coronary heart disease in women. Hu FB, Stampfer MJ, Manson JE, Rimm E, Colditz GA, Rosner BA, Hennekens CH and Willett WC. N Engl J Med 1997:337(21);1491-9. BACKGROUND: The relation between dietary intake of specific types of fat, particularly trans unsaturated fat and the risk of coronary disease remains unclear. We therefore studied this relation in women enrolled in the Nurses' Health Study. METHODS: We prospectively studied 80,082 women who were 34 to 59 years of age and had no known coronary disease, stroke, cancer, hypercholesterolemia, or diabetes in 1980. Information on diet was obtained at base line and updated during follow-up by means of validated questionnaires. During 14 years of follow-up, we documented 939 cases of nonfatal myocardial infarction or death from coronary heart disease. Mutivariate analyses included age, smoking status, total energy intake, dietary cholesterol intake, percentages of energy obtained from protein and specific types of fat, and other risk factors. RESULTS: Each increase of 5 percent of energy intake from saturated fat, as compared with equivalent energy intake from carbohydrates, was associated with a 17 percent increase in the risk of coronary disease (relative risk, 1.17; 95 percent confidence interval, 0.97 to 1.41; P=0.10). As compared with equivalent energy from carbohydrates, the relative risk for a 2 percent increment in energy intake from trans unsaturated fat was 1.93 (95 percent confidence interval, 1.43 to 2.61; P<0.001); that for a 5 percent increment in energy from monounsaturated fat was 0.81 (95 percent confidence interval, 0.65 to 1.00; P=0.05); and that for a 5 percent increment in energy from polyunsaturated fat was 0.62 (95 percent confidence interval, 0.46 to 0.85; P= 0.003). Total fat intake was not signficantly related to the risk of coronary disease (for a 5 percent increase in energy from fat, the relative risk was 1.02; 95 percent confidence interval, 0.97 to 1.07; P=0.55). We estimated that the replacement of 5 percent of energy from saturated fat with energy from unsaturated fats would reduce risk by 42 percent (95 percent confidence interval, 23 to 56; P<0.001) and that the replacement of 2 percent of energy from trans fat with energy from unhydrogenated, unsaturated fats would reduce risk by 53 percent (95 percent confidence interval, 34 to 67; P<.001). CONCLUSIONS: Our findings suggest that replacing saturated and trans unsaturated fats with unhydrogenated monounsaturated and polyunsaturated fats is more effective in preventing coronary heart disease in women than reducing overall fat intake.

nnt.asp reference: Updated New Zealand cardiovascular disease risk-benefit prediction guide. Jackson R. Bmj 2000:320(7236);709-10. [Medline]

chapter3.asp reference: Removing bias in surgical trials. Johnson AG and Dixon JM. British Medical Journal 1997:314(7085);916-7. Abstract not available.

irb.asp reference: . Jonas H. Accessed on

diagnostic.asp reference: Inferences for likelihood ratios in the absence of a "gold standard". Joseph L and Gyorkos T. Medical Decision Making 1996:16(4);412-17. ABSTRACT: Likelihood ratios are extensively used to evaluate the performances of diagnostic tests and to update prior odds of disease to posttest odds. Since few tests are truly 100% accurate, including many used as "gold standards," it is important to be able to estimate likelihood ratios in cases where no such standard is available. In this paper, methods to calculate point and interval estimates for likelihood ratios are described. The results numerically coincide with those reviewed by Centor when a "gold standard" is assumed available, but typically provide wider interval estimates when such a standard is not available, reflecting the increased uncertainty inherent in such situations. Unlike previous techniques, the methods do not require normal approximations or logarithmic transformations, and hence provide accurate estimates even when parameter distributions are highly skewed. The methods are illustrated using the results of two different diagnostic tests for the presence of an intestinal parasitic infection.

diagnostic.asp reference: The value of clock drawing in identifying executive cognitive dysfunction in people with a normal Mini-Mental State Examination score. Juby A, Tench S and Baker V. Cmaj 2002:167(8);859-64. BACKGROUND: Executive cognitive dysfunction can precede the memory disturbances of dementia. People with executive cognitive dysfunction can have a normal Mini-Mental State Examination (MMSE) score but still have severe functional limitations. We evaluated the usefulness of clock drawing in identifying people with executive dysfunction who have a normal MMSE score. METHODS: We reviewed the charts of consecutive patients referred between July 1999 and June 2000 to a multidisciplinary geriatric assessment clinic because of concerns about functional inabilities. The patients had all undergone the Executive Interview for the diagnosis of executive cognitive dysfunction as well as an MMSE and clock-drawing test (scored by 2 methods: one described by Watson and colleagues [the Watson method] and one described by Sunderland and colleagues [the Sunderland method]). RESULTS: We reviewed the charts of 68 patients (40 women, 28 men); their mean age was 79 years (range 55-94). Thirty-six patients had an MMSE score of less than 24, and 32 had a "normal" MMSE score (24-30). Among those with a normal MMSE score, 22 had an abnormal Executive Interview score. Using the Executive Interview as the gold standard, the sensitivity and specificity of the Watson method of scoring clock drawings to predict an abnormal Executive Interview score were 59% and 70% respectively; the corresponding values were 18% and 100% for the Sunderland method. INTERPRETATION: The presence of an abnormal MMSE score alerts clinicians to the possibility of cognitive impairment. For patients referred for geriatric assessment who have a normal MMSE score, a clock-drawing test, scored by either the Watson or the Sunderland method, is a moderately sensitive and specific adjunct for detecting executive cognitive dysfunction. [Medline]

chapter5.asp reference: Maternal nutrition, pregnancy outcome and public health policy. Kramer MS. Cmaj 1998:159(6);663-5. [Medline]

poisson.asp reference: A more powerful test for comparing two Poisson means. Krishnamoorthy K and Thomson J. Accessed on

diagnostic.asp reference: Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection. Lachs MS, Nachamkin I, Edelstein PH, Goldman J, Feinstein AR and Schwartz JS. Ann Intern Med 1992:117(2);135-40. OBJECTIVE: To determine if the leukocyte esterase and bacterial nitrite rapid dipstick test for urinary tract infection (UTI) is susceptible to spectrum bias (when a diagnostic test has different sensitivities or specificities in patients with different clinical manifestations of the disease for which the test is intended). DESIGN: Cross-sectional study. PATIENTS: A total of 366 consecutive adult patients in whom clinicians performed urinalysis to diagnose or exclude UTI. SETTING: An urban emergency department and walk-in clinic. MEASUREMENTS: After the patient encounter, but before dipstick test or culture was done, clinicians recorded the signs and symptoms that were the basis for suspecting UTI and for performing a urinalysis and an estimate of the probability of UTI based on the clinical evaluation. For all patients who received urinalysis, dipstick tests and culture were done in the clinical microbiology laboratory by medical technologists blinded to clinical evaluation. Sensitivity for the dipstick was calculated using a positive result in either leukocyte esterase or bacterial nitrite, or both, as the criterion for a positive dipstick, and greater than 10(5) CFU/mL for a positive culture. RESULTS: In the 107 patients with a high (greater than 50%) prior probability of UTI, who had many characteristic UTI symptoms, the sensitivity of the test was excellent (0.92; 95% CI, 0.82 to 0.98). In the 259 patients with a low (less than or equal to 50%) prior probability of UTI, the sensitivity of the test was poor (0.56; CI, 0.03 to 0.79). CONCLUSIONS: The leukocyte esterase and bacterial nitrite dipstick test for UTI is susceptible to spectrum bias, which may be responsible for differences in the test's sensitivity reported in previous studies. As a more general principle, diagnostic tests may have different sensitivities or specificities in different parts of the clinical spectrum of the disease they purport to identify or exclude, but studies evaluating such tests rarely report sensitivity and specificity in subgroups defined by clinical symptoms. When diagnostic tests are evaluated, information about symptoms in the patients recruited for study should be included, and analyses should be done within appropriate clinical subgroups so that clinicians may decide if reported sensitivities and specificities are applicable to their patients. [Medline]

diagnostic.asp reference: When statistics provide unsatisfying answers: revisiting the breast self-examination controversy. Lerner BH. Cmaj 2002:166(2);199-201. [Medline]

diagnostic.asp reference: Validation of the Cardiovascular Limitations and Symptoms Profile (CLASP) in chronic stable angina. Lewin RJ, Thompson DR, Martin CR, Stuckey N, Devlen J, Michaelson S and Maguire P. J Cardiopulm Rehabil 2002:22(3);184-91. PURPOSE: This study aimed to establish the reliability, validity, and sensitivity of the Cardiovascular Limitations and Symptoms Profile (CLASP) in a group of patients with chronic stable angina. METHODS: After 226 patients with angina had been recruited, they were randomly allocated to one of three groups: a 10-week hospital-based angina management program (n = 75; men = 56; age = 60 +/- 8 years), routine care (n = 74; men = 52; age = 61 +/- 7 years), and exercise therapy (n = 77; men = 60; age = 60 +/- 7 years). All the patients were assessed with CLASP on two occasions: at baseline and at 10 weeks. The Sickness Impact Profile (SIP), the Hospital Anxiety and Depression Scale (HADS), and the Sleep Problems Questionnaire (SPQ) also were administered at the same time. RESULTS: Significant positive correlations between the actual number of angina episodes and the CLASP angina subscale scores (r =.60, P <.001) were observed. The CLASP subscale scores for shortness of breath (r = -.36; P <.001) and ankle swelling (r = -.24; P <.001) were significantly correlated with the total treadmill time. The CLASP tiredness subscale score showed a significant positive correlation with the SPQ score (r =.48; P <.001). The CLASP subscale scores were significantly correlated with their corresponding SIP subscale scores: the tiredness score with the sleep and rest score (r =.49; P <.001), the social and leisure score with the recreation and pastimes score (r =.41; P <.001), the home score with the home management score (r =.45; P <.001), and the mobility score with the mobility (r =.37; P <.001) and total treadmill time scores (r = -.49; P <.001). CONCLUSIONS: The findings show CLASP to be a reliable, valid, sensitive measure of health-related quality of life in patients with chronic stable angina. Before it can be recommended for all patients with heart disorders, similar data will be required from other diagnostic groups such as patients with heart failure or those who have sustained an acute myocardial infarction. [Medline]

ethics.asp reference chapter2.asp reference: Premature discontinuation of clinical trial for reasons not related to efficacy, safety, or feasibility Commentary: Early discontinuation violates Helsinki principles. Lievre M, Menard J, Bruckert E, Cogneau J, Delahaye F, Giral P, Leitersdorf E, Luc G, Masana L, Moulin P, Passa P, Pouchain D, Siest G and Boyd K. BMJ 2001:322(7286);603-606. Abstract not available yet.

microarray.asp reference: Improved statistical inference from DNA microarray data using analysis of variance and a Bayesian statistical framework. Analysis of global gene expression in Escherichia coli K12. Long AD, Mangalam HJ, Chan BY, Tolleri L, Hatfield GW and Baldi P. J Biol Chem 2001:276(23);19937-44. We describe statistical methods based on the t test that can be conveniently used on high density array data to test for statistically significant differences between treatments. These t tests employ either the observed variance among replicates within treatments or a Bayesian estimate of the variance among replicates within treatments based on a prior estimate obtained from a local estimate of the standard deviation. The Bayesian prior allows statistical inference to be made from microarray data even when experiments are only replicated at nominal levels. We apply these new statistical tests to a data set that examined differential gene expression patterns in IHF(+) and IHF(-) Escherichia coli cells (Arfin, S. M., Long, A. D., Ito, E. T., Tolleri, L., Riehle, M. M., Paegle, E. S., and Hatfield, G. W. (2000) J. Biol. Chem. 275, 29672-29684). These analyses identify a more biologically reasonable set of candidate genes than those identified using statistical tests not incorporating a Bayesian prior. We also show that statistical tests based on analysis of variance and a Bayesian prior identify genes that are up- or down-regulated following an experimental manipulation more reliably than approaches based only on a t test or fold change. All the described tests are implemented in a simple-to-use web interface called Cyber-T that is located on the University of California at Irvine genomics web site. [Medline] [Abstract] [Full text] [PDF]

oddsratio.asp reference: Male Pattern Baldness and Coronary Heart Disease: The Physician's Health Study. Lotufo PA. Archives of Internal Medicine 2000:160(165-171. Abstract not available yet.

lognormal.asp reference: Specialists in Strategic and Project Risk Management: Lognormal Distribution Summary. Ltd BCIP. Accessed on 1999.

diagnostic.asp reference: The SCOFF questionnaire and clinical interview for eating disorders in general practice: comparative study. Luck AJ, Morgan JF, Reid F, O'Brien A, Brunton J, Price C, Perry L and Lacey JH. British Medical Journal 2002:325(7367);755-6. [Medline]

autism.asp reference: A population-based study of measles, mumps, and rubella vaccination and autism. Madsen KM, Hviid A, Vestergaard M, Schendel D, Wohlfahrt J, Thorsen P, Olsen J and Melbye M. New England Journal of Medicine 2002:347(19);1477-82. BACKGROUND: It has been suggested that vaccination against measles, mumps, and rubella (MMR) is a cause of autism. METHODS: We conducted a retrospective cohort study of all children born in Denmark from January 1991 through December 1998. The cohort was selected on the basis of data from the Danish Civil Registration System, which assigns a unique identification number to every live-born infant and new resident in Denmark. MMR-vaccination status was obtained from the Danish National Board of Health. Information on the children's autism status was obtained from the Danish Psychiatric Central Register, which contains information on all diagnoses received by patients in psychiatric hospitals and outpatient clinics in Denmark. We obtained information on potential confounders from the Danish Medical Birth Registry, the National Hospital Registry, and Statistics Denmark. RESULTS: Of the 537,303 children in the cohort (representing 2,129,864 person-years), 440,655 (82.0 percent) had received the MMR vaccine. We identified 316 children with a diagnosis of autistic disorder and 422 with a diagnosis of other autistic-spectrum disorders. After adjustment for potential confounders, the relative risk of autistic disorder in the group of vaccinated children, as compared with the unvaccinated group, was 0.92 (95 percent confidence interval, 0.68 to 1.24), and the relative risk of another autistic-spectrum disorder was 0.83 (95 percent confidence interval, 0.65 to 1.07). There was no association between the age at the time of vaccination, the time since vaccination, or the date of vaccination and the development of autistic disorder. CONCLUSIONS: This study provides strong evidence against the hypothesis that MMR vaccination causes autism. [Medline]

chapter1.asp reference: Removal of radiation dose response effects: an example of over-matching. Marsh JL, Hutton JL and Binks K. Bmj 2002:325(7359);327-30. [Medline]

chapter1.asp reference: Evaluating complementary medicine: methodological challenges of randomised controlled trials. Mason S, Tovey P and Long AF. Bmj 2002:325(7368);832-4. [Medline]

diagnostic.asp reference: Why we need large, simple studies of the clinical examination: the problem and a proposed solution. CARE-COAD1 group. Clinical Assessment of the Reliability of the Examination-Chronic Obstructive Airways Disease Group. McAlister FA, Straus SE and Sackett DL. Lancet 1999:354(9191);1721-4. Abstract not available yet. [Medline]

diagnostic.asp reference: A clinical score to reduce unnecessary antibiotic use in patients with sore throat. McIsaac WJ, White D, Tannenbaum D and Low DE. Cmaj 1998:158(1);75-83. OBJECTIVE: To validate a score based on clinical symptoms and signs for the identification of group A Streptococcus (GAS) infection in general practice patients with score throat. DESIGN: A single throat swab was used as the gold standard for diagnosing GAS infection. Clinical information was recorded by experienced family physicians on standardized encounter forms. Score criteria were identified by means of logistic regression modelling of data from patients enrolled in the first half of the study. The score was then validated among the remaining patients. SETTING: University-affiliated family medicine centre in Toronto. PATIENTS: A total of 521 patients aged 3 to 76 years presenting with a new upper respiratory tract infection from December 1995 to February 1997. OUTCOME MEASURES: Sensitivity, specificity and likelihood ratios for identification of GAS infection with the score approach compared with throat culture. Proportion of patients prescribed antibiotics, throat culture use, and sensitivity and specificity with usual physician care and with score-based recommendations were compared. RESULTS: A score was developed ranging in value from 0 to 4. The sensitivity of the score for identifying GAS infection was 83.1%, compared with 69.4% for usual physician care (p = 0.06); the specificity values of the 2 approaches were similar. Among patients aged 3 to 14 years, the sensitivity of the score approach was higher than that of usual physician care (96.9% v. 70.6%) (p < 0.05). The proportion of patients receiving initial antibiotic prescriptions would have been reduced 48% by following score-based recommendations compared with observed physician prescribing (p < 0.001), without any increase in throat culture use. CONCLUSIONS: An age-appropriate sore throat score identified GAS infection in children and adults with sore throat better than usual care by family physicians, with significant reductions in unnecessary prescribing of antibiotics. A randomized trial comparing the 2 approaches is recommended to determine the ability of the score approach to reduce unnecessary prescribing of antibiotics during routine clinical encounters.

Study Suggests Mercury in Vaccine was Not Harmful. McNeil DG, Jr. 2002. autism.asp reference

chapter2.asp reference: Randomised controlled trial of cardiotocography versus Doppler auscultation of fetal heart at admission in labour in low risk obstetric population. Mires G, Williams F and Howie P. British Medical Journal 2001:322(7300);p1457-60; discussion 1460-2. OBJECTIVE: To compare the effect of admission cardiotocography and Doppler auscultation of the fetal heart on neonatal outcome and levels of obstetric intervention in a low risk obstetric population. DESIGN: Randomised controlled trial. SETTING: Obstetric unit of teaching hospital PARTICIPANTS: Pregnant women who had no obstetric complications that warranted continuous monitoring of fetal heart rate in labour. INTERVENTION: Women were randomised to receive either cardiotocography or Doppler auscultation of the fetal heart when they were admitted in spontaneous uncomplicated labour. MAIN OUTCOME MEASURES: The primary outcome measure was umbilical arterial metabolic acidosis. Secondary outcome measures included other measures of condition at birth and obstetric intervention. RESULTS: There were no significant differences in the incidence of metabolic acidosis or any other measure of neonatal outcome among women who remained at low risk when they were admitted in labour. However, compared with women who received Doppler auscultation, women who had admission cardiotocography were significantly more likely to have continuous fetal heart rate monitoring in labour (odds ratio 1.49, 95% confidence interval 1.26 to 1.76), augmentation of labour (1.26, 1.02 to 1.56), epidural analgesia (1.33, 1.10 to 1.61), and operative delivery (1.36, 1.12 to 1.65). CONCLUSIONS: Compared with Doppler auscultation of the fetal heart, admission cardiotocography does not benefit neonatal outcome in low risk women. Its use results in increased obstetric intervention, including operative delivery.

chapter7.asp reference: Potential solutions to the problem of conducting systematic reviews of new health technologies. Moher D and Schachter HM. Cmaj 2002:166(13);1674-5. [Medline]

diagnostic.asp reference: Screening of newborn infants for cholestatic hepatobiliary disease with tandem mass spectrometry. Mushtaq I, Logan S, Morris M, Johnson AW, Wade AM, Kelly D and Clayton PT. Bmj 1999:319(7208);471-7. OBJECTIVE: To assess the feasibility of screening for cholestatic hepatobiliary disease and extrahepatic biliary atresia by using tandem mass spectrometry to measure conjugated bile acids in dried blood spots obtained from newborn infants at 7-10 days of age for the Guthrie test. SETTING: Three tertiary referral clinics and regional neonatal screening laboratories. DESIGN: Unused blood spots from the Guthrie test were retrieved for infants presenting with cholestatic hepatobiliary disease and from the two cards stored on either side of each card from an index child. Concentrations of conjugated bile acids measured by tandem mass spectrometry in the two groups were compared. MAIN OUTCOME MEASURES: Concentrations of glycodihydroxycholanoates, glycotrihydroxycholanoates, taurodihydroxycholanoates, and taurotrihydroxycholanoates. Receiver operator curves were plotted to determine which parameter (or combination of parameters) would best predict the cases of cholestatic hepatobiliary disease and extrahepatic biliary atresia. The sensitivity and specificity at a selection of cut off values for each bile acid species and for total bile acid concentrations for the detection of the two conditions were calculated. RESULTS: 218 children with cholestatic hepatobiliary disease were eligible for inclusion in the study. Two children without a final diagnosis and five who presented at <14 days of age were excluded. Usable blood spots were obtained from 177 index children and 708 comparison children. Mean concentrations of all four bile acid species were significantly raised in children with cholestatic hepatobiliary disease and extrahepatic biliary atresia compared with the unaffected children (P<0.0001). Of 177 children with cholestatic hepatobiliary disease, 104 (59%) had a total bile acid concentration >33 micromol/l (97.5th centile value for comparison group). Of the 61 with extrahepatic biliary atresia, 47 (77%) had total bile acid concentrations >33 micromol/l. Taurotrihydroxycholanoate and total bile acid concentrations were the best predictors of both conditions. For all cholestatic hepatobiliary disease, a cut off level of total bile acid concentration of 30 micromol/l gave a sensitivity of 62% and a specificity of 96%, while the corresponding values for extrahepatic biliary atresia were 79% and 96%. CONCLUSION: Most children who present with extrahepatic biliary atresia and other forms of cholestatic hepatobiliary disease have significantly raised concentrations of conjugated bile acids as measured by tandem mass spectrometry at the time when samples are taken for the Guthrie test. Unfortunately the separation between the concentrations in these infants and those in the general population is not sufficient to make mass screening for cholestatic hepatobiliary disease a feasible option with this method alone. [Medline]

microarray.asp reference: Empirical characterization of the expression ratio noise structure in high-density oligonucleotide arrays. Naef F, Hacker CR, Patil N and Magnasco M. Genome Biol 2002:3(4);RESEARCH0018. BACKGROUND: High-density oligonucleotide arrays (HDONAs) are a powerful tool for assessing differential mRNA expression levels. To establish the statistical significance of an observed change in expression, one must take into account the noise introduced by the enzymatic and hybridization steps, called type I noise. We undertake an empirical characterization of the experimental repeatability of results by carrying out statistical analysis of a large number of duplicate HDONA experiments. RESULTS: We assign scoring functions for expression ratios and associated quality measures. Both the perfect-match (PM) probes and the differentials between PM and single-mismatch (MM) probes are considered as raw intensities. We then calculate the log-ratio of the noise structure using robust estimates of their intensity-dependent variance. The noise structure in the log-ratios follows a local log-normal distribution in both the PM and PM-MM cases. Significance relative to the type I noise can therefore be quantified reliably using the local standard deviation (SD). We discuss the intensity dependence of the SD and show that ratio scores greater than 1.25 are significant in the mid- to high-intensity range. CONCLUSIONS: The noise inherent in HDONAs is characteristically dependent on intensity and can be well described in terms of local normalization of log-ratio distributions. Therefore, robust estimates of the local SD of these distributions provide a simple and powerful way to assess significance (relative to type I noise) in differential gene expression, and will be helpful in practice for improving the reliability of predictions from hybridization experiments. [Medline] [Abstract] [Full text] [PDF]

chapter3.asp reference: Research into complementary and alternative medicine: problems and potential. Nahin RL and Straus SE. British Medical Journal 2001:322(7279);p161-4. Abstract not available.

oddsratio.asp reference: Measured enthusiasm: does the method of reporting trials results alter perceptions of therapeutic effectiveness? Naylor C, Chen E and Strauss B. American College of Physicians 1992:117(11);916-21. ABSTRACT: OBJECTIVE: To compare clinicians' ratings of therapeutic effectiveness when different trial end points were presented as percent reductions in relative compared with absolute risk and as numbers of patients treated to avoid one adverse outcome. DESIGN: Survey, with random allocation of two questionnaires. SETTING: Toronto teaching hospitals. RESPONDENTS: Convenience sample of 100 faculty and housestaff in internal medicine and family medicine. INTERVENTION: One questionnaire presented results for three end points of the Helsinki Heart Study as separate drug trials using only absolute differences in events; the other showed the same end points as relative differences. Both questionnaires included a fourth "trial," showing person-years of treatment needed to prevent one myocardial infarction. MAIN OUTCOME MEASURE: The "trials" were each rated on an 11-point scale, from treatment "harmful" to "very effective." RESULTS: Respondents' ratings of effectiveness varied with the end point. Controlling for end point, ratings of effectiveness by the 50 participants receiving absolute event data were lower than those by 50 participants responding to relative risk reductions (P < 0.001); however, no end-point difference was more than 0.6 scale points. For a "trial" reporting that 77 persons were treated for 5 years to prevent one myocardial infarction, mean ratings were 2.3 or 1.8 scale points lower, respectively (both P < 0.001), than when the same data were shown as relative or absolute risk reductions. CONCLUSIONS: Clinicians' views of drug therapies are affected by the common use of relative risk reductions in both trial reports and advertisements, by end-point emphasis, and, above all, by underuse of summary measures that relate treatment burden to therapeutic yields in a clinically relevant manner.

chapter3.asp reference: An addition to the controversy on sunlight exposure and melanoma risk: a meta-analytical approach. Nelemans PJ, Rampen FH, Ruiter DJ and Verbeek AL. J Clin Epidemiol 1995:48(11);1331-42. Case control studies on the association between sunlight exposure and melanoma risk show considerable differences in design; this could be responsible for the variation in study results. In an attempt to resolve the controversy between study results, the results of 25 publications on case control studies were evaluated using meta-analytical techniques. Comparison of odds ratios between subgroups of studies revealed that the range of odds ratios was far greater for hospital-based studies than for population-based studies. For the latter type of studies, the odds ratios were homogeneous and the pooled odds ratios were 1.57 (95% confidence interval [CI], 1.29-1.91) for intermittent sunlight exposure and 0.73 (95% CI, 0.60-0.89) for chronic exposure. However, among other problems, the lack of standardized measures for sunlight exposure warrants cautious interpretation of these results. It is concluded that evidence to support the intermittent sunlight theory is still far from complete.

chapter3.asp reference: The impact of blinding on the results of a randomized, placebo-controlled multiple sclerosis clinical trial. Noseworthy JH, Ebers GC, Vandervoort MK, Farquhar RE, Yetisir E and Roberts R. Neurology 1994:44(1);p16-20. In the randomized, placebo-controlled, physician-blinded Canadian cooperative trial of cyclophosphamide and plasma exchange, neither active treatment regimens (group I: i.v. cyclophosphamide and prednisone; group II: weekly plasma exchange, oral cyclophosphamide, and prednisone) were superior to placebo (group III: sham plasma exchange and placebo medications) using the blinded, evaluating neurologists' assessments of disease course (primary analysis). All patients were examined by both a blinded and an unblinded neurologist at each assessment in this trial. We compared the blinded and unblinded neurologists' judgment of treatment response and analyzed the clinical behavior of patients who correctly guessed their treatment. The unblinded (but not the blinded) neurologists' scores demonstrated an apparent treatment benefit at 6, 12, and 24 months for the group II patients (not group I or placebo; p < 0.05, two-tailed). There were no significant differences in the time to treatment failure or in the proportions of patients improved, stable, or worse between the group II and group III patients who correctly guessed their treatment assignments and those who did not. Physician blinding prevented an erroneous conclusion about treatment efficacy (false positive, type 1 error).

pilot.asp reference: The Carotene and Retinol Efficacy Trial (CARET) to Prevent Lung Cancer in High-Risk Populations: Pilot Study with Abestos-exposed Workers. Omenn GS. Cancer Epidemiology, Biomarkers & Prevention 1993:2(4);381-387. ABSTRACT: Pilot studies are an essential component for major chemoprevention trials. Prior to initiating the multicenter Carotene and Retinol Efficacy Trial to assess the effectiveness of beta-carotene and retinol for preventing lung cancer, we conducted pilot studies in Seattle between 1985 and 1988 in two high risk populations: current and former heavy smokers and asbestos-exposed workers. The Asbestos Workers Pilot Study for the Carotene and Retinol Efficacy Trial demonstrated that recruitment of asbestos-exposed participants with relevant risk factors was feasible from identified sources. We documented negligible toxicity and high adherence with the protocol, schedule, and intervention. Results from the pilot led to extension of the placebo run-in period, changes in the eligibility criteria, improvements in recruitment strategies and scheduling, elimination of stratification by risk factors in randomization, modifications of study vitamin dosage and of side effects monitoring, and refinement of trial design parameters for Carotene and Retinol Efficacy Trial. The Smokers Pilot is reported in the accompanying article (G. E. Goodman et al., Cancer Epidemiol., Biomarkers & Prev., 2: 389-396, 1993).

chapter1.asp reference: New insights into the physiology and pharmacology of vitamin C. Padayatty SJ and Levine M. Cmaj 2001:164(3);353-5. [Medline]

autism.asp reference: Serious adverse events after measles-mumps-rubella vaccination during a fourteen-year prospective follow-up. Patja A, Davidkin I, Kurki T, Kallio MJ, Valle M and Peltola H. Pediatr Infect Dis J 2000:19(12);1127-34. BACKGROUND: Several disorders have been attributed to measles-mumps-rubella (MMR) vaccination during the past decade. The aim of this prospective follow-up study was to identify serious adverse events causally related to MMR vaccination. METHODS: When the MMR vaccination program was launched in Finland in 1982, a countrywide surveillance system was set up to detect serious adverse events associated with MMR. To obtain detailed case histories vaccinees' clinical charts were reviewed. Serum samples were analyzed to trace concurrent infections. SETTING: All hospitals and health centers in Finland from 1982 through 1996. RESULTS: Immunization of 1.8 million individuals and consumption of almost 3 million vaccine doses by the end of 1996 gave rise to 173 potentially serious reactions claimed to have been caused by MMR vaccination. In all, 77 neurologic, 73 allergic and 22 miscellaneous reactions and 1 death were reported, febrile seizure being the most common event. However, 45% of these events proved to be probably caused or contributed by some other factor, giving an incidence of serious adverse events with possible or indeterminate causal relation with MMR vaccination of 5.3 per 100,000 vaccinees or 3.2 per 100,000 vaccine doses. CONCLUSIONS: Causality between immunization and a subsequent untoward event cannot be estimated solely on the basis of a temporal relation. Comprehensive analysis of the reported adverse reactions established that serious events causally related to MMR vaccine are rare and greatly outweighed by the risks of natural MMR diseases. [Medline]

diagnostic.asp reference: Iron deficiency anemia in the elderly: the diagnostic process. Patterson C, Guyatt GH, Singer J, Ali M and Turpie I. Cmaj 1991:144(4);435-40. OBJECTIVE: To determine the effectiveness of physician probability estimates calculated on the basis of findings from history-taking and physical examination in the diagnosis of iron deficiency anemia in elderly patients. DESIGN: Prospective study. SETTING: Two community hospitals offering secondary and tertiary care. PATIENTS: A total of 259 patients over 65 years of age found to have previously undiagnosed anemia. MEASURES: Physician estimates of the likelihood of iron deficiency before (pretest probability) and after (post-test probability) the laboratory test results were available. The hemogram was available to the physicians when they made their pretest probability estimates. Because the serum ferritin level proved to be the most powerful of the laboratory test results studied, the likelihood ratios associated with the post-test estimates were compared with the ratios associated with the serum ferritin level. MAIN RESULTS: The post-test probability estimates were influenced by the serum ferritin level and the pretest estimates. The post-test estimates derived from the findings obtained through history-taking and physical examination and the laboratory test results (including the serum ferritin level) were slightly less accurate in predicting iron deficiency than the serum ferritin level alone. Nevertheless, a model in which the pretest estimates were used in addition to the serum ferritin level to predict iron deficiency proved to be more powerful than the serum ferritin level alone (p = 0.006). This indicated that the limitations of the post-test estimates were due to a misinterpretation of the serum ferritin level and that the findings from history-taking and physical examination added important diagnostic information. CONCLUSIONS: Physicians must be aware of test properties to provide optimal care to their patients. If test results are properly interpreted, pretest probabilities derived from findings obtained through history-taking and physical examination can add useful information that will lead to more accurate diagnoses. [Medline]

oddsratio.asp reference: What does the odds ratio estimate in a case-control study? Pearce N. Int J Epidemiol 1993:22(6);1189-92. The use of the term 'odds ratio' in reporting the findings of case-control studies is technically correct, but is often misleading. The meaning of the odds ratio estimates obtained in a case-control study differs according to whether controls are selected from person-time at risk (the study base), persons at risk (the base-population at risk at the beginning of follow-up), or survivors (the population at risk at the end of follow-up). These three methods of control selection correspond to estimating the rate ratio, risk ratio, or the odds ratio respectively, by means of calculating the odds ratio in the subjects actually studied. None of these estimation procedures depends on any rare disease assumption. Where the rare disease assumption is relevant is whether the effect which is estimated (e.g. the odds ratio) is approximately equal to some other effect measure of interest (e.g. the risk ratio or rate ratio) in the underlying study base. To avoid confusion on this issue, authors should be encouraged to not only specify the manner in which controls have been selected (e.g. by density sampling) but also the corresponding effect measure which is being estimated (e.g. the rate ratio) by the 'odds ratio' which is obtained in a case-control analysis.

