The Relationship Between FDA Expedited Programs and Post-Market Safety

The use of special expedited development and review pathways at the US Food and Drug Administration (FDA) has increased substantially over time and some policy makers question whether their use reduces post-market drug safety. Three long-standing FDA expedited programs will be analyzed in this study: the priority review designation, accelerated approval, and fast-track designation. The priority review designation, begun in 1992, reduces FDA review times for new drugs from the standard ten month timeline to six months. Accelerated approvals, also begun in 1992, allow firms to conduct their pivotal clinical trial on a surrogate endpoint, which typically decreases clinical trial lengths. Drugs approved via an accelerated approval are required to conduct post-market studies to confirm efficacy and safety findings. Finally, the fast-track designation, begun in 1998, is given to drugs that meet an unmet medical need, and are used to treat a serious or life-threatening disease. For this study, we analyze whether drugs that utilize an expedited program are more likely to experience a post-market safety outcome than drugs that undergo the standard development and review pathway. We use an internal FDA dataset, and include in the study all non-diagnostic drugs approved by the Center for Drug Evaluation and Research (CDER) whose approval application was received by fiscal year 1997, and was approved and launched before December 31, 2009. To determine the relationship between these expedited programs and post-market safety events, we utilize a multivariate regression with drug, company, and regulatory level covariates. We define post-market safety events as a drug either receiving a post-market boxed warning (colloquially known as a “black box warning”), or if a drug is withdrawn from the market for a safety reason. Also, because it is well known that drugs that receive an expedited program are more likely to be novel therapies that treat serious or life-threatening conditions, we also specifically control for these characteristics, as these types of drugs have also been shown to have a higher incidence of post-market safety events. The analysis finds no statistically significant association between using an expedited program and any of the post-market safety events. We conclude that, when controlling for disease severity and drug novelty, the use of expedited programs to decrease development and regulatory review times does not contribute to any increase in drug safety withdrawals or post-market boxed warnings.