Background: The phase 3 clinical trial KEYNOTE-426 suggested a higher efficacy regarding overall survival (OS) and progression-free survival (PFS) of pembrolizumab+axitinib compared to sunitinib as a first-line treatment for patients with advanced renal cell carcinoma. In this analysis, the potential cost-effectiveness of this combination treatment versus sunitinib for patients with advanced clear-cell renal cell carcinoma (accRCC) was examined from the societal perspective in the Netherlands.Methods: For this analysis, a partitioned survival model was constructed. Clinical data were obtained from the published KEYNOTE-426 trial reports; data on costs and (dis-)utilities were derived from published literature. Costs outside of the healthcare sector included treatment-related travel, informal care and productivity loss. Next to a probabilistic scenario analysis, various scenario analyses were performed that aimed at survival extrapolation, different utility values, treatment duration and drug pricing, as well as restricting the cohort to patients with an intermediate or poor prognosis. Further, a budget impact analysis over three years was conducted, in which a sensitivity analysis concerning ranges in costs and the number of patients was applied. Moreover, a scenario concerning increasing market penetration of pembrolizumab+axitinib up to a market share of 80% in the third year was analyzed.Results: The incremental cost-effectiveness ratio (ICER) of pembrolizumab+axitinib was estimated at €368,396/quality-adjusted life year (QALY) gained, with an incremental QALY gain of 0.55 over sunitinib. The probability of cost-effectiveness at a willingness-to-pay threshold of €80,000/QALY was estimated at 0%, a 50% probability was estimated at €340,000/QALY. Cost-effectiveness was not achieved in any of the applied scenarios. The budget impact over three years amounted to €417.3 million upon instantaneous and full replacement of sunitinib, and to €214.9 million with increasing market penetration.Conclusion: Pembrolizumab+axitinib was not estimated to be cost-effective compared to sunitinib as a first-line treatment for patients with accRCC in the Netherlands from a societal perspective. In none of the analyzed scenarios, cost-effectiveness was achieved. However, price reductions and shorter treatment durations might lead to a more favorable ICER.

Joint clinical assessments (JCAs) under the European Union (EU) Regulation 2021/2282 on health technology assessment (HTA-R) and its implementing regulations have been linked to various implementation challenges. However, legal implications of practically relevant issues have mostly remained unexplored. This study investigated potential legal implications of disparities regarding patient population, intervention, comparator, and outcomes (PICOs) in JCAs from respective member states (MSs), and of managing conflicts of interest (CoIs) of experts involved in a JCA. Moreover, we discussed potential consequences for patient access. JCA reports are not legally binding for MS; PICO disparities can underpin the required justification for their non-consideration at national level. Legal action against negative reimbursement decisions due to unjustified non-consideration falls under national jurisdiction. Furthermore, too strict CoI management might leave perspectives of MSs with fewer experts and thus a higher chance of CoI occurrence unheard, requiring corresponding expert elicitation at national level. These implications might lead to an increased workload for health technology developers and national HTA bodies, potentially fostering marketing strategies and access delays. Thorough scoping processes and prioritising the need for a JCA’s scientific excellence could facilitate more streamlined national HTA procedures and accelerated patient access.

Background: The Dutch Committee for the Evaluation of Oncological Agents (cieBOM) assesses the clinical benefit of systemic anti-cancer treatments (SACTs). For SACTs tested in non-randomized trials (NRTs), cieBOM primarily utilizes response-related thresholds as assessment criteria. As sufficiency of NRT-based evidence for benefit assessments is questionable, this study investigated whether and how NRTs can be used to assess the clinical benefit of new SACTs initially appraised by cieBOM based on randomized controlled trials (RCTs). Methods: Using the RCTs underpinning cieBOM recommendations issued between 2015 and 2017, we searched for matching NRTs and applied the NRT-related assessment criteria by cieBOM to them. We then compared the assessment outcomes to the respective RCT-based cieBOM recommendations. Further, we investigated how the assessments would change when applying different response-related thresholds and adding a progression-free survival (PFS) threshold. Results: For 13 of the 37 eligible recommendations, a matching NRT was found. Two treatments were assessed positively and six negatively; five treatments were non-assessable. Two positive recommendations matched a positive NRT-based assessment; one matching negative assessment was found, and one treatment could not be assessed based on either trial results. Adding a > 6 months PFS threshold decreased the number of non-assessable NRTs (five to two). Conclusions: Limited publications and inconsistent data reporting hampered the viability of NRTs for clinical benefit assessments of SACTs beyond the scope of rare indications. Further, response-related assessment criteria alone might not fully grasp the clinical benefit of novel SACTs. NRT-based assessments should be considered with caution due to uncertainty of the trial results.

