Statement by the NIH Director on the IOM report addressing the role of the Recombinant DNA Advisory Committee in oversight of clinical gene transfer protocols

May 22, 2014

Forty years ago, NIH Director Robert S. Stone, M.D., established the Recombinant DNA Advisory Committee (RAC) to bolster oversight of the use of a new technology called recombinant DNA in research. As the science evolved, so too did the role of the RAC which began considering gene transfer experiments in humans in the late 1980s. This research involves the transfer of genetic material into humans with the goal of replacing or compensating for the function of abnormal genes, or to enhance the immune system’s ability to attack cancer cells. At the time, there was limited scientific understanding of this technology and its safety in humans, as well as increasing public concern about the science of genetics. Today, we have the benefit of decades of experience in this area of research, and many of the concerns and uncertainties have been replaced by greater scientific clarity.

To evaluate the role of the RAC in this more established field of research, NIH commissioned a study by the Institute of Medicine (IOM) to review the current state of the science and regulatory and oversight processes. The IOM was asked to consider whether human gene transfer research raises issues of special concern that warrant continuing extra oversight of individual clinical protocols by the RAC. The IOM issued its report

in December 2013 and concluded that with the evolution of the science, the oversight roles of the RAC, the U.S. Food and Drug Administration (FDA), and institutional oversight authorities have become overlapping and arguably redundant. The IOM’s primary recommendation was that the NIH Office of the Director should continue to register all gene transfer protocols and, in consultation with appropriate regulatory and/or oversight authorities, identify protocols for additional public review only if BOTH of the following items are satisfied:

The protocol review could not be adequately performed by other regulatory and oversight processes (for example, the institutional review boards, institutional biosafety committees, and the FDA).
One or more of the following criteria are satisfied:
- Protocol uses a new vector, genetic material, or delivery method that represents a first-in-human experience, thus representing unknown risk.
- Protocol relies on preclinical safety data that were obtained using a new preclinical model system of unknown and unconfirmed value.
- Proposed vector, gene construct, or method of delivery is associated with possible toxicities that are not widely known and that may render it difficult for local and federal regulatory bodies to evaluate the protocol rigorously.

I have considered the IOM report carefully and have decided to accept the IOM committee recommendations on RAC review of gene therapy research. Given the progress in the field, I am confident that the existing regulatory authorities can effectively review most gene transfer protocols and that a streamlined process will reduce duplication and delays in getting gene transfer trials initiated. Issues of concern that may arise in exceptional cases can still be addressed by consulting the expertise of the RAC. NIH will move forward with implementing the IOM recommendations and will be issuing a proposed revision to the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules for public comment in the coming months.

The NIH is committed to the safety of volunteers in human clinical trials. As recommended by the IOM, the NIH Director will retain the flexibility to select protocols for public RAC review that would present a clear and obvious benefit to the scientific community or public, including those that raise important societal or ethical concerns. That authority will continue to exist and will be exercised should there be any doubt in the safety of a specific gene transfer study.

Francis S. Collins, M.D., Ph.D.
Director, National Institutes of Health