Technology Assessment vs. Technology Appraisal-How to Strengthen the Science/Value Dichotomy with EU HTA?

Many countries around the world use health technology assessment (HTA) to inform reimbursement and pricing decisions. HTA is often split into two steps, called assessment and appraisal. While the term HTA itself has been defined by international consortia, there is heterogeneity in the way different stakeholders use the terms assessment and appraisal.

The Role of Medical Societies and the Relevance of Clinical Perspective in the Evolving EU HTA Process: Insights Generated at the 2023 Fall Convention and Survey of the European Access Academy.

Background: This work aimed to determine the role and action points for the involvement of medical societies in the European Health Technology Assessment (EU HTA) Methods: An online pre-convention survey was developed addressing four areas related to the EU HTA: (i) medical societies' role; (ii) role of clinical guidelines; (iii) interface with the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS); and (iv) approaching 'best-available evidence' (BAE). A descriptive analysis of questionnaire outcomes was conducted to inform the European Access Academy (EAA) Fall Convention 2023. Within the working groups (WGs), action points were identified and prioritised.

Navigating the path towards successful implementation of the EU HTA Regulation: key takeaways from the 2023 Spring Convention of the European Access Academy.

Background: The European Regulation on Health Technology Assessment (EU HTA R), effective since January 2022, aims to harmonize and improve the efficiency of common HTA across Member States (MS), with a phased implementation from January 2025. At "midterms" of the preparation phase for the implementation of the Regulation our aim was to identify and prioritize tangible action points to move forward.

Methods: During the 2023 Spring Convention of the European Access Academy (EAA), participants from different nationalities and stakeholder backgrounds discussed readiness and remaining challenges for the Regulation's implementation and identified and prioritized action points.

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.

The role of stakeholder involvement in the evolving EU HTA process: .

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.

How can a joint European health technology assessment provide an 'additional benefit' over the current standard of national assessments? : Insights generated from a multi-stakeholder survey in hematology/oncology.

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).

Development and Pilot Test of the Registry Evaluation and Quality Standards Tool: An Information Technology-Based Tool to Support and Review Registries.

Objectives: Health technology assessment (HTA) bodies are increasingly making use of real-world evidence and data. High-quality registries could be an asset for this; nevertheless, there is a lack of specified standards to assess the quality of data in the registry, or the registry itself. The European Network for Health Technology Assessment Joint Action 3 led the work to develop a tool for the evaluation of clinical registries: the "Registry Evaluation and Quality Standards Tool" (REQueST).

Intraindividual Comparisons to Determine Comparative Effectiveness: Their Relevance for G-BA's Health Technology Assessments.

Objectives: Health technology assessments (HTA) rely on head-to-head comparisons. We searched for intraindividual comparisons (IIC) qualifying as head-to-head design to develop comparative evidence.

Methods: Gemeinsamer Bundesausschuss (G-BA) appraisals between January 2011 and April 2020 were reviewed for inclusion of IIC.

IS THE EUNETHTA HTA CORE MODEL® FIT FOR PURPOSE? EVALUATION FROM AN INDUSTRY PERSPECTIVE.

Objectives: The HTA Core Model® was developed to improve the transferability of health technology assessment (HTA) between settings. The model has been used by HTA agencies but is also of interest to manufacturers, for improving internal evidence generation and communicating with other HTA stakeholders. To establish if the model is fit for purpose from an industry perspective, the pharmaceutical company Roche, collaborating with the European Network for HTA (EUnetHTA), conducted an assessment of the model.

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.

"Market withdrawals" of medicines in Germany after AMNOG: a comparison of HTA ratings and clinical guideline recommendations.

Background: According to the AMNOG act, the German Federal Joint Committee (G-BA) determines the additional benefit of new medicines as a basis for subsequent price negotiations. Pharmaceutical companies may withdraw their medications from the market at any time during the process. This analysis aims to compare recommendations in clinical guidelines and HTA appraisals of medicines that were withdrawn from the German market since the introduction of AMNOG in 2011.

Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany.

Background: In oncology clinical trials, crossover is used frequently but may lead to uncertainties regarding treatment effects.

Objective: To investigate the handling of evidence from crossover trials by the European Medicines Agency (EMA) and the German Federal Joint Committee (G-BA).

Methods: For oncology medicines with early benefit assessments before January 2015, presence of crossover, clinical data, EMA requests for additional data, and G-BA benefit ratings/evidence levels were analyzed from manufacturers' dossiers, G-BA appraisals, European Public Assessment Reports, and original publications.

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.

Inconsistent approaches of the G-BA regarding acceptance of primary study endpoints as being relevant to patients - an analysis of three disease areas: oncological, metabolic, and infectious diseases.

