Our first Electronic Health Records paper focuses on data accrual. It provides a landscape of tools, best practices, use cases and considerations to help stakeholders understand how EHR-sourced real-world data may be useful for regulatory decisions.

Published February 2025

"Regulatory Fit-for-Purpose Considerations for Patient-Generated Health Data" summarizes key indicators of relevance, reliability, and quality used to determine if PGHD is fit-for-purpose, and the white paper offers practical considerations to support the initial development of medical products supported by PGHD collected in real-world settings.

Published May 2024

In "Real-World Evidence to Support Causal Inference: Methodological Considerations for Non-Interventional Studies," we discuss how RWE can complement traditional trials with greater confidence in the ability to infer causality from a real-world study.

Published June 2024

"Applying Real-World Data and Real-World Evidence for Accelerated Approvals and Coverage Decisions" explores the role RWD and RWE may play making regulatory and payer decisions about medical products on the US FDA's accelerated approval pathway.

Published July 2024

"Lessons from Learning Health Care Systems and Recommendations for Successful Implementation" features original research on how U.S. health systems use real-world data to inform their processes and decision-making. Recommendations based on these findings are proposed, so LHS principles can be further applied across organizations.

Published on October 30, 2023

Despite being a well-established method of testing multiple hypotheses within a single clinical trial, master protocols are not fully conceptualized to support RWE studies. In "Harnessing the Potential of Real-World Evidence Master Protocols" we describe key characteristics of RWE MPs and how they can support the development of critical evidentiary needs for medical products.

Published on October 30, 2023

Patient-level data generated in RWE studies can support evidence generation on traditionally underrepresented and understudied patients. "Improving Patient Subgroup Representation with Real-World Data" describes opportunities and challenges for using RWD to improve care across the breadth of all patients.

Published on September 28, 2023

"Aligning Shared Evidentiary Needs Among Payers and Regulators for a Real-World Data Ecosystem" uses disease use cases to explore building a robust real-world data ecosystem. This white paper pools the expertise of both the RWE Collaborative and the Center's Value for Medical Products Consortium.

Published July 2022

In "Point-of-Care Clinical Trials: Integrating Research and Care Delivery", we set a baseline for what defines and constitutes a point-of-care trial and explore the current impediments to implementing these burgeoning research methods.

Published May 2022

Here, we outline a roadmap for developing, enhancing, and utilizing RWE endpoints. Duke-Margolis hosted a webinar to mark the release of "A Roadmap for Developing Study Endpoints in Real-World Settings."

Published August 2020

In "Adding Real-World Evidence to a Totality of Evidence Approach for Evaluating Marketed Product Effectiveness," we explore the feasibility of overcoming the challenges faced by conducting interventional studies in the real world. How do we address ethical, operational resource barriers? What must be considered when demonstrating the credibility of a non-interventional study using secondary data?

Published December 2019

Non-interventional studies using secondary data can better reflect broader patient populations, care settings, and drug uses found in routine clinical practice. However, questions remain as to when these types of studies are applicable. This paper, "Understanding the Need for Non-Interventional Studies Using Secondary Data to Generate Real-World Evidence for Regulatory Decision Making, and Demonstrating Their Credibility," is about credibility and observational methods explores several of those questions.

Published November 2019

By focusing on electronic health records and patient generated health data, "Determining Real-World Data’s Fitness for Use and the Role of Reliability" describes a framework for how researchers and reviewers can systematically evaluate whether RWD are fit for use in regulatory decision-making.

Published September 2019

Not all RWD is created equal. Regulators need access to ample, well-sourced, fit-for-purpose data, and "Characterizing RWD Quality and Relevancy for Regulatory Purposes" explains what that means.

Published October 2018

In our first white paper "A Framework for Regulatory Use of Real-World Evidence," we define real-world data and real-world evidence and provide context to its role in regulatory decision-making. Consider this a foundation upon which subsequent white papers are built.

Published September 2017

Shaping the US & International RWE Policy Landscape: This workstream will build on the RWE Collaborative’s prior work and engagement within the 2022-2024 Regulatory Acceptability of RWE workstream, with the intent to expand its focus on advancing RWE policy in areas of regulatory, payer, and health technology assessment (HTA) consideration. In response to current and anticipated FDA and other regulatory guidance, this workstream will monitor and respond to regulatory draft guidance, maintain updates to Duke-Margolis International Harmonization of RWE Dashboard, and develop written material(s), such as a policy brief or white paper, as a means of elucidating or describing fundamental aspects of the regulatory, payer, and HTA consideration, use, and/or acceptance of RWD/RWE at national and/or international levels. The workstream members will continue to monitor governmental (i.e., FDA and other regulatory draft and final guidance) requests for information or comments with the intent to review and respond accordingly and as deemed sufficient and/or appropriate by the workstream. The workstream will also participate in the development and execution of the annual Duke-Margolis State of RWE Policy event to effectively engage members of the public around pertinent issues and opportunities that are relevant to advancing RWE policy.

