Matthews Jacob H, Bhanderi Shivam, Chapman Stephen J, Nepogodiev Dmitri, Pinkney Thomas, Bhangu Aneel
*Academic Department of Surgery, University of Birmingham, Birmingham, UK†Academic Foundation Trainee, University of Leeds, Leeds, UK.
Ann Surg. 2016 Dec;264(6):982-986. doi: 10.1097/SLA.0000000000001573.
To determine if underreporting of secondary endpoints in randomized controlled trials occurs, using surgical site infection (SSI) as an example.
SSI is a commonly measured endpoint in surgical trials and can act as a proxy marker for primary and secondary endpoint assessments across trials in a range of medical specialties.
Cross-sectional observational study of randomized trials including patients undergoing gastrointestinal surgery published in a representative selection of general medical and general surgical journals. Studies were included if SSI assessment was a prespecified endpoint. Adjusted binary logistic regression was used to identify factors associated with a high rate of SSI detection (≥10%).
From 216 trials including 45,633 patients, the pooled SSI rate was 7.7% (3519/45,633), which was significantly higher when assessed as a primary endpoint (12.6%, 1993/15,861, 49 studies) vs as a secondary endpoint (5.1%, 1526/29,772, 167 studies, P < 0.001). When assessed as a secondary outcome, standardized definitions and formal clinical reviews were used significantly less often. When adjusted for surgical contamination and methodological confounders, secondary assessment was associated with reduced SSI detection compared with primary assessment (adjusted odds ratio 0.24, 95% confidence interval 0.08-0.69, P = 0.008).
Secondary endpoint assessment of SSI in randomized trials was associated with significantly reduced rigor and subsequent detection rates compared with assessment as a primary endpoint. Trial investigators should ensure that primary and secondary endpoint assessments are equally robust. PRISMA guidelines should be updated to promote the conduct of meta-analysis based only on primary outcomes from randomized controlled trials.
以手术部位感染（SSI）为例，确定随机对照试验中次要终点是否存在报告不足的情况。
SSI是外科试验中常用的测量终点，可作为一系列医学专科试验中主要和次要终点评估的替代指标。
对发表在具有代表性的普通医学和普通外科期刊上的随机试验进行横断面观察性研究，纳入接受胃肠手术的患者。如果SSI评估是预先设定的终点，则纳入研究。采用调整后的二元逻辑回归来确定与高SSI检出率（≥10%）相关的因素。
在纳入45633例患者的216项试验中，合并的SSI发生率为7.7%（3519/45633），作为主要终点评估时（12.6%，1993/15861，49项研究）显著高于作为次要终点评估时（5.1%，1526/29772，167项研究，P<0.001）。作为次要结果评估时，标准化定义和正式临床审查的使用频率显著降低。在调整手术污染和方法学混杂因素后，与主要评估相比，次要评估与SSI检出率降低相关（调整后的比值比为0.24，95%置信区间为0.08-0.69，P=0.008）。
与作为主要终点评估相比，随机试验中SSI的次要终点评估与严格程度显著降低及随后的检出率降低相关。试验研究者应确保主要和次要终点评估同样严格。PRISMA指南应更新，以促进仅基于随机对照试验主要结果进行的荟萃分析。
