Discontinued JCAs: Why Joint Clinical Assessments are discontinued

A Joint Clinical Assessment can be discontinued for different reasons. The cases reviewed to date show both regulatory causes and deficiencies in the completeness and methodological traceability of the JCA dossier.

Zumrad / sasanlimab represents a discontinuation following withdrawal of the EMA marketing authorisation application. Catequentinib, Tacquell and sintilimab, by contrast, illustrate the relevance of the requirements under Article 9 of Regulation (EU) 2021/2282 for JCA dossier preparation. The documented deficiencies range from incomplete evidence retrieval and insufficient PICO coverage to methodological transparency, reproducibility and the assessability of indirect comparisons.

The first cases therefore provide concrete insights into the requirements that can become relevant for completing a JCA procedure and the recurring patterns emerging from the documents published to date.

What does “JCA discontinued” mean in the EU-HTA procedure?

“JCA discontinued” means that a Joint Clinical Assessment was not completed with a final JCA report. The term initially describes the procedural status, not automatically the underlying reason.

Based on the cases reviewed so far, at least two different constellations can be distinguished:

This distinction is important. A discontinued JCA is not automatically equivalent to “insufficient clinical efficacy”. In some cases, the regulatory withdrawal is the main issue. In others, the official documents show very clearly that the JCA dossier did not meet the requirements for completeness, transparency and methodological traceability.

Which JCAs have been discontinued?

Based on the documents reviewed, four cases are particularly relevant: Zumrad / sasanlimab, catequentinib, Tacquell and sintilimab.

These cases should therefore not be grouped under a single category such as “JCA failed because of poor evidence”. A more precise interpretation is this: the first discontinued JCAs show that the EU-HTA procedure can become vulnerable both from a regulatory and a methodological perspective if either the authorisation process or the JCA dossier basis does not hold.

Why was the JCA for Zumrad / sasanlimab discontinued?

The JCA for Zumrad / sasanlimab was discontinued because Pfizer withdrew the EMA marketing authorisation application. Zumrad was intended for adults with BCG-naive, high-risk, non-muscle-invasive bladder cancer. The active substance sasanlimab was intended to be used in combination with Bacillus Calmette-Guerin (BCG).

The EMA had already assessed the application and prepared questions for the company. At the time of withdrawal, the EMA was evaluating the company’s responses. The Agency expressed concerns about the study and the conclusions derived from it.

The relevant points included:

1. major changes made while the study was ongoing,
2. a change in the statistical method,
3. uncertainties regarding the appropriateness of the primary endpoint,
4. assessment of the endpoint by investigators in an open-label study setting,
5. the question of whether the observed effect represented a clinically meaningful benefit for patients,
6. lack of support for the primary result from other important endpoints, including survival data,
7. more side effects and more interruptions or discontinuations of BCG treatment under the combination with Zumrad.

Pfizer justified the withdrawal by stating that additional data and analyses were needed to address the CHMP’s questions.

For the interpretation of discontinued JCAs, Zumrad therefore represents a distinct type of case. The case does not primarily show an incomplete JCA dossier under Article 9, but the direct dependency of the JCA on the central authorisation procedure. If the marketing authorisation application is withdrawn, the regulatory basis for completing the JCA no longer exists.

Why did catequentinib, Tacquell and sintilimab become relevant under Article 9?

Catequentinib, Tacquell and sintilimab represent a different type of risk from Zumrad / sasanlimab. The central issue in these cases is missing information, data, analyses and evidence in the JCA dossier and therefore the requirements under Article 9 of Regulation (EU) 2021/2282. The three cases highlight different aspects: evidence completeness and PICO coverage for catequentinib, transparency and reproducibility for Tacquell, and the assessability of indirect comparisons for sintilimab.

Article 9 requires a JCA dossier to contain complete and up-to-date information, data, analyses and evidence to assess the parameters defined in the assessment scope. In addition, the submitted evidence must be complete, analysed using appropriate methods, presented transparently and supported by underlying documentation that allows verification.

The Commission documents on catequentinib, Tacquell and sintilimab show that these requirements are assessed in very concrete terms.

Catequentinib: Why missing evidence completeness became a JCA risk

For catequentinib, one central problem was the lack of transparent and comprehensive identification of the available evidence. The Commission criticised that the available evidence had not been presented and synthesised in a way that allowed assessors to evaluate the completeness and validity of the methodological approach.

