Methods for therapeutic trials in COPD: lessons from the TORCH trial
Methods for therapeutic trials in COPD: lessons from the TORCH trial
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COPD 治疗试验方法：TORCH 试验的经验教训
DOI：
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发表时间：
2009
影响因子：
24.3
通讯作者：
P. Jones
中科院分区：
文献类型：
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作者：
O. Keene;J. Vestbo;Julie A. Anderson;P. Calverley;B. Celli;G. Ferguson;C. Jenkins;P. Jones
TORCH（Towards a Revolution in COPD Health）试验强调了慢性阻塞性肺疾病长期试验设计和分析中的一些重要问题。这些包括收集停止治疗后的急性加重数据、分析急性加重率以及随机化前纳入接受吸入性皮质类固醇（ICS）的患者的影响。当退出研究的患者可获得有效药物时，纳入停止治疗数据可能会掩盖治疗对急性加重率的重要影响。对治疗数据的分析避免了这种偏倚，但需要结合对不同治疗的戒断模式的仔细分析。负二项模型是目前对急性加重率进行统计分析的最佳方法，而对至急性加重时间的分析可以补充这种方法。在TORCH试验中，既往使用ICS的患者的急性加重率高于既往未使用所有研究治疗的患者。回顾性亚组分析表明，与安慰剂相比，ICS可降低急性加重率，无论入组研究前是否使用过ICS。因子分析为联合治疗的试验提供了一种替代分析，但假设治疗之间没有相互作用，这一假设无法通过显著性检验进行验证。关于ICS治疗是否对死亡率有影响，目前还不能得出明确的结论。
The TORCH (Towards a Revolution in COPD Health) trial has highlighted some important issues in the design and analysis of long term trials in chronic obstructive pulmonary disease. These include collection of off-treatment exacerbation data, analysis of exacerbation rates and the effect of inclusion of patients receiving inhaled corticosteroids (ICS) prior to randomisation. When effective medications are available to patients who withdraw, inclusion of off-treatment data can mask important treatment effects on exacerbation rates. Analysis of on-treatment data avoids this bias but it needs to be combined with careful analysis of withdrawal patterns across treatments. The negative binomial model is currently the best approach to statistical analysis of exacerbation rates, while analysis of time to exacerbation can supplement this approach. In the TORCH trial, exacerbation rates were higher among patients with previous use of ICS compared to those with no prior use on all study treatments. Retrospective subgroup analysis suggests ICS reduced exacerbation rates compared with placebo, regardless of prior use of ICS before entry to the study. Factorial analysis provides an alternative analysis for trials with combinations of treatments, but assumes no interaction between treatments, an assumption which cannot be verified by a significance test. No definitive conclusions can yet be drawn on whether ICS treatment has an effect on mortality.