The Institute of Medicine (IOM) Committee on the Independent Review and Assessment of the Activities of the NIH Recombinant DNA Advisory Committee (RAC) was tasked with evaluating the necessity for the additional oversight of individual gene therapy protocols by the RAC. The specific goals of this review were to specify the scientific, safety, and ethical concerns that may justify a special level of oversight for this and potentially other areas and determine whether gene transfer research raises issues of concern that warrant extra oversight by the RAC, considering the current regulatory context. The IOM committee was instructed that if it concluded that this particular function of the RAC should remain intact, it should then describe the criteria that the RAC should use to select protocols for public review. The IOM committee reviewed information collected from a variety of sources, including scientific literature, previous evaluations and progress reports, open-session meetings and conference calls, public testimony and input, and other publicly available resources.
COMMITTEE EXPERTISE
To complete its task, the IOM formed a committee of 11 experts to conduct an 8-month study to respond to the statement of task. The committee was composed of members with expertise in clinical medicine, molecular biology, virology, molecular genetics, high-risk clinical trials, gene transfer technologies, biomedical ethics, law, public policy, and patient advocacy. Appendix C provides biographical information for each committee member.
MEETINGS AND INFORMATION GATHERING ACTIVITIES
The committee deliberated from June 2013 through October 2013 to conduct this expert assessment. During this period, the committee held three 2-day meetings, and committee members also participated in multiple conference calls. Two of the committee meetings were open-session, which allowed committee members to hear input from a wide range of stakeholders and members of the public. Experts in the field of clinical gene transfer research shared their perspectives on the role of the RAC, how and why some protocols are chosen for individual protocol review, the degree of harmonization among oversight bodies, the oversight of gene transfer compared with other cutting-edge areas of science, and the importance of public education and trust in the oversight process. Experts in the field of financial and scientific investment in gene transfer research presented their perspectives on whether individual protocol review by the RAC brings expertise and transparency to the oversight process and whether additional oversight has a significant impact on financial investment in potential gene transfer products. Investors also compared gene transfer oversight in the United States to that in Europe. Patient advocacy groups shared their perspectives on acceptable risk and oversight of clinical gene transfer research.
Each open-session meeting included a public comment period in which the committee invited input from any interested parties. All open-session meetings were held in Washington, DC. A conference call number and online public input tool were provided to allow opportunity for input from individuals unable to travel to the meetings. A link to the public input tool was made available on the National Academies’ website from April 2013 through October 2013, and all online input was catalogued in the study’s public access file. All information provided to the committee from outside sources or through the online input tool is available by request through the National Academies’ Public Access Records Office. The agendas for the two open-session committee meetings are reproduced below.
MEETING ONE
Committee on the Independent Review and Assessment of the Activities of the NIH Recombinant DNA Advisory Committee
June 4, 2013
Keck Center, Room 109
500 Fifth Street, NW
Washington, DC
| 1:00 p.m. | Welcome and Introductory Remarks Larry Gostin, J.D., Committee Chair |
| SESSION 1: THE STATE OF GENE TRANSFER RESEARCH OVERSIGHT |
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| 1:10 p.m. | The Charge to the Committee: A Discussion with the Sponsor Kathy Hudson, Ph.D. Deputy Director for Science, Outreach, and Policy Office of the Director, National Institutes of Health |
| 2:10 p.m. | The RAC Process Jacqueline Corrigan-Curay, J.D., M.D. Acting Director, Office of Biotechnology Activities, National Institutes of Health |
| 2:40 p.m. | Committee Discussion |
| 3:00 p.m. | Presentation—The Role of the FDA in Gene Therapy Products Daniel Takefman, Ph.D. Chief, Gene Therapy Branch, Division of Cellular and Gene Therapies, Office of Cellular, Tissue, and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration |
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3:30 p.m. |
Committee Discussion |
| 3:45 p.m. | Break |
| 4:00 p.m. | Presentation—Perspectives on RAC and Gene Therapy Xandra Breakefield, Ph.D. Former President, American Society for Gene and Cellular Therapy Professor of Neurology, Harvard Medical School Geneticist, Department of Neurology and Radiology, Massachusetts General Hospital |
| 4:20 p.m. | Committee Discussion |
| 4:45 p.m. | Presentation—Patient Perspective Edward R. B. McCabe, M.D., Ph.D. Senior Vice President and Chief Medical Officer, Office of Medicine and Health Promotion, March of Dimes |
| 5:00 p.m. | Follow-Up Discussion with Sponsor |
| 5:15 p.m. | Public Comment Period |
| 5:30 p.m. | Closing Remarks Larry Gostin, J.D., Committee Chair |
