PM2 QUANTIFYING BENEFIT-RISK TRADEOFF PREFERENCES FOR REGULATORY DECISION MAKING

Sunday, October 24, 2010: 2:00 PM
Gold Rush (Sheraton Centre Toronto Hotel)
Course Type: Half Day
Course Level: Beginner

Format Requirements: The instructors will present an overview of methods for benefit-risk evaluation, the advantages and disadvantages of each method, potential use of each method in risk management, and regulatory precedents involving quantitative benefit-risk assessments. The course will provide a detailed tutorial on choice-format conjoint methods (also called discrete-choice experiments) to directly elicit and quantify patient and physician benefit-risk tradeoffs. Participants will complete an actual benefit-risk preference survey and participate in a debriefing on survey design. Recent empirical studies in four therapeutic areas will illustrate key elements of quantitative benefit-risk evaluation methods. The instructors will lead a group discussion on the relevance and acceptability of these methods for regulatory and clinical decision making. Prior experience with survey methods and data analysis is helpful, but not necessary.

Background: Regulators, clinicians, and patients routinely make decisions involving tradeoffs between treatment safety and clinical benefits measured in dissimilar metrics. Both the U.S. Food and Drug Administration and the European Medicines Agency have undertaken initiatives to evaluate approaches and develop guidance for benefit-risk evaluations. This course will help attendees assess methods for systematically quantifying and comparing the benefits and risks of medical interventions, including professional judgment of nominal risk and benefit incidence rates; comparing weighted risk and benefit incidence rates, where each outcome is assigned a relative importance or preference weight; and comparing actual risk exposures with maximum acceptable risks using stakeholders’ stated willingness to accept risk to achieve specified therapeutic benefits. This course will provide attendees criteria for evaluating advantages and disadvantages of different approaches to benefit-risk analysis, hands-on experience in eliciting and interpreting benefit-risk tradeoff data, and examples of how benefit-risk tradeoff data have helped inform regulatory decision-making.

Description and Objectives: Objectives:

To provide

     (1) an understanding of the state of the science and regulatory interest in
          benefit-risk analysis;

     (2) an evaluation of advantages and disadvantages of different approaches
          to benefit-risk analysis; and

     (3) hands-on experience in using stated-preference (SP) methods to quantify
          benefit-risk tradeoffs.

Description:

The instructors will present an overview of methods for benefit-risk evaluation, the advantages and disadvantages of each method, and potential use of each method in risk management. Methods include incremental net benefits, decision-analytic modeling, multi-criteria decision analysis, and patient-preference surveys.  The training session will provide a detailed tutorial on choice-format conjoint methods (sometimes called discrete-choice experiments) to directly elicit and quantify patient and physician benefit-risk tradeoffs. These estimates can provide relative importance weights for use in incremental net benefit calculations, decision modeling, and deriving maximum acceptable risk estimates. 

Participants will complete an actual survey and participate in a debriefing on decision-making heuristics subjects may employ in completing trade-off tasks involving probabilistic outcomes.  Specific topics will include:

     a) defining relevant and realistic treatment attributes to describe alternatives
         in the tradeoff tasks,

     b) overcoming innumeracy and cognitive problems related to communicating
         probability concepts,

     c) devising internal validity tests to assure that subjects successfully completed
         tradeoff tasks involving probabilistic outcomes,

     d) balancing statistical error and potential measurement error resulting from
         cognitive limitations,

     e) using appropriate statistical analysis of cross-section/time-series choice
         data,and

     f) estimating relative importance weights. 

Recent empirical studies in hormone replacement, Crohn’s disease, multiple sclerosis, and irritable bowel syndrome will be used to illustrate key elements of benefit-risk tradeoff methods. The instructors will lead a group discussion on the relevance and acceptability of these methods and specific results for regulatory and clinical decision making.

Course Director:
F. Reed Johnson, PhD
Course Faculty:
A. Brett Hauber, PhD