Operationalizing Electronic Health Record Data Relevance, Reliability, and Quality for RWE Policy Stakeholders: RWE policy stakeholders, including regulators, sponsors, data curators, health systems, and patients, routinely consider electronic health records (EHRs) as data widely used in medical product safety studies and increasingly proposed for use or used in medical product effectiveness studies. This workstream will build on prior Duke-Margolis work and engagement relevant to the title of this workstream and contemplate, curate, and share best practices and tools needed to operationalize fit-for-purpose domains with respect to EHR data relevance, reliability, and quality across areas within the EHR data lifecycle (data accrual, data curation, data transformation). In 2024, the workstream focused on operationalizing aspects of data accrual. In 2025, the workstream will focus on operationalizing aspects of data curation.

Since 2018, the Duke-Margolis Center for Health Policy’s Real-World Evidence (RWE) Collaborative has convened stakeholders representing medical product developers, data companies, payers, research groups, providers, patient networks, as well as experts on regulatory affairs, law, health and data science, and policy, with a shared goal and interest to advance RWE policy. This effort includes convening stakeholders who hold shared goals to advance RWE policy among international agencies, health technology assessment bodies, and regulators. The Duke-Margolis RWE policy research team has developed dashboards and other resources to help internationally focused RWE policy stakeholders track, in one place, relevant and timely regulatory guidance, frameworks, international harmonization documents, and more.

Every year, Duke-Margolis and the RWE Collaborative host a virtual, public convening to highlight the latest developments in RWD/E policy. The live event receives thousands of registrations, and we're pleased to engage with live audience Q&As.

2024 Convening on the State of RWE Policy

2023 Convening on the State of RWE Policy

2022 Convening on the State of RWE Policy

Duke-Margolis frequently hosts public events informed by white papers and workstream activities. RWE Collaborative members and partners have shared scientific and policy expertise on countless panels, which are often covered in the media.

• 2020 Webinar on Developing Study Endpoints in Real-World Settings
• 2020 Conference on Applying Lessons Learned from RWE in the Time of COVID-19 to the Future
• 2020 Webinar on Bolstering RWE Study Credibility and Its Role in a Totality of Evidence Approach
• 2019 Workshop on Developing Real-World Data and Evidence to Support Regulatory Decision-Making
• 2018 Conference on Real-world Data and Evidence
• 2017 Workshop on A Framework for Regulatory Use of Real-World Evidence

• "FDA User Fee Reauthorization and the Value of Real-World Evidence" published in September 2022 by Duke-Margolis
• "Cures 2.0: Building a Modern Health Data Infrastructure" published in October 2021 by Duke-Margolis

The RWE Collaborative diligently watches for guidance documents released by the US Food and Drug Administration. When the docket opens for public comment, the Duke team and workstream partners collaborate on recommendations for FDA. Below are recent comments submitted.

• FDA-2025-N-0287: Exploration of Health Level Seven Fast Healthcare Interoperability Resources for Use in Study Data Created From Real-World Data Sources for Submission to the Food and Drug Administration
• FDA-2025-N-0129: Electronic Study Data Submission; Data Standards; Clinical Data Interchange Standards Consortium Dataset-JavaScript Object Notation
• FDA-2023-D-2318: Demonstrating Substantial Evidence of Effectiveness With One Adequate and Well-Controlled Clinical Investigation and Confirmatory Evidence
• FDA-2022-D-2692: Postmarketing Approaches to Obtain Data on Populations Underrepresented in Clinical Trials for Drugs and Biological Products
• FDA-2022-D-2983: Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products
• FDA-2021-D-1214: Considerations for the Use of Real-World Data and Real-World Evidence to Support Regulatory Decision-Making for Drug and Biological Products
• FDA-2021-D-0548: Data Standards for Drug and Biological Product Submissions Containing Real-World Data
• FDA-2021-D-1146: Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products
• FDA-2020-D-2307: Real-World Data: Assessing Electronic Health Records and Medical Claims Data to Support Regulatory Decision-Marking for Drug and Biological Products; Draft Guidance for Industry

Duke-Margolis Faculty: Policy questions about real-world evidence and big data increasingly interact with every aspect of health care. Duke-Margolis is proud to collaborate with faculty across the wide family of Duke University schools, institutes, centers, and initiatives. If you are a Duke University researcher interested in how RWD/E or how it may overlap with your work, please contact Research Director Rachele Hendricks-Sturrup at rachele.hendricks.sturrup@duke.edu

Bass Connections: Bass bridges the classroom and the real world, giving students a chance to roll up their sleeves and tackle complex societal problems alongside faculty from across Duke. Working in interdisciplinary teams, graduate and undergraduate students collaborate with faculty on cutting-edge research that spans subjects, demographic groups and borders. Bass Connections builds on Duke’s culture of collaboration and fosters knowledge in service to society.