|
Items in cart [0] |
Questions? Call 888-624-8373 |
| Copyright © 2010. National Academy of Sciences. All rights reserved. Terms of Use and Privacy Statement |
Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page R1
Methodological Challenges in Biomedical HIV Prevention Trials
METHODOLOGICAL CHALLENGES IN BIOMEDICAL HIV PREVENTION TRIALS
Committee on the Methodological Challenges in HIV Prevention Trials
Board on Global Health
Stephen W. Lagakos and Alicia R. Gable, Editors
INSTITUTE OF THE MEDICINE OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
OCR for page R2
Methodological Challenges in Biomedical HIV Prevention Trials
THE NATIONAL ACADEMIES PRESS
500 Fifth Street, N.W. Washington, DC 20001
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.
This study was supported by Contract No. 43580 between the National Academy of Sciences and the Bill & Melinda Gates Foundation. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.
International Standard Book Number-13: 978-0-309-11430-1
International Standard Book Number-10: 0-309-11430-6
Additional copies of this report are available from the
National Academies Press,
500 Fifth Street, N.W., Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.
For more information about the Institute of Medicine, visit the IOM home page at: www.iom.edu.
Copyright 2008 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 serpent adopted as a logotype by the Institute of Medicine is a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin.
Suggested citation: IOM (Institute of Medicine). 2008. Methodological challenges in biomedical HIV prevention trials. Washington, DC: The National Academies Press.
OCR for page R3
Methodological Challenges in Biomedical HIV Prevention Trials
“Knowing is not enough; we must apply.
Willing is not enough; we must do.”
—Goethe
INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES
Advising the Nation. Improving Health.
OCR for page R4
Methodological Challenges in Biomedical HIV Prevention Trials
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.
www.national-academies.org
OCR for page R5
Methodological Challenges in Biomedical HIV Prevention Trials
COMMITTEE ON THE METHODOLOGICAL CHALLENGES IN HIV PREVENTION TRIALS
STEPHEN W. LAGAKOS (Chair), Professor of Biostatistics,
Department of Biostatistics, Harvard School of Public Health, Boston
HARVEY J. ALTER, Chief,
Infectious Diseases Section, Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda
RONALD BAYER, Professor,
Department of Sociomedical Sciences, Mailman School of Public Health, Columbia University, New York
SOLOMON R. BENATAR, Professor of Medicine; Director,
Bioethics Centre, Department of Medicine, University of Cape Town, South Africa
RONALD S. BROOKMEYER, Professor of Biostatistics,
Department of Biostatistics;
Chair of the Master of Public Health Program,
Johns Hopkins Bloomberg School of Public Health, Baltimore
CARLOS DEL RIO, Professor of Medicine (Infectious Diseases); Vice Chair for Grady Affairs,
Department of Medicine;
Director for Clinical Sciences and International Research,
Center for AIDS Research;
Director of AIDS International Training and Research Program,
Emory University School of Medicine, Atlanta
DAVID W. FEIGAL, Senior Vice President of Global Regulatory Affairs and Global Safety Surveillance,
Élan Pharmaceuticals, San Francisco
ELS GOETGHEBEUR, Associate Professor,
Department of Applied Mathematics and Computer Science;
Chair,
Center for Statistics, Ghent University, Belgium
LAURA A. GUAY, Associate Professor,
Department of Pathology, Johns Hopkins School of Medicine, Balitimore
SALLY L. HODDER, Director,
HIV Program;
Executive Vice Chair,
Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark
SHABBAR JAFFAR, Reader in Epidemiology,
London School of Hygiene and Tropical Medicine, London, UK
EDWARD K. KIRUMIRA, Professor of Sociology; Dean, Faculty of Social Sciences,
Makerere University, Kampala, Uganda
GEORGE W. RUTHERFORD, Salvatore Pablo Lucia Professor and Vice Chair,
Department of Epidemiology and Biostatistics;
Director,
Institute for Global Health, University of California, San Francisco
OLIVE SHISANA, President and CEO,
South African Human Sciences Research Council, Cape Town, South Africa
GINA WINGOOD, Associate Professor,
Emory University, Rollins School of Public Health, Atlanta
OCR for page R6
Methodological Challenges in Biomedical HIV Prevention Trials
Staff
ALICIA R. GABLE, Study Director
SARAH SCHEENING, Senior Program Associate
KIM LUNDBERG, Research Associate (through August 2007)
RACHEL PASSMAN, Senior Program Assistant
PATRICK KELLEY, Board Director
Consultants
SANDRA HACKMAN, Editor
