OBJECTIVES: The role of RWE in HTA decisions is not well understood. We investigated the role of three RWE study types (external control, patient-reported outcome [PRO], retrospective/database) in HTA decisions, including commonly cited HTA critiques of RWE.

METHODS: IQVIA’s HTA Accelerator^® was used to identify published HTA decisions and develop 49 cases across 17 products. Publicly available reports were reviewed/coded for each case; synthesized findings included the submission contexts, purposes of submitted RWE studies, and whether the RWE studies were deemed fit-for-purpose. Twelve hour-long expert interviews added context to the case review findings.

RESULTS: Many RWE study types have potential roles in HTA decisions, but we found that acceptance of RWE was context-dependent and varied across countries and by the type of scientific question being answered. In our analysis, external control studies contributed to decisions in only 33% of the cases, but did so more frequently than PRO (4%) or other retrospective (0%) studies. Critiques regarding RWE were related to generalizability (inconsistent standard of care, not generalizable to clinical practice, low patient numbers), data quality (completeness/accuracy, mis-defined outcome variables, insufficiently described data), confounding (confounding unmeasured/unjustified, naive comparisons), and data analysis (incorrect adjustment methods, missing/unclear analytical methods). HTA concerns stressed the importance of using country-specific data, aligning to current clinical practice, and submitting complete/sufficiently described RWE.

CONCLUSIONS: Use of RWE in HTA decisions largely depends on study type, specific context of the submission, and meeting HTA expectations regarding confounding, generalizability, and data quality/analysis. While HTA policies regarding RWE highlight these shared basic concerns, RWE planning for HTA is encumbered by a need for greater alignment on specific issues including acceptable study designs and data fitness-for-purpose. Our findings suggest that early and iterative engagement between sponsors and HTA bodies is crucial to ensure that HTA decisions are informed by the highest-quality RWE.