Stop Writing Guidance About Guidance: A Call to Harmonize and Illustrate Real-World Evidence Standards

Ashley Jaksa

Summary: This editorial in Value in Health argues that the real-world evidence (RWE) field has reached a state of "guidance oversaturation," in which regulators, health technology assessment bodies, and professional societies have collectively produced so many overlapping documents that researchers spend disproportionate effort comparing frameworks rather than generating evidence. The author contends that core principles—study design, data quality, fit-for-purpose data selection, methodological rigor—are already substantially aligned across major bodies such as the FDA and EMA. Rather than issuing additional high-level guidance, the field should prioritize two things: global harmonization of existing standards and the development of a transparent, annotated repository of real-world case studies illustrating actual decision-making.

Why it matters: For researchers working with patient registries, claims databases, or EHR-derived data, guidance fragmentation is a genuine operational burden—one that consumes resources without improving evidence quality. The proposal for a precedent-based, annotated case repository is practically interesting: regulatory and HTA decisions frequently hinge on tacit criteria that are never fully articulated in formal guidance, and making that reasoning visible would reduce uncertainty for sponsors and researchers alike. If adopted, harmonization efforts could also reduce the risk of evidentiary fragmentation across jurisdictions, a problem with direct consequences for rare-disease research where datasets are already small and cross-national pooling is often essential.

Expert perspective: This is a well-reasoned editorial making a point that many in the field privately acknowledge but rarely state this directly: the volume of RWE guidance has become its own problem. The argument that core principles already converge across major regulators is important and underappreciated—it suggests that the marginal value of yet another guidance document is low, while the cost in researcher attention is real. The two proposed solutions are sensible, though neither is trivial to execute. Global harmonization of guidance requires sustained political will across agencies that have distinct mandates, legal frameworks, and institutional cultures; the editorial does not fully grapple with what that process would look like in practice. The annotated case repository idea is compelling in principle, but its value depends entirely on how transparent decision-makers are willing to be about their reasoning—an openness that has historically been limited. This editorial does not present new empirical data and should be read as advocacy rather than evidence, but the advocacy is grounded and the diagnosis is credible. Worth reading for anyone who has found themselves assembling a spreadsheet comparing FDA, EMA, NICE, and ICER guidance documents and wondering whether the exercise was worth the effort.

Relevance: Registry and Real-World Data Methods

Source: https://pubmed.ncbi.nlm.nih.gov/42562111/

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