For catequentinib, the documented deficits included:

1. no transparent and comprehensive identification of all available evidence,
2. no sufficient justification for the inclusion or exclusion of evidence,
3. insufficient presentation of the PICOs in accordance with the Commission’s first request,
4. missing explanation of why no relative effectiveness and relative safety results were submitted for certain PICOs,
5. missing justification for not conducting feasibility assessments for indirect comparisons,
6. insufficient documentation of literature searches and study selection,
7. missing or incomplete information on study characteristics,
8. missing results according to the assessment scope,
9. incomplete information for assessing the certainty of results,
10. missing underlying documentation in the appendices.

The catequentinib case therefore shows very clearly that a JCA dossier must not only contain evidence. It must demonstrate that the evidence was searched comprehensively, selected transparently, analysed by PICO and interpreted using a methodologically robust approach.

For market access teams, this is particularly relevant because these requirements have to be met early in the process. Companies that only assess after the assessment scope whether the evidence base has been documented robustly for all relevant PICOs, comparisons and endpoints risk procedural problems in a very tight timeframe.

Tacquell: Why results presentation and reproducibility became decisive

For Tacquell, the main issues were missing PICO-specific information retrievals, insufficient descriptions of methods, missing results presentations and missing documentation. The Commission listed deficits across several dossier sections and appendices.

For Tacquell, the missing elements included:

1. information retrievals for several PICOs,
2. a comprehensive description of the methods for PICO 1, PICO 2 and PICO 6,
3. a justification for the absence of sensitivity analyses,
4. underlying documentation for external comparisons,
5. description of analysis methods for included studies,
6. complete presentation of relative effect measures,
7. Kaplan-Meier curves for time-to-event data,
8. results on relative effectiveness and relative safety according to the assessment scope,
9. search strategies by PICO,
10. documentation of studies, protocols and registry searches,
11. programming code for the unanchored indirect comparison or external comparison.

Tacquell highlights a second point: the requirements do not only concern evidence retrieval, but also the assessability of the results. If relative effect measures, confidence intervals, sensitivity analyses, time-to-event presentations or programming code are missing, assessors cannot adequately verify the results.

For JCA dossiers, reproducibility therefore becomes a practical procedural criterion. The question is not only whether a result is reported. What matters is whether the derivation of that result can be traced and verified within the available timelines.

Sintilimab: Why exchangeability in indirect comparisons became a JCA risk

The JCA dossier for sintilimab still contained substantial gaps in information, methodology and documentation after the European Commission's second request. The updated dossier was submitted on 1 September 2026. The Commission linked the remaining deficiencies to the requirements under Articles 9(2), 9(3) and 9(4) of the EU-HTA Regulation.

For sintilimab, the missing information included sufficient details on the characteristics of the included studies and interventions, study conduct, outcome definitions, follow-up times and imaging intervals. Results for outcomes used in the indirect comparisons were also incomplete, as was information on censored patients in the Kaplan-Meier curves for the ORIENT-11 study. Elements of the evidence retrieval were also missing, including the ClinicalTrials.gov search and the corresponding search strategies and RIS files.

The methodological basis of the comparative evidence was particularly relevant. For all PICOs, the assessment of relative effectiveness and relative safety relied exclusively on indirect comparisons. However, the dossier did not provide sufficient information to assess the exchangeability of the included studies according to evidence-based medicine standards.

The Commission therefore concluded that the relative effectiveness and relative safety of sintilimab versus the comparators in the indirect comparisons could not be assessed.

The case also highlights a practical issue in JCA dossier preparation: according to the Commission, some of the missing information was in principle already available in the Clinical Study Report for ORIENT-11 or in publications on the comparator studies. Available evidence is therefore not sufficient if it is not presented completely and in a form that allows assessors and co-assessors to evaluate it.

What patterns do the first discontinued JCAs show?

The first discontinued JCAs show five recurring risk areas: evidence completeness, PICO coverage, methodological transparency, the assessability of indirect comparisons and reproducibility. The sintilimab case shows particularly clearly that available evidence is not sufficient if the JCA dossier does not contain the information required to assess the exchangeability of the included studies. These risk areas affect both the operational quality of the JCA dossier and the preparation of the underlying evidence.

Evidence completeness in the JCA dossier

A JCA dossier must capture the available evidence completely and transparently. Depending on the research question, this includes not only randomised studies, but also study registries, results registries, HTA reports, information from the EMA dossier, patient registries and, where relevant, other data sources.

For manufacturers, this means that a systematic literature search must not only be performed, but fully documented. Search strategies, search limits, study selection, reasons for inclusion and exclusion and the PICO-specific allocation of evidence must remain verifiable.

PICO coverage in the JCA dossier

The PICO questions from the assessment scope structure the JCA. Each PICO question must be addressed. If no results are submitted for a PICO question, the omission must be explained transparently.

