Beginner’s Guide to Institutional Review Boards (IRBs)
Reasonably, it takes a village to conduct a clinical trial. And among the many vital contributors to successful clinical research in the U.S. is the institutional review board (IRB) – sometimes known as an independent ethics committee (IEC), an ethical review board (ERB), or a research ethics board (REB).
Under Food and Drug Administration (FDA) regulations, an IRB is an independent group of people who review and monitor biomedical and behavioral research involving human subjects. An IRB’s purpose is to protect the participant rights and welfare of human research. In accordance with FDA regulations, an IRB has the authority to approve, require modifications to, or disapprove research when it believes the participant’s rights or welfare are not properly protected.
According to James Riddle, Vice President of Research Services and Strategic Consulting at Advarra, “Probably the most important thing for an individual to know is that, at least here in the United States, there is an independent group of folks who are overseeing research, looking out for your best interest as a patient, somebody other than the sponsor.”
History and Origins of the IRB
The IRB originated in several landmark efforts to instill ethical considerations into research, including the Nuremberg Code of 1945, stemming from Nazi atrocities in World War II. U.S.-based events that helped inspire the IRB include the Tuskegee Syphilis trial, in which Black men with syphilis were denied treatment. The National Research Act, signed into law in 1974, is the legislation that formally created the IRB. The Belmont Report followed in short order and set forth the basic ethical principles underlying biomedical and behavioral research conduct involving:
- Respect for persons
Today, the IRB’s structure and function is codified in 21 CFR Parts 16 and 56, enacted in 1981.
Who Serves on an IRB?
The people serving on an IRB is surprisingly diverse, as it may include lawyers, accountants, local church members, or any other community member who expresses interest in serving, applies for membership, and is accepted. IRB members may serve on a private IRB, through companies like Advarra, or the academic institution may administer their own IRB.
What Elements of Research does the IRB Review?
Both sponsors and independent researchers working on behalf of sponsors are subject to IRB oversight. Sponsors will submit their protocol and information about the investigational product (IP). They’ll also submit the template consent documents and any other materials patients will receive to explain the trial to them. Once these elements are approved, the IRB will turn to review the individuals conducting the research.
Each research site submits a short application to the IRB to verify the investigator has the appropriate credentials, facilities, and staff to safely conduct the trial. The submission should also include:
- The investigator’s curriculum vitae and medical license
- Study information, including:
- The clinic
- Staff involved in the research
- Expected number of participants enrolling in the trial
- Prior experience with conducting trials in this particular disease modality or similar disease conditions
The IRB’s objective is to confirm each investigator is qualified to conduct the trial per the already-approved protocol.
What is the IRB’s Potential Impact on a Trial?
While the IRB does have the power to derail or even terminate a research project, researchers should understand while it is rare, and is never the IRB’s objective. Certainly not at Advarra.
“We want to see projects move forward, we want to see new cures hit the market, we want to see advancement in human health,” says Riddle. “So, what we are most likely to say to a sponsor is something like this: ‘Look, here are the federal regulations. Here’s where your protocol falls short, in our opinion. Take what we’ve said under consideration, update your protocol, and come back to us.’ If the sponsor disagrees with the IRB’s position, they are welcome to appeal the evaluation or ask for clarification. Very rarely is a protocol ever just killed.”
How do Sponsors and Researchers Interact with the IRB?
Once the protocol and investigators are approved and researchers start enrolling and consenting participants, staff will continue to send periodic reports to the IRB. The Board will want to know the number of participants enrolled and any problems stemming from the study. There is significant interaction between the investigators, the sponsor, and the IRB when the investigated drug or device uncovers new risk information. For instance, if new side effects appear, the IRB will decide how to communicate the information to participants. They will also make sure participants understand they can end their participation based on the new information.
Does IRB Oversight Continue Throughout the Trial?
While most of the heavy lifting occurs during research initiation, an IRB will continue to monitor trial activities as long as there are interactions between researchers and participants. In a typical clinical trial, this includes long-term follow up and data gathering, even beyond the point where participants are taking the IP. As long as there is still communication between participants and the investigators, the IRB will be active. This provides participants with the comfort of knowing that if at any point new risk information is revealed, the IRB will make certain they are informed and given the opportunity to exit the trial.
A special thank you to James Riddle for providing insight into this blog.