chapter7.asp reference: Systematic reviews from astronomy to zoology: myths and misconceptions. Petticrew M. Bmj 2001:322(7278);98-101. [Medline]

chapter2.asp reference: Celstial determinants of success in research. Pollex R, Hegele B and Ban MR. Cmaj 2001:165(12);1584. Abstract not available.

diagnostic.asp reference: The likelihood ratio. An improved measure for reporting and evaluating diagnostic test results. Radack KL, Rouan G and Hedges J. Arch Pathol Lab Med 1986:110(8);689-93. The principles and use of likelihood ratios are presented as an aid to the reporting and interpretation of diagnostic data. Likelihood ratios can be determined for multiple levels of test results and provide a readily comprehensible and convenient measure for computing the posttest probability of disease. Unlike sensitivity and specificity, they convey an immediate and direct description of a test's ability to revise the initial probability of disease upward or downward. By incorporating all the raw data, the use of likelihood ratios can improve the assessment of the clinical utility of test results. Their application to the diagnostic performance of serum creatine kinase concentrations in predicting patients with suspected myocardial infarction is discussed.

diagnostic.asp reference: Accuracy of Diagnostic Tests. Rapid-diagnostic.org. Accessed on 2002.

mixed.asp reference: . Report T. Accessed on 2002.

diagnostic.asp reference: Experience colonoscopists missed 24% of adenomas. Rex D, Cutler C and Lemmel GT ea. ACP Journal Club 1997:127(1);16. Abstract not available.

diagnostic.asp reference: Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Rex DK, Cutler CS, Lemmel GT, Rahmani EY, Clark DW, Helper DJ, Lehman GA and Mark DG. Gastroenterology 1997:112(1);24-8. BACKGROUND & AIMS: The miss rate of colonoscopy for neoplasms is poorly understood. The aim of this study was to determine the miss rate of colonoscopy by same day back-to-back colonoscopy. METHODS: Two consecutive same day colonoscopies were performed in 183 patients. The patients were randomized to undergo the second colonoscopy by the same or a different endoscopist and in the same or different position. RESULTS: The overall miss rate for adenomas was 24%, 27% for adenomas < or = 5 mm, 13% for adenomas 6-9 mm, and 6% for adenomas > or = 1 cm. Patients with two or more adenomas at the first examination were more likely than patients with no or one adenoma detected at the first examination to have one or more adenomas at the second examination (odds ratio, 3.3; 95% confidence interval, 1.69-6.46). Right colon adenomas were missed more often (27%) than left colon adenomas (21%), but the difference was not significant. There was evidence of variation in sensitivity between endoscopists, but significant miss rates for small adenomas were found among essentially all endoscopists. CONCLUSIONS: Using current colonoscopic technology, there are significant miss rates for adenomas < 1 cm even with meticulous colonoscopy. Miss rates are low for adenomas > or = 1 cm. The results suggest the need for improvements in colonoscopic technology. [Medline]

chapter2.asp reference: . Robinson DaC. Accessed on 2002.

chapter1.asp reference: Observational Studies. Rosenbaum P (1995) New York: Springer-Verlag.

chapter1.asp reference: Evidence-based medicine and treatment choices. Sackett DL. Lancet 1997:349(9051);570; discussion 572-3. Abstract not available yet. [Medline]

diagnostic.asp reference: Do Japanese statistics on gastric carcinoma need to be revised? Sakamoto J and Yasue M. Lancet 1997:349(9067);1711-2. Abstract not available yet. [Medline]

diagnostic.asp reference: Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy. Salkind AR, Cuddy PG and Foxworth JW. Jama 2001:285(19);p2498-505. CONTEXT: Clinicians frequently withhold antibiotics that contain penicillin based on patients' self-reported clinical history of an adverse reaction to penicillin and the clinicians' own misunderstandings about the characteristics of a true penicillin allergy. OBJECTIVES: To determine the likelihood of true penicillin allergy with consideration of clinical history and to evaluate the diagnostic value added by appropriate skin testing. DATA SOURCES: MEDLINE was searched for relevant English-language articles dated 1966 to October 2000. Bibliographies were searched to identify additional articles. STUDY SELECTION: We included original studies describing the precision of skin testing in diagnosis of penicillin allergy. We excluded studies that did not use both minor and major determinants, provide an explicit definition of penicillin allergy, or list the specific criteria necessary for a positive skin test result. Fourteen studies met the inclusion criteria. DATA EXTRACTION: Three authors independently reviewed and abstracted data from all articles and reached consensus about any discrepancies. DATA SYNTHESIS: Patients' self-reported history has low accuracy for diagnosis of true penicillin allergy. By evaluating studies comparing clinical history to the skin test for penicillin allergy among patients with and without a positive history for penicillin allergy, positive and negative likelihood ratios were calculated. History of penicillin allergy had a positive likelihood ratio of 1.9 (95% confidence interval [CI], 1.5-2.5), while absence of history of penicillin allergy had a negative likelihood ratio of 0.5 (95% CI, 0.4-0.6). CONCLUSIONS: Only 10% to 20% of patients reporting a history of penicillin allergy are truly allergic when assessed by skin testing. Taking a detailed history of a patient's reaction to penicillin may allow clinicians to exclude true penicillin allergy, allowing these patients to receive penicillin. Patients with a concerning history of type I penicillin allergy who have a compelling need for a drug containing penicillin should undergo skin testing. Virtually all patients with a negative skin test result can take penicillin without serious sequelae.

chapter3.asp reference: Inconsistencies and Errors in Alternative Medicine Research. Sampson W. Skeptical Inquirer 1997:21(5);35-38. Abstract not available yet.

qualitative.asp reference: Ethnography and health care. Savage J. Bmj 2000:321(7273);1400-2. [Medline]

diagnostic.asp reference: Differences in diagnostic criteria for gastric carcinoma between Japanese and western pathologists. Schlemper RJ, Itabashi M, Kato Y, Lewin KJ, Riddell RH, Shimoda T, Sipponen P, Stolte M, Watanabe H, Takahashi H and Fujita R. Lancet 1997:349(9067);1725-9. BACKGROUND: There have been many studies on gastric carcinoma in populations with contrasting cancer risks. We aimed to find out whether the criteria for the histological diagnosis of early gastric carcinoma were comparable in Western countries and Japan. METHODS: Eight pathologists from Japan, North America, and Europe individually reviewed 35 microscope slides: 17 gastric biopsy samples and 18 endoscopic mucosal resections taken from 17 Japanese patients with lesions ranging from early gastric cancer to adenoma, dysplasia, and reactive atypia. The pathologists were given a list of pathological criteria and a form on which they were asked to indicate the criteria on which they based each diagnosis. FINDINGS: For seven slides most Western pathologists diagnosed low-grade adenoma/dysplasia, whereas the Japanese diagnosed definite carcinoma in four slides, suspected carcinoma in one, and adenoma in only two. Of 12 slides with high-grade adenoma/dysplasia according to most Western pathologists the Japanese gave the diagnosis of definite carcinoma in 11 and suspected in one. Of six slides showing high-grade adenoma/dysplasia with suspected carcinoma according to most Western pathologists the Japanese diagnosed definite carcinoma in all. There were no major differences in the diagnoses of three slides showing reactive epithelium and seven slides with clearly invasive carcinoma. When the opinion of the majority of the pathologists was taken as the final diagnosis there was agreement between Western and japanese in 11 of the 35 slides (kappa coefficient 0.15 [95% CI 0.01-0.29]). Presence of invasion was the most important diagnostic criterion for most Western pathologists whereas for the Japanese nuclear features and glandular structures were more important. INTERPRETATION: In Japan, gastric carcinoma is diagnosed on nuclear and structural criteria even when invasion is absent according to the Western viewpoint. This diagnostic practice results in almost no discrepancy between the diagnosis of a superficial biopsy sample and that of the final resection specimen. This may also contribute to the relatively high incidence and good prognosis of gastric carcinoma in Japan when compared with Western countries. [Medline]

diagnostic.asp reference: Effect of faecal occult blood screening on mortality from colorectal cancer: results from a randomised controlled trial. Scholefield JH, Moss S, Sufi F, Mangham CM and Hardcastle JD. Gut 2002:50(6);840-844. Background: Three large randomised trials have shown that screening for colorectal cancer using faecal occult blood (FOB) tests can reduce the mortality from this disease. Two national pilot studies have recently been launched in the UK to investigate the feasibility of population screening for colorectal cancer in the National Health Service. The largest of the randomised trials was conducted in Nottingham and randomised 152 850 individuals between the ages of 45 and 74 years to receive biennial Haemoccult (FOB) test kit (intervention group) or to a control group. Aims: We have compared the mortality in the intervention group compared with the control group. Methods: The 152 850 randomised individuals were followed up through local health records and central flagging (Office for National Statistics) over a median follow up period of 11 years. Results: At a median follow up of 11 years there was a 13% reduction in colorectal cancer mortality (95% confidence interval 3-22%) in the intervention group despite an uptake at first invitation of only approximately 50%. The mortality reduction for those accepting screening was 27%. The reduction in mortality was independent of sex and site of tumour. There was no significant difference in mortality from causes other than colorectal cancer between the intervention and control groups. Conclusions: Although the reduction in colorectal cancer mortality was sustained, further follow up of this population is required to determine whether a significant reduction in the incidence of colorectal cancer will be achieved.

chapter5.asp reference diagnostic.asp reference: Prospective cohort study of routine use of risk assessment scales for prediction of pressure ulcers. Schoonhoven L, Haalboom JR, Bousema MT, Algra A, Grobbee DE, Grypdonck MH and Buskens E. Bmj 2002:325(7368);797. OBJECTIVE: To evaluate whether risk assessment scales can be used to identify patients who are likely to get pressure ulcers. DESIGN: Prospective cohort study. SETTING: Two large hospitals in the Netherlands. PARTICIPANTS: 1229 patients admitted to the surgical, internal, neurological, or geriatric wards between January 1999 and June 2000. MAIN OUTCOME MEASURE: Occurrence of a pressure ulcer of grade 2 or worse while in hospital. RESULTS: 135 patients developed pressure ulcers during four weeks after admission. The weekly incidence of patients with pressure ulcers was 6.2% (95% confidence interval 5.2% to 7.2%). The area under the receiver operating characteristic curve was 0.56 (0.51 to 0.61) for the Norton scale, 0.55 (0.49 to 0.60) for the Braden scale, and 0.61 (0.56 to 0.66) for the Waterlow scale; the areas for the subpopulation, excluding patients who received preventive measures without developing pressure ulcers and excluding surgical patients, were 0.71 (0.65 to 0.77), 0.71 (0.64 to 0.78), and 0.68 (0.61 to 0.74), respectively. In this subpopulation, using the recommended cut-off points, the positive predictive value was 7.0% for the Norton, 7.8% for the Braden, and 5.3% for the Waterlow scale. CONCLUSION: Although risk assessment scales predict the occurrence of pressure ulcers to some extent, routine use of these scales leads to inefficient use of preventive measures. An accurate risk assessment scale based on prospectively gathered data should be developed. [Medline]

chapter3.asp reference: Empirical evidence of bias dimensions of methodological quality associated with estimates of treatment effects in controlled trials. Schulz K, Chalmers I, Hayes R and Altman D. JAMA 1995:273(5);408-12. ABSTRACT: OBJECTIVE--To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects. DESIGN--An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects. DATA SOURCES--Meta-analyses from the Cochrane Pregnancy and Childbirth Database. MAIN OUTCOME MEASURES--The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding. RESULTS--Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P < .001). Odds ratios were exaggerated by 41% for inadequately concealed trials and by 30% for unclearly concealed trials (adjusted for other aspects of quality). Trials in which participants had been excluded after randomization did not yield larger estimates of effects, but that lack of association may be due to incomplete reporting. Trials that were not double-blind also yielded larger estimates of effects (P = .01), with odds ratios being exaggerated by 17%. CONCLUSIONS--This study provides empirical evidence that inadequate methodological approaches in controlled trials, particularly those representing poor allocation concealment, are associated with bias. Readers of trial reports should be wary of these pitfalls, and investigators must improve their design, execution, and reporting of trials.

chapter3.asp reference: Randomised trials, human nature, and reporting guidelines. Schulz KF. Lancet 1996:348(9027);596-8. Abstract not available.

chapter3.asp reference: The Landscape and Lexicon of Blinding in Randomized Trials. Schulz KF, Chalmers I and Altman DG. Annals of Internal Medicine 2002:136(3);254-259. Abstract not available.

chapter3.asp reference: Allocation concealment in randomised trials: defending against deciphering. Schulz KF and Grimes DA. Lancet 2002:359(614-618. Proper randomisation rests on adequate allocation concealment. An allocation concealment process keeps clinicians and participants unaware of upcoming assignments. Without it, even properly developed random allocation sequences can be subverted. Within this concealment process, the crucial unbiased nature of randomised controlled trials collides with their most vexing implementation problems. Proper allocation concealment frequently frustrates clinical inclinations, which annoys those who do the trials. Randomised controlled trials are anathema to clinicians. Many involved with trials will be tempted to decipher assignments, which subverts randomisation. For some implementing a trial, deciphering the allocation scheme might frequently become too great an intellectual challenge to resist. Whether their motives indicate innocent or pernicious intents, such tampering undermines the validity of a trial. Indeed, inadequate allocation concealment leads to exaggerated estimates of treatment effect, on average, but with scope for bias in either direction. Trial investigators will be crafty in any potential efforts to decipher the allocation sequence, so trial designers must be just as clever in their design efforts to prevent deciphering. Investigators must effectively immunise trials against selection and confounding biases with proper allocation concealment. Furthermore, investigators should report baseline comparisons on important prognostic variables. Hypothesis tests of baseline characteristics, however, are superfluous and could be harmful if they lead investigators to suppress reporting any baseline imbalances.

chapter3.asp reference: Blinding in randomised trials: hiding who got what. Schulz KF and Grimes DA. Lancet 2002:359(696-700. Blinding embodies a rich history spanning over two centuries. Most researchers worldwide understand blinding terminology, but confusion lurks beyond a general comprehension. Terms such as single blind, double blind, and triple blind mean different things to different people. Moreover, many medical researchers confuse blinding with allocation concealment. Such confusion indicates misunderstandings of both. The term blinding refers to keeping trial participants, investigators (usually health-care providers), or assessors (those collecting outcome data) unaware of the assigned intervention, so that they will not be influenced by that knowledge. Blinding usually reduces differential assessment of outcomes (information bias), but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment (sometimes called co-intervention). Many investigators and readers naively consider a randomised trial as high quality simply because it is double blind, as if double-blinding is the sine qua non of a randomised controlled trial. Although double blinding (blinding investigators, participants, and outcome assessors) indicates a strong design, trials that are not double blinded should not automatically be deemed inferior. Rather than solely relying on terminology like double blinding, researchers should explicitly state who was blinded, and how. We recommend placing greater credence in results when investigators at least blind outcome assessments, except with objective outcomes, such as death, which leave little room for bias. If investigators properly report their blinding efforts, readers can judge them. Unfortunately, many articles do not contain proper reporting. If an article claims blinding without any accompanying clarification, readers should remain sceptical about its effect on bias reduction.

chapter1.asp reference: Case-control studies: research in reverse. Schulz KF and Grimes DA. Lancet 2002:359(431-434. Epidemiologists benefit greatly from having case-control study designs in their research armamentarium. Case-control studies can yield important scientific findings with relatively little time, money, and effort compared with other study designs. This seemingly quick road to research results entices many newly trained epidemiologists. Indeed, investigators implement case-control studies more frequently than any other analytical epidemiological study. Unfortunately, case-control designs also tend to be more susceptible to biases than other comparative studies. Although easier to do, they are also easier to do wrong. Five main notions guide investigators who do, or readers who assess, case-control studies. First, investigators must explicitly define the criteria for diagnosis of a case and any eligibility criteria used for selection. Second, controls should come from the same population as the cases, and their selection should be independent of the exposures of interest. Third, investigators should blind the data gatherers to the case or control status of participants or, if impossible, at least blind them to the main hypothesis of the study. Fourth, data gatherers need to be thoroughly trained to elicit exposure in a similar manner from cases and controls; they should use memory aids to facilitate and balance recall between cases and controls. Finally, investigators should address confounding in case-control studies, either in the design stage or with analytical techniques. Devotion of meticulous attention to these points enhances the validity of the results and bolsters the reader's confidence in the findings.

chapter3.asp reference: Generation of allocation sequences in randomised trials: chance not choice. Schulz KF and Grimes DA. Lancet 2002:359(515-519. The randomised controlled trial sets the gold standard of clinical research. However, randomisation persists as perhaps the least-understood aspect of a trial. Moreover, anything short of proper randomisation courts selection and confounding biases. Researchers should spurn all systematic, non-random methods of allocation. Trial participants should be assigned to comparison groups based on a random process. Simple (unrestricted) randomisation, analogous to repeated fair coin-tossing, is the most basic of sequence generation approaches. Furthermore, no other approach, irrespective of its complexity and sophistication, surpasses simple randomisation for prevention of bias. Investigators should, therefore, use this method more often than they do, and readers should expect and accept disparities in group sizes. Several other complicated restricted randomisation procedures limit the likelihood of undesirable sample size imbalances in the intervention groups. The most frequently used restricted sequence generation procedure is blocked randomisation. If this method is used, investigators should randomly vary the block sizes and use larger block sizes, particularly in an unblinded trial. Other restricted procedures, such as urn randomisation, combine beneficial attributes of simple and restricted randomisation by preserving most of the unpredictability while achieving some balance. The effectiveness of stratified randomisation depends on use of a restricted randomisation approach to balance the allocation sequences for each stratum. Generation of a proper randomisation sequence takes little time and effort but affords big rewards in scientific accuracy and credibility. Investigators should devote appropriate resources to the generation of properly randomised trials and reporting their methods clearly.

chapter4.asp reference: Sample size slippages in randomised trials: exclusions and the lost and wayward. Schulz KF and Grimes DA. Lancet 2002:359(9308);781-5. Proper randomisation means little if investigators cannot include all randomised participants in the primary analysis. Participants might ignore follow-up, leave town, or take aspartame when instructed to take aspirin. Exclusions before randomisation do not bias the treatment comparison, but they can hurt generalisability. Eligibility criteria for a trial should be clear, specific, and applied before randomisation. Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested. In principle, assessment of exclusions after randomisation is simple: none are allowed. For the primary analysis, all participants enrolled should be included and analysed as part of the original group assigned (an intent-to-treat analysis). In reality, however, losses frequently occur. Investigators should, therefore, commit adequate resources to develop and implement procedures to maximise retention of participants. Moreover, researchers should provide clear, explicit information on the progress of all randomised participants through the trial by use of, for instance, a trial profile. Investigators can also do secondary analyses on, for instance, per-protocol or as-treated participants. Such analyses should be described as secondary and non-randomised comparisons. Mishandling of exclusions causes serious methodological difficulties. Unfortunately, some explanations for mishandling exclusions intuitively appeal to readers, disguising the seriousness of the issues. Creative mismanagement of exclusions can undermine trial validity. [Medline]

chapter4.asp reference: Sample size slippages in randomized trials: exclusions and the lost and wayward. Schulz KF and Grimes DA. Lancet 2002:359(781-785. Proper randomisation means little if investigators cannot include all randomised participants in the primary analysis. Participants might ignore follow-up, leave town, or take aspartame when instructed to take aspirin. Exclusions before randomisation do not bias the treatment comparison, but they can hurt generalisability. Eligibility criteria for a trial should be clear, specific, and applied before randomisation. Readers should assess whether any of the criteria make the trial sample atypical or unrepresentative of the people in which they are interested. In principle, assessment of exclusions after randomisation is simple: none are allowed. For the primary analysis, all participants enrolled should be included and analysed as part of the original group assigned (an intent-to-treat analysis). In reality, however, losses frequently occur. Investigators should, therefore, commit adequate resources to develop and implement procedures to maximise retention of participants. Moreover, researchers should provide clear, explicit information on the progress of all randomised participants through the trial by use of, for instance, a trial profile. Investigators can also do secondary analyses on, for instance, per-protocol or as-treated participants. Such analyses should be described as secondary and non-randomised comparisons. Mishandling of exclusions causes serious methodological difficulties. Unfortunately, some explanations for mishandling exclusions intuitively appeal to readers, disguising the seriousness of the issues. Creative mismanagement of exclusions can undermine trial validity.

oddsratio.asp reference: Likelihood of pregnancy in individuals with idiopathic/cryptogenic epilepsy: social and biologic influences. Schupf N. Epilepsia 1994:35(4);750-756. Abstract not available yet.

chapter1.asp reference: Fat chance: diet and ischemic stroke [editorial; comment]. Sherwin R and Price TR. Jama 1997:278(24);2185-6. Abstract not available.

diagnostic.asp reference: The relation of conjunctival pallor to the presence of anemia. Sheth TN, Choudhry NK, Bowes M and Detsky AS. J Gen Intern Med 1997:12(2);102-6. OBJECTIVE: To determine the value of conjunctival pallor in ruling in or ruling out the presence of severe anemia (hemoglobin < or = 90 g/L) and to determine the interobserver agreement in assessing this sign. DESIGN: Patients were prospectively assessed for pallor by at least one of three observers. All observations were made without information of the patient's hemoglobin value or of another observer's assessment. SETTING: Tertiary-care, university-affiliated teaching hospital. PATIENTS: Three hundred and two medical and surgical inpatients. MEASUREMENTS AND MAIN RESULTS: Likelihood ratios (LRs) calculated for conjunctival pallor present, borderline, and absent were as follows: pallor present, LR 4.49 (95% confidence interval [CI] 1.80, 10.99); pallor borderline, LR 1.80 (95% CI 1.18, 2.62); pallor absent, LR 0.61 (95% CI 0.44, 0.80). Kappa scores of interobserver agreement between paired observers were 0.75 and 0.54. CONCLUSIONS: The presence of conjunctival pallor, without other information suggesting anemia, is reason enough to perform a hemoglobin determination. The absence of conjunctival pallor is not likely to be of use in ruling out severe anemia. With well-defined criteria, interobserver agreement is good to very good. [Medline]

lognormal.asp reference: . Shinn JH, Mallon B and Martin S. Accessed on 1992.

diagnostic.asp reference: Likelihood ratios with confidence: sample size estimation for diagnostic test studies. Simel DL, Samsa GP and Matchar DB. J Clin Epidemiol 1991:44(8);763-70. Confidence intervals are important summary measures that provide useful information from clinical investigations, especially when comparing data from different populations or sites. Studies of a diagnostic test should include both point estimates and confidence intervals for the tests' sensitivity and specificity. Equally important measures of a test's efficiency are likelihood ratios at each test outcome level. We present a method for calculating likelihood ratio confidence intervals for tests that have positive or negative results, tests with non-positive/non-negative results, and tests reported on an ordinal outcome scale. In addition, we demonstrate a sample size estimation procedure for diagnostic test studies based on the desired likelihood ratio confidence interval. The renewed interest in confidence intervals in the medical literature is important, and should be extended to studies analyzing diagnostic tests.

diagnostic.asp reference: The influence of prostate volume on the ratio of free to total prostate specific antigen in serum of patients with prostate carcinoma and benign prostate hyperplasia. Stephan C, Lein M, Jung K, Schnorr D and Loening SA. Cancer 1997:79(1);104-9. BACKGROUND: Determining the ratio of free to total prostate specific antigen (f-PSA to t-PSA, calculated as the percentage of f-PSA [f-PSA%]) in serum allow for a clearer distinction between patients with prostate carcinoma (PCa) and patients with benign prostate hyperplasia (BPH) than determining the level of t-PSA alone. To find influencing factors on f-PSA%, the authors investigated prostate volume, TNM classification, and tumor stage. METHODS: The authors measured f-PSA and t-PSA in 36 men with untreated PCa (tumor classification: T1, 2, 3pNO, MO), 44 patients with BPH, and 54 healthy controls. Prostate volume was determined by transrectal ultrasound. RESULTS: The median values of t-PSA and f-PSA% were 7.8 micrograms/L and 10.5% in PCa patients, 4.3 micrograms/L and 20.8% in patients with BPH, and 1.4 micrograms/L and 23.6% in the control group. Patients with PCa had a significantly lower proportion of f-PSA than BPH patients and healthy men. There was no correlation of f-PSA% to TNM stage or tumor grade. In PCa patients a significant positive correlation (correlation coefficient [r] = 0.51, P < 0.001) was found between f-PSA% and prostate volume, whereas there was no significant correlation in BPH patients (r = -0.27, P > 0.05). There was a significant difference in f-PSA% between PCa and BPH patients with prostate volumes smaller than 40 cm3 (9.0% vs. 21.6%, P < 0.01) but not between patients in these 2 groups with prostate volumes exceeding 40 cm3 (15.1% vs. 18.2%, P = 0.11). CONCLUSIONS: Determining the ratio of f-PSA to t-PSA to discriminate between PCa and BPH patients yields significant results only in men with a prostate volume of less than 40 cm3. [Medline]

diagnostic.asp reference: The accuracy of patient history, wheezing, and laryngeal measurements in diagnosing obstructive airway disease. CARE-COAD1 Group. Clinical Assessment of the Reliability of the Examination-Chronic Obstructive Airways Disease. Straus SE, McAlister FA, Sackett DL and Deeks JJ. Jama 2000:283(14);1853-7. CONTEXT: The accuracy of the clinical examination in detecting obstructive airway disease (OAD) is largely unknown because of a paucity of methodologically rigorous studies. OBJECTIVE: To determine the accuracy of patient history, wheezing, laryngeal height, and laryngeal descent in the diagnosis of OAD. DESIGN: Comparison study conducted from November 3, 1998, to December 4, 1998, evaluating 4 clinical examination elements for diagnosis of OAD vs the gold standard of forced expiratory volume in 1 second (FEV1) and FEV1-forced vital capacity (FVC) ratio less than the fifth percentile (adjusted for patient height, age, and sex). SETTING: Twenty-five sites, including primary care and referral practices, in 14 countries. PARTICIPANTS: A total of 309 consecutive patients were recruited (mean age, 56 years; 43% female), 76 (25%) with known chronic OAD, 114 (37%) with suspected chronic OAD, and 119 (39%) with neither known nor suspected OAD. MAIN OUTCOME MEASURES: Sensitivity, specificity, and likelihood ratios (LRs) for each of the 4 elements of the clinical examination compared with the gold standard. RESULTS: Mean FEV1 and FVC values were 2.1 L/s and 2.9 L; 52% had an FEV1 and FEV1-FVC ratio less than the fifth percentile. The LR for wheezing was 2.7 (95% confidence interval [CI], 1.7-4.2) and was not statistically significant in the multivariate model. The LR for laryngeal descent ranged from 0.9 (95% CI, 0.5-1.4) to 1.2 (95% CI, 0.4-3.4), depending on the cut point chosen, and did not enter the multivariate model. Only 4 of the history or physical examination elements we tested were significantly associated with the diagnosis of OAD on multivariate analysis: smoking for more than 40 pack-years (LR, 8.3), self-reported history of chronic OAD (LR, 7.3), maximum laryngeal height of 4 cm [corrected] or less (LR, 2.8), and age at least 45 years (LR, 1.3). Patients having all 4 findings had an LR of 220 (ruling in OAD); those with none had an LR of 0.13 (ruling out OAD). The area under the receiver operating characteristic curve for the model incorporating these 4 factors was 0.86. CONCLUSIONS: Further research is needed to validate our model, but in the meantime, our data suggest that less emphasis should be placed on the presence of individual symptoms or signs (such as wheezing or laryngeal descent) in the diagnosis of OAD.

diagnostic.asp reference: Sensitivity and specificity of observer and self-report questionnaires in major and minor depression following myocardial infarction. Strik JJ, Honig A, Lousberg R and Denollet J. Psychosomatics 2001:42(5);423-8. This study evaluated screening abilities of self-report questionnaires for depression in first myocardial infarction (MI) patients. One month post-MI, 206 patients with first MI were screened for major and minor depression using the 90-item Symptom Check List (SCL-90), the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS), and the 17-item Hamilton Depression Rating Scale (Ham-D). The Structured Clinical Interview for DSM-IV criteria was used as the gold standard. Sensitivity and specificity for different cutoff points, using relative operating characteristics curves, were assessed. The internal consistency for all scales was good. When screening for major and minor depression, the optimal cutoff scores are lower than those for screening major depression only. The SCL-90, BDI, HADS, and Ham-D proved to have acceptable abilities for screening post-MI major and minor depression. [Medline]

lognormal.asp reference: Determining parameters of lognormal distributions from minimal information. Strom DJ and Stansbury PS. Aihaj 2000:61(6);877-80. The lognormal distribution has a number of properties that do not lend themselves to simple "back-of-the-envelope" calculations. Mathematical relationships are presented for the basic parameters of the large population lognormal distribution as a function of characteristics available to, or needed by, the risk analyst. A freeware computer program called LOGNORM4 has been written to take the tedium out of determining various characteristics of lognormal distributions, given 1 of 15 sets of values that uniquely specify a lognormal distribution. [Medline]

chapter2.asp reference: False positive outcomes and design characteristics in occupational cancer epidemiology studies. Swaen GG, Teggeler O and van Amelsvoort LG. Int J Epidemiol 2001:30(5);948-54. BACKGROUND: Recently there has been considerable debate about possible false positive study outcomes. Several well-known epidemiologists have expressed their concern and the possibility that epidemiological research may loose credibility with policy makers as well as the general public. METHODS: We have identified 75 false positive studies and 150 true positive studies, all published reports and all epidemiological studies reporting results on substances or work processes generally recognized as being carcinogenic to humans. All studies were scored on a number of design characteristics and factors relating to the specificity of the research objective. These factors included type of study design, use of cancer registry data, adjustment for smoking and other factors, availability of exposure data, dose- and duration-effect relationship, magnitude of the reported relative risk, whether the study was considered a 'fishing expedition', affiliation and country of the first author. RESULTS: The strongest factor associated with the false positive or true positive study outcome was if the study had a specific a priori hypothesis. Fishing expeditions had an over threefold odds ratio of being false positive. Factors that decreased the odds ratio of a false positive outcome included observing a dose-effect relationship, adjusting for smoking and not using cancer registry data. CONCLUSION: The results of the analysis reported here clearly indicate that a study with a specific a priori study objective should be valued more highly in establishing a causal link between exposure and effect than a mere fishing expedition. [Medline]

irb.asp reference: Content and quality of 2000 controlled trials in schizophrenia over 50 years. Thornley B and Adams C. British Medical Journal 1998:317(7167);1181-1184. ABSTRACT: OBJECTIVE: To provide a comprehensive survey of the content and quality of intervention studies relevant to the treatment of schizophrenia. DESIGN:Data were extracted from 2000 trials on the Cochrane Schizophrenia Group's register. MAIN OUTCOME MEASURES: Type and date of publication, country of origin, language, size of study, treatment setting, participant group, interventions, outcomes, and quality of study. RESULTS: Hospital based drug trials undertaken in the United States were dominant in the sample (54%). Generally, studies were short (54%<6 weeks), small (mean number of patients 65), and poorly reported (64% had a quality score of <=2 (maximum score 5)). Over 600 different interventions were studied in these trials, and 640 different rating scales were used to measure outcome. CONCLUSIONS: Half a century of studies of limited quality, duration, and clinical utility leave much scope for well planned, conducted, and reported trials. The drug regulatory authorities should stipulate that the results of both explanatory and pragmatic trials are necessary before a compound is given a licence for everyday use.

