Submitting a research protocol to the IRB (July 29, 2004).

I usually just watch and advise as others submit research protocols to our Institutional Review Board (IRB). But now I might end up having to submit one myself. I want to perform a secondary data analysis on a data set that was collected several years ago. It should be an educational experience. If I do learn anything valuable, I'll put it on this weblog.

One excellent suggestion I heard is that you should treat the IRB submission as the first draft of the publication that you will eventually send off to the New England Journal of Medicine. Since you don't have ESP, you can't write the results section just yet. But you can write the sections on background, significance, and methods and you can supply most of the bibliography.

One of the most important roles for the IRB is to assess the value and information that this research is expected to produce and balance it against the risks, discomforts, and inconveniences imposed on the research subjects. I talk a bit about scientific validity and IRB review on my web pages, and this weblog entry will give me an opportunity to expand on this topic.

Here are some of the questions that our IRB asks on their submission form:

• Project Title: Secondary analysis of breastfeeding data set
• Sponsor name/Protocol or Grant #: Not applicable
• Primary Investigator: me!
• Sub-Investigator(s): I'm working with Sue Teasley on this project.

Here's where it gets interesting.

• Conflict of Interest Statement: Does a real or potential conflict of interest exist for any investigator named in sections C or D?

I need to write more about conflict of interest. I've mentioned this topic in my web log entry on February 25, 2004. Here, the IRB is probably most interested in financial conflicts of interest.

• Prior Scientific Review?

This project has not had prior review. The IRB wants to make sure that the scientific value of the study outweighs the risks to the research subjects. If research comes from a funded NIH grant, then that represents an endorsement of the scientific merit of the study. That doesn't mean that the IRB won't also look at the scientific merit, but it does provide them with some level of assurance of the quality of the scientific goals of this research.

• Requested Review: [ ] Full Committee [ ] Expedited [ ] Exempt (If requesting exemption from review state rationale as defined by 45 CFR 46.101, 401)

I'm going to argue that this study is exempt because it only involves the use of anonymized data that already exists.

• Study Objectives/Specific Aims and Primary Outcome Variable(s): (clearly state the research question)

The objective of this study is to examine factors that influence infant weight loss between birth and discharge from the birth hospital in a sample of infants who were discharged with their mothers. The primary outcome variable is percent weight loss. We will look at factors like the type of delivery, the age of the mother, and so forth. We also want to investigate factors that influence whether a lactation consultant was assigned to the new mother.

• Background and Significance: (Give brief overview, including previous use in pediatrics, deficiencies in previous studies, relevance to pediatric health care; attach a bibliography. If the study involves treatment, state how study is different from routine care)

I'll need a bit of help for this section, as I am not the subject matter expert. We should probably write a couple of paragraphs: one on the background and one on  significance. A bibliography of any related research in the area will also be useful.

The IRB needs this information to help decide if the problem we are studying is worthwhile and will provide useful information to clinicians and/or researchers in this area.

• Study Design: (State whether study is descriptive or experimental, basic or applied research, single or multi-centered, number of sites, blinded, randomized or convenience sample, placebo controlled, etc. State whether intended as a “pilot” vs “definitive” study. Include plan for statistical analysis including sample size/power analysis and consultation with biostatistician)

This is a bit less relevant, perhaps, because the data was already collected, but I'll spend some time explaining how the sample was collected. This is a cohort of mothers and children recruited from 14 hospitals in the Kansas City metropolitan area.

• Subject Selection Criteria:
  1. Recruitment of Subjects: (State how and by whom potential subjects will first be identified and provide a detailed plan for obtaining permission/assent. Provide letters of support when appropriate)
  2. Expected Sample Size: Total study: [ ] CMH only: [ ]
  3. Inclusion Criteria:
  4. Exclusion Criteria:

Again, this just provides an opportunity to review the process by which the data was collected. If the IRB wants me to change any of these details, perhaps they will offer me a time machine.

• Study Groups: (include information regarding randomization procedures, treatment groups, etc)

Again, this reviews the basic process of the previous research. There was no randomization and no treatment in the study. There are groups (boy babies versus girl babies, young mothers versus old mothers), but these groups do not represent the predominant focus of the research. We just wanted to characterize the factors that influenced breastfeeding for new mothers in the original study and now we want to also characterize the factors that influence weight loss between birth and discharge from the birth hospital.

