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RWD and RWE-focused Demonstration Projects

To promote shared learning and understanding with external stakeholders, FDA continues to oversee and support numerous demonstration (i.e., research) projects through multiple venues and programs including the broad agency announcements, funding opportunity announcements, CERSI grants, and inter-Agency agreements.

The table below lists ongoing and completed demonstration projects.

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Title Contractor Goal | Aims Topic Status

Methods to improve efficiency and robustness of clinical trials using information from real-world data with hidden bias

Duke University & North Carolina State University   To develop innovative statistical methods to address hidden biases when integrating real-world data (RWD) to improve the efficiency and robustness of clinical trials. Tools; Data; Statistics Ongoing

W to Generating Reproducible Real-World Evidence with Multi-Source Data to Capture Unstructured Clinical Endpoints for Chronic Diseases

Harvard-MIT Center for Regulatory Science and Harvard Medical School To develop novel approaches, including strategies for identifying scalable disease-progression endpoints and adverse events, to generate RWE from electronic health record (EHR) data for assessing efficacy and safety of disease modifying treatments (DMTs) used in chronic diseases. Tools; Data; Study design Ongoing

Real-World Data to Generate Real-World Evidence in Regulatory Decision-Making

ECOG-ACRIN Medical Research Foundation To develop a longitudinal approach to real-world data acquisition starting during Phase III trials and feeding into Phase IV. These combined data will be used to generate robust RWE for efficacy and safety of treatments in rare and less common tumors. Data; RCTs Ongoing

Development of novel methods to enable robust comparison of real-world Progression Free Survival (rwPFS) and Clinical Trial PFS in Multiple Myeloma (MM)

Janssen Research & Development, LLC. To develop novel methods for robustly comparing real-world progression free survival (rwPFS) to PFS determined in clinical trials among patients with multiple myeloma (MM). Tools; Study design Ongoing

Effectiveness Research with Real-World Data to Support FDA’s Regulatory Decision-Making

Brigham and Women’s Hospital and Harvard School of Medicine

To explore whether non-interventional study designs could provide credible evidence of drug effect as a randomized design, The Brigham and Women’s Hospital/Harvard Medical School project is emulating thirty completed clinical trials as closely as possible in a consistent, transparent, and reproducible process.

References: Emulating randomized clinical trials with nonrandomized real-world evidence studies: First results from the RCT DUPLICATE initiative - PMC

Emulation of Randomized Clinical Trials With Nonrandomized Database Analyses

Replication; study design; observational
Evaluation of a Deep Learning Enhanced Disease- Monitoring Solution Leveraging Wearable Sensors for Exploring Novel Patient-centered Outcome measures Among Patients with Heart Failure Yale Mayo CERSI Evaluate the feasibility and performance of wearables and smartphone-based mobile health platforms for real-world surveillance of surrogate endpoints for heart failure drug approvals in 150 patients DHTs; tools Ongoing
Chronic Obstructive Pulmonary Disease (COPD), Asthma, and Respiratory Disease Effectiveness (CARE) FDA-Catalyst Use Sentinel data to conduct feasibility assessment of outcome studies and assessment effectives of marketed products FDA-Catalyst; Sentinel; study design; observational Ongoing
Methodological Advances in the Assessment of Uncontrolled Confounding (aka DETECTe) University of North Carolina Inventory existing sensitivity analysis methods that might be useful for assessing uncontrolled confounding in observational RWE studies.  Subsequently, these methods will be tested using clinical trial data to enable evaluation of the methods with less concern regarding the potential influence of data quality on results.  Statistics; Confounding; Methods; tools Complete
Predicting Findings of Ongoing Phase IV RCTs with Real World Data Analyses: An Assessment to Support FDA's Regulatory decision making Brigham and Women’s Hospital and Harvard School of Medicine To gain confidence that non-interventional designs could provide credible evidence of drug effect as a randomized design, The Brigham and Women’s Hospital/Harvard Medical School project emulating seven on-going clinical trials as closely as possible in a consistent, transparent, and reproducible process. Replication; study design; observational Ongoing

