Stimulating development of innovative medicines in the European Union: does a new definition for unmet medical need add value?

The European Commission (EC) has proposed to redefine 'unmet medical need' to steer pharmaceutical innovation and link the definition to incentives and regulatory tools and procedures. A multistakeholder meeting of the Regulatory Science Network Netherlands (RSNN) discussed the impact of this proposal. Four principles were highlighted (flexibility, feasibility, fairness, and sensitivity to risk) that were not considered sufficiently addressed.

Managed Entry Agreements for High-Cost, One-Off Potentially Curative Therapies: A Framework and Calculation Tool to Determine Their Suitability.

Objective: To construct a framework and calculation tool to compare the consequences of implementing different payment models for high-cost, one-off potentially curative therapies and enable decision making to ultimately enhance timely patient access to innovative health interventions.

Methods: A framework outlining steps to determine potentially suitable payment models was developed. Based on the framework, a supporting calculation tool operationalised as an Excel-based model was constructed to quantify the associated costs for an average patient during the timeframe of the intended payment agreement, the total budget impact and associated benefits expressed in quality-adjusted life-years for the total expected lifetime of the patient population.

Uncertainty in Long-Term Relative Effectiveness of Medicines in Health Technology Assessment.

Objectives: Uncertainty regarding the long-term relative effectiveness is an important factor in health technology assessment (HTA) of medicines. This study investigated how different HTA bodies address this uncertainty in their assessments.

Methods: A total of 49 HTA reports from 6 national HTA bodies, assessing 9 medicines for spinal muscular atrophy, cystic fibrosis, and hypercholesterolemia, were included.

An operationalization framework for lifecycle health technology assessment: a Health Technology Assessment International Global Policy Forum Task Force report.

Operationalization guidance is needed to support health technology assessment (HTA) bodies considering implementing lifecycle HTA (LC-HTA) approaches. The 2022 Health Technology Assessment International (HTAi) Global Policy Forum (GPF) established a Task Force to develop a position paper on LC-HTA. In its first paper, the Task Force established a definition and framework for LC-HTA in order to tailor it to specific decision problems.

Lifecycle HTA: promising applications and a framework for implementation. An HTAi Global Policy Forum Task Force report.

The 2022 Health Technology Assessment International (HTAi) Global Policy Forum (GPF) established the goal of developing a position statement and framework for lifecycle HTA (LC-HTA), through a Task Force leveraging multi-stakeholder monthly discussions and GPF member input. The Task Force developed a working definition: LC-HTA is a systematic process utilizing sequential HTA activities to inform decision making where the evidence base, the health technology itself, or the context in which it is applied, has a potential to meaningfully change at different points in its LC. Four key scenarios were identified where it was considered that an LC-HTA approach would add sufficient value to HTA bodies and their key stakeholders to justify the additional resource burden.

Agreement about Availability of Alternative Treatments for Innovative Drugs Assessed by the EMA and HTA Organizations.

The European Medicines Agency (EMA) and European national/regional health technology assessment (HTA) organizations consider the availability of existing treatments when evaluating a new drug. Since disagreement about the availability of alternative treatments may impact patient access to new drugs, this study aimed to investigate whether the EMA and HTA organizations agreed on the availability of alternative treatments and whether a lack of alternative treatments was associated with HTA organizations' added benefit assessment outcomes. For 97 innovative drugs authorized in 2019-2021 (excluding vaccines and diagnostic tools), assessments by the EMA and AEMPS (Spain), AIFA (Italy), HAS (France), IQWiG/G-BA (Germany), NICE (England and Wales), and ZIN (the Netherlands) were identified.

Tools for assessing quality of studies investigating health interventions using real-world data: a literature review and content analysis.

Objectives: We aimed to identify existing appraisal tools for non-randomised studies of interventions (NRSIs) and to compare the criteria that the tools provide at the quality-item level.

Design: Literature review through three approaches: systematic search of journal articles, snowballing search of reviews on appraisal tools and grey literature search on websites of health technology assessment (HTA) agencies.

Data Sources: Systematic search: Medline; Snowballing: starting from three articles (D'Andrea , Quigley and Faria ); Grey literature: websites of European HTA agencies listed by the International Network of Agencies for Health Technology Assessment.

