A Graphical Method for Patient-Level Benefit-Risk of a Medical Product Over Time, with Examples

• Activity Number: 440
• Type: Invited
• Date/Time: Wednesday, August 3, 2011 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Jonathan D. Norton*+
• Companies: U.S. Food and Drug Administration
• Keywords: benefit-risk ; risk-benefit ; graphics ; safety ; longitudinal ; missing data

Abstract

Both FDA and external stakeholders acknowledge a need for improved benefit-risk assessment. This problem is challenging for a number of reasons: benefits and harms tend to be measured on different scales, they may be statistically associated, their relative balance may change over time, and there may be substantial missing data. The Individual Response Profile, a recently-developed method for simultaneously visualizing benefit and risk over time, is presented. This method addresses all of the aforementioned issues, particularly in regard to treatments that provide only symptomatic relief. The underlying model represents a subject's benefit-risk at a given time as one of five discrete clinical states, one being premature study withdrawal. The graphic uses colors to represent each subject's changing state over the course of the clinical trial. The user can quickly grasp how a treatment affects subjects in aggregate, and then further examine how individuals are affected. It is possible to tell whether the beneficial and harmful outcomes are correlated. A chronic pain trial and other worked examples are presented, and inferential approaches are discussed.