Computable Phenotype Implementation for a National, Multicenter Pragmatic Clinical Trial: Lessons Learned From ADAPTABLE

Abstract

Background: Many large-scale cardiovascular clinical trials are plagued with escalating costs and low enrollment. Implementing a computable phenotype, which is a set of executable algorithms, to identify a group of clinical characteristics derivable from electronic health records or administrative claims records, is essential to successful recruitment in large-scale pragmatic clinical trials. This methods paper provides an overview of the development and implementation of a computable phenotype in ADAPTABLE (Aspirin Dosing: a Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness)-a pragmatic, randomized, open-label clinical trial testing the optimal dose of aspirin for secondary prevention of atherosclerotic cardiovascular disease events.

Methods and results: A multidisciplinary team developed and tested the computable phenotype to identify adults ≥18 years of age with a history of atherosclerotic cardiovascular disease without safety concerns around using aspirin and meeting trial eligibility criteria. Using the computable phenotype, investigators identified over 650 000 potentially eligible patients from the 40 participating sites from Patient-Centered Outcomes Research Network-a network of Clinical Data Research Networks, Patient-Powered Research Networks, and Health Plan Research Networks. Leveraging diverse recruitment methods, sites enrolled 15 076 participants from April 2016 to June 2019. During the process of developing and implementing the ADAPTABLE computable phenotype, several key lessons were learned. The accuracy and utility of a computable phenotype are dependent on the quality of the source data, which can be variable even with a common data model. Local validation and modification were required based on site factors, such as recruitment strategies, data quality, and local coding patterns. Sustained collaboration among a diverse team of researchers is needed during computable phenotype development and implementation.

Conclusions: The ADAPTABLE computable phenotype served as an efficient method to recruit patients in a multisite pragmatic clinical trial. This process of development and implementation will be informative for future large-scale, pragmatic clinical trials. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02697916.

Keywords: aspirin; electronic health records; heart disease; patient selection; pragmatic clinical trial.

Figure 1.. ADAPTABLE Inclusion and Exclusion Criteria Versions 1 and 2.

The inclusion and exclusion for the trial at the time of initial computable phenotype development included data elements that were directly mapped to the common data model, identified via sets of code lists, or not available in the common data model. The new criteria added in Version 2 are annotated with blue arrows. PCI = percutaneous coronary intervention; CABG = coronary artery bypass grafting; GI = gastrointestinal.

Figure 2.. ADAPTABLE recruitment metrics.

The computable phenotype identified a large pool of potentially eligible participants at both clinical data research networks and health plan research networks. CDRN = clinical data research network; HPRN = health plan research network.

Figure 3.

Key recommendations from ADAPTABLE computable phenotype implementation.