Considerations for the Integration of Clinical Trials and Real‐World Data
As clinical decision-making increasingly moves toward individualized and context-specific treatment recommendations, reliance on any single evidence source, randomized or observational, may be insufficient. Principled integration of randomized controlled trials and real-world data, grounded in explicit causal frameworks, offers a path toward evidence that is both internally credible and externally relevant. In this article, we describe distinct objectives for the integration of randomized controlled trials and real-world data and discuss how these objectives shape key design and analytic considerations, illustrating the resulting choices through example estimands. We highlight practical issues that commonly arise in applied settings, including data relevance and curation, cross-source comparability, estimand specification, and sensitivity analysis. We aim for this article to help readers evaluate and implement principled approaches to integrating randomized controlled trials and real-world data in ways that can support more reliable treatment recommendations while maintaining regulatory-grade evidentiary standards.
Authors
- Andrew N. Mertens (ORCID: https://orcid.org/0000-0002-1050-6721)
- Larry Han (ORCID: https://orcid.org/0000-0002-0577-9661)
- Charles E. Barr (ORCID: https://orcid.org/0000-0001-9883-1897)
- Nerissa Nance (ORCID: https://orcid.org/0000-0002-8407-2364)
- Salina P. Waddy
- Kara E. Rudolph (ORCID: https://orcid.org/0000-0002-9417-7960)
- Hana Lee (ORCID: https://orcid.org/0000-0002-8684-1040)
- Lei Nie (ORCID: https://orcid.org/0000-0002-7791-9395)
- Shawn Qiu (ORCID: https://orcid.org/0009-0006-5944-0782)
- Margot Lisa-Jing Yann (ORCID: https://orcid.org/0009-0004-9232-0382)
- Jens M. Tarp
- Tianyue Zhou
- Mark J. van der Laan (ORCID: https://orcid.org/0000-0003-1432-5511)
- Kajsa Kvist
- Lauren Dang
- Maya Petersen
- Andy Wilson
- Zhiwei Zhang
- Xu Shi
- Kenneth Wiley
Institutions
- Northeastern University (US)
- National Institutes of Health (US)
- Center for Drug Evaluation and Research (US)
- Novo Nordisk (Denmark) (DK)
- University of Utah (US)
- Brown University (US)
- University of Michigan (US)
- National Institute of Allergy and Infectious Diseases (US)
- Gilead Sciences (United States) (US)
- Columbia University (US)
- University of California, Berkeley (US)
Publication Details
- Journal
- Clinical Pharmacology & Therapeutics
- Published
- 2026-10-05
- DOI
- https://doi.org/10.1002/cpt.70513
- Primary Topic
- Advanced Causal Inference Techniques
- Type
- article
- Field-Weighted Citation Impact
- 0.00