IRBs, others comment on possible change to centralized IRB reviews

Proposed common rule raises issue

The proposed Common Rule changes that would permit a central IRB to review multiple site studies drew passionate responses both for and against the change in the early comments submitted to the U.S. Department of Health and Human Services (HHS).

The changes were published in the Federal Register, on July 25, 2011, as part of an Advanced Notice of Proposed Rulemaking (ANPRM). The Office for Human Research Protections (OHRP) published comments to the ANPRM online at www.regulations.gov.

Those in favor of the change discussed their frustration with the requirement of seeking IRB approval from multiple IRBs when the overlap essentially provides no additional human subjects protection and may even diminish protection and responsibility.

For instance, Warren Grill, PhD, an Addy professor of biomedical engineering at Duke University in Durham, NC, writes in his comment to OHRP that he is in favor of the change because multiple IRB reviews reduces individual responsibility.

"I think that having multiple levels of review, whether it be multiple IRB reviews of the same protocol or a National Institutes of Health [NIH] review and institutional reviews of protocols tends to diffuse responsibility," Grill says. "In fact I would suggest this can actually lead to an abdication of responsibility with the assumption that one of these reviews be someone else has reviewed it, so it's okay, and I'll put a rubber stamp on it."

Others who sent comments to OHRP expressed an opposite fear: "How long before sponsor are placing their studies with sponsor friendly IRB's first to get IRB of record rubber stamps," one commentator asks.

From a practical standpoint, having multiple IRBs review a single protocol introduces delays and unnecessary administrative task time, taking away the time physician researchers might instead spend on science and clinical work, Grill notes.

When IRBs come up with different decisions on the same study, the problem multiplies.

For example, there was a protocol involving deep brain stimulation for treating Parkinson's disease and tremors, Grill says.

"One IRB wanted separate consent forms for Parkinson's and tremors, and another wanted one harmonized consent form," he says. "This was not going to impact risk or the well-being of the participants, but it was an additional administrative burden of having three consent forms for one study."

If HHS moves forward with the proposed change to permit a central IRB to handle multisite study review, then safeguards need to be put in place, says Joann Margaret Glacken, MA, regulatory coordinator at the Feinberg School of Medicine's comprehensive transplant center, Northwestern University, Chicago, IL.

"They have to have a hard and fast mechanism in place to ensure that they're not allowing a principal investigator to go around the institution, working directly with this central IRB, and not engaging the local IRB or their institution," Glacken says. "To me, that would pose a problem because of liability issues."

However the Common Rule is revised, the language should not exclude the required oversight of the actual entity where the principal investigator is employed, adds Glacken, who previously worked as the IRB administrator at the University of Illinois in Rockford, IL.

"I don't see why it's being tweaked," Glacken says. "Institutions have an option where they can draft a memorandum of understanding to allow them to opt out of the review process, saying they like this central IRB and trust them to speak in essence for their institution."

Researchers and IRB officials who commented in favor of the change to a central IRB model cited their frustration with how time-consuming it can be to obtain IRB approval for multisite studies. One physician commented that in her experience an IRB will spend a lot of unnecessary time trying to understand a low-risk, multisite study situation, sometimes even waiving IRB approval in the end.

"I think the IRB approval at the primary institution provides perfectly adequate protection for the subjects involved in these studies that are largely extremely low risk," writes Ellen Link, MD, a clinical professor at the University of Iowa in Iowa City, IA.

Others expressed concern about the lack of local sensitivities if multisite studies were handled solely by a central IRB.

"Central IRBs may not know the special populations at the local site and if an event were to happen, the institution that has been taken out of the review process still has a responsibility for the conduct of the PI at the local site," Glacken writes in her comments to OHRP.

"If you filed an application with the central IRB and then something happens on the local level, how is an institution supposed to know about it? At what point is the local IRB of the institution going to have their voice?" Glacken says. "Are they losing their voice to speak for their own subject population and to protect their own population? That's my concern."

A concrete example of this local voice would be an IRB review of a study that requires birth control. If the study is conducted at a Catholic-based hospital, a central IRB's approval might overlook this particular institution and population's concerns, one commentator says to OHRP.

For the bulk of biomedical research conducted at research institutions, a central IRB's approval would provide adequate human subjects protection, some comments to OHRP noted.

"I am very much in favor of one IRB being responsible for the conduct of a single study being carried out at multiple sites. The oncology cooperative group studies are a perfect example where this process would work," writes John J Leighton Jr., MD, of Albert Einstein Medical Center in Philadelphia, PA.

"The science is high level, the risks are similar regardless of the site, and it would lessen the burdens of the researchers and the local IRBs will still providing a high level of protection to subjects," Leighton comments to OHRP.

The multisite, multiple IRB process is cumbersome, Glacken notes.

"But there has to be a meeting somewhere halfway," she adds. "There are issues on each campus, and every institution has a responsibility to ensure that the research protocols are being conducted on their campus within local standards and with some sort of mechanism of control that is warranted."

Many research institutions have IRB policies that are more stringent than the federal requirements, so they do this to prevent liability to their institutions, she says.

"If you have a central IRB speak for us, then I'm worried about what the repercussions would be to human subjects," Glacken says.

Researchers, like research institutions, want to do the right thing, and they'll continue to look out for the interests of their research subjects even under a central IRB review process, Grill says.

"The vast majority of investigators who are participating in the conduct of that study have a genuine interest and concern for the well-being of the participants, and they may be attuned to the local interest of participants," Grill says.

"We should take one step back and think globally about what we're trying to accomplish," he adds.

"We have a lot of talk about translational research, moving things from bench to bedside, getting things out of the laboratory and into clinical use," Grill says. "I think there is little attention paid to the barriers to doing this and how changes can be made to IRB procedures and practices to streamline them without changing the ability of a potential participant to make an informed decision about whether or not to participate."