Reply to: “Questioning Conclusions and Statements on the German HTA System: A Critical Perspective”

Abstract

We acknowledge the points raised by Tomeczkowski et al.¹ and have conducted a thorough follow-up assessment to address their comments.

Tomeczkowski et al. identified five Gemeinsamer Bundesausschuss (G-BA) submissions, which we evaluated in collaboration with the IQVIA Health Technology Assessment (HTA) Accelerator (HTAA) team, the platform used to identify submissions. Three of the identified submissions met the study inclusion and exclusion criteria and therefore have been added to the manuscript (ceritinib Non-Small Cell Lung Cancer (NSCLC), efmoroctocog alfa hemophilia, and nivolumab Classic Hodgkin Lymphoma (CHL)). The alectinib NSCLC submission was excluded based on evidence that a randomized, phase III, controlled trial (ALUR) was included in this particular submission as primary evidence, which is an exclusion criterion for this study. The selpercatinib NSCLC submission was excluded due to the decision date being outside the study evaluation period. To ensure all potentially eligible submissions were considered, we performed a thorough QC of the source data (IQVIA HTAA platform). Through this process, an additional three National Institute for Health and Care Excellence (NICE) submissions, not identified by Tomeczkowski et al., were included in the manuscript (asfotase alfa pediatric-onset hypophosphatasia, onasemnogene abeparvovec spinal muscular atrophy, and vismodegib basal cell carcinoma).

Tomeczkowski et al. indicated asfotase alfa's evaluation was misrepresented as “no recommendation” despite a positive finding for a subpopulation in the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) report. In this study, we assessed HTA “recommendations” and not “findings,” resulting in “no recommendation” being assigned to all IQWiG submissions. This aligns with the German methodology as G-BA's decisions are relevant for subsequent pricing discussions and has been further clarified in the manuscript text.

We agree it is crucial to distinguish between surrogate and patient-relevant endpoints and acknowledge that G-BA does not recognize the surrogate endpoint progression-free survival (PFS) as inherently patient-relevant. We now state that PFS is potentially considered a patient-relevant endpoint “for NICE and Haute Autorité de Santé (HAS).”

It was also noted that the higher acceptance rate of RWE by NICE compared with G-BA may be attributed to G-BA's role in setting ratings for price premiums rather than for making reimbursement recommendations. We acknowledge that, “in Germany treatments are automatically reimbursed; thus, the added benefit evaluation distinctly informs pricing negotiations and not reimbursement per se. Consequently, this may explain the differences in evaluative criteria for RWE incorporation set by IQWiG and G-BA vs NICE” as per our prior correction.²

We welcome future studies that would expand our systematic literature review search criteria (Data S1) and reporting content to capture additional details mentioned by Tomeczkowski et al.