Does elimination of placebo responders in a placebo run-in increase the treatment effect in randomized clinical trials? A meta-analytic evaluation
Does elimination of placebo responders in a placebo run-in increase the treatment effect in randomized clinical trials? A meta-analytic evaluation
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DOI：
10.1002/da.10134
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发表时间：
2004-01-01
影响因子：
7.4
通讯作者：
Sexton, K
中科院分区：
文献类型：
--
作者：
Lee, S;Walker, JR;Sexton, K
使用安慰剂磨合期，即安慰剂应答者在随机分配到治疗条件之前从研究中退出，被批评为在临床试验中倾向于积极治疗。我们使用荟萃分析方法比较了随机、安慰剂对照临床试验（用选择性血清素再摄取抑制剂[SSRIs]治疗抑郁症）包括安慰剂磨合期和不包括安慰剂磨合期的效果大小。这项研究与早期的荟萃分析研究的不同之处在于，它只考虑了ssri类药物，并且只包括了使用连续测量抑郁症的研究，从而允许对效应大小进行更精确的评估。广泛的文献检索确定了1980年至2000年间发表的43个数据集，将安慰剂与SSRI进行比较，并使用持续的抑郁测量（通常是汉密尔顿抑郁评定量表）。我们只纳入了持续时间至少6周的研究，重点是18-65岁成人原发性急性重度抑郁症的治疗。专注于特定医学疾病中抑郁症的研究未包括在内。疗效分析是基于3047名接受SSRI抗抑郁药物治疗的受试者和3740名接受安慰剂治疗的受试者。在临床试验中，有安慰剂磨合期，随后有安慰剂反应者退出的试验和没有安慰剂反应期的试验，在效应大小上没有统计学上的显著差异。尽管在退出早期安慰剂应答者的研究和不使用这种方法的研究之间缺乏统计学上的显著差异，但这种方法可能会继续被广泛使用，因为它产生了很大的绝对效应。建议未来的研究清楚地描述这些程序，并报告因早期安慰剂反应和其他原因而退出研究的受试者数量。(C) 2004 Wiley-Liss, Inc。
The use of a placebo run-in phase, in which placebo responders are withdrawn from a study before random assignment to treatment condition, has been criticized as favoring the active treatment in clinical trials. We compared the effect size of randomized, placebo-controlled clinical trials (in the treatment of depression with selective serotonin reuptake inhibitors [SSRIs]) that include a placebo run-in phase with those that do not, using a meta-analytic approach. This study differed from earlier meta-analytic studies in that it considered only SSRIs and included only studies using continuous measures of depression, allowing for a more refined assessment of effect size. An extensive literature search identified 43 datasets published between 1980 and 2000 comparing placebo with SSRI and using a continuous measure of depression (usually the Hamilton Depression Rating Scale). We included only studies of at least 6 weeks' duration focusing on treatment for primary acute major depression in adults 18-65 years of age. Studies focusing on depression in specific medical illnesses were not included. Analysis of efficacy was based on 3,047 subjects treated with an SSRI antidepressant and 3,740 subjects treated with a placebo. There was no statistically significant difference in effect size between the clinical trials that had a placebo run-in phase followed by withdrawal of placebo responders and those trials that did not. Despite the lack of a statistically significant difference between studies of withdrawing early placebo responders and those not using this procedure, this approach is likely to continue to be used widely because it produces large absolute effect sizes. It is recommended that future studies clearly describe these procedures and report the number of subjects dropped from the study for early placebo response and other reasons. (C) 2004 Wiley-Liss, Inc.