Maslove David M, Lamontagne Francois, Marshall John C, Heyland Daren K
Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
Department of Medicine, Queen's University, Kingston, ON, Canada.
Crit Care. 2017 Apr 3;21(1):79. doi: 10.1186/s13054-017-1653-x.
Precision medicine is increasingly touted as a groundbreaking new paradigm in biomedicine. In the ICU, the complexity and ambiguity of critical illness syndromes have been identified as fundamental justifications for the adoption of a precision approach to research and practice. Inherently protean diseases states such as sepsis and acute respiratory distress syndrome have manifestations that are physiologically and anatomically diffuse, and that fluctuate over short periods of time. This leads to considerable heterogeneity among patients, and conditions in which a "one size fits all" approach to therapy can lead to widely divergent results. Current ICU therapy can thus be seen as imprecise, with the potential to realize substantial gains from the adoption of precision medicine approaches. A number of challenges still face the development and adoption of precision critical care, a transition that may occur incrementally rather than wholesale. This article describes a few concrete approaches to addressing these challenges.First, novel clinical trial designs, including registry randomized controlled trials and platform trials, suggest ways in which conventional trials can be adapted to better accommodate the physiologic heterogeneity of critical illness. Second, beyond the "omics" technologies already synonymous with precision medicine, the data-rich environment of the ICU can generate complex physiologic signatures that could fuel precision-minded research and practice. Third, the role of computing infrastructure and modern informatics methods will be central to the pursuit of precision medicine in the ICU, necessitating close collaboration with data scientists. As work toward precision critical care continues, small proof-of-concept studies may prove useful in highlighting the potential of this approach.
精准医学越来越被吹捧为生物医学领域一种开创性的新范式。在重症监护病房(ICU)中,危重症综合征的复杂性和模糊性已被确认为采用精准研究和实践方法的根本依据。诸如脓毒症和急性呼吸窘迫综合征等本质上多变的疾病状态,其表现具有生理和解剖学上的弥散性,且在短时间内会发生波动。这导致患者之间存在相当大的异质性,以及采用“一刀切”治疗方法可能会产生差异很大的结果的情况。因此,当前的ICU治疗可被视为不够精准,采用精准医学方法有可能实现大幅改善。精准重症监护的发展和应用仍面临一些挑战,这种转变可能是渐进式的,而非全面性的。本文介绍了应对这些挑战的一些具体方法。首先,新颖的临床试验设计,包括注册随机对照试验和平台试验,提出了如何调整传统试验以更好地适应危重症生理异质性的方法。其次,除了已经与精准医学同义的“组学”技术外,ICU丰富的数据环境可以生成复杂的生理特征,为注重精准的研究和实践提供助力。第三,计算基础设施和现代信息学方法的作用对于在ICU中追求精准医学至关重要,这需要与数据科学家密切合作。随着精准重症监护工作的持续推进,小型概念验证研究可能有助于凸显这种方法的潜力。