Elsevier

The Lancet

Volume 355, Issue 9212, 15 April 2000, Pages 1358-1361
The Lancet

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Pharmacogenetics and future drug development and delivery

https://doi.org/10.1016/S0140-6736(00)02126-7Get rights and content

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Definitions of disease

Precise diagnoses leading to universal specific treatments are, for many illnesses, myths. Classifications of disease change over time as research provides more information. Diseases are collections of symptoms and signs (phenotypes) that appear to be similar, and for many diseases there is no accurate, single diagnostic test. With the addition of biochemical and genetic information, the heterogeneity of common conditions such as diabetes and Alzheimer's disease has become increasingly apparent.

“Right medicine for the right patient”

Pharmacogenetics is not really about disease diagnosis; instead it is about drug efficacy and safety. A patient's response to a drug may depend on one or more factors that can vary according to the alleles that an individual carries. These factors include drug absorption, drug distribution, drug metabolism and elimination, drug concentration at the target site and the number and morphology of target receptors. Advances in genetics will lead to profiles that take account of these variable

Clinical trials and surveillance

Adverse events associated with medicines remain a significant problem.11, 12 Despite the large numbers typically enrolled in clinical trials to evaluate efficacy and safety of new medicines, rare ADRs (less than 1 in 1000) tend to be identified only when the medicine has been used in much broader patient populations—ie, during the initial marketing phase. For example dexfenfluramine, encainide, zomepirac, ticrynafen, benoxaprofen, terfenadine, and troglitazone were associated with major ADRs

What is the alternative?

Prediction of a high rate of efficacy with a pharmacogenetic profile, coupled with a progressive and timely identification of patients likely to experience ADRs would increase the accuracy of drug selection and dose for individual patients. It would obviate the demand for cost effectiveness to be proved in a broad population before a drug can be added to an approved reimbursement list. Nor will use of a beneficial drug be restricted because only a fraction of patients respond.13, 14 With

Clinical “genetic testing”

The application of pharmacogenetics to drug development and the delivery of medicines could be hampered by confusion over the meaning of “genetic testing” (figure 2). The two broad categories—namely, disease-gene-specific tests for mutations in single genes which are highly predictive and causally related to disease or for disease susceptibility gene polymorphisms which provide information about risk; and pharmacogenetic profiles for polymorphisms in drug-metabolism enzymes and drug target

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