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Demystifying the Institutional Review Board
By Adrienne Malik, MD; James Paxton, MD, MBA; and Mark Mycyk, MD on behalf of the SAEM Research Committee
From the outside, it may appear that the Institutional Review Board (IRB) is a group of maleficent specters intent upon derailing the well-intentioned efforts of researchers who are simply in pursuit of undiscovered truths needed to improve the practice of medicine. But those on the inside understand that the IRB exists to protect human subjects from abuses that may be completely incomprehensible to most researchers. As members of the IRB Illuminati, we bring you information from “behind the curtain,” to help you better understand the process, its invaluable function, and some tips on how to tailor your submissions to make them more acceptable to your IRB colleagues. We promise, we are on your side.
Why do we need an IRB?
All institutions engaged in research are required to have an IRB and they all function similarly. The purpose of the IRB is to assure that, both in advance and by periodic review, appropriate steps are taken to protect the rights and welfare of human subjects participating in research. The over-arching focus of this group is on the risk-to-benefit ratio for subjects engaged in research. Regulation from the IRB is needed to prevent citizens from engaging in clinical research that poses an unacceptable risk to their health without adequate benefit to themselves and society. IRBs exist because in the past some very questionable (and at times abhorrent) methods have been employed in the name of research, at the very real and unethical expense of study subjects (e.g., The Tuskegee Study). In short, the IRB exists for the benefit and protection of potential study subjects.
Who are the members of the IRB?
United States Food and Drug Administration regulations [21 CFR 56.107(a)] require that the IRB must have a "diversity of members, including consideration of race, gender, cultural backgrounds and sensitivity to such issues as community attitudes." Consequently, membership in the IRB includes a mix of community members as well as research scientists and other individuals with insight into the research process. In general, IRBs cannot decide on research protocols without adequate representation by “laypersons” from the community. It is important to remember that IRB members are volunteers, with a wide range of backgrounds, including physicians, nurses, pharmacists, lawyers, business leaders, and other members of the community. By law, IRBs must contain at least one non-scientist and one individual not associated with your institution to act as unbiased stakeholders on the behalf of study subjects.
What are the types of IRB submissions?
Submissions to the IRB can be categorized as “exempt” (not requiring IRB oversight), “expedited” (not requiring full committee review) or requiring “full board” review. Although the IRB may offer decision tools to help researchers assess the distinction between these types of submissions, the final determination remains up to the IRB. Expedited submissions are generally low-risk protocols that may be reviewed by a single appointed IRB member, rather than the full IRB. Once an expedited or full-board protocol has been approved, the study team may submit an “amendment” (aka “modification”) to change any aspect of the study, or a “continuation” to
keep the study open beyond the initial approval period (typically 6-12 months). When “unexpected problem” reports are submitted for adverse events that occurred during an ongoing study, the IRB will determine whether the problem represents an isolated incident, a protocol deviation, or something serious enough to require stopping the study altogether.
What really goes on during IRB meetings?
Committees meet regularly to discuss full-board research proposals. The IRB chair will assign a primary (and possibly a secondary) reviewer for each proposed research protocol, and your proposal’s primary reviewer will be that board member who is most familiar with your protocol and will facilitate discussion with other members. Each member of the IRB is eligible to vote for or against a study’s approval, but they are required to recuse themselves if they have a conflict of interest. These discussions can get quite in depth if there is an aspect of a study that is concerning to any one of the IRB members, not just the primary reviewer. Committees must have a quorum (i.e., minimum number) of members present to conduct business, and this quorum usually specifies how many scientists, nonscientists, and community members must be present.
Why does it take so long for them to get back to me?
Most IRBs require submission for evaluation 2-3 weeks in advance of the committee’s meeting date, so that members will have enough time to fully review the proposal. Even if the IRB determination is favorable, it may be 1-2 weeks before a formal letter can be issued to the investigator to communicate their determination. It is helpful for investigators to consider these delays when submitting initial or amendment proposals. Occasionally, approval of a project will be contingent upon a change in the protocol, informed consent form, or other aspect of your study. If this is the case, the IRB will need to confirm that these changes have been implemented prior to giving your study a green light to enroll. A requested change will require additional review by the IRB at their next scheduled meeting.
What is the IRB really looking at in my project submissions?
Although the “scientific merit” of the study is considered, the IRB’s primary purpose is to protect human subjects. Although scientist members of the committee will offer their interpretation of the value of the data to be collected, many members of the committee are not scientists or researchers. If the risk of participation in a study is low, a wellwritten and complete submission has a high likelihood of approval. If the risk associated with participation is high, the study team will need to provide adequate justification for subject enrollment before the IRB can approve the study. Thus, the primary focus of most IRBs is on the risk-to-benefit ratio for participants, so this aspect of the study should be clearly described in the IRB submission.
Before submitting a proposal to the IRB, researchers should consider whether their protocol, informed consent form (ICF), and all other documents are free of cumbersome medical jargon and easily interpretable to nonscientists and patients with limited research training or formal education. It is helpful to bear in mind that while many members of your IRB are physicians or scientists, they may have an area of expertise that is far removed from the scope of your research. Simple explanations and clear, concise language in your protocol will benefit you in your IRB review. Additionally, make sure to include known or anticipated adverse effects of investigational drugs or procedures, and your plan to mitigate the risks to your subjects.
A study’s ICF is subject to significant scrutiny by the IRB. Many submissions are held up due to the consent form being viewed as confusing, unclear, or manipulative by nonmedical members of the IRB. Aim to write an ICF that can be understood by someone with a 6th grade reading level and avoid the use of coercive language.
What other tips do you have for IRB submissions?
Investigators should ensure that they have adequately described their plan for data handling and patient safety monitoring during the study, as these represent other areas of potential risk to subjects that will be closely examined during the IRB review. If you plan to compensate your subjects for participation, make the compensation commensurate with what you are asking them to do.
Lastly, your institutional IRB is very willing to assist you with your proposal or answer any questions you might have. We understand navigating the submission and review process is not always intuitive. Communication from you or your research team is both welcomed and encouraged.
We hope you found this little foray into the enigmatic world of the IRB to be helpful. We look forward to reviewing your next proposal!
ABOUT THE AUTHORS
Dr. Malik is an assistant professor of emergency medicine at the University of Kansas Medical Center in Kansas City, KS. She has been a member of the Kansas University Institutional Review Board since 2020. Dr. Paxton is associate professor of emergency medicine and director of clinical research at Detroit Receiving Hospital/ Wayne State University (WSU) School of Medicine (Detroit, MI). He is a long-time member of the WSU Institutional Review Board, including recent chair of the MP2 IRB Committee (2015-2020). Dr. Mycyk is chair of research in the Department of Emergency Medicine and serves as vice chair of the Institutional Review Board at Cook County Health.