microarray.asp reference: Significance analysis of microarrays applied to the ionizing radiation response. Tusher VG, Tibshirani R and Chu G. Proc Natl Acad Sci U S A 2001:98(9);5116-21. Microarrays can measure the expression of thousands of genes to identify changes in expression between different biological states. Methods are needed to determine the significance of these changes while accounting for the enormous number of genes. We describe a method, Significance Analysis of Microarrays (SAM), that assigns a score to each gene on the basis of change in gene expression relative to the standard deviation of repeated measurements. For genes with scores greater than an adjustable threshold, SAM uses permutations of the repeated measurements to estimate the percentage of genes identified by chance, the false discovery rate (FDR). When the transcriptional response of human cells to ionizing radiation was measured by microarrays, SAM identified 34 genes that changed at least 1.5-fold with an estimated FDR of 12%, compared with FDRs of 60 and 84% by using conventional methods of analysis. Of the 34 genes, 19 were involved in cell cycle regulation and 3 in apoptosis. Surprisingly, four nucleotide excision repair genes were induced, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiation. [Medline] [Abstract] [Full text] [PDF]

diagnostic.asp reference: Accuracy of a single question in screening for depression in a cohort of patients after stroke: comparative study. Watkins C, Daniels L, Jack C, Dickinson H and van Den Broek M. Bmj 2001:323(7322);p1159. Abstract not available.

diagnostic.asp reference placebo.asp reference: Placebo trials and tribulations. Weijer C. Cmaj 2002:166(5);Abstract not available.

microarray.asp reference: Computational method for reducing variance with Affymetrix microarrays. Welle S, Brooks AI and Thornton CA. BMC Bioinformatics 2002:3(1);23. BACKGROUND: Affymetrix microarrays are used by many laboratories to generate gene expression profiles. Generally, only large differences (> 1.7-fold) between conditions have been reported. Computational methods to reduce inter-array variability might be of value when attempting to detect smaller differences. We examined whether inter-array variability could be reduced by using data based on the Affymetrix algorithm for pairwise comparisons between arrays (ratio method) rather than data based on the algorithm for analysis of individual arrays (signal method). Six HG-U95A arrays that probed mRNA from young (21-31 yr old) human muscle were compared with six arrays that probed mRNA from older (62-77 yr old) muscle. RESULTS: Differences in mean expression levels of young and old subjects were small, rarely > 1.5-fold. The mean within-group coefficient of variation for 4629 mRNAs expressed in muscle was 20% according to the ratio method and 25% according to the signal method. The ratio method yielded more differences according to t-tests (124 vs. 98 differences at P < 0.01), rank sum tests (107 vs. 85 differences at P < 0.01), and the Significance Analysis of Microarrays method (124 vs. 56 differences with false detection rate < 20%; 20 vs. 0 differences with false detection rate < 5%). The ratio method also improved consistency between results of the initial scan and results of the antibody-enhanced scan. CONCLUSION: The ratio method reduces inter-array variance and thereby enhances statistical power. [Medline] [Abstract] [Full text] [PDF]

chapter7.asp reference: Visibility of research: FUTON bias. Wentz R. Lancet 2002:360(9341);1256. Abstract not available [Medline]

diagnostic.asp reference: Can the initial clinical assessment of thyroid function be improved? White GH and Walmsley RN. Lancet 1978:2(8096);933-5. The clinical reasons for requesting in-vitro thyroid-function tests were studied in 500 consecutive new patients with no known history of thyroid disease. 23 patients presented with five or more signs or symptoms of thyroid disease, and 18 of these required treatment for thyrometabolic dysfunction. Of 35 subjects with three or four thyroid-associated signs or symptoms, only 1 came to treatment. Of 442 subjects with one or two signs or symptoms, 2 were subsequently treated. These results suggest that there is little value in the biochemical investigation of patients who present with minimal clinical evidence of thyrometabolic disease. [Medline]

diagnostic.asp reference: Does this patient have sinusitis? Diagnosing acute sinusitis by history and physical examination. Williams JJ and Simel D. JAMA 1993:270(10);1242-46. Abstract not available.

diagnostic.asp reference: Likelihood ratios to determine 'does this patient have appendicitis?': comment and clarification [letter; comment]. Witt K, Makela M and Olsen O. Jama 1997:278(10);819; discussion 819-20. Abstract not available.

pilot.asp reference: The role of internal pilot studies in increasing the efficiency of clinical trials. Wittes J and Brittain E. Stat Med 1990:9(1-2);65-71; discussion 71-2. Investigators often design clinical trials without knowing precisely the values of such necessary parameters as the variances or the event rates in the control group. In order to determine reasonable values for such parameters, they may design a small pilot study external to the main trial. In this paper we propose designs, which we term internal pilot studies, that designate a portion of the main trial as a pilot phase. At the end of the internal pilot study, the investigators recompute preselected parameters and recalculate required sample size. The study then proceeds with the modifications dictated by the internal pilot. Final analyses of the results incorporate all data, disregarding the fact that part of the data came from a pilot phase. As one example of this type of design, we consider a study to compare two normally distributed means. By simulation, we show a numerical example for which the effect of the procedure on the alpha-level is negligible, but the potential gain in power considerable. We urge considering a similar approach for a number of types of endpoints. [Medline]

chapter5.asp reference: Interpreting the Number Needed to Treat. Wu LA and Kottke TE. Journal of the American Medical Association 2002:288(7);Abstract not available yet.

placebo.asp reference: We may be in danger of bribing volunteers. Young C. Bmj 2001:322(7277);45. [Medline]

microarray.asp reference: Match-Only Integral Distribution (MOID) Algorithm for high-density oligonucleotide array analysis. Zhou Y and Abagyan R. BMC Bioinformatics 2002:3(1);3. BACKGROUND: High-density oligonucleotide arrays have become a valuable tool for high-throughput gene expression profiling. Increasing the array information density and improving the analysis algorithms are two important computational research topics. RESULTS: A new algorithm, Match-Only Integral Distribution (MOID), was developed to analyze high-density oligonucleotide arrays. Using known data from both spiking experiments and no-change experiments performed with Affymetrix GeneChip(R) arrays, MOID and the Affymetrix algorithm implemented in Microarray Suite 4.0 (MAS4) were compared. While MOID gave similar performance to MAS4 in the spiking experiments, better performance was observed in the no-change experiments.MOID also provides a set of alternative statistical analysis tools to MAS4. There are two main features that distinguish MOID from MAS4. First, MOID uses continuous P values for the likelihood of gene presence, while MAS4 resorts to discrete absolute calls. Secondly, MOID uses heuristic confidence intervals for both gene expression levels and fold change values, while MAS4 categorizes the significance of gene expression level changes into discrete fold change calls. CONCLUSIONS: The results show that by using MOID, Affymetrix GeneChip(R) arrays may need as little as ten probes per gene without compromising analysis accuracy. [Medline] [Abstract] [Full text] [PDF]

diagnostic.asp reference: Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Zweig M and Campbell G. Clin Chem 1993:39(4);561-77. ABSTRACT: The clinical performance of a laboratory test can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy refers to the quality of the information provided by the classification device and should be distinguished from the usefulness, or actual practical value, of the information. Receiver-operating characteristic (ROC) plots provide a pure index of accuracy by demonstrating the limits of a test's ability to discriminate between alternative states of health over the complete spectrum of operating conditions. Furthermore, ROC plots occupy a central or unifying position in the process of assessing and using diagnostic tools. Once the plot is generated, a user can readily go on to many other activities such as performing quantitative ROC analysis and comparisons of tests, using likelihood ratio to revise the probability of disease in individual subjects, selecting decision thresholds, using logistic-regression analysis, using discriminant-function analysis, or incorporating the tool into a clinical strategy by using decision analysis.

antihistamine editorial (5)

Editorials and Conflicts of Interest. Marcia Angell, Jerome P. Kassirer. N Engl J Med 1996: 335(14); 1055-1056. [Medline] [Full text]

The publication of sponsored symposiums in medical journals. L. A. Bero, A. Galbraith, D. Rennie. N Engl J Med 1992: 327(16); 1135-40. [Medline] [Abstract]

The visual analog scale for pain: clinical significance in postoperative patients. C. A. Bodian, G. Freedman, S. Hossain, J. B. Eisenkraft, Y. Beilin. Anesthesiology 2001: 95(6); 1356-61. [Medline]

Problem is greater than editorial indicates. Ivar S Kristiansen. BMJ 2003: 326(7394); 883-. [Full text]

Determining the minimum clinically significant difference in visual analog pain score for children. C. V. Powell, A. M. Kelly, A. Williams. Ann Emerg Med 2001: 37(1); 28-31. [Medline]

Ask >> Bootstrap (2)

The Jackknife, the Bootstrap and Other Resampling Plans. Bradley Efron (1982) Philadelphia: The Society for Industrial and Applied Mathematics. ISBN: 0-89871-179-7.

Overview of Computer Intensive Statistical Inference Procedures. P. Adam Kelly. Accessed on 2003-01-03. people.bcm.tmc.edu/~pakelly/resampling.html

Ask >> NNT (24)

Calculating the number needed to treat for trials where the outcome is time to an event. D. G. Altman, P. K. Andersen. British Medical Journal 1999: 319(7223); 1492-5. [Full text] [PDF]

Calculating and Using NNTs. Bandolier. Accessed on 2003-06-12. www.jr2.ox.ac.uk/bandolier/Extraforbando/NNTextra.pdf

Getting NNTs. Bandolier. Accessed on 2003-07-01. www.jr2.ox.ac.uk/bandolier/band36/b36-2.html

Missing the point (estimate)? Confidence intervals for the number needed to treat. N. J. Barrowman. Cmaj 2002: 166(13); 1676-7.

Calculating the "number needed to be exposed" with adjustment for confounding variables in epidemiological studies. R Bender, M Blettner. Journal of Clinical Epidemiology 2002: 55(5); 525-530. [Medline] [PDF]

Calculating confidence intervals for the number needed to treat. R. Bender. Controlled Clinical Trials 2001: 22(2); 102-10.

Expressing the magnitude of adverse effects in case-control studies: "the number of patients needed to be treated for one additional patient to be harmed". L. M. Bjerre, J. LeLorier. British Medical Journal 2000: 320(7233); 503-6. [Full text] [PDF]

Influence of method of reporting study results on decision of physicians to prescribe drugs to lower cholesterol concentration. H. C. Bucher, M. Weinbacher, K. Gyr. British Medical Journal 1994: 309(6957); 761-4. [Abstract] [Full text]

Numbers needed to treat derived from meta-analysis. Bruce G. Charlton. British Medical Journal 1999: 319(7218); 1199.

The number needed to treat: a clinically useful measure of treatment effect. R. J. Cook, D. L. Sackett. British Medical Journal 1995: 310(6977); 452-4. [Full text]

Confidence limits made easy: interval estimation using a substitution method. L. E. Daly. Am J Epidemiol 1998: 147(8); 783-90.

Beta blockade after myocardial infarction: systematic review and meta regression analysis. Nick Freemantle, J Cleland, P Young, J Mason, J Harrison. British Medical Journal 1999: 318(7200); 1730-1737.

Using numerical results from systematic reviews in clinical practice. H. J. McQuay, R. A. Moore. Ann Intern Med 1997: 126(9); 712-20.

Recombinant or urinary follicle-stimulating hormone? A cost-effectiveness analysis derived by particularizing the number needed to treat from a published meta-analysis. B. Ola, S. Papaioannou, M. A. Afnan, N. Hammadieh, S. Gimba. Fertil 2001: 75(6); p1106-10.

Number needed to screen: development of a statistic for disease screening. C. M. Rembold. British Medical Journal 1998: 317(7154); 307-12. [Abstract] [Full text] [PDF]

Adjusting the number needed to treat: incorporating adjustments for the utility and timing of benefits and harms. R Riegelman, WS Schroth. Medical Decision Making 1993: 13(3); 247-52.

Unqualified success and unmitigated failure: number-needed-to-treat-related concepts for assessing treatment efficacy in the presence of treatment-induced adverse events. M Schulzer, GB Mancini. International Journal of Epidemiology 1996: 25(4); 704-12.

When should an effective treatment be used? Derivation of the threshold number needed to treat and the minimum event rate for treatment. J. C. Sinclair, R. J. Cook, G. H. Guyatt, S. G. Pauker, D. J. Cook. J Clin Epidemiol 2001: 54(3); p253-62.

Applying evidence to the individual patient. S. E. Straus, D. L. Sackett. Ann Oncol 1999: 10(1); 29-32. [Medline]

Benefit-Risk ratios in the assessment of the clinical evidence of a new therapy. AR Willan, BJ O'Brien, DJ Cook. Cont Clin Trials 1997: 18(2); 121-30.

Events per person per year -- a dubious concept. J Windeler, S Lange. BMJ 1995: 310(6977); 454-56. [Full text]

Number needed to treat: Caveat emptor. LA Wu, TE Kottke. Journal of Clinical Epidemiology 2001: 54(2); 111-116.

Interpreting the Number Needed to Treat. Lambert A. Wu, Thomas E. Kottke. Journal of the American Medical Association 2002: 288(7);

Number needed to harm should be measured for treatments. Arnold Zermansky. British Medical Journal 1998: 317(7164); 1014. [Full text]

Ask >> NNT >> Example (3)

Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up. T. Blondal, L. J. Gudmundsson, I. Olafsdottir, G. Gustavsson, A. Westin. British Medical Journal 1999: 318(7179); 285-8. [Abstract] [Full text] [PDF]

Randomised controlled trial shows that glyceryl trinitrate heals anal fissures, higher doses are not more effective, and there is a high recurrence rate. EA Carapeti, MA Kamm, PJ McDonald, SJ Chadwick, D Melville, RK Phillips. Gut 1999: 44(5); 727-30.

Updated New Zealand cardiovascular disease risk-benefit prediction guide. R. Jackson. Bmj 2000: 320(7236); 709-10.

Ask >> Regression to mean (2)

New View of Statistics: Regression to the Mean. Will G Hopkins, Sportscience. Accessed on 2003-03-17. www.sportsci.org/resource/stats/regmean.html

Regression to the Mean. William M.K. Trochim, Cornell University. Accessed on 2003-03-17. trochim.human.cornell.edu/kb/regrmean.htm

Bibliography >> Antihistamine Editorial (6)

Why Review Articles on the Health Effects of Passive Smoking Reach Different Conclusions. Deborah E. Barnes, Lisa A. Bero. JAMA 1998: 279(19); 1566-1570. [Abstract]

How well is the clinical importance of study results reported? An assessment of randomized controlled trials. K. B. Chan, M. Man-Son-Hing, F. J. Molnar, A. Laupacis. Cmaj 2001: 165(9); 1197-202. [Abstract] [Full text] [PDF]

Use of ultramolecular potencies of allergen to treat asthmatic people allergic to house dust mite: double blind randomised controlled clinical trial. G T Lewith, A D Watkins, M E Hyland, S Shaw, J A Broomfield, G Dolan, S T Holgate. British Medical Journal 2002: 324(7336); 520-. [Abstract] [Full text] [PDF]

Conflict of interest in the debate over calcium-channel antagonists. H. T. Stelfox, G. Chua, O. Rourke K, A. S. Detsky. N Engl J Med 1998: 338(2); 101-6.

Immediate and long term effects of weight reduction in obese people with asthma: randomised controlled study. Brita Stenius-Aarniala, T Poussa, J Kvarnstrom, EL Gronlund, M Ylikahri, P Mustajoki. British Medical Journal 2000: 320(7238); 827-832. [Medline] [Abstract] [Full text] [PDF]

Randomised controlled trial of homeopathy versus placebo in perennial allergic rhinitis with overview of four trial series. Morag A Taylor, David Reilly, Robert H Llewellyn-Jones, Charles McSharry, Tom C Aitchison. BMJ 2000: 321471-476. [Medline] [Abstract] [Full text] [PDF]

Bibliography >> Simon (49)

Allergenic materials in the house dust of allergy clinic patients. C. Barnes, J. Tuck, S. Simon, F. Pacheco, F. Hu, J. Portnoy. Annals of Allergy, Asthma, & Immunology 2001: 86(5); 517-23.

A biological monitoring method for o-Toluidine and Aniline in urine using high performance liquid chromatography with electrochemical detection. K.K. Brown, A.W. Teass, S.D. Simon, E.M. Ward. Applied Occupational and Environmental Hygiene 1995: 10(6); 557-565.

Using standard desk-top tools to monitor medical error rates. Cathy A Carroll, Karen S Cox, Susan R Santos, Stephen D Simon. Seminars for Nurse Managers 2002: 10(2); 95-99.

Human Sperm Survival Assay as a Bioassay for the Assisted Reproductive Technologies Laboratory. Christopher J. De Jonge, Grace M. Centola, Michael L. Reed, Robert B. Shabanowitz, Steve D. Simon, Patrick Quinn. Journal of Andrology 2003: 24(1); 16-18. [Full text] [PDF]

Optimization of cytochrome p450 2D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data. R Gaedigk, RR Gotschall, NS Forbes, SD Simon, GL Kearns, JS Leeder. Pharmacogenetics 1999: 9(6); 669-682.

Semen Quality and Hormone Levels Among Radiofrequency Heat Sealer Operators. Barbara Grajewski, Clinton Cox, Steven M Schrader, Steven M Murray, Richard M Edwards, Terry W Turner, James M Smith, Sam S Shekar, Donald P Evenson, Stephen D Simon, David L Conover. J Occup Environ Med 2000: 42(10); 993-1005.

Growth Hormone Responsiveness in Two Groups of Children With Significantly Short Stature. J.A. Grunt, I.D. Schwartz, S.D. Simon, C.P. Howard. The Endocrinologist 2002: 1258-65.

A breast-feeding assessment score to evaluate the risk for cessation of breast-feeding by 7-10 days of age. Robert T Hall, Anne M Mercer, Susan L Teasley, Deanna M McPherson, Stephen D Simon, Susan R Santos, Bridget M Meyers, Nancy E Hipsh. J Pediatr 2002: 141(5); 659-664.

Readmission of breastfeeding infants in the first 2 weeks of life. RT Hall, MT Smith, S Simon. J Perinatol 2000: 20(7); 432-437.

Creatinine excretion rates for renal clearance studies. S. Hellerstein, S. D. Simon, M. Berenbom, P. Erwin, E. Nickell. Pediatr Nephrol 2001: 16(8); p637-43. [Abstract]

Transitioning preterm infants with nasogastric tube supplementation: increased likelihood of breastfeeding. PA Kliethermes, ML Cross, MG Lanese, KM Johnson, SD Simon. J Obstet Gynecol Neonatal Nurs 1999: 28(3); p264-73.

Pulmonary reactivity to vanadium pentoxide following subchronic inhalation exposure in a non-human primate animal model. E. A. Knecht, W. J. Moorman, J. C. Clark, R. D. Hull, R. E. Biagini, D. W. Lynch, T. J. Boyle, S. D. Simon. J Appl Toxicol 1992: 12(6); p427-34.

Numerical accuracy of statistical algorithms for microcomputers. J.P. Lesage, S.D. Simon. Computational Statistics and Data Analysis 1985: 347-57.

Male reproductive effects of lead, including species extrapolation for the rabbit model. W. J. Moorman, S. R. Skaggs, J. C. Clark, T. W. Turner, D. D. Sharpnack, J. A. Murrell, S. D. Simon, R. E. Chapin, S. M. Schrader. Reprod Toxicol 1998: 12(3); p333-46.

Vagal nerve stimulation in refractory epilepsy: the first 100 patients receiving vagal nerve stimulation at a pediatric epilepsy center. J. V. Murphy, R. Torkelson, I. Dowler, S. Simon, S. Hudson. Arch Pediatr Adolesc Med 2003: 157(6); 560-4. [Medline] [Abstract]

The classification of asbestos fibres by scanning electron microscopy and computer-digitizing tablet. S. F. Platek, R. D. Riley, S. D. Simon. Ann Occup Hyg 1992: 36(2); p155-71.

Comparison of the Burkard and Allergenco MK-3 volumetric collectors. Jay Portnoy, Julie Landuyt, Freddy Pacheco, Susan Flappan, Stephen Simon, Charles Barnes. Annals of Allergy, Asthma and Immunology 2000: 8419-24.

Duration of breast-feeding patterns established in the hospital. Influencing factors. Results from a national survey. A. S. Ryan, J. L. Wysong, G. A. Martinez, S. D. Simon. Clin Pediatr (Phila 1990: 29(2); p99-107.

Baby boomer nurses bearing the burden of care: A four-site study of stress, strain, and coping for inpatient registered nurses. S. R. Santos, C. A. Carroll, K. S. Cox, S. L. Teasley, S. D. Simon, L. Bainbridge, M. Cunningham, L. Ott. J Nurs Adm 2003: 33(4); 243-50. [Medline] [Abstract]

Reproductive function in relation to duty assignments among military personnel. S. M. Schrader, R. E. Langford, T. W. Turner, M. J. Breitenstein, J. C. Clark, B. L. Jenkins, D. O. Lundy, S. D. Simon, T. B. Weyandt. Reprod Toxicol 1998: 12(4); 465-8.

Longitudinal study of semen quality of unexposed workers. I. Study overview. S. M. Schrader, T. W. Turner, M. J. Breitenstein, S. D. Simon. Reprod Toxicol 1988: 2(3-4); p183-90.

Measuring male reproductive hormones for occupational field studies. S. M. Schrader, T. W. Turner, M. J. Breitenstein, S. D. Simon. J Occup Med 1993: 35(6); p574-6.

Longitudinal study of semen quality of unexposed workers: sperm head morphometry. S. M. Schrader, T. W. Turner, S. D. Simon. J Androl 1990: 11(1); p32-9.

Longitudinal study of semen quality of unexposed workers. Sperm motility characteristics. S. M. Schrader, T. W. Turner, S. D. Simon. J Androl 1991: 12(2); p126-31.

Semen quality across populations. S.M. Schrader, M. Ayers-Cumbo, T.W. Turner, S.D. Simon, J. Ratcliffe, L. Welch, B. Grajewski, T. Weyandt. Molecular Andrology 1995: 7105-121.

Longitudinal study of semen quality of unexposed workers: seminal plasma characteristics. S.M. Schrader, M.J. Breitenstein, T.W. Turner, S.D. Simon. In: Baccetti B ed. Comparative spermatology 20 years after. 1991; Vol. 75. New York NY: Serno Symposia Publications; 905-908.

Combining reproductive studies of men exposed to 2-ethoxyethanol to increase statistical power. S.M. Schrader, T.W. Turner, J.M. Ratcliffe, L.S. Welch, S.D. Simon. Occupational Hygiene 1996: 2411-415.

Sources of variation of the sperm penetration assay under field study conditions. S.M. Schrader, T.W. Turner, S.D. Simon. ARTA 1991: 2(Suppl 4); 63-74.

Effect of rapid diagnosis of influenza virus type a on the emergency department management of febrile infants and toddlers [In Process Citation]. V. Sharma, M. D. Dowd, A. J. Slaughter, S. D. Simon. Arch Pediatr Adolesc Med 2002: 156(1); p41-3.

Influence of the news media on diagnostic testing in the emergency department. V. Sharma, M. D. Dowd, D. S. Swanson, A. J. Slaughter, S. D. Simon. Arch Pediatr Adolesc Med 2003: 157(3); 257-60. [Medline] [Abstract]

Factors influencing infant visits to emergency departments. Vidya Sharma, SD Simon, JM Bakewell, EF Ellerbeck, MH Fox, DD Wallace. Pediatrics 2000: 106(5); 1031-1039. [Abstract]

Interpreting negative studies. S. D. Simon. J Androl 2001: 22(1); p13-6. [PDF]

Interpreting positive studies. S. D. Simon. J Androl 2001: 22(3); p358-9. [Abstract] [PDF]

Is the randomized clinical trial the gold standard of research? S. D. Simon. Journal of Andrology 2001: 22(6); p938-43. [Abstract] [PDF]

To Err Isn't Only Human. S.D. Simon. Computer Language 1986: 3(3); 71-76.

How to illustrate numerical accuracy problems on any computer. S.D. Simon. Mathematics and Computer Education 1987: 21(1); 11-15.

Assessing the accuracy of ANOVA calculations in statistical software. S.D. Simon, J.P. Lesage. Computational Statistics and Data Analysis 1990: 8(3); 325-332.

Benchmarking numerical accuracy of statistical algorithms. Stephen D Simon, James P Lesage. Computational Statistics and Data Analysis 1988: 7197-209.

The Impact of Collinearity Involving the Intercept Term on the Numerical Accuracy of Regression. Stephen D Simon, James P Lesage. Computer Science in Economics and Management 1988: 1137-152.

Vagal Nerve Stimulation in Refractory Epilepsy: The First 100 Patients Receiving Vagal Nerve Stiumlation at a Pediatric Epilepsy Center. Stephen PhD Simon, Jerome Murphy, MD, MD Torkelson, RN Irene Dowler, Sara LPN Hudson, CCRC. Archive of Pediatric Adolescent Medicine 2003: 157560-564.

Skin carcinogenicity of condensed asphalt roofing fumes and their fractions following dermal application to mice. A Sivak, R Niemeier, D Lynch, K Beltis, S Simon, R Salomon, R Latta, B Belinky, K Menzies, A Lunsford, C Cooper, A Ross, R Bruner. Cancer Letters 1997: 117(1); 113-123.

Lexical stress and lexical access: homographs versus nonhomographs. L. H. Small, S. D. Simon, J. S. Goldberg. Percept Psychophys 1988: 44(3); p272-80.

Normal urinary calcium/creatinine ratios in African-American and Caucasian children. N. P. So, A. V. Osorio, S. D. Simon, U. S. Alon. Pediatr Nephrol 2001: 16(2); p133-9. [Abstract]

Establishment of normal pediatric age-dependent urinary calcium to creatinine ratio. ND So, SD Simon, US Alon. Journal of Investigative Medicine 1999: 47228A.

Focal segmental glomerulosclerosis incidence in idiopathic nephrotic syndrome. T Srivastava, SD Simon, US Alon. Pediatric Nephrol 1998: 12C162.

High incidence of focal segmental glomerulosclerosis in nephrotic syndrome of childhood. T. Srivastava, S. D. Simon, U. S. Alon. Pediatr Nephrol 1999: 13(1); 13-8. [Abstract]

Lung particulate burdens of subjects from the Cincinnati, Ohio urban area. L. E. Stettler, S. F. Platek, R. D. Riley, J. P. Mastin, S. D. Simon. Scanning Microsc 1991: 5(1); p85-92; discussion 92-4.

In vivo percutaneous absorption studies of volatile organic solvents in hairless mice. II. Toluene, ethylbenzene and aniline. A. S. Susten, R. W. Niemeier, S. D. Simon. J Appl Toxicol 1990: 10(3); p217-25.

Semen analysis of military personnel associated with military duty assignments. T. B. Weyandt, S. M. Schrader, T. W. Turner, S. D. Simon. Reprod Toxicol 1996: 10(6); 521-8.

Bibliography >> Simon >> Acknowledgment (1)

Synaptopodin expression in idiopathic nephrotic syndrome of childhood. T. Srivastava, R. E. Garola, J. M. Whiting, U. S. Alon. Kidney Int 2001: 59(1); 118-25.

Bibliography >> Simon >> Presentation (1)

Definitions >> Confidence Interval (4)

Confidence Intervals. Gerard E. Dallal, Tufts University. Accessed on 2003-03-19. www.tufts.edu/~gdallal/ci.htm

How to read a paper. Statistics for the non-statistician. II: "Significant" relations and their pitfalls. T. Greenhalgh. British Medical Journal 1997: 315(7105); 422-5. [Full text]

Interpreting study results: confidence intervals. G Guyatt. Canadian Medical Association Journal 1995: 152169-73. [Full text]

Pertussis vaccination and wheezing illnesses in young children: prospective cohort study. John Henderson, K North, M Griffiths, I Harvey, J Golding. British Medical Journal 1999: 318(7192); 1173-1176. [Medline] [Abstract] [Full text] [PDF]

Definitions >> Confidence Interval >> Advantages (3)

The case for confidence intervals in controlled clinical trials. M. Borenstein. Controlled Clinical Trials 1994: 15(5); 411-28.

Confidence intervals rather than P values: estimation rather than hypothesis testing. M. J. Gardner, D. G. Altman. Br Med J (Clin Res Ed) 1986: 292(6522); 746-50.

Improving interpretation of clinical studies by use of confidence levels, clinical significance curves, and risk-benefit contours. Thomas P. Shakespeare, Val J Gebski, Michael J Veness, John Simes. Lancet 2002: 357(?); 1349-1353.

Definitions >> Kappa (10)

A generalization of Cohen's Kappa agreement measure to interval measurement and multiple raters. KJ Berry. Educational and Psychological Measurement 1998: 48(?); 921-933.

2 x 2 kappa coefficients: measures of agreement or association. D. A. Bloch, H. C. Kraemer. Biometrics 1989: 45(1); 269-87.

Problems with kappa. T. Byrt. Journal Clinical Epidemiology 1992: 45(12); 1452.

High agreement but low kappa: II. Resolving the paradoxes. D. V. Cicchetti, A. R. Feinstein. J Clin Epidemiol 1990: 43(6); 551-8.

The relationship between chi-square statistics from matched and unmatched analyses. A. Donner, K. Y. Li. J Clin Epidemiol 1990: 43(8); 827-31.

High agreement but low kappa: I. The problems of two paradoxes. A. R. Feinstein, D. V. Cicchetti. J Clin Epidemiol 1990: 43(6); 543-9.

Sample Size Determinations for the Two Rater Kappa Statistic. V. F. Flack, A. A. Afifi, P. A. Lachenbruch. Psychometrika 1988: 53(3); 321-325.

The Analysis of Ordinal Agreement Data: Beyond Weighted Kappa. Patrick Graham, Rodney Jackson. Journal of Clinical Epidemiology 1993: 46(9); 1055-1062.

Differences in diagnostic criteria for gastric carcinoma between Japanese and western pathologists. R. J. Schlemper, M. Itabashi, Y. Kato, K. J. Lewin, R. H. Riddell, T. Shimoda, P. Sipponen, M. Stolte, H. Watanabe, H. Takahashi, R. Fujita. Lancet 1997: 349(9067); 1725-9.

Modeling Agreement Among Raters. Martin A. Tanner. Journal of the American Statistical Association 1985: 80(389); 175-180.

Definitions >> Kappa >> Example (4)

Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn. M. A. Alano, E. Ngougmna, E. M. Ostrea, Jr., G. G. Konduri. Pediatrics 2001: 107(3); 519-23.

Does how you do depend on how you think you'll do? A systematic review of the evidence for a relation between patients' recovery expectations and health outcomes. M. V. Mondloch, D. C. Cole, J. W. Frank. Cmaj 2001: 165(2); p174-9.

The relation of conjunctival pallor to the presence of anemia. T. N. Sheth, N. K. Choudhry, M. Bowes, A. S. Detsky. J Gen Intern Med 1997: 12(2); 102-6.

Clinician agreement on physical findings in child sexual abuse cases. S. H. Sinal, M. R. Lawless, D. Y. Rainey, V. D. Everett, D. K. Runyan, T. Frothingham, M. Herman-Giddens, K. St Claire. Arch Pediatr Adolesc Med 1997: 151(5); 497-501.

Definitions >> Likelihood (2)

Scientific Versus Statistical Inference. Peter Dixon, Tenaha O'Reilly. Canadian Journal of Experimental Psychology 1999: 53(2); 133 - 149.

Sifting the evidence. Likelihood ratios are alternatives to P values [In Process Citation]. T. V. Perneger. British Medical Journal 2001: 322(7295); p1184-5.

Definitions >> Normal (4)

Gaussian distribution: FAQ. John D'Errico, Rich Ulrich. Accessed on 2003-08-13. www.pitt.edu/~wpilib/gaussfaq.html

Z table. David M. Lane. Accessed on 2003-05-28. davidmlane.com/hyperstat/z_table.html

Probabilities for the Normal Distribution. Gary H. McClelland. Accessed on 2003-05-28. psych.colorado.edu/~mcclella/java/normal/accurateNormal.html

Carl Friedrich Gauss (1777-1855). Radiation Effects Research Foundation. Accessed on 2003-04-21. staff.rerf.or.jp/~stat/Stat_outside_e/gauss.html

Definitions >> Odds (1)

Odds and Probability. Math Forum @ Drexel. Accessed on 2003-03-25. mathforum.org/Library/drmath/view/56495.html

Definitions >> Ordinal (7)

Pearson's R and Coarsely Categorized Measures. K. A. Bollen, K Barb. American Sociological Review 1981: 46232-39.

Multivariate Analysis and Ordinal Data. F Henry. American Sociological Review 1982: 47299-307.

Ordinal Measures in Multiple Indicator Models: A Simulation of Categorization Error. D. Johnson, J. Creech. American Sociological Review 1983: 48398-407.

Multivariate Analysis of Ordinal Variables. J Kim. American Journal of Sociology 1975: 81261-98.

Multivariate Analysis of Ordinal Variables Revisited. J Kim. American Journal of Sociology 1978: 84448-56.

