European Marketing Authorizations Granted Based on a Single Pivotal Clinical Trial: The Rule or the Exception?

A minimum of two positive, adequate, and well-controlled clinical trials has historically been the gold standard for providing substantial evidence to support regulatory approval of a new medicine. Nevertheless, the present analysis of European Marketing Authorizations granted between 2012 and 2016 showed that 45% of new active substances were approved based on a single pivotal clinical trial. For therapeutic areas such as oncology and cardiovascular diseases, approvals based on a single pivotal trial are the rule rather than the exception, whereas new medicines within the nervous system area were generally supported by two or more pivotal trials. While overall similar trends have been observed in the US, the recent US Food and Drug Administration approvals of nervous system medicines based on a single pivotal trial suggest that a case-by-case scientific evaluation of the totality of evidence is increasingly applied to facilitate faster access of new medicines to patients suffering from serious diseases.