JCA dossier: Structure, evidence requirements and submission under EU HTA

The JCA dossier is the structured submission of clinical evidence by a health technology developer (HTD) for a Joint Clinical Assessment (JCA). It addresses the PICO questions in the final assessment scope and documents relevant studies, evidence searches, direct and indirect comparisons, and findings on relative clinical effectiveness and safety. The medicinal-product dossier template comprises six main sections and Appendices A to D.

Preparing a JCA dossier requires more than reusing a regulatory submission. The HTD must map the available evidence to each PICO, explain missing results, document statistical analyses transparently and provide the underlying materials needed for verification. Submission follows a tight timetable coordinated with the EMA procedure.

Regulatory reference date: October 2026. The technical details below are based on the HTACG Dossier Guidance and Table Template Collection (both version 1.0, adopted in November 2024). Any actual submission must follow the versions and procedural requirements applicable at that time.

JCA dossier at a glance

The JCA dossier provides the evidence relevant to the final assessment scope in a form that enables the assessor and co-assessor to examine the submitted studies and analyses. Its scope and complexity depend primarily on the PICOs and the available comparative evidence.

Difference between the JCA dossier and the JCA report

The JCA dossier is the developer's evidence submission; the JCA report is the output of the subsequent joint clinical assessment. The HTD compiles the studies, analyses and documentation. The assessor and co-assessor examine that evidence against the assessment scope and draft the JCA report.

The JCA report describes relative clinical effects and associated uncertainty. It does not determine clinical added value, pricing or reimbursement at EU level. The process and publication are covered in Joint Clinical Assessment (JCA): Process, timelines and requirements under EU HTA.

Legal framework and documents for preparing a JCA dossier

JCA dossier requirements derive from the EU HTA Regulation, its implementing rules and the documentation issued by the HTA Coordination Group. These sources have distinct functions.

Article 9(3) of Regulation (EU) 2021/2282 requires complete available evidence, appropriate analytical methods, transparent presentation and sufficient underlying documentation. The versions applicable at submission should be checked.

JCA dossier structure: six main sections and Appendices A to D

The official JCA dossier template organises the submission into six main sections and supporting appendices. The main document moves from the technology and assessment questions through methods to clinical results; the appendices provide supporting detail and verification materials.

Content of the six main JCA dossier sections

The six sections must connect the assessment scope, evidence methods and findings in a traceable manner. The executive summary should identify which PICOs are addressed by results, which lack results and what uncertainty surrounds the relative effects.

Background characterises the condition, target population, care context and intervention. Assessment Scope reproduces the final PICOs. Methods documents searches, selection and analyses. Results links findings to the PICOs, while References supports source verification.

The main text should make essential information intelligible without requiring readers to reconstruct conclusions from appendices. Detailed supporting material belongs in the designated annexes and files.

Role of Appendices A to D in the JCA dossier

Appendices A to D provide the additional information needed to verify the submitted clinical evidence. They do not replace a complete account in the main dossier.

Appendix A contains additional study, safety and subgroup details. Appendix B includes risk-of-bias information, certainty of relative effects and methodological details. Appendix C covers key clinical development studies not analysed PICO by PICO in the main text. Appendix D contains source materials such as clinical study reports, search documentation, analysis plans and, where required, code.

The applicable templates and specifications determine the binding subdivision, formats and technical requirements.

Addressing the assessment scope in the JCA dossier

The final assessment scope determines the clinical questions that the JCA dossier must address and document. For dossier preparation, the priority is to translate the final PICOs into evidence searches, study allocation and results presentation, rather than to repeat the scoping process.

Mapping clinical studies to JCA PICOs

Study mapping must show which clinical evidence addresses each PICO comparison. Eligibility criteria, populations, interventions, comparators and outcomes should be checked against the final assessment scope.

A study may address several PICOs, while another PICO may require additional studies or an indirect comparison. The mapping should distinguish direct comparative evidence from studies included in indirect syntheses. The development and consolidation of the scope are covered in JCA scoping and PICO: Assessment scope, comparators and evidence planning under EU HTA.

