New strategies for clinical trials in patients with sepsis and septic shock
New strategies for clinical trials in patients with sepsis and septic shock
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DOI：
10.1097/00003246-200104000-00039
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发表时间：
2001-04-01
影响因子：
8.8
通讯作者：
Opal, S
中科院分区：
文献类型：
--
作者：
Cohen, J;Guyatt, G;Opal, S
目的：在确定新的治疗方式，显着降低死亡率和发病率与败血症的困难，突出了需要重新评估的方法，临床试验设计。联合王国医学研究理事会召集了一个国际工作组来解决这些问题。数据来源：共同主席确定了将成为讨论重点的主题领域，并提名了小组负责人。会前阅读材料分发给小组成员。研究选择和数据提取：小组讨论反馈到全体会议的迭代过程中，然后提出建议。最后，每个工作组都编写了一份建议摘要，并在此报告。首先，研究者不应再仅仅依赖美国胸科医师学会/重症医学会对脓毒症或脓毒症综合征的定义作为进入试验的依据。入选标准应基于三个原则：a）所有患者均应存在感染; B）应存在病理过程的证据，该病理过程代表了拟议干预的生物学合理靶点，例如，与研究药物相关的生物标志物的异常循环水平;以及c）患者应属于适当的严重程度类别其次，研究者应该使用一个已经被验证的器官功能障碍的瘢痕系统，并且可以将其纳入所有脓毒症研究;使用单一系统的协议将简化研究之间的比较，第三，主要结局指标通常应该是死亡率，但在适当的情况下，主要发病率可以被认为是主要终点。无论选择的主要终点的持续时间如何，患者应接受大于或等于90天的随访。第四，样本量需要根据现实的评估，可实现的效果大小的基础上的知识的风险人口，第五，亚组的数量应该很少，并应事先定义的基础上存在的变量前randomization.Conclusions：重要的变化，在几个方面的试验设计可能会提高脓毒症的临床研究的质量，并最大限度地提高机会，确定有效的治疗药物。
Objective: The difficulty in identifying new treatment modalities that significantly reduce the mortality and morbidity rates associated with sepsis has highlighted the need to reevaluate the approach to clinical trial design. The United Kingdom Medical Research council convened an international Working Party to address these issues.Data Sources: The subject areas that were to be the focus of discussion were identified by the co-chairs, and group leaders were nominated. Preconference reading material was circulated to group members.Study Selection and Data Extraction: Small-group discussion fed into an iterative process of feedback from plenary sessions, followed by the formulation of recommendations. Finally, each working group prepared a summary of its recommendations and these are reported herein.Data Synthesis: There were five key recommendations. First, investigators should no longer rely solely on the American college of Chest Physicians/Society of Critical Care Medicine definitions of sepsis or sepsis syndrome as the basis of trial entry. Entry criteria should be based on three principles: a) All patients should have infection; b) there should be evidence of a pathologic process that represents a biologically plausible target for the pro-posed intervention, for example, an abnormal circulating level of a biological marker pertinent to the study drug; and c) patients should fall into an appropriate category of severity (usually severe sepsis), Second, investigators should use a scaring system for organ dysfunctions that has been validated and that can be incorporated into all sepsis studies; agreement on the use of a single system would simplify comparisons between studies, Third, the primary outcome measure generally should be mortality rates, but under appropriate circumstances major morbidities could be considered as primary end points. Regardless of choice of the duration to primary end point, patients should be followed for greater than or equal to 90 days. Fourth, sample size needs to be based on a realistic assessment of achievable effect size based on knowledge of the at-risk population, Fifth, subgroups should be few in number and should be defined a priori on the basis of variables present before randomization.Conclusions: Important changes in several aspects of trial design may improve the quality of clinical studies in sepsis and maximize the chance of identifying effective therapeutic agents.