The Assignment of Numbers to Rank Order Categories. S Labovitz. American Sociological Review 1970: 35515-24.

The Use of Pearson's R with Ordinal Data. R. O'Brien. American Sociological Review 1979: 44851-57.

Definitions >> Population (1)

Yes, Polling Works. Frank Newport. Accessed on 2002-12-03. www.gallup.com/poll/FromtheEd/ed0211.asp

Definitions >> Pvalue (15)

Understanding P-values. Jim Berger, Duke University. Accessed on 2003-03-19. www.stat.duke.edu/~berger/p-values.html

The Case Against Statistical Significance Testing. Ronald P. Carver. Harvard Educational Review 1978: 48(3); 378-399.

Consultation patterns and provision of contraception in general practice before teenage pregnancy: case-control study. D. Churchill, J. Allen, M. Pringle, J. Hippisley-Cox, D. Ebdon, M. Macpherson, S. Bradley. British Medical Journal 2000: 321(7259); 486-9. [Abstract] [Full text] [PDF]

The Earth Is Round (p < .05). Jacob Cohen. American Psychologist 1994: 49(12); 997 - 1003.

On the origins of the .05 level of statistical significance. M Cowles. American Psychologist 1982: 37(5); 553-8.

P Values. Gerard E. Dallal, Tufts University. Accessed on 2003-03-19. www.tufts.edu/~gdallal/pval.htm

Scientific Versus Statistical Inference. Peter Dixon, Tenaha O'Reilly. Canadian Journal of Experimental Psychology 1999: 53(2); 133 - 149.

Basic statistics for clinicians: 1. Hypothesis testing. G. Guyatt, R. Jaeschke, N. Heddle, D. Cook, H. Shannon, S. Walter. Cmaj 1995: 152(1); 27-32. [Full text]

Clinical vs Statistical Significance. Will G Hopkins, Sportscience. Accessed on 2003-03-17. www.sportsci.org/jour/0103/inbrief.htm

Sifting the evidence. Likelihood ratios are alternatives to P values [In Process Citation]. T. V. Perneger. British Medical Journal 2001: 322(7295); p1184-5.

Special Issue: Statistical Significance Testing. Dennis Roberts, Penn State University. Accessed on 2003-03-20. roberts.ed.psu.edu/users/droberts/sigtest.htm

Is statistical significance testing useful in interpreting data? D. A. Savitz. Reprod Toxicol 1993: 7(2); 95-100.

Sifting the evidence- what's wrong with significance tests? Jonathan A C Sterne, George Davey Smith. BMJ 2001: 322226-231. [Medline] [Full text] [PDF]

326 Articles/Books Questioning the Indiscriminate Use of Statistical Hypothesis Tests in Observational Studies. William L. Thompson. Accessed on 2003-03-19. www.cnr.colostate.edu/~anderson/thompson1.html

Gergen versus the mainstream: Are hypothesis in social psychology subject to empirical test? L. Wallach, M. A. Wallach. J. Pers. Soc. Psychol. 1994: 67233-242.

Definitions >> Pvalue >> Controversy (2)

p Values, hypothesis tests, and likelihood: implications for epidemiology of a neglected historical debate. Steven Goodman. American Journal of Epidemiology 1993: 137(5); 485-95.

A Picture is Worth a Thousand p Values: On the Irrelevance of Hypothesis Testing in the Microcomputer Age. Geoffrey R. Loftus. Behavior Research Methods, Instruments & Computers 1993: 25(2); 250-256.

Definitions >> Quota Sample (1)

Trends in smoking during pregnancy in England, 1992-7: quota sampling surveys. Lesley Owen, Ann McNeill, Christine Callum. British Medical Journal 1998: 317(7160); 728.

Definitions >> T Test (1)

hypothesis/ht_normal: Functions. Laszlo Kiss. Accessed on 2003-04-25. lzkiss.netfirms.com/cgi-bin/stat/index.pl?dir=hypothesis&name=ht_normal

Definitions >>Standard Error (1)

Maintaining standards: differences between the standard deviation and standard error, and when to use each. D. L. Streiner. Can J Psychiatry 1996: 41(8); 498-502.

Diagnostic >> Bias (4)

Biases in the assessment of diagnostic tests. C. B. Begg. Stat Med 1987: 6(4); 411-23.

Effect of misclassification of causes of death in verbal autopsy: can it be adjusted? D. Chandramohan, P. Setel, M. Quigley. Int J Epidemiol 2001: 30(3); 509-14.

Sensitivity and specificity of a single diagnostic test in the presence of work-up bias. B. C. Choi. J Clin Epidemiol 1992: 45(6); 581-6.

Diagnostic bias and toxic shock syndrome. M. Harvey, R. I. Horwitz, A. R. Feinstein. Am J Med 1984: 76(3); 351-60. [Medline]

Diagnostic >> Example (4)

Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate. L. A. Eskew, R. L. Bare, D. L. McCullough. J Urol 1997: 157(1); 199-202; discussion 202-3.

Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. D. K. Rex, C. S. Cutler, G. T. Lemmel, E. Y. Rahmani, D. W. Clark, D. J. Helper, G. A. Lehman, D. G. Mark. Gastroenterology 1997: 112(1); 24-8.

Do Japanese statistics on gastric carcinoma need to be revised? J. Sakamoto, M. Yasue. Lancet 1997: 349(9067); 1711-2.

Differences in diagnostic criteria for gastric carcinoma between Japanese and western pathologists. R. J. Schlemper, M. Itabashi, Y. Kato, K. J. Lewin, R. H. Riddell, T. Shimoda, P. Sipponen, M. Stolte, H. Watanabe, H. Takahashi, R. Fujita. Lancet 1997: 349(9067); 1725-9.

Diagnostic >> Fagan Nomogram (2)

Nomogram for Likelihood Ratios. Centre for Evidence-Based Medicine. Accessed on 2003-03-25. www.cebm.net/nomogram.asp

Nomogram for Bayes theorem. TJ Fagan. New England Journal of Medical 1975: 293257.

Diagnostic >> General (3)

Diagnostic Strategies for Common Medical Problems. Edgar R. Black, MD, Donald R. Bordley, MD, Thomas G. Tape, MD, Robert J. Panzer, MD (1999) Philadelphia, Pennsylvania: American College of Physicians.

Index for rating predictive accuracy of screening tests. B. C. Choi. Methods Inf Med 1982: 21(3); 149-53.

Evaluating Medical Tests: Objective and Quantitative Guidelines. Helena Chmura Kraemer (1992) Newbury Park, CA: Sage Publications.

Diagnostic >> Gold Standard (1)

Inferences for likelihood ratios in the absence of a "gold standard". L Joseph, TW Gyorkos. Medical Decision Making 1996: 16(4); 412-17.

Diagnostic >> Guidelines (7)

Mathematical tools for demonstrating the clinical usefulness of biochemical markers. J. C. Boyd. Scand J Clin Lab Invest Suppl 1997: 22746-63.

Toward a checklist for reporting of studies of diagnostic accuracy of medical tests. D. E. Bruns, E. J. Huth, E. Magid, D. S. Young. Clinical Chemistry 2000: 46(7); 893-5.

Systematic reviews in health care: Systematic reviews of evaluations of diagnostic and screening tests. J. J. Deeks. British Medical Journal 2001: 323(7305); 157-62.

Evidence-based diagnostic radiology. A. K. Dixon. Lancet 1997: 350(9076); 509-12.

How to read a paper. Papers that report diagnostic or screening tests. T. Greenhalgh. Bmj 1997: 315(7107); 540-3.

Evidence base of clinical diagnosis: The architecture of diagnostic research. D L Sackett, R B Haynes. BMJ 2002: 324(7336); 539-541. [Full text] [PDF]

Methodology for a multicenter study of serious infections in young infants in developing countries. The WHO Young Infants Study Group. Author Unknown. Pediatr Infect Dis J 1999: 18(10 Suppl); S8-16.

Diagnostic >> Guidelines >> Screening (1)

Users' guides to the medical literature: XVII. How to use guidelines and recommendations about screening. Evidence-Based Medicine Working Group. A. Barratt, L. Irwig, P. Glasziou, R. G. Cumming, A. Raffle, N. Hicks, J. A. Gray, G. H. Guyatt. Jama 1999: 281(21); 2029-34.

Diagnostic >> Likelihood Ratio (11)

Diagnosing Anaemia. Bandolier. Accessed on 2003-03-25. www.jr2.ox.ac.uk/bandolier/band45/b45-6.html

Diagnosing obstructive airway disease. Bandolier. Accessed on 2003-03-25. www.jr2.ox.ac.uk/bandolier/band78/b78-2.html

Diagnosing Prosthetic Joint Infection. Bandolier. Accessed on 2003-03-25. www.jr2.ox.ac.uk/bandolier/band63/b63-5.html

Signs and Symptoms Predict Thyroid Disease. Bandolier. Accessed on 2003-03-25. www.jr2.ox.ac.uk/bandolier/band46/b46-5.html

Using the Result. Bandolier. Accessed on 2003-03-25. www.jr2.ox.ac.uk/bandolier/band28/b28-5.html

Likelihood Ratios. Centre for Evidence-Based Medicine. Accessed on 2003-03-25. www.cebm.net/likelihood_ratios.asp

Pre-test Probability. Centre for Evidence-Based Medicine. Accessed on 2003-03-25. www.cebm.net/pretest_prob.asp

Computer program for the diagnosis and treatment of polycythemia rubra vera. B. Djulbegovic, I. Hozo. MD Comput 1999: 16(1); 83-9.

Accuracy of Diagnostic Tests. HealthTech. Accessed on 2003-03-25. www.rapid-diagnostics.org/accuracy.htm

Why we need large, simple studies of the clinical examination: the problem and a proposed solution. CARE-COAD1 group. Clinical Assessment of the Reliability of the Examination-Chronic Obstructive Airways Disease Group. F. A. McAlister, S. E. Straus, D. L. Sackett. Lancet 1999: 354(9191); 1721-4.

The likelihood ratio. An improved measure for reporting and evaluating diagnostic test results. K. L. Radack, G. Rouan, J. Hedges. Arch Pathol Lab Med 1986: 110(8); 689-93.

Diagnostic >> Likelihood Ratio >> Example (24)

Prevalence of clinical sinusitis in young children followed up by primary care pediatricians. M. Aitken, J. A. Taylor. Archives Pediatrics and Adolescent Medicine 1998: 152(3); 244-8.

Measurement of markers of tobacco smoking in patients with coronary heart disease. G. P. Archbold, M. E. Cupples, A. McKnight, T. Linton. Ann Clin Biochem 1995: 32 ( Pt 2)201-7.

Prospective evaluation of criteria for microbiological diagnosis of prosthetic-joint infection at revision arthroplasty. The OSIRIS Collaborative Study Group. B. L. Atkins, N. Athanasou, J. J. Deeks, D. W. Crook, H. Simpson, T. E. Peto, P. McLardy-Smith, A. R. Berendt. J Clin Microbiol 1998: 36(10); 2932-9. [Medline]

Can the clinical examination diagnose left-sided heart failure in adults? R. G. Badgett, C. R. Lucey, C. D. Mulrow. Jama 1997: 277(21); 1712-9. [Medline]

Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. V. K. Bhutani, L. Johnson, E. M. Sivieri. Pediatrics 1999: 103(1); 6-14.

Early detection of developmental dysplasia of the hip in The Netherlands: the validity of a standardized assessment protocol in infants. M. M. Boere-Boonekamp, T. H. Kerkhoff, P. B. Schuil, G. A. Zielhuis. American Journal of Public Health 1998: 88(2); 285-8.

Screening for alcohol abuse using CAGE scores and likelihood ratios. D. G. Buchsbaum, R. G. Buchanan, R. M. Centor, S. H. Schnoll, M. J. Lawton. Ann Intern Med 1991: 115(10); 774-7.

The diagnostic accuracy of cervico-vaginal fetal fibronectin in predicting preterm delivery: an overview. P. F. Chien, K. S. Khan, S. Ogston, P. Owen. British Journal of Obstetrics and Gynaecology 1997: 104(4); 436-44.

Does this patient have carpal tunnel syndrome? CA D' Arcy, S. McGee. Jama 2000: 283(23); 3110-7.

Does This Patient Have Carpal Tunnel Syndrome? Christopher A D'Arcy, Steven McGee. JAMA 2000: 283(23); 3110-3117.

Acute sinusitis: a cost-effective approach to diagnosis and treatment. LJ Fagnan. American Family Physician 1998: 58(8); 1795-1802; 1805-1806.

Laboratory diagnosis of iron-deficiency anemia: an overview. G. H. Guyatt, A. D. Oxman, M. Ali, A. Willan, W. McIlroy, C. Patterson. J Gen Intern Med 1992: 7(2); 145-53.

A survey of validity and utility of electronic patient records in a general practice. A. Hassey, D. Gerrett, A. Wilson. British Medical Journal 2001: 322(7299); p1401-5. [Abstract] [Full text] [PDF]

A clinical score to reduce unnecessary antibiotic use in patients with sore throat. W. J. McIsaac, D. White, D. Tannenbaum, D. E. Low. Cmaj 1998: 158(1); 75-83. [Medline] [Abstract] [PDF]

Iron deficiency anemia in the elderly: the diagnostic process. C. Patterson, G. H. Guyatt, J. Singer, M. Ali, I. Turpie. Cmaj 1991: 144(4); 435-40. [Medline] [Abstract]

Is this patient allergic to penicillin? An evidence-based analysis of the likelihood of penicillin allergy. A. R. Salkind, P. G. Cuddy, J. W. Foxworth. Jama 2001: 285(19); p2498-505.

The relation of conjunctival pallor to the presence of anemia. T. N. Sheth, N. K. Choudhry, M. Bowes, A. S. Detsky. J Gen Intern Med 1997: 12(2); 102-6.

The accuracy of patient history, wheezing, and laryngeal measurements in diagnosing obstructive airway disease. CARE-COAD1 Group. Clinical Assessment of the Reliability of the Examination-Chronic Obstructive Airways Disease. S. E. Straus, F. A. McAlister, D. L. Sackett, J. J. Deeks. Jama 2000: 283(14); 1853-7.

Clinical prediction of serious bacterial infections in young infants in developing countries. The WHO Young Infants Study Group. Author Unknown. Pediatr Infect Dis J 1999: 18(10 Suppl); S23-31.

Accuracy of a single question in screening for depression in a cohort of patients after stroke: comparative study. C. Watkins, L. Daniels, C. Jack, H. Dickinson, M. van Den Broek. Bmj 2001: 323(7322); p1159. [Full text] [PDF]

Rectal bleeding and colorectal cancer in general practice: diagnostic study. H. Wauters, V. Van Casteren, F. Buntinx. British Medical Journal 2000: 321(7267); 998-9. [Full text] [PDF]

Does this patient have a mole or a melanoma? J. D. Whited, J. M. Grichnik. Jama 1998: 279(9); p696-701.

Does this patient have sinusitis? Diagnosing acute sinusitis by history and physical examination. JW Jr Williams, DL Simel. JAMA 1993: 270(10); 1242-46.

Likelihood ratios to determine 'does this patient have appendicitis?': comment and clarification [letter; comment]. K. Witt, M. Makela, O. Olsen. Jama 1997: 278(10); 819; discussion 819-20.

Diagnostic >> ROC (14)

Comparing diagnostic tests: a simple graphic using likelihood ratios. B. J. Biggerstaff. Statistics in Medicine 2000: 19(5); 649-63.

Slopes of a receiver operating characteristic curve and likelihood ratios for a diagnostic test. BCK Choi. AJE 1998: 148(11); 1127-32.

Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. E. R. De Long, D. M. De Long, D. L. Clarke-Pearson. Biometrics 1988: 44(3); 837-45.

The ratio of free to total serum prostate specific antigen and its use in differential diagnosis of prostate carcinoma in Japan. S. Egawa, S. Soh, M. Ohori, T. Uchida, K. Gohji, A. Fujii, S. Kuwao, K. Koshiba. Cancer 1997: 79(1); 90-8.

Accuracy of clinical diagnosis of cirrhosis among alcohol-abusing men. K. J. Hamberg, B. Carstensen, T. I. Sorensen, K. Eghoje. J Clin Epidemiol 1996: 49(11); 1295-301.

Using the Hospital Anxiety and Depression Scale to screen for psychiatric disorders in people presenting with deliberate self-harm. D. Hamer, D. Sanjeev, E. Butterworth, P. Barczak. Br J Psychiatry 1991: 158782-4.

Screening for anxiety, depressive and somatoform disorders in rehabilitation--validity of HADS and GHQ-12 in patients with musculoskeletal disease. M. Harter, K. Reuter, K. Gross-Hardt, J. Bengel. Disabil Rehabil 2001: 23(16); 737-44.

The magnificent ROC (Receiver Operating Characteristic curve). Jo van Schalkwyk. Accessed on 2003-02-10. www.anaesthetist.com/mnm/stats/roc/

The influence of prostate volume on the ratio of free to total prostate specific antigen in serum of patients with prostate carcinoma and benign prostate hyperplasia. C. Stephan, M. Lein, K. Jung, D. Schnorr, S. A. Loening. Cancer 1997: 79(1); 104-9.

Sensitivity and specificity of observer and self-report questionnaires in major and minor depression following myocardial infarction. J. J. Strik, A. Honig, R. Lousberg, J. Denollet. Psychosomatics 2001: 42(5); 423-8.

Probabilistic analysis of global performances of diagnostic tests: interpreting the lorenz curve-based summary measures. L Wen-Chung. Stats in Medicine 1999: 18(4); 455-71.

Receiver Operating Characteristic (ROC) Literature Research. Kelly H. Zou. Accessed on 2002-11-27. splweb.bwh.harvard.edu:8000/pages/ppl/zou/roc.html

Receiver Operating Characteristic (ROC) Literature Research. Kelly H. Zou, Harvard Medical School. Accessed on 2003-05-09. splweb.bwh.harvard.edu:8000/pages/ppl/zou/roc.html

Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. MH Zweig, G Campbell. Clin Chem 1993: 39(4); 561-77.

Diagnostic >> ROC >> Example (2)

Diagnostic Accuracy of Four Assays of Prostatic Acid Phosphatase: Comparison Using Receiver Operating Characteristic Curve Analysis. JL Carson, JM Eisenberg, LM Shaw, et al:. Journal of the American Medical Association 1985: 253265-669.

The accuracy of patient history, wheezing, and laryngeal measurements in diagnosing obstructive airway disease. CARE-COAD1 Group. Clinical Assessment of the Reliability of the Examination-Chronic Obstructive Airways Disease. S. E. Straus, F. A. McAlister, D. L. Sackett, J. J. Deeks. Jama 2000: 283(14); 1853-7.

Diagnostic >> Screening (9)

10. Screening: Does earlier treatment improve the prognosis? D Coggon, Geoffrey Rose, DJP Barker. British Medical Journal 1997: [Full text]

C-reactive protein--to screen or not to screen? L. Mosca. N Engl J Med 2002: 347(20); 1615-7.

Screening for breast cancer with mammography. O. Olsen, P. C. Gotzsche. Cochrane Database Syst Rev 2001: (4); CD001877. [Medline]

Prolongation of the QT interval and the sudden infant death syndrome. P. J. Schwartz, M. Stramba-Badiale, A. Segantini, P. Austoni, G. Bosi, R. Giorgetti, F. Grancini, E. D. Marni, F. Perticone, D. Rosti, P. Salice. N Engl J Med 1998: 338(24); p1709-14. [Medline] [Abstract] [Full text] [PDF]

Women need better information about routine mammography. H. Thornton, A. Edwards, M. Baum. Bmj 2003: 327(7406); 101-3. [Medline] [Full text] [PDF]

When can a risk factor be used as a worthwhile screening test? N J Wald, AK Hackshaw, CD Frost. British Medical Journal 1999: 319(7224); 1562-1565. [Full text] [PDF]

Case-control studies of the efficacy of screening tests designed to prevent the incidence of cancer. N. S. Weiss. Am J Epidemiol 1999: 149(1); 1-4. [Medline]

Mass screening for rectal neoplasm in Jiashan County, China. G. M. Zheng, B. C. Choi, X. R. Yu, R. B. Zou, Y. W. Shao, X. Y. Ma. J Clin Epidemiol 1991: 44(12); 1379-85. [Medline]

Diagnostic >> Screening >> Example (21)

Occult pneumonias: empiric chest radiographs in febrile children with leukocytosis. R. Bachur, H. Perry, M. B. Harper. Annals of Emergency Medicine 1999: 33(2); 166-73. [Medline]

Effect of false-positive mammograms on interval breast cancer screening in a health maintenance organization. M. L. Burman, S. H. Taplin, D. F. Herta, J. G. Elmore. Annals of Internal Medicine 1999: 131(1); 1-6.

Percentage of free prostate-specific antigen in sera predicts aggressiveness of prostate cancer a decade before diagnosis. H. B. Carter, A. W. Partin, A. A. Luderer, E. J. Metter, P. Landis, D. W. Chan, J. L. Fozard, J. D. Pearson. Urology 1997: 49(3); 379-84.

Is screening for breast cancer with mammography justifiable? PC Gotzsche, O Olsen. Public Health 2000: 355(9198); 129-134.

A randomised study of screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennial screening rounds. O D Jorgensen, O Kronborg, C Fenger. Gut 2002: 50(1); 29-32. [Abstract]

Protective effect of faecal occult blood test screening for colorectal cancer: worse prognosis for screening refusers. Y Niv, M Lev-El, G Fraser, G Abuksis, A Tamir. Gut 2002: 50(1); 33-37. [Abstract]

Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. P. M. Ridker, N. Rifai, L. Rose, J. E. Buring, N. R. Cook. N Engl J Med 2002: 347(20); 1557-65.

The risks of screening: data from the Nottingham randomised controlled trial of faecal occult blood screening for colorectal cancer. M H E Robinson, JD Hardcastle, SM Moss, SS Amar, JO Chamberlain, NC Armitage, JH Scholefield, CM Mangham. Gut 1999: 45(4); 588-592.

Neuroblastoma Screening at One Year of Age. Freimut H. Schilling, Claudia Spix, Frank Berthold, Rudolf Erttmann, Natalja Fehse, Barbara Hero, Gisela Klein, Johannes Sander, Kerstin Schwarz, Joern Treuner, Ulrich Zorn, Joerg Michaelis. N Engl J Med 2002: 346(14); 1047-1053. [Abstract]

Effect of faecal occult blood screening on mortality from colorectal cancer: results from a randomised controlled trial. J H Scholefield, S Moss, F Sufi, C M Mangham, J D Hardcastle. Gut 2002: 50(6); 840-844. [Abstract]

Prospective cohort study of routine use of risk assessment scales for prediction of pressure ulcers. L. Schoonhoven, J. R. Haalboom, M. T. Bousema, A. Algra, D. E. Grobbee, M. H. Grypdonck, E. Buskens. Bmj 2002: 325(7368); 797.

A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, hemoccult. B. Towler, L. Irwig, P. Glasziou, J. Kewenter, D. Weller, C. Silagy. Bmj 1998: 317(7158); 559-65.

Surgery and the reduction of mortality from prostate cancer. P. C. Walsh. N Engl J Med 2002: 347(11); 839-40. [Medline]

Can the initial clinical assessment of thyroid function be improved? G. H. White, R. N. Walmsley. Lancet 1978: 2(8096); 933-5.

Future of preschool vision screening: Conclusions for or against services are invalid without appropriate research evidence [a compilation of letters RE: Future of preschool vision screening]. C Williams, et al. BMJ 1998: 316(7135); 937-940.

Colorectal cancer screening: Now is the time. Sidney J Winawer, Ann G Zauber. Canadian Medical Association Journal 2000: 163(5); 543-544.

The validity of urine examination for urinary tract infections in daily practice. R. A. Winkens, P. Leffers, T. A. Trienekens, E. E. Stobberingh. Fam Pract 1995: 12(3); 290-3.

Screening of Infants and Mortality Due to Neuroblastoma. William G. Woods, Ru-Nie Gao, Jonathan J. Shuster, Leslie L. Robison, Mark Bernstein, Sheila Weitzman, Greta Bunin, Isra Levy, Josee Brossard, Geoffrey Dougherty, Mendel Tuchman, Bernard Lemieux. N Engl J Med 2002: 346(14); 1041-1046. [Abstract]

Screening for prostate cancer: the roles of science, policy, and opinion in determining what is best for patients. S. H. Woolf, S. F. Rothemich. Annu Rev Med 1999: 50207-21.

Review: 4 clinical tests most accurately predict poor outcome in patients with anoxic-ischemic coma. EG Zandbergen. ACP Journal Club 1999: 131(1); 22.

Comparing accuracies of two screening tests in a two-phase study for dementia. Xiao-Hua Zhou. Appl. Statist. 1998: 47(1); 135-47.

Diagnostic >> Sn Sp (2)

Causal modeling to estimate sensitivity and specificity of a test when prevalence changes. B. C. Choi. Epidemiology 1997: 8(1); 80-6.

Sensitivity and specificity and their confidence intervals cannot exceed 100% [letter]. J. J. Deeks, D. G. Altman. British Medical Journal 1999: 318(7177); 193-4.

Diagnostic >> Sn Sp >> Example (21)

Effect of urine latex agglutination tests on the treatment of children at risk for invasive bacterial infection. P. M. Adcock, R. I. Paul, G. S. Marshall. Pediatrics 1995: 96(5 Pt 1); 951-4.

Is C-reactive protein useful in the management of children with suspected bacterial meningitis? D. R. Benjamin, K. E. Opheim, L. Brewer. Am J Clin Pathol 1984: 81(6); 779-82.

Sensitivity of a clinical examination to predict need for radiography in children with ankle injuries: a prospective study. K. Boutis, L. Komar, D. Jaramillo, P. Babyn, B. Alman, B. Snyder, K. D. Mandl, S. Schuh. Lancet 2001: 358(9299); 2118-21.

Analysis of Missed Cases of Abusive Head Truma. Jenny Carole, Kent P Hymel, Alene Ritzen, Steven E Reinert, Thomas C Hay. JAMA 1999: 281(7); 621-626.

The role of clinical suspicion in evaluating a new diagnostic test for active tuberculosis: results of a multicenter prospective trial. A. Catanzaro, S. Perry, J. E. Clarridge, S. Dunbar, S. Goodnight-White, P. A. LoBue, C. Peter, G. E. Pfyffer, M. F. Sierra, R. Weber, G. Woods, G. Mathews, V. Jonas, K. Smith, P. Della-Latta. Jama 2000: 283(5); 639-45.

Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. A. Cogo, A. W. Lensing, M. M. Koopman, F. Piovella, S. Siragusa, P. S. Wells, S. Villalta, H. R. Buller, A. G. Turpie, P. Prandoni. British Medical Journal 1998: 316(7124); 17-20.

Improved serodiagnostic testing for Lyme disease: results of a multicenter serologic evaluation. R. B. Craven, T. J. Quan, R. E. Bailey, R. Dattwyler, R. W. Ryan, L. H. Sigal, A. C. Steere, B. Sullivan, B. J. Johnson, D. T. Dennis, D. J. Gubler. Emerg Infect Dis 1996: 2(2); 136-40.

Sensitivity and specificity of QTc dispersion for identification of risk of cardiac death in patients with peripheral vascular disease. D. Darbar, J. Luck, N. Davidson, T. Pringle, G. Main, G. McNeill, A. D. Struthers. British Medical Journal 1996: 312(7035); 874-8; discussion 878-9. [Abstract] [Full text]

Latex agglutination testing in bacterial meningitis. F. O. Finlay, H. Witherow, P. T. Rudd. Arch Dis Child 1995: 73(2); 160-1.

Sensitivity and specificity of photography and direct ophthalmoscopy in screening for sight threatening eye disease: the Liverpool Diabetic Eye Study. S. P. Harding, D. M. Broadbent, C. Neoh, M. C. White, J. Vora. Bmj 1995: 311(7013); 1131-5. [Abstract] [Full text]

The value of clock drawing in identifying executive cognitive dysfunction in people with a normal Mini-Mental State Examination score. A. Juby, S. Tench, V. Baker. Cmaj 2002: 167(8); 859-64.

Accuracy of screening for gastric cancer using serum pepsinogen concentrations. F Kitahara, K Kobayashi, T Sato, Y Kojima, T Araki, M. A. Fujino. Gut 1999: 44(5); 693-97.

The SCOFF questionnaire and clinical interview for eating disorders in general practice: comparative study. A. J. Luck, J. F. Morgan, F. Reid, A. O'Brien, J. Brunton, C. Price, L. Perry, J. H. Lacey. British Medical Journal 2002: 325(7367); 755-6. [Full text] [PDF]

Value of cerebrospinal fluid leukocyte aggregation in distinguishing the causes of meningitis in children. I. C. Michelow, M. Nicol, C. Tiemessen, C. Chezzi, J. M. Pettifor. Pediatr 2000: 19(1); p66-72.

The predictive value of diagonal ear-lobe crease sign. M. Motamed, N. Pelekoudas. Int J Clin Pract 1998: 52(5); 305-6. [Medline]

Screening of newborn infants for cholestatic hepatobiliary disease with tandem mass spectrometry. I. Mushtaq, S. Logan, M. Morris, A. W. Johnson, A. M. Wade, D. Kelly, P. T. Clayton. Bmj 1999: 319(7208); 471-7. [Medline] [Abstract] [Full text] [PDF]

Experience colonoscopists missed 24% of adenomas. DK Rex, CS Cutler, et al. Lemmel GT. ACP Journal Club 1997: 127(1); 16.

Development and evaluation of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as a diagnostic tool for erectile dysfunction. R. C. Rosen, J. C. Cappelleri, M. D. Smith, J. Lipsky, B. M. Pena. Int J Impot Res 1999: 11(6); p319-26.

Sonographic measurement of uterine cervix at 18-22 weeks' gestation and the risk of preterm delivery. P Taipale, V Hiilesmaa. Obstetrics & Gynecology 1998: 92(6); 902-07.

The child with a non-blanching rash: how likely is meningococcal disease? L. C. Wells, J. C. Smith, V. C. Weston, J. Collier, N. Rutter. Arch 2001: 85(3); p218-22. [Abstract] [Full text]

Diagnosing fever by touch: observational study. K. Whybrew, M. Murray, C. Morley. Bmj 1998: 317(7154); 321. [Full text] [PDF]

Diagnostic >> Sn Sp >> Guidelines (2)

Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests; Draft Guidance for Industry and FDA Reviewers. Center for Devices and Radiological Health, U.S. Food and Drug Administration. Accessed on 2003-07-29. www.fda.gov/cdrh/osb/guidance/1428.html

The STARD Initiative -- Towards Complete and Accurate Reporting of Studies on Diagnostic Accuracy. STARD Group. Accessed on 2003-07-29. www.consort-statement.org/stardstatement.htm

Diagnostic >> Validation (4)

Patterns of psychiatric morbidity in a genito-urinary clinic. A validation of the Hospital Anxiety Depression scale (HAD). P. Barczak, N. Kane, S. Andrews, A. M. Congdon, J. C. Clay, T. Betts. Br J Psychiatry 1988: 152698-700.

The validity of the Hospital Anxiety and Depression Scale. An updated literature review. I. Bjelland, A. A. Dahl, T. T. Haug, D. Neckelmann. J Psychosom Res 2002: 52(2); 69-77.

Genetic test evaluation: information needs of clinicians, policy makers, and the public. W. Burke, D. Atkins, M. Gwinn, A. Guttmacher, J. Haddow, J. Lau, G. Palomaki, N. Press, C. S. Richards, L. Wideroff, G. L. Wiesner. Am J Epidemiol 2002: 156(4); 311-8.

Problems in using the hospital anxiety and depression scale for screening patients in general practice. A. C. Dowell, L. A. Biran. Br J Gen Pract 1990: 40(330); 27-8.

duplicate! (1)

The consort statement: revised recommendations for improving the quality of reports of parallel-group randomized trials [In Process Citation]. D. Moher, K. F. Schulz, D. G. Altman. J Am Podiatr Med Assoc 2001: 91(8); p437-42.

duplicate!!! (2)

A Comparison of the Burkard and Samplaire MK-3 Volumetric Collectors. Charles Barnes, Julie Landuyt, Freddy Pacheco, Susan Flappan, Stephen Simon, Jay Portnoy. 2000:

Semen Quality and Hormone Levels Among Radiofrequency Heat Sealer Operators. Barbara Grajewski, Ph.D, Clinton Cox, Ph.D, Steven M. Schrader, Ph.D, Steven M. Murray, M.S., Richard M. Edwards, B.S., Terry W. Turner, B.S., James M. Smith, Ph.D, Sam S. Shekar, M.D., Donald P. Evenson, Ph.D, Stephen D. Simon, Ph.D, David L. Conover, Ph.D. 1998:

duplicate? (3)

Readmission of Breastfeeding Infants Following Initial Hospital Discharge. R.T. Hall, MD, FAAP, M.T. Smith, BSE, S. Simon, Ph.D.

