University system creates reliance service
UC hopes to serve as national model
Even as multicenter studies with central IRB reviews gain traction, some IRBs are still hesitant to join in. However, coordinating a multisite study among several IRBs within the same university system can be a time and paperwork hassle for both principal investigators and IRBs — and could make previously reluctant IRBs consider a new central reliance agreement.
Several years ago, the University of California system was conducting its multicampus National Institutes of Health studies with one overarching principal investigator or sub-PI at one of the campuses. All five academic medical centers would have the same NIH-funded project but had to get approval from all five IRBs, resulting in a major time drain.
About eight years ago the directors of UC’s academic medical centers got together to develop a memorandum of understanding (MOU), allowing multicampus research to be reviewed by only one IRB. "It was innovative at the time because there was — and, in a lot of cases, still is — reluctance among IRBs for relying on one institution," says Eric Mah, senior director of research compliance and interim Chief Ethics & Compliance Officer at UC San Francisco. "Fast forward to when BRAID began its project in 2012."
The University of California system created the UC Biomedical Research Accreditation, Integration, and Development (UC BRAID) program to increase research collaboration between the five UC campuses, speed multisite research approval, and reduce barriers to approval across the UC system.
"We discovered that dozens of studies were the same protocol, being reviewed by two or more IRBs," Mah says. "It [reliance] would save the investigators time, save the IRB time, and improve the site initiation time for every subsequent site. It would be a win-win for all."
Such a reliance model requires serious support. "Critical to the success of this [program] was developing a service that could handle paperwork, processes, and the relationships between the other sites and the reviewing IRB," Mah says.
For example, Mah says, there may be a principal investigator (PI) at UC San Diego who submits a protocol to the UC San Francisco IRB, but this PI may not be experienced with the UC San Francisco IRB. Enter UC Reliance Services (UCRS), which can act as an interface between the UCSD PI and the UCSF IRB. "UC Reliance Services is kind of like a white-glove treatment concierge service," he says. "There are sometimes differences among sites; for example, different procedures that some sites follow and others don’t, and modifications or protocol amendments that some sites follow and others don’t. UC Reliance Services assists both the reviewing IRB and the PIs. Furthermore, IRB application submissions and post-approval forms are not always the same. The PI doesn’t need to memorize five sets of forms for five potential reviewing IRBs; PIs and the IRBs have a service that helps everyone involved in the process."
UCRS is part of UC BRAID and was established to expand the use of UC MOU, eliminate duplicative IRB reviews, and provide centralized administrative support for industry-sponsored multicampus clinical trials.
UCRS looked at each campus’s reliance processes and individual processes to develop standardized forms and communications. The office helps to reduce the administrative burden on PIs, research staff, and the local IRB offices. "[Reliance Services] also performs regular check-ins with sites to make sure things are going well," Mah says. "We also monitor continuing review and other modifications. Ideally, the local IRB doesn’t experience additional workload. We’ve seen success in half a dozen studies at all five UC academic medical campuses."
Identifying potential multisite studies
Reliance Services also hopes in the near future to identify prospective researchers and studies for multicampus reliance. "One challenge is that not all five IRBs use the same electronic system," Mah says. "Some systems are homegrown, some are commercial systems. We are currently developing a tool where we can search for studies based on sponsors, protocol number, and study title to see whether the study had been approved or is currently undergoing review."
The system is a critical piece for identifying studies that can use central IRB reliance, Mah says. "Identifying potential studies and initiating the reliance at new campuses will be key to remaining competitive," he says. "Reliance Services also helps speed up site initiation. When the research community is small, they [researchers] know their colleagues are doing a study and they may want to do it, too."
Plans for phase two of the database development include prospectively identifying specific researchers at UC campuses. "For example, if a study is approved at UC San Francisco but not [UC] Davis, we could then turn to the database to find a PI in that [San Francisco] research area," Mah says. "We would ask if they can do the study, if they are available and interested. We can match studies in one catchment area to PIs in another, which can help CROs [contract research organizations] and study sites with recruitment and advance their patient subject recruitment in new ways. This can be the future of clinical research."
PIs have largely been satisfied with Reliance Services, Mah says. "I think there’s a lot of appeal when there’s a service specifically devoted to helping them navigate the process," he says. "New site PIs don’t have to submit a full IRB application, which is a huge time savings for them."
The campus IRBs have also been receptive, Mah says, partly due to trust and good relationships. "In many of these relationships, it’s a matter of building trust and the notion that there may be some uncertainty, but they can trust and let go," he says. "We have worked together for a long time — I like to think we have good relationships among the campuses."
"I think there’s a real sense of confidence in the review, primarily because it was coming from another academic medical center and those IRBs possess the expertise to review these studies, particularly the early-phase studies," he continues. "Unlike commercial IRBs — which may lack practicing physicians, or have physicians who are not active researchers — the majority of the academic medical center IRBs are clinicians and active researchers who have the expertise to review the really difficult studies."
So far, six studies have been approved using BRAID and UCRS. Approval time so far has been around two weeks, and getting the approval time down farther is a work in progress. "There were some bumps in the road — we engaged in a failed fast-forward model," Mah says. "It’s okay to be inelegant at times and make mistakes and learn from them. We think we can get approval down to three to five days once it gets going. The current process [for submission and approval], unfortunately, is essentially manual with email and picking up the phone. Technology can help this process and automate it in some ways."
The team at BRAID has also developed the University of California Research eXchange (UC ReX) program, a database that connects researchers to de-identified patient data from all five UC medical centers. The data helps researchers identify potential clinical trial subjects.
"I think it’s an exciting time for our industry and it will change even more in the next five years," Mah says. "It’s a pivotal time for us and hopefully the model we’re using will be helpful to others. We hope that this could serve as a national model."