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Review of the Fialuridine (FIAU) Clinical Trials (1995)
Institute of Medicine (IOM)

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Review of the Fialuridine (FIAU) Clinical Trials

National Academy Press
2101 Constitution Avenue, NW Washington, DC 20418

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 this report were chosen for their special competences and with regard for appropriate balance.

This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.

The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy's 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine.

Support for this project was provided by the U.S. Department of Health and Human Services (Contract No. 282-94-0022). This support does not constitute an endorsement by the U.S. Department of Health and Human Services of the views expressed in the report.

International Standard Book Number 0-309-05279-3

Additional copies of this report are available in limited quantities from
National Academy Press
Box 285 2101 Constitution Avenue, N.W. Washington, DC 20055 Call 800-624-6242 or 202-334-3313 (in the Washington Metropolitan Area)

B543

Copyright 1995 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatlichemuseen in Berlin.

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Front Matter (R1-R10)
Executive Summary (1-15)
Introduction (16-19)
Clinical Trials (20-33)
Hepatitis B and Other Viral Diseases (34-41)
Clinical Trials of FIAC at Memorial Sloan-Kettering Cancer Center (42-50)
Oclassen Clinical Trial R89-001-01 (51-54)
Oclassen Clinical Trial R90-001-01 (NIH Protocol 91-AI-0031) (55-60)
Oclassen Clinical Trial R91-001-10 (NIH Protocol 91-DK-AI-213) (61-65)
Eli Lilly Trial H3X-MC-PPPA (66-69)
Eli Lilly Trial H3X-MC-PPPG (70-72)
Eli Lilly Trial H3X-MC-PPPC (NIH Protocol 93-DK-0031) (73-89)
Summary of Patient Interviews (90-92)
Overall Assessment of the Trials (93-97)
Recent Studies of FIAU Toxicity (98-103)
Review of the FDA Task Force Report 'Fialuridine: Hepatic and Pancreatic Toxicity' (104-120)
Review of 'Report to the Advisory Committee to the Director, National Institutes of Health' (121-132)
FDA-Proposed Changes to the Code of Federal Regulations (133-142)
Ancillary Issues Raised During the Period Following The H3X-MC-PPPC Trial (143-149)
Conclusions and Recommendations (150-154)
Appendix A: Chronology of FIAU/FIAC Clinical Trials (155-164)
Appendix B: Bibliography and References (165-177)
Appendix C: Agendas from the Three Committee Meetings (178-183)
Appendix D: Informed Consent Documents (184-243)
Appendix E: Example of Oclassen Fax Data Summaries (244-245)
Appendix F: FIAC and FIAU Preclinical Toxicity Studies (246-250)
Appendix G: Patient Summaries, Lilly Trial H3X-MC-PPPA (251-255)
Appendix H: Statistical Analysis of Mortality in the FIAU/FIAC Clinical Trials (256-265)
Glossary (266-269)