The EU HTA Regulation and Joint Clinical Assessment: What It Means for Systematic Evidence Synthesis in Germany and the EU

Regulation (EU) 2021/2282, the EU HTA Regulation, entered into force on 11 January 2022 and has applied since 12 January 2025 [1]. This piece of EU pharmaceutical regulation creates a mandatory EU-level joint clinical assessment (JCA) of new medicines, moving clinical evidence assessment to EU level, starting with cancer medicines and ATMPs. For teams that produce a systematic review or clinical evidence dossier, evidence synthesis becomes a regulatory deliverable.

Joint clinical assessments phase in by product type, for medicines whose marketing authorisation application is submitted after each date (Table 1) [1]. Use the dates in Article 7(2) of the Official Journal text when quoting an exact day.

A medicine enters JCA scope when its marketing authorisation application, under the centralised procedure, is submitted after the date for its product group. ATMPs and orphan medicines qualify through the centralised procedure even without a new active substance, and new therapeutic indications of medicines that already had a JCA are also covered [1]. From 12 January 2025 the Commission may also select certain high-risk medical devices and in vitro diagnostics for joint clinical assessment [1].

The JCA is a clinical assessment only. In Germany, the national early benefit assessment under section 35a of the Social Code Book V (AMNOG) continues, and the G-BA states that it will usually begin after the European assessment [2]. Because the joint assessment is tied to the marketing authorisation application, the evidence base has to be ready earlier than a national-only launch would require. Teams that wait for the national dossier to start their searches risk repeating work.

• Answer the agreed PICO questions. Population, intervention, comparator and outcome questions define what the assessment examines, and Member States contribute their national requirements [1]. A dossier may need to answer several PICO questions, not one. Our guide to the PICO framework explains the structure.
• Make the evidence base traceable. Report every database, register and other source, with full search strategies and dates, so that the search is reproducible [5].
• Cover unpublished evidence. Trial registries, regulatory documents and conference abstracts can hold data that journals do not. Our guide to grey literature in systematic reviews shows where to look.
• Plan comparisons early. Where head-to-head trials are missing, teams usually need an indirect treatment comparison or network meta-analysis, and the method should be pre-specified.

1. Place your product in Table 1 and note when the marketing authorisation application will be submitted.
2. Confirm the PICO scope you must answer, including the appropriate comparator the G-BA specifies for the German dossier.
3. Write one search protocol that can serve both the joint assessment and the German dossier.
4. Document searches to PRISMA-S from the first day, not at submission [5], and report selection with a PRISMA 2020 flow diagram [6].
5. Align timelines with the German clock: the company submits its dossier no later than market launch, the G-BA (usually through IQWiG) publishes the benefit assessment within three months, and the G-BA passes its resolution after a further three months [4].

Germany’s seats in the Member State Coordination Group on HTA (HTACG) are held by the Federal Ministry of Health, the G-BA and IQWiG. The G-BA is responsible for German input on the PICO scope, and IQWiG works as an assessor or co-assessor in joint assessments [2, 3]. IQWiG’s own national methods are summarised in our guide to the IQWiG General Methods.

For HTA Germany, the national process runs on a fixed legal clock, so an evidence team now serves two audiences with one evidence base: the joint report and the German dossier. Keep search methods, selection criteria and extracted data consistent across both, under one regulatory evidence dossier plan.