IRBs fail to assess trials’ scientific merit, putting participants at risk

Thousands of people volunteer for clinical research trials in the United States every year. They put their bodies on the line, often seeking benefits from experimental treatments because existing care is ineffective. For most clinical trials, independent institutional review boards (IRBs) are legally required to review the protocol before enrollment can begin.

The majority of experimental treatments don’t work. Most people participating in clinical trials don’t gain direct benefits, so the risks and burdens volunteers face cannot be ethically justified by the possibility of direct benefit. Instead, they are justified by gains in scientific knowledge that might benefit others down the road.

IRBs are supposed to protect trial participants’ interests by assessing a trial’s scientific merit, as described in the trial’s protocol. Our research shows they often don’t do that.

Many IRBs routinely ignore the legal requirement to assess scientific merit, giving clinical trials a stamp of ethical approval without this essential assessment. This is not only a violation of the regulations, it is an insult to the trust that volunteers place in the research enterprise and their sacrifice.

How do we know this? We have observed IRB deliberations, reviewed the published literature on studies of IRB practices, and studied and surveyed IRB practices.

In one IRB deliberation, one of us (S.P.H.) heard statements such as, “I can tell that this is junk science, but if the investigators want to hang themselves, it’s not my responsibility to stop them.”

A 2023 qualitative interview study with experienced IRB chairs and members found that IRB members often consider evaluating the scientific merit of the study to be outside of their scope.

We also recently completed an investigation into guidance and standards-of-practice materials among a cohort of U.S. IRBs, which we have submitted for peer review at a medical journal. We found little evidence suggesting that these boards assessed the scientific rigor of proposed studies.

As we spoke with IRB chairs and members throughout this investigation, we were told again and again that the scientific merit of the study they are evaluating is out of their scope and that tools or techniques to potentially help IRBs conduct rigorous scientific assessments were of no interest.

So despite the regulations, which make it clear that an assessment of scientific merit is required, and that IRBs have an important duty to protect participants from low-quality trials, the evidence shows that IRBs do not fulfill this duty. Without such assessments, IRBs are not meeting their ethical duty to protect trial participants, and people should not be recruited to participate in trials for which the scientific methods employed cannot answer the hypothesis suggested.

This is a betrayal of the trust that trial volunteers place in the research enterprise.

In 2023, the U.S. Government Accountability Office published the results of an investigation into IRB oversight. It found that IRBs have been operating with essentially no external oversight. Neither government regulators overseeing IRBs nor the IRB’s home institutions diligently check to see if these boards are actually doing their jobs to protect volunteers’ health and interests.

Based on this report, the GAO recommended that the federal Department of Health and Human Services’ Office of Human Research Protections and the Food and Drug Administration be more diligent in conducting routine inspections of IRBs. The GAO also observed a lack of clear standards for how IRBs should be evaluated to see if they are actually fulfilling their mandate of protecting participants’ interests and safeguarding the integrity of the research enterprise.

Although we were encouraged by some of the GAO’s recommendations, were dismayed that recommendations to assess scientific merit were absent from the GAO report and discussions. IRBs need to take the assessment of scientific merit seriously, as this is a necessary requirement for any credible assessment of the risks and benefits in a clinical trial.

To be clear: We believe in research oversight and the mission of IRBs. Our aim in studying and critiquing IRBs is not to add tedious or unnecessary barriers for investigators, which could bring the clinical trial enterprise to a grinding halt. But we want to see IRBs doing their jobs, fulfilling their duties, and doing right by clinical trial volunteers.

IRBs do not need to wait for the Office of Human Research Protections or the FDA to draft new guidance and tell them how to improve. We offer two straightforward improvements they can and should make immediately:

Be transparent. IRBs currently operate behind closed doors. Neither their activities nor their judgments are ever made public. We believe IRBs should make their deliberations public, with anonymization as required to protect investigators’ privacy and intellectual property interests. This is not a new idea. But it is a good one.

Develop sound guidance. IRBs should develop — or adopt — comprehensive guidance materials for assessing a trial’s scientific merit. They should make this guidance public. They should systematically document that they hold the trials they review to this standard.

We see these changes as the bare minimum for restoring the trust IRBs have thus far abused. Until they are made, potential trial participants should not assume that “ethics approval” from an IRB carries any assurance that a trial has scientific merit. On the contrary, they should be highly cautious about invitations to enroll in clinical trials, and should not enroll in one without conducting their own due diligence.

We recognize that asking potential clinical trial participants to conduct their own scientific due diligence is an additional — and frankly unjust — burden to place upon research volunteers. But they have no other choice until IRBs demonstrate they are fulfilling their duty.

Spencer Phillips Hey, Ph.D., is the chief science officer of Prism Analytic Technologies, Inc. Michael S. Wilkes, M.D., Ph.D., is a professor of medicine at the University of California Davis School of Medicine.