Association of expedited review programmes with postmarketing safety events of new drugs approved by the US food and drug administration between 2007 and 2017

Abstract

ObjectiveTo explore the associations between the risks of postmarketing safety events of new drugs and the four expedited programmes of priority review, accelerated approval, fast track and breakthrough therapy established by the US Food and Drug Administration (FDA); and to investigate whether multiple uses of expedited programmes, and the combinations of expedited programmes with orphan designation, were relevant to different safety profiles.DesignCohort study.SettingUSA.ParticipantsAll new drugs approved by the FDA between 1 January 2007 and 31 December 2017, followed up until 10 April 2021.Outcome measuresSafety events included safety-related withdrawal, new boxed warning, drug safety communication, postapproval risk evaluation mitigation strategy and safety-related labelling changes. The duration from marketing approval to the occurrence of a safety event was measured.MethodCox models were performed to determine the factors related to the time-to-safety event.ResultsThe FDA approved 338 new drugs between 2007 and 2017, among which 53.6% (181) were under expedited review and 32.2% (109) received two or more expedited programmes. It took median time of 1.75 years (IQR 1.10–2.93) and 2.31 years (IQR 1.33–4.21), respectively, for new drugs to be observed of their first event and first serious event. The raised risk for first safety event was found to associate with breakthrough therapy (adjusted HR 1.83; 95% CI 1.21 to 2.77; p=0.004), and with the combination of accelerated approval with orphan designation (adjusted HR 2.84; 95% CI 1.12 to 7.23; p=0.028). Triple or more use of expedited programmes correlated with higher risk for first serious event (adjusted HR 4.16; 95% CI 1.69 to 10.22; p=0.002).ConclusionsThe increased risks of the breakthrough therapies, accelerated orphan drugs and triple or more use of expedited programmes indicated the necessity for intensive postmarketing risk surveillance.