Use of RWE in HTA Submissions: A Systematic Review of Case Studies Across Three HTA Agencies Reveals Continued Concerns Around Internal Validity and Unmeasured Confounding
Author(s)
Philipp Liedtke, MSc.
Simon-Kucher, Cologne, Germany.
Simon-Kucher, Cologne, Germany.
OBJECTIVES: Real-world evidence (RWE) is increasingly used to establish the comparative effectiveness of novel therapies. Systematic reviews on the role of RWE in HTA decision-making remain scarce and limited to specific therapeutic areas. This comprehensive analysis aimed to identify the most common critiques raised by HTA agencies and the impact of RWE on HTA decisions in two key contexts: (1) when RWE was used to construct external control arms (ECAs), and (2) when RWE served as the primary data source for a novel drug in HTA reassessments.
METHODS: HTA cases involving RWE submissions from 2020-2024 in these two contexts were systematically identified. The analysis focused on three European HTA agencies: G-BA (Germany), NICE (UK), and HAS (France). A total of 42 relevant cases were included. Specific critiques from HTA reports were identified and evaluated against a predefined catalogue of methodological critiques developed based on RWE guidelines and existing literature. Cases were then assessed on whether RWE was considered for the HTA decisions and the extent of impact on the final HTA outcome.
RESULTS: All identified cases involved either orphan or oncology drugs, or both. Acceptance of RWE differed across agencies, with NICE considering RWE in 93% of identified cases, compared to 21% at G-BA and 14% at HAS. However, the impact on outcomes was limited, with RWE submissions being associated with favorable HTA decisions in only 36% (NICE) and 14% (G-BA and HAS) of all cases reviewed. Most frequent critiques were unmeasured confounding (57%) and concerns about internal validity (55%).
CONCLUSIONS: Use of RWE for comparative effectiveness remains largely confined to orphan and oncology drugs. Frequently raised methodological concerns around unmeasured confounding and internal validity continue to hinder its acceptance and influence in HTA decisions. Manufactures should focus on prospectively planning ECAs and ensuring registries collect relevant patient characteristics to enable robust adjusted comparisons.
METHODS: HTA cases involving RWE submissions from 2020-2024 in these two contexts were systematically identified. The analysis focused on three European HTA agencies: G-BA (Germany), NICE (UK), and HAS (France). A total of 42 relevant cases were included. Specific critiques from HTA reports were identified and evaluated against a predefined catalogue of methodological critiques developed based on RWE guidelines and existing literature. Cases were then assessed on whether RWE was considered for the HTA decisions and the extent of impact on the final HTA outcome.
RESULTS: All identified cases involved either orphan or oncology drugs, or both. Acceptance of RWE differed across agencies, with NICE considering RWE in 93% of identified cases, compared to 21% at G-BA and 14% at HAS. However, the impact on outcomes was limited, with RWE submissions being associated with favorable HTA decisions in only 36% (NICE) and 14% (G-BA and HAS) of all cases reviewed. Most frequent critiques were unmeasured confounding (57%) and concerns about internal validity (55%).
CONCLUSIONS: Use of RWE for comparative effectiveness remains largely confined to orphan and oncology drugs. Frequently raised methodological concerns around unmeasured confounding and internal validity continue to hinder its acceptance and influence in HTA decisions. Manufactures should focus on prospectively planning ECAs and ensuring registries collect relevant patient characteristics to enable robust adjusted comparisons.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
RWD190
Topic
Health Policy & Regulatory, Health Technology Assessment, Real World Data & Information Systems
Disease
Oncology, Rare & Orphan Diseases