Accelerated Approval

Abstract In 1992, the Food and Drug Administration (FDA) promulgated regulations for the Accelerated Approval program, which allowed drugs to gain approval based on unvalidated surrogate endpoints, or an effect on a clinical endpoint other than survival, or approval with restricted distribution. Initially, the program was primarily targeted at AIDS and cancer treatments, but it is now available for a wide array of diseases, and it has grown beyond small molecules to encompass biologic products, vaccines, and other product areas. Because of the severity of the illnesses being addressed and the potential for a “meaningful clinical benefit,” the FDA is generally willing to accept a higher risk to benefit ratio for an accelerated approval to provide earlier treatment for patients despite the lack of definitive evidence of the ultimate clinical benefit. Although a drug that is given accelerated approval might reach the market, the company sponsoring the drug is required to complete the necessary research to determine efficacy with a “Phase IV” study with “due diligence.” A problem with the definition of diligence, as well as enforcement mechanisms, has lead to some contention about the level of compliance by the drug industry. Despite these issues, the program alone, or in concert with other FDA approval programs, has to date brought some 50 lifesaving drugs to market months or years faster than would have happened through the traditional process. This information, together with advances in the science and technology of the clinical evaluation of biopharmaceuticals and the more powerful voice of patient advocacy in determining regulatory agency policy, ought to ensure that accelerated approval will expand its reach both therapeutically and geographically.