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.
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
and was last modified on
2008-07-14.
dot edu or click on the email link at the top of the
page.
Category: Research ethics