MEETING TWO
Committee on the Independent Review and Assessment of the Activities of the NIH Recombinant DNA Advisory Committee
August 6, 2013
Keck Center, Room 100
500 Fifth Street, NW
Washington, DC
| 9:00 a.m. | Welcome and Introductory Remarks Larry Gostin, J.D., Committee Chair |
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SESSION 2:
FINANCIAL AND SCIENTIFIC INVESTMENT
| 9:10 a.m. | Panel Discussion Session Objectives: Understand the current state of regulation of gene transfer research and compare its regulatory landscape to other areas of science. Discuss any models that exist for gene transfer oversight, including those that add value or may no longer be necessary. Explore the investigator experience of individual gene transfer protocol review by the RAC. |
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| Moderator: | Howard Federoff, M.D., Ph.D. Committee Member |
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| Panelists: | Barry Byrne, M.D., Ph.D. Director of the University of Florida Powell Gene Therapy Center Professor of Pediatrics, Molecular Genetics, and Microbiology Associate Chair of Pediatrics University of Florida |
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| Helen Heslop, M.D. Professor in the Department of Medicine Director of Adult Stem Cell Transplant Program Baylor College of Medicine |
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| Elizabeth Hohmann, M.D. Chair and Director of Partners Human Research Committee Partners Healthcare |
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| Carl June, M.D. Richard W. Vague Professor in Immunotherapy Director of the Translational Research Program University of Pennsylvania |
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| Margaret Riley, J.D. Professor of Law Professor of Medicine University of Virginia |
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| 10:30 a.m. | Panel Discussion Session Objectives: Explore the state of clinical gene transfer oversight from the perspective of those who analyze the regulatory context when making decisions about whether to invest finances or scientific resources in the field. |
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| Moderator: | Alta Charo, J.D. Committee Member |
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| Panelists: | Jeffrey Chulay, M.D. Chief Medical Officer and Vice President of Regulatory Affairs Applied Genetic Technologies Corporation |
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| Todd Foley, M.B.A. Managing Director MPM Capital |
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| Manuel Litchman, M.D. Vice President and Global Program Head, CTL019 Oncology Global Development Novartis Pharmaceuticals Corp. |
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| SESSION 3: PATIENT ADVOCACY EFFORTS AND PERSPECTIVES |
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| 11:15 a.m. | Panel Discussion Session Objectives: Discuss the patient, consumer, and public perspective on oversight of clinical gene transfer protocols and how patients who may benefit from future gene therapies view the relevant regulatory landscape. |
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| Moderator: | Sharon Terry Committee Member |
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| Panelists: | Nicholas Dainiak, M.D., FACP Clinical Professor of Medicine Chairman of Medicine Yale University School of Medicine |
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| Jennifer Farmer, M.S., CGC Executive Director Friedreich’s Ataxia Research Alliance |
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| Margie Frazier, Ph.D., LISW-S Executive Director Batten Disease Support and Research Association |
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| 12:30 p.m. | Lunch | |
SESSION 4:
OVERSIGHT OF CONTROVERSIAL SCIENCE
| 1:45 p.m. | Panel Discussion Session Objectives: Explore the policy implications of emerging sciences and the underlying reasons for establishing layers of oversight. Understand overlapping ethical, legal, and social issues that warrant elevated scrutiny of gene transfer research and other areas of scientific research. Discuss assessments of oversight in gene transfer research and other areas. |
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| Moderator: | Jeffrey Kahn, Ph.D., M.P.H. Committee Member |
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| Panelists: | Alexander Capron, L.L.B. Professor of Law and Medicine University of Southern California |
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| Ellen Wright Clayton, M.D., J.D. Professor of Pediatrics Professor of Law Vanderbilt University |
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| Hank Greely, J.D. Professor of Law Stanford University |
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| Peter Palese, Ph.D. Professor and Chair of the Department of Microbiology Mount Sinai Icahn School of Medicine |
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| Steven Rosenberg, M.D., Ph.D. Chief of Surgery National Cancer Institute National Institutes of Health |
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| 3:00 p.m. | Public Comment Period Harry Malech, M.D. President-Elect, American Society of Gene and Cell Therapy |
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| 3:15 p.m. | Concluding Remarks Larry Gostin, J.D., Committee Chair |
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