Background: Policymakers face challenges in developing pricing policies for potentially innovative healthcare technologies (pIHTs) that balance limited budgets, access, and incentives for innovation. This study aimed to map existing evidence and identify knowledge gaps regarding price determinants and pricing policies for pIHTs and their effect on access and sustainability. Methods: We conducted a scoping Review of scientific and grey literature in English published between 2014 and September 2023 with pre-specified inclusion and exclusion criteria to identify stakeholder-informed price determinants, pricing policies applied by European Economic Area (EEA) or Organisation for Economic Cooperation and Development (OECD) member states, and their access-related impacts. Literature databases and various stakeholder organisation websites were searched. Further records were included through snowballing and manual addition. Results: 135 Records were included. Stakeholder views on price determinants were available from 15 records and predominantly involved value-based determinants. Pricing policies in EEA/OECD member states are heterogeneous and often feature a mix of policy interventions and implementation methods. External price referencing (EPR), while yielding short-term affordability improvements, is associated with price inequities and launch strategies impairing patient access. Policies combining pricing methods and considering a pIHT’s value have more positive access-related impact but may face feasibility and implementation challenges. Two records mentioned medical device pricing; none featured environmental aspects. Conclusion: While EPR is commonly applied across Europe, value-informed pricing in connection with health technology assessment is more favoured regarding pIHT access in the literature. Knowledge gaps concern medical device pricing, stakeholder views on price determinants, and the implementation of environmental aspects in pIHT pricing.

Background: The objective of this work was to support the implementation of the European Health Technology Assessment Regulation (EU HTAR) and optimize performance of the evolving EU HTA system. Therefore, an inclusive multi-stakeholder framework of key performance indicators (KPI) for success measurement was developed. Methods: A modified Delphi-procedure was applied as follows: (1) development of a generic KPI pool at the Fall Convention 2024 of the European Access Academy (EAA); (2) review of initial pool and identification of additional KPIs; (3) development of prioritized KPIs covering patient, clinician, Health Technology Developer (HTD), and System/Member State (MS) perspectives, and (4) consolidation of the stakeholder-centric KPIs after EAA’s Spring Convention 2025. Results: Steps 1 and 2 of the Delphi procedure revealed 14 generic KPI domains. Steps 3 and 4 resulted in four prioritized KPIs for patients (patient input; utilization of patient-centric outcome measures; time to access; equity); six for clinicians (population/intervention/comparator/outcomes (PICO); addressing uncertainty; clinician involvement; transparency; equity and time to access); four for HTDs (PICO; joint scientific consultation (JSC) process; joint clinical assessment (JCA) process; time to national decision making); five from a system/MS perspective (PICO; learning and training the health system; reducing duplication; equity and time to access). The scope of, e.g., the PICO-related KPI, differed between stakeholder groups. Also, several KPIs intentionally reached beyond the remit of EU HTA as they are also dependent on MS-specific factors including national health systems and budgets. Discussion and Conclusions: The KPI framework developed here presents a step towards the generation of systematic multi-stakeholder evidence to support a successful implementation of the EU HTAR. The relevance of the identified stakeholder-centric KPIs is confirmed by their alignment with the Health System Goals suggested in the context of “Performance measurement for health improvement” by the World Health Organisation. Implementation of the framework, i.e., measurement of KPIs, is envisioned to provide evidence to inform the 2028 revision of the EU HTAR.