Approvals of drugs with uncertain benefit–risk profiles in Europe

• There is a pressure for early access to new drugs for unmet medical needs.
• Conditional approvals aim to achieve this goal.
• Conditional approvals are granted to drugs with unsettled benefit–risk profiles.
• Fulfilment of obligations imposed to cover the information gap is suboptimal.
• Early approval may put ineffective and/or unsafe drugs onto the market for long periods.

PurposeThis paper examines conditional approvals that allow the marketing of medicines with unsettled benefit–risk profiles in the European Union.MethodsWe identified medicines that had received conditional approval from the European Medicines Agency in the period January 2006–June 2015. We searched the reasons and bases for approvals, the median time to address the specific obligations imposed in order to cover the information gap and allow regular authorisations, and their extent of fulfilment.ResultsOf the 26 products conditionally authorised two were withdrawn for commercial reasons, ten were switched to regular approval, and 14 are still under conditional approval. Conditional approval was granted mainly to medicinal products intended for seriously debilitating disease or life-threatening disease. The median time to address the specific obligations was four years (range 0.2 to 7.7). There were delays or discrepancies in the fulfilment of these obligations in more than one third of the authorisation procedures.ConclusionsIn most cases there was limited evidence supporting the positive benefit–risk balance at the time of approval. Delays or discrepancies in the fulfilment of obligations allow medicinal products with unsettled benefit–risk profiles onto the market for several years. This should be taken into account when further early or step-wise licensing strategies are considered.