Clinical research studies and trials are important steps in successfully translating knowledge gained in the laboratory into interventions that improve human health. They enable researchers to understand the mechanisms underlying disease, improve disease diagnosis, and test the safety and efficacy of potential new drugs and interventions in patients and healthy volunteers. However, launching human studies can be complicated and sometimes takes many months.
A major contributor to the time delays is the complex research protocol review and approval process. For each new study or trial that a scientist proposes, an institutional review board (IRB) — made up of scientific, nonscientific and community members — must review and approve the study. IRB oversight ensures that the investigators have safeguards in place to protect human participants from harm, and that the research is conducted safely and in the most ethical way.
The IRB review process can be especially cumbersome for researchers and IRB staff conducting multisite research (i.e., conducted at several locations). Yet, multisite studies are critical to translational research because they provide researchers with access to larger numbers of participants, which can enhance the validity of results. Multisite studies are designed to foster collaboration among investigators, which can improve problem-solving and idea-generation.
Traditionally, each site’s IRB separately reviews a study or trial protocol. If one of the IRBs requests changes to the protocol, each of the other IRBs must also review and approve those changes, a process that can be time-consuming and inefficient. Researchers also must comply with the rules and processes created by each IRB, which adds to the challenges. This complicated review process may discourage some researchers from initiating important studies.
Addressing these challenges is a key part of NCATS’ mission to make translational research more efficient. NCATS’ Clinical and Translational Science Awards (CTSA) program, which supports more than 60 research institutions nationwide, is designed to encourage collaboration across institutions and to remove or minimize common translational barriers, such as those involved in IRB oversight. Improving this process could ease burdens on investigators, encourage them to conduct more multisite studies, and help them obtain trial results faster to speed development of new preventions, diagnostics and treatments for patients.
Several CTSA grantees have achieved significant progress in this area using a concept called IRB reliance. In the IRB reliance model, institutions develop networks in which each of the IRBs in a multisite study agrees to rely on a single involved IRB to review, approve and monitor the study. That IRB is designated as the “IRB of Record,” and it takes on most or all of the human subjects protection responsibilities for the study. The other IRBs agree to rely on the decision-making of the IRB of Record. A critical part of any reliance system is a shared infrastructure that enables all participating organizations in the reliance agreement to submit and access materials on studies and trials in which they are participating.
Within the CTSA program, institutions participating in IRB reliance networks have shown that efficient and centralized oversight can accelerate translational science.
IRB Reliance in Action
Among the many casualties from the April 2013 Boston Marathon bombing were dozens of patients who sustained blast-related ear injuries. In the days and weeks following the tragedy, Boston-area clinicians found themselves treating large numbers of patients with blast traumas to the ear, injuries rarely seen outside combat zones.
Doctors at Massachusetts Eye and Ear Infirmary (Mass. Eye and Ear), affiliated with Harvard Medical School, realized that if they could learn more about the nature of blast-related ear injuries by studying bombing victims, they could provide more effective treatments and better prepare the medical community to respond to such tragedies. The doctors acted quickly to create a team with four other Harvard-affiliated hospitals — plus three other sites — to design a high-quality multisite study. They also needed rapid IRB approval due to the unusual opportunity to study a large number of ear injuries from the same blast, and to observe patients as they healed.
Fortunately, with CTSA program support, Harvard already had an IRB reliance network in place via Harvard Catalyst, (the Harvard CTSA). The lead investigators at the seven sites involved in the study requested their IRBs to rely on Mass. Eye and Ear as the IRB of Record for this study. Within days, the participating institutions agreed. The Mass. Eye and Ear IRB immediately reviewed and approved the study, and patients began enrolling at all sites soon thereafter. Study investigators then began collecting data on the characteristics of blast trauma ear injuries, how they heal, how they respond to treatments such as steroids, and how hearing loss persists or improves over time. This data collection and analysis is ongoing with preliminary results expected to be published this summer.
