Recommendation	Rationale
Be explicit about the value add of the use of RWE in each phase of signal management for your organization	The benefits of RWE in terms of incremental evidence supporting pharmacovigilance decision‐making must exceed the potential negative impact of unreliable RWE on decision‐making, and the opportunity cost of obtaining and analyzing RWE in lieu of synthesizing other evidence. Earlier signal detection may offset harm to patients, whereas elimination of false positive signals may benefit patient safety and public health and save resources for other activities etc. In general, more robust and comprehensive evidence may increase confidence in decisions.
Share experiences and insights from use of RWE in signal management with the broader community	Postmortem reviews in the scientific literature from both methodological and clinical perspectives are scarce but would enable the pharmacovigilance community to learn from each other's experiences. If scientific publication is not feasible, other modes of dissemination may be explored.
Determine the scope and nature of RWD required for prioritized use cases for your organization	The selected RWD sources should be able to answer a broad enough range of questions likely to emerge as part of the organization's signal management activities, so must include an appropriate set of medicinal products and adverse events and should cover relevant health care settings and appropriate geographies. Consider data catalogues such as https://catalogues.ema.europa.eu
Before incorporating analyses of RWE in signal management, ensure that your organization has the appropriate resources to do so effectively.	Current signal management activities are unlikely to be replaced in the short‐term (although there may be opportunities to close some signals more rapidly with timely access to RWE during signal management). Organizations with few resources, may await more solid tools/infrastructure and guidance, before starting to build this capacity.
If you plan to incorporate analyses of RWE in signal management, perform pilot evaluations for the integration of RWE in your pharmacovigilance use case(s) and share their results	Pilot evaluations enable assessment of performance under realistic conditions, help ensure that surrounding processes are well‐specified, and may allow organizations to evaluate operational considerations for effects on their current pharmacovigilance workflow.