(C-163) Harmonizing Standards: Recommendations for Mitigating Gaps in Real-World Evidence (RWE) Feasibility Guidance

Background: Regulators are emphasizing transparent and robust reporting of feasibility assessment results for RWE studies. A prior ISPE funded initiative mapped 14 feasibility criteria (e.g., reliability, relevance, etc.) across 14 RWE publications and found missing or variable guidance. To build on that assessment, feasibility criteria were mapped across 46 RWE guidelines published through 2024. Results demonstrated a need for global feasibility criteria harmonization and five notable areas requiring further guidance were identified. Here we aim to substantiate and characterize the five potential gaps.

Objectives: To determine if gaps exist and characterize content to inform recommendations for (1) steps in feasibility conduct, (2) operational methods for feasibility evaluations, (3) multi-country/data source assessments, (4) data controller quality management requirements, and (5) templates for disseminating feasibility results.

Methods: Eligibility criteria were applied to 46 RWE guidelines (included for recency [2021-2024] and excluded if not published by a health authority or in English). A deep dive of 17 eligible guidelines by EnCePP, ICH, the Australian government, Anvisa (Brazil), CADTH (Canada), NMPA (China), EMA (EU), MHRA and NICE (UK), and the FDA (US) was completed. Binary (yes/no) questions assessed the presence of the content of interest. Definitions and search terms were also developed for each question. Descriptions to characterize the gaps in each guideline were recorded for comparison. Two independent reviewers read and applied search terms to each guideline. Discrepancies between the mapped binary results and descriptive characterizations were adjudicated by a third reviewer.

Results: Mapping the gaps across RWE guidelines confirmed the hypothesis and recommendations were provided to mitigate gaps. Among the 17 guidelines, 15 (88.2%) did not include templates for disseminating feasibility results, 14 (82.4%) did not mention stages/steps required for the feasibility assessment, 13 (76.5%) lacked operational methods to conduct the feasibility assessment, 12 (70.6%) were missing guidance on conducting feasibility assessments for multi-country and multi-data source studies, and 8 (47.1%) did not provide requirements for data controllers related to transparent reporting of source-level data quality processes. All 17 guidelines had > 1 gap, 13 (76.5%) had > 3 gaps, and 6 (35.3%) had all 5 gaps.

Conclusions: While the focus of RWE guidance may differ between documents, feasibility critically informs study design and the quality of resulting RWE. This analysis identifies important gaps in guidance and provides an IQVIA Insight Guide with recommendations for researchers.