As Prescribed


FDA recently released the framework for its Real World Evidence (RWE) program, educating stakeholders about the agency’s approach to RWE when making efficacy decisions. The document is notable more for its discussion of the limitations rather than the potential for RWE. Although FDA plans to issue a number of RWE guidance documents and conduct RWE stakeholder events, the path to routine use of RWE looks to be a long and winding one.

Crucial to understanding FDA’s RWE approach is understanding the distinction between Real World Data (RWD) (e.g., data on patient health status and/or delivery of routine healthcare from a variety of sources) and RWE (e.g., clinical evidence on the use and potential benefits/risks of medical products derived from RWD). FDA intends to limit RWE use to supplemental indications and label changes for approved drugs/biologics (e.g., adding/modifying indications, changing dose/dosing regimens and routes of administration, adding new patient populations, adding comparative effectiveness/safety information). Moreover, while the life sciences industry tends to see the opportunities from RWD (e.g., electronic health record, medical claims/patient billing, patient/disease registry, and mobile device data), FDA primarily sees this information as an RWE source. This is not to say, however, that RWD is without use, as FDA plans to allow its use to improve study efficiency.

Although FDA states that it has some experience with RWD/RWE (see its 2013 electronic healthcare data guidance and 2017 medical device guidance), it also acknowledges that it has a lot to learn. To assist in evaluating the utility of RWD/RWE, FDA will ask three questions:

  • Is the RWD fit for use?
  • Can the study design used to generate RWE from RWD provide adequate scientific evidence to help answer regulatory questions?
  • Does the study conduct meet regulatory requirements for monitoring and data collection?

Some interesting FDA comments on RWE/RWD to note are the following:

  • There may be a lack of observational study transparency, making it more difficult to use the data, because sponsors are not required to register these studies on This hesitation may cause more observational study sponsors to consider registering trials in NIH’s database
  • A lack of data system standards (e.g., electronic health record lab results, patient co-morbidity listings, etc.) limits data value and reflects a need for standardization
  • A lack of universal patient numbers makes it impossible to avoid patient experience duplication while protecting patient privacy
  • International data may have limited FDA utility due to healthcare system differences

There are many open questions and issues concerning RWE/RWD. The framework is just the beginning of FDA’s journey (the agency has a number of next steps, including the issuance of guidance documents and demonstration projects). In the meantime, however, it would appear that until FDA reaches the end of its journey, the agency may be hesitant to broadly rely on RWD/RWE. Sponsors considering the use of RWD/RWE would be wise to first discuss their RWE/RWD uses with FDA to ensure agreement on its utility.