Introduction: 

Randomized controlled trials (RCTs) yield the highest level of evidence but are notoriously difficult to perform in surgery. Surgical RCTs may be hampered by slow accrual, the surgical learning curve, and lack of financial support. Alternative RCT designs such as stepped-wedge randomized controlled trials (SW-RCTs), registry-based randomized controlled trials (RB-RCTs), and trials-within-cohorts (TwiCs) may overcome several of these difficulties. This review provides an overview of alternative RCT designs used in surgical research.

Methods: 

We systematically searched PubMed, EMBASE, and Cochrane Central for surgical SW-RCTs, RB-RCTs, and TwiCs. A surgical RCT was defined as a randomized trial that studied interventions in patients undergoing general surgery, regardless of the affiliation of the corresponding author. Exponential regression analysis was performed to assess time trends.

Results: 

Overall, 41 surgical RCTs using alternative designs were identified, including 17 published final RCT reports and 24 published protocols of ongoing RCTs. These included 25 SW-RCTs (61%), 13 RB-RCTs (32%), and 3 TwiCs (7%). Most of these RCTs were performed in Europe (63%) and within gastrointestinal/oncological surgery (41%). The total number of RCTs using alternative designs exponentially increased over the last 7 years (P<0.01), with 95% (n=39/41) of the total number published within this time frame. The most reported reasons for using alternative RCT designs were avoidance of contamination for SW-RCTs and generalizability of the trial population for RB-RCTs and TwiCs.

Conclusions: 

Alternative RCT designs are increasingly used in surgical research, mostly in Europe and within gastrointestinal/oncological surgery. When adequately used, these alternative designs may overcome several difficulties associated with surgical RCTs.

中文翻译：

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手术中的替代随机试验设计：系统评价

介绍： 

随机对照试验 (RCT) 产生了最高水平的证据，但在手术中很难进行是出了名的。手术 RCT 可能会因招募缓慢、手术学习曲线和缺乏资金支持而受到阻碍。替代 RCT 设计，如阶梯楔形随机对照试验 (SW-RCTs)、基于注册的随机对照试验 (RB-RCTs) 和队列内试验(TwiCs) 可能会克服其中的几个困难。本综述概述了外科研究中使用的替代 RCT 设计。

方法： 

我们系统地搜索了 PubMed、EMBASE 和 Cochrane Central 的外科 SW-RCT、RB-RCT 和 TwiC。外科 RCT 被定义为一项随机试验，该试验研究了接受普通手术的患者的干预措施，无论通讯作者的隶属关系如何。进行指数回归分析以评估时间趋势。

结果： 

总体而言，确定了 41 项使用替代设计的手术 RCT，包括 17 项已发表的最终 RCT 报告和 24 项已发表的正在进行的 RCT 方案。其中包括 25 个 SW-RCT (61%)、13 个 RB-RCT (32%) 和 3 个 TwiC (7%)。大多数这些随机对照试验是在欧洲（63%）和胃肠道/肿瘤手术（41%）内进行的。在过去 7 年中，使用替代设计的 RCT 总数呈指数增长（P <0.01），其中 95%（n=39/41）在此时间范围内发表。使用替代 RCT 设计的报告最多的原因是避免 SW-RCT 的污染以及 RB-RCT 和 TwiC 的试验人群的普遍性。

结论： 

替代 RCT 设计越来越多地用于外科研究，主要是在欧洲和胃肠道/肿瘤手术中。如果使用得当，这些替代设计可以克服与外科 RCT 相关的几个困难。