Dropout rates in placebo-controlled and active-control clinical trials of antipsychotic drugs - A meta-analysis
Dropout rates in placebo-controlled and active-control clinical trials of antipsychotic drugs - A meta-analysis
复制标题
DOI：
10.1001/archpsyc.62.12.1305
复制
发表时间：
2005-12-01
影响因子：
--
通讯作者：
Fleischhacher, W
中科院分区：
文献类型：
--
作者：
Kemmler, G;Hummer, M;Fleischhacher, W
背景：抗精神病药物的随机临床试验的中途退出率一直被报道很高，而安慰剂对照设计的使用被认为是其中一个原因。目的：通过对相关临床试验的可用数据进行荟萃分析来研究这一假设。资料来源：对PubMed和MEDLINE列出的期刊进行全面搜索。研究选择：符合以下标准的第二代抗精神病药物利培酮、奥氮平、奎硫平、阿米司匹林、齐拉西酮和阿立哌唑的双盲随机对照临床试验：未入选的有精神分裂症或分裂情感障碍的患者群体，主要终点为精神病理症状的变化资料提炼：样本量、平均年龄、基线疾病严重程度、辍学率、试验设计、试验持续时间和发表年份。资料综合：共找到31篇符合纳入标准的试验，涉及10058名受试者。第二代抗精神病药物(优势比，2.34；95%可信区间，1.58-3.47)和经典抗精神病药物(优势比，2.10；95%可信区间，1.29-3.40)的第二代抗精神病药物(优势比，2.10；95%可信区间，1.29-3.40)的加权平均脱落率在安慰剂对照试验(PCTS)中显著高于积极对照试验：481%(PCTS)比28.3%(积极对照试验)。在PCT中，安慰剂组的流失率显著高于第二代抗精神病药物组(60.2%比48.1%；优势比1.63；95%可信区间1.37-1.94)。在同时使用第二代和经典抗精神病药物的试验子集中，使用经典抗精神病药物的脱落率显著更高。结论：使用安慰剂对照设计对观察到的脱落率有很大影响。由于高辍学率影响了这类研究的普适性，建议在评估抗精神病药物的临床概况时，除了PCT外，还需要考虑具有替代设计的研究。
Context: Dropout rates in randomized clinical trials of antipsychotic drugs have consistently been reported to be high, and the use of a placebo-controlled design is hypothesized to be one of the reasons for this.Objective: To investigate this hypothesis in a meta-analysis of available data from pertinent clinical trials.Data Sources: Comprehensive search of PubMed- and MEDLINE-listed journals.Study Selection: Double-blind randomized controlled clinical trials of the second-generation antipsychotics risperidone, olanzapine, quetiapine, amisulpride, ziprasidone, and aripiprazole meeting the following criteria: unselected patient population with a diagnosis of schizophrenia or schizoaffective disorder, change in psychopathologic symptoms as the primary end point, and trial duration of 12 weeks or less.Data Extraction: Sample size, mean age, baseline disease severity, dropout rate, trial design, trial duration, and publication year.Data Synthesis: Thirty-one trials meeting the inclusion criteria were found, comprising 10 058 subjects. Weighted mean dropout rates in the active treatment arms were significantly higher in placebo-controlled trials (PCTs) than in active-control trials: 48.1% (PCTs) vs 28.3% (active-control trials) for second-generation antipsychotics (odds ratio, 2.34; 95% confidence interval, 1.58-3.47) and 55.4% (PCTs) vs 37.2% (active-control trials) for classical antipsychotics (odds ratio, 2. 10; 95% confidence interval, 1.29-3.40). Within PCTs, attrition rates were significantly higher in the placebo arms than with second-generation antipsychotics (60.2% vs 48.1%; odds ratio, 1.63; 95% confidence interval, 1.37-1.94). Within the subset of trials in which both second-generation and classical antipsychotics were used, dropout rates were significantly higher with classical antipsychotics.Conclusions: Use of a placebo-controlled design had a major effect on the dropout rates observed. Because high dropout rates affect the generalizability of such studies, it is suggested that, in addition to the PCTs, studies with alternative designs need to be considered when evaluating an antipsychotic's clinical profile.