Characteristics of Single Pivotal Trials Supporting Regulatory Approvals of Novel Non-orphan, Non-oncology Drugs in the European Union and United States from 2012-2016.

For regulatory approval of a new medicine, the gold standard for demonstration of efficacy has traditionally been a minimum of two positive, adequate, and well-controlled clinical trials. Nevertheless, drugs to treat cancer and rare diseases are usually approved based on a single and often uncontrolled pivotal trial. In contrast, little is known about single pivotal trial approvals for non-orphan, non-oncology drugs. Between 2012 and 2016, 23 novel therapeutic drugs were approved by the US Food and Drug Administration (FDA) and/or the European Medicines Agency (EMA) for 27 non-orphan, non-oncology indications each based on a single pivotal trial. Although there was considerable variation in the nature and strength of the efficacy evidence supporting these drug approvals, the majority (85%) of the pivotal trials were randomized and controlled. For all superiority trials, the primary outcome was met with a statistical significance of P ≤ 0.005. Most approvals were supported by additional efficacy data from nonpivotal studies.