For Germany, this is particularly relevant because the scoping phase already determines which populations, interventions, comparators and endpoints may later become relevant for the national translation of the evidence. If the PICOs relevant for Germany are not robustly covered, this creates a risk for the delta dossier and the national AMNOG preparation.

Methodological transparency in the JCA dossier

Indirect comparisons, external comparisons, sensitivity analyses and deviations from methodological guidance documents must be justified. A JCA dossier must show why a method was chosen and why other methodological options were not applied.

This applies in particular to feasibility assessments for indirect comparisons. If no indirect comparison is conducted, a mere statement that evidence is missing is not sufficient. A transparent justification is needed to explain why the comparison is not possible or not methodologically acceptable.

Exchangeability in indirect comparisons in the JCA dossier

Indirect comparisons require the included studies to be sufficiently comparable with regard to characteristics relevant to the comparison. The JCA dossier must therefore contain the information needed to assess exchangeability. This includes study characteristics, interventions, outcome definitions, follow-up times and the study results used in the indirect comparisons.

Sintilimab illustrates the practical consequences of insufficient information particularly clearly. Because relative effectiveness and relative safety for all PICOs were to be assessed exclusively through indirect comparisons, the insufficient information prevented an adequate assessment of exchangeability. According to the Commission, the relative effectiveness and relative safety of sintilimab versus the comparators could therefore not be assessed.

Reproducibility in the JCA dossier

Assessors must be able to verify the submitted results. This requires underlying documents such as clinical study reports, study protocols, statistical analysis plans, documentation of evidence syntheses and, where applicable, programming code.

Reproducibility is therefore not a purely technical detail. It determines whether relative effects, indirect comparisons and sensitivity analyses can be assessed reliably within the JCA timelines.

Which requirements should manufacturers review before submitting the JCA dossier?

The first discontinued JCAs show that JCA readiness begins well before submission of the JCA dossier. Manufacturers need to assess early whether evidence retrieval, PICO coverage, methodology, results presentation and underlying documentation provide a complete and traceable basis for assessment.

For market access, HTA and evidence generation teams, seven key review questions emerge:

1. Are all PICOs from the JCA assessment scope addressed with evidence or a transparent justification?
2. Is the systematic literature search complete, current and reproducibly documented?
3. Are study selection, reasons for exclusion and PICO allocation described transparently?
4. Are indirect comparisons, feasibility assessments, external comparisons and sensitivity analyses methodologically justified?
5. Is sufficient information on study characteristics, interventions, endpoints, follow-up and results available to assess exchangeability in indirect comparisons?
6. Are relative effect measures, confidence intervals, Kaplan-Meier curves, safety results and missing data fully presented?
7. Are Clinical Study Reports, study protocols, statistical analysis plans, Appendix D documentation and, where applicable, programming code available for verification?

The catequentinib, Tacquell and sintilimab cases illustrate different consequences of insufficient JCA readiness. The decisive question is not simply whether evidence exists. It must be prepared for the relevant PICOs and documented in sufficient detail to allow assessors and co-assessors to evaluate the methods and results within the JCA procedure.

What does a discontinued JCA mean for the AMNOG procedure?

A discontinued JCA does not automatically end the national benefit assessment in Germany. For the AMNOG procedure, the main consequence is that no final European JCA report is available as a clinical reference point for the national assessment.

The requirements of the German early benefit assessment remain in place. These include the appropriate comparator therapy, patient-relevant endpoints, relevant patient groups and subgroups, national requirements for analysis methods and the currency of the evidence.

Manufacturers should therefore also prepare for a scenario in which a JCA is not completed or is not completed in time. A discontinued JCA changes the European reference available for the national procedure, but it does not replace the need for independent preparation of the German AMNOG assessment.

What the first discontinued JCAs show for JCA dossier preparation

The first discontinued JCAs show that the completeness and methodological traceability of the JCA dossier can be decisive for whether an assessment can be completed. The cases reviewed to date point to different causes: withdrawal of a marketing authorisation application as well as deficiencies in evidence completeness, PICO coverage, methodological transparency, exchangeability and reproducibility.

Catequentinib, Tacquell and sintilimab illustrate in particular how concretely the requirements under Article 9 are applied to JCA dossier content. The availability of evidence alone is not sufficient. Evidence must be comprehensively identified, prepared for the relevant PICOs and documented in a way that allows methods and results to be assessed within the available timelines.

For manufacturers, JCA readiness therefore becomes an early evidence-planning task. Evidence retrieval, PICO coverage, indirect comparisons, sensitivity analyses and underlying documentation should not first be brought together shortly before JCA dossier submission. The first discontinued procedures show that these elements can determine whether the submitted evidence can be fully assessed.