Pharmacogenetic biomarkers for predicting drug response

Abstract

Drug response shows significant interpatient variability and evidence that genetics influences outcome of drug therapy has been known for more than five decades. However, the translation of this knowledge to clinical practice remains slow. Using examples from clinical practice six considerations about the implementation of pharmacogenetics (PGx) into routine care are discussed: the need for PGx biomarkers; the sources of genetic variability in drug response; the amount of variability explained by PGx; whether PGx test results are actionable; the level of evidence needed for implementation of PGx and the sources of information regarding interpretation of PGx data.

Keywords::

• drug efficacy
• drug safety
• implementation
• pharmacodynamics
• pharmacogenetics
• pharmacogenomics
• pharmacokinetics

Acknowledgements

This work was supported by an unrestricted grant from the Royal Dutch Association for the Advancement of Pharmacy, The Hague, The Netherlands.

Financial & competing interests disclosure

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Drug response is a heritable trait.

• Biomarkers are needed for predicting drug response.

• Pharmacogenetic biomarkers in genes involved in both pharmacokinetics and pharmacodynamics predispose for toxicity and efficacy.

• The influence of genetic biomarkers on outcomes or key determinants of drug response and risk of toxicity can be quantified.

• Genetic biomarkers should be combined with other determinants of drug response.

• Pharmacogenetic studies should report actionable results.

• Observational evidence from well-designed and replicated studies may be acceptable to guide dose adjustments in case of gene-drug interactions.

• Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetic Working Group guidelines are available that provide evidence-based dosing recommendations for gene-drug interactions.