An Inclusive Civil Society Dialogue for Successful Implementation of the EU HTA Regulation: Call to Action to Ensure Appropriate Involvement of Stakeholders and Collaborators.

OBJECTIVES: Stakeholder involvement has long been considered a success factor for a joint European health technology assessment (HTA) process, and its relevance is now anchored in the EU HTA Regulation's (EU HTAR) legislative wording. Therefore, we aimed to explore the roles, challenges, and most important activities to increase the level of involvement per stakeholder group. METHODS: At the 2022 Fall Convention of the European Access Academy (EAA), working groups addressed the involvement of patients, clinicians, regulators, health technology developers (HTD), and national HTA bodies and payers within the EU HTA process. Each working group revisited the pre-convention survey results, determined key role characteristics for each stakeholder, and agreed on the most important activities to fulfill the role profile. Finally, the activities suggested per group were prioritized by plenary group. RESULTS: The prioritized actions for patients included training and capacity building, the establishment of a patient involvement committee, and the establishment of a patient unit at the EC secretariat. For clinicians, it included alignment on evidence assessment from a clinical vs. HTA point of view, capacity building, and standardization of processes. The most important actions for regulators are to develop joint regulatory-HTA guidance documents, align processes and interfaces under the regulation, and share discussions on post-licensing evidence generation. HTDs prioritized scientific advice capacity and the review of the scoping process, and further development of the scope of the assessment report fact checks. The top three actions for national HTA bodies and payers included clarification on the early HTD dialogue process, political support and commitment, and clarification on financial support. CONCLUSIONS: Addressing the activities identified as the most important for stakeholders/collaborators in the EU HTA process (e.g., in the implementation of the EU HTA Stakeholder Network and of the guidance documents developed by the EUnetHTA 21 consortium) will be key to starting an "inclusive civil society dialogue", as suggested by the European Commission's Pharmaceutical Strategy.

The role of stakeholder involvement in the evolving EU HTA process: Insights generated through the European Access Academy's multi-stakeholder pre-convention questionnaire.

Involvement of all relevant stakeholders will be of utmost importance for the success of the developing EU HTA harmonization process. A multi-step procedure was applied to develop a survey across stakeholders/collaborators within the EU HTA framework to assess their current level of involvement, determine their suggested future role, identify challenges to contribution, and highlight efficient ways to fulfilling their role. The 'key' stakeholder groups identified and covered by this research included: patients', clinicians', regulatory, and Health Technology Developer representatives. The survey was circulated to a wide expert audience including all relevant stakeholder groups in order to determine self-perception by the 'key' stakeholders regarding involvement in the HTA process (self-rating), and in a second, slightly modified version of the questionnaire, to determine the perception of 'key' stakeholder involvement by HTA bodies, payers, and policymakers (external rating). Predefined analyses were conducted on the submitted responses. Fifty-four responses were received (patients 9; clinicians: 8; regulators: 4; HTDs 14; HTA bodies: 7; Payers: 5; policymakers 3; others 4). The mean self-perceived involvement score was consistently lower for each of the 'key' stakeholder groups than the respective external ratings. Based on the qualitative insights generated in the survey, a RACI Chart (Responsible/Accountable/Consulted/Informed) was developed for each of the stakeholder groups to determine their roles and involvement in the current EU HTA process. Our findings suggest extensive effort and a distinct research agenda are required to ensure adequate involvement of the key stakeholder groups in the evolving EU HTA process.

Timely, consistent, transparent assessment of market access evidence: implementing tools based on the HTA Core Model® in a pharmaceutical company.

