The Coriell personalized medicine collaborative pharmacogenomics appraisal, evidence scoring and interpretation system

Neda Gharani,Neda Gharani,Catharine B Stack,Margaret A Keller,Margaret A Keller,Michael F Christman,Catharine B Stack,Laura M Hodges,Michael F Christman,Erynn S Gordon,Margaret A Keller,Erynn S Gordon,Tara J Schmidlen,Tara J Schmidlen,Daniel E Lynch,Daniel E Lynch

doi:10.1186/gm499

Abstract

Implementation of pharmacogenomics (PGx) in clinical care can lead to improved drug efficacy and reduced adverse drug reactions. However, there has been a lag in adoption of PGx tests in clinical practice. This is due in part to a paucity of rigorous systems for translating published clinical and scientific data into standardized diagnostic tests with clear therapeutic recommendations. Here we describe the Pharmacogenomics Appraisal, Evidence Scoring and Interpretation System (PhAESIS), developed as part of the Coriell Personalized Medicine Collaborative research study, and its application to seven commonly prescribed drugs.

Highlights

It has long been recognized that there is significant variability in drug response with respect to efficacy, optimal dose, and adverse drug reactions (ADRs)
Identification of key PGx gene(s) and drug-specific key genetic variants Once a drug is selected for evaluation, the Food and Drug Administration (FDA) drug label, the peer-reviewed scientific and clinical literature, and public web-based databases are searched for studies that report drug-related genotype–phenotype associations
Seven drugs/drug class and nine associated genes have been approved for PGx reporting to Coriell Personalized Medicine Collaborative (CPMC) participants

Summary

Introduction

It has long been recognized that there is significant variability in drug response with respect to efficacy, optimal dose, and adverse drug reactions (ADRs). Such a system should identify the genetic components that have sufficient data to support clinical or diagnostic utility, present evidence-based interpretations of genetic results in the context of particular drugs, provide clear recommendations for the application of specific results, and highlight areas with gaps in knowledge that need further investigation The outcome of such a critical appraisal should guide further studies aimed both at addressing the specific gaps in knowledge about a gene’s effects on a specific drug (termed a ‘drug-gene pair’) and at validating further the predictive biomarkers, allowing therapeutics and diagnostics developers and regulators to make meaningful riskbenefit assessments that will pave the way to clinical adoption of the PGx guidelines [11]. This requires a multifaceted approach that includes routine integration of PGx in the design and outcomes analysis of clinical drug trials; retrospective studies that link patient health outcomes with medical/medication histories, gleaned through self-reported or EMR data [12,13]; and prospective, population-based, comparative effectiveness research [14,15]

Methods

Discussion

Conclusion