Gene transfer research is a rapidly advancing field that involves the introduction of a genetic sequence into a human subject for research or diagnostic purposes. Clinical gene transfer trials are subject to regulation by the U.S. Food and Drug Administration (FDA) at the federal level and to oversight by institutional review boards (IRBs) and institutional biosafety committees (IBCs) at the local level before human subjects can be enrolled. In addition, at present all researchers and institutions funded by the National Institutes of Health (NIH) are required by NIH guidelines to submit human gene transfer protocols for advisory review by the NIH Recombinant DNA Advisory Committee (RAC). Some protocols are then selected for individual review and public discussion.

Oversight and Review of Clinical Gene Transfer Protocols provides an assessment of the state of existing gene transfer science and the current regulatory and policy context under which research is investigated. This report assesses whether the current oversight of individual gene transfer protocols by the RAC continues to be necessary and offers recommendations concerning the criteria the NIH should employ to determine whether individual protocols should receive public review. The focus of this report is on the standards the RAC and NIH should use in exercising its oversight function. Oversight and Review of Clinical Gene Transfer Protocols will assist not only the RAC, but also research institutions and the general public with respect to utilizing and improving existing oversight processes.

Contents

• THE NATIONAL ACADEMIES
• COMMITTEE ON THE INDEPENDENT REVIEW AND ASSESSMENT OF THE ACTIVITIES OF THE NIH RECOMBINANT DNA ADVISORY COMMITTEE
• Reviewers
• Preface
• Acronyms and Abbreviations
• Summary
  • CRITERIA FOR GENE TRANSFER RESEARCH REVIEW
  • EVOLUTION OF OVERSIGHT OF EMERGING CLINICAL RESEARCH
  • REFERENCES
• 1. Introduction
  • CHARGE TO THE COMMITTEE
  • WHAT IS GENE TRANSFER RESEARCH
  • OVERSIGHT OF CLINICAL GENE TRANSFER TRIALS
  • EARLY RESPONSES
  • STUDY ORIGIN AND STRATEGY
  • REFERENCES
• 2. Gene Transfer Research: The Evolution of the Clinical Science
  • GENE TRANSFER RESEARCH
  • RECOMBINANT DNA
  • EARLY EXPERIENCE IN HUMAN GENE TRANSFER RESEARCH
  • UNDERSTANDING RISKS IN GENE TRANSFER
  • CURRENT UNDERSTANDING OF THE SAFETY OF GENE TRANSFER
  • CHARACTERISTICS OF GENE TRANSFER TRIALS
  • REGULATORY STATUS OF GENE TRANSFER PRODUCTS
  • REMAINING CONCERNS IN GENE TRANSFER RESEARCH
  • CONCLUSION
  • REFERENCES
• 3. Oversight of Gene Transfer Research
  • NIH AND THE RECOMBINANT DNA ADVISORY COMMITTEE
  • OTHER ENTITIES WITH REGULATORY OVERSIGHT OF GENE TRANSFER RESEARCH
  • RAC RELATIONSHIP TO OTHER GENE TRANSFER REGULATION AND OVERSIGHT BODIES
  • INTERNATIONAL RESEARCH OVERSIGHT AND REGULATIONS
  • ASSESSING GENE TRANSFER RESEARCH OVERSIGHT
  • CONCLUSION
  • REFERENCES
• 4. Evolution of Oversight of Emerging Clinical Research
  • LIMIT PUBLIC REVIEW OF SELECTED GENE TRANSFER PROTOCOLS
  • CRITERIA TO GUIDE PROTOCOL REVIEW
  • SPECIAL REVIEW OF OTHER EMERGING SCIENCES AND TECHNOLOGIES
  • REFERENCES
• APPENDIXES
  • A Data Sources and Methods
  • B Historical and Policy Timelines for Recombinant DNA Technology
  • C Committee Biographies

This project was supported by Contract/Grant No. HHSN263201200074I between the National Academy of Sciences and the National Institutes of Health. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the views of the organizations or agencies that provided support for the project.

Suggested citation:

IOM (Institute of Medicine). 2014. Oversight and review of clinical gene transfer protocols: Assessing the role of the Recombinant DNA Advisory Committee. Washington, DC: The National Academies Press.

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.