The Application of Pharmacogenomics in Observational Safety Studies
Patient variations in response to medications are of major clinical concern. Pharmacogenomics is the study of the extent to which genetic variability can influence these responses. This is of particular importance with regard to the effectiveness of the medications and also adverse drug reactions.
Knowing how patients respond to medicines enables treatment to be tailored more specifically, maximising benefit and minimising harm. For example, prior knowledge of a patient's drug metabolism status can aid the selection of a drug, dosage regimen, and prediction of drug-drug interactions. Mutations in genes encoding drug metabolising enzymes may have large effects on blood concentrations of drugs and subsequent individual responses to certain medicines. These genetic mutations may have an impact on susceptibility to ADRs and also on the efficacy of medicines. Thus the identification of genetic risk factors has the ability to reduce drug-related morbidity.
The effect of genetic variability on disease susceptibility and drug treatment has been studied extensively at the patient level, but less so at population level. It is necessary to establish the clinical relevance of specific genetic mutations in drug metabolism by conducting controlled, prospective studies in large populations of individuals. As the DSRU has conducted an extensive number of pharmacoepidemiological studies, it is ideally placed to integrate these two components.
The DSRU is currently collaborating with other academic units investigating the genetic susceptibility of certain patients to drug-induced cardiac arrhythmias. The Drug-Induced Arrhythmia (DARE) study hopes to enhance the understanding of pro-arrhythmia and its risk factors.