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
ClinicalTrials.gov 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).”