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- Herausgeber: tredition
- Kategorie: Fachliteratur
- Sprache: Englisch
The regulation on European Health Technology Assessment (EU HTA) entered into force on 11 January 2022 and will apply from 12 January 2025. It introduces joint clinical assessments and joint scientific consultations at the European level for new health technologies, including pharmaceuticals and medical devices. While market access, pricing and reimbursement will continue to be the responsibility of EU member states, EU HTA will nevertheless have an immense impact on these national market access activities. This book serves as a practical guide designed to help developers of pharmaceuticals prepare for the upcoming EU HTA process.
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Veröffentlichungsjahr: 2023
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EU HTA 101 (Update from October 2024)
Dr. Thomas Ecker (Editor)
EU HTA 101
How to prepare for European Health Technology Assessment for Pharmaceuticals
Update from October 2024
Editor:
Dr. Thomas Ecker
Ecker + Ecker GmbH / Accessus Health GmbH
Hamburg, Germany
Contact: [email protected] / [email protected]
ISBN Softcover:
978-3-384-03093-1
ISBN E-Book:
978-3-384-03094-8
© All rights reserved. No part of this book may be reproduced in any form or by any means, especially photocopying, editing, translating, microfilming, and saving to electronic systems, without the prior permission of the publisher, except for uses permitted by copyright law.
The reproduction of generally descriptive terms, trademarks, corporate data, etc, in this book does not imply that these are free for use by anyone. Without separate note, any authorized use is subject to the regulations of trademark law. The rights of the respective trademark owner are to be observed.
The publisher, the authors, and the editor assume that all data and information is complete and correct at the time of the publication. Neither the publisher nor the authors or the editor take any responsibility, explicitly or implicitly, for the content of the book or any potential errors or statements made.
Market Access Core Model® is a registered trademark of Ecker + Ecker GmbH
Project management:
Dr. Marie Groneberg, Petra Schulze
Copy editing:
Matthew Gaskins (Edition October 2023)
Cover design:
sehstrand - Silke Schumacher
Printing and distribution:
tredition GmbH, Heinz-Beusen-Stieg 5, 22926 Ahrensburg, Germany
Preface
European Health Technology Assessment (EU HTA) is still evolving. In fact, it has not even begun. So why already an update?
The answer is simple: Products that will undergo assessment from 2025 onwards are already in clinical phase 3. Their study design was set long ago. This means that many companies do not have the luxury of “waiting and seeing” until the dust settles. They have to make crucial decisions now to prepare as best they can for a scenario that could not have been anticipated earlier. This urgency to prepare applies not only to them but also to many others who will soon face similar decisions. Both are the audience of this book.
And a lot has happened since the publication of the first edition in October 2023, not least four Implementing Acts and six guidance documents, and one scientific specification.
Most of you might be familiar with preparing national HTA submissions. But EU HTA is different. And it also impacts national submissions. So take the time and reflect upon this new challenge.
The structure of this book follows our Market Access Core Model®. At the time of finalizing this book we are at version 2.7 and will continue to evolve, in parallel to adoption of the EU HTA process.
Three words of caution: This book was completed in October 2024, and any changes thereafter have not been taken into account. However, we aim to provide a timely update.
Additionally, it is important to note that the focus of this book is on medicinal products, specifically pharmaceuticals, rather than devices and diagnostics.
Finally, this book provides insights towards an ideal EU HTA process. As such, in bears great promises. But reality not always lives up to this ideal. And especially during the first years of implementation scope of surprise will be rich. So be careful by setting realistic expectations.
Special thanks to all members of our European Partner Network, covering all 27 EU member states, all EEA countries, as well as Switzerland and UK. You provided excellent feedback on the applicability of the Market Access Core Model® to your country, and great input towards our internal PICO exercises.
This update would not have been possible without the incredible support of our EU HTA expert group and the contributions of many authors within Ecker + Ecker and Accessus Health.
Thank you very much – you are a fantastic team!
