Exploring human biology with N-of-1 clinical trials.
Exploring human biology with N-of-1 clinical trials.
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通过 N-of-1 临床试验探索人类生物学。
DOI：
10.1017/pcm.2022.15
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Goetz,LH
中科院分区：
文献类型：
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作者：
Schork,NJ;Beaulieu-Jones,B;Liang,WS;Smalley,S;Goetz,LH
利用当代数据密集型、高通量“组学”分析技术（如基因组学、转录组学、蛋白质组学和代谢组学）对人类进行的研究明确表明，人类在分子水平上存在很大差异。这些差异，这是由每个人的独特的行为和环境暴露加剧，影响个人对健康干预措施，如饮食和药物的反应。关于根据个体的细微差别的基因组、生理、行为等特征为个体定制健康干预措施的最佳方式的问题促使了当前对“精确”医学的重视。这篇综述的目的是描述如何设计和执行N-1（或个性化）多变量临床试验可以推进该领域。这些试验从全人的角度关注个人对健康干预措施的反应，利用新兴的健康监测技术，可用于解决精准医学时代最相关的问题。这包括如何验证可能指示干预措施的适当活动的生物标志物，以及如何识别可能对个体有益的干预措施。我们还认为，多变量N-of-1和聚合N-of-1试验是在精准医学时代推进生物医学和转化科学的理想工具，因为从中获得的见解不仅可以阐明如何治疗或预防疾病，而且还可以提供见解如何为那些首先寻求关注其健康问题的个人提供实时护理。
Studies on humans that exploit contemporary data-intensive, high-throughput ‘omic’ assay technologies, such as genomics, transcriptomics, proteomics and metabolomics, have unequivocally revealed that humans differ greatly at the molecular level. These differences, which are compounded by each individual’s distinct behavioral and environmental exposures, impact individual responses to health interventions such as diet and drugs. Questions about the best way to tailor health interventions to individuals based on their nuanced genomic, physiologic, behavioral, etc. profiles have motivated the current emphasis on ‘precision’ medicine. This review’s purpose is to describe how the design and execution of N-of-1 (or personalized) multivariate clinical trials can advance the field. Such trials focus on individual responses to health interventions from a whole-person perspective, leverage emerging health monitoring technologies, and can be used to address the most relevant questions in the precision medicine era. This includes how to validate biomarkers that may indicate appropriate activity of an intervention as well as how to identify likely beneficial interventions for an individual. We also argue that multivariate N-of-1 and aggregated N-of-1 trials are ideal vehicles for advancing biomedical and translational science in the precision medicine era since the insights gained from them can not only shed light on how to treat or prevent diseases generally, but also provide insight into how to provide real-time care to the very individuals who are seeking attention for their health concerns in the first place.