• Methods/Observations/Measurements: (Identify those specific observations and measurements (Outcome Variables) to be used to test the stated hypothesis Indicate. Include what subjects are expected to do, tests they will have, when blood will be drawn, etc. Include a study flow chart if applicable. Include study safety parameters. Be specific. Attach a copy of data collection forms for all investigator initiated studies.)

The original data collection involved an interview with the mother at the birth hospital, a review of the medical records of the birth, and a telephone follow-up call seven to ten days after birth.

• Confidentiality of Subjects and Data
  1. What subject identifiers are used in study documents?
  2. Where will data be stored and how will confidentiality be maintained?
  3. Will tissue/blood samples be stored beyond the end of the study? [ ] Y [ ] N [ ] NA
  a. If yes, explain, and specify what subject identifiers will be retained on the samples:
  b. Is this clearly stated in the consent form?
  4. What will happen to data and samples if subject withdraws prior to completing the study?

This is important to specify for this project, because the risk of a confidentiality breach is the only serious risk in this study. I will show that all important direct personal identifiers (name, address, medical record number) and indirect identifiers (birthdate and zip code) have not been collected or have already been removed from the data set. This is a very important issue in general and I have a web page about confidentiality and privacy concerns.

• Drug(s): [ ] NA [ ] New use of approved drug [ ] New drug [ ] Other (explain)
  IND #: [ ]
  Drug name: [ ]
  Study Phase #: [ ]
  Route of Administration: [ ]
  How is drug supplied? [ ]
  Dosing Regimen: [ ]
  Possible side effects: [ ]
  (Add as needed. List all drugs involved)

There are no drugs in this study, of course, but if there were, the IRB would need to know if this was an already approved drug or one that is currently under investigation.

• Device: [ ] N/A [ ] New use of approved device [ ] New device IDE # [ ]
  Sponsor’s assessment of risk: [ ] Non-significant risk device: [ ] Significant risk
  Investigator’s opinion of risk: [ ] Non-significant risk device: [ ] Significant risk
  Rationale for risk assessment:

The same issues apply for new medical devices.

• Investigational Procedure: (e.g., surgical procedure, wound care, positioning, etc) Describe and explain why it is investigational)

We are not physically intervening with these subjects in this study. If we were, we would describe this investigational procedure in detail.

• Financial Obligations: (Do not attach budget)
  1. List procedures/tests/equipment required by the study which will be funded by the study:
  2. If applicable, list procedures/tests/equipment required by the study for which the subject (and/or third party payor) will be responsible:
  3. Describe subject reimbursement (vs. compensation) and give rationale for amounts, (Explain how incentives will be prorated)

There are no financial obligations in this study. For those studies where this is an issue, the IRB is concerned with whether some of the financial obligations might create a conflict of interest and also whether undue financial burdens are being imposed on the research subject.

• Known and Potential Risks and Benefits of Study Participation:
  1. State all known and potential risks to participants involved in this study
  2. How will all risks of study participation be managed and minimized, including risks from study procedures and drugs?
  3. Investigator’s Assessment of Risk: (according to 45 CFR Part 46 Subpart D)
  [ ] Category 1 Research not involving greater than minimal risk.
  [ ] Category 2 Research involving greater than minimal risk but presenting the prospect of direct benefit to the individual subjects.
  [ ] Category 3 Research involving greater than minimal risk and no prospect of direct benefit to the individual subjects, but likely to yield generalizable knowledge about the subject’s disorder or condition.
  [ ] Category 4 Research not otherwise approvable which presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children.
  4. Provide statement explaining your choice:
  5. State the benefits of study participation:

This is obviously research not involving greater than minimal risk. The category of risk will determine the level of IRB review as well as whether one or both parents need to provide permission.

As I further prepare the IRB submission, I will update this page. I may also add a few links the help to further clarify the issues that the IRB faces when reviewing research protocols.

This webpage was written by Steve Simon and was last modified on 2008-07-14. Send feedback to ssimon at cmh dot edu or click on the email link at the top of the page. Category: Research ethics