A literature review of quality assessment and applicability to HTA of risk prediction models of coronary heart disease in patients with diabetes.

This literature review had two objectives: to identify models for predicting the risk of coronary heart diseases in patients with diabetes (DM); and to assess model quality in terms of risk of bias (RoB) and applicability for the purpose of health technology assessment (HTA). We undertook a targeted review of journal articles published in English, Dutch, Chinese, or Spanish in 5 databases from 1st January 2016 to 18th December 2022, and searched three systematic reviews for the models published after 2012. We used PROBAST (Prediction model Risk Of Bias Assessment Tool) to assess RoB, and used findings from Betts et al.

Importance of aligning the implementation of new payment models for innovative pharmaceuticals in European countries.

Introduction: The uptake of complex technologies and platforms has resulted in several challenges in the pricing and reimbursement of innovative pharmaceuticals. To address these challenges, plenty of concepts have already been described in the scientific literature about innovative value judgment or payment models, which are either (1) remaining theoretical; or (2) applied only in pilots with limited impact on patient access; or (3) applied so heterogeneously in many different countries that it prevents the health care industry from meeting expectations of HTA bodies and health care payers in the evidence requirements or offerings in different jurisdictions.

Areas Covered: This paper provides perspectives on how to reduce the heterogeneity of pharmaceutical payment models across European countries in five areas, including 1) extended evaluation frameworks, 2) performance-based risk-sharing agreements, 3) pooled procurement for low volume or urgent technologies, 4) alternative access schemes, and 5) delayed payment models for technologies with high upfront costs.

Perspectives on how to build bridges between regulation, health technology assessment and clinical guideline development: a qualitative focus group study with European experts.

Objective: Improving synergy among regulation, health technology assessment (HTA) and clinical guideline development is relevant as these independent processes are building on shared evidence-based grounds. The two objectives were first to assess how convergence of evidentiary needs among stakeholders may be achieved, and second, to determine to what extent convergence can be achieved.

Design: Qualitative study using eight online dual-moderator focus groups.

Systemic anticancer treatment in the Netherlands: Few hospitals treat many patients, many hospitals treat few patients.

Introduction: The correlation between patient volume and clinical outcomes is well known for various oncological treatments, especially in the surgical field. The current level of centralisation of systemic treatment of (hemato-)oncology indications in Dutch hospitals is unknown.

Objectives: The aim of this study was to gain insight in patient volumes per hospital of patients treated with systemic anticancer treatment in the Netherlands.

Uncertainty management in regulatory and health technology assessment decision-making on drugs: guidance of the HTAi-DIA Working Group.

Objectives: Uncertainty is a fundamental component of decision making regarding access to and pricing and reimbursement of drugs. The context-specific interpretation and mitigation of uncertainty remain major challenges for decision makers. Following the 2021 HTAi Global Policy Forum, a cross-sectoral, interdisciplinary HTAi-DIA Working Group (WG) was initiated to develop guidance to support stakeholder deliberation on the systematic identification and mitigation of uncertainties in the regulatory-HTA interface.

The Beneluxa Initiative domain task force health technology assessment: a comparison of member countries' past health technology assessments.

Objective: This study aimed to compare assessments between Beneluxa Initiative member countries' assessments and identify alignments and divergences.

Methods: A retrospective comparative analysis was performed that investigated (i) number and type of assessed indications (for Austria (AT), Belgium (BE), Ireland (IE), and the Netherlands (NL)); (ii) added benefit conclusions (for BE, IE, and NL); and (iii) the main arguments underlying differences in conclusions (for BE, IE, and NL). Data were retrieved directly from agency representatives and from public HTA reports.

Adverse Events to SARS-CoV-2 (COVID-19) Vaccines and Policy Considerations that Inform the Funding of Safety Surveillance in Low- and Middle-Income Countries: A Mixed Methods Study.

Introduction/objective: Rapid global approval of coronavirus disease 2019 (COVID-19) vaccines and concurrent introduction in high-income countries and low- and middle-income countries (LMIC) highlights the importance of equitable safety surveillance of adverse events following immunization (AEFIs). We profiled AEFIs to COVID-19 vaccines, explored reporting differences between Africa and the rest of the world (RoW), and analyzed policy considerations that inform strengthening of safety surveillance in LMICs.

