比较精神分裂症抗精神病药物的开放性随机对照试验结果是否存在偏差?探索性元分析和亚组分析。

IF 3 Q2 PSYCHIATRY Schizophrenia (Heidelberg, Germany) Pub Date : 2024-02-15 DOI:10.1038/s41537-024-00442-8
Stefan Leucht, Spyridon Siafis, Johannes Schneider-Thoma, Aran Tajika, Josef Priller, John M Davis, Toshi A Furukawa
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摘要

最近的一项荟萃流行病学研究显示,盲法随机对照试验(RCT)和开放式随机对照试验(RCT)的结果并无重大差异。与开放式随机对照试验相比,同意接受双盲随机对照试验的患者可能更少,从而影响了试验的普遍性,因此这个问题非常重要。然而,这一问题在精神分裂症中尚未得到解决。我们使用了一个急性期抗精神病药物随机试验数据库。只要有至少一项开放性和一项盲法 RCT 可用于两种药物的比较,我们就会通过随机效应荟萃分析和亚组检验对结果进行对比。研究的主要结果是以正负综合征量表(Positive and Negative Syndrome Scale)测量的总体症状,并辅以七项次要疗效和副作用结果。我们还研究了开放性 RCT 是否偏向于新近推出的抗精神病药物、疗效较差或更易产生副作用的抗精神病药物以及药品赞助商。共有 183 项 RCT(155 项盲法 RCT 和 28 项开放式 RCT),34715 名参与者参与了两种活性药物的比较。结果表明,对两种活性药物进行研究的开放式和盲法 RCT 之间没有普遍差异。在 122 项分组测试中,只有 12 项测试的 p 值低于 0.1,4 项低于 0.05,如果对多重测试进行 Bonferroni 校正,只有一项测试具有显著性。不过,也有一些例外情况,并不总是证实最初假设的偏差方向。由于开放性 RCT 的数量相对较少,我们的分析是探索性的,但这一基本问题应得到更多的科学关注。目前,至少在敏感性分析中,荟萃分析应排除开放性 RCT。
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Are the results of open randomised controlled trials comparing antipsychotic drugs in schizophrenia biased? Exploratory meta- and subgroup analysis.

A recent meta-epidemiological study did not reveal major differences between the results of blinded and open randomised-controlled trials (RCTs). Fewer patients may consent to double-blind RCTs than to open RCTs, compromising generalisability, making this question very important. However, the issue has not been addressed in schizophrenia. We used a database of randomised, acute-phase antipsychotic drug trials. Whenever at least one open and one blinded RCT was available for a comparison of two drugs, we contrasted the results by random-effects meta-analysis with subgroup tests. The primary outcome was overall symptoms as measured by the Positive and Negative Syndrome Scale, supplemented by seven secondary efficacy and side-effect outcomes. We also examined whether open RCTs were biased in favour of more recently introduced antipsychotics, less efficacious or more prone to side-effects antipsychotics, and pharmaceutical sponsors. 183 RCTs (155 blinded and 28 open) with 34715 participants comparing two active drugs were available. The results did not suggest general differences between open and blinded RCTs, which examined two active drugs. Only 12 out of 122 subgroup tests had a p-value below 0.1, four below 0.05, and if a Bonferroni correction for multiple tests had been applied, only one would have been significant. There were some exceptions which, however, did not always confirm the originally hypothesized direction of bias. Due to the relatively small number of open RCTs, our analysis is exploratory, but this fundamental question should be given more scientific attention. Currently, open RCTs should be excluded from meta-analyses, at least in sensitivity analyses.

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