The era of genomics: Impact on sepsis clinical trial design
The era of genomics: Impact on sepsis clinical trial design
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基因组学时代：对脓毒症临床试验设计的影响
作者：
A. Cariou;J. Chiche;J. Charpentier;J. Dhainaut;J. Mira
本文旨在解决遗传学对重症监护医学领域临床试验设计的可预测影响，重点是脓毒症的病理生理学及其治疗。资料来源发表的文章报道了脓毒症和脓毒性休克的研究，或评估了遗传学和药物基因组学在治疗危重疾病中的影响。数据分析由于大多数常见疾病，包括败血症已被证明是由我们的基因遗传差异的影响，完成人类基因组计划和人类单核苷酸多态性图谱的伴随出版都有助于改变我们的医学方法。基因分型技术和生物信息学的进步使得单核苷酸多态性的检测成为可能，这引起了药物基因组学的爆炸性发展，药物基因组学研究个体基因型与药物治疗结果之间的相互作用。药物基因组学无疑将以不同的方式用于改善未来的医疗保健和临床研究。尽管治疗分配主要基于表型，但遗传特征将有助于研究人员确定适合临床试验的受试者，促进临床试验结果的解释，并为未来药物或现有产品确定新的靶点。由于药物反应的个体间差异是一个重要的临床问题，药物基因组学研究的第二个主要目标是通过确定适当的治疗靶点和改变药物特异性和毒性的遗传多态性来减少对治疗的不良反应。最终，遗传信息将用于选择最有效的治疗剂和最佳剂量，以引起给定个体的预期药物反应。实施遗传标准对患者人群进行分层，并对治疗风险和益处进行个体评估，这是制药业面临的一个重大挑战。结论在未来，基因芯片阵列等技术将增强遗传医学，并提供新的见解，病人对疾病的易感性，使预后的危险因素，更快的诊断和准确的预测个人对药物的反应更好的评估。这种方法对预防和治疗疾病的可预测后果可能会使医学发生革命性变化。
ObjectiveThis 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. Data SourcesPublished articles reporting studies on sepsis and septic shock or assessing the influence of genetics and pharmacogenomics in the treatment of critical illnesses. Data AnalysisBecause 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. ConclusionsIn 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.
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影响因子：
6
作者：
Chinnaiyan, AM;Huber-Lang, M;Ward, PA
通讯作者：
Ward, PA
种群和遗传多态性。
DOI：
--
发表时间：
1999
期刊：
Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology
影响因子：
--
作者：
Weber,WW
通讯作者：
Weber,WW
心血管药物代谢的分子基础：对预测临床重要药物相互作用的影响。
影响因子：
37.8
作者：
Abernethy,DR;Flockhart,DA
通讯作者：
Flockhart,DA
影响因子：
--
作者：
Lorenz, E;Mira, JP;Schwartz, DA
通讯作者：
Schwartz, DA