Identifying Indicators of Adverse Drug Reactions

Adverse Drug Reactions (ADRs) are a considerable problem facing patients, health care providers, government regulatory bodies and pharmaceutical companies. Although only a very small percentage of patients may experience adverse reactions to particular drugs, that small percentage can incur health problems causing medical expenses. Tort claims, filed against drug manufacturers, add to the cost of making new drugs available. Therefore all parties concerned (with the possible exception of attorneys) have a vested interest in identifying people who are at risk with respect to specific medications.

Fortunately advances in genome sequencing technology may provide the means by which at risk patients can be identified by correlating genetic traits to specific drug sensitivities. Distinguishing single nucleotide polymorphisms (SNPs) may yield significant payoffs in this respect.

Genome-wide approaches to identify pharmacogenetic contributions to adverse drug reactions, a paper authored by M R Nelson, S-A Bacanu, M Mosteller, L Li, C E Bowman, A D Roses, E H Lai and M G Ehm and published in The Pharmacogenomics Journal (2009, 9, 23–33; doi:10.1038/tpj.2008.4) alludes to research intended to identify ADR pharmacogenetic risk factors. Quoting the abstract:

Adverse drug reactions (ADRs) have a major impact on patients, physicians, health care providers, regulatory agencies and pharmaceutical companies. Identifying the genetic contributions to ADR risk may lead to a better understanding of the underlying mechanisms, identification of patients at risk and a decrease in the number of events. Technological advances have made the routine monitoring and investigation of the genetic basis of ADRs during clinical trials possible. We demonstrate through simulation that genome-wide genotyping, coupled with the use of clinically matched or population controls, can yield sufficient statistical power to permit the identification of strong genetic predictors of ADR risk in a prospective manner with modest numbers of ADR cases. The results of a 500 000 single nucleotide polymorphism analysis of abacavir-associated hypersensitivity reaction suggest that the known HLA-B gene region could be identified with as few as 15 cases and 200 population controls in a sequential analysis.