Reviewing the HTA and Regulatory Policy Landscape on Acceptability Standards for Real-World Evidence

OBJECTIVES: IDERHA (Integration of Heterogeneous Data and Evidence towards Regulatory and HTA Acceptance) is a European Innovative Health Initiative (IHI) project launched in 2023, aiming to enable the safe, secure, and streamlined sharing of heterogeneous healthcare data. The objective of this study is to accelerate policy development and build consensus on the use of real-world data (RWD) and real-world evidence (RWE) in regulatory and Health Technology Assessment (HTA) decision-making for medicines and medical technologies by reviewing global acceptability standards.

METHODS: A literature search was conducted on MEDLINE ALL, Embase, and relevant organizational websites (e.g., US FDA, EMA, NICE). Included documents were policies, standards, frameworks, or guidance on RWE use, published from 2017 to January 2024, in English or with English translations. Documents were excluded if superseded by updated versions. Data extraction focused on guidance for RWE use, study design, data quality, and transparency.

RESULTS: To our knowledge, this is the first review to look across policies for regulatory and HTA, cover both medicines and medical devices, and have a global scope. The review analyzed 50 policy or guidance documents from 29 organizations, with 32 coming from regulatory, 14 from HTA, and 4 from third-party organizations. Results of the data extraction were broken down into 7 broad categories: definitions of RWD/RWE; uses of RWD and RWE; guidance on study design and conduct; data collection, curation, and characterization; data quality assessment; ethics, governance, trust, and transparency; intersection of RWD/RWE and artificial intelligence.

CONCLUSIONS: The review revealed progress in technical and methodological approaches to RWE but highlights areas needing further exploration, including alignment on analytical approaches, relevance to digital health, intersections with AI, and regulatory-HTA evidence standards alignment. Future work will prioritize advancing emerging best practices and addressing policy gaps to enhance RWE acceptance in regulatory and HTA decision-making by developing policy recommendations.