Effect of variability in the 7-day baseline pain diary on the assay sensitivity of neuropathic pain randomized clinical trials: An ACTTION study
Effect of variability in the 7-day baseline pain diary on the assay sensitivity of neuropathic pain randomized clinical trials: An ACTTION study
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DOI：
10.1016/j.pain.2014.05.009
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发表时间：
2014-08-01
期刊：
影响因子：
7.4
通讯作者：
Dworkin, Robert H.
中科院分区：
文献类型：
--
作者：
Farrar, John T.;Troxel, Andrea B.;Dworkin, Robert H.
假设患者基线7天疼痛评级日记的变异程度对疼痛治疗随机临床试验的检测灵敏度有潜在影响。为了解决这个问题，我们通过镇痛、麻醉和成瘾临床试验转化、创新、机会和网络（ACTTION）公私合作伙伴关系从美国食品药品监督管理局（FDA）获得了临床试验数据，并协调了12项带状疱疹后神经痛（PHN）和疼痛性糖尿病周围神经病变（DPN）临床试验（4项加巴喷丁和8项普瑞巴林）的患者水平数据。使用探索性逻辑回归开发模型，以检查可用的基线因素和治疗（安慰剂与活性药物）之间的相互作用，以预测患者对治疗的反应（即改善>30%）。我们的分析表明，安慰剂治疗组中基线7天日记标准差较高的患者缓解的可能性增加，而不影响活性药物治疗组的缓解可能性，证实了我们的假设。此外，PHN模型中存在较小但显著的年龄-治疗相互作用，DPN模型中存在较小的体重-治疗相互作用。患者的性别、基线疼痛水平和研究方案仅对总体缓解的可能性有影响。我们的研究结果表明，至少在某些疾病过程中，排除具有高度可变的基线7天日记的患者有可能提高这些镇痛药临床试验的检测灵敏度，尽管在增加研究样本的同质性时必须考虑外部效度的降低。(C)2014年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
The degree of variability in the patient baseline 7-day diary of pain ratings has been hypothesized to have a potential effect on the assay sensitivity of randomized clinical trials of pain therapies. To address this issue, we obtained clinical trial data from the Food and Drug Administration (FDA) through the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership, and harmonized patient level data from 12 clinical trials (4 gabapentin and 8 pregabalin) in postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Models were developed using exploratory logistic regression to examine the interaction between available baseline factors and treatment (placebo vs active medication) in predicting patient response to therapy (ie, >30% improvement). Our analysis demonstrated an increased likelihood of response in the placebo-treated group for patients with a higher standard deviation in the baseline 7-day diary without affecting the likelihood of a response in the active medication-treated group, confirming our hypothesis. In addition, there was a small but significant age-by-treatment interaction in the PHN model, and small weight-by-treatment interaction in the DPN model. The patient's sex, baseline pain level, and the study protocol had an effect only on the likelihood of response overall. Our results suggest the possibility that, at least in some disease processes, excluding patients with a highly variable baseline 7-day diary has the potential to improve the assay sensitivity of these analgesic clinical trials, although reductions of external validity must be considered when increasing the homogeneity of the investigated sample. (C) 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.