Advancing Principled Pharmacoepidemiologic Research to Support Regulatory and Healthcare Decision Making: The Era of Real-World Evidence

Rohini K Hernandez¹, Cathy W Critchlow², Nancy Dreyer³, Timothy L Lash⁴, Robert F Reynolds⁵, Henrik T Sørensen⁶, Jeff L Lange¹, Nicolle M Gatto^{7

8}, Rachel E Sobel⁹, Edward Chia-Cheng Lai^{10

11}, Marieke Schoonen¹², Jeffrey S Brown¹³, Jennifer B Christian¹⁴, M Alan Brookhart¹⁵, Brian D Bradbury^{1

16}

Affiliations

¹ Center for Observational Research, Amgen Inc., Thousand Oaks, California, USA.
² Real World Evidence Strategies, Thousand Oaks, California, USA.
³ University of North Carolina, Chapel Hill, North Carolina, USA.
⁴ Department of Epidemiology, Emory University, Atlanta, Georgia, USA.
⁵ Global Epidemiology, GSK, New York, New York, USA.
⁶ Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University, Aarhus, Denmark.
⁷ Aetion, New York, New York, USA.
⁸ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
⁹ Regeneron Pharmaceuticals, Tarrytown, New York, USA.
¹⁰ School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
¹¹ Population Health Data Center, National Cheng Kung University, Tainan, Taiwan.
¹² Center for Observational Research, Amgen Ltd, Uxbridge, UK.
¹³ TriNetX, Cambridge, Massachusetts, USA.
¹⁴ Target RWE, Durham, North Carolina, USA.
¹⁵ Department of Population Health Sciences, Duke University, Durham, North Carolina, USA.
¹⁶ Department of Epidemiology, University of California, Los Angeles, California, USA.

PMID: 39807817
PMCID: PMC11924150
DOI: 10.1002/cpt.3563

Review

Advancing Principled Pharmacoepidemiologic Research to Support Regulatory and Healthcare Decision Making: The Era of Real-World Evidence

Rohini K Hernandez et al. Clin Pharmacol Ther. 2025 Apr.

. 2025 Apr;117(4):927-937.

doi: 10.1002/cpt.3563. Epub 2025 Jan 14.

Authors

Affiliations

¹ Center for Observational Research, Amgen Inc., Thousand Oaks, California, USA.
² Real World Evidence Strategies, Thousand Oaks, California, USA.
³ University of North Carolina, Chapel Hill, North Carolina, USA.
⁴ Department of Epidemiology, Emory University, Atlanta, Georgia, USA.
⁵ Global Epidemiology, GSK, New York, New York, USA.
⁶ Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University, Aarhus, Denmark.
⁷ Aetion, New York, New York, USA.
⁸ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA.
⁹ Regeneron Pharmaceuticals, Tarrytown, New York, USA.
¹⁰ School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
¹¹ Population Health Data Center, National Cheng Kung University, Tainan, Taiwan.
¹² Center for Observational Research, Amgen Ltd, Uxbridge, UK.
¹³ TriNetX, Cambridge, Massachusetts, USA.
¹⁴ Target RWE, Durham, North Carolina, USA.
¹⁵ Department of Population Health Sciences, Duke University, Durham, North Carolina, USA.
¹⁶ Department of Epidemiology, University of California, Los Angeles, California, USA.

PMID: 39807817
PMCID: PMC11924150
DOI: 10.1002/cpt.3563

Abstract

A compilation of factors over the past decade-including the availability of increasingly large and rich healthcare datasets, advanced technologies to extract unstructured information from health records and digital sources, advancement of principled study design and analytic methods to emulate clinical trials, and frameworks to support transparent study conduct-has ushered in a new era of real-world evidence (RWE). This review article describes the evolution of the RWE era, including pharmacoepidemiologic methods designed to support causal inferences regarding treatment effects, the role of regulators and other health authorities in establishing distributed real-world data networks enabling analytics at scale, and the many global guidance documents on principled methods of producing RWE. This article also highlights the growing opportunity for RWE to support decision making by regulators, health technology assessment groups, clinicians, patients, and other stakeholders and provides examples of influential RWE studies. RWE holds promise to address important questions that clinical trials typically do not answer about treatment benefits and risks, and to ultimately impact public health by helping to guide decision making across the healthcare ecosystem.

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Conflict of interest statement

RKH, JLL, MS, and BDB are employees of and own stock in Amgen, Inc. CWC owns stock in Amgen, Inc. ND declares no competing interest for this work. TLL is a member of the Amgen Methods Advisory Council, for which he receives consulting fees and travel support. RFR is an employee and shareholder of GSK. The views described herein are his and do not necessarily represent those of GSK. HTS declares that The Department of Clinical Epidemiology, Aarhus University, and Aarhus University Hospital receive funding from various companies in the form of research grants to (and administered by) Aarhus University. None of these grants are related to the present paper. NMG is an employee of and has stock options in Aetion, Inc., which provides consultation and analytic services to biopharmaceutical and device companies, government organizations, and payers in healthcare. RES is an employee and shareholder of Regeneron Pharmaceuticals and holds stock in Pfizer. ECCL reports research funding from Amgen, Novatis, Pfizer, Sanofi, Takeda, Roche, IQVIA, Clarivate, Adelphi, the Taiwan National Science and Technology Council (NSTC 113‐2628‐B‐006‐009‐), and the Taiwan National Health Research Institutes, outside the submitted work, with no conflicts of interest. JSB declares no competing interest for this work. JBC is employed by and owns stock in TargetRWE. MAB serves on scientific advisory committees for the American Academy of Allergy, Asthma & Immunology, Amgen, the Brigham and Women's Hospital, Gilead/Kite, Intercept, National Institute of Diabetes and Digestive and Kidney Diseases, and Regeneron, and owns equity in AccompanyHealth, Target RWE, and VitriVax.

Figures

**Figure 1**
Select RWE legislation, capability builds, and guidance documents from across the globe. CNODES: Canadian Network of Observational Drug Effect Studies; CADTH: Canadian Agency for Drugs and Technologies in Health; ENCePP: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance; NICE: National Institute for Clinical Excellence; RWE: Real‐world Evidence; DARWIN EU(R): Data Analysis and Real World Interrogation Network; MHLW: Ministry of Health, Labour and Welfare; MID‐NET: Medical Information Database Network; PMDA: Pharmaceuticals and Medical Devices Agency: FDA: Food & Drug Administration; CMS: Center for Medicare & Medicaid Services; NMPA: National Medical Products Administration.

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References

1. ICH‐reflection‐paper‐pursuing‐opportunities‐harmonisation in using real‐world data to generate real‐world evidence, with a focus on effectiveness of medicines. European Medicines Agency <https://www.ema.europa.eu/en/documents/scientific‐guideline/ich‐reflecti...> (2024). Accessed October 16, 2024.
1. Concato, J. & Corrigan‐Curay, J. Real‐world evidence—where are we now? N. Engl. J. Med. 18, 1680–1682 (2022). - PubMed
1. Schulz, K. & Horton, D. Randomised controlled trial: gold standard. In Essential Concepts in Clinical Research: Randomised Controlled Trials and Observational Epidemiology (Elsevier, New York, 2019).
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Advancing Principled Pharmacoepidemiologic Research to Support Regulatory and Healthcare Decision Making: The Era of Real-World Evidence

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Advancing Principled Pharmacoepidemiologic Research to Support Regulatory and Healthcare Decision Making: The Era of Real-World Evidence

Authors

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Abstract

Conflict of interest statement

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