BACKGROUND:In the absence of well-powered, randomised, direct-comparison trials, indirect comparisons are the only option for comparing treatment strategies. Several methodologies have been developed and each has sparked criticism. Using direct comparisons of escitalopram versus venlafaxine extended release (XR), we explore the differences between the two compounds through indirect comparisons. METHODS:The CENTRAL, Medline and Embase databases were interrogated, focusing on randomized placebo-controlled clinical trials involving adult patients treated for major depressive disorder in the acute phase. Corresponding authors were contacted to reduce missing data. Effect sizes were derived from each study's primary outcome. For indirect comparisons, a global effect size was computed through meta-regression. For direct comparisons, the studies were considered separately due to missing data. Non-inferiority assessments were employed. The conclusion of the meta-regression was then compared with the conclusions made in direct comparison trials. RESULTS:Ten placebo-controlled studies--six assessing escitalopram and four assessing venlafaxine XR--and two direct comparison studies were retrieved. Escitalopram was found to be non-inferior to venlafaxine XR in both indirect and direct comparisons with results of mean -0.02 (unilateral 95% confidence interval [CI] -0.16 to infinity) and 0.23 (95% CI -0.01 to infinity), respectively. Results obtained by both indirect and direct comparisons were similar. Investigating the influence of age, gender repartition and severity at baseline suggests that results are consistent. Results were also considered robust against publication bias. CONCLUSIONS:This empirical finding suggests that escitalopram is non-inferior to venlafaxine XR. This reinforces the evidence found in direct comparisons trials. Indirect comparisons through meta-regression may be suitable to support decision-making. To fully assess its potential, further evaluation of this methodology, using other examples, is needed.

译文

背景:在缺乏功能强大,随机,直接比较试验的情况下,间接比较是比较治疗策略的唯一选择。已经开发了几种方法,每种方法都引发了批评。使用艾司西酞普兰与文拉法辛缓释(XR)的直接比较,我们通过间接比较探索了两种化合物之间的差异。
方法:对CENTRAL,Medline和Embase数据库进行了调查,重点是随机对照安慰剂对照的临床试验,该试验涉及在急性期接受过重度抑郁症治疗的成年患者。与通讯作者联系以减少丢失的数据。效果大小来自每项研究的主要结果。对于间接比较,通过meta回归计算全局效应大小。对于直接比较,由于缺少数据,将研究单独考虑。采用非自卑性评估。然后将荟萃回归的结论与直接比较试验中得出的结论进行比较。
结果:十项安慰剂对照研究-六项评估艾司西酞普兰和四项评估文拉法辛XR-并检索到两项直接比较研究。在间接和直接比较中,依西酞普兰均不低于文拉法辛XR,均值分别为-0.02(单边95%置信区间[CI] -0.16至无穷大)和0.23(95%CI -0.01至无穷大)。 。通过间接和直接比较获得的结果相似。在基线时调查年龄,性别划分和严重程度的影响表明结果是一致的。结果也被认为对发表偏见是有力的。
结论:该经验发现表明艾司西酞普兰不逊于文拉法辛XR。这加强了直接比较试验中发现的证据。通过元回归进行的间接比较可能适合于支持决策。为了充分评估其潜力,需要使用其他示例对这种方法进行进一步评估。

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