Documenting PICO coverage in the JCA dossier

The dossier must show which PICOs have results and which cannot be supported by suitable evidence. A large clinical development programme does not necessarily answer every question in the assessment scope.

For each PICO, the studies, comparison type, outcomes and analyses should be identifiable. Missing results should be stated and explained. Documented coverage is not equivalent to a positive methodological assessment of the evidence.

Handling missing comparative evidence

Missing direct or indirect evidence must be reported transparently in the JCA dossier. The HTD should explain whether gaps arise from absent studies, unsuitable comparators, different populations, unmeasured outcomes or the infeasibility of a defensible synthesis.

Documentation cannot replace missing data, but it enables a clear assessment of the evidence available for each question.

Differences in scope across the first published JCA dossiers

The first published JCA dossiers show that a common template must accommodate very different evidence packages. Tovorafenib, lurbinectedin, tarlatamab and onasemnogene abeparvovec differed in PICO numbers, available direct comparisons and the need for indirect analyses.

The practical implication for dossier preparation is the same: studies, analyses and missing results must be mapped clearly to the relevant PICOs. Detailed findings from the four assessments are discussed in the insight Joint Clinical Assessment: What the first four JCA reports reveal about evidence assessment.

Evidence identification and study selection for the JCA dossier

The JCA dossier must systematically identify the available clinical evidence relevant to the assessment scope. Search strategies, dates, selection decisions and PICO mapping must be documented so that the process is reproducible and verifiable.

Systematic evidence searches across JCA PICOs

JCA evidence searches cover multiple sources and must not be restricted to the developer's pivotal trials. Central source categories include:

1. Clinical effectiveness and safety studies conducted by the HTD and relevant third-party studies.

2. Bibliographic databases, notably MEDLINE and Cochrane CENTRAL.

3. Trial registries, results registries and relevant clinical-trial databases.

4. Existing HTA reports from relevant countries.

5. Clinical effectiveness and safety data submitted for EMA authorisation.

6. Patient registries where relevant to the question.

Sources, search dates and complete strategies should be recorded. The final assessment scope and applicable HTACG guidance determine the precise requirements.

Currency of literature searches in the JCA dossier

Under the HTACG Dossier Guidance version 1.0, the cut-off date for systematic searches must be no more than three months before JCA dossier submission. For every source searched systematically, the date and full reproducible search strategy must be documented. Updates should be aligned with the submission timetable.

The dossier should also identify whether further clinical data are expected and when. Search updates, evidence completeness and the submission timetable must therefore be managed together.

Study selection and PICO-specific allocation

Study selection must follow documented inclusion and exclusion criteria for the relevant PICOs. The dossier should explain why identified studies were included or excluded and which comparisons they inform.

HTACG Dossier Guidance version 1.0 specifies exclusion of studies for which only abstracts are available, including conference abstracts or posters, because the available detail is insufficient to appraise study methods and findings. Exclusions must be documented; included studies must be mapped to PICOs and supported by appropriate records.

Presenting direct and indirect comparisons in the JCA dossier

Direct and indirect comparisons must be documented so that reviewers can trace the evidence base, analysis and findings. The methodological validity of those comparisons is addressed in the evidence-assessment guide; this section focuses on dossier presentation.

Documenting direct comparative studies

Direct comparative studies must be mapped to the relevant PICOs and described using their essential characteristics. These include design, population, intervention, comparator, endpoints, sponsor and supporting documentation.

Standard tables distinguish direct evidence from studies contributing to indirect synthesis. Even a direct comparison must be demonstrably relevant to the specific PICO population and outcomes.

Documenting indirect evidence syntheses

Indirect comparisons require transparent documentation of the evidence network, included studies and analytical approach. Network meta-analysis and population-adjusted comparisons may be relevant depending on the evidence available.

The dossier should describe study selection, network connections, populations, statistical models and resulting effect estimates. Labelling an analysis merely “MAIC” or “NMA” is insufficient.

