An opportunity to shape the EU HTA process?

On January 11^th 2022 Regulation (EU) 2021/2282, the European regulation on health technology assessment (EU HTA regulation), came into force which establishes the clinical assessment of medicinal products, high risk medical devices and class D in vitro diagnostics at European instead of national level. The implementation of the regulation will start in January 2025 with oncology products and ATMPs, followed by orphan medicinal products in January 2028 and all further products in scope in January 2030.

In order to facilitate a smooth implementation of the regulation, EUnetHTA 21 is not only assigned to perform 6-8 Joint Scientific Consultations (JSC) as well as 1-2 Joint Clinical Assessments (JCAs) but also to develop urgently needed guidance documents until 2023. EUnetHTA 21 is a consortium consisting of 13 European HTA bodies with Germany being the only country represented by two HTA bodies, the German Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG) and the German Federal Joint Committee (Gemeinsamer Bundesausschuss, G-BA). The developed guidance documents in combination with the learnings from the performed JSCs and JCAs will later be adopted by the Coordination Group and/or considered for the drafting of implementing legislation by the European Commission. Hence, the content and quality of these documents is of utmost importance for all stakeholders: regulators, HTA-bodies, patients, experts, clinicians and finally health technology developers (HTDs).

Each draft deliverable is written by a hands-on group consisting of a selection of EUnetHTA 21 members and made available for public consultation. After consideration of the comments received, the deliverable is adapted by the hands-on group, reviewed, validated and endorsed by all EUnetHTA 21 members, and finally published together with all comments received during the public consulation as well as EUnetHTA 21's response to those comments. Timelines for duration of the public consultation phase and timepoint of publication of the final deliverable are provided in an overall project plan.

Deliverable D4.2 describes the scoping process, which is used to define the relevant PICOs (Population, Intervention, Comparator and Outcomes) which shall meet all member states needs and have to be presented by the HTD in the dossier and are subsequently assessed by the assessor and co-assessor.

Public consultation for this deliverable took place from May 2^nd to May 31^st, 2022, and publication of the final deliverable was scheduled for July 29^th, 2023. With more than 130 pages of comments received from different stakeholders, including SKC, the publication of its final version was delayed to "ensure it is fit-for-purpose with the HTA regulation" and only made available last week on September 12^th.

Although most comments addressed similar topics and argued predominantly in the same direction, only few led to alterations of the deliverable. Some comments resulted in further clarifications, but the vast majority were not implemented. The most relevant changes between the draft and final version of the deliverable but also comments which were not considered are listed below. In case you are interested in an even more detailed overview of the implemented and disregarded comments and EUnetHTA 21's rational, we are happy to share and discuss with you a respective analysis upon request.

• A specification that input from EU patients and experts will be taken into account and provided to member states (MS) during the PICO survey, since involvement of EU patients and clinical experts is a requirement per EU HTA regulation. National input is not enforceable on the basis of the EU HTA regulation and has to be realized on MS level.

• Binding deadlines for MS (e.g. for PICO survey) and HTA bodies (e.g. for information to HTD) were not added, as D4.2 only contains unique timelines stated in the EU HTA regulation.
• Input from MS in the PICO survey will not be binding on national level. Mandatory use of the PICO that a MS provides in the PICO survey is not a (legal) requirement from the EU HTA regulation and the discussion on the national process is considered out of the scope of the regulation and this guideline. It is up to the MS to decide how their input into the scoping process will affect their processes on the national level.
• The HTD will not be informed how many and which MS require which PICO. EUnetHTA 21 states that the information on individual MS PICOs would not have any further positive impact to the JCA process and will therefore not be provided.
• Rules and procedures for a potential change in the finalized PICO if any of the PICO-elements change from the assumptions used at the time of scoping (e.g., due to a late label change) are needed. However, a label change during the EMA process is assumed to be "relatively infrequent" (10% of the cases) by EUnetHTA 21. This will partly be addressed in an implementing act (interaction with EMA), as presently no solution can be given.
• MS will list the most relevant comparators according to their policy question. Off-label comparators are not excluded by default and no clear criteria for their selection will be provided.
• The 'OR'-description for optional comparators during the scoping process may lead to the exclusion of the comparator (or other best available evidence) in the trial. However, EUnetHTA 21 argues that it is rather unlikely that the most relevant, evidence based, comparator is listed by one MS only and therefore will not be part of the final PICOs. To obtain the lowest number of PICOs, not all optional PICOs may be selected as a consequence of the consolidation process. A situation where, due to the response of a single MS, a relevant (optional) comparator is excluded, might be resolved through this process.
• MS are free to define their Intervention and Population, according to their national needs. The population of the Summary of medicinal Product Characteristics (SmPC) is (only) the starting point of the PICO survey. A clear rational (medical or other) for their PICO input will not be requested from the MS, given that the rationale for a PICO is the research question coming from their health care system.

Overall, the assessment of the changes made, and the comments dismissed paint a disappointing picture of consideration of the more than 130 pages of comments received for this important deliverable, most of which were carefully researched and well substantiated. Thus, it is very clear that currently the HTA bodies have by far the greatest influence on the design of guidance documents for the EU HTA process, and that other stakeholders such as patient representatives and HTDs are formally consulted but can hardly influence the content.

However, since adoption by the Coordination Group and/or consideration for the drafting of implementing legislation by the European Commission are still pending, further engagement in stakeholder networks and an open exchange of opposing views on and potential implications of certain decisions and wordings are of great importance.

SKC is an active member of the EUnetHTA 21 stakeholder network participating in the public consultation of draft deliverables. Thus, and by participating in additional related conferences as well as by monitoring relevant sources, we also keep up with current developments and new available information and can use this directly for indication-specific as well as holistic strategy development for our clients.

In case you are interested in more information on and discussion of the new requirements under the EU HTA regulation, are looking for a strategic sparring partner for preparing your company or individual departments for the new regulation or whish for support in preparing a JSC or JCA for the first time, get in touch with us!

Sources:

• Regulation (EU) 2021/2282
• EUnet HTA project plan
• Deliverable D4.2
• EUnetHTA 21 Public Consultation: Merged comment form D4.2 – Scoping phase