Objectives We conducted a multi-stakeholder survey to determine key areas where a joint European health technology assessment (HTA) could provide ‘additional benefit’ compared to the status quo of many parallel independent national and subnational assessments. Methods Leveraging three iterative Delphi cycles, a semiquantitative questionnaire was developed covering evidence challenges and heterogeneity of value drivers within HTAs across Europe with a focus on hematology/oncology. The questionnaire consisted of five sections: i) background information; ii) value drivers in HTA assessments today; iii) evolving evidence challenges; iv) heterogeneity of value drivers across Europe; v) impact of Europe’s Beating Cancer Plan (EBCP). The questionnaire was circulated across n = 189 stakeholder institutions comprising HTA and regulatory bodies, clinical oncology associations, patient representatives, and industry associations. Results N = 30 responses were received (HTA bodies: 9; regulators: 10; patients’ and physicians’ associations: 3 each; industry: 5). Overall, 17 countries and EU level institutions were represented in the responses. Consistency across countries and stakeholder groups was high. Most relevant value drivers in HTAs today (scale 1, low to 5, high) were clinical trial design (mean 4.45), right endpoints (mean 4.40), and size of comparative effect (mean 4.33). Small patient numbers (mean 4.28) and innovative study designs (mean 4.1) were considered the most relevant evolving evidence challenges. Heterogeneity between regulatory and HTA evidence requirements and heterogeneity of the various national treatment standards and national HTA evidence requirements was high. All clinical and patient participants stated to have been with EBCP initiatives. Conclusions For a European HTA to provide an ‘additional benefit’ over the multitude of existing national assessments key methodological and process challenges need to be addressed. These include approaches to address uncertainty in clinical development; comparator choice; consistency in approaching patient-relevant endpoints; and a transparent and consistent management of both HTA and regulatory procedures as well as their interface, including all involved stakeholder groups.

Objectives Key challenges for a joint European Health Technology Assessment (HTA) include consolidated approaches towards the choice of adequate comparator(s), selection of endpoints that are relevant to patients with a given disease, dealing with remaining uncertainties as well as transparent and consistent management of related processes. We aimed to further crystallize related core domains within these four areas that warrant further research and scrutiny. Methods Building on the outcomes of a previously conducted questionnaire survey, four key areas, processes, uncertainty, comparator choice and endpoint selection, were identified. At the inaugural convention of the European Access Academy dedicated working groups were established defining and prioritizing core domains for each of the four areas. The working groups consisted of ~ 10 participants each, representing all relevant stakeholder groups (patients/ clinicians/ regulators/ HTA & payers/ academia/ industry). Story books identifying the work assignments were shared in advance. Two leads and one note taker per working group facilitated the process. All rankings were conducted on an ordinal Likert Response Scale scoring from 1 (low priority) to 7 (high priority). Results Identified key domains include for processes: i) address (resource-) challenge of multiple PICOs (Patient/ Intervention/ Comparator/ Outcomes), ii) time and capacity challenges, iii) integrating all involved stakeholders, iv) conflicts and aligning between different multi-national stakeholders, v) interaction with health technology developer; for uncertainty: i) early and inclusive collaboration, ii) agreement on feasibility of RCT and acceptance of uncertainty, iii) alignment on closing evidence gaps, iv) capacity gaps; for comparator choice: i) criteria for the choice of comparator in an increasingly fragmented treatment landscape, ii) reasonable number of comparators in PICOs, iii) shape Early Advice so that comparator fulfils both regulatory and HTA needs, iv) acceptability of Indirect Treatment Comparisons (ITC), v) ensure broad stakeholder involvement in comparator selection; for endpoint selection: i) approaching new endpoints; ii) patient preferences on endpoints; iii) position of HTA and other stakeholders; iv) long-term generation and secondary use of data; v) endpoint challenges in RCTs. Conclusions The implementation of a joint European HTA assessment is a unique opportunity for a stronger European Health Union. We identified 19 domains related to the four key areas, processes, uncertainty, comparator choice and endpoint selection that urgently need to be addressed for this regulation to become a success.

The Italian National Health Service (Servizio Sanitario Nazionale, SSN) is structured at comprehensive levels such as collective prevention and public health, cure and rehabilitation assistance, and pharmaceutical services, with the primary objective of guaranteeing universal access of all Italian citizens, on equal terms, to equitable provision of health services. Italy was used as a case study to explore their healthcare system and their economic regulation and reimbursement of pharmaceuticals. The Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) is responsible for regulation related to efficacy, safety and quality, pricing and negotiations for reimbursement of medicines. Among the various negotiation criteria defined in specific legislation, biosimilars and generics enter the Italian market with a discount of at least 20% to the reference medicine. Price review occurs in a periodical basis and upon the emergence of new evidence of efficacy and safety arising from pharmacovigilance or upon request of changes in the therapeutic indications and/or dosage. In addition, conducting the monitoring and analysis of pharmaceutical consumption and expenditure contributes for planning health policy interventions, since it allows for prompt identification of emerging phenomena, framing prescription behaviours, and verifying the effectiveness of regulatory interventions at regional and national levels. Efficacy, safety, and cost-effectiveness analyses are conducted before the introduction of the medicines in the Italian market. It continues to be performed when the drug in on the market with health technologies assessment, constituting a process of permanent investigation of the clinical, economic and social consequences of the medicine’s utilisation. In addition, it allows controlling expenses and identifying avoidable costs.