Allowing for non-adherence to treatment in a randomized controlled trial of two antidepressants (citalopram versus reboxetine): an example from the GENPOD trial.
Allowing for non-adherence to treatment in a randomized controlled trial of two antidepressants (citalopram versus reboxetine): an example from the GENPOD trial.
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DOI：
10.1017/s0033291714000221
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发表时间：
2014-10
影响因子：
6.9
通讯作者：
White, I. R.
中科院分区：
文献类型：
--
作者：
Wiles, N. J.;Fischer, K.;Cowen, P.;Nutt, D.;Peters, T. J.;Lewis, G.;White, I. R.
荟萃分析表明瑞波西汀可能不如其他抗抑郁药有效。由于对瑞波西汀的依从性较低以及随后对缺失结果数据的处理，此类比较可能会产生偏差。这项研究说明了如何调整不同的不依从性，从而对瑞波西汀与西酞普兰在初级保健抑郁症患者中的疗效进行公正的估计。采用结构平均模型 (SMM) 方法，利用抑郁症治疗反应基因和临床预测因子 (GENPOD) 试验数据，对瑞波西汀与西酞普兰的疗效进行依从性调整估计。进行意向治疗（ITT）分析，将有效性估计值与之前荟萃分析的结果进行比较。 6 周时，随机接受西酞普兰治疗的患者中有 92% 仍在服用药物，而随机接受瑞波西汀治疗的患者中这一比例为 72%。在 ITT 分析中，只有微弱的证据表明服用瑞波西汀的患者的结果比服用西酞普兰的患者稍差[调整后的平均贝克抑郁量表 (BDI) 评分差异：1.19，95% 置信区间 (CI) –0.52 至 2.90，p = 0.17]。当使用 SMM 方法计算平均 BDI（–0.29，95% CI –3.04 至 2.46，p = 0.84）或其他心理健康结果时，没有证据表明疗效存在差异。没有证据表明抑郁症患者服用和耐受瑞波西汀和西酞普兰的疗效存在差异。 SMM 方法可以在标准统计软件中实施，以调整不同的不依从性，并生成治疗效果的公正估计，以比较两种（或多种）主动干预措施。
Meta-analyses suggest that reboxetine may be less effective than other antidepressants. Such comparisons may be biased by lower adherence to reboxetine and subsequent handling of missing outcome data. This study illustrates how to adjust for differential non-adherence and hence derive an unbiased estimate of the efficacy of reboxetine compared with citalopram in primary care patients with depression. A structural mean modelling (SMM) approach was used to generate adherence-adjusted estimates of the efficacy of reboxetine compared with citalopram using GENetic and clinical Predictors Of treatment response in Depression (GENPOD) trial data. Intention-to-treat (ITT) analyses were performed to compare estimates of effectiveness with results from previous meta-analyses. At 6 weeks, 92% of those randomized to citalopram were still taking their medication, compared with 72% of those randomized to reboxetine. In ITT analysis, there was only weak evidence that those on reboxetine had a slightly worse outcome than those on citalopram [adjusted difference in mean Beck Depression Inventory (BDI) scores: 1.19, 95% confidence interval (CI) –0.52 to 2.90, p = 0.17]. There was no evidence of a difference in efficacy when differential non-adherence was accounted for using the SMM approach for mean BDI (–0.29, 95% CI –3.04 to 2.46, p = 0.84) or the other mental health outcomes. There was no evidence of a difference in the efficacy of reboxetine and citalopram when these drugs are taken and tolerated by depressed patients. The SMM approach can be implemented in standard statistical software to adjust for differential non-adherence and generate unbiased estimates of treatment efficacy for comparisons of two (or more) active interventions.