Department of Biostatistics and Epidemiology, Anesthesiology, and Neurology, University of Pennsylvania, Philadelphia, PA, USA University of Pennsylvania, Philadelphia, PA, USA Queen's University, Kingston, ON, Canada Pain Research Informatics, Multimorbidities and Education Center, VA Connecticut Healthcare, New Haven, CT, USA Department of Psychiatry, Yale University, New Haven, CT, USA Analgesic Solutions, Natick, MA, USA Tufts University, Boston, MA, USA United States Food and Drug Administration, Silver Spring, MD, USA California Pacific Medical Center Research Institute, San Francisco, CA, USA University of Washington, Seattle, WA, USA University of Rochester, Rochester, NY, USA.
Pain. 2014 Aug;155(8):1622-1631. doi: 10.1016/j.pain.2014.05.009. Epub 2014 May 14.
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.
患者基线 7 天疼痛日记评分的变异性程度被假设对疼痛治疗的随机临床试验的测定敏感性有潜在影响。为了解决这个问题，我们通过食品和药物管理局（FDA）的 Analgesic、Anesthetic 和 Addiction Clinical Trial Translations、Innovations、Opportunities、and Networks（ACTION）公私合作伙伴关系，从后发性神经痛（PHN）和糖尿病性周围神经痛（DPN）的 12 项临床试验中获得了临床试验数据，并对来自 4 项加巴喷丁和 8 项普瑞巴林的 12 项临床试验中的患者水平数据进行了协调。我们使用探索性逻辑回归建立了模型，以检查可用基线因素与治疗（安慰剂与活性药物）之间的相互作用，从而预测患者对治疗的反应（即，>30%的改善）。我们的分析表明，在基线 7 天日记标准差较高的安慰剂治疗组中，患者的反应可能性增加，而不会影响活性药物治疗组的反应可能性，这证实了我们的假设。此外，在 PHN 模型中，年龄与治疗的交互作用较小但显著，在 DPN 模型中，体重与治疗的交互作用较小。患者的性别、基线疼痛水平和研究方案仅对总体反应可能性有影响。我们的结果表明，至少在某些疾病过程中，排除基线 7 天日记变化较大的患者有可能提高这些镇痛临床试验的测定敏感性，尽管在增加研究样本的同质性时，必须考虑降低外部有效性。
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