An estimated 48 percent of the population takes at least one prescription drug in a given month. Drugs provide great benefits to society by saving or improving lives. Many drugs are also associated with side effects or adverse events, some serious and some discovered only after the drug is on the market. The discovery of new adverse events in the postmarketing setting is part of the normal natural history of approved drugs, and timely identification and warning about drug risks are central to the mission of the Food and Drug Administration (FDA). Not all risks associated with a drug are known at the time of approval, because safety data are collected from studies that involve a relatively small number of human subjects during a relatively short period.

Written in response to a request by the FDA, Ethical and Scientific Issues in Studying the Safety of Approved Drugs discusses ethical and informed consent issues in conducting studies in the postmarketing setting. It evaluates the strengths and weaknesses of various approaches to generate evidence about safety questions, and makes recommendations for appropriate followup studies and randomized clinical trials. The book provides guidance to the FDA on how it should factor in different kinds of evidence in its regulatory decisions.

Ethical and Scientific Issues in Studying the Safety of Approved Drugs will be of interest to the pharmaceutical industry, patient advocates, researchers, and consumer groups.

Contents

• THE NATIONAL ACADEMIES
• COMMITTEE ON ETHICAL AND SCIENTIFIC ISSUES IN STUDYING THE SAFETY OF APPROVED DRUGS
• Reviewers
• Preface
• In Memoriam
• Abstract
• Summary
  • CHARGE TO THE COMMITTEE
  • COMMITTEE’S APPROACH TO ITS CHARGE
  • BENEFIT–RISK ASSESSMENT AND MANAGEMENT THROUGHOUT A DRUG’S LIFECYCLE
  • EVIDENCE AND DECISION-MAKING
  • SELECTION AND OVERSIGHT OF REQUIRED POSTMARKETING STUDIES
  • RESPONSES TO THE CHARGE QUESTIONS
  • FINDINGS AND RECOMMENDATIONS
• 1. Introduction
  • THE EVOLUTION OF THE FOOD AND DRUG ADMINISTRATION’S RESPONSIBILITIES IN THE POSTMARKETING SETTING
  • THE CONTEXT OF THIS REPORT
  • CHARGE TO THE COMMITTEE
  • THE COMMITTEE’S APPROACH TO ITS CHARGE
  • OVERVIEW OF THE REPORT
  • REFERENCES
• 2. Incorporating Benefit and Risk Assessment and Benefit–Risk Management into Food and Drug Administration Decision-Making
  • EVALUATING BENEFIT AND RISK OVER A DRUG’S LIFECYCLE
  • THREE-STAGE FRAMEWORK FOR REGULATORY DECISION-MAKING
  • BENEFIT AND RISK ASSESSMENT AND MANAGEMENT PLAN DOCUMENT
  • SPECIAL CONSIDERATIONS IN THE DECISION OF WHETHER TO REQUIRE A POSTMARKETING STUDY
  • SUMMARY
  • FINDINGS AND RECOMMENDATIONS
  • REFERENCES
• 3. Evidence and Decision-Making
  • STATISTICAL INFERENCE AND DECISION-MAKING
  • WHY SCIENTISTS DISAGREE
  • REFERENCES
• 4. Selection and Oversight of Required Postmarketing Studies
  • THE POSTMARKETING CONTEXT
  • REQUIRING OBSERVATIONAL STUDIES AND RANDOMIZED CONTROLLED TRIALS
  • DESIGN, ANALYTIC, AND ETHICAL CONSIDERATIONS IN SELECTING SPECIFIC OBSERVATIONAL AND RCT DESIGNS TO REQUIRE
  • THE FOOD AND DRUG ADMINISTRATION’S ETHICAL OBLIGATIONS REGARDING THE CONDUCT AND OVERSIGHT OF REQUIRED POSTMARKETING STUDIES
  • SUMMARY
  • FINDINGS AND RECOMMENDATIONS
  • REFERENCES
• 5. Synthesis
  • RESPONSES TO THE CHARGE QUESTIONS
  • REFERENCES
• A Other Elements of the Food and Drug Administration Amendments Act
• B Committee’s Letter Report
• C Open Session Agendas
• D Decision Conferencing and Multicriteria Decision Analysis
• E Benefit and Risk Assessment and Management Plan Document Template
• F Committee Biosketches

This study was supported by Contract No. HHSF223200810020I between the National Academy of Sciences and the Food and Drug Administration. 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.

Suggested citation:

IOM (Institute of Medicine). 2012. Ethical and Scientific Issues in Studying the Safety of Approved Drugs. Washington, DC: The National Academies Press.

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.