Critical Path Institute Proposal for RFA-FD-20-030
ABSTRACT
Historically, FDA has utilized real-world evidence (RWE) as a key component of its efforts to
assure post-marketing surveillance and evaluation of medical product safety. The 21st
Century Cures Act mandates FDA to develop a framework that expands the use of RWD
and RWE to support approvals of a new indications for an already approved drug. By
leveraging data generated through the normal practice of medicine, signals of safety and
efficacy for new indications can be identified in already approved therapies. However, as
most existing RWD was generated without the regulatory standards in mind, significant
challenges exist to ensure RWD is fit-for-purpose to generate RWE capable of informing
regulatory decisions. Efforts to use existing RWD to answer regulatory questions can identify
these challenges and corresponding solutions, but this endeavor requires a significant
amount of data and regulatory science expertise to fully optimize the use of RWD to extract
actionable RWE. The Critical Path Institute (C-Path) has that data expertise and will execute
a pilot project to facilitate the use of RWD to generate RWE in neonates, with learnings
being broadly applicable to other therapeutic areas. Each year in the U.S., 10% of neonates
are born preterm and there is an urgent need to improve survival and outcome. However,
there is minimal new drug development and most existing drugs have insufficient evidence
to support safety, efficacy, and dosage in this high-risk population. C-path will leverage its
Data Collaboration Center processes and infrastructure to develop an RWD Analytics
Platform. RWD will be accessed through collaborations with investigators and data
scientists. Specific algorithms and mechanisms will be implemented to extract RWD from
relevant sources (aggregated databases and EMRs), curate and standardize data, and
enable analyses to generate actionable RWE. When data are analyzed remotely, C-Path will
validate processing workflows for quality assurance. Data thus extracted will address two
key unmet needs in the neonatal population: 1) current lack of actionable reference values
for routine laboratory tests (as a function of gestational/postnatal age) and 2) lack of disease
progression model for bronchopulmonary dysplasia. A gaps analysis will identify key lessons
specific to neonates relating to the access, quality, extraction, curation, standardization, and
analysis of RWD, and potential solutions to optimally generate actionable RWE identified,
and shared with key stakeholders in the neonatal community. Lessons learned with this
high-risk population can then be generalized to other therapeutic areas.
