Swimming in the Sea of RWE Guidance: Why More Guidance Will Not Help Researchers Swim.

The global use of real-world data (RWD) and real-world evidence (RWE) in regulatory and health technology assessment (HTA) decisions has led to a crucial need for alignment on what constitutes high-quality RWE. Regulators, HTA bodies, and professional societies have issued an abundance of guidance documents, resulting in a state of guidance oversaturation. The existence of multiple initiatives to track this guidance is itself indicative of the challenge researchers face in interpreting and aligning with decision-maker expectations. While the proliferation of guidance forces researchers into exhaustive 'compare and contrast' exercises, multiple publications have documented substantial alignment on core principles, including study design, data quality, the importance of fit-for-purpose data, and methodological rigor. For example, the fundamental requirements for RWD quality are similar between the FDA and EMA. This convergence suggests that additional, redundant guidance is not the answer to addressing remaining gaps. Instead of producing new, high-level guidance, future efforts should pivot toward two critical areas. First, global harmonization of existing guidance is necessary to reduce the resource burden on sponsors and prevent evidentiary fragmentation across jurisdictions. Second, a transparent, annotated repository of diverse case studies must be developed to build operational transparency in RWE use and decision-making. This repository should capture why specific data and methodological decisions were made, how the evidence was evaluated, and how it was ultimately used in decision-making. By shifting the focus from guidance to transparent, precedent-based learning and harmonized standards, the industry can establish a more predictable and efficient pathway for decision-grade RWE integration.