Review of the Reported Measures of Clinical Validity and Clinical Utility as Arguments for the Implementation of Pharmacogenetic Testing: A Case Study of Statin-Induced Muscle Toxicity.

Marleen E Jansen,W Rodenburg,E J F Houwink,T Rigter,M Weda,Martina C Cornel,T M C Fleur

doi:10.3389/fphar.2017.00555

Abstract

Advances from pharmacogenetics (PGx) have not been implemented into health care to the expected extent. One gap that will be addressed in this study is a lack of reporting on clinical validity and clinical utility of PGx-tests. A systematic review of current reporting in scientific literature was conducted on publications addressing PGx in the context of statins and muscle toxicity. Eighty-nine publications were included and information was selected on reported measures of effect, arguments, and accompanying conclusions. Most authors report associations to quantify the relationship between a genetic variation an outcome, such as adverse drug responses. Conclusions on the implementation of a PGx-test are generally based on these associations, without explicit mention of other measures relevant to evaluate the test's clinical validity and clinical utility. To gain insight in the clinical impact and select useful tests, additional outcomes are needed to estimate the clinical validity and utility, such as cost-effectiveness.

Highlights

Health care professionals, scientists, and policy makers have recognized the potential of precision medicine to optimize therapeutic outcomes
“Our findings provide further support for a role for SLCO1B1 genotype in simvastatin-associated myopathy, and suggest that this association may be stronger for simvastatin compared with atorvastatin.”
Results from PGx studies on statins for cardiovascular disease are often summarized as associations between the genotype and phenotype: from effective drug levels to ADRs

Summary

Introduction

Scientists, and policy makers have recognized the potential of precision medicine to optimize therapeutic outcomes. Appropriate therapeutic choices could be made by prospectively identifying patients through pharmacogenetic (PGx) tests. Numerous barriers for the successful implementation of PGx have been described (Horgan et al, 2014; Tan-Koi et al, 2015): from lack of evidence for clinical practice to unawareness amongst health care professionals about PGx. PGx is successfully applied in some health care settings, predominantly in specialized cancer care (Horgan et al, 2014). PGx is successfully applied in some health care settings, predominantly in specialized cancer care (Horgan et al, 2014) It is not always clear how decisions whether or not to implement PGx testing in a health care practice are made, and which evidence is needed for these decisions

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Conclusion