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G-Ba Does not Adjust Evidence Requirements in Early Benefit Assessment in Cases of Pre-Defined, Efficacy-Based Cross-Over Decisions in Oncology Trials

BACKGROUND In Germany, a comparative effectiveness assessment in the form of an early benefit assessment (EBA) is mandatory for new medicines.1–3 The G-BA (Federal Joint Committee) is charged with evaluating a medicine’s additional benefit.1,4 Besides the extent of additional benefit versus an appropriate comparator, the quality of the evidence base, i.e. the evidence level, is evaluated in the EBA.2,4,5 Pre-defined treatment switching, also called ‘cross-over’, is often seen in oncology clinical trials. Cross-over is usually implemented for ethical reasons, i.e. to ensure access to a beneficial-treatment for all patients,6–8 but may confound data analysis, especially intention-to-treat (ITT)-analysis, by improving efficacy in the control arms.7,9–11 OBJECTIVES Accounting for the ethical demand and the methodological issues, we investigated the impact of cross-over in clinical trials of oncology medicines evaluated by the EMA as well as by the G-BA in the German EBA process. Specifically, we determined whether the G-BA reflected the circumstances under which cross-over was implemented in its decision and if drugs with a cross-over were disadvantaged in their benefit assessment with regards to the evidence level.