IRBs continue to navigate many changes in how they are structured, whether these involve collaboration with other institutions or maintaining a solo mission.

As some IRBs and research institutions seek more efficient ways to achieve quality human research protection during multisite trials, new models have emerged. One of the newest is the National IRB Reliance Initiative (NIRI).

NIRI’s IRB Reliance agreement — also called IRBrely — offers institutions and researchers a way to streamline IRB review processes and reduce administrative burden.1,2

The NIRI effort is consistent with National Institutes of Health (NIH) draft policy of Dec. 3, 2014, that promoted the use of one IRB in multisite clinical research studies. IRBrely was created by a committee of investigators from eight Clinical and Translational Science Award (CTSA) institutions with funding from the National Center for Advancing Clinical and Translational Science, says Barbara Bierer, MD, professor of medicine, pediatrics, at Brigham and Women’s Hospital and Harvard Medical School in Boston. Bierer also is senior reliance advisor for NIRI.

The group developed a draft agreement and standard operating procedures (SOPs) are being piloted in a national clinical trial centered at Duke University and involving institutions from New England to California, Bierer adds.

Another new model is IRBshare, a shared review model, which is a very different concept than the central IRB review, says Julie A. Ozier, MHL, CIP, director of the human research protection program at Vanderbilt University in Nashville, TN.

IRBshare is based on one alliance agreement with each site involved in a multisite study, Ozier says. “We have 54 sites across 28 states, and this was rolled out in the fall of 2012.”

The national initiative brings together and builds on the successes of these existing reliance networks, she adds.

Specifically, the Harvard Catalyst IRB reliance model, started in 2008, provides systematic standards and shared cooperation among Harvard’s 11 schools and 17 affiliated academic health centers, as well as additional signatories throughout New England.1

After the Boston Marathon bombing in April 2013, researchers found the Harvard Catalyst network very useful: Boston physicians were able to quickly study the outcome of blast-related ear injuries after the bombing because of rapid IRB approval from seven hospitals in an IRB reliance network, according to NIH’s National Center for Advancing Translational Sciences (http://www.ncats.nih.gov/pubs/features/irb-reliance).

The idea behind IRBshare was this question: “How can we get multicenter studies started up quickly to reduce start-up time?” Ozier says.

“We also asked, ‘Why don’t IRBs talk to one another?’” she says. “If IRBs talked with one another about their determinations, they could help each other out.”

IRBshare works this way: One IRB is the first to review a study. Once the protocol is reviewed and approved, all the documents are put into a portal, and all the other IRBs can choose to rely on that review, adding their own local context and local required language, Ozier explains.

For example, once an investigator agrees to use IRBshare, then a research site that is a member of IRBshare can agree to use IRBshare, Ozier adds.

“It’s a tool to document who is relying on who and what document they’re using to rely,” she says.

“The caveat to IRBshare is that while they share the initial review and would share every other major review, continuing reviews, and major amendments, the local IRBs would all be responsible for this study at the local level,” Ozier says. “So any kind of minor changes, such as a change in personnel, would be managed at the local site and wouldn’t go back up the system for review because it’s a local issue.”

This way, local IRBs still have some control; they also review adverse events and noncompliance, Ozier adds. “They would give information to any coordinating center or sponsor, but not to other IRBs.”

While there are central IRB models, commercial/independent IRBs, and IRBshare, the reliance model provides the most flexibility for research institutions, Bierer notes.

“It’s not a central IRB, and it’s not a designated IRB,” Bierer explains. “But research sites can use one IRB for its initial review of a multisite study, as well as subsequent reviews and continuing reviews.”

They also can choose not to defer their review to another IRB, she adds.

The difference between the reliance model and the central IRB model is how the main IRB is designated and how the other IRBs choose to collaborate with that IRB, Bierer explains.

“In a central IRB there is a designated IRB of record,” Bierer explains. “If you sign on to these protocols, you are required to go to the designated central IRB regardless of who the principal investigator is.”

In the reliance model, there is flexibility in selecting the IRB that will do the review. Other collaborating IRBs can provide expertise related to their board’s knowledge and experience, she says.

“One might have specific IRBs constituted for certain expertise, such as prisoner research or pediatric care,” Bierer says.

Further, the collaborating IRBs are not required to rely on, but can exercise independent oversight for the trial, Bierer says.

“You might have a situation where an IRB would like special oversight of an investigator, or where the study population at one institution is likely to be very different from other sites,” Bierer explains.

“In these situations, an IRB might want to perform a local review,” she adds. “Although we feel like the number of times this is going to be true is very, very small, we want to allow for institutions to make an affirmative decision, rather than enforcing a universal requirement.”

Since rolling out IRBshare, there has been more collaboration between the involved IRBs, Ozier notes.

When compared to a national average of about a month for IRB reviews, the IRBshare model is faster — about 17 days from submission to approval, Ozier says.

“It cuts in half the turnaround time for studies,” she says.

Another benefit is that IRBshare promotes consistency because the IRBs do talk with one another. “Anytime they disagree, they talk,” she says. “They either come into the alliance or agree to disagree; it’s very transparent in that regard.”

IRBshare also decreased analysis time in the pre-review process, Ozier says.

“It’s an abbreviated protocol application,” she says. “It’s really just asking about the things locally that they’re going to be doing, the local subjects’ injuries, local HIPAA provisions, managing the drug locally, and those kinds of things.”

Not all IRBs are satisfied with retaining some of the responsibility of local reviews, Ozier says.

“I think a lot of IRBs would like to just rely on and not have that added responsibility of the local reviews,” she adds.

“They have signed on, and the feedback is great — but it’s only part of the picture,” she says. “They really are okay with giving up the responsibility and letting another IRB do the whole review for them.”

Some IRBs like the central IRB model better, she adds.

“So we’re creating a central IRB model within IRBshare,” Ozier says. “We haven’t rolled it out yet.”

From an investigator’s perspective, any type of shared review is a more efficient process.

“Investigators uniformly appreciate not having to go to individual IRBs,” she says. “I haven’t spoken to any investigator who has anything but appreciation for our easing the administrative burden of clinical research.”

Also, the reliance agreement frees up full-board IRB review time.

“These multisite studies involve significant work for an IRB,” Bierer says. “Substantively, this new system will be able to save time and money; it will streamline not only the initial review, but also study amendments and continuing reviews, and ensure coordination of communications regarding adverse events and others.”

In some traditional multisite study reviews, the workload is substantial, she adds.

“Suppose you have five IRBs reviewing the same protocol. One IRB reviews it and approves it, but the second IRB reviews it and makes a slight change to the informed consent. The first IRB has to re-review the changed document and approve the change,” Bierer explains. “You could go back and forth amongst these IRBs multiple times before you have an aligned IRB approval on a study.”

The difference between the reliance model and the central IRB model is in how the main IRB is designated and how the other IRBs choose to collaborate with that IRB.

Bierer sees the national IRB reliance effort as the next step toward harmonization of workflow approaches, definitions, and education of human research protection staff.

“The foundation of the National IRB Reliance Initiative is building trust and coordination,” she says. “We would like to stand for something that works for the nation.”

References

  1. Winkler SJ, Witte E, Bierer IS. The Harvard Catalyst Common Reciprocal IRB Reliance Agreement: an innovative approach to multisite IRB review and oversight. Clan Trans Sci. 2015;8(1):57-66.
  2. Cola PA, Raider C, Stressed JE. Ohio CTSAs implement a Reliant IRB Model for investigator-initiated multicenter clinical trials. Clan Trans Sci. 2013;6(3):176-178.