Individual variation in the response to drugs is an important clinical issue and may range from a lack of therapeutic effect to serious adverse drug reactions.
Pharmacogenetics is defined as the study of genetic variation as a determinant of drug response. It can complement information on clinical factors and disease sub-phenotypes to optimise the prediction of treatment response.
This heterogeneity of response has important policy implications if individual patients not responding to conventional agents are denied access to other agents based on clinical trial evidence and systematic reviews that show no overall benefit. While clinical variables such as disease severity, age, concomitant drug use and illnesses are potentially important determinants of the response to drugs, heterogeneity in drug disposition (absorption, metabolism, distribution, and excretion) and targets (such as receptors and signal transduction modulators) may be an important cause of inter-individual variability in the therapeutic effects of drugs (see Pharmacogenomics: translating functional genomics into rational therapeutics. Science 1999;286(5439):487-91). Identification of variation in genes which modify the response to drugs provides the opportunity to optimise safety and effectiveness of the currently available drugs and develop new drugs for paediatric and adult populations (see Drug discovery: a historical perspective. Science 2000;287(5460):1960-4).
|Annex 1.||Guidance on conducting systematic revies and meta-analyses of completed comparative pharmacoepidemiological studies of safety outcomes|