Background: Previous evaluations of oncological medicines in the German early benefit assessment (EBA) procedure have demonstrated inconsistent acceptance of endpoints by regulatory authorities and the Federal Joint Committee (G-BA). Accepted standard endpoints for regulatory purposes are frequently not considered as patient-relevant in the German EBA system. In this study the acceptance of clinically acknowledged primary endpoints (PEPs) from regulatory trials in EBAs conducted by the G-BA was evaluated across three therapeutic areas.

Comparison of post-authorisation measures from regulatory authorities with additional evidence requirements from the HTA body in Germany - are additional data requirements by the Federal Joint Committee justified?

Objectives: The aim of this study was to compare post-authorisation measures (PAMs) from the European Medicines Agency (EMA) with data requests in fixed-termed conditional appraisals of early benefit assessments from the German Federal Joint Committee (G-BA).

Methods: Medicinal products with completed benefit assessments during an assessment period of 3.5 years were considered.

[The influence of framework conditions for integrated care programs on their potential of evaluation].

Aim And Methods: A common justification of the failure to perform scientific evaluations of integrated care programs (in accordance with Sect. 140 SGB V) is the high level of expenditure which is strongly influenced by the conditions of the particular program. Two practical examples will be used to outline frameworks of integrated care programs that may create obstacles to evaluation.

Early Benefit Assessments in Oncology in Germany: How Can a Clinically Relevant Endpoint Not Be Relevant to Patients?

After 4 years of early benefit assessment (EBA) in Germany, it is becoming evident that the Federal Joint Committee (FJC) frequently considers well-established clinical endpoints as not being relevant to patients. Focusing on assessments of oncology medicines, we analysed the FJC's view on primary endpoints and compared it with the approach used by regulatory authorities. Mortality data were accepted by both stakeholders.

Analysis of endpoints used in marketing authorisations versus value assessments of oncology medicines in Germany.

Background And Aims: In Germany, a mandatory early benefit assessment (EBA) by the Federal Joint Committee (G-BA) is required for reimbursement of new marketing-authorised medicines. Additional benefit is based on patient-relevant endpoints in mortality, morbidity and health-related quality of life (HRQoL). We aimed to compare endpoints and related benefit categories used in marketing authorisation to those considered by G-BA in the field of oncology.

Patient relevant endpoints in oncology: current issues in the context of early benefit assessment in Germany.

Unlabelled: The German AMNOG healthcare reform includes a mandatory early-benefit-assessment (EBA) at launch. As per German social code, EBA is based on registration trials and includes evaluation of the patient-relevant effect of the new medicines compared to an appropriate comparator as defined by the Federal Joint Committee (G-BA). Current EBA decisions released have unveiled issues regarding the acceptance of some patient-relevant endpoints as G-BA and IQWiG are grading the endpoints, focusing on overall survival as the preferred endpoint in oncology.

Early benefit assessment (EBA) in Germany: analysing decisions 18 months after introducing the new AMNOG legislation.

Objectives: Since the introduction of the German health care reform in January 2011, an early benefit assessment (EBA) is required for all new medicines. Pharmaceutical manufacturers have to submit a benefit dossier for evaluation by the Institute for Quality and Efficiency in Health Care (IQWiG). A final decision is made by the Federal Joint Committee (G-BA).

Cost of illness in rheumatoid arthritis in Germany in 1997-98 and 2002: cost drivers and cost savings.

Objective: Comparison of overall RA-related costs and of relative contribution of single-cost domains before and after the introduction of TNF-blocking agents in Germany.

Methods: Two cohorts of RA outpatients (ACR '87 criteria) with long-standing disease are assessed in terms of disease-related costs and cost composition (n = 106 patients in 1997-98 and n = 180 patients in 2002 with similar patient characteristics). Full-cost analyses are performed including direct disease-related costs (medical and non-medical) and productivity costs as collected by patient questionnaires.

Cost-efficacy comparison among three antiretroviral regimens in HIV-1 infected, treatment-experienced patients.

Background And Objective: In the face of increasing antiretroviral (ARV) treatment options and costs, payers are progressively challenged with prioritising resources. The cost effectiveness of the ARV agent enfuvirtide has been shown to be comparable to that of other available HIV treatment strategies, based on Markov modeling. However, an evaluation of enfuvirtide treatment costs that considers the impact of virological and immunological responses to therapy may provide a more clinically meaningful perspective for primary HIV healthcare providers.

Content comparison of health-related quality of life instruments for COPD.

Background: Due to the increasing importance of quality of life assessments in chronic obstructive pulmonary disease (COPD) patients, and the increased use of the International Classification of Functioning, Disability and Health (ICF) for comparative purposes it is essential to understand the relationship between health-related quality of life (HRQL) instruments and the ICF.

Objective: The objective of this study was to compare the content of recommended COPD-specific HRQL instruments using the ICF as reference. COPD-specific instruments mentioned in widely accepted guidelines were linked to the ICF using standardized linking rules.