The meeting of the Advisory Committee to the Director (ACD), National Institutes of Health, was convened via conference call on Friday, July 14, 2000, in Room 151, Building 1, National Institutes of Health (NIH), Bethesda, Maryland. The entire meeting was open to the public beginning at approximately 12:15 p.m. Dr. Ruth L. Kirschstein presided as Acting Chair.
William R. Brody, M.D., Ph.D.
Christine K. Cassel, M.D.
Steven Chu, Ph.D.
Yank D. Coble, Jr., M.D.
Victor J. Dzau, M.D.
Rebecca Eisenberg, J.D.
Elaine V. Fuchs, Ph.D.
Ting-Kai Li, M.D.
Jane A. Menken, Ph.D.
Shirley M. Tilghman, Ph.D.
Phillip L. Williams
Thomas R. Cech, Ph.D.
Eric S. Lander, Ph.D.
Philip Needleman, Ph.D.
Ruth J. Simmons, Ph.D.
Larry L. Smarr, Ph.D.
Arthur D. Ullian
Donald E. Wilson, M.D.
NIH Employees Present:
Vida Beaven, Ph.D., OD/NIH
John Burklow, OCLP
Sarah Carr, OBA
Donna J. Dean, Ph.D., OD/NIH
Robert Lanman, OGC
Janice C. Ramsden, OD/NIH
P. Pearl O'Rourke, M.D., OSP
Amy Patterson, M.D., OBA
Lana Skirboll, Ph.D., OSP
I. Call to Order
Dr. Ruth L. Kirschstein, Acting Chair, called the meeting to order and welcomed the members participating in the conference call.
II. Interim Report of the Working Group on NIH Oversight of Clinical Gene Transfer Research
Dr. Christine K. Cassel, Chair of the Working Group on NIH Oversight of Clinical Gene Transfer Research, summarized the recommendations stated in the Interim Report (Appendix A) for discussion by, and consideration of, the members of the ACD.
Dr. Kirschstein explained the difference in the governance of an Institutional Review Board (IRB) and an Institutional Biosafety Committee (IBC). The IRB is governed by the Federal Policy for the Protection of Human Subjects and reviews human subjects research conducted with federal funds. The IBC is governed by the NIH Guidelines for Research Involving Recombinant DNA Molecules and is responsible for and authorized by the research institution to review and approve potentially biohazardous lines of research.
Currently, to undertake human gene transfer studies, investigators must obtain IRB and IBC approvals of the protocol and then submit a copy of the proposed research protocol to the Office of Biotechnology Activities (OBA)/Recombinant DNA Advisory Committee (RAC), which is advisory to the NIH Director. Protocols must comply with the policies and procedures for the conduct of clinical research involving gene transfer as set forth in the NIH Guidelines. Protocols that present novel scientific, ethical or safety issues are reviewed by RAC at a meeting which is open to the public.
Investigators must receive authorization from the Food and Drug Administration (FDA), as well as approval from the IRB and IBC, in order to initiate a gene transfer clinical trial. Those investigators governed by the NIH Guidelines are required to submit their proposals to OBA/RAC, but neither submission to RAC nor RAC discussion are necessary prior to the initiation of such a trial.
There was some concern expressed as to whether an investigator may appeal a RAC recommendation. In response to this concern, Dr. Kirschstein stated that the protocol could be resubmitted to the RAC, which would require more data and a re-review. Dr. Skirboll added that the RAC does not have the authority to hold up initiation of the trial and that the final decision is under FDA authority and requires IRB approval.
In response to a concern related to considerable variation in review procedures by IRBs, Dr. Cassel said that the IRBs and IBCs should take RAC considerations seriously.
Some concern was raised as to whether the lack of expertise regarding gene transfer studies by members of an IBC would result in delay of the start of the protocol. Dr. Cassel responded by saying that there would be a requirement for the IBC to submit to the RAC, in writing, a reason for the delay. She went on to explain that the only intervention on the part of NIH would be to withhold funding. There is a safety factor built in since the FDA is represented on the RAC. Dr. Kirschstein added that the Office of Human Research Protection (formerly the Office of Protection from Research Risks) also could be involved and reminded the group that the RAC is subject to the same advisory rules as the ACD.
