HealthPals’ CLINT Demonstrates First Large-Scale RCT Replication with Veradigm’s EHR Data

Key Takeaways:

  • Approximately 80% of non-COVID-19 clinical trials have been suspended, stopped, or delayed due to difficulties in trial initiation and recruitment.
  • Solutions to these pandemic-induced challenges can be found in Real-World Data (RWD) and Real-World Evidence (RWE).
  • CLINT (HealthPals, Inc.) is a novel, guideline-encoded population health platform capable of generating machine learning-based insights on RWD at scale.
  • To demonstrate the capabilities of CLINT, particularly its ability to leverage RWD for the generation of ECAs, HealthPals has successfully duplicated a large randomized controlled trial (ROCKET-AF) using Electronic Health Record (EHR) data.
  • This replication establishes CLINT as the first operational RWD analytics platform capable of replicating RCT results in EHR data.
Figure 1: A timeline of clinical trials disrupted due to Covid-19. Source: GlobalData

A Solution to the COVID-induced RCT dilemma: RWD/RWE and External Control Arms

Real-World Data (RWD) and Real-World Evidence (RWE) have demonstrated their potential value in the R&D, clinical trial and regulatory spaces in a number of major ways. The FDA has used RWD and RWE to monitor post-market safety and adverse events and to make regulatory decisions while medical product developers have used RWD and RWE to support clinical trial designs (e.g., large simple trials, pragmatic clinical trials) and generate observational studies to produce innovative, new treatment approaches.

EXTERNAL CONTROL ARMS

External control arms (ECAs) are a specific use case for RWD/RWE in which patient cohorts are derived from external, real world data to provide a comparison control arm for an experimental arm in a clinical trial. ECAs are matched to experimental arms in such a way as to simulate the effects of randomization by:

  • Facilitating causal inference.
  • Providing the basis for statistical inference.

ECA Technology: Duplicating the Rocket-AF Trial

To demonstrate the ability of CLINT to leverage RWD, generate ECAs and unlock the potential of clinical RWD (and specifically EHR RWD), HealthPals, in collaboration with Veradigm, a division of Allscripts and owner of the largest source of de-identified ambulatory longitudinal patient EHR records available (over 150M patients), duplicated the ROCKET-AF study, a large, landmark, cardiovascular clinical trial using EHR data [5]. For full details on the methodology and results, download the white paper here. RCT replication was accomplished using the HealthPals CLINT platform to:

  • Identify eligible experimental and control patients.
  • Match control patients to the experimental cohort using methods capable of balancing the cohorts with respect to confounding variables.
Figure 2: Flowchart cohort diagram detailing the critical filtering steps and the resulting number of patients at each stage of the process.
Figure 3 Experimental (Rivaroxaban) and Control (Warfarin) Arm Cohort Comparisons
Table 1: Events Per 100 Patient Years
Figure 4: Cumulative stroke and embolism events in RWD (left) compared with cumulative events from the ROCKET-AF study (right) [5].

The Future of RWD/RWE and ECAs — and HealthPals’ Role

In the COVID-19 era and beyond, we must extract maximum value from available real-world datasets to help address the staggering costs and risks of RCT conduction, especially when resources and time windows will be severely restricted due to the pandemic. Currently, there is a paucity of analytic engines powerful enough to extract this value across disease states in a scalable, operational platform. The HealthPals’ CLINT platform is capable of generating highly detailed RWD analysis at scale. We present the duplication of ROCKET-AF, a large, landmark cardiovascular clinical trial as a demonstration of the power of this class-leading technology.

SOURCES

  1. DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: New estimates of R&D costs. J Health Econ. 2016;47: 20–33.
  2. Faster New Drug Approval Phases Are More Than Offset by Longer Clinical Times in U.S. Tufts Center for the Study of Drug Development Impact Report. 16 Jul 2020.
  3. van Dorn A. COVID-19 and readjusting clinical trials. Lancet. 2020;396: 523–524.
  4. Franklin JM, Patorno E, Desai RJ, Glynn RJ, Martin D, Quinto K, et al. Emulating Randomized Clinical Trials with Nonrandomized Real-World Evidence Studies: First Results from the RCT DUPLICATE Initiative. Circulation. 2020. doi:10.1161/CIRCULATIONAHA.120.051718
  5. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365: 883–891.

I’m a Stanford Cardiologist and Assoc Prof. I also co-founded HealthPals, a Precision Population Health company that reduces chronic disease burden globally.

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