TABLE OF CONTENTS

APPENDIX M. POINTS TO CONSIDER IN THE DESIGN AND SUBMISSION OF PROTOCOLS FOR THE TRANSFER OF RECOMBINANT DNA MOLECULES INTO ONE OR MORE HUMAN RESEARCH PARTICIPANTS (POINTS TO CONSIDER) ii

Appendix M-I. Requirements for Protocol Submission, Review, and Reporting – Human Gene Transfer Experiments iii

Appendix M-I-A. Requirements for Protocol Submission iii

Appendix M-I-B. RAC Review Requirements iv

Appendix M-I-B-1. Initial RAC Review iv

Appendix M-I-B-2. Public RAC Review and Discussion iv

Appendix M-I-C. Reporting Requirements v

Appendix M-I-C-1. Initiation of the Clinical Investigation v

Appendix M-I-C-2. Additional Clinical Trial Sites v

Appendix M-I-C-3. Annual Reports v

Appendix M-I-C-4. Safety Reporting v

Appendix M-I-C-4-a. Safety Reporting: Content and Format vi

Appendix M-I-C-4-b. Safety Reporting: Time frames for Expedited Reports vi

Appendix M-I-C-5. Confidentiality vi

Appendix M-I-D. Safety Assessment in Human Gene Transfer Research vi

Appendix M-II. Description of the Proposal vii

Appendix M-II-A. Objectives and Rationale of the Proposed Research vii

Appendix M-II-A-1. Use of Recombinant DNA for Therapeutic Purposes vii

Appendix M-II-A-2. Transfer of DNA for Other Purposes vii

Appendix M-II-B. Research Design, Anticipated Risks and Benefits vii

Appendix M-II-B-1. Structure and Characteristics of the Biological System vii

Appendix M-II-B-2. Preclinical Studies, Including Risk-Assessment Studies viii

Appendix M-II-B-2-a. Delivery System viii

Appendix M-II-B-2-b. Gene Transfer and Expression viii

Appendix M-II-B-2-c. Retrovirus Delivery Systems viii

Appendix M-II-B-2-d. Non-Retrovirus Delivery/Expression Systems ix

Appendix M-II-B-3. Clinical Procedures, Including Research Participant Monitoring ix

Appendix M-II-B-4. Public Health Considerations ix

Appendix M-II-B-5. Qualifications of Investigators and Adequacy of Laboratory and Clinical Facilities ix

Appendix M-II-C. Selection of the Human Subjects x

Appendix M-III. Informed Consent x

Appendix M-III-A. Communication About the Study to Potential Participants x

Appendix M-III-B. Informed Consent Document x

Appendix M-III-B-1. General Requirements of Human Subjects Research x

Appendix M-III-B-1-a. Description/Purpose of the Study x

Appendix M-III-B-1-b. Alternatives x

Appendix M-III-B-1-c. Voluntary Participation x

Appendix M-III-B-1-d. Benefits xi

Appendix M-III-B-1-e. Possible Risks, Discomforts, and Side Effects xi

Appendix M-III-B-1-f. Costs xi

Appendix M-III-B-2. Specific Requirements of Gene Transfer Research xi

Appendix M-III-B-2-a. Reproductive Considerations xi

Appendix M-III-B-2-b. Long-Term Follow-Up xi

Appendix M-III-B-2-c. Request for Autopsy xi

Appendix M-III-B-2-d. Interest of the Media and Others in the Research xi

Appendix M-IV.