Genotype-based clinical trials in cardiovascular disease.
Genotype-based clinical trials in cardiovascular disease.
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DOI：
10.1038/nrcardio.2015.64
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Rihal CS
中科院分区：
文献类型：
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作者：
Pereira NL;Sargent DJ;Farkouh ME;Rihal CS
共识实践指南和临床治疗进展的实施通常基于大型随机临床试验(RCT)的结果。然而，随机对照试验通常告知我们对假定为同种人群的平均治疗效果，但治疗干预措施很少使整个目标人群受益。事实上，多项随机对照试验已经证明，在药物反应和不良反应的发展过程中都存在个体间的差异。药物基因组学领域承诺将正确的药物提供给正确的患者。随着技术、统计和计算方法的进步以及细胞和动物模型系统的使用，这一领域取得了实质性进展。然而，药物遗传学原则的临床实施一直很困难，因为缺乏显示出益处的随机对照试验。对于患者来说，进行此类试验的潜在好处包括个体化治疗，以最大限度地提高疗效并将不良反应降至最低。这些试验还将使调查人员能够减少样本量，从而控制试验赞助商的费用。进行基于基因的随机对照试验需要考虑多个伦理、法律和实践问题。电子健康记录中嵌入的先发制人的基因分型是否会排除进行基于基因的随机对照试验的需要，还有待观察。
Consensus practice guidelines and the implementation of clinical therapeutic advances are usually based on the results of large, randomized clinical trials (RCTs). However, RCTs generally inform us on an average treatment effect for a presumably homogeneous population, but therapeutic interventions rarely benefit the entire population targeted. Indeed, multiple RCTs have demonstrated that interindividual variability exists both in drug response and in the development of adverse effects. The field of pharmacogenomics promises to deliver the right drug to the right patient. Substantial progress has been made in this field, with advances in technology, statistical and computational methods, and the use of cell and animal model systems. However, clinical implementation of pharmacogenetic principles has been difficult because RCTs demonstrating benefit are lacking. For patients, the potential benefits of performing such trials include the individualization of therapy to maximize efficacy and minimize adverse effects. These trials would also enable investigators to reduce sample size and hence contain costs for trial sponsors. Multiple ethical, legal, and practical issues need to be considered for the conduct of genotype-based RCTs. Whether pre-emptive genotyping embedded in electronic health records will preclude the need for performing genotype-based RCTs remains to be seen.