Pharmacogenomics – a minor rather than major force in clinical medicine

ABSTRACT

Introduction

Pharmacogenomics (PGx) is touted as essential for the future of precision medicine. But the opportunity cost of PGx from the prescribers’ perspective is rarely considered. The aim of this article is to critique PGx-guided prescribing using clinical pharmacology principles so that important cases for PGx testing are not missed by doctors responsible for therapeutic decision making.

Areas covered

Three categories of PGx and their limitations are outlined – exposure PGx, response PGx, and immune-mediated safety PGx. Clinical pharmacology reasons are given for the narrow scope of PGx-guided prescribing apart from a few medical specialties. Clinical problems for doctors that may arise from PGx are then explained, including mismatch between patients’ expectations of PGx testing and the benefits or answers it provides.

Expert opinion

Contrary to popular opinion, PGx is unlikely to become the cornerstone of precision medicine. Sound clinical pharmacology reasons explain why PGx-guided prescribing is unnecessary for most drugs. Pharmacogenomics is important for niche areas of prescribing but has limited clinical utility more broadly. The opportunity cost of PGx-guided prescribing is currently too great for most doctors.

KEYWORDS:

• Pharmacogenomics
• pharmacogenetics
• precision medicine
• personalized medicine
• pharmacogenomic-guided prescribing
• precision dosing

Article highlights

• Despite mostly positive views of pharmacogenomics (PGx), the opportunity cost of PGx-guided prescribing is not well considered in the literature.

• It is useful to think of PGx in three categories for clinical practice. Exposure PGx is concerned with how much drug patients are exposed to, response PGx is about ensuring that patients have the correct molecular targets, and immune-mediated safety PGx aims to reduce the risk of catastrophic drug responses.

• Clinical pharmacology reasons for the narrow scope of PGx include: most drug responses are influenced by many covariates; many dose-exposure-response relationships are poorly characterized; most drugs do not require precision dosing; genotype penetrance is variable; clinical trial population to patient mismatch; most drugs are well monitored clinically; variable adherence renders PGx powerless; and new drugs avoid PGx-guided prescribing and old drugs lose favor when PGx becomes important.

• Clinical problems that may arise from PGx include: unrealistic expectations from patients; incorrect use by prescribers; time consuming prescribing; medico-legal implications; PGx fatigue; and undermining of clinical pharmacology with other medical specialties.

• Pharmacogenomics is a minor rather than major force in clinical medicine, important for niche areas of prescribing, but with limited clinical utility more broadly. The opportunity cost of PGx-guided prescribing is currently too large for most doctors.

• Referral to a clinical pharmacologist with PGx experience is recommended for patients with histories of medication-related problems at standard doses.

Declaration of interest

The author receives remuneration from Sonic Genetics for pharmacogenomics consultancy. The author has 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

I gratefully acknowledge the many discussions with colleagues and patients about pharmacogenomics over the last two decades that shaped the ideas in this article. Particular thanks to Professor Sepehr Shakib, Professor Graeme Suthers, Professor Ric Day, Associate Professor Matthew Doogue, Professor Carl Kirkpatrick and Dr Sam Mostafa.

Additional information

Funding

This paper was not funded.