Projects

Calibrating real-world evidence studies in oncology against randomized trials-
ENCORE (Emulation of iNterventional trials in Clinical Oncology with Real-world Evidence)
Funded by FDA
TASKS
Develop and expand a process to evaluate the ability of RWE to support evidence of effectiveness in oncology. This includes systematic evaluation of the suitability of data in relation to the study design.
Demonstrate and examine the systematic process by emulating 12 oncology trials across 4 cancers and assessing the results of RCT-RWE study pairs.
IMPACT
Building on a process co-developed with the FDA through RCT-DUPLICATE, this expansion to oncology is going to emulate the approach to 12 randomized clinical trials using multiple EHR data sources. The process includes an emphasis on transparency with documented assessment of data fitness of the RWD source for each trial and conducting extensive sensitivity analyses to assess robustness of findings and trial eligibility criteria (e.g., age, race, comorbidity). 
Real-world evidence to support labeling expansions for effectiveness claims using a two-stage trial emulation process
Funded by FDA
TASKS
We will design ​a two-stage process for using RWE to support labeling expansions for effectiveness claims that is aligned with regulatory requirements
We will demonstrate and empirically test the process with historical and ongoing RCTs for supplemental indications  
IMPACT
This project is a logical extension of RCT-DUPLICATE and will result in a 2-stage process that increases confidence in RWE findings for sNDA submissions. It will also provide guidance on when its use would be appropriate.

Effectiveness research with Real World Data to support FDA’s regulatory decision making: A Real World Evidence demonstration project

Funded by FDA
TASKS
We will identify and select a representative set of 30 completed phase 3/4 RCTs relevant to regulatory science.
We will set up a scalable analytics platform with Medicare and commercial claims databases; we will use RWD to reproduce RCTs and compare findings. We will assess reasons for success and failure to replicate using extensive sensitivity analyses.​
We will convene expert panels and workshops to produce empirically-based recommendations on when it is possible to use RWD successfully and how to best implement such studies.

IMPACT

The planned replication of selected RCTs using claims databases with standardized high-quality methodology will result in actionable insights on the factors that decide which clinical effectiveness questions can be answered with RWD and if not, describe what the main reasons were. Such findings will lay the groundwork for regulators to gain confidence in their decision making of whether an RCT can be substituted with a RWD study. 

Predicting findings of ongoing Phase 4 RCTs with Real World Data analyses: An assessment to support FDA’s regulatory decision making

Funded by FDA
TASKS
We will identify a suitable set of 7 ongoing phase 4 RCTs relevant to regulatory decision making that are assessed as being implementable in a comparable way with healthcare databases
We will set up a scalable analytics platform with commercial claims databases; we will use RWD to reproduce RCTs and compare findings. We will assess reasons for success and failure to replicate using extensive sensitivity analyses. ​
We will convene expert panels to expand existing recommendations with our new prospective empirical evidence, that was blinded towards RCT findings, on a) when it is possible to use RWD analyses successfully, b) how to best implement such studies, and c) what a quality assurance process could look like. ​
IMPACT
This project will provide prospective empirical evidence blinded towards RCT findings on when and how RWE will be able to substitute or augment RCTs. It will also provide a structured and tested decision-making process to instill confidence in identifying those RWD analyses that have a high likelihood of providing actionable evidence.

Randomized Cardiovascular Trials Duplicated Using Prospective Longitudinal
Insurance Claims: Applying Techniques of Epidemiology 

Funded by NHLBI
AIMS
​Prospectively replicate a large sample of published RCTs of cardiovascular outcomes using a variety of designs and analysis methods in RWD. 
​​Prospectively duplicate ongoing RCTs of cardiovascular outcomes using a variety of potential designs and analysis methods in RWD.
​Adapt meta-analysis methodology to isolate trial characteristics and design and analysis factors contributing to replication success.
​Convene a workshop of trial and RWD experts to discuss findings, develop guidance, and determine additional evidence needs.
IMPACT
This project focuses on replication of RCTs of cardiovascular outcomes that are not part of a regulatory approval submission, including trials funded by NIH, and trials of cardiovascular safety. It will further broaden the set of designs and analyses implemented in each replication to explore how RWD findings are impacted by these choices. In addition, as part of this project, we will develop methodology for evaluating the agreement between RCT and RWD findings as a function of trial characteristics and design and analysis factors. 

Other Prospective Replications

We are prospectively replicating several ongoing randomized trials to determine if RCT results can be predicted prior to the release of findings. We provide links to papers describing the trials and the corresponding RWD study if completed.