Coolsen Marielle M E, Clermonts Stefan H E M, van Dam Ronald M, Winkens Bjorn, Malagó Massimo, Fusai Giuseppe K, Dejong Cornelis H C, Olde Damink Steven W M
Department of Surgery, Maastricht University Medical Centre, PO Box 5800, 6202 AZ, Maastricht, The Netherlands,
World J Surg. 2014 Jun;38(6):1468-75. doi: 10.1007/s00268-013-2421-y.
Few randomized controlled trials (RCTs) have been performed in patients undergoing pancreaticoduodenectomy (PD). An important factor contributing to this is the large number of patients needed to adequately power RCTs for relevant clinical single endpoints. A PD-specific composite endpoint (CEP) could solve this problem. The aim of the present study was to develop a PD-specific CEP, consisting of complications related to PD, allowing reduction in sample sizes and improving the ability to compare outcomes.
PD-specific CEP components were selected after a systematic review of the literature and consensus between 25 international pancreatic surgeons. Ultimately, prospective cohorts of patients who underwent PD in two high-volume HPB centers (London, UK, and Maastricht, NL) were used to assess the event rate and effect of implementing a PD-specific CEP.
From a total of 18 single-component endpoints, intra-abdominal abscess, sepsis, post-PD hemorrhage, bile leakage, gastrojejunostomy leakage, leakage of the pancreatic anastomosis, delayed gastric emptying, and operative mortality within 90 days were selected to be included the PD-specific CEP. All eight components had consensus definitions and a Dindo-Clavien classification of 3 or more. The incidence of the PD-specific CEP was 24.7 % in the Maastricht cohort and 23.3 % in the London cohort. These incidence rates led to a twofold reduction in the theoretical calculated sample size for an adequately powered RCT on PD using this CEP as a primary endpoint.
The proposed PD-specific CEP enables clinical investigators to adequately power RCTs on PD and increases the feasibility, comparability, and utility in meta-analysis.
针对接受胰十二指肠切除术（PD）的患者开展的随机对照试验（RCT）较少。造成这种情况的一个重要因素是，要为相关临床单一终点的RCT提供足够的检验效能，需要大量患者。一个针对PD的复合终点（CEP）可以解决这个问题。本研究的目的是开发一个针对PD的CEP，其由与PD相关的并发症组成，从而能够减少样本量并提高比较结果的能力。
在对文献进行系统回顾并经25位国际胰腺外科医生达成共识后，选择了针对PD的CEP组成部分。最终，利用在两个高容量的肝胆胰中心（英国伦敦和荷兰马斯特里赫特）接受PD的患者前瞻性队列，来评估实施针对PD的CEP的事件发生率及效果。
从总共18个单组分终点中，选择腹腔内脓肿、脓毒症、PD术后出血、胆漏、胃空肠吻合口漏、胰腺吻合口漏、胃排空延迟和90天内手术死亡率纳入针对PD的CEP。所有8个组分都有共识定义且Dindo-Clavien分级为3级或更高。在马斯特里赫特队列中，针对PD的CEP发生率为24.7%，在伦敦队列中为23.3%。这些发生率使以该CEP作为主要终点、具备足够检验效能的PD-RCT理论计算样本量减少了一半。
所提出的针对PD的CEP使临床研究人员能够为PD-RCT提供足够的检验效能，并提高了荟萃分析中的可行性、可比性和实用性。
