ISPOR and ISPE issue call to action for RWE transparency

ISPOR and ISPE have published a joint position statement outlining recommended practices to increase transparency across the lifecycle of real-world evidence studies.

The Baseline

• ISPOR and ISPE have announced recommendations to improve transparency across real-world evidence studies.
• The practices include protocol preregistration, structured protocols, data quality assessments, and transparency statements.
• The societies aim to improve the reproducibility, credibility, and evaluation of real-world evidence research. Researchers and other stakeholders can support the statement through its dedicated LinkedIn page.

ISPOR—The Professional Society for Health Economics and Outcomes Research and the International Society for Pharmacoepidemiology (ISPE) have announced the publication of a joint statement setting out recommendations for documenting the design, conduct and reporting of real-world evidence (RWE) studies.

The statement comes as RWE is increasingly considered in regulatory, clinical and policy decision-making. As the societies explain, while RWE offers tremendous potential, “it also presents very real concerns that continue to cast shadows on its credibility.” The recommendations seek to address these concerns through practices including protocol preregistration, structured study protocols, data quality assessments and transparency statements.

The societies describe transparency as “fundamental to the reproducibility, credibility, and usefulness of RWE.” By providing a record of “what was planned, what was implemented, what was amended, and why,” the societies say this documentation allows stakeholders to examine methodological decisions and potential sources of bias.

However, the statement distinguishes transparency from the validity of the research itself:

“Transparency does not guarantee that a study is valid, nor does a lack of transparency imply flawed methods,” the societies state.

Validity depends on factors including rigorous study design, appropriate data and sound analytic choices; transparent documentation instead provides information that can be used to evaluate these elements.

To support this documentation in practice, the societies point to several existing resources. These include the RWE Registry, launched in 2021 as part of an earlier ISPOR–ISPE collaboration, as well as the HMA-EMA Catalogues and ClinicalTrials.gov, which provide mechanisms for protocol preregistration and reporting.

The statement also highlights the HARmonized Protocol Template to Enhance Reproducibility (HARPER), developed through an ISPOR–ISPE collaboration as a structured framework for describing intended study design and implementation. HARPER has been incorporated into guidance from organizations including ICH, ENCePP, CIOMS, NICE and CMS.

Other resources referenced include data quality assessment tools and guidance from EMA, NICE and the US FDA, alongside approaches for sharing analytic code, phenotyping logic, and reproducible workflows. ISPOR and ISPE journals encourage transparency statements with open science badges, while the societies say their conferences will recognize open science practices in oral and poster presentations.

Shirley Wang (Harvard Medical School and Brigham and Women’s Hospital) highlighted the role of wider adoption in implementing these approaches:

“Many of the tools already exist. The challenge is building them into everyday practice. This will require researchers, institutions, journals, data providers, funders, regulators, and other decision makers to signal collectively that transparency is something our field values and expects.”

The emphasis on transparency reflects wider efforts to establish clearer expectations for RWE research. The Evidence Base has previously examined a five-domain RWE transparency framework proposed by Shirley Wang and Anton Pottegård, covering protocols, preregistration, data, code sharing and reporting checklists, as well as updated Journal of Comparative Effectiveness Research author guidelines encouraging transparency statements for RWE studies.

The position statement concludes with recommendations for these practices to be used more consistently across the RWE community. These include preregistering future study protocols, using structured templates such as HARPER, publishing data quality metrics, and including structured transparency statements with open science badges in manuscripts and presentations. The societies also recommend incorporating transparent research practices into academic training, with senior researchers, journals, and peer reviewers supporting their adoption. Summarizing their position, ISPOR and ISPE state that:

“Transparency must become a shared expectation across our community.”

Researchers and other stakeholders can support the statement through the Joint Position Statement on Scientific Transparency for Real-World Evidence Studies LinkedIn page.