OCR for page R7
Methodological Challenges in Biomedical HIV Prevention Trials
Reviewers
This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s (NRC’s) Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:
Zvavahera Michael Chirenje, Department of Obstetrics and Gynaecology, University of Zimbabwe
Thomas J. Coates, UCLA AIDS Institute and Division of Infectious Diseases at the David Geffen School of Medicine, University of California, Los Angeles
Myron Cohen, Division of Infectious Diseases, University of North Carolina
François Dabis, Université Victor Segalen, Bordeaux, France
Susan Ellenberg, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine
David Holtgrave, Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health
Jeffrey Kahn, Center for Bioethics, University of Minnesota
OCR for page R8
Methodological Challenges in Biomedical HIV Prevention Trials
Veronica Miller, Forum for Collaborative HIV Research, Department of Prevention & Community Health, George Washington University
Steve Morin, Center for AIDS Prevention Studies, Division of Prevention Science, Department of Medicine, University of California, San Francisco
James D. Neaton, Division of Biostatistics, School of Public Health, University of Minnesota
Suniti Solomon, Voluntary Health Services, Y.R. Gaitonde Centre for AIDS Research and Education, Chennai, India
Steffanie A. Strathdee, Division of International Health & Cross-Cultural Medicine, School of Medicine, University of California, San Diego
Jeremy Sugarman, Berman Institute of Bioethics and Department of Medicine, Johns Hopkins University
Scott Zeger, Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health
Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations nor did they see the final draft of the report before its release. The review of this report was overseen by Dr. Kristine M. Gebbie, Columbia University School of Nursing, and Dr. Paul A. Volberding, San Francisco VA Medical Center and Department of Medicine, University of California, San Francisco. Appointed by the NRC and the Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.
OCR for page R9
Methodological Challenges in Biomedical HIV Prevention Trials
Contents
Summary
1
Introduction
27
Charge to the Committee,
28
Scope of Work,
29
Study Process,
32
Study Considerations,
32
Report Structure,
33
1
The Status and Challenges of Biomedical HIV Prevention Trials
37
Recent Late-Stage Trials of Non-Vaccine Biomedical Preventions,
47
Methodological Challenges in Biomedical HIV Prevention Trials,
55
Behavioral and Sociocultral Influences on Biomedical Trials,
58
2
Basic Design Features: Size, Duration, and Type of Trials, and Choice of Control Group
69
Trial Sample Size and Duration,
69
Efficacy vs. Effectiveness Trials,
75
Choice of Control Group,
82
3
Design Considerations: Risk-Reduction Counseling
88
Ethical Reasons for Risk-Reduction Counseling,
89
Effectiveness of Behavioral Risk-Reduction Interventions,
90
OCR for page R10
Methodological Challenges in Biomedical HIV Prevention Trials
Adapting Efficacious Behavioral Risk-Reduction Interventions,
96
Evaluating Behavioral Risk-Reduction Interventions in the Context of a Biomedical Intervention Trial,
97
Summary,
99
4
Design Considerations: Pregnancy
104
When Pregnancy Occurs During Trials,
105
Statistical Implications of Pregnancies Occurring During Trials,
106
Collecting Information on Benefits and Risks,
107
5
Design Considerations: Adherence
119
Defining Adherence,
120
Measuring Adherence, Sexual Behavior, and Condom Use,
123
Strategies to Improve Adherence,
131
Analyzing Adherence,
135
6
Design Considerations: Recruitment and Retention
148
Recruitment Strategies,
148
Retention Strategies,
151
7
Site Preparedness
160
Developing Capacity and Infrastructure,
161
Protocol Development,
168
Pretrial Research,
169
Ensuring Sustainability,
170
8
Estimating HIV Incidence
175
Direct Longitudinal Follow-Up: Cohort Studies,
176
Biomarkers of Recent Infection,
177
Mathematical Models,
181
9
Interim Monitoring and Analysis of Results
186
Ensuring Effective Interim Monitoring,
186
Analyzing Trial Results,
196
10
Alternative Designs
204
Factorial and Other Multiarm Designs,
205
Discordant Couple Designs,
211
Noninferiority Designs,
214
Cluster Randomization,
215
Dynamic Designs,
219
OCR for page R11
Methodological Challenges in Biomedical HIV Prevention Trials
APPENDIXES
A
Public Committee Meeting Agendas
225
B
Acronyms
234
C
Supporting Materials for Chapter 2
236
D
Methods for Analyzing Adherence
245
E
Committee Biographies
250
OCR for page R12
Methodological Challenges in Biomedical HIV Prevention Trials
This page intentionally left blank.
