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full development of compounds. The availability of genomic samples in large phase
IV trials provides a valuable resource for further understanding the molecular basis of
disease heterogeneity, providing data that feeds back into the drug discovery process
in target identifi cation and validation for the next generation of improved medicines.

Pharmacogenomics and Clinical Trials

Examples of role of pharmacogenomics in clinical trials are listed in Table 5.3.
The knowledge of pharmacogenetics and pharmacogenomics is already improv-
ing the conduct of clinical trials based on genotyping stratifi cation and development
of individualized healthcare or personalized medicines. Current applications of
pharmacogenomics include development by prospective genotyping in phase I tri-
als, to ensure that a subject population is representative with respect to drug metabo-
lism phenotypes. The banking of genetic material from later stage trials for
retrospective studies on drug response is becoming more frequent, but is not yet
standard in the industry. Retrospective studies using collections of DNA that supply
medical information on specifi c disease types, drug response and ethnic composi-
tion could build a foundation for the evolution of medicine from diagnosis and treat-
ment towards prediction and prognosis which are important components of
integrated personalized medicine. Figure 5.2 shows various steps for the application
of pharmacogenomics in clinical trials. Some examples of use of pharmacogenomics
in clinical studies are shown in Table 5.4.

Table 5.3 Role of pharmacogenomics in clinical trials

Identifi cation of variations in large number of genes that affect drug action

Stratifi cation of patients in clinical trials according to genotype

Reduction of the total number of patients required for clinical trials

Prediction of optimal doses of the drug in different patient populations

Reduction in drug development time by demonstrating effi cacy in specifi c populations

Prediction of adverse reactions or therapeutic failures based on the genotype of the patient

Prediction of drug-drug interactions

© Jain PharmaBiotech

Clinical trials for relationship

between candidate gene

variants and efficacy/ safety

sequence

Controlled clinical trials

on populations stratified

by genotyping sequence

Identification of the target for

drug action

Identification of the

mechanism of action of drug

Identification of the candidate

gene

© Jain PharmaBiotech

Fig. 5.2 Steps in the application of pharmacogenomics in clinical trials

5 Pharmacogenomics