New Paper Provides Roadmap for Using Real-World Data in FDA Drug Approvals and Label Expansions
Slipstream, a technology consulting partner focused exclusively on the life sciences industry, has announced the publication of a new peer-reviewed paper addressing how pharmaceutical and biotechnology companies can use real-world data (RWD) and real-world evidence (RWE) to support U.S. Food and Drug Administration (FDA) drug approvals and label expansions.
Published in Clinical Pharmacology and Therapeutics, the paper, titled A Practical Guide to Implementing Real-World Evidence as Primary Basis for Approval and Label Expansion, provides practical guidance for sponsors navigating the increasingly complex regulatory environment surrounding the use of RWD and RWE.
The publication is intended to address the gap between FDA guidance on real-world evidence and the practical challenges involved in designing, conducting, documenting and submitting studies that rely on real-world data as a major component of a regulatory evidence package.
The paper is co-authored by Dr. Tracy Mayne, Senior Vice President of Regulatory and Life Sciences Research at Slipstream Life Sciences; Dr. Alan Brookhart of Duke University and Headwater Science; and Dr. Nancy Dreyer, President of Dreyer Strategies. The authors draw on their combined experience working with real-world evidence and FDA regulatory submissions to provide sponsors with an experience-based framework for applying FDA expectations in actual drug development programs.
Addressing the Practical Challenges of Real-World Evidence
The use of RWD and RWE in pharmaceutical development has expanded significantly as regulators, sponsors and researchers seek additional sources of evidence beyond conventional randomized clinical trials.
Real-world data can be generated from a variety of healthcare sources, including electronic health records, insurance claims, registries and other routinely collected healthcare information. When appropriately designed and analyzed, studies using such data can provide evidence about treatment effects, safety and clinical outcomes in patient populations encountered in routine medical practice.
However, generating evidence from RWD that can support a regulatory decision requires more than simply accessing a large healthcare database. Sponsors must demonstrate that the data are fit for purpose and that the study design, analytical methods, data provenance, documentation and interpretation are sufficiently rigorous to address the regulatory question.
The authors argue that these practical considerations can create significant challenges for pharmaceutical and biotechnology companies attempting to translate FDA RWD/RWE guidance into an operational development program.
“The FDA has provided road maps on how real-world evidence can be used, but there remain numerous gaps when it comes to their practical application,” said Tracy Mayne, SVP of Regulatory and Life Sciences Research at Slipstream.
The newly published guide is designed to help address those gaps by focusing on how sponsors can implement the principles outlined in FDA guidance during the actual planning and execution of an RWE program.
From Regulatory Guidance to Implementation
FDA guidance documents provide frameworks for understanding how RWD and RWE can potentially contribute to regulatory decision-making. However, sponsors must translate those principles into detailed operational decisions.
These decisions can begin well before a study is launched. Companies need to determine whether available data can answer the regulatory question, whether the relevant patient population can be adequately identified, whether outcomes can be reliably measured, and whether the study design can address potential sources of bias and confounding.
The paper focuses on these practical aspects of RWE implementation, drawing on the authors’ direct experience with FDA submissions.
Rather than presenting real-world evidence as a simple alternative to randomized clinical trials, the authors emphasize the importance of applying rigorous methodological and documentation standards. This includes careful attention to the research question, data sources, study population, endpoint definitions, statistical methods and analysis plans.
Dr. Alan Brookhart said real-world data can generate credible evidence in situations where randomized trials may not be feasible or ethical, but emphasized that the resulting studies still require a high level of rigor.
“Real-world data can provide credible evidence when randomized trials are infeasible or unethical, but only when the study is designed and documented with the same rigor we expect of a trial,” Brookhart said.
He added that the guide is intended to help sponsors address critical details early in the development process, when changes to study plans and methodologies are generally easier to make.
Importance of Early Planning
One of the central themes of the publication is the importance of addressing regulatory and methodological requirements at an early stage.
RWE programs can involve multiple data sources, analytical approaches and stakeholders. If issues related to data quality, endpoint definitions or study design are identified late in the process, correcting them can require substantial additional work or may limit the usefulness of the resulting evidence.
Early planning can allow sponsors to identify potential limitations before data are analyzed and determine whether alternative sources or methods are needed.
The authors’ experience-based approach is designed to help companies evaluate these considerations before committing significant resources to an RWE program.
This can be particularly important when RWE is intended to serve as a primary basis for an FDA approval or label expansion rather than as supplemental information accompanying evidence from a conventional clinical trial.
The paper therefore addresses questions related not only to whether RWD are available, but whether the data and resulting study can produce evidence that is sufficiently reliable and well documented for regulatory submission.
Relevance to Oncology and Rare Diseases
According to Slipstream, many current use cases for regulatory RWE involve oncology and rare diseases. In these therapeutic areas, conventional randomized placebo-controlled trials can sometimes present significant practical or ethical challenges.
