On April 27, the National institutes of Health (NIH) enacted a new administrative model for the review of proposed human gene trials; the new guidelines upend a process that has been in place for more than 40 years. Predictably, reaction throughout the industry is mixed. Larger firms are adjusting quickly to the change and retooling their processes to comply with the new model. At the other end of the spectrum, some IRBs, including IntegReview, declined to comment on the changes, stating that the matter is still under internal review.
Under the previous model, proposed clinical studies were initially reviewed for potential safety and ethical concerns by the NIH Recombinant DNA Advisory Committee (RAC). In the new model, two local entities will provide initial regulatory oversight of recombinant DNA research: the Institutional Biosafety Committee (IBC), which monitors compliance with NIH Guidelines as well as biosafety and public health issues, and the Institutional Research Board (IRB), which oversees scientific, ethical and regulatory issues.
The NIH has decided to simplify the oversight process for well-characterized technology in order to reduce its oversight role. It cited recommendations issued last year by its Institute of Medicine (IOM), after reviewing the accumulation of safety data from years of research, increased experience with the risks associated with gene transfer research and overlapping reporting and oversight available within the FDA, the RAC and the local regulatory IBC/IRB panels.
The new NIH Guidelines restrict RAC reviews to “exceptional cases that meet specific risk criteria.” Most requests for RAC review will now originate within the local boards (IBCs/IRBs) responsible for vetting the initial clinical site.
At document released by Quorum Review IRB, entitled “Final Action under the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid,” lists specific steps the company has taken to implement the new process and affirms its commitment to making RAC-style assessments of the affected research studies.
According to Dr. Carrie D. Wolinetz, NIH associate director for Science Policy, the new guidelines offer significant benefits. “Oversight bodies will be able to make the determination regarding whether the trial would benefit from RAC review, thus allowing trials that would not significantly benefit [from such review] to progress through the regulatory process more efficiently,” said Wolinetz.
In the past, all reviews were initially submitted to the RAC for pre-review; if the RAC saw nothing that presented a special risk, approval moved forward. Risk factors such as new genetic material or a “first-in-humans” delivery experience would be noted and, in some cases, public discussion would occur. A report would then be returned to the initial site, often with specific notes and conditions to address. Under the new guidelines, the local IBC/IRB will have the authority to approve protocols that do not present unusual risks, as well as the responsibility for recommending risky trials for RAC review. This makes the local boards the new gatekeepers.
At WIRB-Copernicus Group (WCG), Director of IBC Services David Emery, Ph.D., agrees that the new registration process is more streamlined, but adds that many IBCs and IRBs have become accustomed to the RAC pre-review, which provided “valuable details for follow-up” that will no longer be available to local teams. He predicted that it could catch some organizations off-guard.
Joan Robbins, Ph.D., senior vice president of biosafety and gene therapy at WCG, agreed that some IRB/IBC groups may find it more difficult to pre-evaluate studies the RAC has not reviewed. “The technology is exploding—DNA plasmas, T-cell therapy, viruses and new gene-editing techniques. … Even in well-characterized areas, it may be difficult to perform a thorough expert evaluation in advance.”
“These days there are not always enough experts to go around,” added Emery. “It can be very challenging to engage those you need.”
With the new registration process, Wolinetz emphasizes that the NIH remains the final authority. He said, “[We] must concur with the oversight bodies that the trial would benefit from RAC review in order for a public discussion to occur. … Even if the oversight bodies do not request RAC discussion, the NIH Director can select protocols for review that may present significant scientific, societal, or ethical concerns. These measures should facilitate an even application of the requirements.”
To streamline the protocol submission process, the NIH has reduced the paperwork described under Appendix M. As Wolinetz explained: “The information requested is limited to that which is necessary for oversight bodies to determine RAC review eligibility and to support GeMCRIS [an interactive, online NIH database], which facilitates safety reporting and provides access to information about human gene transfer protocols registered with the NIH.”
Emery admitted that completing lengthy questionnaires can be arduous; however, he is concerned that some of the details omitted in the new format might be important. He said, “The local biosafety committee may have to reconnect with the PI or the program sponsor to identify a specific gene or delivery method that had not been listed in the appendix. Details are essential when conducting risk and safety assessments.”
When asked whether the new guidelines will help accelerate trials or add regulatory burden to IRBs, Robbins of WCG observed that it would probably do both. “It will accelerate the process of registration of the trials with the NIH, but will place an additional regulatory burden on IRBs.”
The advantage belongs to those who adapt quickly to the new realities.
This article was reprinted from Volume 20, Issue 17, of CWWeekly, a leading clinical research industry newsletter providing expanded analysis on breaking news, study leads, trial results and more. Subscribe »