Graf Jürgen, Doig Gordon S, Cook Deborah J, Vincent Jean-Louis, Sibbald William J
Medical Clinic I, Department of Cardiology, University Hospital Aachen, Aachen, Germany.
Crit Care Med. 2002 Feb;30(2):461-72. doi: 10.1097/00003246-200202000-00032.
To systematically evaluate the methodological quality of randomized clinical trials and to determine whether randomized clinical trials of sepsis improved in methodological quality over time.
Computerized MEDLINE search of articles published in any language from 1966 to 1998 combined with a manual search of bibliographies of published articles and communication with known experts in the field.
All randomized clinical trials of sepsis, severe sepsis, and septic shock performed in adults and published as full articles.
Abstracts of all retrieved records were reviewed and the inclusion criteria were applied. All selected articles were classified into (a) trials designed to detect differences in mortality as the primary end point, or (b) trials focusing on surrogate outcome measures (i.e., physiological or biochemical parameters). All retrieved trials were then graded for methodological quality using an objective grading scheme developed specifically for this study. The data selection and extraction process was carried out independently by two of the authors; any disagreement was resolved by discussion.
Seventy-four randomized clinical trials involving septic patients qualified for inclusion in this study (40 reporting mortality outcomes, 34 reporting other surrogate outcomes). Trials reporting mortality as the primary outcome had significantly higher quality scores compared with trials reporting surrogate outcome measures (29.6 +/- 1.0 vs. 24.3 +/- 0.8, p =.0006). From 1976 to 1998, trial methodology improved significantly over time (an average of 0.36 points per year, p =.021). Mortality outcome trials improved an average of 0.58 points per year (p =.0011) whereas surrogate outcome trials did not demonstrate an improvement in methodological quality over time (p =.249).
The methodological limitations identified in this article can help to target further improvement in trial design to enhance the validity of findings from future randomized clinical trials of sepsis.
系统评价随机临床试验的方法学质量，并确定脓毒症随机临床试验的方法学质量是否随时间推移有所改善。
对1966年至1998年以任何语言发表的文章进行计算机化MEDLINE检索，并结合对已发表文章参考文献的手工检索以及与该领域知名专家的交流。
所有针对成人进行的、以全文形式发表的脓毒症、严重脓毒症和脓毒性休克的随机临床试验。
对所有检索到的记录的摘要进行审查，并应用纳入标准。所有选定的文章分为以下两类：(a) 旨在检测死亡率差异作为主要终点的试验，或(b) 侧重于替代结局指标（即生理或生化参数）的试验。然后使用专门为此研究开发的客观评分方案对所有检索到的试验进行方法学质量分级。数据选择和提取过程由两位作者独立进行；任何分歧通过讨论解决。
74项涉及脓毒症患者的随机临床试验符合本研究的纳入标准（40项报告死亡率结局，34项报告其他替代结局）。与报告替代结局指标的试验相比，将死亡率作为主要结局报告的试验质量得分显著更高（29.6±1.0对24.3±0.8，p = 0.0006）。从1976年到1998年，试验方法学随时间显著改善（平均每年0.36分，p = 0.021）。死亡率结局试验平均每年改善0.58分（p = 0.0011），而替代结局试验的方法学质量未随时间显示出改善（p = 0.249）。
本文确定的方法学局限性有助于针对试验设计的进一步改进，以提高未来脓毒症随机临床试验结果的有效性。