Table of Contents
Cover
Half Title Page
Title Page
Copyright
Preface
1 Market Access Core Model
2 Framework and Relevant Actors
2.1 Journey towards the EU HTA regulation: First initiatives and key milestones
2.1.1 EUnetHTA Project 2006–2008
2.1.2 EUnetHTA Collaboration 2009
2.1.3 Joint Actions and beyond
2.2 Constitutive framework
2.2.1 Regulation (EU) 2021/2282 (HTAR)
2.2.2 Implementing Acts
2.2.3 Regulatory approval vs. HTA
2.2.4 EU pharma legislation
2.2.5 Guidelines
2.2.6 Guidance documents by the Coordination Group
2.2.7 National rules
2.3 Institutions and stakeholders
2.3.1 EUnetHTA and EUnetHTA 21 consortium
2.3.2 Coordination Group on Health Technology Assessment
2.3.3 European Commission
2.3.4 Member states
2.3.5 Stakeholder network
2.3.6 European Medicines Agency
3 National Strategy Development
3.1 Objective and overview
3.2 WP1.1: Identifying the route of reimbursement
3.3 WP1.2: PICO simulation
3.4 WP1.3: Gap analysis
3.5 WP1.4: Price simulation
3.6 WP1.5: Market access strategy development
3.6.1 Strategies for developing the PICO
3.6.2 Strategies beyond PICO
3.6.3 Dossier submission
3.6.4 Internal price references
3.6.5 External price references
3.6.6 Implementation
3.7 WP1.6: National scientific consultation
3.8 WP1.7: Early Access programmes
3.9 WP1.8: Stakeholder management
3.10 WP1.9: Monitoring
3.11 WP1.10: Strategy update
4 Eu Strategy Development
4.1 Objective and Overview
4.2 WP2.1: Verification of EU HTA obligation
4.3 WP2.2: Simulation of consolidated PICO
4.4 WP2.3: Gap Analysis
4.5 WP2.4: Consolidated price simulation
4.6 WP2.5: Consolidated HTA strategy
4.6.1 Strategies around Joint Scientific Consultation (JSC)
4.6.2 Strategies around assessment scope and submission for joint clinical assessment (EU dossier production)
4.6.3 Strategies around EU HTA assessment (JCA report)
4.6.4 Alignment within the organisation
4.7 WP2.6: Scientific Consultation
4.7.1 General process
4.7.2 Formats
4.7.3 Consultation request
4.7.4 Potential alternative avenues for getting HTA scientific consultation
4.8 WP2.7: Stakeholder management
4.9 WP2.8: Monitoring
4.10 WP2.9: Strategy Update
5 Eu Dossier Production
5.1 Objective and overview
5.2 WP3.1: Identifying anticipated PICOs
5.3 WP3.2: Statistical feasibility
5.4 WP3.3: EU dossier outline
5.5 WP3.4: EU dossier outline and national alignment
5.6 WP3.5: Statistical analysis
5.7 WP3.6: Dossier draft
5.8 WP3.7: Communication of final PICOs
5.9 WP3.8: Adaptation of dossier to final PICOs
5.10 WP3.9: Quality assurance
5.11 WP3.10: Dossier submission
5.12 WP3.11: Stakeholder management
5.13 WP3.12: Monitoring
6 Eu Assessment
6.1 Objective and overview
6.2 JCA report – A general overview
6.2.1 General process
6.2.2 Timeline of the EU assessment phase
6.2.3 Incomplete dossier or no dossier submission
6.2.4 Contents of the JCA report
6.2.5 Updates of JCAs
6.3 WP5.1: Factual accuracy check
6.3.1 Factual accuracy check: Practical considerations
6.3.2 Commercially confidential information
6.4 WP5.2: Review of JCA report
6.5 WP5.3: Lessons learned
6.6 WP5.4: Stakeholder management
6.7 WP5.5: Monitoring
7 National Dossier Production
7.1 Objective and overview
7.2 WP4.1: Statistical feasibility
7.3 WP4.2: Dossier outline
7.4 WP4.3: Statistical analysis
7.5 WP4.4: Dossier preparation
7.6 WP4.5: Dossier alignment
7.7 WP4.6: Quality assurance
7.8 WP4.7: Dossier submission
7.9 WP4.8: Stakeholder management
7.10 WP4.9: Monitoring
8 National Assessment
8.1 Objective and overview
8.2 WP6.1: Assessment strategy
8.3 WP6.2: Dossier defense
8.4 WP6.3: Stakeholder management
8.5 WP6.4: Monitoring
8.6 WP6.5: Review the national HTA report
9 National Price Negotiation
9.1 Objective and overview
9.2 WP7.1: Negotiation strategy
9.3 WP7.2: Negotiation preparation
9.3.1 Evidence and price referencing
9.3.2 Scope of decision, and decision-making mechanism
9.3.3 Notification
9.4 WP7.3: Actual negotiation
9.5 WP7.4: Conflict resolution
9.6 WP7.5: Price submission
9.7 WP7.6: Stakeholder management
9.8 WP7.7: Monitoring
9.9 WP7.8: Lessons learned
9.10 WP7.9: Regional negotiation
10 Getting Started
10.1 Monitoring
10.1.1 Constitutive framework
10.1.2 Relevant actors
10.1.3 Dynamics
10.2 Organisational set-up
10.2.1 Roles and responsibilities
10.2.2 Key processes
10.2.3 Adaptation of organisational structure
10.2.4 Resource requirements
10.3 HTA pipeline management
10.3.1 Verifying your HTA route: European or national HTA?
10.3.2 HTA planning per asset and indication: timeline, resources, responsibilities
10.3.3 Ad hoc approach and long-term preparation
10.4 Mock-up
10.4.1 National phase
10.4.2 European phase
10.5 Roadmap for internal preparation
List of Abbreviations
Key Modifications in the Update from October 2024
EU HTA 101
Cover
Title Page
Copyright
Preface
Preface
Key Modifications in the Update from October 2024
EU HTA 101
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1 Market Access Core Model
Dr. Thomas Ecker1
From the outside, the proposed EU HTA might seem like a complex maze of rules and regulations: 36 articles packed into 32 pages just for the regulation itself, in addition to more than 60 high-quality deliverables from EUnetHTA 21– not to mention the various Implementing Acts and corresponding guidelines, most of them still under development. All of these components are aimed at supporting national Health Technology Assessment (HTA) and Pricing & Reimbursement (P&R) as thei main pillars of market access in 27 countries. It is easy to feel lost, even for those who consider the general concept of HTA to be common knowledge. So how can you see the forest for the trees?
This book does not aim to provide a detailed description of individual national market access systems within the context of EU HTA. Instead, it focuses on outlining general principles, enabling the reader to gain a comprehensive overview. To achieve this, adequate methodology is required. This should be generic enough to apply to most scenarios yet specific enough to offer practical guidance. This is where the Market Access Core Model comes into play.
