The dossier brings together the assessment scope, systematic evidence identification, study selection, methods, direct and indirect comparisons, and results on relative effectiveness and relative safety. A defining feature is its PICO-based structure: the assessment scope determines which populations, comparators and health outcomes need to be addressed and how the available evidence is organised.
The JCA dossier is therefore more than a collection of clinical study results. Its preparation requires alignment between PICO scoping, evidence retrieval, statistical analysis, evidence synthesis, data presentation and the underlying documentation submitted with the dossier.
Last regulatory review: September 2026. Template names, section numbering and technical specifications should be checked against current EU HTA primary sources before publication.
What is a JCA dossier under EU HTA?
A JCA dossier is the manufacturer's submission of information, data, analyses and other clinical evidence required for the European Joint Clinical Assessment. The information must follow international standards of evidence-based medicine and take applicable methodological guidance adopted by the HTACG into account. Deviations from applicable methodological guidance must be described and justified.
For medicinal products, the dossier template is set out in Annex I to Commission Implementing Regulation (EU) 2024/1381. The HTACG guidance explains how that template should be completed and is supplemented by a dedicated collection of table templates for presenting evidence.
The dossier covers more than the pivotal studies used for marketing authorisation. It includes the clinical background, assessment scope, evidence identification, study-selection methods, statistical analyses, direct and indirect evidence, relative effectiveness, relative safety and extensive underlying documentation.
What is the difference between a JCA dossier and a JCA report?
The JCA dossier is submitted by the Health Technology Developer, while the JCA report is produced through the European assessment process.
The dossier is an input into the assessment. It contains the evidence and analyses submitted by the HTD against the defined assessment scope.
The JCA report is an output of the assessment. It documents the assessors' evaluation of the relative clinical effects based on the submitted evidence and the JCA process. The terms should therefore not be used interchangeably.
Which official documents define the JCA dossier?
The JCA dossier requirements for medicinal products are distributed across the EU HTA legal framework, the official dossier template and supporting HTACG guidance.
Commission Implementing Regulation (EU) 2024/1381 and the JCA dossier template
Commission Implementing Regulation (EU) 2024/1381 establishes procedural rules for Joint Clinical Assessments of medicinal products and contains the JCA dossier template in Annex I. The template defines the information that the HTD is required to submit.
HTACG guidance for completing the JCA dossier
The Guidance on filling in the joint clinical assessment dossier template – Medicinal products explains how the individual sections of the template should be completed. It also specifies methodological and reporting expectations for areas including evidence identification, study selection, direct and indirect comparisons, subgroup analyses and presentation of results.
JCA dossier table template collection
The HTACG Table Template Collection supplements the main guidance and provides predefined formats for presenting the evidence. The collection contains 46 table templates covering evidence identification, study characteristics, PICO-specific study allocation, direct and indirect comparisons, effectiveness, safety, subgroup analyses and supporting information. The tables can be adapted to the specific information and analyses presented.
Technical specifications for JCA dossier submission
Separate technical specifications define how the underlying documentation should be organised and submitted. These requirements cover file properties and naming conventions as well as supporting materials such as references, literature-search documentation, programming code, Clinical Study Reports (CSRs), Statistical Analysis Plans (SAPs), evidence-synthesis reports and clinical documentation submitted to the EMA.
How is the JCA dossier structured?
The JCA dossier for medicinal products consists of six main sections and supporting Appendices A to D.
| Section | Main content |
|---|---|
| 1. Overview | Product and HTD information, previous HTAR assessments and executive summary |
| 2. Background | Medical condition, target population, clinical management and medicinal product |
| 3. Assessment scope | PICOs defined for the JCA |
| 4. Methods | Study selection, evidence retrieval, data analysis and evidence synthesis |
| 5. Results | Evidence identification, included studies, relative effectiveness and relative safety |
| 6. References | Sources cited in the dossier |
| Appendix A | Additional detailed study, safety and subgroup information |
| Appendix B | Information for assessing certainty of relative effects, including risk of bias |
| Appendix C | Main development studies not included in the PICO-specific presentation |
| Appendix D | Underlying documentation |
The structure shows that the JCA dossier combines clinical context, assessment questions, methodology, results and reproducibility documentation in one submission.