Dr. Skirboll stated that this recommendation should encourage earlier submission of a protocol and went on to explain that, if a protocol is submitted eight weeks before a RAC meeting, there is no problem; however, if it is submitted later than eight weeks before the meeting, it would have to wait for review until the next RAC meeting. She added that there is a fifteen day turnaround time between the arrival of a protocol in OBA and informing the investigator of OBA's plans for RAC review.
Dr. Kirschstein told the members of the ACD that, while most research related to recombinant DNA and gene transfer is funded by NIH, many of the protocols are not, but are performed by industry. There was some discussion as to whether all protocols could be submitted to OBA. Some concern was expressed as to the increased workload. Dr. Kirschstein explained that the OBA staff is being doubled as well as being provided with an increased budget.
Dr. Cassel reported that even though some protocols are funded by industry, most of the funding still comes from institutions receiving their funds from NIH. Dr. Kirschstein replied that, if a gene transfer protocol is performed in an institution which does not receive NIH funds for recombinant DNA research, there is no requirement that it be reviewed by RAC.
There was some concern related to whether the required oversight is appropriate. Dr. Cassel stated that this issue is addressed in the appendices of the final draft report. Dr. Kirschstein told the ACD members that she, other NIH staff and Dr. Cassel would review the oversight statement and develop a revision if it is not strong enough.
A motion was made and passed unanimously to accept the Interim Report prepared by the Working Group.
The meeting ended at approximately 12:50 p.m. on July 14, 2000.
I hereby certify that the foregoing minutes are accurate and complete.
Ruth L. Kirschstein, M.D. Acting Chairperson Advisory Committee to the Director National Institutes of Health
William R. Brody, M.D., Ph.D. President Johns Hopkins University Baltimore, MD 21218-2688
Christine K. Cassel, M.D. Professor and Chairperson Department of Geriatrics and Adult Development The Mount Sinai School of Medicine New York, NY 10029-6574
Thomas R. Cech, Ph.D. Distinguished Professor Department of Chemistry and Biochemistry University of Colorado Boulder, CO 80309-0215
Steven Chu, Ph.D. Professor Physics Department Stanford University Stanford, CA 94305-4060
Yank D. Coble, Jr., M.D. Physician Jacksonville, FL 32205
Victor J. Dzau, M.D. Chairman Department of Medicine Brigham and Women's Hospital Boston, MA 02115
Rebecca S. Eisenberg Professor of Law Stanford Law School Crown Quadrangle Stanford, CA 94305-8610
Elaine V. Fuchs, Ph.D. Amgen Professor of Basic Sciences The University of Chicago Department of Molecular Genetics and Cell Biology Chicago, IL 60637
Eric S. Lander, Ph.D. Professor of Biology Massachusetts Institute of Technology Director, Whitehead Institute/MIT Center for Genome Research Cambridge, MA 02139-1561
Ting-Kai Li, M.D. Distinguished Professor Indiana University School of Medicine Indianapolis, IN 46202-5124
Jane A. Menken, Ph.D. Population Program Institute of Behavioral Science University of Colorado at Boulder Boulder, CO 80309-0484
Philip Needleman, Ph.D. Chief Scientist Monsanto Company St. Louis, MO 63167
Ruth Simmons, Ph.D. President Smith College Northampton, MA 01063
Larry L. Smarr, Ph.D. Director National Center for Supercomputing Applications University of Illinois Champaign, IL 61820
Shirley M. Tilghman, Ph.D. Lewis Thomas Laboratory Department of Molecular Biology Princeton University Princeton, NJ 08544
Arthur D. Ullian Chairman, Task Force on Science, Health Care and The Economy Boston, MA 02110
Phillip L. Williams Vice Chairman (Retired) The Times Mirror Company Pacific Palisades, CA 90272
Donald E. Wilson, M.D. Vice President for Medical Affairs Dean, School of Medicine University of Maryland, Baltimore Baltimore, MD 21201-1559
Executive Secretary Ruth L. Kirschstein, M.D. National Institutes of Health Bethesda, MD 20892