Let’s begin with the common denominator and the underlying basic idea: HTA in individual European countries predates EU HTA by several decades. As more and more countries adopted their own specific HTA procedures, the need for harmonisation and synergy at the European level became obvious. After all, the European Medicines Agency (EMA) covers 30 countries – Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, the Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden – and each has its own unique market access procedures. But if all of these procedures are different, what could possibly be the common denominator?
The answer lies in recognising that the individual market access procedures share a common link: the assessment of the clinical (and economic) evidence for medicinal products, specifically their HTA. It is through these interconnected assessments that the national market access procedure is formed, representing one of the key challenges when launching a new medicinal product (Figure 1).
Figure 1: National market access as the key challenge
For the scope of this book, the term “national market access” encompasses both the national Health Technology Assessment and the national Pricing & Reimbursement (P&R) processes (Figure 2).
Figure 2: National market access encompassing both national HTA and national P&R
From the perspective of a pharmaceutical company, the national market access work stream can be delineated into four distinct phases (Figure 3).
Figure 3: Four phases of national market access
These four phases comprise the national work stream of the Market Access Core Model:
• National strategy development: This phase involves identifying the appropriate reimbursement process, simulating the likely outcome of the evidence evaluation and pricing decision, and developing the market access strategy based on these insights. Additionally, if applicable, the proposed approach is discussed with the pertinent authorities through a national scientific consultation, while also monitoring other (similar) procedures.
• National dossier production: In this phase, the strategy developed in the previous phase is executed by defining the outline of the evidence package (dossier), formulating the HTA Statistical Analysis Plan (SAP), and conducting the corresponding statistical analyses. It also encompasses the preparation of the actual dossier, quality check, dossier submission and product launch (if applicable).
• National assessment: Once the dossier is submitted, the national assessment phase begins. This involves developing the assessment strategy, interacting with authorities, and reviewing the final documents.
• National price negotiation: This phase encompasses developing the negotiation strategy, preparing the negotiation, conducting the actual negotiation process and resolution procedure, notifying the relevant authorities of the final price and reimbursement conditions, and, if needed, regional negotiation including tenders.
Lastly, stakeholder management and monitoring activities are crucial and should be addressed continuously throughout all phases of national market access.
So far, so good!
EU HTA is an additional work stream that runs parallel to national market access (Figure 4).
Figure 4: EU HTA as a parallel work stream to national market access
In other words, there are two market access work streams that need to be managed simultaneously to prepare for product launch. Both work streams are linked to each other (Figure 5). But we will come to that later – it will be a recurring theme throughout this book.
Figure 5: EU HTA and national market access are linked to each other
Let’s return to EU HTA for now. It consists of two key activities: Joint Clinical Assessment (JCA) (as specified in Section 1 of Regulation 2021/2282) and Joint Scientific Consultation (as specified in Section 2 of the same Regulation). From a company perspective, there are three distinct phases (Figure 6) that form the EU HTA work stream of the Market Access Core Model.
Figure 6: Three phases of EU HTA work stream
• EU strategy development: This phase involves deciding whether the EU HTA obligation is applicable, consolidating the likely clinical questions (“PICO” – patients/population, intervention, comparison and outcomes) and the probable outcome of the assessment, conducting a consolidated price simulation, developing the EU HTA strategy based on national reimbursement strategies, and, if available, seeking some form of scientific consultation, ideally through Joint Scientific Consultation.
• EU dossier production: This phase begins with identifying the anticipated (consolidated) PICO, assessing statistical feasibility, establishing the dossier’s outline, aligning with national outlines, constructing the actual statistical model, and preparing the preliminary dossier. It also entails communicating the final PICO, adapting the dossier according to the final PICO, conducting a quality check, submitting the dossier, and engaging with the Coordination Group.
• EU assessment: In this phase, the joint clinical assessment takes place without the participation of the pharmaceutical company. The company’s role is limited to preparing the factual accuracy check.
Lastly, it is important to note that monitoring activities and stakeholder management are relevant throughout all phases of EU HTA, just as they are in the national market access work stream.
Clearly, these two work streams are not entirely separate but need to be managed in parallel. Let’s now examine the full picture, shown in Figure 7.
Figure 7: Market Access Core Model encompassing national market access and EU HTA work stream (overview)
Figure 7 illustrates how both processes are linked to each other. For instance:
• EU strategy development is reliant on input from national strategy development.
• National dossier production must align with EU dossier production.
• Timing is crucial because the inclusion of additional analyses in the national dossier submission depends on the outcome of the JCA report.
Thus, to succeed in EU HTA, both EU HTA and national market access work streams must be managed together.
The national market access strategy serves as the foundation for the EU HTA strategy (Figure 8). If there are changes in the national market access strategy, EU strategy development may need to adapt accordingly. In cases where there is no national market access, there is no need for EU HTA from the perspective of that particular country, and thus no EU strategy is necessary. Additionally, the value of the EU HTA strategy depends on its ability to support the national market access work stream effectively.
Figure 8: National strategy development informs EU strategy development
The next phase, EU dossier production, is informed by the preceding phase of EU strategy development (Figure 9). The quality of EU dossier production can be evaluated by comparing it against the requirements set forth in EU strategy development. Changes in the EU strategy may have implications for EU dossier production.
Figure 9: EU dossier production flows from EU strategy development
Moving on to the EU assessment phase, we see that it is a function of EU dossier production because the EU HTA dossier serves as its foundation (Figure 10).
