Two discontinued JCAs reveal emerging evidence standards as EU HTA assessments gather pace

Two Joint Clinical Assessments (JCAs) have been discontinued after assessors identified significant gaps in the submitted dossiers, providing an early indication of the evidentiary and documentation standards emerging under the EU HTA Regulation as additional assessments move toward publication.

The Baseline

• JCAs for Tacquell and catequentinib have been discontinued due to missing information in the submitted dossiers.
• The deficiencies differed in nature, with catequentinib raising concerns around evidence completeness and Tacquell focused more on methodological reporting and documentation.
• The discontinuations provide an early indication of the evidentiary and documentation standards emerging under the JCA process, with further reports expected soon.

Two weeks after publication of the first JCA report under the EU Health Technology Assessment Regulation (HTAR), two JCAs have now been discontinued, marking the first assessments halted because the submitted evidence package did not meet the requirements of the new process.

Updated information published on the European Commission's JCA assessment pages confirms the discontinuation of the JCAs for the advanced therapy medicinal product (ATMP) Tacquell, indicated for advanced melanoma, and catequentinib, which was under assessment for synovial sarcoma and leiomyosarcoma.

Unlike the earlier discontinuation of the sasanlimab JCA following withdrawal of its European Medicines Agency (EMA) application, both cases stemmed from deficiencies identified by assessors in the submitted dossiers following a second request for additional information under Article 10(5) of Regulation (EU) 2021/2282.

Why were the assessments discontinued?

For catequentinib, assessed by the Dental and Pharmaceutical Benefits Agency (TLV) in Sweden and co-assessed by the Norwegian Medical Products Agency (NoMA), the assessors identified broad concerns regarding the completeness and transparency of the evidence package. The document highlighted the absence of a transparent identification of all available evidence, insufficient justification for the inclusion or exclusion of studies, and a lack of information required to assess several PICOs within the assessment scope.

Similar concerns were identified in the Tacquell assessment, which was led by the National Authority for Health (HAS) in France and co-assessed by the Agency for Health Technology Assessment and Tariff System (AOTMiT) in Poland. However, rather than questioning whether all relevant evidence had been identified and submitted, the assessors' concerns focused primarily on how the available evidence had been analyzed, documented, and presented.

They requested additional information on literature searches, analytical methods, sensitivity analyses, and external comparisons, alongside missing statistical details such as relative effect measures, confidence intervals, p-values, Kaplan–Meier curves, and risk-of-bias assessments. The dossier was also found to lack supporting documentation for certain claims and information needed to assess the certainty and robustness of the submitted evidence.

Lessons from the first JCA experience

The developments come as stakeholders continue to examine the practical implications of the new EU HTA framework. The first completed JCA for tovorafenib (Ojemda) demonstrated the challenges of generating comparative evidence in rare diseases, particularly where randomized data are limited, and indirect comparisons carry substantial uncertainty.

The discontinuation of the Tacquell and catequentinib assessments highlights a different aspect of implementation: the degree to which the process depends not only on the availability of evidence, but also on the ability of developers to document, justify, and present that evidence in accordance with the requirements of the HTAR and associated methodological guidance.

For Mark Orchard (Cogentia Healthcare Consulting) the distinction between the completed tovorafenib assessment and the discontinued JCAs is particularly noteworthy. He explained 

"The key implication for companies preparing for EU HTA appears to be that where evidence of no evidence is provided, as with the Ipsen JCA, the HTACG are accepting of this, and the JCA report is published with an acknowledgement of these gaps. Where the manufacturer has not clearly demonstrated the lack of available evidence, JCAs are at risk of being discontinued."

Dmitry Goldenberg (Simon-Kucher) sees a broader message emerging from the reports.

"Reading through the reports, I came away with the impression that the EU JCA process is placing a huge emphasis on transparency, reproducibility, and the ability to justify every step in the evidence package."

He added that, for those working in market access, HEOR, evidence generation, and clinical development, these discontinuations may represent some of the clearest early signals yet of how the EU HTA framework is likely to operate in practice.

The cases also reinforce the importance of evidence planning well before dossier submission. While concerns around the number of PICOs generated through the scoping process have been widely discussed since the introduction of the HTAR, in his latest article in the Journal of Comparative Effectiveness Research, Sreeram Ramagopalan (King's College London) argues that the more significant challenge is often the availability of comparative evidence capable of addressing those questions.

"Several lessons follow for companies bringing oncology products and ATMPs through this framework. The first is that PICO proliferation is not, on its own, the binding constraint; the binding constraint is the availability of usable comparative evidence for each question."

Ramagopalan also notes that even where the number of PICOs is relatively limited, developers may still struggle to generate evidence capable of addressing them.

"A scope of only eight PICOs still left seven unanswered here. Companies should map, as early as trial design, which PICOs their evidence can realistically support and which they cannot, and should be candid about the proportion of a likely scope that will go unaddressed."

More assessments on the horizon

The cases emerge during a first year of implementation that has so far seen fewer assessments than originally projected. The Member State Coordination Group on Health Technology Assessment (HTACG) previously estimated that around 50 medicinal product JCAs could be initiated in 2026, including approximately 35 oncology products and 15 ATMPs. At present, however, only 14 JCAs are listed as ongoing. While it remains too early to draw conclusions from these figures, the lower volume means that each assessment is being scrutinized closely by stakeholders seeking to understand how the new framework will operate in practice.

As additional JCA reports are published, these early cases may offer important insights into the evidentiary and procedural standards that developers will be expected to meet under the new system. Stakeholders will not have to wait long for further indications of how the framework is evolving. According to the latest meeting report from the HTACG group has reached consensus on the JCA and summary reports for Zepzelca (lurbinectedin) and Imdelltra (tarlatamab), both orphan medicinal products for the treatment of extensive-stage small cell lung cancer in adults.

The endorsed reports will now be submitted to the European Commission for procedural review before publication, providing the next opportunity for stakeholders to examine how the JCA framework is being applied in practice and whether the lessons emerging from these early assessments continue to hold.