Evidence >> Apples >> Adjustment (33)

Evidence >> Apples >> Case Control (15)

Estimating the population attributable risk for multiple risk factors using case-control data. P. Bruzzi, S. B. Green, D. P. Byar, L. A. Brinton, C. Schairer. American Journal of Epidemiology 1985: 122(5); 904-14.

A nested case-control study of the effectiveness of screening for prostate cancer: research design. J. Concato, P. Peduzzi, A. Kamina, R. I. Horwitz. J Clin Epidemiol 2001: 54(6); 558-64. [Medline]

On choosing the control group in case-control studies. A. R. Feinstein, R. I. Horwitz. J Chronic Dis 1983: 36(4); 311-3. [Medline]

Choosing cases and controls: the clinical epidemiology of "clinical investigation". A. R. Feinstein, R. I. Horwitz. J Clin Invest 1988: 81(1); 1-5. [Medline]

An analysis of Berkson's bias in case-control studies. A. R. Feinstein, S. D. Walter, R. I. Horwitz. J Chronic Dis 1986: 39(7); 495-504. [Medline]

The case-control study. A practical review for the clinician. G. F. Hayden, M. S. Kramer, R. I. Horwitz. Jama 1982: 247(3); 326-31. [Medline]

Analysis of clinical susceptibility bias in case-control studies. Analysis as illustrated by the menopausal syndrome and the risk of endometrial cancer. R. I. Horwitz, A. R. Feinstein. Arch Intern Med 1979: 139(10); 1111-3. [Medline]

Community surveillance bias and the estrogen-endometrial cancer dispute. R. I. Horwitz, A. R. Feinstein. CA Cancer J Clin 1979: 29(4); 252-6. [Medline]

Methodologic standards and contradictory results in case-control research. R. I. Horwitz, A. R. Feinstein. Am J Med 1979: 66(4); 556-64. [Medline]

The problem of "protopathic bias" in case-control studies. R. I. Horwitz, A. R. Feinstein. Am J Med 1980: 68(2); 255-8. [Medline]

Experimental trials and case-control studies in the analysis of causality. R. I. Horwitz, A. R. Feinstein. Pathol Res Pract 1982: 174(3); 198-220. [Medline]

Case-control research. Temporal precedence and other problems of the exposure-disease relationship. R. I. Horwitz, A. R. Feinstein, M. R. Harvey. Arch Intern Med 1984: 144(6); 1257-9. [Medline]

Alternative data sources and discrepant results in case-control studies of estrogens and endometrial cancer. R. I. Horwitz, A. R. Feinstein, J. R. Stremlau. Am J Epidemiol 1980: 111(4); 389-94. [Medline]

Clinical complexity and epidemiologic uncertainty in case-control research. Fenoterol and asthma management. R. I. Horwitz, W. Spitzer, S. Buist, D. Cockcroft, P. Ernst, B. Habbick, B. Hemmelgarn, M. McNutt, A. S. Rebuck, S. Suissa. Chest 1991: 100(6); 1586-91. [Medline]

Scientific standards and the design of case-control research. T. F. Imperiale, R. I. Horwitz. Biomed Pharmacother 1989: 43(3); 187-96. [Medline]

Evidence >> Apples >> Case Control >> Weaknesses (1)

A collection of 56 topics with contradictory results in case-control research. L. C. Mayes, R. I. Horwitz, A. R. Feinstein. Int J Epidemiol 1988: 17(3); 680-5. [Medline]

Evidence >> Apples >> Case Studies (3)

Case studies, single-subject research, and N of 1 randomized trials: comparisons and contrasts. C. L. Backman, S. R. Harris. Am J Phys Med Rehabil 1999: 78(2); 170-6. [Medline]

The value of single-case research. S. K. Millard. Int J Lang Commun Disord 1998: 33 Suppl370-3. [Medline]

Single case research in mental health. T. Ricketts. Nurs Times 1998: 94(23); 52-5. [Medline]

Evidence >> Apples >> Casecontrol (14)

Reye's syndrome in the United States from 1981 through 1997. E. D. Belay, J. S. Bresee, R. C. Holman, A. S. Khan, A. Shahriari, L. B. Schonberger. New England Journal of Medicine 1999: 340(18); 1377-82. [Abstract] [Full text] [PDF]

A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. D. M. Cardo, D. H. Culver, C. A. Ciesielski, P. U. Srivastava, R. Marcus, D. Abiteboul, J. Heptonstall, G. Ippolito, F. Lot, P. S. McKibben, D. M. Bell. N Engl J Med 1997: 337(21); 1485-90. [Abstract] [Full text] [PDF]

Reye's syndrome. M. Casteels-Van Daele, C. Van Geet, C. Wouters, E. Eggermont. Lancet 2001: 358(9278); 334.

Testicular cancer risk in relation to use of disposable nappies. H. Moller. Arch Dis Child 2002: 86(1); 28-9.

Risk of testicular cancer in subfertile men: case-control study. H. Moller, N. E. Skakkebaek. British Medical Journal 1999: 318(7183); 559-62.

The disappearance of Reye's syndrome--a public health triumph. A. S. Monto. N Engl J Med 1999: 340(18); p1423-4.

Hospital controls versus community controls: differences in inferences regarding risk factors for hip fracture. D. J. Moritz, J. L. Kelsey, J. A. Grisso. Am J Epidemiol 1997: 145(7); 653-60.

Case-control studies: research in reverse. K. F. Schulz, D.A. Grimes. Lancet 2002: 359431-434.

Sources of Bias in Studies among Infertility Clients. Erik Tielemans, Alex Burdorf, Egbert te Velde, Rob Weber, Roelof van Kooij, Dick Heederik. Am. J. Epidemiol. 2002: 156(1); 86-92.

Design issues in case-control studies. S. Wacholder. Stat Methods Med Res 1995: 4(4); p293-309.

Selection of controls in case-control studies. I. Principles. S. Wacholder, J. K. McLaughlin, D. T. Silverman, J. S. Mandel. Am J Epidemiol 1992: 135(9); p1019-28.

Selection of controls in case-control studies. II. Types of controls. S. Wacholder, D. T. Silverman, J. K. McLaughlin, J. S. Mandel. Am J Epidemiol 1992: 135(9); p1029-41.

Selection of controls in case-control studies. III. Design options. S. Wacholder, D. T. Silverman, J. K. McLaughlin, J. S. Mandel. Am J Epidemiol 1992: 135(9); p1042-50.

Are risk factors for sudden infant death syndrome different at night? S. M. Williams, E. A. Mitchell, B. J. Taylor. Arch Dis Child 2002: 87(4); 274-8.

Evidence >> Apples >> Casecontrol >> Weaknesses (1)

Dietary fat and breast cancer risks. An epidemiologic perspective. G. R. Howe. Cancer 1994: 74(3 Suppl); 1078-84.

Evidence >> Apples >> Cluster (1)

Extending the CONSORT statement to cluster randomized trials: for discussion. D. R. Elbourne, M. K. Campbell. Stat Med 2001: 20(3); 489-96.

Evidence >> Apples >> Cluster >> Example (2)

Preventing injuries in children: cluster randomised controlled trials in primary care. D Kendrick, P Marsh, K Fielding, P Miller. British Medical Journal 1999: 318(7189); 980-83. [Medline] [Abstract] [Full text] [PDF]

Effect of community based management in failure to thrive: randomised controlled trial. C. M. Wright, J. Callum, E. Birks, S. Jarvis. Bmj 1998: 317(7158); 571-4. [Medline] [Abstract] [Full text] [PDF]

Evidence >> Apples >> Cohort (1)

Cigarette smoking and diabetes mellitus: evidence of a positive association from a large prospective cohort study. J. C. Will, D. A. Galuska, E. S. Ford, A. Mokdad, E. E. Calle. Int J Epidemiol 2001: 30(3); p540-6.

Evidence >> Apples >> Cohort >> Example (1)

Male Pattern Baldness and Coronary Heart Disease. Paulo A. Lotufo, C. U. Chae, U. A. Ajani, C. H. Hennekens, J. E. Manson. Archives of Internal Medicine 2000: 160(2); 165-171.

Evidence >> Apples >> Concealed (5)

Comparing like with like: some historical milestones in the evolution of methods to create unbiased comparison groups in therapeutic experiments. I. Chalmers. Int J Epidemiol 2001: 30(5); 1156-64. [Medline]

Randomised trials, human nature, and reporting guidelines. K. F. Schulz. Lancet 1996: 348(9027); 596-8.

Allocation concealment in randomised trials: defending against deciphering. K. F. Schulz, D.A. Grimes. Lancet 2002: 359614-618.

Generation of allocation sequences in randomised trials: chance not choice. K. F. Schulz, D.A. Grimes. Lancet 2002: 359515-519.

Empirical evidence of bias dimensions of methodological quality associated with estimates of treatment effects in controlled trials. KF Schulz, I Chalmers, RJ Hayes, DG Altman. JAMA 1995: 273(5); 408-12.

Evidence >> Apples >> Concealed Allocation (1)

The unpredictability paradox: review of empirical comparisons of randomised and non-randomised clinical trials. Regina Kunz, Andrew D. Oxman. British Medical Journal 1998: 317(7167); 1185-1190. [Medline] [Abstract] [Full text] [PDF]

Evidence >> Apples >> Control Group (3)

Chapter 7: The Rise of the Flow Theorists and the Fall of Science. James Buchal. Accessed on 2003-07-08. www.buchal.com/tgsh/chap7/c7fn.htm

Statistical Humor. Department of Epidemiology & Biostatistics, The University of Western Ontario. Accessed on 2003-07-08. www.uwo.ca/epidem/Consulting_Services/bsuhum.htm

Evidence-based dentistry: What is it, and what does it have to do with practice? I. Anecdote vs Data? Case for Evidence-based Decision Making. J.W. Robbins, P. Neilson, M. Grace, M.G. Newman, R. Niederman. Accessed on 2003-07-08. www.quintpub.com/news.php3?current_id=7

Evidence >> Apples >> Covariate Imbalance (2)

Bias in treatment assignment in controlled clinical trials. T. C. Chalmers, P. Celano, H. S. Sacks, H. Smith, Jr. N Engl J Med 1983: 309(22); 1358-61. [Medline]

Broken Brains or Flawed Studies? A Critical Review of ADHD Neuroimaging Research. Jonathan Leo. The Journal of Mind and Behavior 2003: 24(1); 29-56. [PDF]

Evidence >> Apples >> Crossover >> Advantages (1)

The case for cross-over trials in phase III. B Jones. Statistics in Medicine 1995: 14(9-10); 1025-38.

Evidence >> Apples >> Crossover >> Example (1)

Randomised crossover trial comparing the performance of Clinical Terms Version 3 and Read Codes 5 byte set coding schemes in general practice. P. J. Brown, V. Warmington, M. Laurence, A. T. Prevost. Bmj 2003: 326(7399); 1127. [Medline] [Abstract] [Full text] [PDF]

Evidence >> Apples >> Ecologic (5)

Modeling treatment effects on binary outcomes with grouped-treatment variables and individual covariates. S. C. Johnston, T. Henneman, C. E. McCulloch, M. van der Laan. Am J Epidemiol 2002: 156(8); 753-60.

The Semi-individual Study in Air Pollution Epidemiology: A Valid Design as Compared to Ecologic Studies. Nino Kunzli, Ira B. Tager. Environmental Health Perspectives 1997: 105(10); 1078-1083.

Ecologic studies in epidemiology: concepts, principles, and methods. H. Morgenstern. Annu Rev Public Health 1995: 1661-81.

Medicine and the Media: Did Monica really say that? Hugh Tunstall-Pedoe. British Medical Journal 1998: 3171023. [Full text]

Ecological study for reasons for sharp decline in mortality from ischaemic heart disease in Poland since 1991. WA Zatonski, AJ McMichael, JW Powles. British Medical Journal 1998: 316(7137); 1047-1051. [Medline] [Abstract] [PDF]

Evidence >> Apples >> Ecologic >> Weaknesses (1)

Dietary fat and breast cancer risks. An epidemiologic perspective. G. R. Howe. Cancer 1994: 74(3 Suppl); 1078-84.

Evidence >> Apples >> Example (7)

The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group. NEJM 1994: 330(15); 1029-35.

Influence of maternal age at delivery and birth order on risk of type 1 diabetes in childhood: prospective population based family study. Bart's-Oxford Family Study Group. P. J. Bingley, I. F. Douek, C. A. Rogers, E. A. Gale. British Medical Journal 2000: 321(7258); 420-4. [Medline] [Abstract] [Full text] [PDF]

Statistical Inquiries into the Efficacy of Prayer. Sir Francis Galton. Fortnightly Review 1872: 12125-135. [Full text] [PDF]

Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. C. H. Hennekens, J. E. Buring, J. E. Manson, M. Stampfer, B. Rosner, N. R. Cook, C. Belanger, F. La Motte, J. M. Gaziano, P. M. Ridker, W. Willett, R. Peto. N Engl J Med 1996: 334(18); 1145-9.

Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. G. S. Omenn, G. E. Goodman, M. D. Thornquist, J. Balmes, M. R. Cullen, A. Glass, J. P. Keogh, F. L. Meyskens, Jr., B. Valanis, J. H. Williams, Jr., S. Barnhart, M. G. Cherniack, C. A. Brodkin, S. Hammar. Journal of the National Cancer Institute 1996: 88(21); 1550-9. [Medline]

Observational Studies. PR Rosenbaum (1995) New York: Springer-Verlag.

Comparison of maternal and infant outcomes between vacuum extraction and forceps deliveries. S. W. Wen, S. Liu, M. S. Kramer, S. Marcoux, A. Ohlsson, R. Sauve, R. Liston. Am J Epidemiol 2001: 153(2); 103-7.

Evidence >> Apples >> General (1)

Data Companion - Types of Research Studies. Susan G. Komen Breast Cancer Foundation. Accessed on 2003-07-08. www.komen.org/bci/abc/dc/dc_studies.asp

Evidence >> Apples >> Hierarchy (1)

Randomized, Controlled Trials, Observational Studies, and the Hierarchy of Research Designs. John Concato, Nirav Shah, Ralph I. Horwitz. The New England Journal of Medicine 2000: 342(25); 1887-1892. [Medline]

Evidence >> Apples >> Historical (5)

Impact of Cost Reduction Programs on Short-Term Patient Outcome and Hospital Cost of Total Knee Arthroplasty. William L. Healy, Richard Iorio, John Ko, David Appleby, David W. Lemos. J Bone Joint Surg Am 2002: 84(3); 348-353. [Medline] [Abstract] [Full text] [PDF]

A Challenge for HD Researchers. Ken Pidock, Huntington's Disease Advocacy Center. Accessed on 2003-06-20. www.hdac.org/features/article.php?p_articleNumber=32

The way forward for clinical research. Sir Michael Rawlins, Pharmafocus. Accessed on 2003-06-20. www.pharmafile.com/Pharmafocus/Features/feature.asp?fID=354

Randomized versus Historical Controls for Clinical Trials. H Sacks, TC Chalmers, H Jr Smith. The American Journal of Medicine 1982: 72(2); 233-240.

Randomized versus historical controls for clinical trials. H. Sacks, T. C. Chalmers, H. Smith, Jr. Am J Med 1982: 72(2); 233-40. [Medline]

Evidence >> Apples >> Imbalance (11)

Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46 000 women from Royal College of General Practitioners' oral contraception study. V. Beral, C. Hermon, C. Kay, P. Hannaford, S. Darby, G. Reeves. British Medical Journal 1999: 318(7176); 96-100.

Low-weight neonatal survival paradox in the Czech Republic. E. Carlson, J. M. Hoem. Am J Epidemiol 1999: 149(5); 447-53.

Severity of comorbidity, not type of surgery, affects outcome of prostatectomy. J. Concato, J. G. Elmore, R. I. Horwitz, S. F. Schiff, A. R. Feinstein. Trans Assoc Am Physicians 1990: 10390-5. [Medline]

Problems of comorbidity in mortality after prostatectomy. J. Concato, R. I. Horwitz, A. R. Feinstein, J. G. Elmore, S. F. Schiff. Jama 1992: 267(8); 1077-82. [Medline]

Differences between women and men in survival after myocardial infarction. Biology or methodology? N. H. Fiebach, C. M. Viscoli, R. I. Horwitz. Jama 1990: 263(8); 1092-6. [Medline]

Exclusion bias and the false relationship of reserpine and breast cancer. R. I. Horwitz, A. R. Feinstein. Arch Intern Med 1985: 145(10); 1873-5. [Medline]

Detection bias in endometrial cancer. R. I. Horwitz, A. R. Feinstein, S. J. Robboy. Lancet 1982: 1(8264); 164. [Medline]

The role of susceptibility bias in epidemiologic research. R. I. Horwitz, M. J. McFarlane, T. A. Brennan, A. R. Feinstein. Arch Intern Med 1985: 145(5); 909-12. [Medline]

Truths about the NINDS study: setting the record straight. Jeffrey Mann. West J Med 2002: 176(3); 192-194. [Medline] [Full text] [PDF]

Detection bias and relation of benign breast disease to breast cancer. A. L. Silber, R. I. Horwitz. Lancet 1986: 1(8482); 638-40. [Medline]

Crude rates, without standardisation for age, are always misleading. Hugh Tunstall-Pedoe. BMJ 1998: 317(7156); 475b-. [Full text]

Evidence >> Apples >> Matching (5)

Hypothesis: Comparisons of inter- and intra-individual variations can substitute for twin studies in drug research. W. Kalow, B. K. Tang, L Endrenyi. Pharmacogenetics 1998: 8(4); 283-289.

Removal of radiation dose response effects: an example of over-matching. J. L. Marsh, J. L. Hutton, K. Binks. Bmj 2002: 325(7359); 327-30. [Medline] [Full text] [PDF]

Influence of variation in birth weight within normal range and within sibships on IQ at age 7 years: cohort study. Thomas D Matte, Michaeline Bresnahan, Melissa D Begg, Ezra Susser. BMJ 2001: 323(7308); 310-314. [Medline] [Abstract] [Full text] [PDF]

Paired versus Two-Sample Design for a Clinical Trial of Treatments with Dichotomous Outcome: Power Considerations. S Wacholder, CR Weinberg. Biometrics 1982: 38(3); 801-812.

Matching in epidemiology as a paradigm for twin research on the Etiology of Disease. C White. Acta Geneticae Medicae Et Gemellologiae 1981: 30(1); 77-86.

Evidence >> Apples >> Matching >> Example (2)

Home versus hospital deliveries: follow up study of matched pairs for procedures and outcome. Ursula Ackermann-Liebrich, Thomas Voegeli, Kathrin Gunter-Witt, Isabelle Kunz, Maja Zullig, Christian Schindler, Margrit Maurer, Zurich Study Team. BMJ 1996: 313(7068); 1313-1318. [Medline] [Abstract] [Full text]

Helicobacter pylori infection and early onset myocardial infarction: case-control and sibling pairs study. John Danesh, Linda Youngman, Sarah Clark, Sarah Parish, Richard Peto, Rory Collins. BMJ 1999: 319(7218); 1157-1162. [Medline] [Abstract] [Full text] [PDF]

Evidence >> Apples >> Matching >> Stratification (1)

Stratified randomization for clinical trials. W. N. Kernan, C. M. Viscoli, R. W. Makuch, L. M. Brass, R. I. Horwitz. J Clin Epidemiol 1999: 52(1); 19-26. [Medline]

Evidence >> Apples >> Observational (19)

A comparison of observational studies and randomized, controlled trials. K. Benson, A. J. Hartz. New England Journal of Medicine 2000: 342(25); 1878-86.

Invited commentary: Rare side effects of obstetric interventions: Are observational studies good enough? P. Buekens. Am J Epidemiology 2001: 153(2); 108-9.

Trends in mortality in older women: findings from the Nun Study. S. M. Butler, D. A. Snowdon. J Gerontol B Psychol Sci Soc Sci 1996: 51(4); S201-8. [Medline]

Data dredging, bias, or confounding. George Davey Smith, Shah Ebrahim. BMJ 2002: 325(7378); 1437-1438. [Medline] [Full text] [PDF]

Systematic reviews and lifelong diseases. H. E. Elphick, A. Tan, D. Ashby, R. L. Smyth. Bmj 2002: 325(7360); 381-4. [Full text] [PDF]

Observational studies of cause-effect relationships: an analysis of methodologic problems as illustrated by the conflicting data for the role of oral contraceptives in the etiology of rheumatoid arthritis. J. M. Esdaile, R. I. Horwitz. J Chronic Dis 1986: 39(10); 841-52. [Medline]

Double standards, scientific methods, and epidemiologic research. A. R. Feinstein, R. I. Horwitz. N Engl J Med 1982: 307(26); 1611-7. [Medline]

Statistics in Action. M.H. Gail. Journal of the American Statistical Association 1996: 91(433); 1-13.

Research Fables from the Sisters Grinn, No. 1. The Hunch-test of Notre Dame.. Jeanne Grace, University of Rochester School of Nursing. Accessed on 2003-05-27. www.urmc.rochester.edu/SON/Fables/hunchbck.htm

Epidemiologic methods and methodologic vigilance. R. I. Horwitz, D. F. Ransohoff. J Gen Intern Med 1988: 3(3); 298-9. [Medline]

How Good Is the Evidence Linking Breastfeeding and Intelligence? Anjali Jain, John Concat, John M. Leventhal. Pediatrics Journals 2002 (April): 109(6); 1044-1053.

Problems and approaches in investigating the role of micronutrients in the aetiology of cancer in humans. J. Little. Br Med Bull 1999: 55(3); 600-18.

Interpreting the evidence: choosing between randomised and non-randomised studies. M McKee, A Britton, N Black, K McPherson, C Sanderson, C Bain. British Medical Journal 1999: 319(7205); 312-15. [Medline] [Full text] [PDF]

The Cochrane Lecture. The best and the enemy of the good: randomised controlled trials, uncertainty, and assessing the role of patient choice in medical decision making. K. McPherson. J. Epidemiol. Community Health 1994: 48(1); 6-15. [Medline]

The arrogance of preventive medicine. D. L. Sackett. Cmaj 2002: 167(4); 363-4.

Humility in observational studies. J. D. Shelton. Science 2002: 297(5590); 2208.

Fat chance: diet and ischemic stroke [editorial; comment]. R. Sherwin, T. R. Price. Jama 1997: 278(24); 2185-6.

Smoking as "independent" risk factor for suicide: illustration of an artifact from observational epidemiology? G. D. Smith, A. N. Phillips, J. D. Neaton. Lancet 1992: 340(8821); 709-12.

Epidemiology faces its limits. G. Taubes. Science 1995: 269(5221); p164-9.

Evidence >> Apples >> Observational >> Advantages (2)

Why we need observational studies to evaluate the effectiveness of health care. N. Black. British Medical Journal 1996: 312(7040); 1215-8. [Medline] [Full text]

Evidence from case-control and cohort studies for adverse drug reaction: a case study of analgesic nephropathy. Wei-Ya Zhang. Accessed on 2003-07-08. www.biomedcentral.com/abstracts/cochrane/1/pc149/

Evidence >> Apples >> Observational >> Comparison (1)

Randomized, Controlled Trials, Observational Studies, and the Hierarchy of Research Designs. John Concato, Nirav Shah, Ralph I. Horwitz. The New England Journal of Medicine 2000: 342(25); 1887-1892. [Medline]

Evidence >> Apples >> Observational >> Example (1)

Dietary Fat Intake and the Risk of Coronary Heart Disease in Women. Frank B. Hu, Meir J. Stampfer, JoAnn E. Manson, Eric Rimm, Graham A. Colditz, Bernard A. Rosner, Charles H. Hennekens, Walter C. Willett. N Engl J Med 1997: 337(21); 1491-1499. [Abstract] [Full text] [PDF]

Evidence >> Apples >> Observational >> Strengths (1)

Developing improved observational methods for evaluating therapeutic effectiveness. R. I. Horwitz, C. M. Viscoli, J. D. Clemens, R. T. Sadock. Am J Med 1990: 89(5); 630-8. [Medline]

Evidence >> Apples >> Observational >> Weaknesses (1)

Bias or biology: evaluating the epidemiologic studies of L-tryptophan and the eosinophilia-myalgia syndrome. R. I. Horwitz, S. R. Daniels. J Rheumatol Suppl 1996: 4660-72. [Medline]

Evidence >> Apples >> Overview (2)

Study designs in medical research. Ronald Thisted. Accessed on 2003-06-20. galton.uchicago.edu/~thisted/courses/315/lectures/0297.pdf

What is a P-value?. Ronald Thisted. Accessed on 2003-06-20. www.stat.uchicago.edu/~thisted/Distribute/pvalue.pdf

Evidence >> Apples >> Randomization (62)

The mythology of randomization. U. Abel, A. Koch. Accessed on 2003-06-30. www.symposion.com/nrccs/abel.htm

Randomization and baseline comparisons in clinical trials. DF Altman, CJ Dore. Lancet 1990: 335149 - 153.

The Paired Availability Design: An Update. S. G. Baker. Accessed on 2003-06-30. www.symposion.com/nrccs/baker.htm

Clinical trials. Simple megatrials are not sufficient. D. Barer. British Medical Journal 1999: 318(7191); 1138. [Medline] [Full text]

Randomised controlled trials in psychiatry. Trials show that psychotherapy is effective for wide range of psychological conditions. H. Barker. British Medical Journal 2000: 320(7228); 186. [Medline] [Full text]

Reflections on randomised controlled trials in surgery. M. Baum. Lancet 1999: 353 Suppl 1SI6-8.

Unconventional therapies and cancer. M. Begin, E. Kaegi. Cmaj 1999: 161(6); 686-7.

Integrative medicine and systemic outcomes research: issues in the emergence of a new model for primary health care. I. R. Bell, O. Caspi, G. E. Schwartz, K. L. Grant, T. W. Gaudet, D. Rychener, V. Maizes, A. Weil. Arch Intern Med 2002: 162(2); 133-40. [Medline]

Evidence from randomised trials on the long-term effects of hormone replacement therapy. V. Beral, E. Banks, G. Reeves. Lancet 2002: 360(9337); 942-4. [Medline]

Coronary artery surgery study (CASS): a randomized trial of coronary artery bypass surgery. Comparability of entry characteristics and survival in randomized patients and nonrandomized patients meeting randomization criteria. CASS Principal Investigators and Their Associates. Journal of the American College of Cardiology 1984: 3(1); 114-28. [Medline]

Comparing like with like: some historical milestones in the evolution of methods to create unbiased comparison groups in therapeutic experiments. I. Chalmers. Int J Epidemiol 2001: 30(5); 1156-64. [Medline]

Experimental Study versus Non-Experimental Study: The Non-Experimental (Non-Randomized) Study as a Methodological Compromise. K. Dannehl. Accessed on 2003-06-30. www.symposion.com/nrccs/dannehl.htm

Evidence based conclusions on the efficacy of a treatment - What can be learned from risk assessment?. L. Edler. Accessed on 2003-06-30. www.symposion.com/nrccs/ledler.htm

Problems of Randomized Trials. A.R. Feinstein. Accessed on 2003-06-30. www.symposion.com/nrccs/feinstein.htm

Advances in Clinical Trials in theTwentieth Century. Lloyd D. Fisher. Annual Review 1999: 20109-124.

A Nonparametric Test for Evaluating Coherent Alternativesin Nonrandomised Studies. O. Gefeller, L. Pralle. Accessed on 2003-06-30. www.symposion.com/nrccs/gefeller.htm

Randomized Controlled Trials: Evidence Biased Psychiatry. David Healy, Alliance for Human Research Protection. Accessed on 2002-www.researchprotection.org/COI/healy0802.html

The Analysis of Intervention Effects Using Observational Data Bases. C. Heuer, U. Abel. Accessed on 2003-06-30. www.symposion.com/nrccs/heuer.htm

Proof versus plausibility: rules of engagement for the struggle to evaluate alternative cancer therapies. L. J. Hoffer. Cmaj 2001: 164(3); 351-3.

Methodological Contributions to Clinical Research: Random Sampling, Randomization, and Equivalence of Contrasted Groups in Psychotherapy Outcome Research. Louis M Hsu. Journal of Consulting and Clinical Psychology 1989: 57(1); 131-137.

Comparison of evidence of treatment effects in randomized and nonrandomized studies. J. P. Ioannidis, A. B. Haidich, M. Pappa, N. Pantazis, S. I. Kokori, M. G. Tektonidou, D. G. Contopoulos-Ioannidis, J. Lau. Jama 2001: 286(7); p821-30.

Amniotomy or oxytocin for induction of labor. Re-analysis of a randomized controlled trial. M. J. Keirse. Acta Obstet Gynecol Scand 1988: 67(8); p731-5.

Discussion: Why Clinical Trials in the Evaluation of Life Style Evaluation? Genell L. Knatterud, PhD. Control Clinical Trials 1997: 18(6); 514-516.

"The 60-Minutes-Myocardial Infarction Project": Comparison with a Registry and a Randomized Clinical Trial. A. Koch, A. Hörmann, H. Löwel, J. Senges. Accessed on 2003-06-30. www.symposion.com/nrccs/koch.htm

Breastfeeding and infant growth: biology or bias? M. S. Kramer, T. Guo, R. W. Platt, S. Shapiro, J. P. Collet, B. Chalmers, E. Hodnett, Z. Sevkovskaya, I. Dzikovich, I. Vanilovich. Pediatrics 2002: 110(2 Pt 1); 343-7.

The unpredictability paradox: review of empirical comparisons of randomised and non-randomised clinical trials. Regina Kunz, Andrew D. Oxman. British Medical Journal 1998: 317(7167); 1185-1190. [Medline] [Abstract] [Full text] [PDF]

Problems of Randomized Controlled Trails (RCT) in Surgery. R. Lefering, E. Neugebauer. Accessed on 2003-06-30. www.symposion.com/nrccs/lefering.htm

The Psychic Staring Effect: An Artifact of Pseudo Randomization. David F. Marks, John Colwell. Skeptical Inquirer 2000: 24(5); 41-44 and 49.

Evaluating complementary medicine: methodological challenges of randomised controlled trials. S. Mason, P. Tovey, A. F. Long. Bmj 2002: 325(7368); 832-4.

Reference - controlled observational studies - a new tool for post marketing studies and for evaluation of preventive measures. J. Michaelis. Accessed on 2003-06-30. www.symposion.com/nrccs/michaeli.htm

Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease. GS Omenn, GE Goodman, MD Thornquist, J Balmes, MR Cullen, A Glass, JP Keogh, FL Meyskens, B Valanis, JH Williams, S Barnhart, S Hammar. The New England Journal of Medicine 1992: 334(18); 1150-1155.

Difficulties of Randomised Controlled Trials. House of Lords United Kingdom Parliament. Accessed on 2002-12-31. www.parliament.the-stationery-office.co.uk/pa/ld199900/ldselect/ldsctech/123/12323.htm

Issues to Consider When Designing RCTs for CAM Therapies. House of Lords United Kingdom Parliament. Accessed on 2002-12-23. www.parliament.the-stationery-office.co.uk/pa/ld199900/ldselect/ldsctech/123/12315.htm#a68

Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. S. J. Pocock, R. Simon. Biometrics 1975: 31(1); 103-15.

Understanding controlled trials: Randomisation methods in controlled trials. Chris Roberts, David Torgerson. BMJ 1998: 317(7168); 1301-1310. [Full text] [PDF]

Understanding controlled trials: Baseline imbalance in randomised controlled trials. Chris Roberts, David J Torgerson. BMJ 1999: 319(7203); 185-. [Full text] [PDF]

Randomised block design is more powerful than minimisation [letter]. N. Ross. British Medical Journal 1999: 318(7178); 263-4.

Estimation from nonrandomized treatment comparisons using subclassification on propensity scores. D. B. Rubin. Accessed on 2003-06-30. www.symposion.com/nrccs/rubin.htm

Why randomized controlled trials fail but needn't: 1. Failure to gain "coal-face" committment and to use the uncertainty principle. DL Sackett, J Hoey. Canadian Medical Association Journal 2000: 162(9); 1311-1314. [Medline] [Full text] [PDF]

Assessing the quality of randomization from reports of controlled trials published in obstetrics and gynecology journals. KF Schulz, I Chalmers, DA Grimes, DG Altman. JAMA 1994: 272125 - 8.

