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Pharmacogenetics in drug discovery and development: a translational perspective
Allen D. RosesAbstract | The ability to predict a patients drug response on the basis of their genetic information is expected to decrease attrition during the development of new, innovative drugs, and reduce adverse events by being able to predict individual patients at risk. Most pharmacogenetic investigations have focused on drug-metabolism genes or candidate genes that are thought to be involved in specific diseases. However, robust new genetic tools now enable researchers to carry out multi-candidate gene-association and genome-wide studies for target discovery and drug development. Despite the expanding role of pharmacogenetics in industry, however, there is a paucity of published data. New forms of effective and efficient collaboration between industry and academia that may enhance the systematic collection of pharmacogenetic data are necessary to establish genetic profiles related to drug response, confirm pharmacogenetic associations and expedite the development of new drugs and diagnostic tests.
Improving predictions of drug efficacy and safety is crucial to the future medical and commercial success of drug discovery and development. Targeting therapies to patients who are most likely to benefit and reducing the risk of adverse events will facilitate the approval of new, innovative medicines.
In addition, these factors will also help provide a firm rationale for reimbursement by increasingly cost-constrained health-care systems. Pharmacogenetics (PGx) the study of genetic variation and its effects on the response to drugs, vaccines or other pharmaceutical agents will play a key role in these changes.
The most important step for the success of drug discovery and the creation of a robust pharmaceutical pipeline (FIG. 1) is the
demonstration of efficacy in early stage, relatively small clinical trials (known as proof of concept). PGx testing contributes to this step by defining the subpopulation of patients who experience efficacy (as opposed to those who will not respond), thus avoiding dependence on the average response of
the whole treated population1,2. It is now increasingly possible to use genetic information to differentiate responders early in drug development that is, during the clinical trials necessary for registration3,4. In particular, the growing application of genetic strategies that are based on customized candidate gene arrays and/or genome-wide association scanning will enhance the identification of patients within populations who...