Joint Clinical Assessment: How the First JCAs Are Reshaping Evidence Assessment in Europe

With Tovorafenib (OJEMDA), Lurbinectedin, and Tarlatamab, three very different Joint Clinical Assessments have now been published. Despite covering different therapeutic areas and evidence situations, they reveal a remarkably consistent assessment philosophy. The first JCAs suggest that Europe is establishing a common framework for determining which clinical evidence can be trusted and under which conditions.

The first three Joint Clinical Assessments represent distinct stages in the evolution of European evidence assessment.

The OJEMDA JCA demonstrated that simply generating clinical evidence is not sufficient. Eight PICOs were defined within the assessment scope, but comparative evidence was available for only part of these research questions. This was the first clear indication that the assessability of evidence itself had become an explicit component of the European assessment process.

The Lurbinectedin JCA shifted the focus towards evidence quality. Clinical outcomes were consistently interpreted in the context of risk of bias, data maturity, patient-reported outcomes, and statistical uncertainty. The central question was no longer only whether a treatment effect existed, but how reliable that effect could be considered.

The Tarlatamab JCA takes this one step further. Direct randomized comparisons, Bucher indirect comparisons, Network Meta-Analyses (NMAs), and Matching-Adjusted Indirect Comparisons (MAICs) are not treated equally. Instead, European assessors explicitly evaluate the methodological assumptions, limitations, and uncertainties associated with each evidence source. This represents the clearest indication to date that a hierarchy of evidence trustworthiness is emerging within European HTA.

The key difference between previous HTA assessments and a Joint Clinical Assessment lies in the assessment framework itself. While traditional HTA procedures primarily focused on the magnitude of a clinical treatment effect, JCAs additionally evaluate the credibility of the evidence supporting that effect.

To achieve this, assessors evaluate not only study results but also:

• the completeness of the evidence base,
• the appropriateness of comparator selection,
• the quality of indirect comparisons,
• the transparency of statistical analyses,
• the relevance of patient-reported outcomes.

Clinical evidence is therefore no longer judged solely by its results, but also by its methodological robustness. This shift is likely to have a greater long-term impact on European HTA than any individual clinical outcome.

A successful evidence strategy for Joint Clinical Assessments relies on three key principles.

1. Plan Appropriate Comparators Early

Missing or methodologically inadequate comparator data can only be addressed to a limited extent once development has progressed. Comparator selection therefore becomes a strategic decision during clinical development rather than at the time of HTA submission.

2. Ensure Transparent Evidence Generation

European HTA assessors evaluate not only study findings but also how these findings were generated. Systematic literature reviews, transparent methodology, and robust statistical analyses are becoming increasingly important.

3. Explain Uncertainty Transparently

Indirect comparisons, Network Meta-Analyses, and MAICs remain valuable evidence-generation tools. However, their credibility depends on whether assumptions, limitations, and potential sources of bias are clearly documented and justified.

As a result, clinical development, evidence generation, biostatistics, and HTA strategy are becoming far more closely integrated. Successful Joint Clinical Assessments begin long before dossier submission. They start with evidence planning.

The first Joint Clinical Assessments demonstrate that Europe is creating more than a common assessment procedure. A shared methodological standard is emerging that defines which evidence is considered robust and under which conditions clinical results can be interpreted with confidence.

For manufacturers, this represents a significant shift in perspective. Future assessments will depend not only on the quality of individual clinical trials, but on the quality of the overall evidence strategy. Organisations that integrate comparator strategy, endpoint selection, evidence synthesis, and methodological transparency from an early stage will be better positioned for successful Joint Clinical Assessments.

For national HTA procedures, including Germany's AMNOG process, this development has another important consequence. The more transparently European evidence is assessed with respect to its strengths and uncertainties, the more important its national interpretation becomes. This is precisely where the Delta Dossier gains strategic relevance, not as a repetition of the Joint Clinical Assessment, but as the targeted translation of European evidence into the context of national HTA requirements.