Data Pharmaceuticals Regulation

FDA Guidance on using Real-World Data for regulatory Decision-Making

Last month, FDA released guidance on the use of real-world evidence to support regulatory decision-making for new drugs.  Below are some of the key points from this guidance document:

  • Legislative mandate. The 21st Century Cures Act (Cures Act), signed December 2016, mandated that the FDA consider how to incorporate real world data (RWD) into regulator decisionmaking.  The guidance issues addresses part 312 (Investigational New Drug Application)
  • Types of real-world data.  FDA defines RWD as “…data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources.” RWD sources explicitly named in the guidance include “registries, electronic health records (EHRs), and medical claims.” Questionnaires, laboratory tests, and imaging studies that are part of a standard clinical trial protocol are not considered real-world data.
  • Uses of RWD.  Three primary uses are identified: (i) to identify potential participants for a randomized controlled trial, (ii) to ascertain endpoints or outcomes (e.g., occurrence of stroke or other discrete events, hospitalization, survival) in a randomized controlled trial, or (iii) to serve as a comparator arm in an externally controlled trial (this includes historically controlled trials).
  • Data source selection. The study protocol should contain an appendix describing the data sources evaluated and why the particular data set was selected. Additionally, the key data elements (i.e., variables) that will be used from the relevant data source should be described.
  • Logistics for FDA interactions.   The guidance notes that manufacturer early engagement with FDA “…will help address the appropriateness of using a non-interventional study design and the proposed data sources to address the research question of interest.”  A study protocol and statistical analysis plan (SAP) are required to be submitted to FDA to validate the methods. The study design should be posted to or European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP)
  • Use of proprietary RWD. “If certain RWD are owned and controlled by other entities, sponsors should have agreements in place with those entities to ensure that relevant patient-level data can be provided to FDA and that source data15 necessary to verify the RWD are made available for inspection as applicable…If an appropriate justification exists for why a sponsor cannot submit patient-level data to FDA through traditional channels, regulatory pathways exist for third parties to provide patient-level data to FDA to support a sponsor’s marketing application. Specifically, the third-party provider can choose to open either a pre-investigational new drug application (pre-IND) or a Type V drug master file (DMF).”

The full guidance document is available here.