The 21st Century Cures Act (Cures Act), signed into law on December 13, 2016, is intended to accelerate medical product development and bring innovations faster and more efficiently to the patients who need them. Among other provisions, the Cures Act added section 505F to the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355g). Pursuant to this section, FDA created a framework for a program (RWE Program) to evaluate the potential use of real-world evidence (RWE) in regulatory decision-making.

FDA is issuing this guidance as part of its RWE Program to satisfy, in part, the mandate under section 505F of the FD&C Act to issue guidance about the use of RWE to help support approval of a new indication for a drug already approved under section 505(c) of the FD&C Act or to help support postapproval study requirements.


For the purposes of this guidance, the term interventional study (also referred to as a clinical trial) is a study in which participants, either healthy volunteers or volunteers with the condition or disease being studied, are assigned to one or more interventions, according to a study protocol, to evaluate the effects of those interventions on subsequent health-related outcomes. One example of an interventional study is a traditional randomized controlled trial in which some participants are randomly assigned to receive a drug of interest (test article), whereas others receive an active comparator drug or placebo. Other examples of interventional study designs include randomized clinical trials with pragmatic elements (e.g., broad eligibility criteria, recruitment of participants in routine care settings) and single-arm trials. For the purposes of this guidance, a non-interventional study (also referred to as an observational study) is a type of study in which patients received the marketed drug of interest during routine medical practice and are not assigned to an intervention according to a protocol.

Examples of non-interventional study designs include, but are not limited to, (1) observational cohort studies, in which patients are identified as belonging to a study group according to the drug or drugs received or not received during routine medical practice, and subsequent biomedical or health outcomes are identified and (2) case-control studies, in which patients are identified as belonging to a study group based on having or not having a health-related biomedical or behavioral outcome, and antecedent treatments received are identified.