Table 2.

ENACT RWD/RWE use-case examples and value proposition hypotheses for the use case of FDA-regulated medical products

Translation phase	T1: To humans	T2: To patients	T3: To practice	T4: To population
Types of Research (jobs to be done)	Preclinical Research: Connect the basic science of disease with human medicine	Clinical Research: Understand a disease in humans and the effects of interventions	Clinical Implementation: Understand the adoption of evidence-based interventions into routine care/practice	Public Health Research: Assess the effects of current interventions at the population level and identify gaps
Goals (gains to achieve)	To develop model interventions for disease prevention and treatment.	To demonstrate intervention effects in order to obtain regulatory approval; or support clinical or public health recommendations.	To disseminate and evaluate translation processes and validate effects in real-world settings.	The goal is to inform policy and development of new interventions and adaptations to improve human health.
	RWE focus: exploratory epidemiologic analyses to understand disease trajectory given current clinical practice	RWE focus: hypothesis-testing of interventions with strong internal validity measures	RWE focus: evaluate clinical translation with strong external validity measures	RWE focus: promoting a learning health system
Challenges (pains to reduce)	Translation of novel approaches to clinical application	Speed of evidence generation	Scalability and sustainability of evidence translation	Health disparities
ENACT RWD/RWE Value Proposition (hypotheses to test)	A large, affordable, open-access network of de-identified EHR data to increase CTSA capacity for translational research to:
	Better design of FDA-regulated products given real-world healthcare delivery context	Modernize and accelerate the development and evaluation of FDA-regulated products	Strengthen post-market surveillance and labeling of FDA-regulated products	Invigorate public health preparedness and response of FDA, patients & consumers

EHR = electronic health record; FDA = US Food and Drug Administration; RWD = real-world data; RWE = real-world evidence.

Adapted from the NIH National Centers for Advancing Translational Science [30], FDA Regulatory Science Framework [9], and value proposition design [26].