Presentation (CTI)

OBJECTIVES: The EU Joint Clinical Assessment (JCA) requires a systematic approach to identify treatment effect modifiers (TEMs) and prognostic variables (PVs) for indirect treatment comparisons (ITCs) but provides limited operational guidance on how this should be implemented. Following presentation of our TEMs/PV identification framework at ISPOR Europe 2025, updated JCA methodological guidance and JCA assessments published to date have provided further insight into assessor expectations. This study updates the framework with a particular focus on systematic literature review (SLR) identification and extraction.
METHODS: The original five-step TEMs/PVs identification framework was reviewed against emerging evidence sources including updated methodological JCA guidance (May 2026), JCA reports and appendices published to date (e.g., tovorafenib, April 2026), and assessor - developer clarification exchanges. Evidence sources were reviewed to identify new expectations regarding TEM/PV identification, evidence requirements and reporting. Findings were mapped to the existing framework and used to refine framework components and develop a standardised variable-level extraction template.
RESULTS: Updated JCA guidance and reporting confirm that an SLR is now expected for TEMs/PV identification prior to an ITC, with an existing review accepted only if recent and considered to be of adequate quality covering the full decision-problem. The completeness of the candidate set of TEMs/PVs in the submission and the clinical rationale for inclusion/exclusion were scrutinized. We converted the extraction step of the framework into a standardised template capturing, per variable: operational definition, outcome and PICO segment; source and analysis type with sample sizes; effect-modification evidence (interaction p-value, within- vs across-subgroup direction, confidence intervals, magnitude, pre-specification); prognostic evidence (uni-/multivariable analyses, adjustment); credibility (plausibility, consistency, risk of bias).
CONCLUSIONS: Early JCA experience signals a clear expectation for rigorous, SLR-based identification of TEMs and PVs, with a transparently documented extraction process. The updated framework presented offers practical, actionable guidance including a standardized extraction template for developers preparing ITCs for JCA.