Rare diseases may involve small patient populations, making recruitment into traditional trials difficult. In oncology, rapidly evolving standards of care, serious disease severity and available treatment options can create circumstances in which certain conventional trial designs may not be appropriate.
The authors note, however, that the potential role of RWD is not limited to these therapeutic areas.
Any indication in which a randomized placebo-controlled trial is infeasible or unethical may provide an opportunity to consider how real-world data could contribute to an overall evidence package.
The appropriateness of RWE depends on the specific regulatory question, available data, study design and other scientific considerations. Consequently, the paper focuses on principles that can be applied across therapeutic areas rather than limiting its recommendations to a single disease category.
Experience From FDA Submissions
A key feature of the paper is the authors’ direct involvement in regulatory submissions incorporating real-world evidence.
Slipstream said the three authors have participated in multiple FDA submissions that have utilized RWE. Their combined experience includes work at a time when regulatory expectations around RWD and RWE have continued to develop.
This practical experience provides the basis for the paper’s focus on implementation challenges that may not be fully apparent from high-level regulatory guidance.
Dr. Nancy Dreyer described the publication as an effort to address practical questions that arise when companies evaluate whether their RWD, study design and study execution are sufficiently robust for inclusion in a regulatory evidence package.
“This piece addresses many practical questions about whether real-world data, study design and execution are good enough for submission in a regulatory evidence package, all lessons learned through the school of hard knocks,” Dreyer said.
The authors’ experience also reflects the evolving nature of the RWE regulatory environment. As sponsors gain more experience using real-world evidence in submissions, lessons from completed programs can help inform future study planning and execution.
Companion to DIA 2026 Presentation
The new publication follows a presentation delivered by the authors at the DIA 2026 Innovation Theater.
The DIA session provided an early discussion of the practical considerations associated with implementing RWE in a regulatory environment increasingly focused on the quality, relevance and reliability of real-world data.
The peer-reviewed publication expands on that discussion by providing a more detailed resource for pharmaceutical and biotechnology companies considering RWE-based regulatory strategies.
Slipstream has made the full DIA presentation available through its website, providing another resource for sponsors and other stakeholders interested in the use of real-world evidence in drug development and regulatory submissions.
Supporting a More Structured RWE Development Process
The increasing availability of healthcare data has created new opportunities for pharmaceutical companies to study treatment outcomes outside traditional clinical trial settings. At the same time, the regulatory use of these data requires careful consideration of data quality, study design and evidence generation.
For sponsors considering an RWE strategy, questions may include whether the available data adequately represent the target patient population, whether relevant outcomes can be measured consistently, and whether the study can account for factors that could influence treatment comparisons.
Additional considerations can involve how the data were collected, how missing information is addressed, how the analysis is prespecified and how the study results are documented for regulatory review.
The guide published by Slipstream, Brookhart and Dreyer is intended to help companies address these issues systematically.
Rather than viewing RWE simply as a source of additional information, the publication presents it as a potential component of a structured regulatory evidence strategy when the scientific and regulatory circumstances are appropriate.
Open-Access Publication
The paper is available through open access in Clinical Pharmacology and Therapeutics, allowing pharmaceutical, biotechnology, clinical research and regulatory professionals to review the authors’ recommendations.
The publication comes as FDA expectations surrounding RWD and RWE continue to evolve. For sponsors, understanding the distinction between having access to real-world data and generating regulatory-grade evidence from those data remains an important consideration.
The authors’ focus on practical implementation is intended to help reduce uncertainty for companies developing RWE strategies for initial drug approval or subsequent label expansion.
The paper also highlights the importance of integrating regulatory considerations into RWE planning from the beginning of a program. By identifying potential data and methodological limitations early, sponsors may have greater opportunity to make appropriate adjustments before a study reaches the submission stage.
As the pharmaceutical industry continues to explore evidence-generation approaches beyond traditional randomized clinical trials, the ability to design rigorous and transparent RWE programs is expected to remain an important part of regulatory strategy.
Slipstream’s new publication provides an experience-based resource for companies evaluating that pathway, particularly those seeking to determine whether their real-world data, study design and execution are capable of supporting an FDA regulatory submission.
The authors’ combined experience with multiple FDA submissions involving RWE forms the foundation of the guide and reflects the increasingly practical role that real-world evidence can play in modern drug development. While RWE does not eliminate the need for rigorous evidence generation, the paper outlines how sponsors can approach the process with greater structure, early planning and attention to the standards expected for regulatory decision-making.
About Slipstream: Slipstream is a technology consulting partner exclusively focused on life sciences. Its teams operate as an extension of their clients, bringing deep domain expertise across R&D, enterprise platforms, data, and operations to help organizations accelerate research, optimize operations, and improve patient outcomes. Learn more about Slipstream Life Sciences at slipstreamls.com.