Patients' preferences and randomised trials. W. A. Silverman, D. G. Altman. Lancet 1996: 347(8995); p171-4.

Casting and Drawing Lots. W.A. Silverman, I. Chalmers. In: ed. Controlled Trials from History. By, I Chalmers, I. Milne, and U. Trohler. 2001; Vol.

Patient Heterogeneity in Clinical Trials. Richard Simon. Cancer Treatment Reports 1980: 64(2-3); 405-410.

Randomized controlled trials in surgery. M. J. Solomon, A. Laxamana, L. Devore, R. S. McLeod. Surgery 1994: 115(6); p707-12.

Ginkgo for memory enhancement: a randomized controlled trial. P. R. Solomon, F. Adams, A. Silver, J. Zimmer, R. DeVeaux. Jama 2002: 288(7); 835-40.

Effect of Sleep deprivation on surgeons' dexterity on laparoscopy simulator. N J Taffinder, IC McManus, Y Gul, RC Russell, A Darzi. The Lancet 1998: 352(9135); 1191.

Minimization: A new method of assigning patients to treatment and control groups. Donald R. Taves. Clinical Pharmacology and Therapeutics 1974: 15(5); 443-453.

Effect of preoperative abstinence on poor postoperative outcome in alcohol misusers: randomised controlled trial. H Tonnesen, J Rosenberg, HJ Nielsen, V Rasmussen, C Hauge, IK Pedersen, H Kehlet. British Medical Journal 1999: 318(7194); 1311-1316.

Contamination in trials: is cluster randomisation the answer? David J Torgerson. BMJ 2001: 322(7282); 355-357. [Full text]

Use of unequal randomisation to aid the economic efficiency of clinical trials. David J Torgerson, Marion K Campbell. BMJ 2000: 321759. [Full text] [PDF]

Understanding controlled trials: What is Zelen's design? David J Torgerson, Martin Roland. BMJ 1998: 316(7131); 606. [Full text]

Understanding controlled trials: What is a patient preference trial? David Torgerson, Bonnie Sibbald. BMJ 1998: 316(7128); 360. [Full text]

Minimisation: the platinum standard for trials? Randomisation doesn't guarantee similarity of groups; minimisation does [editorial] [see comments]. T Treasure, KD MacRae. BMJ 1998: 317(7155); 362-63.

Minimisation is much better than the randomised block design in certain cases. Tom Treasure, KD MacRae. British Medical Journal 1999: 318(7195); 1420.

Can postmarketing surveillance studies (Anwendungsbeobachtungen) give meaningful answers to important questions? A critical discussion of 5 examples.. M. Wadepuhl. Accessed on 2003-06-30. www.symposion.com/nrccs/wadepuhl.htm

Investigating Therapies of Potentially Great Benefit: ECMO. J.H. Ware. Statistical Science 1989: 4(4); 298-317.

Mammography and the politics of randomised controlled trials. J. Wells. Bmj 1998: 317(7167); 1224-9. [Full text] [PDF]

Randomised controlled trial of laparoscopic versus open mesh repair for inguinal hernia: outcome and cost. J. Wellwood, M. J. Sculpher, D. Stoker, G. J. Nicholls, C. Geddes, A. Whitehead, R. Singh, D. Spiegelhalter. Bmj 1998: 317(7151); 103-10.

The protective effect of auto-immune buccal urine therapy (AIBUT) against the Raynaud phenomenon. C. W. Wilson. Med Hypotheses 1984: 13(1); 99-107.

Randomised controlled trials in primary care: case study. Sue Wilson. British Medical Journal 2000: 32124-27. [Medline] [Full text] [PDF]

Comparison of St John's wort and imipramine for treating depression: randomised controlled trial. H. Woelk. Bmj 2000: 321(7260); p536-9.

Use of randomisation in the Medical Research Council's clinical trial of streptomycin in pulmonary tuberculosis in the 1940s. Alan Yoshioka. British Medical Journal 1998: 317(7167); 1220-1223.

Evidence >> Apples >> Randomization >> Advantages (1)

Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women. S Hulley, D Grady, T Bush, C Furberg, D Herrington, B Riggs, E Vittinghoff. JAMA 1998: 280(7); 605-613.

Evidence >> Apples >> Randomization >> Ethics (1)

Randomisation and patient choice. I. Chalmers, T. C. Chalmers. Lancet 1994: 344(8926); 892-3. [Medline]

Evidence >> Apples >> Randomization >> Example (2)

Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. G. S. Omenn, G. E. Goodman, M. D. Thornquist, J. Balmes, M. R. Cullen, A. Glass, J. P. Keogh, F. L. Meyskens, B. Valanis, J. H. Williams, S. Barnhart, S. Hammar. New England Journal of Medical 1996: 334(18); 1150-5.

Chemoprevention of Lung Cancer: The Rise and Demise of Beta-Carotene. Gilbert S. Omenn. Annu. Rev. Public Health 1998: 1973-99.

Evidence >> Apples >> Randomization >> Guidelines (1)

Randomisation in clinical trials. E. M. Beller, V. Gebski, A. C. Keech. Med J Aust 2002: 177(10); 565-7. [Medline] [Full text] [PDF]

Evidence >> Apples >> Randomization >> Weaknesses (4)

Problems in the "evidence" of "evidence-based medicine". A. R. Feinstein, R. I. Horwitz. Am J Med 1997: 103(6); 529-35. [Medline]

The double-blind, randomized, placebo-controlled trial: gold standard or golden calf? T. J. Kaptchuk. J Clin Epidemiol 2001: 54(6); 541-9. [Medline]

The Di Bella multitherapy trial. Randomised controlled trials may not always be absolutely needed [letter]. A Liberati, N Magrini, L Patoia, L Pagliaro. British Medical Journal 1999: 318(7190); 1073-4.

Understanding controlled trials: What are pragmatic trials? Martin Roland, David J Torgerson. BMJ 1998: 316(7127); 285-. [Full text]

Evidence >> Apples >> Randomize >> Ethics (1)

Randomize the first patient. T. C. Chalmers. N Engl J Med 1977: 296(2); 107. [Medline]

Evidence >> Apples >> Randomized (1)

Comparability of randomised groups. Douglas G. Altman. The Statistician 1985: 34125-136.

Evidence >> Apples >> Randomized >> Weaknesses (1)

Problems in the conduct and analysis of randomized clinical trials. Are we getting the right answers to the wrong questions? L. Rabeneck, C. M. Viscoli, R. I. Horwitz. Arch Intern Med 1992: 152(3); 507-12. [Medline]

Evidence >> Apples >> Residual Confounding (2)

Risk of adverse birth outcomes in populations living near landfill sites. P. Elliott, D. Briggs, S. Morris, C. de Hoogh, C. Hurt, T. K. Jensen, I. Maitland, S. Richardson, J. Wakefield, L. Jarup. British Medical Journal 2001: 323(7309); 363-8.

Is Residual Confounding a Reasonable Explanation for the Apparent Protective Effects of Beta-carotene Found in Epidemiologic Studies of Lung Cancer in Smokers? Daniel O. Stram, Mark Huberman and Anna H. Wu. Am. J of Epidemiology 2002: 155(7); 622-628.

Evidence >> Apples >> Singlecase (1)

Single-case Reseach Designs for the Science and Practice of Neurotherapy. Neville Blampied, Arreed Barabasz, Marianne Barabasz. Journal of Neurotherapy 1996: 1(4);

Evidence >> Apples >> Stratification >> Example (2)

How to evaluate and improve the quality and credibility of an outcomes database: validation and feedback study on the UK Cardiac Surgery Experience. Leon G Fine, Bruce E Keogh, Shan Cretin, Maria Orlando, Mairi M Gould. BMJ 2003: 326(7379); 25-28. [Medline] [Abstract] [Full text] [PDF]

Workforce retention in rural and remote Australia: determining the factors that influence length of practice. J. S. Humphreys, M. P. Jones, J. A. Jones, P. R. Mara. Med J Aust 2002: 176(10); 472-6. [Medline] [Full text] [PDF]

Evidence >> Apples >> Vitamin C (21)

Clinical Evaluaation of Vitamin C and other Micronutrients in the Treatment of Cancer. Gerald MD Batist. Journal of Orthomolecular Medicine 2000: 15(4); 189-192.

Protocol for the use of vitamin C in the treatment of cancer. E. Cameron. Med Hypotheses 1991: 36(3); 190-4. [Medline]

The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. E. Cameron, A. Campbell. Chem Biol Interact 1974: 9(4); 285-315. [Medline]

Innovation vs. quality control: an 'unpublishable' clinical trial of supplemental ascorbate in incurable cancer. E. Cameron, A. Campbell. Med Hypotheses 1991: 36(3); 185-9. [Medline]

Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. E. Cameron, L. Pauling. Proc Natl Acad Sci U S A 1976: 73(10); 3685-9. [Medline]

Experimental studies designed to evaluate the management of patients with incurable cancer. E. Cameron, L. Pauling. Proc Natl Acad Sci U S A 1978: 75(12); 6252. [Medline]

Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. E. Cameron, L. Pauling. Proc Natl Acad Sci U S A 1978: 75(9); 4538-42. [Medline]

Ascorbic acid and cancer: a review. E. Cameron, L. Pauling, B. Leibovitz. Cancer Res 1979: 39(3); 663-81. [Medline]

Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. E. T. Creagan, C. G. Moertel, J. R. O'Fallon, A. J. Schutt, M. J. O'Connell, J. Rubin, S. Frytak. New England Journal of Medical 1979: 301(13); 687-90.

Ascorbic acid in the prevention and treatment of cancer. K. A. Head. Altern Med Rev 1998: 3(3); 174-86. [Medline] [Full text]

Antiocidant Nutrients and Cancer. Abram Hoffer, MD, PhD, FRCP(C). Journal of Orthomolecular Medicine 2000: 15(4); 193-200.

Vitamin C as Cancer Therapy: An Overview. L.J. Hoffer, MD, PhD, C MD Tamayo, M.A. Dr. PH Richardson. Journal of Orthomolecular Medicine 2000: 15(4); 175-180.

Dietary factors and risk of breast cancer: combined analysis of 12 case-control studies. G. R. Howe, T. Hirohata, T. G. Hislop, J. M. Iscovich, J. M. Yuan, K. Katsouyanni, F. Lubin, E. Marubini, B. Modan, T. Rohan, et al. J Natl Cancer Inst 1990: 82(7); 561-9.

Vitamin C and cancer: examination of the Vale of Leven trial results using broad inductive reasoning. M. Jaffey. Med Hypotheses 1982: 8(1); 49-84. [Medline]

The antioxidant vitamins and cardiovascular disease. A critical review of epidemiologic and clinical trial data. P. Jha, M. Flather, E. Lonn, M. Farkouh, S. Yusuf. Ann Intern Med 1995: 123(11); 860-72.

Vitamin C status and mortality in US adults. Catherine M Loria, Michael J Klag, Laura E Caulfield, Paul K Whelton. Am J Clin Nutr 2000: 72(1); 139-145. [Abstract] [Full text] [PDF]

High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. C Moertel. New England Journal of Medicine 1985: 312(3); 137-141.

Reevaluation of ascorbate in cancer treatment: emerging evidence, open minds and serendipity. S. J. Padayatty, M. Levine. J Am Coll Nutr 2000: 19(4); 423-5. [Medline]

New insights into the physiology and pharmacology of vitamin C. S. J. Padayatty, M. Levine. Cmaj 2001: 164(3); 353-5.

Clinical and Experimental Experiences with Intravenous Vitamin C. Neil H. PA-C Riordan, Hugh D. MD Riordan, Joseph PhD Casciari. Journal of Orthomolecular Medicine 2000: 15(4); 201-13.

Micronutrients, antioxidants and risk of cancer. C. J. Schorah. Bibl Nutr Dieta 1995: (52); 92-107. [Medline]

Evidence >> Autism (24)

MMR and Autism - can a controversy be more one-sided?. Michael E. Allen. Accessed on 2003-01-15. www.healthwatch-uk.org/mmr.pdf

Measles-Mumps-Rubella immunisation, autism and inflammatory bowel disease: update. Janaki Amin, Melanie Wong. Accessed on 2003-01-03. www.health.gov.au/pubhlth/cdi/cdi2308/cdi2308e.htm

Even more on MMR. Bandolier. Accessed on 2003-03-25. www.jr2.ox.ac.uk/bandolier/band88/b88-2.html

Time trends in autism and in MMR immunization coverage in California. L. Dales, S. J. Hammer, N. J. Smith. Jama 2001: 285(9); 1183-5. [Medline]

Measles-mumps-rubella and other measles-containing vaccines do not increase the risk for inflammatory bowel disease: a case-control study from the Vaccine Safety Datalink project. R. L. Davis, P. Kramarz, K. Bohlke, P. Benson, R. S. Thompson, J. Mullooly, S. Black, H. Shinefield, E. Lewis, J. Ward, S. M. Marcy, E. Eriksen, F. Destefano, R. Chen. Arch Pediatr Adolesc Med 2001: 155(3); 354-9. [Medline]

Autism and measles-mumps-rubella vaccination: controversy laid to rest? F. DeStefano, R. T. Chen. CNS Drugs 2001: 15(11); 831-7. [Medline]

Do children who become autistic consult more often after MMR vaccination? S. DeWilde, I. M. Carey, N. Richards, S. R. Hilton, D. G. Cook. Br J Gen Pract 2001: 51(464); 226-7.

Measles vaccines: a review of adverse events. P. Duclos, B. J. Ward. Drug Saf 1998: 19(6); 435-54.

MMR and autism: further evidence against a causal association. C. P. Farrington, E. Miller, B. Taylor. Vaccine 2001: 19(27); 3632-5.

No evidence for a new variant of measles-mumps-rubella-induced autism. E. Fombonne, S. Chakrabarti. Pediatrics 2001: 108(4); E58. [PDF]

Learning diabilities information, support and other resources for UK patients. Sarah Greening. Accessed on 2003-01-03. www.equip.nhs.uk/topics/neuro/learning.html

MMR vaccine and autism, revisited. Ronald J. Kallen. Accessed on 2003-01-03. www.autism-biomed.org/mmr-rev.htm

MMR, autism and inflammatory bowel disease: responding to patient concerns using an evidence-based framework. C. R. MacIntyre, P. B. McIntyre. Med J Aust 2001: 175(3); 127-8.

A population-based study of measles, mumps, and rubella vaccination and autism. K. M. Madsen, A. Hviid, M. Vestergaard, D. Schendel, J. Wohlfahrt, P. Thorsen, J. Olsen, M. Melbye. New England Journal of Medicine 2002: 347(19); 1477-82.

Frequently Asked Questions. Measles-Mumps-Rubella Vaccine and Autism.. Institute of Medicine. Accessed on 2003-01-03. www.iom.edu/iom/iomhome.nsf/WFiles/FAQ-2pager/$file/FAQ-2pager.PDF

Serious adverse events after measles-mumps-rubella vaccination during a fourteen-year prospective follow-up. A. Patja, I. Davidkin, T. Kurki, M. J. Kallio, M. Valle, H. Peltola. Pediatr Infect Dis J 2000: 19(12); 1127-34.

Neurological adverse events associated with vaccination. S. Piyasirisilp, T. Hemachudha. Curr Opin Neurol 2002: 15(3); 333-8.

FAQs (frequently asked questions) about MMR Vaccine & Autism (Measles, Mumps, and Rubella). Centers for Disease Control and Prevention. Accessed on 2003-01-03. www.cdc.gov/nip/vacsafe/concerns/autism/autism-mmr.htm

Vaccination and autoimmunity-'vaccinosis': a dangerous liaison? Y. Shoenfeld, A. Aron-Maor. J Autoimmun 2000: 14(1); 1-10.

Does measles-mumps-rubella (MMR) vaccination cause inflammatory bowel disease and autism? B. Strauss, M. Bigham. Can Commun Dis Rep 2001: 27(8); 65-72.

Autism and measles, mumps, and rubella vaccine: no epidemiological evidence for a causal association. B. Taylor, E. Miller, C. P. Farrington, M. C. Petropoulos, I. Favot-Mayaud, J. Li, P. A. Waight. Lancet 1999: 353(9169); 2026-9.

Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study. B. Taylor, E. Miller, R. Lingam, N. Andrews, A. Simmons, J. Stowe. Bmj 2002: 324(7334); 393-6. [Medline] [Abstract] [Full text] [PDF]

Anti-vaccinationists past and present. R. M. Wolfe, L. K. Sharp. Bmj 2002: 325(7361); 430-2. [Medline] [Full text] [PDF]

Evidence >> Blinding (20)

A comparison of active and simulated chiropractic manipulation as adjunctive treatment for childhood asthma. J. Balon, P. D. Aker, E. R. Crowther, C. Danielson, P. G. Cox, D. O'Shaughnessy, C. Walker, C. H. Goldsmith, E. Duku, M. R. Sears. New England Journal of Medicine 1998: 339(15); 1013-20. [Medline] [Abstract] [Full text] [PDF]

Why Bogus Therapies Seem to Work. Barry L. Beyerstein. Skeptical Inquirer 1997: 21(5); [Full text]

Controlled trial of acupuncture for severe recidivist alcoholism. M. L. Bullock, P. D. Culliton, R. T. Olander. Lancet 1989: 1(8652); 1435-9.

How study design affects outcomes in comparisons of therapy. I: Medical. GA Colditz, JN Miller, F. Mosteller. Stat Med 1989: 8(4); 441-454.

Physician interpretations and textbook definitions of blinding terminology in randomized controlled trials. P. J. Devereaux, B. J. Manns, W. A. Ghali, H. Quan, C. Lacchetti, V. M. Montori, M. Bhandari, G. H. Guyatt. Jama 2001: 285(15); 2000-3. [Medline] [Abstract] [Full text] [PDF]

"Double blind, you are the weakest link- good-bye!" P.J. Devereaux, M. Bhandari, V. M. Montori, B.J. Manns, W.A. Ghali, G. H. Guyatt. ACP Journal Club 2002: 136A11-A12.

Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment. A. Hrobjartsson, P. C. Gotzsche. N Engl J Med 2001: 344(21); 1594-602. [Abstract] [Full text] [PDF]

Removing bias in surgical trials. A. G. Johnson, J. M. Dixon. British Medical Journal 1997: 314(7085); 916-7. [Full text]

Empirical evidence of design-related bias in studies of diagnostic tests. JG Lijmer, BW Mol, S Heisterkamp, GJ Bonsel, MH Prins, JH van der Meulen, PM Bossuyt. JAMA 1999: 282(11); 1061-1066.

The difficulties of double blinding. J. Mercer. Science 2002: 297(5590); 2208. [Medline]

An addition to the controversy on sunlight exposure and melanoma risk: a meta-analytical approach. P. J. Nelemans, F. H. Rampen, D. J. Ruiter, A. L. Verbeek. J Clin Epidemiol 1995: 48(11); 1331-42.

The impact of blinding on the results of a randomized, placebo-controlled multiple sclerosis clinical trial. J. H. Noseworthy, G. C. Ebers, M. K. Vandervoort, R. E. Farquhar, E. Yetisir, R. Roberts. Neurology 1994: 44(1); p16-20.

Inconsistencies and Errors in Alternative Medicine Research. W Sampson. Skeptical Inquirer 1997: 21(5); 35-38.

Blinding in randomised trials: hiding who got what. K. F. Schulz, D.A. Grimes. Lancet 2002: 359696-700.

The Landscape and Lexicon of Blinding in Randomized Trials. K.F. Schulz, I. Chalmers, D.G. Altman. Annals of Internal Medicine 2002: 136(3); 254-259.

Blinding and exclusions after allocation in randomised controlled trials: survey of published parallel group trials in obstetrics and gynaecology. Kenneth F Schulz, David A Grimes, Douglas G Altman, Richard J Hayes. BMJ 1996: 312(7033); 742-744. [Abstract] [Full text]

Assessing Allocation Concealment and Blinding in Randomised Controlled Trials: Why bother? KF Schulz. Evid Based Nurs 2001: 44 - 6.

Experimenter Effects in Scientific Research: How Widely Are They Neglected? Rupert Sheldrake. 1998: 12(1); 73-78. [Abstract] [PDF]

Understanding controlled trials randomisation methods: concealment. DJ Torgerson, C Roberts. BMJ 1999: 319(7206); 375-76. [Full text] [PDF]

ABC of complementary medicine: Acupuncture. Andrew Vickers, Catherine Zollman. BMJ 1999: 319(7215); 973-976. [Full text] [PDF]

Evidence >> Guidelines (2)

Improving radiology research methods: what is being asked and who is being studied? J. Eng, S. S. Siegelman. Radiology 1997: 205(3); 651-5.

Users' guides to the medical literature: XVI. How to use a treatment recommendation. GH Guyatt, J Sinclair, DJ Cook, P Glasziou. JAMA 1999: 281(19); 1836-1843.

Evidence >> Leftout >> Attrition (9)

Article makes simple errors and could cause unnecessary deaths. C. Baigent, R. Collins, R. Peto. British Medical Journal 2002: 324(7330); 167. [Medline] [Full text] [PDF]

Statistical issues in randomized trials of cancer screening. S. G. Baker, B. S. Kramer, P. C. Prorok. BMC Med Res Methodol 2002: 2(1); 11. [Abstract] [Full text] [PDF]

Quantification of the completeness of follow-up. T. G. Clark, D. G. Altman, B. L. De Stavola. Lancet 2002: 359(9314); 1309-10. [Medline]

Hold the Lard! The Atkins Diet still doesn't work.. Michael Fumento. Accessed on 2002-12-06. www.reason.com/hod/mf120502.shtml

Attrition in prevention research. W. B. Hansen, L. M. Collins, C. K. Malotte, C. A. Johnson, J. E. Fielding. J Behav Med 1985: 8(3); 261-75.

Tracking and follow-up of 16,915 adolescents: minimizing attrition bias. T. C. Morrison, D. R. Wahlgren, M. F. Hovell, J. Zakarian, S. Burkham-Kreitner, C. R. Hofstetter, D. J. Slymen, K. Keating, S. Russos, J. A. Jones. Control Clin Trials 1997: 18(5); 383-96.

Tracking and attrition in longitudinal school-based smoking prevention research. P. L. Pirie, S. J. Thomson, S. L. Mann, A. V. Peterson, Jr., D. M. Murray, B. R. Flay, J. A. Best. Prev Med 1989: 18(2); 249-56.

Sample size slippages in randomised trials: exclusions and the lost and wayward. K. F. Schulz, D. A. Grimes. Lancet 2002: 359(9308); 781-5. [Medline] [Abstract]

Intention to Treat Analysis in Clinical Trials When There are Missing Data. Streiner, D, J Geddes. Evid Based Ment Health 2001: 4(3); 70-71.

Evidence >> Leftout >> Compliance (15)

Influence of Adherence Treatment and Response of Cholesterol on Mortality in the Coronary Drug Project. Coronary Drug Project Research Group. New England Journal of Med 1980: 3031038-1041. [Abstract]

Risk Factor Changes after Cessation of Intervention in the Multiple Risk Factor Intervention Trial. Jeffery A Cutler, Gregory A Grandits, Richard H Grimm, H. Emerson Thomas, James H Billings, Nicholas H Wright. Preventive Medicine 1991: 20(2); 183-196.

Should we pay the patient? Review of financial incentives to enhance patient compliance. Antonio Giuffrida, David J Torgerson. BMJ 1997: 315(7110); 703-707. [Abstract] [Full text]

Effect of diet and smoking intervention on the incidence of coronary heart disease. Report from the Oslo Study Group of a randomised trial in healthy men. I. Hjermann, K. Velve Byre, I. Holme, P. Leren. Lancet 1981: 2(8259); 1303-10.

The Oslo Study: diet and antismoking advice: Additional results from a 5-year primary preventive trial in middle-aged men. Ingar Holme, Ingvar Hjermann, Anders Helgeland, Paul Leren. Preventive Medicine 1985: 14(3); 279-292.

Adherence to treatment and health outcomes. R. I. Horwitz, S. M. Horwitz. Arch Intern Med 1993: 153(16); 1863-8. [Medline]

Treatment adherence and risk of death after a myocardial infarction. R. I. Horwitz, C. M. Viscoli, L. Berkman, R. M. Donaldson, S. M. Horwitz, C. J. Murray, D. F. Ransohoff, J. Sindelar. Lancet 1990: 336(8714); 542-5. [Medline]

Randomised study of long term outcome after epidural versus non-epidural analgesia during labour. C. J. Howell, T. Dean, L. Lucking, K. Dziedzic, P. W. Jones, R. B. Johanson. Bmj 2002: 325(7360); 357. [Medline] [Abstract] [Full text] [PDF]

A Method for the Analysis of Randomized Trials with Compliance Information: An Application to Multiple Risk Factor Intervention Trial. SD Mark, JM Robins. Controlled Clinical Trials 1993: 14(2); 79-97.

Enhancing patients' compliance. Peter A Meredith, A E Raffle, K Morgan, Antonio Giuffrida, David J Torgerson. BMJ 1998: 316(7128); 393b-394. [Full text]

Intention-to-treat principle. V. M. Montori, G. H. Guyatt. Cmaj 2001: 165(10); p1339-41. [Medline] [Full text] [PDF]

Relationship between Baseline Risk Factors and Coronary Heart Disease and Total Mortality in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group. Preventive Medicine 1986: 15(3); 254-273. [Medline]

Mortality Rates After 10.5 Years for Participants in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group. JAMA 1990: 263(13); 1795-1801. [Medline]

The Relationship of Smoking Cessation to Coronary Heart Disease and Lung Cancer in the Multiple Risk Factor Intervention Trial (MRFIT). JK Ockene, LH Kuller, KH Svendsen, E Meilahn. American Journal of Public Health 1990: 80(8); 954-958.

Problems in the conduct and analysis of randomized clinical trials. Are we getting the right answers to the wrong questions? L. Rabeneck, C. M. Viscoli, R. I. Horwitz. Arch Intern Med 1992: 152(3); 507-12. [Medline]

Evidence >> Leftout >> Dropouts (1)

General FAQ #25: Handling missing or incomplete data. Information Technology Services, UT Austin. Accessed on 2003-04-04. www.utexas.edu/cc/faqs/stat/general/gen25.html

Evidence >> Leftout >> Exclusions (24)

A controlled trial of immunotherapy for asthma in allergic children. N. F. Adkinson, Jr., P. A. Eggleston, D. Eney, E. O. Goldstein, K. C. Schuberth, J. R. Bacon, R. G. Hamilton, M. E. Weiss, H. Arshad, C. L. Meinert, J. Tonascia, B. Wheeler. New England Journal of Medicine 1997: 336(5); 324-31. [Abstract] [Full text] [PDF]

Including elderly people in clinical trials. Jerry Avorn. BMJ 1997: 315(7115); 1033-1034. [Full text]

Unjustified exclusion of elderly people from studies submitted to research ethics committee for approval: descriptive study. A. Bayer, W. Tadd. British Medical Journal 2000: 321(7267); 992-3. [Full text] [PDF]

Clinical trials should be designed to include elderly people. Jacqueline Bene, Richard Liston. BMJ 1998: 316(7148); 1905a-. [Full text]

Statistical Assumptions as Empirical Commitments. Richard A. Berk, David A. Freedman. Accessed on 2001-August. stat-www.berkeley.edu/~census/berk2.pdf

Exclusion of elderly people from clinical research: a descriptive study of published reports. G. Bugeja, A. Kumar, A. K. Banerjee. British Medical Journal 1997: 315(7115); 1059. [Full text]

Ethical implications of rejecting patients for clinical trials. T. C. Chalmers. Jama 1990: 263(6); 865. [Medline]

Applying results of randomised trials to clinical practice: impact of losses before randomisation. M. E. Charlson, R. I. Horwitz. Br Med J (Clin Res Ed) 1984: 289(6454); 1281-4. [Medline]

An algebraic analysis of biases due to exclusion, susceptibility, and protopathic prescription in case-control research. A. R. Feinstein, R. I. Horwitz. J Chronic Dis 1981: 34(8); 393-403. [Medline]

Post-randomisation exclusions: the intention to treat principle and excluding patients from analysis. D. Fergusson, S. D. Aaron, G. Guyatt, P. Hebert. Bmj 2002: 325(7365); 652-4. [Full text] [PDF]

Participation in Research and Access to Experimental Treatments by HIV-Infected Patients. Allen L. Gifford, William E. Cunningham, Kevin C. Heslin, Ron M. Andersen, Terry Nakazono, Dale K. Lieu, Martin F. Shapiro, Samuel A. Bozzette, the HIV Cost and Services Utilization Study Consortium. N Engl J Med 2002: 346(18); 1373-1382. [Abstract] [Full text] [PDF]

Research Fables from the Sisters Grinn, No. 11. Chicken Little.. Jeanne Grace, University of Rochester School of Nursing. Accessed on 2003-05-27. www.urmc.rochester.edu/SON/Fables/clittle.html

The exclusion of the elderly and women from clinical trials in acute myocardial infarction. J. H. Gurwitz, N. F. Col, J. Avorn. Jama 1992: 268(11); 1417-22.

AAP Washington Office Testimony: Off-Label Drug Use. Ralph Kauffman. Accessed on 2002-12-13. www.aap.org/advocacy/washing/offlabel.htm

Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection. M. S. Lachs, I. Nachamkin, P. H. Edelstein, J. Goldman, A. R. Feinstein, J. S. Schwartz. Ann Intern Med 1992: 117(2); 135-40. [Medline]

Why Are There So Few Papers on Elderly Patients in Thorax? M Mamun. Thorax 1998: 53233. [Full text]

Placebos, active control groups, and the unpredictability paradox. K. M. Mattocks, R. I. Horwitz. Biol Psychiatry 2000: 47(8); 693-8. [Medline]

Methodologic problems of exercise testing for coronary artery disease: groups, analysis and bias. J. T. Philbrick, R. I. Horwitz, A. R. Feinstein. Am J Cardiol 1980: 46(5); 807-12. [Medline]

The limited spectrum of patients studied in exercise test research. Analyzing the tip of the iceberg. J. T. Philbrick, R. I. Horwitz, A. R. Feinstein, R. A. Langou, J. P. Chandler. Jama 1982: 248(19); 2467-70. [Medline]

Comorbidity of chronic diseases in general practice. F. G. Schellevis, J. van der Velden, E. van de Lisdonk, J. T. van Eijk, C. van Weel. J Clin Epidemiol 1993: 46(5); 469-73.

Nicotine patch therapy in adolescent smokers. T. A. Smith, R. F. House, Jr., I. T. Croghan, T. R. Gauvin, R. C. Colligan, K. P. Offord, L. C. Gomez-Dahl, R. D. Hurt. Pediatrics 1996: 98(4 Pt 1); 659-67.

The Effect of School Dropout Rates on Estimates of Adolescent Substance Use among Three Racial/Ethnic Groups. Randall C. Swaim, F Beauvais, EL Chavez, ER Oetting. American Journal of Public Health 1997: 87(1); 51-55. [Medline]

Physicians' reasons for not entering eligible patients in a randomized clinical trial of surgery for breast cancer. K. M. Taylor, R. G. Margolese, C. L. Soskolne. N Engl J Med 1984: 310(21); p1363-7.

Representation of older patients in cancer treatment trials. EL Trimble, CL Carter, D Cain, B Freidlin, RS Ungerleider, MA Friedman. Cancer 1994: 74(7); 2208-14.

Evidence >> Leftout >> Exclusions >> Differential (1)

Exclusion bias and the false relationship of reserpine and breast cancer. R. I. Horwitz, A. R. Feinstein. Arch Intern Med 1985: 145(10); 1873-5. [Medline]

Evidence >> Leftout >> Exclusions >> Women (1)

Estimation of gender bias in clinical trials. C. L. Meinert, A. K. Gilpin. Stat Med 2001: 20(8); p1153-64.

Evidence >> Leftout >> Generalizability (1)

Assessing the generalizability of smoking studies. J. R. Hughes, G. A. Giovino, R. M. Klevens, M. C. Fiore. Addiction 1997: 92(4); 469-72. [Medline] [Abstract]

Evidence >> Leftout >> Intention To Treat (1)

Advances in Clinical Trials in theTwentieth Century. Lloyd D. Fisher. Annual Review 1999: 20109-124.

