CIOMS Working Group XIII: RWD and RWE in Regulatory Decision Making
A global multi-stakeholder consensus framework that defines when and how real-world data and real-world evidence should enter regulatory decision making across the product lifecycle, setting expectations for research questions, fitness-for-purpose, study design, governance, and transparency.
What it is
— Real-World Data and Real-World Evidence in Regulatory Decision Making, the consensus report of the Council for International Organizations of Medical Sciences (CIOMS) Working Group XIII (CIOMS WG XIII), published by CIOMS in 2024 with a peer-reviewed report summary appearing in Pharmacoepidemiology and Drug Safety in 2025. CIOMS is a Geneva-based international NGO (established jointly by WHO and UNESCO) whose working groups produce global, multi-stakeholder consensus guidance. Unlike a reporting checklist maintained by EQUATOR (STROBE, RECORD-PE) or a critical-appraisal instrument (ROBINS-I, Newcastle-Ottawa), WG XIII is a decision framework: it harmonizes terminology and articulates the triggers, objectives, research questions, design features, governance, ethics, and timing that determine whether RWD can generate RWE fit to support a regulatory action. It is descriptive and principles-based, not a numbered scorecard, and it deliberately spans the full lifecycle from pre-authorization through post-marketing safety and effectiveness.
When to use
— Reach for CIOMS WG XIII at the framing stage of any non-interventional or hybrid study whose results are intended to inform a regulatory decision (FDA, EMA, or other national agencies), and as a shared reference when an industry team, a regulator, and an academic partner must agree on whether an RWE question is answerable and worth pursuing. It is the appropriate lens when you are deciding whether RWD/RWE is the right evidence source for a given objective (e.g., an external control arm, a label expansion, a safety characterization, or an imposed/voluntary PASS), and what design and data conditions would make that evidence credible. Decision rule for choosing WG XIII versus its siblings: use WG XIII to establish the regulatory rationale, evidence objective, and fitness expectations; switch to HARPER or StaRT-RWE when you move to writing the study protocol template; use the ENCePP Guide on Methodological Standards and the ENCePP Checklist for EU PASS methodological conduct; and use STROBE / RECORD-PE at the manuscript-reporting stage. WG XIII complements, and does not replace, agency-specific guidance such as the FDA RWE Framework or EMA/HMA RWE guidances.
What it requires
— The framework drives substantive expectations rather than checklist ticks. It asks that teams (1) state a precise, decision-relevant research question and the regulatory objective it serves, with the estimand (target population, treatment strategies, intercurrent-event handling, summary measure) made explicit; (2) demonstrate fitness-for-purpose of the data source(s) — relevance (do the data capture the population, exposure, outcomes, and covariates needed?) and reliability (provenance, completeness, accuracy, traceability, and data quality/QC) — before analysis; (3) validate phenotypes and operational definitions for exposure, outcomes, and key covariates (algorithm performance, e.g., PPV/sensitivity); (4) align time zero and follow-up to avoid immortal-time and related design biases; (5) pre-specify confounding control and address measured and unmeasured confounding; (6) plan for attrition, missing data, and censoring; (7) pre-register protocol and analysis plans and commit to transparency and reproducibility (versioned code lists, study registration); and (8) carry quantitative bias and sensitivity analyses through to interpretation. Governance, patient privacy, ethics, and multi-region regulatory acceptability run throughout.
When NOT to use — limitations and common misapplications
— WG XIII is not a reporting checklist and not a risk-of-bias or quality-scoring instrument; completing or citing it does not document a study or grade its internal validity, and it cannot substitute for STROBE/RECORD-PE at write-up or for ROBINS-I at appraisal. It frames the assessment of fitness-for-purpose but does not perform it — invoking WG XIII does not certify that a database is fit; that judgment must be evidenced. It is not a protocol template: do not use it where HARPER or StaRT-RWE is required to specify the design, and do not treat it as a replacement for the ENCePP Guide on Methodological Standards governing EU PASS conduct. The deepest failure mode is framework-as-theater: citing the consensus to lend regulatory gloss to a study while leaving estimands vague, phenotypes unvalidated, time zero misaligned, and confounding unaddressed. Adopting its principles does not make an observational comparison causal; the design, comparator, and analysis still have to earn that. Finally, regional regulatory acceptance varies, so WG XIII consensus does not guarantee any single agency's acceptance of a given study.
How it maps to this catalog
— Each WG XIII expectation is implemented by concrete catalog concepts. The estimand and intercurrent-event requirement is operationalized by `estimands-ate-att-intercurrent-events-rwe` and traced via `estimand-analysis-traceability-rwe`, with `picots-framework-rwe` structuring the question. Fitness-for-purpose maps to `fit-for-purpose-data-assessment-rwe`, plus `database-feasibility-attrition-funnel-rwe` and `claims-analysis` for source-specific feasibility and provenance. Phenotype/algorithm validation is implemented by `diagnosis-phenotype-algorithm-1ip-2op-time-window-rwe`, `claims-outcome-algorithm-ppv-sensitivity-rwe`, and `ehr-phenotyping-algorithms-rwe`. Time-zero alignment and the new-user/active-comparator design are realized through `time-zero-index-date-alignment-rwe`, `immortal-time-bias-handling`, and `active-comparator-new-user` (often within `target-trial-emulation`). Confounding control is delivered by `high-dimensional-propensity-score-hdps-rwe` and `propensity-score-methods-psm-iptw`. Attrition, missing data, and sensitivity/quantitative bias analysis are covered by `attrition-and-loss-to-follow-up-rwe`, `unmeasured-confounding-probabilistic-bias-analysis-rwe`, and `e-value-sensitivity-analysis`. Applied note: for a claims- or EHR-based external-control or PASS study, WG XIII is the upstream rationale and acceptability layer — establish the regulatory objective and data fitness with it, build the protocol with HARPER/StaRT-RWE, implement the design and analysis with the concepts above, and report with RECORD-PE/STROBE.