Quantitative Benefit-Risk Analysis for Evaluating Drug Therapies

Abstract

Despite the fact that benefit–risk analysis is a necessary component of the review of new drugs for potential regulatory approval in the presence of known adverse side effects, and of the review of already-approved drugs for possible withdrawal from the market when unanticipated adverse events are discovered, formal quantitative tools for benefit–risk analysis are few. This paper proposes a quantitative method that utilizes receiver operating characteristic (ROC) curves to find an optimal dose of a drug that maximizes the differential between the benefit of the intended effect and the risk of adverse side effects, where costs associated with lack of benefit and risk can be incorporated. The method can be applied separately to subpopulations of different sensitivities and to different adverse events to give a full picture of the trade-offs between the benefit afforded by the drug and the risk it incurs, and potentially to allow the drug to be approved only selectively for specific subpopulations, or at different doses for different subpopulations.

Key Words:

• Adverse event
• AUC
• Drug withdrawal
• ROC curve
• Sensitive subpopulation

ACKNOWLEDGMENT

The first author's work was supported by FDA purchase order no. HHSF223201010733P.

Notes

The views expressed in this article do not necessarily represent those of the U.S. Food and Drug Administration.