Methods: Using a convergent mixed-methods design we compared the rate and profile of COVID-19 vaccines' AEFIs reported to VigiBase by Africa versus the RoW, and interviewed policymakers to elicit considerations that inform the funding of safety surveillance in LMICs.

When Reality Does Not Meet Expectations-Experiences and Perceived Attitudes of Dutch Stakeholders Regarding Payment and Reimbursement Models for High-Priced Hospital Drugs.

This study aimed to identify the current experiences with and future preferences for payment and reimbursement models for high-priced hospital therapies in the Netherlands, where the main barriers lie and assess how policy structures facilitate these models. A questionnaire was sent out to Dutch stakeholders (in)directly involved in payment and reimbursement agreements. The survey contained statements assessed with Likert scales, rankings and open questions.

Reimbursement and payment models in Central and Eastern European as well as Middle Eastern countries: A survey of their current use and future outlook.

There is growing interest in innovative reimbursement and payment models in Central and Eastern European (CEE) and Middle Eastern (ME) countries. A questionnaire was sent to payers from CEE and ME countries regarding the current use of, future preferences for and perceived barriers with these models. Twenty-seven healthcare payers from 11 countries completed the survey.

Outcome-based reimbursement in Central-Eastern Europe and Middle-East.

Outcome-based reimbursement models can effectively reduce the financial risk to health care payers in cases when there is important uncertainty or heterogeneity regarding the clinical value of health technologies. Still, health care payers in lower income countries rely mainly on financial based agreements to manage uncertainties associated with new therapies. We performed a survey, an exploratory literature review and an iterative brainstorming in parallel about potential barriers and solutions to outcome-based agreements in Central and Eastern Europe (CEE) and in the Middle East (ME).

Regulatory reliance pathways during health emergencies: enabling timely authorizations for COVID-19 vaccines in Latin America.

Objectives: To map the timing and nature of regulatory reliance pathways used to authorize COVID-19 vaccines in Latin America.

Methods: An observational study was conducted assessing the characteristics of all COVID-19 vaccine authorizations in Latin America. For every authorization it was determined whether reliance was used in the authorization process.

Do Health Technology Assessment organisations consider manufacturers' costs in relation to drug price? A study of reimbursement reports.

Introduction: Drug reimbursement decisions are often made based on a price set by the manufacturer. In some cases, this price leads to public and scientific debates about whether its level can be justified in relation to its costs, including those related to research and development (R&D) and manufacturing. Such considerations could enter the decision process in collectively financed health care systems.

Delayed payment schemes in Central-Eastern Europe and Middle-East.

The need for innovative payment models for health technologies with high upfront costs has emerged due to affordability concerns across the world. Early technology adopter countries have been experimenting with delayed payment schemes. Our objective included listing potential barriers for implementing delayed payment models and recommendations on how to address these barriers in lower income countries of Central and Eastern Europe (CEE) and the Middle East (ME).

Cost-effectiveness of clopidogrel vs. ticagrelor in patients of 70 years or older with non-ST-elevation acute coronary syndrome.

Objective: The POPular AGE trial showed that clopidogrel significantly reduced bleeding risk compared with ticagrelor without any signs of an increase in thrombotic events. The aim of this analysis was to estimate the long-term cost-effectiveness of clopidogrel compared with ticagrelor in these patients aged 70 years or older with non-ST-elevation acute coronary syndrome (NSTE-ACS).

Methods And Results: A 1-year decision tree based on the POPular AGE trial in combination with a lifelong Markov model was developed to compare clopidogrel with ticagrelor in terms of clinical outcomes, costs, and quality-adjusted life years (QALYs) in elderly patients (above 70 year) with NSTE-ACS.

Reported Challenges in Health Technology Assessment of Complex Health Technologies.

Objectives: With complex health technologies entering the market, methods for health technology assessment (HTA) may require changes. This study aimed to identify challenges in HTA of complex health technologies.

Methods: A survey was sent to European HTA organizations participating in European Network for HTA (EUnetHTA).