The Maze of RWE Frameworks: An Environmental Scanning and Comparison Across Regulatory and HTA Bodies

OBJECTIVES: Differences in guidance for the use of real-world evidence (RWE) in healthcare decision-making creates complexity in preparing for regulatory and reimbursement submissions which should be untangled. In addition, the number of RWE frameworks and guidance continues to quickly increase. This study aimed to conduct an environmental scan (review) of RWE frameworks and guidance documents across regulatory and health technology assessment (HTA) agencies.

METHODS: The websites of the United States (US) Food and Drug Administration (FDA), European Medicines Agency (EMA), United Kingdom’s Medicines and Healthcare products Regulatory Agency, Taiwan FDA, Canadian Agency for Drugs and Technologies in Health (CADTH), Institute for Clinical and Economic Review, Institute for Quality and Efficiency in Health Care (IQWiG), and EUnetHTA were systematically searched in June 2023 for RWE guidance including white papers. Using a pre-designed form, data on scope and recommendations were extracted from each document. Guidance on artificial intelligence or digital technologies were excluded. Results were synthesized by four topics (study planning, choosing fit-for-purpose data, study conduct, and reporting) to identify similarities and differences.

RESULTS: Forty-two documents were identified, of which seven were from HTA bodies. All except two (NICE, US FDA) were published after 2018. FDA and EMA documents covered all four topics. NICE and CADTH frameworks provided a centralised document with all RWE submission requirements. Only EMA, NICE, and IQWiG guidance included specific analytical suggestions. The NICE framework included the most complete list of RWE quality tools by study design and addressed specific methodological topics by RWE use. Similarities and differences of RWE requirements such as study registration and common data elements were noted.

CONCLUSIONS: Keeping updated with the rapid publication of RWE frameworks and guidance across organisations remains a challenge for stakeholders. Closer collaboration among organisations to standardise RWE practices for regulatory and reimbursement submissions can facilitate timely medicines assessment and access for patients.