Real-World Evidence: FDA´s Considerations for Non-Interventional Studies

The FDA issued a new draft guidance as part of a series of guidance documents under its Real-World Evidence (RWE) Program. The document provides recommendations to sponsors who are considering submitting a non-interventional study ("observational study") to contribute to a demonstration of substantial evidence of effectiveness and/or drug safety. Specifically, the guidance discusses attributes regarding the design and analysis of a non-interventional study that sponsors should consider when proposing a non-interventional study for such regulatory purposes.

The agency previously already published a guidance that describes regulatory considerations for non-interventional studies involving the use of RWD, including RWD access, study monitoring, safety reporting, and other sponsor responsibilities (Considerations for the Use of Real-World Data and Real-World Evidence To Support Regulatory Decision-Making for Drug and Biological Products).

Data Sources

Sponsors should demonstrate the appropriateness of the proposed data sources to address specific hypotheses and research questions. Given that data sources used in a non-interventional study design are often generated for purposes other than research, it is important that sponsors understand the potential limitations of such data sources and determine whether those limitations can be addressed or if another data source should be pursued. Each protocol or accompanying documents should concisely describe each of the elements listed below:

  • Description of the proposed data sources (including how the data were originally collected) 
  • Rationale for choosing the data sources
  • Relevance of the data to the drug-outcome association of interest
  • Appropriateness of the information on relevant confounding factors
  • Available information on data reliability
  • Description of common data models used
  • Available information on the timing of assessments for key data elements and completeness of these key data elements
  • Explanation of how the proposed coding is appropriate based on operational definitions of key variables
  • Appropriateness of the data relative to the target patient population
  • Quality assurance activities that will be performed on the extracted original source data
  • Existing or potential links to other data sources
  • Plans for additional data collection

For more information please see the draft guidance Real-World Evidence: Considerations Regarding Non-Interventional Studies for Drug and Biological Products.

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