Methodological assumptions, sensitivity analyses and supporting files

Supporting documentation must disclose the assumptions and analytical steps needed to scrutinise indirect comparisons. This may include effect modifiers, prognostic variables, heterogeneity, consistency, missing data and sensitivity analyses.

The main dossier summarises the method; detailed protocols, statistical analysis plans and synthesis reports belong in the appropriate appendices. The scientific conditions and limitations are covered in JCA evidence assessment: Methodological requirements for RCTs, indirect comparisons and non-randomised evidence.

Presenting effectiveness and safety results in the JCA dossier

The JCA dossier must present relative clinical effects and uncertainty clearly for the relevant PICOs. Effect measures and presentation formats depend on the endpoint, design and analysis.

Effectiveness results and relative effect measures

Effectiveness findings should include suitable effect estimates, measures of uncertainty and analysis-population details. Time-to-event endpoints may require hazard ratios and Kaplan–Meier plots; binary and continuous endpoints call for appropriate absolute or relative measures.

The data cut-off, population and comparator underlying each result must be clear. Confidence intervals and other precision measures support interpretation.

Safety data and adverse events

Safety results must link adverse events and other safety endpoints to the relevant studies and comparisons. Analysis populations, observation periods and the type of comparison should be specified.

Depending on the scope, specific adverse-event categories and additional safety analyses may be needed. The dossier presents the evidence; the subsequent assessment judges its implications.

Subgroup analyses and uncertainty

Subgroup analyses should be documented when relevant to the PICOs or potential treatment-effect differences. Prespecified and post hoc analyses should be distinguished.

Subgroup definitions, methods, results and missing analyses should be transparent. Detailed interpretation of interaction tests, multiplicity and bias is covered in the guide on JCA evidence assessment.

Tables, statistical documentation and supporting materials for the JCA dossier

Standardised tables and underlying documentation enable assessors to verify the studies and analyses reported in the dossier. A complete submission therefore extends beyond the narrative main document.

HTACG table templates for evidence presentation

The HTACG Table Template Collection version 1.0 contains 46 numbered table templates for presenting clinical evidence in the JCA dossier. Adopted on 28 November 2024, it supplements the dossier guidance. The templates cover evidence identification, PICO mapping, study characteristics, direct and indirect comparisons, effectiveness, safety and subgroup analyses.

HTDs select the tables appropriate to their evidence and may adapt them to the data and analyses. The collection does not impose a blanket requirement to complete all 46 tables. The main dossier text, tables and appendices must remain consistent. For adverse events, descriptive tables with patient counts and percentages belong in the main dossier; relative effect estimates and detailed System Organ Class/Preferred Term analyses are presented in an appendix.

Underlying documentation in Appendix D

Appendix D provides the materials needed to trace dossier statements back to their sources. Depending on the requirements, these include references, full search strategies, clinical study reports (CSRs), study protocols, statistical analysis plans (SAPs), evidence-synthesis reports and relevant EMA submission materials.

Files must be complete, clearly attributable and available in the required formats. Technical specifications also govern file properties and naming conventions.

Programming code and statistical reproducibility

Certain analyses require additional technical evidence beyond a statistical analysis plan to permit verification. These may include in particular code and outputs where analyses cannot be adequately described by a standard method alone.

Whether code must be submitted, and in what form, depends on the current technical specifications. Submitted results, plans, outputs and tables should agree.

Preparing and submitting the JCA dossier

Operational dossier preparation starts before the final assessment scope is communicated. The short submission period leaves limited time to develop extensive new searches, indirect comparisons and supporting documentation after scoping.

Evidence and documentation planning before the final assessment scope

Early JCA dossier planning should inventory existing studies, potential comparator evidence and required documentation. Preliminary searches, data access, analysis plans and technical files can be organised in advance.

Simulating potential PICOs is a planning approach, not a substitute for the official assessment scope. Scenario development is covered in the guide on JCA scoping and PICO; this guide addresses implementation in a complete evidence package.

