[Health-Related Quality of Life in the Context of Early Benefit Assessment of Drugs According to § 35a of the German Social Code Book V: A Challenging Endpoint for all the Involved Stakeholders].

Considering repeated demands to present data on health-related quality of life (HRQoL) in the context of early benefit assessment of drugs in Germany, on the one hand, and the ongoing methodical debates on this outcome, on the other, the question about its significance in the evaluation procedure has been raised. Published documents of the first 90 early benefit assessments were extracted in order to estimate the importance of HRQoL in the assessment process for each involved stakeholder, and synoptically evaluated. The main challenge is to quantify a qualitative effect variable and to estimate its value. In several early benefit assessments, HRQoL had not been elicited a priori. In many cases where some data on HRQoL are presented, no added benefit can be derived. Finally, in most of the remaining assessments, no added benefit was recognized by IQWiG or the Federal Joint Committee. Even though the incorporation of HRQoL in clinical trial protocols is increasing, the endpoint is mostly conceptualized in an explorative manner. Hence, there is heterogeneity in the identified evidence. Beyond missing statistical significance, the assessment reports refer to a range of different methodological limitations, leading the responsible stakeholders to exclude HRQoL from their assessments, e. g. a high proportion of missing patient data or difficulties in the interpretation of the measurement results are mentioned. Regarding the implemented assessment approaches, inconsistencies in the applied conceptual and methodological standards were uncovered. To increase the importance of the endpoint HRQoL in the context of the early benefit assessment of drugs, establishing reliable measurement standards by consensus seems to be necessary. Furthermore, the valuation criteria should be made more transparent and attempts must be made to harmonize them with the approval process for at least the first early assessment of a new drug.