Figure 10: EU assessment flows from EU dossier production
National dossier production is more complex. It adheres to the requirements set forth in the national strategy development phase and must align with the EU dossier and EU assessment (Figure 11). Therefore, changes in all three phases – national strategy, EU dossier and EU assessment – can impact the national dossier. The quality of the national dossier can be evaluated by assessing its compliance with the requirements from all three directions.
Figure 11: National dossier production flows from national strategy development, EU dossier production and EU assessment
National assessment, in turn, depends on findings from the EU assessment and the national dossier (Figure 12).
Figure 12: National assessment flows from EU assessment and national dossier production
Lastly, national price negotiation builds upon the findings of the national assessment, but also potentially the EU assessment (Figure 13). Consequently, deviations between the EU or national assessment and the initial assumptions can lead to different outcomes during the national price negotiation.
Figure 13: National price negotiation flows from national assessment and potentially the EU assessment
In summary, there are numerous interdependencies that must be observed, monitored and managed throughout this process (Figure 14). Moreover, everything hinges on the specific national strategies of all countries involved.
Figure 14: National assessment flows from EU assessment and national dossier production
Each of these seven phases consists of a specific set of work packages, with 33 work packages at the national level and 26 at the EU level, leading to a total of 59 work packages in the Market Access Core Model (Figure 15).
Figure 15: Market Access Core Model® (Version 2.7)
The underlying structure of this book is based on the Market Access Core Model. On terminology: Each of the chapters from 3 to 9 addresses one of the seven phases of either the national or EU HTA work stream. Each phase comprises several work packages, which will be discussed in the respective chapter (Figure 16).
Figure 16: From work stream to individual work package
Before diving into the details, let’s establish some context regarding the framework and key actors in Chapter 2.
1 TE prepared the first edition of this chapter and updated this chapter in October 2024.
2 Framework and relevant actors
Antonia Brozek, Dr. Stephanie Stengel, Dr. Thomas Ecker2
2.1 Journey towards the EU HTA regulation: First initiatives and key milestones
Regulation (EU) 2021/2282 of the European Parliament and of the Council of 15 December 2021 on health technology assessment and amending Directive 2011/24/EU (referred to in this book as “the HTAR”) represent a ground-breaking step in the regulation of benefit assessments for new therapies in Europe. The HTAR became effective in January 2022 after lengthy and sometimes contentious negotiations. As explained in Chapter 1, its primary goals are to facilitate more timely access to new therapies for patients, avoid duplication of work, and promote consistency in clinical assessments of health technologies. EU HTA is conducted in parallel with the EMA regulatory approval process.
The precursor of joint HTA at the European level was central authorisation. As early as 1995, the EMA published the results of the first centrally authorised human medicine, setting an example for harmonising not only the authorisation procedures for medicines in the EU but also setting expectations for the joint benefit assessment of health technologies.
Building on this achievement, the European Commission funded three key projects to facilitate collaboration in HTA methods and operations between 1994 and 2002: EUR-ASSESSP, HTA-Europe, and ECHTA/ECAHIP. Following this, in 2004, the European Commission and Council of Ministers identified HTA as a political priority and acknowledged the need to establish a European network dedicated to HTA. In response to a Commission call in 2005, a consortium of organisations from various European countries, led by the Danish Centre for Evaluation and Health Technology Assessment, initiated the activities that led to the inception of the EUnetHTA Project.
2.1.1 EUnetHTA Project 2006–2008
The EUnetHTA Project expanded upon previous collaborative efforts in European HTA and established an organisation with a total of 64 partners. These included 50 organisations from European countries, along with five partners from Australia, Canada, Israel, and the United States, as well as nine international organisations.
The EUnetHTA Project had a three-year work programme aiming to establish an efficient and sustainable network for HTA across Europe. Its focus was to develop and implement practical tools to support HTAs in member states. The strategic goal of the network was to connect HTA agencies, research institutions, and health ministries, facilitating the exchange of information, supporting health policy decisions by the member states, and providing assistance to countries with limited HTA experience.
To accomplish these goals, work packages were created to achieve a broad range of key deliverables (Table 1).
Table 1: Work packages, objectives, and deliverables in the EUnetHTA Project 2006–2008
Specific objectives
Key deliverables
Work Package 1: Coordination
• To establish the organisational and structural framework for the network with a supporting secretariat
• The EUnetHTA organisational structure including a supporting secretariat
• Interim and final technical reports; EUnetHTA conference presenting the project results
• Development of proposal for future HTA collaboration in Europe from 2009 onwards
• Sharing of information about assessments of two specific health technologies (human papillomavirus infection, age-related macular degeneration)
Work Package 2: Communications
• To effectively disseminate and handle HTA results, information sharing, and coordination of HTA activities through the development and implementation of elaborate communication strategies and description of clearinghouse functionality
• Communication strategy.
• A clearinghouse functionality – detailed identification of the clearinghouse needs of different target groups and consecutive structure development to be ready for practical application after three years.
• EUnetHTA conference presenting the project results
• Website/Information platform
• Working prototype of the “HTA Information System” to enable networking and a platform for EUnetHTA tools
Work Package 3: Evaluation
• -
• Internal evaluation of the project
• Framework for external evaluation
Work Package 4: HTA Core Model
• To produce generic Core Models for HTAs on two essential categories of health technology questions: interventions and treatment, as well as core HTAs on selected topics for each category
• HTA Core Model
• Pilot examples of HTA core information for medical/surgical interventions and diagnostic technologies
• A handbook on the HTA Core Model
Work Package 5: HTA Adaption Toolkit
• To develop and implement generic tools for adapting assessments made for one country to new contexts.
