ISPE updates RWE position statement with priorities for methods, AI and patient engagement

ISPE has updated its position statement on real-world evidence, calling for rigorous methods, clear evidentiary standards and responsible use of emerging technologies. The 2026 paper reflects the field’s current role in medical product development and evaluation, while identifying methodological advances, AI and patient engagement as priorities for future progress.

The Baseline

• ISPE’s Board of Directors endorsed the updated RWE position paper on November 4, 2026, revising its first statement released in February 2020.
• The statement calls for fit-for-purpose data, prespecified protocols and transparent, reproducible analyses to support healthcare decisions.
• Priorities include addressing methodological challenges, supporting appropriate use of AI and digital technologies, and involving patients early in evidence generation.

The International Society for Pharmacoepidemiology (ISPE) has updated its position on real-world evidence (RWE), revising its first statement released in February 2020. The 2026 paper sets out priorities for researchers, regulators, HTA bodies and industry as RWE use develops across the medical product lifecycle.

The update was led by Donna Rivera, Mehmet Burcu and Montse Soriano Gabarró, in collaboration with ISPE members, including John Diaz-Decaro, Grammati Sarri and Sengwee Toh.

“ISPE affirms that high-quality, fit-for-purpose RWE is essential for informed regulatory, clinical, and policy decision-making in medical product development worldwide,” the paper states. “ISPE supports the rigorous, transparent, and ethical generation and use of RWE, and calls for continued collaborative efforts to advance the field.”

The statement describes the contribution of RWE to regulatory review, HTA and postmarketing evaluation. While randomized controlled trials remain the gold standard for regulatory approval of new molecular entities and other health technologies, RWE can provide pivotal evidence on safety and effectiveness when supported by appropriate designs, robust data and interdisciplinary expertise. It can also complement trials through longer follow-up and evaluation of outcomes in more diverse populations and routine care settings.

To support these applications, ISPE urges researchers to prespecify protocols, assess whether data are fit-for-purpose and use transparent, reproducible analyses. Further methodological advances are needed to address confounding, missing data, measurement error and increasingly complex data sources. The paper highlights existing contributions, including target trial emulation, external control designs and the HARmonized Protocol Template to Enhance Reproducibility (HARPER).

The update follows a joint call to action from ISPOR and ISPE in September to strengthen transparency in RWE, reinforcing that emphasis through its recommendations for study planning and reporting.

ISPE priorities AI and digital health technologies feature in the society’s future agenda. ISPE identifies a continuing role in shaping methods, applications and policy as these technologies mature, while safeguarding data integrity and evidence quality. Its Digital Technology and Artificial Intelligence Special Interest Group, established in 2025, provides a forum for sharing good practices, developing methodological skills and supporting education and interdisciplinary collaboration. Amongst their activities the group is currently conducting a living scoping review of AI applications across the RWE lifecycle to systematically map published applications and approaches, their reported benefits and challenges, and gaps in the evidence.

The new position statement also calls for early engagement with patients and other stakeholders in study design, outcome selection and dissemination. It encourages approaches that support equity and align evidence generation with patient needs.

The paper concludes:

“As a global leader in RWE, ISPE will be instrumental in advancing high-quality clinical evidence generation that improves medical product development, healthcare decision-making, and patient outcomes and health.”