Arguing for Adaptive Clinical Trials in Sepsis.
Arguing for Adaptive Clinical Trials in Sepsis.
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DOI：
10.3389/fimmu.2018.01502
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发表时间：
2018
影响因子：
7.3
通讯作者：
Angus DC
中科院分区：
文献类型：
--
作者：
Talisa VB;Yende S;Seymour CW;Angus DC
脓毒症是由于对感染的反应失调而导致的危及生命的器官功能障碍。脓毒症患者表现出广泛的异质性，源于遗传，分子和临床因素以及病原体的差异，为开发有效的治疗方法带来了挑战。知识方面的一些差距也造成了这种情况：（i）识别可能从特定治疗中受益的患者的生物标志物是未知的;（ii）治疗剂量和持续时间往往知之甚少;（iii）短期死亡率，一种常见的结局指标，经常被批评为不敏感。到目前为止，大多数脓毒症试验使用传统的设计特征，并且在很大程度上未能确定新的治疗方法，这些新的治疗方法具有超过标准治疗的增量获益。传统的试验也经常作为药物评价过程的一部分进行，该过程分为几个阶段，每个阶段都需要单独的试验，从开始到设计和执行到将结果纳入临床实践都有很长的时间延迟。相比之下，适应性临床试验设计便于同时评估几种候选治疗方法，在试验过程中从新发现中学习，并且与传统试验设计相比，可以有效地构建以得出更及时的结论。如果将这些试验纳入电子健康记录，作为学习健康系统的一部分，则可以加速临床实践中新疗法的采用。在这篇综述中，我们讨论了脓毒症治疗评估中的挑战，并探讨了适应性试验方法学最新进展的潜在益处和弱点，以应对这些挑战。
Sepsis is life-threatening organ dysfunction due to dysregulated response to infection. Patients with sepsis exhibit wide heterogeneity stemming from genetic, molecular, and clinical factors as well as differences in pathogens, creating challenges for the development of effective treatments. Several gaps in knowledge also contribute: (i) biomarkers that identify patients likely to benefit from specific treatments are unknown; (ii) therapeutic dose and duration is often poorly understood; and (iii) short-term mortality, a common outcome measure, is frequently criticized for being insensitive. To date, the majority of sepsis trials use traditional design features, and have largely failed to identify new treatments with incremental benefit over standard of care. Traditional trials are also frequently conducted as part of a drug evaluation process that is segmented into several phases, each requiring separate trials, with a long time delay from inception through design and execution to incorporation of results into clinical practice. By contrast, adaptive clinical trial designs facilitate the evaluation of several candidate treatments simultaneously, learn from emergent discoveries during the course of the trial, and can be structured efficiently to lead to more timely conclusions compared to traditional trial designs. Adoption of new treatments in clinical practice can be accelerated if these trials are incorporated in electronic health records as part of a learning health system. In this review, we discuss challenges in the evaluation of treatments for sepsis, and explore potential benefits and weaknesses of recent advances in adaptive trial methodologies to address these challenges.
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DOI：
10.1136/bmj.i2375
发表时间：
2016-05-17
期刊：
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影响因子：
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作者：
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影响因子：
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影响因子：
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DOI：
10.1177/1740774515621721
发表时间：
2016-02
期刊：
Clinical trials (London, England)
影响因子：
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作者：
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影响因子：
28.2
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