By: Robert M. Califf, M.D., Commissioner of Food and Drugs
What we now call real-world data (RWD) have been used for years in medical product development to inform study design and endpoint selection, identify potential participants and trial sites, and assess safety in the post-marketing setting.
Related, real-world evidence (RWE) is the clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD. I’d like to catch up with you today on some of the challenges and advancements in RWD and RWE.
Understanding RWD, RWE and Challenges in the Ecosystem
It’s important to understand that RWD relate to patient health status and/or the delivery of health care routinely collected from a variety of sources. Examples of RWD include data derived from electronic health records, medical claims data, data from product or disease registries, and data gathered from other sources (such as digital health technologies) that can inform on health status. The key distinction is that RWD are not collected in a special research clinic or setting.
In addition to appropriate analysis, the study design is an essential part of producing RWE; and RWE can be generated by various types of study designs. These include non-interventional studies as well as interventional studies such as randomized trials with outcomes collected using RWD sources—so-called point-of-care trials—and externally controlled trials with control arms derived from RWD sources.
There is more recent interest in using RWE for regulatory decision-making in the pre-market setting, including to support a determination regarding a medical product’s effectiveness and inform benefit-risk analysis of devices for new intended uses. Realizing the full potential of RWE in regulatory decision-making presents several challenges, and work is underway at the FDA to better understand this area.
One challenge is finding fit-for-purpose RWD. Data from routine-care settings are focused on patients at the bedside or in the clinic, requiring consideration of the data’s reliability and relevance to address regulatory questions. For example, information on clinical measures of disease severity can be lacking in healthcare insurance claims, and we need better ways of examining unstructured data in electronic health records. Another category of challenges involves safeguarding patient privacy while having suitable mechanisms for data access and inspection by regulatory agencies. These challenges will require continued collaboration among a range of stakeholders including regulators, industry, academia and the clinical research community.
In this rapidly evolving world with a plethora of digital data, the FDA intends to help develop the best methods for RWD and RWE in the domains of data quality, study design and analysis.
FDA Guidance on Real-World Evidence and Data
The FDA has published a series of guidances to help advance real world evidence and recently published three additional guidances in this series:
- Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices, which updates and clarifies how the FDA evaluates RWD to determine if it is sufficient to be used in regulatory decision making for medical devices and provides expanded recommendations for sponsors collecting RWD.
- Real-World Data: Assessing Registries to Support Regulatory Decision-Making for Drug and Biological Products, which provides considerations for sponsors proposing to design a registry or to use an existing registry to support regulatory decision-making about a drug’s effectiveness or safety.
- Data Standards for Drug and Biological Product Submissions Containing Real-World Data, which addresses considerations for the use of data standards currently supported by the FDA in applicable drug submissions containing study data derived from RWD sources.
Supporting a robust data infrastructure, developing new methods and analytical tools, and integrating RWE with traditional clinical trial evidence will require collaboration across the clinical care, research and technology sectors, in addition to direct involvement of patients. To help in this context, the FDA is supporting research (or “demonstration”) projects that seek to improve the quality of RWD and RWE. Strengthening systems for generating and gathering new and better data and analyzing those data to provide reliable evidence to inform and improve the many decisions we make as consumers, patients, families, clinicians and regulators, is key.
The FDA is already capable of reviewing submissions that include or rely entirely on RWD. Enabling advanced data analytics, including RWD, is also incorporated in the FDA’s Information Technology Strategy for FY 2024-2027. Ongoing agency initiatives will continue to promote awareness of, and consistency in, reviewing submissions with RWD.
Stay tuned in 2024 for an emphasis across our U.S. Health and Human Services agencies on RWE, including point of care prospective clinical trials, in the post-market and health policy arenas.
Catch up with you next time.