EU HTA in Germany: What JCA means for AMNOG and the Delta-Dossier

What is Health Technology Assessment (HTA)?

Health Technology Assessment (HTA) is the systematic evaluation of health technologies to support decision-making in healthcare systems. Depending on the system, assessments may consider clinical effectiveness and safety as well as economic, organisational, social and ethical aspects.

The EU HTA Regulation does not harmonise every HTA decision across Member States. For medicines, mandatory European cooperation focuses in particular on the joint assessment of clinical evidence. Economic assessments and decisions on reimbursement and pricing remain national.

The Joint Clinical Assessment therefore does not determine the added benefit or monetary value of a medicine in Germany. It produces a common European report on clinical evidence, which is then considered in national HTA processes.

What does EU HTA cover?

The EU HTA Regulation establishes several forms of cooperation between Member States. For pharmaceutical companies, Joint Clinical Assessments and Joint Scientific Consultations are particularly relevant.

Which medicines are covered by EU HTA and when?

Mandatory JCAs are being introduced gradually. EU HTA readiness will therefore move from a concern for selected oncology and ATMP programmes to a standard part of European market access planning.

JCA and JSC under EU HTA: What is the difference?

JSC supports the planning of future evidence, while JCA assesses the clinical evidence that has actually been generated. This distinction makes populations, comparators, endpoints and evidence gaps relevant during clinical development, not only during dossier preparation.

How does a Joint Clinical Assessment work?

1. Start of the JCA in connection with the European marketing authorisation procedure
2. European scoping of the assessment questions
3. Definition of the assessment scope and relevant PICOs
4. Finalisation and submission of the JCA dossier by the manufacturer
5. Joint clinical assessment of the submitted evidence
6. Finalisation and publication of the JCA report
7. Consideration of the European assessment in national HTA processes

What does EU HTA mean for Germany

EU HTA creates a common European framework for the clinical assessment of health technologies. In the pharmaceutical sector, the focus is primarily on the Joint Clinical Assessment. Clinical data will be assessed jointly at European level so that Member States do not have to review the same evidence independently several times.

For Germany, this development is particularly relevant because AMNOG already provides an established procedure for early benefit assessment. The EU HTA Regulation therefore does not replace national assessment. Instead, it creates a new interface: European JCA results must be integrated into a national procedure that continues to follow its own assessment standards.

This particularly concerns the question of which populations, comparators, endpoints and subgroups are relevant for Germany. Even when a European JCA dossier is available, it remains necessary to assess whether the evidence it contains is sufficient for the German benefit assessment or whether additional national preparation is required.

For pharmaceutical companies, this creates a new planning task. EU HTA can reduce duplication if European and national requirements are considered together at an early stage. If this alignment does not succeed, parallel requirements emerge: a European JCA dossier on one side and a still demanding AMNOG dossier on the other.

Why JCA does not replace the AMNOG procedure

The Joint Clinical Assessment creates a common European basis for clinical assessment. It describes the submitted evidence, relevant effects and results in relation to the questions considered in the European procedure. However, it does not automatically result in a decision on the added benefit of a medicine in Germany.

The assessment of added benefit remains part of the national AMNOG procedure. The German assessment perspective, the appropriate comparator therapy, patient-relevant endpoints, methodological requirements and the requirements for the national dossier remain decisive. Pricing and reimbursement decisions also remain anchored at national level.

This creates an important distinction: the JCA can provide evidence that is referenced in the national procedure. But it does not automatically answer the German assessment question. What remains decisive is whether the European evidence fits the German question, particularly with regard to populations, comparator therapy, endpoints, subgroups and analysis methods.

For pharmaceutical companies, this means that a JCA dossier can be an important foundation, but it does not replace the strategic preparation of the AMNOG dossier. Companies that only address the national assessment after publication of the JCA report risk identifying too late where European and German requirements diverge.

Where EU HTA and AMNOG meet in practice

The key question is not whether JCA results will become relevant in the German AMNOG procedure. The key question is how they can be used there. European and German assessment processes do not automatically follow the same research question, the same comparator standard or the same methodological requirements.

The central transition point already lies in PICO scoping. At European level, population, intervention, comparator and outcomes are defined and consolidated for the JCA. For Germany, however, the decisive factor remains which question underlies the national benefit assessment. If the European PICO structure does not sufficiently reflect the German assessment perspective, additional translation work will be required later.

The appropriate comparator therapy is particularly relevant. While the JCA may bundle several European comparison questions, the German early benefit assessment is oriented towards the comparator therapy determined by the G-BA. If the evidence addressed in the JCA deviates from the comparator therapy relevant for Germany, a reference to the European dossier will not be sufficient.

Differences can also arise with endpoints, subgroups and analysis methods. Not every endpoint considered in the European procedure will automatically be suitable for the German benefit assessment. National requirements for analyses, evidence currency and dossier structure also remain relevant.

This means that the actual interface between EU HTA and AMNOG does not begin only when the national dossier is submitted. It begins earlier: with the question of whether European evidence is planned, structured and updated in such a way that it can be used robustly in the German procedure.

AMNOG process in Germany: what EU HTA changes — and what remains national

The AMNOG process is Germany’s early benefit assessment procedure for new medicines. Since 2011, it has provided the national framework for assessing the added benefit of a new medicine against the appropriate comparator therapy and for linking this assessment to subsequent price negotiations with the National Association of Statutory Health Insurance Funds. The procedure is based on §35a SGB V.

