Assessment of the Implementation of Pharmacogenomic Testing in a Pediatric Tertiary Care Setting

Abstract

Key Points Question What is the clinical utility of a pharmacogenomic testing program that uses both point-of-care and preemptive approaches to assess potential responses to drugs in a pediatric tertiary care setting? Findings In this cohort study of 172 pediatric patients, pharmacogenomic testing of 6 pharmacogenes ( CYP2D6 , CYP2C9 , CYP2C19 , CYP3A5 , TPMT , and VKORC1 ) provided results that warranted deviation from standard treatment regimens in approximately 40% of patients in the point-of-care evaluation of targeted drugs and 80% of patients in the preemptive evaluation of a broader range of drugs for potential therapy. Meaning The study’s findings suggest that a pharmacogenomic program using both point-of-care targeted drug–guided testing and preemptive whole-genome sequencing–guided testing enhances the knowledge necessary for patient care decision-making, providing informed rationales for drug selection and dosing options.

Identifying the prevalence of clinically actionable drug‐gene interactions in a health system biorepository to guide pharmacogenetics implementation services

“…Similar to our investigation, other investigators evaluated DGIs using linked prescription and genetic data and have reported between 1% and 73% of patients experienced a clinically significant DGI 10,24,25,29–33 . The wide variability in reported clinically significant DGIs can likely be attributed to differences in the evaluated genes and medications, as well as the population demographics of the cohorts.…”

“…Similar to our investigation, other investigators evaluated DGIs using linked prescription and genetic data and have reported between 1% and 73% of patients experienced a clinically significant DGI. 10 , 24 , 25 , 29 , 30 , 31 , 32 , 33 The wide variability in reported clinically significant DGIs can likely be attributed to differences in the evaluated genes and medications, as well as the population demographics of the cohorts. For example, Van Dreist et al reported 42%–48% of study participants had a DGI; the higher exposure was observed in a cohort of patients who were recruited to the PREDCIT study and therefore had a higher likelihood for being prescribed a cardiovascular medication with PGx recommendations.…”

Clinical Implications of Pharmacogenomic Testing in the Real World—Insights From a Pediatric Program

“…Cohn and colleagues address this question by reporting the outcomes of a pilot program combining reactive and preemptive approaches for PGx testing in a pediatric tertiary hospital. Two cohorts were offered PGx testing for a panel of 6 genes with high evidence of actionability, with the support of a PGx consultation for the interpretation of the findings.…”

Characterizing pharmacogenetic programs using the consolidated framework for implementation research: A structured scoping review

“…Despite variability in the choice of test provider and target selection, almost all centers made use of genotyping rather than sequencing approaches, though there were two exceptions. The Hospital for Sick Children in Toronto, as part of a clinical trial, compared pre-emptive against reactive-testing ( 50 ). Pre-emptive pharmacogenetic testing involved the reanalysis of whole genome sequencing (WGS) data undertaken as part of separate investigations for congenital cardiac malformations.…”