The executive summary already needs to reflect the assessment scope. It should identify PICOs for which no results were submitted, summarise relative effectiveness and relative safety for each PICO, distinguish direct from indirect evidence and describe the degree of certainty of the relative effects.
How does the assessment scope define the JCA dossier?
The JCA assessment scope defines the PICOs that the Health Technology Developer must address and therefore determines which comparative evidence needs to be identified, analysed and presented in the dossier.
PICO in the JCA framework comprises:
- Patient population
- Intervention
- Comparator
- Health outcomes
The dossier must reproduce the assessment scope communicated to the HTD. If results are not submitted for a PICO included in the scope, the dossier must identify that PICO and explain the omission.
The PICO structure continues throughout the dossier. Study-selection criteria can differ between PICOs, evidence needs to be mapped to the relevant PICO questions, methods should be described by PICO where appropriate, and results on relative effectiveness and relative safety are presented against the applicable PICO.
This makes PICO coverage an operational dossier requirement rather than only a scoping exercise.
A clinical development programme may contain substantial evidence while still providing incomplete coverage of the final JCA assessment scope if the relevant populations or comparators differ from those directly investigated.
What do the first JCA dossiers look like in practice?
The formal structure of a JCA dossier is defined by the European template. However, the complexity of the actual evidence package is largely determined by the assessment scope. The first published JCA dossiers already illustrate very different situations: from a single PICO supported by directly relevant randomised evidence to multiple PICOs requiring different direct and indirect evidence approaches.
| JCA dossier | Assessment scope | Evidence situation |
|---|---|---|
| Tovorafenib (Ojemda) | 8 PICOs | Comparative analyses for 2 PICOs; population-adjusted indirect comparisons |
| Lurbinectedin (Zepzelca) | 1 PICO | Direct randomised evidence from IMforte |
| Tarlatamab (Imdylltra) | 7 PICOs | Direct evidence, MAIC, network meta-analysis and descriptive evidence |
Tovorafenib: eight PICOs and limited comparative evidence
The tovorafenib JCA dossier illustrates how multiple populations and comparators can substantially expand the evidence requirements. The assessment scope comprised eight PICOs. According to the dossier, comparative efficacy and safety analyses could not be provided for six of these PICOs. Population-adjusted indirect comparisons were conducted for PICO 5 and PICO 7.
The case therefore illustrates that a broad assessment scope is not necessarily covered by the existing clinical development programme. The dossier also has to document transparently where suitable comparative evidence is unavailable.
Lurbinectedin: one PICO supported by direct RCT evidence
The evidence situation for lurbinectedin is considerably more straightforward. Its assessment scope comprises one PICO comparing lurbinectedin plus atezolizumab with atezolizumab as maintenance therapy. The randomised Phase III IMforte trial provides direct comparative evidence for this question.
However, even a directly relevant RCT does not automatically address every element requested in the assessment scope. PFS2 was not a prespecified endpoint in IMforte and was not systematically collected. Patients with CNS metastases were also excluded, meaning that the requested subgroup analysis for this population could not be performed.
Tarlatamab: different evidence approaches within one dossier
The tarlatamab JCA dossier illustrates a third situation. Its assessment scope comprises seven PICOs. Depending on the population and comparator, these are addressed using different evidence approaches: direct evidence from the Phase III DeLLphi-304 trial, matching-adjusted indirect comparisons (MAICs), network meta-analyses (NMAs), and a descriptive comparison for PICO 7.
Taken together, the first dossiers demonstrate an important practical point: the template alone does not determine the workload of a JCA dossier. What matters is how well the assessment scope can be addressed by the clinical development programme and the available comparative evidence.
How is evidence identified for the JCA dossier?
The HTD must conduct an information-retrieval process designed to identify the evidence required for all PICOs in the JCA assessment scope.