• A toolkit for adapting core HTA results from existing HTAs into other contexts published on the web
• An HTA Glossary of adaptation terms
• Applicability testing on the basis of existing HTA reports in various national environments using the toolkit
Work Package 6: Transferability of HTA to health policy
• To develop and implement effective tools to transfer HTA results into applicable health policy advice in the member states and EU – including systems for identification and prioritisation of topics for HTAs and assessment of impact of HTA advice
• EUnetHTA open forum for stakeholders to exchange views and expectations/feedback on HTA
• A book containing a systematic overview of the HTA and health care policy links in selected member states and EU representing different health systems, remuneration systems, etc. – “HTA and health policy-making in Europe: current status, challenges and potential”
• A meeting with stakeholders and discussion/topic catalogue
• A strategy proposal for stakeholder involvement in the future
Work Package 7: Monitoring development of emerging and new technologies and prioritisation
• To structure prioritisation for HTA and provide health care decision makers with policy-relevant information on new and emerging technologies
• To provide tools to monitor the development of health technologies and to share data and results of this monitoring
• A newsletter providing structured information about high impact emerging/new technologies
• A web-based toolkit to facilitate European collaboration on evidence generation on promising health technologies
Work Package 8: System to support HTA in member states with limited institutionalisation of HTA
• To establish a support system for countries without institutionalised HTA activity
• Handbook on HTA capacity building for members states with limited institutionalisation of HTA, based on a survey of HTA organisations
• Information management in HTA organisations – Survey report
• HTA organisations report
• HTA curricula worldwide
One of the project’s most important achievements was the HTA Core Model®, which provides a structured framework for HTA information and offers guidance on essential content. By standardising the elements in HTA reports, this approach aims to promote transparency, improve report quality, and facilitate information extraction.
The HTA Core Model® identified nine domains as being relevant for HTA (Figure 17). Four of these are clinical (dark blue), and five are non-clinical (light blue).
Figure 17: HTA Core Model® (dark blue: clinical domains; light blue: non-clinical domains)
In each domain of the HTA Core Model®, specific topics are identified, such as mortality in the domain “clinical effectiveness”, accompanied by corresponding issues that the user can transform into concrete research questions, such as, “What is the effect of the technology on mortality?”
Within the framework of EUnetHTA Joint Action 1 (JA1), pilot assessments were conducted to test the HTA Core Model® on two new technologies: multi-slice computed tomography angiography and drug-eluting stents. Building on these assessments and users’ initial experiences with the tool, the HTA Core Model® has been revised and developed further, resulting in the release of version 3.0.
2.1.2 EUnetHTA Collaboration 2009
Building on the progress made during the EUnetHTA Project from 2006 to 2008, the EU-netHTA Collaboration 2009 was initiated with funding provided by its participants. The collaboration aimed to establish a permanent framework for cooperation in the field of HTA in Europe. In 2009, when the European Commission published a call for collective initiatives in public health, the EUnetHTA Collaboration submitted a funding application in response. This initiative ultimately led to the creation of the EUnetHTA Joint Actions (JAs), with the goal of advancing and deepening European networking in HTA.
2.1.3 Joint Actions and beyond
The EUnetHTA JAs were designed to deepen scientific cooperation and develop a common understanding in the field of HTA at the EU level. These cooperative efforts were funded under the EU Health Programmes.
Joint Action 1 (2010–2012)
The overarching objective of JA1 was to establish an effective and sustainable HTA collaboration in Europe, providing added value at the European, national, and regional levels. In particular, JA1 aimed to facilitate collaboration among HTA agencies across Europe and deliver context-specific reporting of HTA results. A detailed overview of the work packages, objectives, and final deliverables can be found in Table 2.
Table 2: Work packages, objectives, and deliverables in Joint Action 1 (2010–2012)
Specific objectives
Key deliverables
Work Package 1: Coordination
• To facilitate the achievement of the EUnetHTA Joint Action general objective of putting into practice an effective and sustainable HTA collaboration in Europe that brings added value at the European, national, and regional levels
• Interim and final technical and financial reports from the Joint Action
Work Package 2: Dissemination
• To facilitate coherent, effective, and sustainable external communication of the JA EU-netHTA, where its aims, objectives, work in progress, results and final products are known to all partners, identified stakeholders and target groups in the EU and national/regional levels
• Building on the communication strategy developed during EUnetHTA 2006-08 Project
Work Package 3: Evaluation
• To develop a general strategy and a business model for sustainable European collaboration on HTA
• To develop HTA tools and methods
• To apply and field test the developed tools and methods
• Analysis of results from evaluation activities (questionnaire and interviews)
• A report of evaluation results included into the final report from the Joint Action 1
Work Package 4: Core HTA
• To develop principles, methodological guidance as well as functional tools and policies for: producing, publishing, storing, and retrieving structured HTA information and core HTAs (including a new application of the HTA Core Model on screening)
• To develop two joint Core HTAs and methods for the production of Core HTAs on common topics, including experimenting with different methods of collaboration among agencies and agreeing upon methods to select topics and to involve stakeholders in the assessment process
• An online tool & service for producing, publishing, storing, and retrieving HTA information
• Screening the application of the HTA Core Model
• Two completely new core HTAs on topics that are pertinent to several HTA agencies and that can be utilised when producing local HTA reports in the same topics
Work Package 5: Relative Effectiveness Assessment of Pharmaceuticals