Understanding the use of existing real-world data for medical product evaluation

Yale-Mayo CERSI

Reference: Real-world Using linked administrative claims and EHR data for commercially insured and Medicare Advantage beneficiaries aggregated by OptumLabs, goals of the Yale-Mayo Clinic CERSI RWE project were to:
emulate the characteristics of trial populations based on pre-specified inclusion and exclusion criteria of two ongoing clinical trials; emulate the results of these ongoing clinical trials; and
once complete, compare the emulated populations and results to the actual trial population and results

Cardiovascular Outcomes Associated With Degarelix vs Leuprolide for Prostate Cancer Treatment - PMC (nih.gov)

Emulating the GRADE trial using real world data: retrospective comparative effectiveness study

Replication; study design; observational Complete
Evaluating EHR
Vesalius Trial
Duke Clinical Research Institute Develop and pilot test a reusable framework to provide practical guidance to site investigators for transforming raw EHR data to fit-for-purpose real world data to support efficient trial recruitment and long-term follow- up. EHR; data Ongoing
Targeted Learning Framework for Causal Effect Estimation Using Real World Data Putnam Data Science  Examine the role of Targeted Maximum Likelihood Estimation (TMLE) and Super Learning in causal effect estimation for clinical trials and observational studies. TMLE and Super Learning will be compared to parametric propensity score-based methods in the context of data from a clinical trial, a second clinical trial with right censoring, and an observational study using secondary RWD Statistics; machine learning; methods; tools Complete
Developing Data Standards for RWE International Business Machines (IBM) Corps     Map RWE standards to existing CDISC standards, assess gaps, and make structural recommendations to FDA. Will create a roadmap for developing submission standards for RWD submitted to FDA by sponsors. data Complete
Using m-Health to Measure Impact in Functionality, Behavior, Activity and Sleep Patterns in Children and Adolescents Treated with Psychotropics University of MD CERSI This project aims to develop a novel tool to improve the post-marketing evaluation of psychotropics in pediatric populations by leveraging the use of mobile technologies. The goal is to inform regulatory decision-making by developing a mobile application to 1) fill the gap in the capture of real-time behavioral and activity data; 2) ease the burden on patients, caregivers, and providers struggling to capture relevant and actionable data related to treatment and care management; 3) identify severity of mood, behavior and function after psychotropic treatment initiation or change, and 4) measure rates of adverse events/ secondary effects and characterize patterns of treatment adherence. DHTs; tools; pediatric Complete

Integrating Clinical trials and Real World Endpoints data (ICAREdata) Data Capture and Standardization Study


Project Goal: Explore the ability to create curated standardized outcome responses within an existing EHR system.

Test the mCODE FHIR-based standard for data collection from EHRs in Alliance clinical trials

Compare these data to those obtained from standard research EDC system (Medidata Rave)

Confirm that EHR-based study data are as accurate as those collected via Medidata Rave EDC

EHR; data Ongoing

Adverse Event Reporting in the Integrating Clinical trials and Real World Endpoints Data (ICAREdata) Initiative


Project goals: Explore the ability to create curated standardized adverse event information within an existing EHR system.

Test a mCODE-compatible structured data model for CTCAE embedded within the EHR

Develop and test ICAREdata methods for collecting CTCAE data directly from EHR

Assess usability, burden, and acceptance by providers

EHR; data Ongoing

Advancing standards and methodologies to generate real-world evidence from real-world data through a neonatal pilot project

Critical Path

Overall project goal(s): Explore RWD/RWE utility in the neonatal population using neonatal broncho-pulmonary dysplasia as an example

Develop a Real-World Data and Analytics Platform (RW-DAP) which can access RWD to generate RWE

Execute a pilot project that generates RWE to support regulatory decision making in neonatal drug development

Identify gaps that hinder the optimal use of existing RWD

Maximize prospective collection of RWD to generate RWE

Data; pediatric Ongoing

Transforming Real-world evidence with Unstructured and Structured data to advance Tailored therapy (TRUST)


Overall project goal(s): Explore how data quality affects RWE study conclusions  

Understand the impact of underlying data quality on real-world evidence results

Define a pathway to enable high-validity evidence through advanced data and technologies

Data Ongoing

Enhancing evidence generation by linking randomized clinical trials (RCTs) to real-world data (RWD)

Brigham and Women’s Hospital and Harvard School of Medicine

Overall project goal(s): Explore utility of linking RCTs to RWE

Demonstrate how linking RCTs with RWD can enhance RCTs and help calibrate RWE studies. 

