By Daniel Kavanagh, PhD and Currien MacDonald, MD, CIP
Independent oversight is an essential part of ensuring the rights and welfare of people who participate in clinical research. Institutional Review Board (IRB) oversight is required for research involving human subjects, and Institutional Biosafety Committee (IBC) review is required for research involving recombinant or synthetic nucleic acid molecules. While the primary role of the IRB is to protect all aspects of the rights and welfare of research subjects, the primary role of the IBC in clinical trials is to protect study staff and the general public, as well as research subjects, specifically from risks associated with gene transfer agents. Considering their overlapping yet separate missions, the IRB and the IBC have the potential to cooperate and effect synergistic improvement in the efficiency, rigor, and quality of the review of proposed research.
IRB and IBC Coordination Should be Synergistic, not Duplicative
Currently, there is no regulatory requirement or standard best practice for the integration or coordination of IRB and IBC reviews. If they occur in a non-cooperative process, however, changes made to the protocol or study conduct in response to comments from the IRB or IBC may not be communicated to the other in a timely or clear manner. This could cause confusion, delays or require re-reviews by one or both committees. However, with a change in perspective and effective management, the required dual review can instead create opportunities to improve the quality of both reviews.
Opportunities for Improvement -- Reduce Start-up Time and Improve Quality
An IRB may be local to the institution or it may be a central IRB, granted the authority to act as the IRB of record on behalf of the local clinical site. Recent federal mandates have pointed to the benefits of central IRB review, and the pending change to the Common Rule mandates central IRBs for federally funded research with very limited exceptions. There is significant evidence that central IRB review significantly reduces study start-up time.
Centralized IBC review analogous to the central IRB review process is not currently possible as the NIH Guidelines include requirements for members who are local to the clinical site. However, the management and administration of IBC review can be centralized, with local IBCs created and managed through a central office. This allows one point on contact for a study sponsor and an IBC management team very familiar with the requirements of a specific clinical protocol being conducted by multiple clinical sites.
Local IBC approval time at clinical institutions takes a mean time of 16 weeks; centralization of the process through an experienced IBC partner such as WCG Biosafety reduces the IBC approval time by 75%, to a mean of 4 weeks.
Additionally, at many institutions where there are no experts in human gene therapy on the IRB, the IRB often elects to hold a submitted protocol until IBC review has been completed, and to rely on the comments from the completed IBC review as providing consultative expertise to the IRB. This means that not only are the local IRB and IBC review longer, but they are conducted sequentially rather than in parallel, resulting in even longer approval and start-up times for the study site. Therefore, the next step is integrating IRB and IBC reviews to improve timelines for overall study start-up.
By combining these two processes, synergy of issue spotting, communication, and resolution efforts can be significantly improved. From startup, changes in research, adverse event reporting, and ongoing review, the IBC’s and IRB’s distinct but overlapping requirements each need to be met. The outcomes and requirements from the IRB and IBC could have important impact on each other. For example, adverse event information about a recombinant product which arises during the course of a study may prompt the IRB to place restrictions on the research pending further information that the experts from the IBC could have readily supplied.
Ensuring that the IRB and IBC reviewing a study have the necessary components to go beyond cooperation to synergy is quite complex. There are three key components critical to an integrated IRB and IBC review. Each of the components has a hallmark metric to evaluate those components, which any central IRB/IBC should be able to provide to a sponsor who is initiating a gene therapy trial. The three key components are:
- Experience in reviewing gene transfer research;
- Breadth of expertise in review, including oncology, rare diseases, and congenital disorders;
- Capacity of review capabilities.
By coordinating IBC and IRB review processes, synergy of issue spotting, communication, and resolution can result. With the potential risks and benefits of gene transfer research, the necessary review by the oversight bodies has the potential to add value or unnecessarily derail the process. Due diligence in researching the practices of the oversight bodies may provide insight into the quality of their reviews.