• To develop principles, methodological guidance as well as functional online tools and policies for REA by identifying areas where methodological guidance is needed and by providing it, suggesting ways to integrate REA of pharmaceuticals as a special version of the Core Model
• To test and implement a REA group of pharmaceuticals in line with the core HTA development
• Methodological guidance that will be appropriate for the assessment of relative effectiveness of pharmaceuticals
• A relative effectiveness assessment of a (group) of pharmaceuticals
Work Package 6: Information Management System
• To provide a contemporary information management system which ensures compatibility and interoperability across the WPs’ tools to support collaborative HTA work and ensure rapid dissemination of HTA results within the JA
• An Information Management System (IMS) and the related documentation, processes, and policies
Work Package 7: New Technologies
• To support the collaboration on new technologies and to contribute to reducing duplication of work by exchanging information on and developing tools to facilitate evidence generation
• To exchange information on current assessments of new health technologies
• An operational web-based toolkit including database containing information on evidence generation on new technologies
• A quarterly communication protocol for information flow on ongoing/planned national assessments of same technologies
Work Package 8: Strategy and Business Model Development
• To develop and construct a detailed business model for collaboration addressing the sustainability of the HTA collaboration within EU
• A stakeholder involvement policy for implementation through a Stakeholder Forum (i.e., European umbrella organisations of policymakers, patient organisations, health care professionals, industry, health related media)
• Development of a collaborative business model for sustainability
An important objective of JA1 was to develop the following nine methodological guidelines to foster a common understanding of the methodology applied in HTAs of medicinal products:
• Clinical endpoints
• Composite endpoints
• Surrogate endpoints
• Safety
• Health-related quality of life
• Choice of comparator
• Direct and indirect treatment comparisons
• Internal validity
• Applicability
These guidelines served as the foundation for developing the deliverables that were produced as part of EUnetHTA 21 and preceded the guidance documents from the Coordination Group.
Within JA1, Europe saw its first joint assessments. These spanned various subjects, from assessing the potential benefits of population-based systematic screening for abdominal aorta aneurysms to evaluating several diagnostic tests for predicting breast cancer recurrence. A further assessment was conducted for pazopanib, a medicinal product indicated for the treatment of advanced renal cell cancer. This evaluation was based on a submission file provided by the marketing authorisation holder. Importantly, the three pilot assessments conducted using the HTA Core Model® revealed divergent perceptions and methodological approaches, underscoring the need for deepening and further developing a common methodology and understanding of HTA.
Joint Action 2 (2012–2015)
In early 2011, the EU and its member states made a direct appeal for the formation of a sustainable HTA network, which gained formal recognition at the European level through Directive 2011/24/EU. Article 15 of this directive specified that the EU must provide support and enable collaboration in HTA by creating a voluntary network of national authorities or bodies designated by the member states.
In response to this directive, EUnetHTA Joint Action 2 (JA2) was launched, aiming to meet the HTA collaboration and coordination needs articulated by the EU and its member states. To meet this aim, a number of objectives were formulated, such as creating a comprehensive strategy, laying down guiding principles, and presenting an implementation plan for sustained European collaboration in HTA. A detailed overview of objectives and deliverables is given in Table 3.
Table 3: Work packages, objectives, and deliverables in Joint Action 2 (2012–2015)
Specific objectives
Key deliverables
Work Package 1: Coordination
• To coordinate the activities in the WPs and assist the Secretariat with timely reporting and providing information on request
• To adjust the JA1 standard operating procedure (SOP) manual (with details on management/governance, procedures and forms) and develop and update a three-year JA2 Work Plan as needed
• To prepare reports to the EAHC and ensure rigorous quality assurance of JA 2
• To organise three annual Plenary Assembly (PA) and six WP1 meetings in different member states. Representatives of DG SANCO, EAHC, DG RTD and other relevant EU bodies (e.g., EMA, CIE) and representatives of the JA2 Stakeholder Forum will be invited to the PA meeting and at the level of work packages where appropriate and at their own expense. PA will decide the JA’s working and management plan, providing the opportunity for JA participants to meet and strengthen JA dynamics. JA 2 EC will be responsible for potential conflict resolutions between the partners and stakeholder involvement activities
• Recommendations on the implementation of a sustainable
• European network for HTA
• Final report from the JA
Work Package 2: Dissemination
• Dissemination of the joint action
• Report on yearly training courses on EUnetHTA tools and methodology
Work Package 3: Evaluation
• To test the capacity of national HTA bodies to produce structured core HTA information (full core/rapid HTAs) together and apply it in national context (including collection of data on costs and overall efficiency of the production in the network)
• To implement, pilot, and further develop models and tools as well as production processes to support collaborative production of core HTA information with reinforced secretariat and coordination function
• To produce recommendations on the design and running of the EU HTA cooperation process based on analysis of various coordination capacities for the permanent secretariat function and further testing of involvement of stakeholders in network activities
• To provide a conceptual and information management infrastructure and related services to support the piloting of collaborative production of HTAs by partner agencies and facilitate the tasks and team working of the other WPs
• To increase awareness and understanding of the usefulness of the EUnetHTA tools, methods, and results among EUnetHTA partners and stakeholders. Develop and test a methodological basis for European cooperation on HTA including guidelines for distinct methodological issues and quality improvement of evidence generation for HTA
• -
Work Package 4: Testing collaborative production of HTA information for national adaptation and reporting