EU HTA does not replace this national decision framework. The Joint Clinical Assessment can provide a common European clinical evidence base, but it does not determine the added benefit of a medicine in Germany. The German assessment remains driven by the Federal Joint Committee, IQWiG, the appropriate comparator therapy, patient-relevant endpoints, subgroups, evidence currency and the national dossier structure.

For pharmaceutical companies, this means that AMNOG preparation starts well before national submission. The benefit dossier is usually prepared in parallel with the regulatory process and needs to be aligned early with the German assessment logic. This includes early G-BA advice, clarification of the appropriate comparator therapy, assessment of whether the evidence is transferable to the German care context and planning of additional analyses for Module 4.

From market entry to price negotiation

For a medicine with a new active substance, the benefit dossier must be submitted at the time of first market entry in Germany. Market entry is tied to the first listing in the Lauer-Taxe, usually on the 1st or 15th of a month. Separate timelines apply for indication extensions, and the G-BA also offers a formal completeness review that is useful no later than three weeks before final submission.

After submission, the benefit assessment is usually prepared by IQWiG. For orphan drugs, the G-BA performs the benefit assessment, while IQWiG addresses the target population and costs. The dossier and the benefit assessment are published three months after dossier submission. This is followed by a three-week written comments phase and an oral hearing at the G-BA.

The G-BA resolution is usually issued within around six months after dossier submission and forms the basis for the subsequent price negotiation with the National Association of Statutory Health Insurance Funds. Under EU HTA, this national process logic remains intact and cannot be inferred from the European report alone.

Why the appropriate comparator therapy remains the national anchor

The appropriate comparator therapy is the central national comparator in the AMNOG process. Added benefit generally needs to be demonstrated against this comparator. It reflects the German standard of care and is determined by the G-BA.

This becomes particularly important under EU HTA. A JCA may include several European comparison questions or reflect different clinical practice contexts. For Germany, however, the decisive question is whether the evidence is robust against the comparator therapy relevant to the German AMNOG procedure.

Where the JCA dossier does not sufficiently answer this national question, the Delta-Dossier becomes necessary. It needs to explain which evidence is usable against the German comparator benchmark and where additional national analyses or justification are required.

Regulatory approval and German benefit assessment follow different logics

Regulatory approval and German benefit assessment are separate procedures. Regulatory approval asks whether a medicine is effective, safe and of sufficient quality. German benefit assessment asks whether the medicine provides an added patient-relevant benefit compared with the appropriate comparator therapy.

The pivotal clinical trial is therefore not automatically sufficient for AMNOG. What matters is whether the study population matches the approved indication, treatment follows the product information, evidence is transferable to the German care context, endpoints are patient-relevant and the comparison against the appropriate comparator therapy is methodologically robust.

These aspects are addressed in Module 4 of the German benefit dossier and often require additional analyses. This is exactly why EU HTA can provide an important evidence base without replacing national assessment logic.

Where the Delta-Dossier fits into the AMNOG process

The Delta-Dossier becomes relevant at the interface between the European JCA dossier and the German AMNOG dossier. It assesses which parts of the European evidence package can be used for German benefit assessment and where national additions are required.

The Delta-Dossier is therefore not a shortened AMNOG dossier. It is the national translation layer that prepares European JCA evidence for robust use in the German AMNOG process.

A concrete practical example is the new insight on the first JCA for Tovorafenib/OJEMDA, which shows how PICO structure, comparator data, endpoints and uncertainty still need to be translated into national German decision logic.

• Reuse: use or specifically reference JCA content
• Selection: select relevant PICOs, populations, comparators and results
• Adaptation: adapt European analyses to national methodological requirements
• Addition: add national content, evidence updates, data cuts and supplementary analyses

When should preparation for JCA and AMNOG begin?

Preparation should begin well before the dossiers are drafted. As soon as PICO scenarios, potential comparators or national evidence requirements become foreseeable, differences between the European and German assessments can be identified.

Practical preparation models place initial activities approximately 1.5 to 2 years before planned JCA dossier submission. These include PICO data gathering, feasibility assessments, considerations around real-world data and indirect treatment comparisons, and systematic evidence packages. Closer to submission, activities include final analyses, trial readouts, alignment of local HTA content and evidence updates.

The later differences in populations, comparators, endpoints or evidence requirements are identified, the less room remains for additional evidence and analyses in Germany. European JCA preparation and national HTA planning should therefore be treated as connected workstreams.

What do the first Joint Clinical Assessments show for Germany?

The first published and discontinued JCAs show that PICO coverage, comparators, methodological usability and timing need to be considered together.

The first JCA for tovorafenib/OJEMDA covered several populations and a total of eight PICOs, while comparative evidence was available for only part of the questions. A matching-adjusted indirect comparison (MAIC) against dabrafenib plus trametinib was submitted but could not be used in the same way for Germany. The final JCA report was also not available when the German procedure started. The case demonstrates the limits of automatic transfer of European evidence.

Discontinued JCAs also highlight operational requirements: gaps in evidence completeness, PICO-specific analyses, methodological descriptions, relative effect measures, sensitivity analyses and underlying documentation can limit usability.