By: Rose Pagano and Suzanne M. Sensabaugh, MS, MBA

The FDA released this guidance to help sponsors and applicants using real-world data (RWD) to produce real-world evidence (RWE) for a regulatory submission. This encompasses submissions for investigational new drug applications (INDs), new drug applications (NDAs), and biologics license application (BLAs) that have RWE to prove their safety and effectiveness in relation to regulatory decisions.

RWD is classified as data related to patient health status and/or the delivery of health care that are routinely collected from a variety of sources. This may include data deduced from electronic health records (EHRs), medical claims and billing data, data from product and disease registries, patient-generated data, and data gathered from other sources that can inform on health status. RWE is considered to be clinical evidence concerning the usage and potential benefits or risks of a medical product determined from RWD analysis. RWE can be generated from gathering information about the effectiveness or safety outcomes from an RWD source in randomized clinical trials or observational studies.

 The guidance includes example submissions that would utilize RWD and/or RWE. These submissions can be presented in different forms such as a new protocol to a current IND, a final study report submitted to an NDA or BLA supplement, or a meeting package that includes the RWE information. Study objectives may be sustained by including RWE. This can be done in the form of IND submissions for randomized clinical trials that have RWD to capture clinical outcomes or safety data. Another way RWE may be presented is through new protocols for single arm trials that use RWE as an external control. Furthermore, observational studies that generate RWE can be submitted to support an efficacy supplement. Lastly, clinical trials or observational studies using RWE to fulfill a postmarketing requirement to assess safety or effectiveness can support a regulatory decision.

It is important to note that the FDA does not plan on tracking RWE submissions that are not associated with a specific product or are not used to support a regulatory decision regarding safe and/or effectiveness. Feasibility studies using RWE, studies using RWD to perform explanatory analyses, or natural history studies for development of a clinical outcome assessment would all be considered submissions that sponsors and applicants need not identify as containing RWE. The FDA is available for sponsors and applicants to consult the appropriate review division with questions regarding certain submissions related to RWE.

 In the cover letter for a regulatory submission, the sponsor or applicant needs to identify the submission as containing RWE by including the necessary information. In the cover letter, the sponsor should list the purposes for using RWE in the submission and provide evidence in support of the effectiveness or safety for a new product approval. Additionally, sponsors should provide evidence supporting the labeling changes for an approved product by detailing anything that added or modified an indication, change in dose, use in a new population, adding comparative effectiveness information, and adding safety information.

Ultimately, this guidance contained useful information concerning RWD and RWE.


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Suzanne M. Sensabaugh is a regulatory affairs consultant who advanced the development of over 130 biologics, biosimilars, and combination products since 2009. She also provides expertise as a GMP consultant. She can be reached at