EU HTA flawed by design?
Guideline development for the European health technology assessment
In order to facilitate a smooth implementation of the EU HTA regulation until it is in effect for oncology products and advanced therapy medicinal products (ATMPs) in 2025, EUnetHTA 21, a consortium of national HTA bodies, is commissioned to develop deliverables as guidance documents in which the methodological and procedural details of the EU HTA process are described.
Before each deliverable is published in its final form, it undergoes a public consultation process where stakeholders can comment on and recommend changes to a draft version of the deliverable. As part of the EUnetHTA 21 Stakeholder Network SKC is involved in the public consultation process of every deliverable relevant for our clients.
With the publication of deliverables D4.3.1 "Practical guideline for direct and indirect comparisons", D4.5 "Practical guideline on applicability of evidence", D4.6 "Practical guideline on validity of clinical studies", D5.1 "Guidance for submission dossier" and D5.2 "Guidance for JCA report" on December 16th, 2022 and D4.4 "Endpoints" on January 26th 2023 over half of the deliverables eligible for public consultation are now available in their final version.
Overview of the status of EUnetHTA 21 deliverables eligible for public consultation (as of February 1st 2023)
|D4.3.1/2||Practical/ Methodological Guideline on Direct and indirect comparisons||Published with delay|
|D4.4||Endpoints||Published with delay|
|D4.5||Applicability of evidence||Published with delay|
|D4.6||Validity of clinical studies||Published with delay|
|D4.7.1/2||Assessment of High-Risk Medical Devices||Published|
|D5.1||JCA/CA Submission Dossier Template||Published with delay|
|D5.2||JCA/CA Assessment Report Template||Published with delay|
|D5.3.1/2||Procedural guidelines for appointing assessors and co-assessors; HTAb technical expert working groups||Published|
|D4.7.3/4||EUDAMED data reporting template / Guidance for EUDAMED-based TISP process||Public consultation completed in time, publication of final version delayed|
|D7.1.1/2/3||Guidance for the interaction between HTD and HTA (for JCA and JSC)||Public consultation completed in time, publication of final version delayed|
|D7.2/3||Guidance and template for the interaction with patient representative, healthcare professional and other experts||Public consultation completed in time, publication of final version delayed|
|D6.2/3/4||JSC Template Briefing Book, Template JSC Report Procedural Guidance JSC||Public consultation pending (01.-31. August 2023)|
Comparison of recent batch of final deliverables
A comparison of this recent batch of final deliverables with their respective drafts provided the following main insights:
Similar to deliverable D4.2, barely any substantial changes were made as a result of the public consultation process - adopted comments were mostly related to wording issues (e.g., "Effectiveness: describes how well a treatment works in practice; [...]" was changed to "Effectiveness: describes how well a treatment works in patients; [...]" in deliverable D4.3.1).
- The numerous comments asking for a harmonized European methodology (especially with regards to statistical requirements) were rejected across several deliverables. Hence, it becomes apparent that EUnetHTA 21 does not aim to design a consolidated pan-European EU HTA process. Instead, the individual requirements of every member state will simply be collected and will have to be addressed by the health technology developer simultaneously.
- The large number of comments asking for special consideration of the challenges orphan drugs and ATMPs face with regards to the conduction of clinical trials and generation of evidence was also disregarded. Instead, EUnetHTA 21 doubled down on their conception that single-arm trials are not compatible with the principles of the EU HTA regulation ("The HTAR clearly defines JCA as 'the scientific compilation and the description of a comparative analysis of the available clinical evidence on a health technology in comparison with one or more other health technologies or existing procedures' (Article 2). Considering the above, we reaffirm that individual uncontrolled studies (single-arm trial, case-series for example) are of limited value in the HTAR context, because they cannot allow a comparative/relative evaluation, which is the cornerstone of HTA, as reminded in the HTAR (Article 2 and 9)."- D4.6 Public consultation comments and responses).
However, when pivotal trials for orphan drugs and ATMPs are designed as single-arm trials this is not due to a preference of the HTD, but because a low disease prevalence and/or incidence in combination with ethical concerns do not allow for a different study design. Ethical considerations and the actual feasibility of studies were thus not taken into account in the design of the guidelines. Although it will remain in the hands of individual member states whether they will accept single-arm trials for the benefit assessment of a novel health technology, it is hard to imagine a destructive judgment of the evidence in the European JCA report will not have a negative impact on the national HTA process for these health technologies.
A pro forma process?
Looking at the lack of comment adoption and their often insufficiently justified rejection in this latest set of final deliverables, one could get the impression that the public consultation is a pro forma process without serious intend to involve stakeholders and jointly shape an efficient and meaningful EU HTA.
Although there is a chance for further modification of the deliverable contents when they are adopted by the European Commission (EC) through the implementing acts planned for Q4 2024, it is doubtful whether there will be significant changes since an EC HTA working group has already reviewed the published deliverables. To still facilitate the urgently needed change, several interest groups are becoming increasingly active, as the German Pharmaceutical Industry Association (Bundesverband der Pharmazeutischen Industrie e. V., BPI) published a position paper together with the German Association of Research-Based Pharmaceutical Manufacturers (Verband Forschender Arzneimittelhersteller, VFA) criticizing the current state of affairs regarding the EU HTA process and EUCOPE announced that they will work together with the European Expert Group of Orphan Drug Incentives to ensure that the EU HTA process will not lead to a growing discrimination of orphan drugs.
We are the market access special forces.
In the face of these developments, it becomes increasingly clear that for the successful market access of a novel health technology under the EU HTA regulation, the preparation of a sound pan-European value story, an early gap analysis and the development of a conclusive strategy to address potential evidence gaps both on a European and on a national level are key success factors.
In case you are interested in discussing these recent developments and their potential implications for your product, are looking for a strategic sparring partner to optimize your companies EU HTA strategy or you are looking for strategic and operational support for the preparation of a JSC or JCA under a framework that addresses all crucial success factors, get in touch with us! We are also happy to share a detailed comparison of each final deliverable with its draft upon request. We are the market access special forces.
- 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
- EUnetHTA: Joint HTA work
- EUnetHTA: D4.3.1 Direct and indirect comparisons
- EUnetHTA: D4.6 Public Consultation comments and responses
- EC: Updated rolling plan - Implementation of the Regulation on health technology assessment (December 2022)
- BPI Pressemeldung (11.01.2023)
About the author
M.Sc. Drug Research and Development
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