Evidence >> Leftout >> Refusals (18)

Effect of UK national guidelines on services to treat patients with acute low back pain: follow up questionnaire survey. A. G. Barnett, M. R. Underwood, M. R. Vickers. British Medical Journal 1999: 318(7188); 919-20. [Full text] [PDF]

Characteristics of non-responders and the impact of non-response on prevalence estimates of dementia. F. Boersma, J. A. Eefsting, W. van den Brink, W. van Tilburg. International Journal of Epidemiology 1997: 26(5); 1055-62.

Influence of race, clinical, and other socio-demographic features on trial participation. G. Corbie-Smith, C. M. Viscoli, W. N. Kernan, L. M. Brass, P. Sarrel, R. I. Horwitz. J Clin Epidemiol 2003: 56(4); 304-9. [Medline]

Quality improvement report: Improving design and conduct of randomised trials by embedding them in qualitative research: ProtecT (prostate testing for cancer and treatment) study. Commentary: presenting unbiased information to patients can be difficult. J. Donovan, N. Mills, M. Smith, L. Brindle, A. Jacoby, T. Peters, S. Frankel, D. Neal, F. Hamdy. Bmj 2002: 325(7367); 766-70.

Imputing nonresponses to mail-back questionnaires. J. W. Drane. Am J Epidemiol 1991: 134(8); 908-12.

Refusal and information bias associated with postal questionnaires and face-to-face interviews in very elderly subjects. R. Hebert, G. Bravo, N. Korner-Bitensky, L. Voyer. J Clin Epidemiol 1996: 49(3); p373-81.

Non-response bias in a lifestyle survey. A. Hill, J. Roberts, P. Ewings, D. Gunnell. J Public Health Med 1997: 19(2); p203-7.

A comparison on nonresponse in mail, telephone, and face-to-face surveys. J. J. Hox, D De Leeuw. Quality and Quantity 1994: 28(4); 329-344.

Do safety practices differ between responders and non-responders to a safety questionnaire? D. Kendrick, R. Hapgood, P. Marsh. Injury Prevention 2001: 7(2); 100-3. [Medline] [Abstract] [Full text] [PDF]

PEDAKSI: methodology for collecting data about survey non-respondents. Peter J. Lynn, Institute for Social & Economic Research. Accessed on 2002-February. www.irc.essex.ac.uk/pubs/workpaps/2002-05.php

Separating Refusal Bias and Non-Contact Bias: Evidence from UK National Surveys. Peter J. Lynn, Paul Clarke, Institute for Social & Economic Research. Accessed on 2001-November. www.irc.essex.ac.uk/pubs/workpaps/wp2001-24.php

The Online Health Care Revolution: How the Web helps Americans take better care of themselves. Pew Internet & American Life Project. Accessed on 2003-06-12. www.pewinternet.org/reports/toc.asp?Report=26

Methods for the design and administration of web-based surveys. T. K. Schleyer, J. L. Forrest. J Am Med Inform Assoc 2000: 7(4); 416-25. [Medline] [Abstract] [Full text] [PDF]

Nonresponse bias and early versus all responders in mail and telephone surveys. J. Siemiatycki, S. Campbell. Am J Epidemiol 1984: 120(2); p291-301.

Quality of response in different population groups in mail and telephone surveys. J. Siemiatycki, S. Campbell, L. Richardson, D. Aubert. Am J Epidemiol 1984: 120(2); p302-14.

What are the characteristics of general practitioners who routinely do not return postal questionnaires: a cross sectional study. N. Stocks, D. Gunnell. J Epidemiol Community Health 2000: 54(12); p940-1.

Representativeness and response rates from the Domestic/International Gastroenterology Surveillance Study (DIGEST). J. G. Tijssen. Scand J Gastroenterol Suppl 1999: 23115-9.

Standard Definitions: Final Dispostions of Case Codes and Outcomes Rates for Surveys. Mischael W. Traugott, Murray Edelman, Warren J. Mitofsky, The American Association for Public Opinion Research. Accessed on 2000-www.aapor.org/default.asp?page=survey_methods/standards_and_best_practices/standard_definitions

Evidence >> Leftout >> Refusals >> Nonresponse (2)

Response rates to mail surveys published in medical journals. D. A. Asch, M. K. Jedrziewski, N. A. Christakis. Journal Clinical Epidemiology 1997: 50(10); 1129-36.

Adjustment of reported prevalence of respiratory symptoms for non-response in a multi-centre health survey. S. Chinn, E. Zanolin, E. Lai, D. Jarvis, C. M. Luczynska, P. G. Burney. Int J Epidemiol 1995: 24(3); 603-11.

Evidence >> Leftout >> Refusers (3)

Mortality and cancer rates in nonrespondents to a prospective study of older women: 5-year follow-up. K. M. Bisgard, A. R. Folsom, C. P. Hong, T. A. Sellers. American Journal of Epidemiology 1994: 139(10); 990-1000.

Differences between respondents and non-respondents in a population-based cardiovascular disease study. M. H. Criqui, E. Barrett-Connor, M. Austin. Am J Epidemiol 1978: 108(5); 367-72.

The Tromso Heart Study: responders and non-responders to a health questionnaire, do they differ? B. K. Jacobsen, D. S. Thelle. Scand J Soc Med 1988: 16(2); p101-4.

Evidence >> Leftout >> Volunteer (23)

Do volunteer subjects bias clinical trials? G. Amori, R. H. Lenox. J Clin Psychopharmacol 1989: 9(5); 321-7. [Medline]

Volunteer bias in human sexuality research: evidence for both sexuality and personality differences in males. A. F. Bogaert. Arch Sex Behav 1996: 25(2); 125-40. [Medline]

Reducing volunteer bias: using left-over specimens to estimate rates of HIV infection among inmates in Ontario, Canada. L. M. Calzavara, C. Major, T. Myers, J. Schlossberg, M. Millson, E. Wallace, J. Rankin, M. Fearon. Aids 1995: 9(6); 631-7. [Medline]

A genetic bias in clinical trials? Cytochrome P450-2D6 (CYP2D6) genotype in general vs selected healthy subject populations [letter]. S. Chen, S. Kumar, W. H. Chou, J. S. Barrett, P. J. Wedlund. Br J Clin Pharmacol 1997: 44(3); 303-4.

Selection bias in observational and experimental studies. J. H. Ellenberg. Stat Med 1994: 13(5-7); 557-67.

A comparison of cigarette smokers recruited through the Internet or by mail. J. F. Etter, T. V. Perneger. Int J Epidemiol 2001: 30(3); 521-5.

Uptake of screening and prevention in women at very high risk of breast cancer. D. Evans, F. Lalloo, A. Shenton, C. Boggis, A. Howell. Lancet 2001: 358(9285); 889-90.

Using the Internet for surveys and health research. G. Eysenbach, J. Wyatt. J Med Internet Res 2002: 4(2); E13. [Medline] [Full text]

Healthy volunteer effect in industrial workers. P. Froom, S. Melamed, E. Kristal-Boneh, J. Benbassat, J. Ribak. J Clin Epidemiol 1999: 52(8); 731-5. [Medline]

Random versus volunteer selection for a community-based study. M. Ganguli, M. E. Lytle, M. D. Reynolds, H. H. Dodge. J Gerontol A Biol Sci Med Sci 1998: 53(1); M39-46. [Medline]

The healthy control subject in psychiatric research: impulsiveness and volunteer bias. J. P. Gustavsson, M. Asberg, D. Schalling. Acta Psychiatr Scand 1997: 96(5); 325-8.

Volunteer bias in nonrandomized evaluations of the efficacy of needle-exchange programs. H. Hagan, J. P. McGough, H. Thiede, S. G. Hopkins, N. S. Weiss, E. R. Alexander. J Urban Health 2000: 77(1); 103-12. [Medline]

Sperm output of healthy men in Australia: magnitude of bias due to self-selected volunteers. D. J. Handelsman. Hum Reprod 1997: 12(12); 2701-5. [Medline]

Selection bias in Teratology Information Service pregnancy outcome studies. K. A. Johnson, P. A. Weber, K. L. Jones, C. D. Chambers. Teratology 2001: 64(2); 79-82. [Medline]

Healthy volunteer effect in a cohort study: temporal resolution in the Adventist Health Study. K. D. Lindsted, G. E. Fraser, M. Steinkohl, W. L. Beeson. J Clin Epidemiol 1996: 49(7); 783-90. [Medline]

An examination of bias in volunteer subject selection: findings from an in-depth child abuse study. F. S. Mandel, M. Weiner, S. Kaplan, D. Pelcovitz, V. Labruna. J Trauma Stress 2000: 13(1); 77-88. [Medline]

The healthy volunteer in clinical pharmacology: personality and motivation. F. P. Meyer, R. Haschke, F. W. Rohl. Eur J Clin Pharmacol 1995: 48(2); 91-6. [Medline]

Informed consent as a source of bias in clinical research. D. S. Schubert, M. B. Patterson, F. T. Miller, K. J. Brocco. Psychiatry Res 1984: 12(4); 313-20. [Medline]

Quality-of-life research on the Internet: feasibility and potential biases in patients with ulcerative colitis. R. M. Soetikno, R. Mrad, V. Pao, L. A. Lenert. J Am Med Inform Assoc 1997: 4(6); 426-35. [Medline] [Abstract] [Full text] [PDF]

Characteristics of research volunteers for inpatient cocaine studies: focus on selection bias. M. Sofuoglu, S. Dudish-Poulsen, K. K. Nicodemus, D. A. Babb, D. K. Hatsukami. Addict Behav 2000: 25(5); 785-90. [Medline]

Volunteer bias in sexuality research. D. S. Strassberg, K. Lowe. Arch Sex Behav 1995: 24(4); 369-82. [Medline]

Subject selection bias in alcoholics volunteering for a treatment study. D. B. Strohmetz, A. I. Alterman, D. Walter. Alcohol Clin Exp Res 1990: 14(5); 736-8. [Medline]

Are Subjects in Pharmacological Treatment Trials of Depression Representative of Patients in Routine Clincal Practice. M. Zimmerman, J.I. Mattia, Michael A. Posternak. American Journal of Psychiatry 2002: 159(3); 469-473.

Evidence >> Leftout >> Zelen Design (15)

The relative efficiency of Zelen's prerandomization design for clinical trials. D. Anbar. Biometrics 1983: 39(3); 711-8. [Medline]

Prerandomization: an alternative to classic randomization. The effects on recruitment in a controlled trial of arthroscopy for osteoarthrosis of the knee. R. W. Chang, J. Falconer, S. D. Stulberg, W. J. Arnold, A. R. Dyer. J Bone Joint Surg Am 1990: 72(10); 1451-5. [Medline]

Zelen randomisation. S. M. Gore. Lancet 1984: 2(8396); 226-7. [Medline]

Using the Zelen design in randomized controlled trials: debates and controversies. C. S. Homer. J Adv Nurs 2002: 38(2); 200-7. [Medline]

Advantages and drawbacks of the Zelen design for randomized clinical trials. R. I. Horwitz, A. R. Feinstein. J Clin Pharmacol New Drugs 1980: 20(7); 425-7. [Medline]

Randomization and efficiency in Zelen's single-consent design. J. Matts, R. McHugh. Biometrics 1987: 43(4); 885-94. [Medline]

Ethics, data-dependent designs, and the strategy of clinical trials: time to start learning-as-we-go? C. R. Palmer. Stat Methods Med Res 2002: 11(5); 381-402. [Medline]

Informed consent: ethical, legal, and medical implications for doctors and patients who participate in randomised clinical trials. M. J. Peckham, et al. Bmj 1983: 286(6371); 1117-21. [Medline]

Ethics and statistics in randomized clinical trials. R. M. Royall, R. H. Bartlett, R. G. Cornell, D. P. Byar, W. D. Dupont, R. J. Levine, F. Lindley, R. J. Simes, M. Zelen. Stat Sci 1991: 6(1); 52-88. [Medline]

Statistical options in clinical trials. M. Zelen. Semin Oncol 1977: 4(4); 441-6. [Medline]

Alternatives to classic randomized trials. M. Zelen. Surg Clin North Am 1981: 61(6); 1425-32. [Medline]

Strategy and alternate randomized designs in cancer clinical trials. M. Zelen. Cancer Treat Rep 1982: 66(5); 1095-100. [Medline]

Innovations in the design of clinical trials in breast cancer. M. Zelen. Breast Cancer Res Treat 1983: 3(2); 137-42. [Medline]

Statistical issues in the planning of prevention studies. M. Zelen. Cancer Invest 1988: 6(5); 615-20. [Medline]

Randomized consent designs for clinical trials: an update. M. Zelen. Stat Med 1990: 9(6); 645-56. [Medline]

Evidence >> Leftout >> Zelen Design >> Apples >> Randomization (2)

The randomization and stratification of patients to clinical trials. M. Zelen. J Chronic Dis 1974: 27(7-8); 365-75. [Medline]

A new design for randomized clinical trials. M. Zelen. N Engl J Med 1979: 300(22); 1242-5. [Medline]

Evidence >> Misc (3)

The dark side of evidence-based medicine. R. I. Horwitz. Cleve Clin J Med 1996: 63(6); 320-3. [Medline]

Evidence >> Misc >> Abstracts (4)

The accuracy of abstracts in psychology journals. A. H. Harris, S. Standard, J. L. Brunning, S. L. Casey, J. H. Goldberg, L. Oliver, K. Ito, J. M. Marshall. J Psychol 2002: 136(2); 141-8.

More informative abstracts revisited. R. B. Haynes, C. D. Mulrow, E. J. Huth, D. G. Altman, M. J. Gardner. Ann Intern Med 1990: 113(1); 69-76.

Can the accuracy of abstracts be improved by providing specific instructions? A randomized controlled trial. R. M. Pitkin, M. A. Branagan. Jama 1998: 280(3); 267-9.

Accuracy of data in abstracts of published research articles. R. M. Pitkin, M. A. Branagan, L. F. Burmeister. Jama 1999: 281(12); 1110-1.

Evidence >> Misc >> Analysis (3)

Analysis and interpretation of cost data in randomised controlled trials: review of published studies. Julie A Barber, Simon G Thompson. BMJ 1998: 317(7167); 1195-1200. [Abstract] [Full text] [PDF]

Pitfalls of pharmacoepidemiology. D. C. Skegg. Bmj 2000: 321(7270); p1171-2. [Full text] [PDF]

Acupuncture for treatment of chronic neck pain. Andrew Vickers, Dominik Irnich, Martin Krauss. BMJ 2001: 323(7324); 1306-. [Full text]

Evidence >> Misc >> Conflict (70)

The Pharmaceutical Industry. Don't Talk. American Medical Student Association. Accessed on 2003-05-08. www.amsa.org/hp/conflict.cfm

Disclosure of Authors' Conflicts of Interest: A Follow-up. M Angell, RD Utiger, AJ Wood. N Engl J Med 2000: 342586 - 587.

Is academic medicine for sale? M. Angell. N Engl J Med 2000: 342(20); 1516-8. [Medline] [Full text]

Editorials and Conflicts of Interest. Marcia Angell, Jerome P. Kassirer. N Engl J Med 1996: 335(14); 1055-1056. [Medline] [Full text]

Scientific quality of original research articles on environmental tobacco smoke. DE Barnes, LA Bero. Tob Control 1997: 619 - 26. [Medline] [Abstract]

Why Review Articles on the Health Effects of Passive Smoking Reach Different Conclusions. Deborah E. Barnes, Lisa A. Bero. JAMA 1998: 279(19); 1566-1570. [Abstract]

Disclosure policies for gifts from industry to academic faculty. L. A. Bero. Jama 1998: 279(13); 1031-2. [Medline] [Full text] [PDF]

The publication of sponsored symposiums in medical journals. L. A. Bero, A. Galbraith, D. Rennie. N Engl J Med 1992: 327(16); 1135-40. [Medline] [Abstract]

Influences on the quality of published drug studies. L. A. Bero, D. Rennie. Int J Technol Assess Health Care 1996: 12(2); 209-37. [Medline]

The Publication of Sponsored Symposiums in Medical Journals. LA Bero, A Galbraith, D Rennie. N Engl J Med 1992: 3271135 - 1140. [Medline]

Influences on the Quality of Published Drug Studies. LA Bero, D Rennie. Int J Technol Assess Health Care 1996: 12209 - 237.

Ethics issues in academic-industry relationships in the life sciences: the continuing debate. D. Blumenthal. Acad Med 1996: 71(12); 1291-6. [Medline] [Abstract]

Participation of life-science faculty in research relationships with industry. D. Blumenthal, E. G. Campbell, N. Causino, K. S. Louis. N Engl J Med 1996: 335(23); 1734-9. [Medline] [Abstract] [Full text] [PDF]

Relationships between academic institutions and industry in the life sciences--an industry survey. D. Blumenthal, N. Causino, E. Campbell, K. S. Louis. N Engl J Med 1996: 334(6); 368-73. [Medline] [Abstract] [Full text] [PDF]

Uneasy Alliance - Clinical Investigators and the Pharmaceutical Industry. T Bodenheimer. N Engl J Med 2000: 342(20); 1539 - 1544. [Medline]

Uneasy alliance--clinical investigators and the pharmaceutical industry. T. Bodenheimer. N Engl J Med 2000: 342(20); 1539-44. [Medline] [Full text] [PDF]

Assessing faculty financial relationships with industry: A case study. E. A. Boyd, L. A. Bero. Jama 2000: 284(17); 2209-14. [Medline] [Abstract] [Full text] [PDF]

Financial Conflict-of-Interest Policies in Clinical Research: Issues for Clinical Investigators. E. A. Boyd, M. K. Cho, L. A. Bero. Acad Med 2003: 78(8); 769-74. [Medline] [Abstract] [Full text] [PDF]

Tobacco Industry Efforts to Defeat the Occupational Safety and Health Administration Indoor Air Quality Rule. Katherine Bryan-Jones, Lisa A. Bero. Am J Public Health 2003: 93(4); 585-592. [Abstract]

Conflict of interest and the American Journal of Bioethics. K. A. Carroll, G. McGee. American Journal of Bioethics 2002: 2(3); 1-2. [Medline]

Policies on faculty conflicts of interest at US universities. M. K. Cho, R. Shohara, A. Schissel, D. Rennie. Jama 2000: 284(17); 2203-8. [Medline] [Abstract] [Full text] [PDF]

The Quality of Drug Studies Published in Symposium Proceedings. MK Cho, LA Bero. Ann Intern Med 1996: 124485 - 489. [Medline]

Relationships between authors of clinical practice guidelines and the pharmaceutical industry. N. K. Choudhry, H. T. Stelfox, A. S. Detsky. Jama 2002: 287(5); 612-7. [Medline] [PDF]

Funding source, trial outcome and reporting quality: are they related? Results of a pilot study. Tammy Clifford, Nicholas Barrowman, David Moher. BMC Health Services Research 2002: 2(1); 18. [Abstract] [Full text] [PDF]

What scientists funded by the tobacco industry believe about the hazards of cigarette smoking. K. M. Cummings, R. Sciandra, A. Gingrass, R. Davis. Am J Public Health 1991: 81(7); 894-6.

Sponsorship, Authorship and Accountability. F Davidoff, CD DeAngelis, JM Drazen, J Hoey, L Hojgaard, R Horton, S Kotzin, MG Nicholls, M Nylenna. MJA 2001: 175(6); 294-296. [Full text]

Source of funding and outcome of clinical trials. RA Davidson. J Gen Intern Med 1986: 1155 - 158. [Medline]

Conflict of Interest and the Public Trust. CD DeAngelis. JAMA 2000: 2842237 - 2238.

The uncertainty principle and industry-sponsored research. B. Djulbegovic, M. Lacevic, A. Cantor, K. K. Fields, C. L. Bennett, J. R. Adams, N. M. Kuderer, G. H. Lyman. Lancet 2000: 356(9230); 635-8.

Institutions, Contracts, and Academic Freedom. Jeffrey M. Drazen. N Engl J Med 2002: 347(17); 1362-1363. [Abstract]

Financial Associations of Authors. Jeffrey M. Drazen, Gregory D. Curfman. N Engl J Med 2002: 346(24); 1901-1902. [Full text] [PDF]

On being a whistleblower: the Needleman case. C. B. Ernhart, S. Scarr, D. F. Geneson. Ethics Behav 1993: 3(1); 73-93. [Medline]

Unconventional cancer therapies: What we need is rigorous research, not closed minds. E. Ernst. Chest 2000: 117(2); 307-8. [Full text] [PDF]

Avoiding conflicts of interest in drug research. A. R. Feinstein, R. I. Horwitz. N Engl J Med 1979: 301(18); 1009. [Medline]

Evaluation of conflict of interest in economic analyses of new drugs used in oncology. M Friedberg, B Saffran, TJ Stinson. JAMA 1999: 2821453 - 1457.

New England Journal loosens its rules on conflict of interest. S Gottlieb. BMJ 2002: 3241474. [Full text] [PDF]

Reference bias in reports of drug trials. P. C. Gotzsche. Br Med J (Clin Res Ed) 1987: 295(6599); 654-6.

Objectivity in Research. U.S. National Institutes of Health. Accessed on 2003-08-15. grants1.nih.gov/grants/guide/notice-files/not95-179.html

Declaring financial competing interests: survey of five general medical journals. A. Hussain, R. Smith. British Medical Journal 2001: 323(7307); p263-4. [Medline] [Full text] [PDF]

Print media coverage of research on passive smoking. Gail E. Kennedy, L. A. Bero. Tobacco Control 1999: 8(3); 254-260.

Association between competing interests and authors' conclusions: epidemiological study of randomised clinical trials published in the BMJ. L. L. Kjaergard, B. Als-Nielsen. British Medical Journal 2002: 325(7358); 249.

Association between competing interests and authors' conclusions: epidemiological study of randomised clinical trials published in the BMJ. LL Kjaergard, B Als-Nieslen. BMJ 2002: 325249 - 252. [Abstract] [Full text] [PDF]

Conflict of Interest Policies in Science and Medical Journals: Editorial Practices and Author Disclosures. S Krimsky, LS Rothenberg. Sci Eng Ethics 2001: 7205 - 218. [PDF]

Problem is greater than editorial indicates. Ivar S Kristiansen. BMJ 2003: 326(7394); 883-. [Full text]

When statistics provide unsatisfying answers: revisiting the breast self-examination controversy. B. H. Lerner. Cmaj 2002: 166(2); 199-201.

Nonfinancial conflicts of interest in research. N. G. Levinsky. N Engl J Med 2002: 347(10); 759-61. [Medline] [Abstract]

Pharmaceutical industry sponsorship and research outcome and quality: systematic review. Joel Lexchin, Lisa A Bero, Benjamin Djulbegovic, Otavio Clark. BMJ 2003: 326(7400); 1167-1170. [Abstract] [Full text] [PDF]

Conflict-of-interest policies for investigators in clinical trials. B. Lo, L. E. Wolf, A. Berkeley. N Engl J Med 2000: 343(22); 1616-20. [Medline] [Abstract] [Full text] [PDF]

Integrity in Science Award Is Neither. Steven Milloy, Fox News. Accessed on 2003-07-11. www.foxnews.com/story/0,2933,91600,00.html

Academic Relationships with Industry: A New Model for Biomedical Research. H Moses, JB Martin. JAMA 2001: 285(7); 933 - 935. [PDF]

Academic freedom in clinical research. D. G. Nathan, D. J. Weatherall. New England Journal of Medicine 2002: 347(17); 1368-71. [Medline] [Abstract]

Academic freedom in clinical research. D. G. Nathan, D. J. Weatherall. N Engl J Med 2002: 347(17); 1368-71. [Medline] [Full text] [PDF]

Salem comes to the National Institutes of Health: notes from inside the crucible of scientific integrity. H. L. Needleman. Pediatrics 1992: 90(6); 977-81. [Medline]

Reply to Ernhart, Scarr, and Geneson. H. L. Needleman. Ethics Behav 1993: 3(1); 95-101. [Medline]

A reply to Scarr and Ernhart. H. L. Needleman. Pediatrics 1993: 91(2); 519-21. [Medline]

Deficits in psychologic and classroom performance of children with elevated dentine lead levels. H. L. Needleman, C. Gunnoe, A. Leviton, R. Reed, H. Peresie, C. Maher, P. Barrett. N Engl J Med 1979: 300(13); 689-95. [Medline]

Get-the-lead-out guru challenged. J. Palca. Science 1991: 253(5022); 842-4. [Medline]

Guidelines for Clinical Investigator Involvement in Industry-sponsored Clinical Trials. Edward A. Panacek, Roger J. Lewis, Society for Academic Emergency Medicine. Accessed on 2003-05-08. www.saem.org/download/edward.pdf

Tobacco industry research: collaboration, not confrontation, is the best approach. CJ Proctor. British Medical Journal 1998: 317(?); 333-39.

Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome. U. Ravnskov. British Journal of Medicine 1992: 305(6844); 15-19.

Economic incentives in clinical investigation. A. S. Relman. N Engl J Med 1989: 320(14); 933-4. [Medline]

A Study of Manufacturer-Supported Trials of Nonsteroidal Anti-inflammatory Drugs in the Treatment of Arthritis. PA Rochon, JH Gurwitz, RW Simms, PR Fortin, DT Felson, KL Minaker, TC Chalmers. Arch Intern Med 1994: 154157 - 163. [Medline]

Bias in analytic research. D. L. Sackett. J Chronic Dis 1979: 32(1-2); 51-63.

Of whistleblowers, investigators, and judges. S. Scarr, C. B. Ernhart. Ethics Behav 1993: 3(2); 199-206. [Medline]

Blood lead levels, scientific misconduct and the Needleman case. 3. A reply from Scarr and Ernhart. S. Scarr, C. B. Ernhart. Am J Public Health 1996: 86(1); 113-4; author reply 114-5. [Medline]

Childhood Lead Poisoning and Tainted Science. Edgar J. Schoen. Accessed on 2003-08-13. www.roizen.com/ron/schoen.html

Review of the quality of studies on the economic effects of smoke-free policies on the hospitality industry. M Scollo, A Lal, A Hyland, S Glantz. BMJ Tob Control 2003: 12(1); 13-20. [Medline] [Abstract] [Full text] [PDF]

Beyond conflict of interest. Transparency is the key [editorial]. R. Smith. Bmj 1998: 317(7154); 291-2. [Full text] [PDF]

Conflict of interest in the debate over calcium-channel antagonists. H. T. Stelfox, G. Chua, O. Rourke K, A. S. Detsky. N Engl J Med 1998: 338(2); 101-6.

A Frank Statement to Cigarette Smokers. Tobacco Industry Research Committee. Accessed on 2003-06-18. www.pmdocs.com/getimg.asp?pgno=0&start=0&bool=Frank%20Statement&docid=2015002376

Evidence >> Misc >> Exercise (4)

Postmarketing surveillance study of a non-chlorofluorocarbon inhaler according to the safety assessment of marketed medicines guidelines. J. G. Ayres, C. D. Frost, W. F. Holmes, D. R. Williams, S. M. Ward. British Medical Journal 1998: 317(7163); 926-30. [Medline] [Abstract] [Full text] [PDF]

Obstetric care and proneness of offspring to suicide as adults: case-control study. Bertil Jacobson, Marc Bygdeman. British Medical Journal 1998: 317(7169); 1346-1349. [Medline] [Abstract] [Full text] [PDF]

Use of ultramolecular potencies of allergen to treat asthmatic people allergic to house dust mite: double blind randomised controlled clinical trial. G T Lewith, A D Watkins, M E Hyland, S Shaw, J A Broomfield, G Dolan, S T Holgate. British Medical Journal 2002: 324(7336); 520-. [Abstract] [Full text] [PDF]

Midline episiotomy and anal incontinence: retrospective cohort study. Lisa B Signorello, Bernard L Harlow, Amy K Chekos, John T Repke. British Medical Journal 2000: 320(7227); 86-90. [Medline] [Abstract] [Full text] [PDF]

Evidence >> Misc >> Guidelines (44)

Systems to Rate the Strength of Scientific Evidence. Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. Accessed on 2003-07-28. www.ahcpr.gov/clinic/epcsums/strengthsum.htm

The importance of design and analysis in clinical trials. A. Antczak-Bouckoms, T. C. Chalmers. J Oral Implantol 1988: 14(1); 36-42. [Medline]

Centre for Evidence-Based Medicine. Douglas Badenoch. Accessed on 2002-11-27. minerva.minervation.com/cebm/

JSCAN-Online. P. Badrinath, A.G. Nicol. Accessed on 2002-11-27. jscan.uaeu.ac.ae/

A ScHARR Introduction to Evidence Based Practice on the Internet. Andrew Booth. Accessed on 2002-11-27. www.nettingtheevidence.org.uk/

Discern online. Quality criteria for consumer health information. Deborah Charnock, Sasha Shepperd. Accessed on 2002-11-27. www.discern.org.uk/

The Cochrane Library. The Cochrane Collaboration. Accessed on 2002-11-27. www.update-software.com/Cochrane/default.HTM

Critical appraisal in clinical practice: sometimes irrelevant, occasionally invalid. A. Coomarasamy, P. Latthe, S. Papaioannou, M. Publicover, H. Gee, K. S. Khan. J R Soc Med 2001: 94(11); 573-7.

Users' Guides to Evidence-Based Practice. Centre for Health Evidence. Accessed on 2002-11-27. www.cche.net/usersguides/main.asp

Uncertainty. D. A. Grimes. Lancet 2002: 360(9341); 1242.

Users' guides to the medical literature: II. How to use an article about therapy or prevention: A. Are the results of the study valid? GH Guyatt, DL Sackett, DJ Cook. JAMA 1993: 270(21); 2598-2601.

Users' guides to the medical literature: II. How to use an article about therapy or prevention: B. What are the results and will they help me in caring for my patients? GH Guyatt, DL Sackett, DJ Cook. JAMA 1994: 271(1); 59-63.

Users' guides to the medical literature. IX. A method for grading health care recommendations. GH Guyatt, DL Sackett, JC Sinclair, RSA Hayward, DJ Cook, RJ Cook. JAMA 1995: 274(22); 1800-4.

Transferring evidence from research into practice: 2. Getting the evidence straight. R. B. Haynes, D. L. Sackett, J. A. Gray, D. L. Cook, G. H. Guyatt. ACP Journal Club 1997: 126(1); A14-6.

Transferring evidence from research into practice: 1. The role of clinical care research evidence in clinical decisions. R. B. Haynes, D. L. Sackett, J. M. Gray, D. J. Cook, G. H. Guyatt. ACP Journal Club 1996: 125(3); A14-6.

Transferring evidence from research into practice: 4. Overcoming barriers to application. R. B. Haynes, D. L. Sackett, G. H. Guyatt, D. J. Cook, J. A. Gray. ACP Journal Club 1997: 126(3); A14-5.

EBM Education Center of Excellence. UNC Health Sciences Library. Accessed on 2002-11-27. www.hsl.unc.edu/ahec/ebmcoe/pages/index.htm

Guidelines for the design and conduct of clinical trials on dentine hypersensitivity. G. R. Holland, M. N. Narhi, M. Addy, L. Gangarosa, R. Orchardson. J Clin Periodontol 1997: 24(11); 808-13.

Randomised Controlled Trials. A user's guide.. Alejandro R Jadad, British Medical Journal. Accessed on 2002-11-27. www.bmjpg.com/rct/contents.html

Users' guides to the medical literature. III. How to use an article about a diagnostic test. A. Are the results of the study valid? R Jaeschke, GH Guyatt, DL Sackett. JAMA 1994: 271(5); 389-91.

Users' guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients? R Jaeschke, GH Guyatt, DL Sackett. JAMA 1994: 271(9); 703-7.

Published criteria for evaluating health related web sites: review. P. Kim, T. R. Eng, M. J. Deering, A. Maxfield. British Medical Journal 1999: 318(7184); 647-9. [Medline] [Abstract] [Full text] [PDF]

Finding answers to questions in evidence based medicine (EBM). Atle Klovning. Accessed on 2002-11-27. www.uib.no/isf/people/atle/ebm.htm

Reporting, appraising, and integrating data on genotype prevalence and gene-disease associations. J. Little, L. Bradley, M. S. Bray, M. Clyne, J. Dorman, D. L. Ellsworth, J. Hanson, M. Khoury, J. Lau, T. R. O'Brien, N. Rothman, D. Stroup, E. Taioli, D. Thomas, H. Vainio, S. Wacholder, C. Weinberg. Am J Epidemiol 2002: 156(4); 300-10.

Randomised controlled trial of the READER method of critical appraisal in general practice. D. MacAuley, E. McCrum, C. Brown. British Medical Journal 1998: 316(7138); 1134-7. [Medline] [Abstract] [Full text] [PDF]

Evaluation of Designs for Clinical Trials of Neuroprotective Agents in Head Injury. S.G. Machado, G.D. Murray, G.M. Teasdale. Journal of Neurotrauma 1999: 16(12); 1131-1138.