Checking PICO coverage before JCA dossier submission

Each PICO should undergo a documented completeness check before submission. An internal PICO matrix can consolidate the review:

The matrix supports internal quality assurance and does not replace official templates.

Documenting previous Joint Scientific Consultations in the JCA dossier

Where a medicinal product has undergone a Joint Scientific Consultation (JSC), the health technology developer must explain any departures from the evidence recommended in the later JCA dossier. This requirement follows Annex I(e) to Regulation (EU) 2021/2282. The HTACG Dossier Guidance describes the documentation and inclusion of JSC recommendations in Appendix D.9.

The JSC outcome document is not legally binding. Nevertheless, the developer must transparently describe how the evidence actually generated differs from earlier scientific recommendations. The separate guide on Joint Scientific Consultations addresses the consultation’s eligibility, process and legal status.

Submission and operational quality assurance

JCA dossier submission requires coordinated scientific and technical quality assurance. The deadlines following the first submission request are explained in the JCA process guide.

Before submission, teams should check file completeness, search currency, PICO mapping, consistent values, references and file readability. Responsibilities across clinical, biostatistics, evidence review, medical writing and regulatory operations should be explicit.

Completeness checks and requests for additional information in the JCA process

After submission, the European Commission checks whether the dossier meets Regulation (EU) 2021/2282 requirements. This completeness check is distinct from the subsequent scientific assessment of clinical evidence.

Scope of the JCA dossier completeness check

The check determines whether required information, data, analyses and documentation have been submitted on time and in the prescribed form. Article 9(3) requires completeness of available evidence, appropriate methods, transparent presentation and verifiable underlying documentation.

Formal completeness does not mean that every comparison will be judged methodologically robust. Evidence gaps and unanswered PICOs still need transparent reporting.

Second request for missing dossier components

If the Commission finds that the dossier does not meet the requirements, it may issue a second request for missing evidence or documentation. The HTD must supply the requested items within the applicable deadline.

Before first submission, the team should establish who will assess such requests, retrieve files and coordinate timely responses. Specific deadlines are set out in the process guide and implementing rules.

Consequences of an incomplete or late JCA dossier

If the dossier remains non-compliant or late after the second request, the JCA is discontinued under Article 10(6) of Regulation (EU) 2021/2282. The Commission publishes the reasons and informs the HTD.

Article 10(7) allows re-initiation under specified conditions. Compliance with dossier requirements is therefore essential to the continuation of the assessment.

JCA dossier and national HTA procedures

The European JCA dossier does not automatically replace evidence packages or analyses required for national HTA. National authorities consider the published JCA report, while country-specific questions and non-clinical assessment domains remain possible.

Reuse of JCA evidence in national procedures

Evidence from the JCA dossier can support national HTA when it is mapped to national assessment questions. Germany retains the AMNOG process and its dossier requirements. In France, the competent committees of the Haute Autorité de santé (HAS) continue the national assessment.

Article 13 of Regulation (EU) 2021/2282 governs consideration of the JCA report and avoids duplicate requests for evidence already submitted at EU level. Manufacturers should therefore coordinate EU dossier preparation with national evidence planning. The national procedures are discussed in separate Delta Dossier guides. For Germany, the guide to the AMNOG dossier explains the structure, modules and requirements of the national dossier.

The distinction between European evidence submission and national translation is described in the insights Five theses on the Delta-Dossier and EU HTA in Germany: What JCA means for AMNOG and the Delta-Dossier.

Sources and regulatory references

• Regulation (EU) 2021/2282, notably Articles 9, 10 and 13 and Annex I.

• Commission Implementing Regulation (EU) 2024/1381, including the medicinal-product dossier template.

• HTA Coordination Group: Guidance on filling in the joint clinical assessment dossier template – Medicinal products, version 1.0 (2024).

• HTA Coordination Group: Table Template Collection, version 1.0 (46 numbered templates; adopted 28 November 2024), and technical specifications for underlying documentation.

• European Commission: Published Joint Clinical Assessment reports and summary reports.