A meta-analysis of the placebo rates of remission and response in clinical trials of active Crohn's disease
A meta-analysis of the placebo rates of remission and response in clinical trials of active Crohn's disease
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DOI：
10.1053/j.gastro.2004.01.024
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发表时间：
2004-05-01
期刊：
影响因子：
29.4
通讯作者：
Lewis, JD
中科院分区：
文献类型：
--
作者：
Su, CY;Lichtenstein, GR;Lewis, JD
背景与目的：安慰剂对照随机临床试验（PC-RCT）通常用于评估克罗恩病（CD）的治疗方法。了解安慰剂的缓解率和应答率以及了解影响这些缓解率和应答率的设计因素，对于设计未来评价CD药物治疗的临床试验非常重要。本研究的目的是评估接受安慰剂治疗的活动性CD患者的缓解率和应答率，并确定影响这些比率的因素。方法：我们对1966年至2001年MEDLINE中确定的活动性CD治疗评价PC-RCT进行了系统回顾和荟萃分析。结果如下：安慰剂缓解率和应答率的汇总估计值分别为18%（95%置信区间，14%-24%;范围，0%-50%）和19%（95%置信区间，13%-28%;范围，0%-46%），两项研究之间均存在显著异质性（缓解率P < 0.01，应答率P < 0.03）。在多变量模型中，研究持续时间、研究访视次数和入组克罗恩病活动指数评分是安慰剂缓解率的重要预测因素，其中研究持续时间最重要。然而，没有一个因素可以解释所有的异质性。影响安慰剂应答率的因素与影响安慰剂缓解率的因素相似。当以应答而不是缓解来衡量结局时，活性治疗的绝对获益通常大于安慰剂。结论：PC-RCT中活动性CD的安慰剂缓解率和应答率是可变的。研究持续时间、研究访视次数和入组时的疾病严重程度对安慰剂缓解率有很大影响。
Background & Aims: Placebo-controlled, randomized clinical trials (PC-RCTs) are commonly used to assess therapies for Crohn's disease (CD). Knowledge of the placebo rates of remission and response and understanding of design factors that influence these rates is important for designing future clinical trials evaluating pharmacotherapy of CD. The aims of this study were to estimate rates of remission and response in patients with active CD receiving placebo and to identify factors influencing these rates. Methods: We performed a systematic review and meta-analysis of PC-RCTs evaluating therapies for active CD identified from MEDLINE from 1966 to 2001. Results: The pooled estimates of the placebo rates of remission and response were 18% (95% confidence interval, 14%-24%; range, 0%-50%) and 19% (95% confidence interval, 13%-28%; range, 0%-46%), respectively, both with significant heterogeneity among studies (P < 0.01 for remission, P < 0.03 for response). In multivariate models, study duration, number of study visits, and entry Crohn's Disease Activity Index score were important predictors of the placebo remission rate, with study duration the most important. However, no single factor could account for all of the heterogeneity. Factors that influence the placebo response rates were similar to those affecting the placebo remission rates. The absolute benefit of active treatment beyond placebo was generally larger when outcome was measured by response than remission. Conclusions: Placebo remission and response rates in PC-RCTs for active CD are variable. Study duration, number of study visits, and disease severity at entry have a large influence on placebo remission rates.