Ready or not, IRBs across the United States have only 10 months remaining to change the way they handle reviews of multisite research that is funded by the National Institutes of Health (NIH).

IRBs will need to become either a relying IRB or a single IRB of record for those nonexempt human subjects research protocols after May 25, 2017, according to the Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research, published June 21, 2016.

NIH received 167 comments on its draft proposal of Dec. 3, 2014, including many with concerns about how this would be a complicated and difficult-to-implement unfunded mandate. Some commenters suggested NIH continue with a voluntary single IRB model with incentives, or base the use of a single IRB model on evidence-based practice.

“There’s a lot of emphasis these days on evidence-based medicine, and we forget the fact that the phrase really means something,” says Alexander M. Capron, JD, former board chair of the Public Responsibility in Medicine and Research (PRIM&R) and professor at the University of Southern California in Los Angeles. Last year, Capron had written a comment to NIH on behalf of PRIM&R. His letter suggested NIH not pursue the single IRB policy as it was described in the draft policy, published in December 2014.

NIH has made sweeping statements about its single IRB policy and its benefits to research organizations, but there are no data backing up those claims, Capron says.

“What we have are anecdotes and impressions about this change, but we don’t have data,” he says.

There’s also the possibility that this change will result in a large growth of commercial IRBs, consolidation, and closing of smaller, institutional IRBs, Capron says.

It’s even possible that some small research sites will stop being research sites because they might not feel equipped to make judgments about IRB of record agreements and they’re concerned about their own liability under a relying IRB arrangement, he adds. “It’s not just they get out of the IRB business, but they get out of the research business, and if that happens, it could change the extent to which patients, who are seen at those institutions, come into the process of developing and testing drugs and devices.”

NIH’s final policy on requiring a single IRB of record answered a few commenter concerns, but left others in limbo.

“One of my biggest remaining concerns is this model they’ve implemented takes you down the path of using 20, 50, potentially 100 different central IRBs,” says David L. Wynes, PhD, vice president for research administration at Emory University in Atlanta.

“It’s simply the logistics,” Wynes says. “What this means is we have to have a mechanism for tracking these 20 to 100 IRBs.”

NIH’s new policy states that its goal is to “enhance and streamline the IRB review process in the context of multisite research so that research can proceed as effectively and expeditiously as possible.”

The final policy also addresses IRBs’ and other commenters’ concerns about a burdensome implementation, saying that any challenges associated with implementation will be short-lived. “Once the transition to the new way of operating is made, the benefits of widespread use of sIRBs [selected IRBs of record] will outweigh any costs and, ultimately, reduce burdens to the research process,” the NIH final policy says.

“I’ve been a proponent of using a central IRB for many years, but my feeling is you should use as few as possible because you have to set up these complex relationships,” Wynes says. “And NIH policy is set on getting approval and not on other parts of the relationship, which are extremely complicated and involved.”

IRBs and institutions will have to review their operational structure and the potential costs of becoming an IRB of record before deciding how they should proceed, notes Karen Hansen, director of the institutional review office of the Fred Hutchinson Cancer Center in Seattle.

Fred Hutchinson has established many IRB-of-record agreements and currently has more than 100 sites that rely on the organization for IRB reviews, but getting to this point has taken decades, Hansen says. (See story on preparing for single IRB of record change in this issue.)

“Institutions have to make a decision on how they want to approach the potential of increasing demands for a single IRB in multisite trials, as required by the new policies,” Hansen says. “I think people have to look at how many multisite trials they currently engage in and how many in the future they might be engaging in.”

‘Significant Investment with Unknown Payoff’

Use of single IRBs of record can be effective, but this will depend on whether the IRB of record is well-prepared for its role, notes David Borasky, MPH, CIP, vice president of quality management at Copernicus Group, a WIRB-Copernicus Group (WCG) company in Princeton, NJ.

In comments submitted to NIH after the draft policy was published, WCG raised concern about the lack of a description of characteristics necessary for a central IRB. In the final policy, NIH committed to issuing guidance by May 2017, which may include how single IRBs are selected, Borasky says.

“We’re hoping the guidance will reflect our concerns and the concerns of other commenters,” he says.

IRBs that plan to serve as the IRB of record will need to prepare for this role through an investment in resources, new policies and procedures, and other changes, Borasky suggests.

“It’ll be a significant investment with an unknown payoff,” he adds.

IRBs of record will have both direct and indirect costs associated with this role, and there will need to be a mechanism for recouping that expense, Wynes says.

“If you are charging for these additional costs, you will have to document it,” he adds. “Somebody has to pay the direct cost, and there has to be a mechanism for charging this cost to the grant.”

One concern some commenters, including Wynes, had after the draft policy was published was that it did not clarify which multisite studies would need an IRB of record. The final policy answered this question by saying that only multisite studies in which more than one institution was following the same protocol would need the central IRB, Wynes says.

“If two places are working on a grant together, they could be doing completely different things,” he explains. “And so NIH changed that in the final policy.”

Twenty-three Qualifying Words

Another concern NIH has already attempted to address involves the development of a template for IRB reliance agreements, Capron says.

NIH recently published a 19-page template with a long title: National Center for Advancing Translational Sciences Streamlined Multisite Accelerated Resources for Trials Institutional Review Board (SMART IRB) Reliance Master Common Reciprocal Institutional Review Board Authorization Agreement. The template is available online at http://bit.ly/29GXyeA.

While this is a good-faith effort on NIH’s behalf, it demonstrates the complexities of this change to a single IRB of record, Capron notes.

“That agreement has a name with 23 qualifying words,” he says. “So institutions entering into an agreement like this are going to be faced with a lot to consider, including a lot of issues about responsibility between the reviewing IRB and the IRB that cedes its authority to that IRB.”

For institutional IRBs that would like to see central IRB models could look at what many independent IRBs already are doing for many industry studies. (See story on specific policy concerns in this issue.)

“By and large, more and more institutions for industry-sponsored research have decided it’s in their best interest as good research partners to allow reliance on a single IRB,” Borasky says.

“We work hard with institutions to include the specific language they want in the informed consent,” he adds.

That’s one example of how an IRB of record must communicate with the relying institutions. The central IRB also should know all of its partners’ state laws and requirements, Borasky adds.

The change might result in more institutions relying on independent IRBs.

As NIH releases guidance to help IRBs adjust to this change, the human research protections world will learn more about what the change will mean for the industry as well as for individual IRBs and institutions. But for now, there are more questions than answers, some say.

“This is flying in the fog without instruments, as far as I am concerned,” Capron says.

Editor’s note: The Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research is available at: http://bit.ly/29xH0Yw.