To investigate the G-BA’s decisions regarding patient-relevance of non-OS endpoints across breast cancer (BC), chronic lymphocytic leukaemia, melanoma, non-small cell lung cancer, ovarian cancer, and prostate cancer (PC).
All published G-BA appraisal reports (January 2011–October 2020) in the 6 selected indications were reviewed and relevant data were extracted for analysis.
Reviewed G-BA appraisals (n=101) yielded 307 individual decisions regarding patient-relevance of non-OS endpoints, employing 56 different outcome measures. Although in 74% of decisions (n=226/307) non-OS endpoints were deemed patient-relevant in general, in 79% (179/226) of these cases, no additional medical benefit was granted either due to lack of compliance with G-BA’s methodological requirements, inadequate/missing data, or statistically insignificant results. The G-BA did not accept progression-free survival, metastasis-free survival, complete remission, and objective response rate measured per imaging or laboratory tests. Patient-relevance decisions for health status (n=59), quality of life (n=103), and pain (n=10) related endpoints were positive across all indications. Decisions regarding the patient-relevance of other non-OS endpoints were indication-specific and variable, e.g. relapses as proxy for the failure of therapy with curative intent were judged patient-relevant in both BC (neoadjuvant and adjuvant settings) and melanoma (adjuvant setting), and symptomatic progression in the palliative setting in PC was judged patient-relevant. In comparison, time-to-first-subsequent-therapy and time-to-onset-of-cytotoxic-therapy were judged patient-relevant in principle, but not accepted due to methodological deficiencies, and/or lack of correlation with patient-relevant side-effects of subsequent treatment.
Strict compliance with methodological requirements and specific relevance to disease context and treatment setting were key drivers of G-BA’s acceptance of patient-relevance for non-OS endpoints. The impact of G-BA’s stringent methodological requirements on establishing the holistic patient-relevance of non-OS endpoints requires further debate.
© 2021 Published by Elsevier Inc.