*Department of Surgery and Transplantation, University Hospital of Zurich, Zurich, Switzerland †Department of Surgery, Division of Gastrointestinal and Transplantation Surgery, Erasmus MC University Medical Centre Rotterdam, Rotterdam, The Netherlands ‡Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France §Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland. ¶Hospital Paul Brousse, Université Paris Sud, Paris, France.
Ann Surg. 2014 Nov;260(5):757-62; discussion 762-3. doi: 10.1097/SLA.0000000000000948.
To test whether the newly developed comprehensive complication index (CCI) is more sensitive than traditional endpoints for detecting between-group differences in randomized controlled trials (RCTs).
A major challenge in RCTs is the choice of optimal endpoints to detect treatment effects. Mortality is no longer a sufficient marker in studies, and morbidity is often poorly defined. The CCI, integrating all complications including their severity in a linear scale ranging from 0 (no complication) to 100 (death), is a new tool, which may be more sensitive than other traditional endpoints to detect treatment effects on postoperative morbidity.
The CCI was tested in 3 published RCTs from European centers evaluating pancreas, esophageal and colon resections. To compare the sensitivity of the CCI with traditional morbidity endpoints, for example, presence of any (yes/no) or only the most severe complications, all postoperative events were assessed, and the CCI calculated. Treatment effects and sample size calculations were compared using the CCI and traditional endpoints.
Although RCTs failed to show between-group differences using any or most severe complications, the CCI revealed significant differences between treatment groups in 2 RCTs-after pancreas (P=0.009) and esophageal surgery (P=0.014). The CCI in the RCT on colon resections confirmed the absence of between-group differences (P=0.39). The required sample sizes in trials are up to 9 times lower for the CCI than for traditional morbidity endpoints.
This study demonstrates superiority of the CCI to traditional endpoints. The CCI may serve as an appealing endpoint for future RCTs and may reduce the sample size.
检验新开发的综合并发症指数（CCI）是否比传统终点更能检测随机对照试验（RCT）中的组间差异。
RCT 面临的主要挑战是选择最佳终点来检测治疗效果。死亡率不再是研究中的充分标志物，发病率通常定义不明确。CCI 将所有并发症及其严重程度整合到一个线性尺度上，范围从 0（无并发症）到 100（死亡），是一种新工具，可能比其他传统终点更能敏感地检测术后发病率的治疗效果。
在 3 项来自欧洲中心的评估胰腺、食管和结肠切除术的已发表 RCT 中检验 CCI。为了比较 CCI 与传统发病率终点的敏感性，例如存在任何（是/否）或仅最严重的并发症，评估了所有术后事件，并计算了 CCI。使用 CCI 和传统终点比较了治疗效果和样本量计算。
尽管 RCT 未能使用任何或最严重的并发症显示组间差异，但 CCI 在 2 项 RCT 中显示治疗组之间存在显著差异-胰腺手术后（P=0.009）和食管手术后（P=0.014）。结肠切除术 RCT 中的 CCI 证实组间无差异（P=0.39）。CCI 的试验所需样本量比传统发病率终点低 9 倍。
本研究表明 CCI 优于传统终点。CCI 可作为未来 RCT 的有吸引力的终点，并可能减少样本量。
