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

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.

A Stepwise Screening Protocol for Multiple Myeloma.

BACKGROUND: Monoclonal gammopathies and multiple myeloma should be screened in the primary care setting. METHODS: The screening strategy consisted of an initial interview supported with the analysis of basic laboratory test results and the increasing laboratory workload in the following steps was developed based on characteristics of patients with multiple myeloma. RESULTS: The developed 3-step screening protocol includes evaluation of myeloma-related bone disease, two renal function markers, and three hematologic markers. In the second step, the erythrocyte sedimentation rate (ESR) and the level of C-reactive protein (CRP) were cross-tabulated to identify persons qualifying for confirmation of the presence of monoclonal component. Patients with diagnosed monoclonal gammopathy should be referred to a specialized center to confirm the diagnosis. The screening protocol testing identified 900 patients with increased ESR and normal level of CRP and 94 of them (10.4%) had positive immunofixation. CONCLUSIONS: The proposed screening strategy resulted in an efficient diagnosis of monoclonal gammopathy. The stepwise approach rationalized the diagnostic workload and cost of screening. The protocol would support primary care physicians, standardizing the knowledge about the clinical manifestation of multiple myeloma and the method of evaluation of symptoms and diagnostic test results.