Recommendation	Rationale
Foster cross‐disciplinary collaboration between pharmacovigilance specialists, pharmacoepidemiology specialists, and RWD partners, and strengthen multidisciplinary knowledge and perspectives.	Input from end users is vital to ensure that developed analytical methods and infrastructure are fit for purpose, meeting practical needs and requirements in pharmacovigilance. Effective integration of RWE in signal management requires synthesis of evidence from RWD, individual case reports, the scientific literature and more. This, in turn, requires collaboration between those with pharmacovigilance and pharmacoepidemiological expertise, as well as those with detailed understanding of the strengths and limitations of the analyzed RWD sources.
When possible, collaborate with other organizations to develop infrastructure, tools, and guidance for use of RWE in signal management	Many organizations face similar challenges. Pooling resources may help overcome the obstacles to broader use of RWE in signal management.
Develop and make available reference sets for benchmark evaluation of methods and RWD sources for diverse signal management use cases	Reference sets are required to understand operating characteristics of analytical methods and datasets. Benchmark evaluations should be possible for any stakeholder to execute for their environment. They can aid in interpreting evidence in light of expected false positive/false negative rates. They may also provide a basis for comparative evaluations of methods and RWD sources. For signal detection, they should include time‐indexed safety signals (with contextual information regarding which signals led to regulatory action, etc.).
Seek to ensure that resources created to support use of RWE in signal management (validated phenotypes, reproducible analytical workflows, benchmark reference sets, and more) remain available and open to continual updating and refinement based on feedback.	Pooling resources may help overcome the obstacles to broader use of RWE in signal management. Evolution of resources is necessary to reflect current scientific best practices and knowledge. Otherwise, they may not be relied upon for regulatory decision‐making. Whether a method meets required standards can ideally be empirically measured through benchmark studies.
To the extent possible, use standard pharmacoepidemiological terminology for describing analytical methods across the signal management use cases.	A common language for describing analytical methods will enable pharmacovigilance organizations to compare and choose between these. The descriptions should use standard epidemiological terminology when available and specify the individual analytical components and design choices to enable scientists to understand the unique and common aspects of different methods and identify opportunities for combining the strengths of different analytical strategies.