"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.

Cited at least 2 times since publication on July 20, 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.

Cited at least 4 times since publication on May 11, 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."

Cited at least 10 times since publication on August 28, 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?

Cited at least 24 times since publication on December 19, 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.

Cited at least 20 times since publication on November 25, 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.

Cited at least 48 times since publication on September 26, 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.

Cited at least 40 times since publication on October 1, 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.

Cited at least 100 times since publication on September 13, 2017

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.

Regulatory Acceptability of RWD and RWE…This annual workstream aims to determine and describe fundamental aspects of the regulatory acceptability of RWD/E at the national and international level. The workstream will continue to monitor new developments and respond to new regulatory guidance as relevant. To learn more, contact Assistant Research Director Trevan Locke at trevan.lock@duke.edu

Operationalizing Electronic Health Record Data Relevance, Reliability, and Quality for RWE Policy Stakeholders… This workstream will build on relevant literature covering data quality and relevancy dimensions and consider reliability as an additional dimension within the scope of "fit-for-purpose data.” The workstream will review relevant and timely policy developments and efforts to ultimately contemplate considerations and best practices that operationalize EHR data relevance, reliability, and quality. To learn more, contact Research Associate Nora Emmott at nora.emmott@duke.edu

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.

• 2024 Convening on the State of RWE Policy
• 2023 Convening on the State of RWE Policy
• 2022 Convening on the State of RWE Policy
• 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-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