This article aims to address the predictable impact of genetics
on the design of clinical trials in the field of critical care medicine, with emphasis on the pathophysiology of sepsis
and its treatment.
Published articles reporting studies on sepsis
and septic shock or assessing the influence of genetics
in the treatment of critical illnesses.
Because most common diseases including sepsis
have been shown to be influenced by inherited differences in our genes, completion of the Human Genome Project and the concomitant publication of the human single nucleotide polymorphism
map both contribute to change our approach to medicine. Advances in genotyping techniques and bioinformatics enabling detection of single nucleotide polymorphisms have caused an explosion in pharmacogenomics
—the research dealing with the interactions of an individual’s genotype and the outcome of a drug therapy. Pharmacogenomics
will undoubtedly be used to improve future health care and clinical research in different ways. Whereas treatment allocation has been based mainly on phenotype, genetic characterization will help researchers to identify suitable subjects for clinical trials, to facilitate interpretation of the results of clinical trials, and to identify novel targets for future drugs or new markets for current products. As interindividual variability in drug response is a substantial clinical problem, the second major objective of pharmacogenomic research is to decrease adverse responses to therapy through determination of adequate therapeutic targets and genetic polymorphisms that alter drug specificity and toxicity. Ultimately, genetic information will be used to select the most effective therapeutic agent and the optimal dosage to elicit the expected drug response for a given individual. Implementation of genetic criteria for stratification of patient populations and individual assessment of treatment risks and benefits emerges as a major challenge to the pharmaceutical industry.
In the future, technologies such as gene chip array will enhance genetic medicine and provide novel insights into a patient’s susceptibility to disease, enabling a better assessment of prognostic risk factors, quicker diagnosis, and accurate prediction of individual responsiveness to drugs. The predictable consequences of such an approach on the prevention and treatment of diseases could revolutionize medicine.