Accelerated approval of non-cancer drugs by the US Food and Drug Administration: A protocol for a meta-epidemiological investigation

The US Food and Drug Administration (FDA)9s accelerated approval program, in which drugs are approved on the basis of surrogate endpoints, has been a source of controversy in the context of risk-benefit trade-offs. The FDA recently reported on the 25-year experience with the program and concluded that the low failure rate in post-approval confirmatory trials was evidence that the program was operating effectively. However, many studies have revealed manufacturers9 poor adherence to obligation of conducting confirmatory trials, and also concerned the harm and cost of cancer drugs approved through this program based on the limited evidence. To date, few studies have investigated accelerated approval of non-cancer drugs. Therefore, the purpose of this study is to review trends in the FDA9s utilization of its accelerated approval program for non-cancer drugs and clarify the status of fulfillment of social obligations by the FDA and sponsors in the program. The FDA9 s documents will be reviewed at Drugs@FDA to identify pre-approval and confirmatory trials and regulatory updates for drug indications granted accelerated approval other than cancer treatments. We will further search PubMed, Google/Google Scholar, and the sponsors9 websites to match each identified confirmatory trial to publications in the medical literature.