OBJECTIVES: Evidence requirements and assessment methods access differ between health technology assessment (HTA) agencies. The HTA Core Model® provides a standardized approach to HTA, targeting evidence sharing and collaboration between participating HTA bodies. It is fit for purpose from an industry perspective and was used by pharmaceutical company Roche to develop a framework for internal assessment of evidence required for market access and coverage/reimbursement ("access evidence"). METHODS: Tools were developed to systematically scope, assess, plan, and summarize access evidence generation. The tools were based mainly on the first four HTA Core Model® domains and rolled-out in selected development teams in 2017. Five months after full implementation, the impact of tools was assessed in an internal survey. RESULTS: Systematic access evidence generation started with the Access Evidence Questionnaire, to scope evidence requirements and identify evidence gaps. Findings were summarized in the Access Evidence Metric, which assessed the alignment of available/planned evidence against HTA bodies' requirements and developed scope mitigation strategies. The Access Evidence Plan was then used to plan and document (additional) evidence generation. Once generated, evidence was summarized in the Access Evidence Dossier. A survey of twenty-seven Roche employees involved in evidence generation showed that the tools made discussions around access strategies and evidence more efficient and transparent. CONCLUSIONS: The HTA Core Model® provided a useful framework around which to optimize internal evidence generation and assessment. The benefits of using a standardized HTA approach in industry mirror those expected from implementing the HTA Core Model® in HTA agencies.

Leveraging EUnetHTA's conceptual framework to compare HTA decision drivers in France, Italy, and Germany from a manufacturer's point of view.

BACKGROUND: Health Technology Assessments (HTA) procedures differ substantially across the various European countries. We reviewed recent appraisals of a pharmaceutical manufacturer in three major European markets (France; Italy; Germany) and identified and categorized related decision drivers. METHODS: New marketing authorisation between January 2011 and August 2017, and Roche being the Marketing Authorization Holder, were included. Outcome of HTA appraisals by the Haute Autorité de Santé (HAS), Agenzia Italiana del Farmaco (AIFA), and Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA) were reviewed. Respective decision drivers were identified and commonalities and differences across the three countries were determined leveraging the EUnetHTA conceptual taxonomy (i.e. the 9 domains of the EUnetHTA core model). RESULTS: Within that time period Roche received European marketing authorization for eight new molecular entities (10 indications, respectively). Outcome of HTA appraisals was heterogeneous across the three countries. However, the four clinical domains of the EUnetHTA core model were driving the national HTA appraisals, with the clinical effectiveness domain being of most importance. Important drivers related to the other three clinical domains included the target patient population (subgroups, Germany), the current management of the condition (unmet need, Italy), the regulatory status (Orphan Designation, Germany), as well as safety considerations (all three countries). Average time between EMA approval and full commercial availability of new medicines was 63 (Germany), 459 (Italy), and 557 days (France). CONCLUSIONS: The clinical domains of the EUnetHTA framework are mainly driven by national HTA appraisals, providing a suitable starting point for further developing a joint European view on value and evidence. Underlying topics and issues still reveal considerable differences.

Different Weights of the Evidence-Based Medicine Triad in Regulatory, Health Technology Assessment, and Clinical Decision Making.

Evidence-based medicine (EBM) is defined as a systematic approach to clinical problem solving by the integration of best research evidence with real-world clinical expertise and patient values. Since those early days, decision requirements expanded from patient-centric clinical decision making to a population-based view including regulatory health technology assessments (HTAs). Regulatory bodies mainly rely on the totality of research evidence, which includes preclinical and all available clinical data. HTA bodies primarily focus on clinical data with a strong preference for comparative data from randomized controlled clinical trials (RCTs). Conversely, bedside clinical decisions are largely driven by real-world clinical expertise, which takes into account the individual patients' preferences, as well as the availability of supportive research evidence. While the focus on research evidence is a typical feature of the early part of the adoption curve for innovative technologies, HTA decision makers need to ensure that clinical expertise is also appropriately included in their decisions, in order to avoid beneficial medications from being not available to patients.

Utility values in health technology assessments: a statistician's perspective.

This paper provides an introduction to utilities for statisticians working mainly in clinical research who have not had experience of health technology assessment work. Utility is the numeric valuation applied to a health state based on the preference of being in that state relative to perfect health. Utilities are often combined with survival data in health economic modelling to obtain quality-adjusted life years. There are several methods available for deriving the preference weights and the health states to which they are applied, and combining them to estimate utilities, and the clinical statistician has valuable skills that can be applied in ensuring the robustness of the trial design, data collection and analyses to obtain and handle this data. In addition to raising awareness of the subject and providing source references, the paper outlines the concepts and approaches around utilities using examples, discusses some of the key issues, and proposes areas where statisticians can collaborate with health economic colleagues to improve the quality of this important element of health technology assessment.