The assessment scope determines the scope of the information retrieval. According to the HTACG guidance, a complete dossier requires systematic searching for available evidence across all defined PICOs.
Which evidence sources must be searched for the JCA dossier?
The JCA evidence-retrieval process systematically considers six main sources:
- Clinical efficacy and safety studies performed or sponsored by the HTD and relevant studies by third parties.
- Bibliographic databases, including at least MEDLINE and the Cochrane Central Register of Controlled Trials.
- Study and study-results registries, including relevant clinical-trial databases.
- Existing HTA reports on the medicinal product from relevant EEA countries and specified non-European jurisdictions.
- Clinical safety and efficacy evidence submitted to the EMA as part of the regulatory submission.
- Patient registries, where relevant.
The dossier must document the sources searched and the date of each search. Search strategies are provided as underlying documentation.
How current must JCA dossier literature searches be?
The cut-off date for the evidence searches should be no more than three months before submission of the JCA dossier.
The dossier should also state whether new data relevant to the assessment scope are expected to become available.
This creates a direct connection between dossier timing and evidence completeness: the evidence package needs to be sufficiently current for submission while remaining aligned with all PICOs in the assessment scope.
How are studies selected for each JCA dossier PICO?
Study selection for the JCA dossier follows the assessment scope and the inclusion and exclusion criteria defined for the relevant PICO.
The HTD must document how studies identified through the information-retrieval process were selected. Sufficient documentation must be available to assess study methods and results; the guidance states that studies available only as abstracts, such as conference abstracts or posters, should be excluded.
The study-selection logic also depends on the comparator structure of the PICO.
How is direct evidence selected for a JCA dossier?
Where suitable studies directly compare the intervention with the PICO comparator in the relevant population, they can provide direct comparative evidence.
The dossier identifies the relevant studies by PICO and documents, among other elements:
- study design,
- intervention and comparator,
- whether the study supported marketing authorisation,
- whether it was HTD-sponsored,
- and which supporting documentation is available.
The Table Template Collection explicitly separates studies providing direct evidence from studies providing indirect evidence for each PICO.
When does a JCA dossier require indirect comparisons?
Indirect evidence becomes relevant where the available studies do not directly compare the intervention with the comparator required by the assessment scope.
Depending on the available evidence network, this can require conventional indirect treatment comparisons, network meta-analysis or population-adjusted approaches.
The JCA guidance distinguishes comparator scenarios and corresponding study-selection pathways. The number and nature of PICOs can therefore materially change the evidence-synthesis work required for the dossier.
The first JCA dossiers already illustrate these different evidence situations in practice. While lurbinectedin addresses its single PICO with direct randomised evidence, population-adjusted indirect comparisons were used for two of the eight PICOs in the tovorafenib dossier. The tarlatamab dossier combines direct evidence with MAICs and network meta-analyses within the same assessment.
How are indirect comparisons presented in a JCA dossier?
A JCA dossier using indirect comparisons must describe and justify the evidence-synthesis methods and provide sufficient information to assess the assumptions underlying the comparison.
The relevant evidence-synthesis protocol and Statistical Analysis Plan must be included in the underlying documentation. Detailed methodological information is provided in Appendix B.2, while the main methods section summarises the methods and their justification.
Which elements must be addressed for indirect comparisons in a JCA dossier?
The dossier should address areas including:
- construction of the evidence network,
- selection of connecting paths,
- potentially relevant common comparators,
- inclusion and exclusion of studies,
- potential treatment-effect modifiers,
- prognostic variables or confounders where relevant,
- exchangeability assumptions,
- heterogeneity and consistency,
- estimation of treatment effects,
- missing data,
- sensitivity analyses,
- and the plausibility of underlying methodological assumptions.
For population-adjusted methods in anchored networks, the guidance additionally requires information on baseline characteristics after adjustment and a comparison with results without adjustment.
The Table Template Collection explicitly accommodates methods such as Bucher indirect treatment comparisons, network meta-analysis and matching-adjusted indirect comparisons (MAIC) when presenting indirect evidence.
