Pragmatic Trials in Genomic Medicine: The Integrating Pharmacogenetics In Clinical Care (I-PICC) Study

Abstract

Pragmatic clinical trials (PCTs) have an established presence in clinical research and yet have only recently garnered attention within the landscape of genomic medicine. Using the PRagmatic-Explanatory Continuum Indicator Summary 2 (PRECIS-2) as a framework, this paper illustrates the application of PCT principles to The Integrating Pharmacogenetics In Clinical Care (I-PICC) Study, a trial of pharmacogenetic testing prior to statin initiation for cardiovascular disease prevention in primary care. The trial achieved high engagement with providers (85% enrolled of those approached) and enrolled a representative sample of participants for which statin therapy would be recommended. The I-PICC Study has a high level of pragmatism, which should enhance the generalizability of its findings. The PRECIS-2 may be useful in the design and evaluation of PCTs of genomic medicine interventions, contributing to the generation of evidence that can bridge the gap between genomics innovation and clinical adoption.

Trial registration: ClinicalTrials.gov NCT02871934.

Conflict of interest statement

The authors declared no competing interests for this work.

© 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.

Figures

Figure 1

Study timeline for the Integrating Pharmacogenetics in Clinical Care Study. Risk scores are 10‐year CVD risk scores as calculated using American College of Cardiology/American Heart Association Pooled Cohort Risk Assessment Equations.22 *10‐year CVD risk scores calculated for 1,455 patients and added to potentially eligible patient database (not including African American women). **10‐year CVD risk scores calculated for 1,019 additional patients between February 8, 2018, and February 27, 2018, and added to potentially eligible patient database (including patients from all demographic backgrounds). ***First date of regular 10‐year CVD risk score calculations begin on a daily basis for potentially eligible patients using the birthday parity method as described by Vassy et al.21 CVD, cardiovascular disease; EHR, electronic health record; IRB, Institutional Review Board.

Figure 2

The Integrating Pharmacogenetics in Clinical Care (I‐PICC) Study design and workflow. Study staff, with clinical trial management software support, interface directly with providers, patients, the electronic health records (EHRs), and the corporate data warehouse (CDW) to recruit and enroll participants, introduce SLCO1B1 pharmacogenetic (PGx) testing and its results, and track patient clinical outcomes within the context of routine care.

Figure 3

PRagmatic‐Explanatory Continuum Indicator Summary 2 (PRECIS‐2) rating scale (left) and mapping of the Integrating Pharmacogenetics in Clinical Care study design to the PRECIS‐2 wheel (right).

Figure 4

Average patient enrollment per week between December 13, 2016, and July 17, 2018, for the Integrating Pharmacogenetics in Clinical Care (I‐PICC) Study. Time segments are separated by modifications to the I‐PICC Study recruitment design and workflow after first patient enrollment. Risk scores are 10‐year CVD risk scores as calculated using American College of Cardiology/American Heart Association Pooled Cohort Risk Assessment Equations.22 Regular CVD risk score calculations refer to the daily generation of 10‐year CVD risk scores using the birthday parity method as described by Vassy et al.21 CVD, cardiovascular disease.

Figure 5

Provider engagement in the Integrating Pharmacogenetics in Clinical Care Study SLCO1B1 genetic testing intervention. Five hundred fourteen total SLCO1B1 genetic test orders were distributed by study staff to 41 enrolled providers between December 13, 2016, and July 17, 2018. *There were 425 (83%) orders (including orders on both adequate and inadequate specimens) that were signed. **Eighty‐nine (17%) orders were declined or not acted upon within seven days of collection, the maximum timeframe in which the Veterans Affairs Boston Healthcare System laboratory retains clinical specimens for assessment.