Selection of Endpoints in Clinical Trials: Trends in European Marketing Authorization Practice in Oncological Indications

Abstract Objectives To determine the types of endpoints that were the basis for efficacy assessment of medicines used in particular groups of oncological indications. Changes in the endpoints applied in marketing authorization practice were also considered. Methods The analysis included marketing authorization applications (MAAs) for medicines used in oncological indications that were first-time approved by the European Medicines Agency (EMA) between 2009 and 2017, and the extensions of the analyzed medicines. Results The analysis covered 125 MAAs: first-time approved (62%) and extensions (38%). In the analyzed trials, the endpoints that were reported most frequently included overall survival (OS), progression-free survival (PFS), and overall response rate (in 94.4%, 92.8%, 87.2% of MAAs, respectively). The following trends were observed: decreased significance of OS as a primary endpoint and increased significance of PFS as a primary endpoint (hematological indications). An analysis of MAAs for which the OS results were immature confirms the increased significance of PFS and new efficacy indicators (ie, pathological complete response). Conclusions An analysis of EMA's marketing authorization practice proves that the use of surrogate endpoints is becoming increasingly common in evaluating oncological health technologies. EMA's guidelines underline the role played by surrogates in the process of assessing efficacy of new therapies. Results of an analysis demonstrate that protocols of clinical trials define surrogates as primary endpoints more and more often. Furthermore, a positive decision on granting marketing authorization is possible also in situations when only such clinical data are available.