How are relative effectiveness and relative safety reported in the JCA dossier?
The JCA dossier reports relative effectiveness and relative safety for the clinical studies and evidence syntheses relevant to the assessment scope.
Results must be presented for direct and indirect comparisons where applicable. The dossier should report individual study results separately even where those studies are subsequently combined in an evidence synthesis.
Effect estimates are accompanied by statistical information such as point estimates, confidence intervals and p-values as applicable. The dossier also records information about prespecification, multiplicity control and statistical significance against a prespecified alpha level.
How are effectiveness outcomes reported in the JCA dossier?
The Table Template Collection provides separate formats for:
- dichotomous outcomes,
- time-to-event outcomes,
- continuous outcomes.
For time-to-event outcomes, for example, the template can include the number of analysed and censored patients, median time to event, number of events, hazard ratio, confidence interval and statistical testing information.
Outcome measurement instruments also require methodological description where relevant. For Patient-Reported Outcome Measures or Clinician-Reported Outcome Measures, the dossier should describe the instrument and provide information supporting its measurement properties. Responder definitions such as a Minimal Important Difference should be described and justified when used.
How are safety outcomes reported in the JCA dossier?
The JCA table templates distinguish between the presentation of safety in the main dossier and more detailed analyses in the appendices.
In the main dossier, safety tables are generally descriptive, presenting numbers and percentages of patients with events. Relative effect estimates for adverse events and detailed adverse-event tables by System Organ Class and Preferred Term are provided in the appendix.
How are subgroup analyses reported in the JCA dossier?
The dossier should describe methods used to investigate effect modification and subgroup analyses.
The guidance requires interaction testing for effect modification and asks the HTD to report the subgroup analyses conducted, justify cut-off values and state whether analyses were prespecified and controlled for multiplicity.
The Table Template Collection contains dedicated subgroup formats for dichotomous, time-to-event and continuous outcomes.
Which tables are used in the JCA dossier?
The JCA Table Template Collection contains 46 templates covering the evidence pathway from study identification to PICO-specific comparative results and supporting analyses.
The templates can be grouped into several functional areas:
| JCA dossier table category | Examples of information presented |
|---|---|
| Evidence identification | HTD studies, database searches, registries, HTA reports and EMA studies |
| PICO evidence mapping | Relevant studies and available documentation by PICO |
| Study characteristics | Design, population, interventions, follow-up and data cuts |
| Direct evidence | Effectiveness and safety results against the PICO comparator |
| Indirect evidence | Evidence networks and indirect comparative results |
| Subgroup analyses | Subgroup-specific effects and interaction testing |
| Supporting analyses | Detailed safety, study methodology and patient flow |
One particularly important template is the list of relevant studies by PICO question. It explicitly maps studies to individual PICOs and distinguishes direct from indirect evidence.
The tables therefore do not merely standardise formatting. They make the relationship between the assessment scope, available studies and comparative evidence visible throughout the dossier.
Which supporting documents must accompany the JCA dossier?
The JCA submission includes extensive underlying documentation in addition to the main dossier.
Appendix D is structured as follows:
| Appendix | Supporting documentation |
|---|---|
| D.1 | Full texts of references |
| D.2 | Documentation of information retrieval |
| D.3 | Programming code and relevant outputs |
| D.4 | Study reports for original clinical studies |
| D.5 | Study reports for evidence-synthesis studies |
| D.6 | Clinical safety and efficacy data from the EMA submission |
| D.7 | Relevant HTA reports |
| D.8 | Information on registry-based studies |
| D.9 | Information on Joint Scientific Consultations |
The technical specifications require submitted files to be readable, saveable and printable without a password. HTD-generated PDFs should also be navigable, electronically annotatable and extractable and should not contain watermarks.
Which statistical documentation must accompany the JCA dossier?
Where analyses and calculations cannot be adequately described by a specific standard method, programming code and relevant outputs must be submitted. The technical specifications define a structure for linking the code, input data and outputs to the corresponding analyses.
