Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Clin Transl Gastroenterol. 2020 Nov;11(11):e00255. doi: 10.14309/ctg.0000000000000255.
Chronic constipation (CC) is a recurrent functional bowel disorder worldwide. The purpose of this study is to examine its pooled placebo response rate and compare placebo response level in randomized controlled trials (RCTs) with different endpoint assessments.
PubMed, Cochrane Library, and Embase were electronically searched for therapeutic RCTs of CC with placebo control. Data extraction and assessment of risk of bias were performed independently by 2 reviewers. All the statistical calculation and analysis were performed using R 3.6.0. Our protocol has registered in PROSPERO with registration number: CRD42019121287.
There were 46 studies included with 5,992 constipated patients allocated to the placebo arm in total. The pooled placebo response rate was 28.75% (95% confidence interval: 23.83%-33.67%) with significant heterogeneity among trials ((Equation is included in full-text article.)= 93.6%). Treatment efficacy assessed using subjective improvement had a significantly higher placebo response rate than that assessed with improvement in complete (spontaneous) bowel movements or composite improvement (41.40% vs 18.31% or 20.35%, P < 0.001). According to the results of meta-regression, active treatment and endpoint assessment were most likely to lead to the huge heterogeneity among studies.
Patients with CC have significant response level to placebo. Based on findings in this study, we do not recommend subjective improvement as endpoint while designing therapeutic RCTs for chronic constipated patients.
慢性便秘（CC）是一种全球范围内反复发作的功能性肠病。本研究旨在评估其汇总安慰剂反应率，并比较不同终点评估的随机对照试验（RCT）中的安慰剂反应水平。
通过电子检索 PubMed、Cochrane 图书馆和 Embase，以获取 CC 安慰剂对照治疗的 RCT 研究。由 2 位评审员独立进行数据提取和偏倚风险评估。所有的统计计算和分析均使用 R 3.6.0 进行。我们的方案已在 PROSPERO 中注册，注册号为：CRD42019121287。
共纳入 46 项研究，总计 5992 例便秘患者被分配到安慰剂组。汇总的安慰剂反应率为 28.75%（95%置信区间：23.83%-33.67%），各试验间存在显著的异质性（(Equation is included in full-text article.)=93.6%）。采用主观改善评估的治疗效果的安慰剂反应率显著高于采用完全（自发）排便改善或综合改善评估的安慰剂反应率（41.40%比 18.31%或 20.35%，P<0.001）。根据荟萃回归的结果，积极治疗和终点评估最有可能导致各研究间存在巨大的异质性。
CC 患者对安慰剂有显著的反应水平。基于本研究的结果，我们不建议将主观改善作为慢性便秘患者治疗 RCT 的终点。