“Launching the study would have been challenging, if not impossible, without the IRB reliance agreements,” said Alicia Quesnel, an otolaryngologist at Mass. Eye and Ear and lead researcher of the study. “The streamlined IRB process allowed us to avoid a great deal of redundancy and overlap so we could focus our efforts on enrollment, data collection and analysis.”
Since 2010, Harvard University and its affiliated academic healthcare centers have used the Harvard Catalyst IRB reliance agreement to manage protocols for more than 1,100 multisite studies. Currently, the network includes more than 20 institutions affiliated with Harvard, as well as other academic health centers, some but not all CTSA program-affiliated, in the Boston area. Soon the agreement will include institutions in other New England states. The Harvard Catalyst regulatory team is collecting data to measure the network’s progress; so far, the numbers paint a promising picture. The network IRBs seem to embrace the reliance process: Of the more than 1,100 requests, network IRBs agreed to rely on another IRB for more than 85 percent of the requested studies.
Reliance Opens Doors to New Opportunities
Other CTSA institutions across the country have created their own local reliance agreements in recent years. In Ohio, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland Clinic, MetroHealth, the University of Cincinnati, Cincinnati Children’s Hospital Medical Center, The Ohio State University and Nationwide Children’s Hospital created — with support from their related CTSA grants — an IRB reliance agreement network comprised of eight affiliated sites. The network includes institutions within the affiliated health systems that do not have direct CTSA program support, thus facilitating collaborative studies at many institutions and enabling the enrollment of more potential participants.
Although the Ohio reliance network is relatively new, 20 multisite protocols have used a single IRB of Record between mid-2012 and the end of 2013. Before the Ohio group built a centralized online submission system called HUB to store and access study information, approval took an average of 25 days; now, that average is eight days.
“The system is making studies possible that would not have been otherwise,” said Philip Cola, vice president, Research and Technology at University Hospitals Case Medical Center and director, Regulatory Knowledge and Support Core of the CWRU CTSA. For example, researchers from MetroHealth in Cleveland, a county-operated health care system with a small population base, were able to launch several maternal-fetal health studies under a reliance agreement with the University Hospitals system. By conducting the studies at two sites, the investigators were able to boost the numbers of participants so that the study could be completed more quickly.
These agreements also can provide researchers with access to technology that typically is not available to them. When another group of MetroHealth researchers wanted to initiate imaging studies that included functional electronic stimulation, a technology not available at MetroHealth, they collaborated with a reliance network institution with the required technology. This access enabled the investigators to conduct a study more easily than prior to the development of the reliance network.
A Nationwide Movement
In 2006, several California institutions supported by CTSA grants began building their own IRB reliance network. The current agreement includes 10 University of California campuses, including five with CTSA grants and the Lawrence Berkeley National Laboratory. The network originally covered low-risk studies only, and 600 such multisite protocols have used a single IRB of Record. The IRB reliance network recently expanded to include higher risk interventional research in which participants receive experimental therapies or treatments. These studies require closer IRB oversight, which is streamlined by a single, dedicated IRB of Record.
The Harvard, Ohio and California reliance network examples reflect a CTSA program-led approach to more efficient and potentially more careful oversight of research with human participants. CTSA program-supported institutions in states such as Wisconsin, Minnesota, Texas and Oregon also have established IRB reliance agreement networks. The leaders in these regional networks are expanding their participating institutions and sharing their experience within and outside of the CTSA consortium.
Innovation in IRB practice exemplifies the NCATS “3Ds,” the development, demonstration and dissemination of transformational improvements in the efficiency and effectiveness of translational science.
“These regional IRB reliance networks are addressing a major roadblock to efficient clinical studies,” said NCATS Director Christopher P. Austin, M.D. “The progress developed across CTSA institutions in IRB reliance is now driving further innovation and participation across the consortium. IRB reliance is just one of the many NCATS-supported innovations that is making the Center’s mission — to speed translation and improve human health — a reality.”
Posted May 2014