For original clinical studies, the underlying documentation includes complete CSRs, associated appendices, study protocols and Statistical Analysis Plans as applicable. Evidence-synthesis studies similarly require detailed reports and their supporting methodological documentation.
This makes reproducibility and traceability important operational requirements of JCA dossier preparation.
When should preparation of the JCA dossier start?
Preparation of the JCA dossier should distinguish between content that can be developed before the final assessment scope and work that depends on the final PICOs.
The final PICO scope determines important parts of study selection, comparator-specific evidence retrieval, evidence synthesis and results presentation. Waiting for final PICOs before beginning all dossier activities would therefore compress substantial evidence and production work into the formal submission period.
A practical preparation model separates reusable dossier foundations from PICO-dependent activities:
| JCA dossier work that can start earlier | Work dependent on the final assessment scope |
|---|---|
| Clinical evidence inventory | Final PICO-to-study mapping |
| Availability check for CSRs, protocols and SAPs | PICO-specific study selection |
| Background and disease information | Comparator-specific evidence searches |
| Study documentation | Final direct/indirect evidence strategy |
| Evidence-retrieval infrastructure | PICO-specific evidence synthesis |
| Data and analysis availability assessment | Additional statistical analyses |
| Submission-document inventory | Final PICO-specific results presentation |
This distinction is particularly important when the assessment scope contains multiple populations or comparators. Each additional PICO can create new requirements for evidence identification, study selection, analysis and presentation.
The first published dossiers illustrate how different the resulting evidence requirements can be: from a single PICO supported by directly relevant RCT evidence for lurbinectedin, to seven PICOs requiring several evidence approaches for tarlatamab, and eight PICOs for tovorafenib, only two of which could be addressed with comparative analyses. Preparation should therefore start before completion of the dossier template and consider potential populations, comparators, outcomes and resulting evidence gaps at an early stage.
How does the JCA dossier connect to national HTA in Germany?
The JCA dossier provides the European clinical evidence submission but does not replace the German AMNOG dossier or the national assessment of added benefit.
European PICOs can differ from the assessment question relevant to Germany, particularly with regard to population and comparator. National requirements also remain for areas outside the JCA clinical assessment.
The practical question after the European submission is therefore which JCA evidence can support the German dossier and which analyses or national information must be added.
For the detailed interface between both submissions, see JCA dossier and AMNOG dossier: what Germany still requires.
For the strategic implications of comparator choice, endpoints, evidence updates and timing, see Five theses on the Delta-Dossier.
The JCA dossier is the European execution layer, not the German translation
The JCA dossier is the structured evidence package a manufacturer builds for the European Joint Clinical Assessment: assessment scope, PICO-specific evidence identification, direct and indirect comparisons, relative effectiveness and safety, and extensive underlying documentation.
That execution task is distinct from what happens afterwards in Germany. The JCA dossier answers the European PICO questions; it does not determine the German appropriate comparator therapy, national populations, epidemiology, treatment costs or the G-BA's added-benefit decision.
For manufacturers, the practical sequence is therefore: build the JCA dossier against the European assessment scope, then translate the resulting evidence into the German AMNOG dossier through the Delta-Dossier work described in the linked guides below.
JCA dossier at a glance
| JCA dossier element | Requirement |
|---|---|
| Purpose | Evidence submission for the Joint Clinical Assessment |
| Submitted by | Health Technology Developer |
| Legal framework | Regulation (EU) 2021/2282 and Implementing Regulation (EU) 2024/1381 |
| Core structure | Six main sections plus supporting appendices |
| Assessment structure | Based on the JCA assessment scope and PICOs |
| Evidence identification | Systematic retrieval across defined evidence sources |
| Comparative evidence | Direct and, where relevant, indirect comparisons |
| Results | Relative effectiveness and relative safety |
| Supporting material | References, search documentation, programming code, study reports and evidence-synthesis documentation |
| Data presentation | Dedicated JCA table templates |