The revised Common Rule’s provision that a single IRB should review protocols for multisite studies raises questions about how these IRBs handle conflicts of interest, local knowledge, and other issues.
When a group of researchers sought to answer these questions, they found a big obstacle: Some IRBs, including the largest ones, were unwilling to participate.1
“We thought when single IRBs were mandated, they played an increasingly important role that affects everyone’s lives, and we thought it’d be important to understand best practices,” says Robert Klitzman, MD, professor of psychiatry and director of online and in-person masters of bioethics programs at Columbia University in New York City.
Investigators wanted to understand the challenges and what helped IRBs meet those challenges.
“We conducted this study, and I was surprised — or, I should say I was struck — and disappointed that commercial for-profit IRBs were much less likely to agree to participate, and it was significant,” Klitzman says. “None of the major, large, for-profit IRBs agreed to participate. This is concerning to me because IRBs are set up to be paragons of ethical behaviors and practices.”
Close to 90% of drugs approved by the Food and Drug Administration (FDA) are handled by one for-profit IRB, according to 2015 data, Klitzman says.
“As an ancient author said, ‘Who is guarding the guard?’ If they’re watching researchers to make sure they’re ethical, who’s watching the IRBs?” he asks.
Ethical Concerns Raised
While there is no evidence that any IRBs are doing a poor job, there also are no data on how they make decisions and handle ethical considerations. When IRBs that are overseeing the vast majority of drugs approved by the FDA do not talk with investigators about their work, there are major ethical issues and concerns raised, he adds.
Advarra, a large, independent IRB in Columbia, MD, responded to an emailed request for comment about Klitzman’s study. At press time, IRB Advisor did not receive responses from WIRB-Copernicus Group or Pearl IRB.
“We believe protecting participants in research is paramount,” says Michele Russell-Einhorn, JD, chief compliance officer and institutional official for Advarra. “Therefore, research on the effectiveness and underlying operations of IRB review is important for better understanding IRB review and identifying possible improvements to ensure that the system is adequately and appropriately protecting patients. Advarra is an active participant in AEREO (the Consortium to Advance Effective Research Ethics Oversight) and participated in the National Institutes of Health-funded study looking at increased use of single IRBs for multicenter clinical trials.”
About 40% of IRBs agreed to participate in the study. This included close to 82% of academic IRBs and half of government single IRBs, but only 23% of commercial single IRBs. Some of the IRBs that refused full participation, which included board observations and individual interviews, cited privacy or confidentiality concerns and insufficient time and resources.1
How Well Are Subjects Protected?
Without data from the largest IRBs, researchers have no information on the safety of human subjects, Klitzman says.
“The scientific enterprise depends on transparency, principles of communitarianism, a sharing of best practices, and an openness that is crucial to make sure there is integrity for IRBs that are overseeing the vast majority of drugs approved by the FDA,” he explains. “To say, ‘We’re not even going to talk to you about what we’re doing,’ is, to me, something that raises major ethical issues and concerns.”
Although the nation’s largest IRBs are accredited, this does not answer the investigators’ concerns. “Accreditation agencies look at the process — not the content of reviews,” Klitzman says. “They don’t look at how risks are evaluated; they look at the minutes collected.”
The Office for Human Research Protections (OHRP) also provides oversight, but only for federally sponsored studies. “If there’s a problem, usually there would be a for-cause audit. It would be around a particular study, as opposed to observing IRBs to see how much concern there is about risk, how much concern about autonomy, and concern about local knowledge, racial issues,” Klitzman adds.
The oversight provided by research into IRB operations might be more important as research institutions increasingly rely on large, commercial IRBs. This shift was underway, partly due to understaffed institutional IRBs, before the revised Common Rule mandated an IRB of record for multisite studies. Now, the shift appears to be increasing, he says.
“What’s happening is a lot of studies are saying, ‘Let’s have one of the large, commercial IRBs do it,’” Klitzman says. “They’ll outsource to a large, single IRB.”
The solution would be for accreditation organizations and OHRP to collect data on IRB issues related to risk, local knowledge, and other issues.
“I think the Department of Health and Human Services, which has jurisdiction over the Common Rule, could say single IRBs should have outside review about their functioning,” Klitzman says. He suggests lawmakers could pass legislation that would require IRBs to be audited.
Large, commercial IRBs have the right to refuse to participate in research about IRB operations, but their refusal shows a lack of transparency when they often review studies funded by taxpayers at early stages of research, Klitzman says.
“American citizens and people from all over the world are affected by the benefits and risks of the drugs they are studying,” he says. “I think there is a serious question of whether they have some responsibility to be open to assure people, whose lives are at risk, about the quality of their decision-making and review process.”
- Klitzman R, Appelbaum PS, Murray A, et al. When IRBs say no to participating in research about single IRBs. Ethics Hum Res 2020;42:36-40.