Presentation (CTI)

OBJECTIVES: While RCTs remain the gold standard for clinical evidence, the EU HTA guidelines acknowledge the relevance of non-randomized evidence (NRE) from real-world data (RWD) when more robust evidence is unavailable - a likely scenario for multiple PICOs. Observational studies and external control arms for single-arm trials are increasingly utilized to address evidence gaps. However, the absence of randomization necessitates robust methods to mitigate confounding bias. Propensity score (PS) methods are emphasized as an essential approach to account for confounding factors in effect estimation.
METHODS: This study aims to advance a standardized framework for applying PS methods to non-randomized comparisons by: 1) extracting information from EU HTA guidelines, national HTA methodologies, and German HTA benefit assessments and as well as from Routine Practice Data Collection (RPDC) procedures, such as statistical analysis plans, study protocols, and HTA resolutions (data extracted up to 12-31-2024); 2) comparing EU HTA guidelines with national HTA methodologies, particularly information from Germany's detailed procedures on PS methods and confounder adjustment; and 3) identifying key methodological differences across jurisdictions and their impact on NRE acceptance.
RESULTS: Although methodological criteria for NRE with PS adjustments are outlined in the EU HTA guidelines, significant uncertainty persists regarding what will be considered in Joint Clinical Assessments and the level of rigor required to meet these standards. Relying on RWD challenges submissions, as sufficiently defined approaches remain unclear. In contrast, national practices, especially from Germany, offer valueable insights as RWD is actively integrated into its HTA processes with rigorous methodologies, as in RPDC and confounder adjustment for HTA dossiers. These differences underscore the need for standardized criteria to improve NRE acceptance across jurisdictions.
CONCLUSIONS: The development of a decision framework helps strengthen the integration of RWD in HTA evaluations, enhancing methodological rigor and consistency of evidence assessments to adeptly and successfully navigate the EU HTA process.