Cost-effectiveness analyses are integrated in evidence-based recommendations for market access and reimbursement of new products, provided by health technology assessment (HTA) bodies, in several countries. The objective was to compare economic protocols submitted for a same product to three HTA bodies, assessing if the same cost-effectiveness analysis and methodology was implemented and if the results provided consistent ICERs. We focused on the 3 following HTA bodies (Haute Autorité de Santé (HAS), National Institute for Health and care Excellence (NICE) and Canada's Drug and Health Technology Agency (CADTH)). The thirteen HAS opinions assessed from September 2021 to February 2022 were eligible for the analysis and selected if the health technology appraisal was available for the three HTA bodies. Comparison of economic protocols were performed using the published opinions for HAS, the Company evidence submission for NICE and the pharmacoeconomic reviews for CADTH. Thirteen methodological items were reviewed and compared. Among the thirteen opinions, four were available for the three HTA bodies: EVRYSDI® (spinal muscular atrophy), VENCLYXTO® (acute myeloid leukemia), KEYTRUDA® (metastatic colorectal cancer (MCC) and esophageal cancer (OC)). Eight items were common between submissions for KEYTRUDA® (MCC), seven for EVRYSDI®, two for KEYTRUDA® (OC) and one for VENCLYXTO®. Objective, simulated population, and treatment duration were the most common items, whereas time horizon and utilities were systematically different. These differences conduct to important range in ICER estimations (for instance, between £43,225 for NICE, €107,407 for HAS, $142,861 for CADTH for KEYTRUDA® (OC)). Heterogeneity is observed in the methodology of cost-effectiveness analyses submitted for a same product to the three considered HTA bodies. The differences in some key structural choices and hypotheses lead to heterogenous ICERs estimations, key driver for evidence-based guidance and reimbursement process.

For healthcare products liable to offer moderate to major Clinical Added Value (CAV), the CEESP issues an economic opinion in parallel of the TC which grants the level of CAV. The CAV is based on demonstrated therapeutic progress – in terms of efficacy or safety – compared to existing alternatives. The objective was to compare CEESP and TC conclusions for products with a CAV of level V (no therapeutic progress). All published CEESP opinions from February 2014 to May 2022 were eligible. Opinions on drugs or vaccine, with a CAV V granted by the TC, were selected. An extraction grid was developed with the following items from the TC and CEESP appraisals: CAV V justification, indication, efficacy comparison method, data source, methodological reservation. On the 165 CEESP opinions identified, 27 were granted a CAV V by the TC. The main reasons were the absence of relevant comparators, indirect treatment comparison method, safety concerns or limited effect size. Less than 50% (12 out of the 27) of the opinions were issued at least one major reservation or major uncertainty by the CEESP. Most of opinions with a reservation (9/12) were consistent with the TC concerns (especially clinical data and relative efficacy estimation). No pattern was observed in therapeutic areas (oncology, neurology, cardiology), or ICER result. When requested, the parallel medico-technic and economic appraisals provided by the TC and CEESP, respectively, can lead to misleading conclusions. Indeed, when a CAV V is issued by the TC, introduction of the new product on the French market must show cost savings, resulting in an irrelevant assessment of the cost-effectiveness analysis by the CEESP. The relevance of a joint evaluation between the two committees could be considered to avoid this inconsistency.