Recognizing the potential design complexities and ethical issues associated with clinical trials for gene therapies, the Forum on Regenerative Medicine of the National Academies of Sciences, Engineering, and Medicine held a 1-day workshop in Washington, DC, on November 13, 2019. Speakers at the workshop discussed patient recruitment and selection for gene-based clinical trials, explored how the safety of new therapies is assessed, reviewed the challenges involving dose escalation, and spoke about ethical issues such as informed consent and the role of clinicians in recommending trials as options to their patients. The workshop also included discussions of topics related to gene therapies in the context of other available and potentially curative treatments, such as bone marrow transplantation for hemoglobinopathies. This publication summarizes the presentation and discussion of the workshop.

Contents

• The National Academies of SCIENCES • ENGINEERING • MEDICINE
• PLANNING COMMITTEE ON EXPLORING NOVEL CLINICAL TRIAL DESIGNS FOR GENE-BASED THERAPIES
• FORUM ON REGENERATIVE MEDICINE
• Reviewers
• Acknowledgments
• Acronyms and Abbreviations
• 1. Introduction and Overview
  • ORGANIZATION OF THE WORKSHOP AND PROCEEDINGS
  • LESSONS FROM THE DEVELOPMENT OF A GENE THERAPY TO TREAT CHILDREN AND ADULTS WITH INHERITED VISION LOSS
• 2. Developing First-in-Human Gene Therapy Clinical Trials
  • USING NATURAL HISTORY STUDIES IN CLINICAL DEVELOPMENT
  • DEVELOPMENT OF GENE THERAPY FOR SPINAL MUSCULAR ATROPHY
  • ETHICAL DIMENSIONS OF FIRST-INHUMAN GENE TRANSFER TRIALS
  • DISCUSSION
• 3. Understanding the Complexities of Patient Selection, Enrollment, and the Consent Process
  • THE COMPLEXITIES OF PATIENT SELECTION, ENROLLMENT, AND CONSENT IN THE CONTEXT OF HEMATOPOIETIC STEM CELL TRANSPLANTATION TO TREAT SICKLE CELL DISEASE
  • THE COMPLEXITIES OF PATIENT SELECTION, ENROLLMENT, AND CONSENT IN THE CONTEXT OF GENE THERAPIES TO TREAT SICKLE CELL DISEASE
  • THE COMPLEXITIES OF PATIENT SELECTION, ENROLLMENT, AND CONSENT IN THE CONTEXT OF GENE THERAPY FOR SEVERE COMBINED IMMUNODEFICIENCY
  • THE CHALLENGES OF USING GENE THERAPY TO TREAT DUCHENNE MUSCULAR DYSTROPHY
  • PATIENT AND FAMILY PERSPECTIVES
  • DISCUSSION
• 4. Developing Endpoints for Gene Therapy Clinical Trials
  • DEVELOPING ENDPOINTS FOR CLINICAL TRIALS
  • ENDPOINTS FOR GENE THERAPY CLINICAL TRIALS IN POMPE DISEASE
  • A NOVEL OUTCOME MEASURE FOR GENE THERAPY FOR A FORM OF CONGENITAL BLINDNESS
  • DETERMINING OPTIMAL ENDPOINTS FOR GENE THERAPY IN SICKLE CELL DISEASE
  • DISCUSSION
• 5. Integrating Gene-Based Therapies into Clinical Practice: Exploring Long-Term Clinical Follow-Up of Patients
  • PERSPECTIVES FROM THE FOOD AND DRUG ADMINISTRATION ON LONG-TERM FOLLOW-UP STUDIES
  • LONG-TERM SURVEILLANCE OF EXPOSED PEDIATRIC AND ADOLESCENT CANCER SURVIVORS
  • LONG-TERM FOLLOW-UP FOR GENE AND CELLULAR THERAPIES
  • ROLE OF THE CYSTIC FIBROSIS FOUNDATION IN ADDRESSING POST-APPROVAL REGULATORY OBLIGATIONS
  • A PATIENT'S PERSPECTIVE ON LONG-TERM FOLLOW-UP STUDIES
  • DISCUSSION
• 6. Reflections on the Workshop and Potential Opportunities for Next Steps
  • POSSIBLE NEXT STEPS FOR IMPROVING THE DESIGN OF GENE THERAPY CLINICAL TRIALS
  • ONGOING CHALLENGES FOR GENE THERAPY CLINICAL TRIALS
  • FINAL REMARKS AND SUMMARY
• References
• Appendixes
  • Appendix A. Workshop Agenda
  • Appendix B. Speaker Biographical Sketches
  • Appendix C. Statement of Task
  • Appendix D. Registered Attendees

Suggested citation:

National Academies of Sciences, Engineering, and Medicine. 2020. Exploring novel clinical trial designs for gene-based therapies: Proceedings of a workshop. Washington, DC: The National Academies Press. http://0-doi-org.brum.beds.ac.uk/10.17226/25712.

Digital Object Identifier: http://0-doi-org.brum.beds.ac.uk/10.17226/25712

Additional copies of this publication are available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.

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