Risk/Benefit Assessment of New Drugs: Perspectives of a Former FDA Advisory Committee Member

Abstract

Determining the benefit/risk profile of a new drug based on information presented and discussed at Food and Drug Administration (FDA) advisory committee hearings can be at times as much subjective as it is objective. The clinical experience and expertise residing in the make-up of the committee varies considerably with respect to interpretation of reproductive and other animal toxicology data, biostatistics, epidemiology, and pharmacokinetics, as well as in specialized areas such as receptor physiology, biochemistry, and pharmacology. Since the FDA does not mandate that a precise amount of safety data be included in any new drug application (NDA) submission, it becomes the responsibility of the advisory committee to perform a risk/benefit analysis based on its knowledge of current standards of care and practice, as well as by comparisons with the existing medical and surgical approaches to a disease state. Ultimately, advisory committee members must rely on clinical judgment to reach a decision. The purpose of this paper is primarily to review the process by which advisory committee members assess drug safety relative to efficacy. While a number of measures are already built into the process of drug development and postmarketing surveillance to ensure the safety of new drugs, this activity should be continually reviewed. Increasing use of experts from other advisory committees as well as external consultants, and requiring pharmacoeconomic and outcomes management studies as part of NDA submissions, will no doubt improve the ability of advisory committees to render the most appropriate recommendations for new drug approval based on risk/benefit assessment.