An integrated pharmacoeconomic-pharmacokinetic framework for prioritizing and testing clinically important drug-gene interactions

Pharmacogenetics (PGx) testing is emerging as a promising approach to inform precise and optimal medication decisions. However, there is a paucity of data examining the utility of these guidelines in Asian populations as the vast majority of known PGx associations were discovered in populations of European descent.

Leveraging on the SG100K database, we thus aim to develop comprehensive research findings on the prevalence of clinically actionable drug-gene interactions and recommend dosing changes tailored to our Singaporean population appropriate for age, weight and renal function, or that should warrant further clinical investigation. This will be done using the following aims:

1) Evaluate the occurrence of known drug-gene interactions based on EHR data and its impact on efficacy and toxicity

2) Explore genotype-drug response associations using SG100K and linked EHR datasets augmented by a dedicated pipeline for haplotyping highly polymorphic drug metabolizing enzyme CYP2D6

3) Develop a pharmacokinetics-informed framework for evaluating and ranking both known and novel drug-gene sets for clinical action to make dose recommendations

Together, we aim to give clarity to the clinically important drug-gene interactions in Asians, and how to manage them.