Leverage RCT-RWD linked data sets to extend patients’ follow-up time beyond trial completion, to compare RWD-based and RCT measurements, to generalize RCT results to real-world target populations, and to investigate the underlying reasons for potential discrepancies between RCTs and RWE studies.

Data; RCTs; study design; administrative claims Ongoing

Common Data Model Harmonization (Phase II)

Elligo Health Research  Project Goal: Collaboration with OND to leverage the Common Data Model Harmonization (CDMH) data infrastructure using Real-World Data (RWD) derived from the delivery of health care in routine clinical settings to conduct a feasibility study. Data Ongoing

Applying novel statistical approaches to develop a decision framework for hybrid randomized controlled trial designs which combine internal control arms with patients' data from real-world data source

Genentech/ University of North Carolina

Overall project goal(s):

Evaluation of hybrid designs and their operating characteristics, when applied to time-to-event endpoints

Assessment of the designs beyond time-to-event settings when applied to diseases in different therapeutic areas, especially rare diseases

Development of R-Packages supporting study design simulations and offering training workshops on the use of the packages to review staff at the FDA

Study design; statistics; methods; tools Ongoing

Roflumilast or Azithromycin to prevent COPD exacerbations (RELIANCE)


Overall project goal(s): Explore utility of linking administrative claims data to patient clinical trial data by linking RELIANCE trial participants to their CMS claims data to improve ascertainment of trial outcomes  including first hospitalization, all-cause death, healthcare utilization, and medication adherence.

Test distributed regression methods with vertically partitioned data

FDA-Catalyst; Sentinel; RCTs; statistics; study design; administrative claims   Ongoing

FDA MyStudies    


Overall project goal(s):

Implement several enhancements to the FDA-Catalyst MyStudies mobile application (app) platform to improve usability and facilitate the collection of detailed patient information

Enable implementation of the app to facilitate collection of patient-reported data from (1) PCORI pragmatic trial and (2) registry selected by the FDA:

Improving outcomes in Limited Juvenile Idiopathic Arthritis (LIMIT-JIA)

Study of a Prospective Adult Research Cohort with IBD (SPARC IBD)

Click to learn more about FDA MyStudies

FDA-Catalyst; Sentinel; DHTs; study design Ongoing



RWE use for implementation of a large, prospective, pragmatic trial embedded in commercial health plans; Assess educational interventions for patients diagnosed with Afib

Reference: Effect of Mailing Educational Material to Patients With Atrial Fibrillation and Their Clinicians on Use of Oral Anticoagulants: A Randomized Clinical Trial

FDA-Catalyst; Sentinel; study design Complete

Duke Harmony

Duke Clinical Research Institute 

Explores whether EHRs are fit to facilitate clinical research recruitment and be used for endpoints.

Electronic health data changes the conduct of clinical trials through less data work at local sites and an improved ability to find participants

Data; EHR Complete
Real-world evidence to support labeling expansions for effectiveness claims using a two-stage trial emulation process Brigham and Women’s Hospital This project will design a two-stage process that leverages RWE to support labeling expansions which uses Bayesian approaches to integrate the knowledge gained in a first stage randomized clinical trial (RCT) emulation. The method takes as input the results of an RCT for an initial indication and real-world evidence (RWE) based emulation of that trial to increase confidence in decision-making for a supplemental indication based on RWE. In doing so, they hope to demonstrate and empirically test the process with historical and ongoing RCTs for supplemental indications.   Replication; study design Ongoing
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