Excerpt

The IOM Committee on Reviewing the HIVNET 012 Perinatal HIV Prevention Study met three times and held numerous meetings by conference call between September 2004 and March 2005, and its work led to the present report. Early in its deliberations, the committee concluded that the validity of the trial's findings ultimately rested on the following elements: (1) the integrity of the study design, treatment assignment, and treatment adherence, addressed in Chapter 3; (2) the completeness and accuracy of efficacy and safety data, addressed in Chapter 4; and (3) the study's adherence to ethical principles for conducting clinical research, addressed in Chapter 5.

The committee reviewed relevant materials provided by NIH, by the investigators, previous auditors, and from a variety of other sources. In addition, the committee obtained copies of a subset of primary source documents from Uganda, as well as information from the study database maintained for HIVNET 012 by the Statistical Center for HIV/AIDS Research and Prevention (SCHARP). After its review of these materials, the committee reached its findings about the key aspects of study design and implementation. In its work, the committee was aware of one important aspect of the broader context in which the HIVNET 012 study occurred and was audited: the procedural guidelines and standards for clinical research are always evolving, and the Westat site visit occurred more than 4 years after the initiation of the HIVNET 012 trial. This report describing the committee's analysis and findings contains six chapters and three appendixes.

Contents

• The National Academies
• Committee on Reviewing the HIVNET 012 Perinatal HIV Prevention Study
• Reviewers
• Foreword
• Executive Summary
• 1. Introduction
  • CHARGE TO THE COMMITTEE
  • STUDY PROCESS
  • FRAMING OF THE COMMITTEE'S DELIBERATION
  • REFERENCES
• 2. Overview of HIVNET 012
  • RESULTS
  • KEY EVENTS DURING HIVNET 012
  • REFERENCES
• 3. Study Design, Treatment Assignment, and Adherence to Study Regimens
  • BACKGROUND
  • CHOICE OF UGANDA AS STUDY SITE
  • CHOICE OF DRUG REGIMENS
  • ELIGIBILITY CRITERIA
  • DESIGN AND IMPLEMENTATION OF THE RANDOMIZATION PROCEDURES
  • SAMPLE SIZE
  • STATISTICAL METHODS
  • DRUG MANAGEMENT
  • ADHERENCE
  • REFERENCES
• 4. Efficacy and Safety
  • DESIGN OF EFFICACY AND SAFETY ENDPOINTS
  • STUDY IMPLEMENTATION WITH REGARD TO THE ENDPOINTS
  • COMMITTEE'S REVIEW OF THE COMPLETENESS AND ACCURACY OF EFFICACY AND SAFETY ENDPOINTS
  • HYPERBILIRUBINEMIA
  • COMPARISONS TO OTHER PERINATAL HIV PREVENTION STUDIES USING NVP AND AZT
  • REFERENCES
• 5. Review of Ethical Issues
  • THE INVESTIGATIONAL NEW DRUG APPLICATION
  • COMPLIANCE WITH REQUIREMENTS FOR INSTITUTIONAL REVIEW BOARDS
  • THE USE OF A PLACEBO ARM
  • COMPLIANCE WITH INFORMED CONSENT
  • REFERENCES
• 6. Response to the Charge to the Committee
  • FINDINGS REGARDING THE STUDY DESIGN
  • FINDINGS REGARDING THE IMPLEMENTATION OF THE STUDY
  • FINDINGS REGARDING DATA COLLECTION AND QUALITY CONTROL
  • FINDINGS REGARDING THE STUDY CONCLUSIONS
  • REFERENCES
• Appendixes
  • Appendix A Agendas of Information-Gathering Meetings
  • Appendix B Comparisons to Other Perinatal HIV Prevention Studies Using NVP and ZDV
  • Appendix C Committee Biographies

This study was supported by Contract No. N01-OD-4-2139, Task Order No. 146 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 author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

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.