Transportability Analyses in Comparative Effectiveness Research: A Conceptual Framework and Methodological Principles...

Transportability considerations are increasingly important to answer research questions in comparative effectiveness research (CER) to support the transfer of evidence on medicinal products across countries or settings. As drug development costs rise and healthcare systems and professionals face economic and resource pressures, leveraging existing data and evidence generated across borders or settings can improve efficiency and inform decisions in product development and decision-making (regulatory, health technology assessment [HTA] and clinical care). Differences in population characteristics, healthcare systems, and data availability, including coding discrepancies, may present significant challenges to the transportability of CER evidence. Without rigorous methodological approaches, the utility of transportability analyses is limited.

This article provides a structured framework for considering transportability exercises in CER analyses. We outlined key methodological principles, when and why to use transportability exercises in CER, feasibility assessments including effect modifier identification and causal inference techniques such as weighting, outcome regression, and combined methods to guide transportability analytical approaches in CER. By synthesizing existing literature and expert insights, we identified opportunities and trade-offs in applying transportability methods to support decisions across the product lifecycle.

To enhance the adoption of transportability analyses, we proposed best practices for researchers, regulators, HTA bodies, and industry stakeholders. These include early engagement with regulatory agencies and HTA bodies, transparent documentation of data assumptions, quality, fitness, and comparability assessments while ensuring robust analytical approaches. We also emphasized the need for standardized reporting guidelines and cross-country collaborations to validate transportability methods in real-world settings and communicate uncertainty in transported evidence.

Transportability analyses offer a powerful tool for extending the applicability of CER findings across healthcare systems, improving evidence generation efficiency, and supporting global drug development and evaluation. By implementing best practices that promote a rigorous and transparent approach to the design and conduct of such analyses, stakeholders can maximize the value of transported treatment effects while ensuring scientific rigor and decision-making relevance. Future research should focus on empirical testing and validation of transportability methods targeting different questions across the product lifecycle and the development of harmonized regulatory and HTA methodological standards. "This manuscript is endorsed by the International Society for Pharmacoepidemiology (ISPE)." Official Endorsement was received on 5/13/26.