Institutional review boards (IRBs) play a central role in protecting the rights, safety, and welfare of participants involved in clinical research. From reviewing study protocols and informed consent documents to monitoring ongoing safety reporting throughout a trial, IRBs help ensure research is conducted ethically and in compliance with Food and Drug Administration (FDA) regulations and the Federal Policy for the Protection of Human Subjects (also know as the “Common Rule”).
Understanding how IRBs operate—including their historical foundation, membership structure, review responsibilities, and oversight throughout the study lifecycle—is essential for sponsors, investigators, and research institutions alike.
What is an institutional review board (IRB) in clinical research?
Under 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 participant rights and the 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, SVP of global review operations 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.
- Beneficence.
- Justice.
Today, IRB operations are governed by FDA regulations under 21 CFR Parts 50 and 56, as well as the Common Rule (45 CFR 46), which applies to many federally funded research studies.
Who serves on an IRB?
IRB membership is intentionally diverse. Boards may include physicians, scientists, nurses, pharmacists, lawyers, ethicists, accountants, clergy members, and community representatives. This diversity helps ensure research is evaluated from scientific, ethical, and participant-centered perspectives.
IRB members may serve through independent organizations such as Advarra or through academic medical centers, hospitals, and research institutions that administer their own IRBs.
What does an IRB review during a cinical trial?
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 a single IRB (sIRB)?
Many multisite clinical trials now use a single IRB (sIRB) model. Under this approach, one IRB oversees ethical review for all participating study sites, helping streamline study startup and reduce duplicative reviews while maintaining participant protections.
What is the IRB’s potential impact on a trial?
Although IRBs have the authority to suspend or terminate research that does not adequately protect participants, this outcome is relatively uncommon.
“Advarra wants to see projects move forward, we want to see new cures hit the market, we want to see advancement in human health,” says Riddle.
In many situations, IRBs work collaboratively with sponsors and investigators to resolve concerns and strengthen participant protections.
“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 IRB’s 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. IRBs routinely review:
- Enrollment updates.
- Protocol deviations.
- Adverse events (AEs)
- New safety findings.
- Continuing review materials.
The Board will want to know the number of participants enrolled and any problems stemming from the study. If a clinical trial uncovers new risks or side effects, the IRB may require updated informed consent language or additional participant communications to ensure participants understand the new information and their ongoing right to end their participation based on new findings.
Does IRB Ooversight continue throughout the trial?
While most of the heavy lifting occurs during research initiation, IRB oversight continues as long as researchers maintain interactions with study participants or continue collecting identifiable participant data.
In many clinical trials, this includes long-term follow up and data gathering, even beyond the point where participants stop receiving the investigational product.
As long as there is still communication between participants and the investigators, the IRB will be active. Ongoing IRB oversight helps ensure participants are informed if new safety information emerges during or after the active treatment period.
Key Takeaways
- Institutional review boards (IRBs) protect the rights and welfare of clinical trial participants.
- IRBs review study protocols, informed consent documents, investigator qualifications, and participant safety information.
- FDA regulations and the Common Rule govern many forms of human subject research in the United States.
- IRBs can approve, require modifications to, suspend, or terminate research studies.
- IRB oversight continues throughout the duration of a clinical trial.
A special thank you to James Riddle for providing insight into this blog.