Evidence-based medicine: an incomplete method for informing treatment choices. A. Maynard. Lancet 1997: 349(9045); 126-8. [Medline]

Users' guides to the medical literature XIX. Applying clinical trial results B. Guidelines for determining whether a drug is exerting (more than) a class effect. FA McAlister, A Laupacis, GA Wells, DL Sackett. JAMA 1999: 282(14); 1371-7.

Users' Guides to the Medical Literature. Finlay A. McAlister, A Laupacis, G. A. Wells, D. L. Sackett. JAMA 1999: 282(14); 1371-1377.

JAMA Rational Clinical Examination series bibliography. UCSF School of Medicine. Accessed on 2002-11-27. medicine.ucsf.edu/resources/guidelines/rational.html

Transferring evidence from research into practice: 3. Developing evidence-based clinical policy. J. A. Muir Gray, R. B. Haynes, D. L. Sackett, D. J. Cook, G. H. Guyatt. ACP Journal Club 1997: 126(2); A14-6.

Users' guides to the medical literature. I. How to get started. AD Oxman, DL Sackett, GH Guyatt. JAMA 1993: 270(17); 2093-5.

Rules of evidence and clinical recommendations for the management of patients. D. L. Sackett. Can J Cardiol 1993: 9(6); 487-9.

Evidence-based medicine and treatment choices. D. L. Sackett. Lancet 1997: 349(9051); 570; discussion 572-3. [Medline]

Evidence-based Medicine How to Practice and Teach EBM. David L. Sackett, MD, Scott W. Richardson, William Rosenberg, Brian R. Haynes (1998) Edinburgh: Churchill Livingstone.

Why Sackett's analysis of randomized controlled trials fails, but needn't. Stanley H Shapiro, Kathleen Cranley Glass. CMAJ (Journal of the Canandian Medical Association) 2000: 163(7); 834-835. [Full text] [PDF]

HTA. Health Technology Assessment. Phillip Simons. Accessed on 2002-11-27. www.hta.nhsweb.nhs.uk/index.htm

A Proposal for Structured Reporting of Randomized Controlled Trials. Standards of Reporting Trials Group. JAMA 1994: 272(24); 1926-1931. [Medline]

Using research findings in clinical practice. S. E. Straus, D. L. Sackett. British Medical Journal 1998: 317(7154); 339-42. [Full text]

Centre for Clinical Effectiveness. Boyd Dr. Strauss. Accessed on 2003-05-09. www.med.monash.edu.au/healthservices/cce/

Critical Appraisal Skills Programme. Public Health Resource Unit. Accessed on 2002-11-27. www.phru.org.uk/~casp/index.htm

RES&WCE - How to find the evidence. South and West Health Care Libraries Unit. Accessed on 2002-11-27. www.shef.ac.uk/~scharr/reswce/reswce.htm

Evidence-based medicine for occupational health. J. H. Verbeek, F. J. van Dijk, A. Malmivaara, C. T. Hulshof, K. Rasanen, E. E. Kankaanpaa, K. Mukala. Scand J Work Environ Health 2002: 28(3); 197-204.

Users' guides to the medical literature. VIII. How to use clinical practice guidelines. B. What are the recommendations, and will they help you in caring for your patients? MC Wilson, RS Hayward, SR Tunis, EB Bass, G Guyatt. JAMA 1995: 274(20); 1630-2.

Evidence >> Misc >> Objectivity (1)

Row Over Breast Cancer Screening Shows that Scientists Bring "Some Subjectivity Into Their Work. S. Mayor. British Medical Journal 2001: 323(7319); 956. [Medline] [Full text] [PDF]

Evidence >> Misc >> Overview (5)

Bias. Bandolier. Accessed on 2003-03-25. www.jr2.ox.ac.uk/bandolier/band80/b80-2.html

The Glossary of Mathematical Mistakes. Paul Cox. Accessed on 2003-06-10. www.mathmistakes.com/

Where's the Evidence? Debates in Modern Medicine. William A. Silverman (1998) New York: Oxford University Press.

Design and analysis of prostate cancer trials. R. Sylvester. Acta Urologica Belgica 1994: 62(1); 23-29.

Content and quality of 2000 controlled trials in schizophrenia over 50 years. Ben Thornley, C Adams. British Medical Journal 1998: 317(7167); 1181-1184. [Abstract] [Full text] [PDF]

Evidence >> Misc >> Peer Review (1)

Evaluating the quality of articles published in journal supplements compared with the quality of those published in the parent journal. P. A. Rochon, J. H. Gurwitz, C. M. Cheung, J. A. Hayes, T. C. Chalmers. Jama 1994: 272(2); 108-13. [Medline]

Evidence >> Misc >> Quality (16)

Poor-quality medical research: what can journals do? D. G. Altman. Jama 2002: 287(21); 2765-7.

Improving the quality of reporting of randomized controlled trials. The CONSORT statement. C. Begg, M. Cho, S. Eastwood, R. Horton, D. Moher, I. Olkin, R. Pitkin, D. Rennie, K. F. Schulz, D. Simel, D. F. Stroup. Jama 1996: 276(8); 637-9.

Reviewing the reviewers: the quality of reporting in three secondary journals. P. J. Devereaux, B. J. Manns, W. A. Ghali, H. Quan, G. H. Guyatt. Cmaj 2001: 164(11); 1573-6. [Abstract] [Full text] [PDF]

Four newspaper stories. Brad Efron, Susan Holmes. Accessed on 2003-06-20. www.stanford.edu/class/stat30/rr2.pdf

The case for better research standards in peripheral thrombolysis: poor quality of randomized trials during the past decade. T. K. Egglin, R. I. Horwitz. Acad Radiol 1996: 3(1); 1-9. [Medline]

Exposing Flawed Science. Rick Groleau, Nova. Accessed on 2003-04-30. www.pbs.org/wgbh/nova/holocaust/pseudoscience.html

A quality assessment of randomized control trials of primary treatment of breast cancer. A. Liberati, H. N. Himel, T. C. Chalmers. J Clin Oncol 1986: 4(6); p942-51.

The methodological quality of randomized controlled trials of homeopathy, herbal medicines and acupuncture. K. Linde, W. B. Jonas, D. Melchart, S. Willich. Int J Epidemiol 2001: 30(3); p526-31.

The Assert Statement. H. Mann. Accessed on 2003-06-30. www.assert-statement.org/

Assessing the quality of randomized controlled trials: an annotated bibliography of scales and checklists. D. Moher, A. R. Jadad, G. Nichol, M. Penman, P. Tugwell, S. Walsh. Control Clin Trials 1995: 16(1); p62-73.

Assessing the quality of randomized controlled trials. Current issues and future directions. D. Moher, A. R. Jadad, P. Tugwell. Int J Technol Assess Health Care 1996: 12(2); 195-208.

Research into complementary and alternative medicine: problems and potential. R. L. Nahin, S. E. Straus. British Medical Journal 2001: 322(7279); 161-4. [Full text]

Truth survival in clinical research: an evidence-based requiem? T. Poynard, M. Munteanu, V. Ratziu, Y. Benhamou, V. Di Martino, J. Taieb, P. Opolon. Ann Intern Med 2002: 136(12); 888-95.

Clinical trials in general surgical journals: are methods better reported? L. P. Schumm, J. S. Fisher, R. A. Thisted, J. Olak. Surgery 1999: 125(1); 41-5.

Review of randomised controlled trials of traditional chinese medicine. Jin-Ling Tang, SY Zhan, E Ernst. BMJ 1999: 319(7203); 160-61. [Medline] [Full text]

Many reports of RCTs give insufficient data for Cochrane reviewers. EH Walters, JA Walters. BMJ 1999: 319(7204); 257. [Full text]

Evidence >> Misc >> Statistical Validity (1)

How to read a paper: Statistics for the non-statistician. I: Different types of data need different statistical tests. Trisha Greenhalgh. BMJ 1997: 315(7104); 364-366. [Full text]

Evidence >> Mountain >> A Priori (1)

Specifying objectives and outcomes for clinical trials. V. Gebski, I. Marschner, A. C. Keech. Med J Aust 2002: 176(10); 491-2. [Medline] [Full text] [PDF]

Evidence >> Mountain >> Absolute (2)

Evidence based purchasing: understanding results of clinical trials and systematic reviews. T. Fahey, S. Griffiths, T. J. Peters. British Medical Journal 1995: 311(7012); 1056-9; discussion 1059-60. [Medline] [Abstract] [Full text]

Who benefits from medical interventions? G. D. Smith, M. Egger. Bmj 1994: 308(6921); p72-4. [Medline] [Full text]

Evidence >> Mountain >> Absolute Risk (8)

Completeness of reporting trial results: effect on physicians' willingness to prescribe. M. Bobbio, B. Demichelis, G. Giustetto. Lancet 1994: 343(8907); 1209-11.

General practice registrar responses to the use of different risk communication tools in simulated consultations: a focus group study. Adrian Edwards. British Medical Journal 1999: 319(7212); 749-752.

Absolutely relative: how research results are summarized can affect treatment decisions. L Forrow, WC Taylor, RM Arnold. The American Journal of Medicine 1992: 92(2); 121-24.

Communicating the benefits of chronic preventive therapy: does the format of efficacy data determine patients' acceptance of treatment? J Hux, CD Naylor. Medical Decision Making 1995: 15(2); 152-7.

Absolute and relative truth in clinical trials. D. Julian. Lancet 2002(June): 359(9321); 1945-1946.

Consider absolute risks in SIDS prevention. Stuart Logan. Arch Dis Child 2000: 83(5); 457.

Women need better information about routine mammography. H. Thornton, A. Edwards, M. Baum. Bmj 2003: 327(7406); 101-3. [Medline] [Full text] [PDF]

"Absolute" is inappropriate for quantitative risk estimation. Hugh Tunstall-Pedoe. BMJ 2000: 320(7236); 723-. [Full text]

Evidence >> Mountain >> Causation (3)

Smoking and stroke: a causative role. Heavy smokers with hypertension benefit most from stopping. M. I. Aldoori, S. H. Rahman. British Medical Journal 1998: 317(7164); 962-3.

HORMESIS: The Dose-Response Revolution. E. J. Calabrese, L. A. Baldwin. Annu Rev Pharmacol Toxicol 2003: 43175-97. [Medline] [Abstract]

From Association to Causation: Some Remarks on the History of Statistics. D Freedman. Statistical Science 1999: 14(3); 243-258.

Evidence >> Mountain >> Clinical (24)

Grapefruits and drugs: when is statistically significant clinically significant? D. R. Abernethy. J Clin Invest 1997: 99(10); 2297-8. [Medline] [Full text] [PDF]

Clinically significant changes in pain along the visual analog scale. S. B. Bird, E. W. Dickson. Ann Emerg Med 2001: 38(6); 639-43. [Medline]

The visual analog scale for pain: clinical significance in postoperative patients. C. A. Bodian, G. Freedman, S. Hossain, J. B. Eisenkraft, Y. Beilin. Anesthesiology 2001: 95(6); 1356-61. [Medline]

The association of nonsteroidal anti-inflammatory drugs with upper gastrointestinal tract bleeding. J. L. Carson, B. L. Strom, K. A. Soper, S. L. West, M. L. Morse. Arch Intern Med 1987: 147(1); 85-8.

How well is the clinical importance of study results reported? An assessment of randomized controlled trials. K. B. Chan, M. Man-Son-Hing, F. J. Molnar, A. Laupacis. Cmaj 2001: 165(9); 1197-202. [Abstract] [Full text] [PDF]

Power of outcome measurements to detect clinically significant changes in pulmonary rehabilitation of patients with COPD. J. P. de Torres, V. Pinto-Plata, E. Ingenito, P. Bagley, A. Gray, R. Berger, B. Celli. Chest 2002: 121(4); 1092-8. [Medline]

Is it clinically significant? Sergio Erill. Lancet 2002: 359(9318); 1708. [Full text] [PDF]

What is the chance that this study is clinically significant? A proposal for Q values. G. W. Froehlich. Eff Clin Pract 1999: 2(5); 234-9. [Medline] [Full text]

Statistical Significance and Clinical Relevance: A Contradiction?. Dieter Dr. Hauschke, Statistical Solutions. Accessed on 2003-06-24. www.statsol.ie/equivtest/hauschke1.htm

Clinical versus statistical considerations in the design and analysis of clinical research. R. I. Horwitz, B. H. Singer, R. W. Makuch, C. M. Viscoli. J Clin Epidemiol 1998: 51(4); 305-7. [Medline]

Interpreting thresholds for a clinically significant change in health status in asthma and COPD. P. W. Jones. Eur Respir J 2002: 19(3); 398-404. [Medline]

Quality of life questionnaires: does statistically significant = clinically important? E. F. Juniper. J Allergy Clin Immunol 1998: 102(1); 16-7. [Medline] [Full text] [PDF]

Does the clinically significant difference in visual analog scale pain scores vary with gender, age, or cause of pain? A. M. Kelly. Acad Emerg Med 1998: 5(11); 1086-90. [Medline]

An assessment of clinically useful measures of the consequences of treatment. A Laupacis, DL Sackett, RS Roberts. New England Journal of Med 1988: 318(26); 1728-1733.

Effect of homoeopathy on pain and other events after acute trauma: placebo controlled trial with bilateral oral surgery. P. Lokken, P. A. Straumsheim, D. Tveiten, P. Skjelbred, C. F. Borchgrevink. British Medical Journal 1995: 310(6992); 1439-42. [Medline] [Abstract] [Full text]

Interventions for promoting smoking cessation during pregnancy. J. Lumley, S. Oliver, E. Waters. Cochrane Database Syst Rev 2000: (2); pCD001055. [Abstract]

A proposal to use confidence intervals for visual analog scale data for pain measurement to determine clinical significance. S. Mantha, R. Thisted, J. Foss, J. E. Ellis, M. F. Roizen. Anesth Analg 1993: 77(5); 1041-7. [Medline]

A randomized controlled trial of fentanyl for abortion pain. M. J. Rawling, E. R. Wiebe. Am J Obstet Gynecol 2001: 185(1); 103-7. [Medline]

Assessing clinically significant change: application to the SCL-90-R. N. Schmitz, N. Hartkamp, G. H. Franke. Psychol Rep 2000: 86(1); 263-74. [Medline]

The Crack Baby Epidemic That Wasn't. What Statistics Mean, and Don't Mean. Neala S. Schwartzberg. Accessed on 2003-07-15. www.biomednet.com/hmsbeagle/50/people/op_ed.htm

Multiple doses of secretin in the treatment of autism: a controlled study. E. Sponheim, G. Oftedal, S. B. Helverschou. Acta Paediatr 2002: 91(5); 540-5. [Medline]

Clinical utility and clinical significance in the assessment and management of pain in vulnerable infants. B. Stevens, S. Gibbins. Clin Perinatol 2002: 29(3); 459-68. [Medline]

Conflicting clinical trials and the uncertainty of treating mild hypertension. P. J. Toth, R. I. Horwitz. Am J Med 1983: 75(3); 482-8. [Medline]

Minimum clinically significant VAS differences for simultaneous (paired) interval serial pain assessments. L. G. Yamamoto, J. T. Nomura, R. L. Sato, R. M. Ahern, J. L. Snow, T. T. Kuwaye. Am J Emerg Med 2003: 21(3); 176-9. [Medline] [Abstract]

Evidence >> Mountain >> Clinical Significance (2)

Orthopaedic POEMS and reliable research. K. C. Peacock. J Bone Joint Surg Am 2001: 83-A(3); p464. [Medline] [Full text] [PDF]

Determining the minimum clinically significant difference in visual analog pain score for children. C. V. Powell, A. M. Kelly, A. Williams. Ann Emerg Med 2001: 37(1); 28-31. [Medline]

Evidence >> Mountain >> Data Quality (7)

Misclassification of exposure: coffee as a surrogate for caffeine intake. J. Brown, N. Kreiger, G. A. Darlington, M. Sloan. American Journal of Epidemiology 2001: 153(8); 815-20.

Maternal recall of pregnancy history: accuracy and bias in schizophrenia research. S. L. Buka, J. M. Goldstein, L. J. Seidman, M. T. Tsuang. Schizophrenia Bulletin 2000: 26(2); 335-50.

Completeness of ascertainment of prenatal smoking using birth certificates and confidential questionnaires: variations by maternal attributes and infant birth weight. PRAMS Working Group. Pregnancy Risk Assessment Monitoring System. P. M. Dietz, M. M. Adams, J. S. Kendrick, M. P. Mathis. Am J Epidemiol 1998: 148(11); 1048-54.

Comparison of epidemiologic data from multiple sources. R. I. Horwitz. J Chronic Dis 1986: 39(11); 889-96. [Medline]

Assessing the reliability of epidemiologic data obtained from medical records. R. I. Horwitz, E. C. Yu. J Chronic Dis 1984: 37(11); 825-31. [Medline]

Problems and proposals for interview data in epidemiological research. R. I. Horwitz, E. C. Yu. Int J Epidemiol 1985: 14(3); 463-7. [Medline]

Whether and Why Pediatric Researchers Report Race and Ethnicity. Catherine Walsh, Lainie F. Ross. Arch Pediatr Adolesc Med 2003: 157(7); 671-675. [Abstract]

Evidence >> Mountain >> Equivalence (1)

Assessing Equivalence: An Alternative to the Use of Difference Tests for Measuring Disparities in Vaccination Coverage. Lawrence E. Barker, Elizabeth T. Luman, Mary M. McCauley, Susan Y. Chu. Am. J. Epidemiol. 2002: 156(11); 1056-1061.

Evidence >> Mountain >> Fishing (17)

Multiple significance tests and the Bonferroni correction. Martin Bland. Accessed on 2002-11-29. www.hms.harvard.edu/orsp/coms/BiosafetyResources/Statistics/Multiple_significance_tests_and_the_Bonferroni_correction.htm

The Method of Multiple Working Hypotheses. TC Chamberlin. The Scientific Monthly 1944: 59357 - 62.

There must be something buried in here somewhere. Jerry Dallal. Accessed on 2003-05-15. www.tufts.edu/~gdallal/multtest.htm

Do multiple outcome measures require p-value adjustment? R. J. Feise. BMC Med Res Methodol 2002: 2(1); 8.

Empirical-Bayes adjustments for multiple comparisons are sometimes useful. S. Greenland, J. M. Robins. Epidemiology 1991: 2(4); 244-51.

Intersection-Union Procedures for Some Restricted Models. Yosef Hochberg, Michael C. Mosier. Accessed on 2000-7 June. www.bioinf.uni-hannover.de/~mcp2000/abstracts/abstr29.html

Assessing cause and effect from trials: a cautionary note. D. Howel, R. Bhopal. Control Clin Trials 1994: 15(5); 331-4.

Multiple Comparisons with Repeated Measures. David C. Howell. Accessed on 2003-01-20. www.uvm.edu/~dhowell/StatPages/More_Stuff/RepMeasMultComp/RepMeasMultComp.html

Multiple Comparisons Theory and Methods. Jason C. Hsu (1996) London: Chapman & Hall.

Simultaneous Statistical Inference Second Edition. Rupert G. Miller (1981) New York: Springer-Verlag.

Quantitative Evaluation of Multiplicity in Epidemiology and Public Health Research. Kenneth J. Ottenbacher. American Journal of Epidemiology 1998: 147(7); 615-619.

What's wrong with Bonferroni adjustments. T. V. Perneger. British Medical Journal 1998: 316(7139); 1236-8. [Full text]

No adjustments are needed for multiple comparisons. K. J. Rothman. Epidemiology 1990: 1(1); 43-6.

Cured and broiled meat consumption in relation to childhood cancer: Denver, Colorado (United States). S. Sarasua, D. A. Savitz. Cancer Causes Control 1994: 5(2); 141-8.

Multiple comparisons and related issues in the interpretation of epidemiologic data. D. A. Savitz, A. F. Olshan. Am J Epidemiol 1995: 142(9); 904-8.

Multiple comparisons and related issues in the interpretation of epidemiologic data. David Savitz. American Journal of Epidemiology 1995: 142(9); 904-07.

Invited Commentary: Re: "Multiple Comparisons and Related Issues in the Interpretation of Epidemiologic Data". John R. Thompson. American Journal of Epidemiology 1998: 147(9); 801-811.

Evidence >> Mountain >> Misclassification (1)

Misclassification of smoking status and lung cancer risk from environmental tobacco smoke in never-smokers. F. Nyberg, I. Isaksson, J. R. Harris, G. Pershagen. Epidemiology 1997: 8(3); 304-9.

Evidence >> Mountain >> Outcome >> Objective >> Validity (1)

Psychological Stress and Cardiovascular Disease: Empirical Demonstration of Bias in a Prospective Observational Study of Scottish Men * Commentary: Psychosocial factors and health---strengthening the evidence base. John Macleod, George Davey Smith, Pauline Heslop, Chris Metcalfe, Douglas Carroll, Carole Hart, John Lynch. BMJ 2002: 324(7348); 1247-. [Medline] [Abstract] [Full text] [PDF]

Evidence >> Mountain >> Outcomes (3)

Understanding controlled trials: What outcomes should be measured? Martin Roland, David Torgerson. BMJ 1998: 317(7165); 1075-1080. [Full text] [PDF]

Marginal costs and benefits. David J Torgerson, Anne Spencer. BMJ 1996: 312(7022); 35-36. [Full text]

Economics Notes: Measuring outcomes in economic evaluations. David Torgerson, James Raftery. BMJ 1999: 318(7195); 1413-. [Full text] [PDF]

Evidence >> Mountain >> Outliers (3)

Some Remarks on Wild Observations. William H. Kruskal. Accessed on 2002-11-27. www.tufts.edu/~gdallal/out.htm

Finding the Antarctic Ozone Hole. OzDASL. Accessed on 2003-08-13. www.statsci.org/data/general/ozonehol.html

Ozone Depletion, History and politics. Brien Sparling. Accessed on 2002-11-27. www.nas.nasa.gov/About/Education/Ozone/history.html

Evidence >> Mountain >> Particularizing (6)

Changes in clinical trials mandated by the advent of meta-analysis. T. C. Chalmers, J. Lau. Stat Med 1996: 15(12); 1263-8; discussion 1269-72. [Medline]

Applying the results of trials and systematic reviews to individual patients. P. Glasziou, G. H. Guyatt, A. L. Dans, L. F. Dans, S. Straus, D. L. Sackett. ACP Journal Club 1998: 129(3); A15-6.

Can treatment that is helpful on average be harmful to some patients? A study of the conflicting information needs of clinical inquiry and drug regulation. R. I. Horwitz, B. H. Singer, R. W. Makuch, C. M. Viscoli. J Clin Epidemiol 1996: 49(4); 395-400. [Medline]

Decision analysis and the implementation of research findings. R. J. Lilford, S. G. Pauker, D. A. Braunholtz, J. Chard. British Medical Journal 1998: 317(7155); 405-9. [Full text]

Pronouncements about the need for "generalizability" of randomized controlled trial results are humbug. D.L. Sackett. Control. Clinical Trials 2000: 2182S.

Conflicting clinical trials and the uncertainty of treating mild hypertension. P. J. Toth, R. I. Horwitz. Am J Med 1983: 75(3); 482-8. [Medline]

Evidence >> Mountain >> Post Hoc (1)

Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs? Peter Juni, Anne WS Rutjes, Paul A Dieppe. BMJ 2002: 324(7349); 1287-1288. [Full text] [PDF]

Evidence >> Mountain >> Posthoc (8)

Things to know and do about cancer clusters. T. Aldrich, T. Sinks. Cancer Invest 2002: 20(5-6); 810-6.

Dangers of using "optimal" cutpoints in the evaluation of prognostic factors. D. G. Altman, B. Lausen, W. Sauerbrei, M. Schumacher. Journal of the National Cancer Institute 1994: 86(11); 829-35.

Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. L. C. Clark, G. F. Combs, Jr., B. W. Turnbull, E. H. Slate, D. K. Chalker, J. Chow, L. S. Davis, R. A. Glover, G. F. Graham, E. G. Gross, A. Krongrad, J. L. Lesher, Jr., H. K. Park, B. B. Sanders, Jr., C. L. Smith, J. R. Taylor. Jama 1996: 276(24); 1957-63.

Journals should see original protocols for clinical trials. C J Hawkey. BMJ 2001: 323(7324); 1309-. [Medline] [Full text]

Randomised controlled trial of cardiotocography versus Doppler auscultation of fetal heart at admission in labour in low risk obstetric population. G. Mires, F. Williams, P. Howie. British Medical Journal 2001: 322(7300); 1457-60; discussion 1460-2. [Medline] [Abstract] [Full text] [PDF]

Celestial determinants of success in research. R. Pollex, B. Hegele, M.R. Ban. Cmaj 2001: 165(12); 1584. [Medline] [Full text] [PDF]

Cancer Clusters: Finding Vs. Feelings. David Robinson, Medscape. Accessed on 2003-05-09. www.medscape.com/viewarticle/442554_1

False positive outcomes and design characteristics in occupational cancer epidemiology studies. G. G. Swaen, O. Teggeler, L. G. van Amelsvoort. Int J Epidemiol 2001: 30(5); 948-54.

Evidence >> Mountain >> Precision (1)

Why randomized controlled trials fail but needn't: 2. Failure to employ physiological statistics, or the only formula a clinician-trialist is ever likely to need (or understand!). D. L. Sackett. Cmaj 2001: 165(9); p1226-37. [Medline] [Full text] [PDF]

Evidence >> Mountain >> Reliability (2)

Do health interview surveys yield reliable data on chronic illness among older respondents? M. Beckett, M. Weinstein, N. Goldman, L. Yu-Hsuan. American Journal of Epidemiology 2000: 151(3); 315-23.

Age of First Use: Its Reliability and Predictive Utility. Erich Labouvie, Marsha E. Bates, Robert J. Pandina. Journal of Studies on Alcohol 1997: 58(6); 638-643.

Evidence >> Mountain >> Retrospective (1)

Recall bias in a case-control surveillance system on the use of medicine during pregnancy. M. Rockenbauer, J. Olsen, A. E. Czeizel, L. Pedersen, H. T. Sorensen. Epidemiology 2001: 12(4); p461-6.

Evidence >> Mountain >> Retrospective >> Recall Bias (3)

Records, recall loss, and recall bias in pregnancy: a comparison of interview and medical records data of pregnant and postnatal women. H. E. Bryant, N. Visser, E. J. Love. American Journal of Public Health 1989: 79(1); 78-80. [Medline]

Determinants of recall and recall bias in studying drug and chemical exposure in pregnancy. Y. Feldman, G. Koren, K. Mattice, H. Shear, E. Pellegrini, S. M. MacLeod. Teratology 1989: 40(1); 37-45.

Recall of Early Menstrual History and Menarcheal Body Size: After 30 Years, How Well Do Women Remember? A. Must, S.M. Phillips, E.N. Naumova, M. Blum, S. Harris, B. Dawson-Hughes, W. M. Rand. Am. J of Epidemiology 2002: 155(7); 672-679.

Evidence >> Mountain >> Sample Size (5)

The prevalence of negative studies with inadequate statistical power: an analysis of the plastic surgery literature. K. C. Chung, L. K. Kalliainen, S. V. Spilson, M. R. Walters, H. M. Kim. Plast Reconstr Surg 2002: 109(1); 1-6; discussion 7-8. [Medline]

Putting trials on trial--the costs and consequences of small trials in depression: a systematic review of methodology. M. Hotopf, G. Lewis, C. Normand. J Epidemiol Community Health 1997: 51(4); p354-8.

Epidemiological appraisal of studies of residential exposure to power frequency magnetic fields and adult cancers. C. Y. Li, G. Theriault, R. S. Lin. Occup Environ Med 1996: 53(8); 505-10. [Medline]

The ethics of tiny trials. B. Phillips. Arch Dis Child 2002: 87(3); 258.

Epidemiology of silicone-related disease. S. H. Swan. Semin Arthritis Rheum 1994: 24(1 Suppl 1); 38-43. [Medline]

Evidence >> Mountain >> Samplesize (4)

Negative results of randomized clinical trials published in the surgical literature: equivalency or error? J. B. Dimick, M. Diener-West, P. A. Lipsett. Arch Surg 2001: 136(7); 796-800.

Distinguishing between "no evidence of effect" and "evidence of no effect" in randomised controlled trials and other comparisons. William Odita Tarnow-Mordi, MJ Healy. Arch Dis Child 1999: 80(3); 210-213.

Cost effectiveness calculations and sample size. David J Torgerson, Marion K Campbell. BMJ 2000: 321697.

Elevated blood lead levels in children of construction workers. EA Whelan, GM Piacitelli, B Gerwel, TM Schnorr, CA Mueller, J Gittleman, TD Matte. American Journal of Public Health 1997: 87(8); 1352-55.

Evidence >> Mountain >> Subgroup (16)

Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. L. Allan, H. Hays, N. H. Jensen, B. L. de Waroux, M. Bolt, R. Donald, E. Kalso. British Medical Journal 2001: 322(7295); 1154-8. [Medline] [Abstract] [Full text] [PDF]

Analysis of clinical trial outcomes: some comments on subgroup analyses. M. E. Buyse. Controlled Clinical Trials 1989: 10(4 Suppl); 187S-194S.

The miracle of DICE therapy for acute stroke: fact or fictional product of subgroup analysis? Carl E Counsell, Mike J Clarke, Jim Slattery, Peter A G Sandercock. British Medical Journal 1994: 309(6970); 1677-1681.

Coronary Heart Disease and All-Causes Mortality in the Multiple Risk Factor Intervention Trial: Subgroup Findings and Comparisons with Other Trials. Jeffrey A Cutler, James D Neaton, Stephen B Hulley, Lewis Kuller, Oglesby Paul, Jeremiah Stamler. Preventive Medicine 1985: 14(3); 293-311.

Interpreting the results of secondary end points and subgroup analyses in clinical trials: should we lock the crazy aunt in the attic? N. Freemantle. British Medical Journal 2001: 322(7292); 989-91. [Medline] [Full text] [PDF]

Randomised, clinically controlled trial of intensive geriatric rehabilitation in patients with hip fracture: subgroup analysis of patients with dementia. T. M. Huusko, P. Karppi, V. Avikainen, H. Kautiainen, R. Sulkava. British Medical Journal 2000: 321(7269); p1107-11. [Medline] [Abstract] [Full text] [PDF]

Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastatic breast cancer. J. N. Ingle, J. E. Krook, S. J. Green, T. P. Kubista, L. K. Everson, D. L. Ahmann, M. N. Chang, H. F. Bisel, H. E. Windschitl, D. I. Twito, et al. J Clin Oncol 1986: 4(2); p178-85.

Determination of who may derive most benefit from aspirin in primary prevention: subgroup results from a randomised controlled trial. T W Meade. British Medical Journal 2000: 32113-17. [Medline] [Abstract] [Full text] [PDF]

Determination of who may derive most benefit from aspirin in primary prevention: subgroup results from a randomised controlled trial. T W Meade, P J Brennan. BMJ 2000: 321(7252); 13-17. [Medline] [Abstract] [Full text] [PDF]

Coronary Heart Disease Death, Nonfatal Acute Myocardial Infarction and Other Clinical Outcomes in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group. The American Journal of Cardiology 1986: 58(1); 1-13. [Medline]

A Consumer's Guide to Subgroup Analyses. Andrew D. Oxman, Gordon H. Guyatt. Annals of Internal Medicine 1992: 116(1); 78-84.

Subgroups, treatment effects, and baseline risks: some lessons from major cardiovascular trials. AB Parker, CD Naylor. American Heart Journal 2000: 139(6); 952-61. [Medline]

Misleading subgroup analyses in GISSI [letter]. R. Peto. Am J Cardiol 1990: 66(7); 771-2.

Repeated doses of porcine secretin in the treatment of autism: a randomized, placebo-controlled trial. W. Roberts, L. Weaver, J. Brian, S. Bryson, S. Emelianova, A. M. Griffiths, B. MacKinnon, C. Yim, J. Wolpin, G. Koren. Pediatrics 2001: 107(5); pE71.

Supplemental Therapeutic Oxygen for Prethreshold Retinopathy of Prematurity (STOP-ROP), A Randomized, Controlled Trial. I: Primary Outcomes. STOP-ROP Multicenter Study Group. Pediatrics 2000: 105(2); 295-310. [Medline]

Analysis and Interpretation of Treatment Effects in Subgroups of Patients in Randomized clinical trials. S Yusuf. JAMA 1991: 266(1); 93-98.

Evidence >> Mountain >>