Department of Psychiatry, University of Toronto, Toronto, Canada.
J Clin Psychiatry. 2012 Feb;73(2):e277-87. doi: 10.4088/JCP.11r07204.
Differences in dosing may influence results of pharmaceutical industry-sponsored medication trials. This study aims to determine the relationship between sponsorship and antidepressant dosing and efficacy in randomized controlled trials for major depressive disorder.
Trials were identified through English-language searches of MEDLINE and PsycINFO (January 1996-June 2010) using specific drug names and classes and depressive disorder or major depression and double blind or double-blind method. Other limitations included human subjects and treatment study designs using the clinical queries option. Other sources were also searched following a strict set of inclusion and exclusion criteria.
Randomized controlled trials were included if they examined antidepressant treatment for major depressive disorder, reported mean final medication dosages, acknowledged an association with industry, and included study arms of medications produced by the associated manufacturer and a competitor ("sponsor" and "nonsponsor" arms) (58 trials involving 15,026 patients from 101 citations identified).
Data on dosing, efficacy, baseline severity, and adverse events were extracted by 2 of the authors.
Meta-analyses were used to examine dosing and efficacy data. Using consensus guidelines for medication dosing, we determined that sponsor medication was dosed relatively higher than nonsponsor medication, in 37% (22/60) of comparisons as opposed to 5% (3/60) in which the nonsponsor medication was dosed higher (χ²₂ = 25.9, P < .001). Trials in which sponsor drugs were dosed higher than nonsponsor drugs demonstrated higher remission rates for the sponsor drug (OR = 1.28, 95% CI = 1.11-1.47, P < .001). These results were confirmed using regulatory dosing guidelines. There was no significant correlation between dosing or outcome with baseline severity or adverse events.
Sponsor drugs are dosed higher than nonsponsor drugs in antidepressant randomized controlled trials, and higher dosing is associated with better sponsor drug outcomes in some cases.
用药剂量的差异可能会影响制药业赞助的药物试验结果。本研究旨在确定在重性抑郁障碍随机对照试验中，赞助与抗抑郁药物剂量和疗效之间的关系。
通过在 MEDLINE 和 PsycINFO 中进行特定药物名称和类别以及抑郁障碍或重性抑郁和双盲或双盲方法的英语搜索，确定了试验。其他限制包括人类受检者和使用临床查询选项的治疗研究设计。根据严格的纳入和排除标准，还搜索了其他来源。
如果试验检查了抗抑郁药物治疗重性抑郁障碍、报告了平均最终药物剂量、承认与工业界有关联并包括与制造商相关的药物和竞争药物（“赞助商”和“非赞助商”手臂）的研究臂（从 101 个引文确定的 58 项试验，涉及 15026 名患者），则将随机对照试验纳入研究。
两名作者提取了剂量、疗效、基线严重程度和不良事件的数据。
使用荟萃分析来检查剂量和疗效数据。使用药物剂量共识指南，我们确定在 37%（22/60）的比较中，赞助商药物的剂量相对高于非赞助商药物，而在 5%（3/60）的比较中，非赞助商药物的剂量更高（χ²₂ = 25.9，P <.001）。在赞助商药物剂量高于非赞助商药物的试验中，赞助商药物的缓解率更高（OR = 1.28，95% CI = 1.11-1.47，P <.001）。使用监管剂量指南也得到了相同的结果。剂量或结局与基线严重程度或不良事件之间没有显著相关性。
在抗抑郁随机对照试验中，赞助商药物的剂量高于非赞助商药物，在某些情况下，较高的剂量与赞助商药物的较好结局相关。