• To test the capacity of national HTA bodies to produce structured core HTA information (full core/rapid HTAs) together and apply it in national context (including collection of data on costs and overall efficiency of the production in the network)
• To implement, pilot, and further develop models and tools as well as production processes to support collaborative production of core HTA information with reinforced secretariat and coordination function
• To develop and test a methodological basis for European cooperation on HTA including guidelines for distinct methodological issues and quality improvement of evidence generation for HTA
• -
Work Package 5: Applying the HTA Core Model for Rapid Assessment for national adaptation and reporting
• To test the capacity of national HTA bodies to produce structured core HTA information (full core/rapid HTAs) together and apply it in national context (including collection of data on costs and overall efficiency of the production in the network)
• To implement, pilot, and further develop models and tools as well as production processes to support collaborative production of core HTA information with reinforced secretariat and coordination function
• To develop and test a methodological basis for European cooperation on HTA including guidelines for distinct methodological issues and quality improvement of evidence generation for HTA
• Pilot rapid assessments
Work Package 6: Information Management Infrastructure and Services (IMIS)
• Provision of an information management infrastructure and the related services to support the piloting of collaborative production of HTAs by partner agencies and facilitate the tasks and team working of the other WPs
• Report on Information Management Infrastructure and Services
Work Package 7: Methodology development and evidence generation: Guidelines and pilots production
• To implement, pilot, and further develop models and tools as well as production processes to support collaborative production of core HTA information with reinforced secretariat and coordination function
• To develop and test a methodological basis for European cooperation on HTA including guidelines for distinct methodological issues and quality improvement of evidence generation for HTA
• Guidelines and pilots to improve quality and adequacy of initial and additional evidence generation
• Methodological guidelines and templates to support production of core HTA information and rapid assessments
Work Package 8: Maintenance of HTA Core Model infrastructure to support shared production and sharing of HTA information
• To implement, pilot, and further develop models and tools as well as production processes to support collaborative production of core HTA information with reinforced secretariat and coordination function
• To provide a conceptual and information management infrastructure and related services to support the piloting of collaborative production of HTAs by partner agencies and facilitate the tasks and team working of the other WPs
• To develop and test a methodological basis for European cooperation on HTA including guidelines for distinct methodological issues and quality improvement of evidence generation for HTA
• Upgraded and updated application package of HTA Core Model
The activities carried out in JA2 included establishing processes for early dialogues, early (rapid) HTAs such as rapid relative effectiveness assessments (REAs), and full/comprehensive HTAs. Additionally, a strong emphasis was placed on implementing and further developing suitable tools, such as the HTA Core Model®, as well as developing, testing, and refining methodological guidance.
Within the scope of JA2, a total of 11 early dialogues took place, with nine focusing on medicinal products and two on medical devices. Furthermore, the initiative conducted three full/comprehensive assessments along with 12 REAs, divided equally between medicinal products and other technologies. An overview of the assessments can be found in Table 4. Additionally, during JA2, five new methodological guidelines were developed.
Table 4: Overview of the assessments carried out as part of JA2
JA2: Full/comprehensive assessments
• Faecal immunochemical test (FIT) versus guaiac-based faecal occult blood test (FOBT) for colorectal cancer screening (Core HTA 1)
• Use of intravenous immunoglobulins for alzheimer’s disease including mild cognitive impairment (Core HTA 2)
• Structured telephone support (STS) for adult patients with chronic heart failure (Core HTA 3)
JA2: Rapid relative effectiveness assessment (REA) of medicinal products
• Canagliflozin for the treatment of type 2 diabetes mellitus
• Sorafenib for the treatment of progressive, locally advanced or metastatic, differentiated (papillary/follicular/hürthle cell) thyroid carcinoma, refractory to radioactive Iodine
• Rapid relative effectiveness assessment of new pharmaceuticals for the treatment of chronic hepatitis C
• Ramucirumab in combination with paclitaxel as second-line treatment for adult patients with advanced gastric or gastro-oesophageal junction adenocarcinoma
• Vorapaxar for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI)
• Zostavax for the prevention of herpes zoster and postherpetic neuralgia
JA 2: Rapid relative effectiveness assessment (REA) of other technologies
• Balloon eustachian tuboplasty for the treatment of eustachian tube dysfunction
• Biodegradable stents for the treatment of refractory or recurrent benign oesophageal stenosis
• Duodenal-jejunal bypass sleeve for the treatment of obesity with or without type 2 diabetes mellitus
• Endovascular therapy using mechanical thrombectomy devices for acute ischaemic stroke
• Renal denervation systems for treatment-resistant hypertension
• Transcatheter implantable devices for mitral valve repair in adults with chronic mitral valve regurgitation
Importantly, JA2 also involved an evaluation of how frequently its assessments were used at the national level. This revealed 40 examples of national uptake, a finding viewed by EU-netHTA as a success.
The inclusion of a stakeholder forum was another crucial component of JA2, seeking to promote efficient information exchange with relevant stakeholders. Ultimately, 19 organisations representing patients/consumers, health care providers, payers, and industry took part.
In their executive summary, published in May 2016, EUnetHTA concluded with their vision of establishing a standardised process for European HTAs by 2019. This vision aimed to ensure the production of HTAs that are fit for purpose, efficient, and of high quality.
Joint Action 3 (2016–2021)
As part of Joint Action 3 (JA3), 81 organisations from 29 countries participated in the EU-netHTA collaboration led by the Dutch National Health Care Institute (ZIN) as project coordinator.
