Personalized Medicine

Personalized medicine tailors therapies, disease prevention and health maintenance to the individual, with pharmacogenomics serving as a key tool to improve outcomes and prevent adverse effects. ^[1] It is closely paired with precision medicine, the two being described together as instruments to investigate pathological processes before clinical symptoms appear and to guide physicians toward a targeted therapy. ^[2] Its rationale is inter-individual variability in drug efficacy and safety, which is common, is likely to grow with an ageing treated population, and is partly explained by genomic factors. ^[3] Beyond drugs, personalized nutrition builds on the food exposome and its interactions with the genome and other biological characteristics such as metabolism and the microbiome. ^[4] In prevention, a precision-prevention approach identifies people at increased risk and targets them for specific interventions such as risk-reducing medication, alongside population-wide reduction of modifiable risk factors. ^[5]

Pharmacogenomics uses genetic variation in pharmacogenes (drug-metabolizing enzymes, drug transporters and receptors) as clinically relevant biomarkers of drug response. ^[1] Advances in genomics have turned pharmacogenetics, traditionally focused on single gene-drug pairs, into pharmacogenomics encompassing the wider -omics fields such as proteomics, transcriptomics, metabolomics and metagenomics. ^[1] Inherited variations in approximately 20 genes affecting about 80 medications have been identified as actionable in the clinic. ^[6] The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes standardized, evidence-based, peer-reviewed gene/drug guidelines on how to use genomic data to inform prescribing. ^[6] CYP2D6 is involved in the metabolism of about 20% of commonly used drugs, and pharmacogenomic guidelines for at least 48 CYP2D6-substrate drugs give recommendations based on predicted metaboliser phenotype. ^[7]

The most common cardiovascular implementation is CYP2C19 genotyping to predict clopidogrel response and select antiplatelet therapy after percutaneous coronary intervention, with further examples in warfarin dosing and statin prescribing. ^[8] Approximately 30% of individuals inherit a deficiency in the CYP2C19 enzyme, which reduces clopidogrel effectiveness. ^[8] A nationwide study in the Netherlands estimated that applying Dutch Pharmacogenetics Working Group (DPWG) guidelines could alter 5.4% of prescriptions through dose adjustments or alternative drugs. ^[7] In psychiatry, several recent large studies indicate a benefit and cost-effectiveness of pre-emptive genotyping, although many heritable factors behind differences in response to psychiatric drugs remain unknown. ^[9] For vitamin D supplementation, a review of meta-analyses and randomized trials found inconsistent benefits overall and concluded that people with baseline deficiency or selected high-risk conditions are most likely to benefit, supporting a precision-prevention approach. ^[10] A narrative review concluded that precision nutrition markedly improves risk factors of obesity

Personalization is not only genomic: in menopause care there is no one-size-fits-all transdermal estradiol dose, and the optimal level varies with tissue sensitivity, assay method, clinical endpoint and patient preferences. ^[14] Likewise, an international consensus states that structured exercise prescriptions for older adults should be customized and monitored like any other medical treatment, considering dose-response relationships. ^[15] Barriers to pharmacogenetic testing include limited clinician confidence in applying results, limited reimbursement in some cases, the need for more outcomes and economic data, and limited inclusion in clinical guidelines. ^[16] Implementation also requires modifying clinical pathways and closing a large pharmacogenomics knowledge gap in the health-care workforce. ^[3] Clinical application faces unknown validity across ethnic groups, underlying bias in health care and the need for real-world validation. ^[1] Medical societies often rely on randomized trial data, which are not always feasible or ethical in pharmacogenetics, so the strength of evidence required for implementation remains debated.