The Food and Drug Administration and the Future of Drug Development for the Treatment of Diabetes.

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The U.S. Food and Drug Administration (FDA) regulates the marketing of drugs in the United States. The FDA staff faces substantial challenges in evaluating preclinical and clinical trial data for a proposed new drug and deciding whether the resultant benefit-risk assessment supports marketing approval. Any approval decision will be associated with uncertainty regarding the drug's true risks and benefits because of the inherent limits of testing in pre-approval development programs, the sample sizes included in clinical trials, and the structured environment of clinical trials versus patterns of use in general clinical practice. Indeed, the only way to completely avoid the occurrence of unanticipated risks after drug approval would be to stop approving new drugs. How the FDA deals with this uncertainty in benefit-risk assessment will profoundly affect treatment options for people with diabetes and for the health care professionals who care for them. The challenges facing the FDA in the field of diabetes have been all too well illustrated in recent years. After many years of treating patients with a relatively limited pharmacological armamentarium, the past 20 years have witnessed the discovery of new drug targets and the development of new therapeutic options for people with diabetes. However, the risks of rapid advances have also become apparent. The introduction of thiazolidinediones was greeted with excitement because of their potential to change treatment paradigms. The subsequent withdrawal of troglitazone because of hepatotoxicity concerns made clear the potential hazards of early adoption of new drugs.1 In 2007, analyses suggesting that rosiglitazone increased cardiovascular event rates in people with type 2 diabetes2 caused concern among both patients and physicians. Subsequent publications and regulatory reviews motivated by the rosiglitazone analyses fundamentally changed the landscape for diabetes drug development. Cardiovascular events, including myocardial infarctions (MIs) and stroke, are major causes of mortality and …