The strategic objectives outlined by EUnetHTA JA3 included the development of a sustainable European model for future HTA collaboration. In JA3, several procedural changes were made compared to JA2. Their aim was to improve the usability, transparency, and inclusiveness of REAs, with a focus on the requirements of HTA bodies. Additionally, JA3 sought to improve transparency through the publication on the EUnetHTA website of guidance, templates, and further information on EUnetHTA activities.
Beyond REAs, JA3 focused on several other important HTA activities. One of these was the initiation of early dialogues, during which various HTA agencies offered advice to health technology developers about the generation of evidence. Additionally, JA3 was involved in activities related to post-launch evidence generation (PLEG). Lastly, JA3 partners also recognised the need to expand their collaborative HTA efforts to include horizon scanning and reassessment activities.
A detailed overview of work packages, objectives, and deliverables in JA3 is given in Table 5.
Table 5: Work packages, objectives, and deliverables in Joint Action 3 (2016–2021)
Specific Objectives
Key Deliverables
Work Package 1: Network Coordination
• To provide scientific and technical coordination support for European collaboration activities in HTA to the integration of those activities in the whole life cycle of technologies, which lead to the development of a final sustainable model for the scientific and technical mechanism of a permanent cooperation in HTA
• To provide coordination support to the network and the Joint Action 3 activities that increase the use, quality and efficiency of joint HTA work at the European level to support evidence-based, sustainable and equitable choices in health care and health technologies, and to ensure re-use in regional and national HTA reports and activities, notably in order to avoid duplication of assessments
• Sustainable model for the scientific and technical mechanism of a permanent European cooperation on HTA
• Work plan for continuous interaction between regulators (EMA) and European scientific and technical cooperation (JA3)
• SOP manual and 4-year work plan
• JA3 interim and final reports
• Final version of the metric tool to monitor and provide feedback on the use and uptake of national implementation of joint products
• Work plan for continued interaction post-2020 between regulators (EMA) and the Joint Action 3
• Sustainable model for European cooperation: Final Implementation Report
• Network infrastructure and technical support for collaborative work
• Final report from the Joint Action 3 (technical and financial)
Work Package 2: Dissemination
• Disseminate information on Joint Action 3 both to general public and the stakeholders
• Actively identify and engage stakeholders throughout the course of the project in order to ensure that the results of the project are applicable and appropriate to stakeholders
• Develop post-2020 model of European HTA network in terms of effective communication with the key stakeholders
• Improve knowledge, capacity and use of the EUnetHTA methodologies, tools and products in close collaboration with Work Package 6
• Leaflet
• Stakeholder analysis and stakeholder registry
• Report on overall training strategy and EU-netHTA portfolio
• Dissemination plan
• Final report describing the JA3 dissemination activities and strategies to support the development of a sustainable network in terms of communication.
• Layman version of the final report, written for the interested public as a target group
Work Package 3: Evaluation
• Verify if Joint Action 3 is being implemented as planned and reaches the objectives through evaluation activities
• Identify to what extent the individual work packages enable Joint Action 3 to meet its objective, a sustainable mechanism of HTA cooperation in Europe
• Contribute to the development and evaluation of the metrics tools to monitor and evaluate the uptake of EUnetHTA products at the national, regional and local level
• Annual reports on efficiency gains and added value
• Final report on findings from the project and analysis of how to bring the knowledge forward after 2020
Work Package 4: Joint Production
• To produce joint health technology assessments. The joint assessments should be fit for purpose, of high quality, of timely availability, and cover the whole range of health technologies
• To refine the production processes of joint assessment reports based on lessons learned and experiences from Joint Action 2 and probe a stepped roll-out of additional collaborative assessments yielding timely information
• To develop and refine a system of horizon scanning, topic selection and prioritisation in close collaboration with the Liaison Committee and relevant Work Packages
• To develop a process that facilitates the implementation of the joint assessment in the national and regional practice
• To provide input on final processes and recommendations for a sustainable model of European collaboration on joint assessments after 2020
• Produce joint assessments and collaborative assessments:
• 18 Joint Assessments and 25 Collaborative Assessments on other technologies
• 33 Joint Assessments and 4 Collaborative Assessments on pharmaceuticals. Please find them here in the REA table
• Deliver a refined production process for joint assessments (relative effectiveness assessments)
• Implement a stepwise work division towards decentralised project management
• Develop and refine a system for horizon scanning, topic selection and prioritisation of health technologies for relative effectiveness assessments
• Facilitate the implementation of joint assessments in national/local practice
• Provide input on recommendations for a sustainable model of European collaboration on joint assessments after 2020
Work Package 5: Lifecycle Approach to improve Evidence Generation
• Early dialogues (initial evidence generation)
• Post-Launch Evidence Generation (PLEG) and Registries
• Develop and establish an organisational structure for EDs
• Evaluate how the collection of fees from industry and the redistribution among partners could best be implemented
• Deliver 33–35 Early Dialogues
• Conduct 8 PLEG pilots on technologies (drugs, devices, procedures) or diseases of common interest. Such pilots consist of:
- Defining a common research question for additional (post-launch) evidence generation
- Defining a minimum data set for registries or a core common protocol
- Whenever possible, sharing the produced additional data
• Produce a practical tool to assess the quality of registry data to be used in HTA (“Quality standards for Registries tool”), mainly building upon the work of the PARENT Joint Action
• Produce a document summarising key learnings from JA3 and providing recommendations for a permanent HTA cooperation on PLEG
Work Package 6: Quality Management, Scientific Guidance and Tools
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