Despite the extensive body of evidence that informs regulatory decisions on pharmaceutical products, significant uncertainties persist, including the underlying variability in human biology, factors associated with the chemistry of a drug, and limitations in the research and clinical trial process itself that might limit the generalizability of results. As a result, regulatory reviewers are consistently required to draw conclusions about a drug's safety and efficacy from imperfect data. Efforts are underway within the drug development community to enhance the evaluation and communication of the benefits and risks associated with pharmaceutical products, aimed at increasing the predictability, transparency, and efficiency of pharmaceutical regulatory decision making. Effectively communicating regulatory decisions necessarily includes explanation of the impact of uncertainty on decision making.

On February 12 and May 12, 2014, the Institute of Medicine's Forum on Drug Discovery, Development, and Translation held public workshops to advance the development of more systematic and structured approaches to characterize and communicate the sources of uncertainty in the assessment of benefits and risks, and to consider their implications for pharmaceutical regulatory decisions. Workshop presentations and discussions on February 12 were convened to explore the science of identifying and characterizing uncertainty in scientific evidence and approaches to translate uncertainties into decisions that reflect the values of stakeholders. The May 12 workshop presentations and discussions explored tools and approaches to communicating about scientific uncertainties to a range of stakeholders in the drug development process. Characterizing and Communicating Uncertainty in the Assessment of Benefits and Risks of Pharmaceutical Products summarizes the presentation and discussion of both events. This report explores potential analytical and communication approaches and identifies key considerations on their development, evaluation, and incorporation into pharmaceutical benefit-risk assessment throughout the entire drug development lifecycle.

Contents

• THE NATIONAL ACADEMIES
• PLANNING COMMITTEE ON CHARACTERIZING AND COMMUNICATING UNCERTAINTY IN THE ASSESSMENT OF BENEFITS AND RISKS OF PHARMACEUTICAL PRODUCTS
• FORUM ON DRUG DISCOVERY, DEVELOPMENT, AND TRANSLATION
• Reviewers
• Acronyms
• 1. Introduction
  • THE IMPACT OF UNCERTAINTY ON REGULATORY DECISION MAKING
• 2. Identifying and Characterizing Uncertainty
  • KEY SOURCES OF UNCERTAINTY IN BENEFIT–RISK ASSESSMENT AND ASSOCIATED CHALLENGES
  • REDUCING UNCERTAINTY THROUGH MAXIMIZING THE VALUE OF EVIDENCE
  • METHODS TO ADDRESS UNCERTAINTY IN THE POSTMARKET PHASE
  • APPROACHES TO ASSESSING INTERNAL AND EXTERNAL VALIDITY OF RCTs
• 3. The Regulators' Challenge
  • UNIQUE CHALLENGES OF THE PHARMACEUTICAL REGULATORY SETTING
  • COMMUNICATING WITH THE PUBLIC ABOUT BENEFIT, HARM, AND UNCERTAINTY
• 4. Basic Methodologies and Applications for Understanding and Evaluating Uncertainty
  • APPLYING DECISION SCIENCE IN THE DRUG REVIEW PROCESS
  • APPLYING DECISION THEORY APPROACHES TO REGULATORY DECISION MAKING
  • FDA APPROACHES TO DECISION MAKING
• 5. Communicating Uncertainty
  • OVERVIEW OF RISK COMMUNICATION
  • INCREASING PUBLIC AWARENESS AND UNDERSTANDING OF UNCERTAINTY
  • COMMUNICATING UNCERTAINTY: FDA AND MEDIA MESSAGES ABOUT TYSABRI
  • CHALLENGES AND OPPORTUNITIES TO IMPROVE COMMUNICATION ABOUT UNCERTAINTY
• 6. Final Reflections on Ways to Characterize and Communicate Uncertainty
  • IDENTIFYING AND MITIGATING UNCERTAINTY THROUGH MAXIMIZING THE VALUE OF EVIDENCE
  • CHARACTERIZING AND UNDERSTANDING UNCERTAINTIES
  • ELICITING VALUES FROM STAKEHOLDERS, PARTICULARLY PATIENTS
  • COMMUNICATING UNCERTAINTY ABOUT BENEFIT AND RISK ASSESSMENTS OF PHARMACEUTICAL PRODUCTS
• References
• APPENDIXES
  • Appendix A Workshop Agenda
  • Appendix B FDA Case Studies
  • Appendix C Bibliography
  • Appendix D Participant Biographies

Rapporteurs: Denise Caruso, Rebecca A. English, and Anne B. Claiborne.

This activity was supported by contracts between the National Academy of Sciences and the U.S. Department of Health and Human Services (HHSN26300023 [Under Base #HHSN263201200074I] and HHSF22301026T [Under Base #HHSF223200810020I]), AbbVie Inc., American Diabetes Association, American Society for Microbiology, Amgen Inc., Association of American Medical Colleges, AstraZeneca, Burroughs Wellcome Fund, Critical Path Institute, Doris Duke Charitable Foundation, Eli Lilly and Company, FasterCures, Friends of Cancer Research, GlaxoSmithKline, Johnson & Johnson, March of Dimes Foundation, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., and Sanofi. The views presented in this publication do not necessarily reflect the views of the organizations or agencies that provided support for the activity.

Suggested citation:

IOM (Institute of Medicine). 2014. Characterizing and communicating uncertainty in the assessment of benefits and risks of pharmaceutical products: Workshop summary. Washington, DC: The National Academies Press.

NOTICE: The workshop that is the subject of this workshop summary 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.