Clinical trial outcome in neuropathic pain - Relationship to study characteristics
Clinical trial outcome in neuropathic pain - Relationship to study characteristics
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DOI：
10.1212/01.wnl.0000275528.01263.6c
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发表时间：
2008-01-22
期刊：
影响因子：
9.9
通讯作者：
Dworkin, Robert H.
中科院分区：
文献类型：
--
作者：
Katz, Jennifer;Finnerup, Nanna B.;Dworkin, Robert H.
背景：最近的几项随机临床试验发现，尽管先前的临床前和临床研究结果令人鼓舞，但正在评估的治疗神经病理性疼痛的药物与安慰剂在主要疗效终点方面没有显著差异。目前尚不清楚这些试验之所以不成功，是因为药物确实缺乏疗效，还是试验的特点损害了治疗益处的论证。目的：确定与安慰剂对照神经性疼痛试验阳性(即支持药物)与阴性结果相关的因素。方法：我们使用综合荟萃分析中提供的信息和106个临床试验的附加评分来检验神经性疼痛治疗的阳性与阴性临床试验结果相关的研究特征。结果：单变量分析表明，药物与安慰剂比较的结果更有可能是积极的，药物应答率越高，安慰剂应答率越低，研究发表得越早。在为确定研究特征对试验结果的独立贡献而进行的多变量分析中，更大的药物反应、更少的安慰剂反应和更大的样本量每一个都与积极的结果唯一相关。此外，更高的药物反应率和平行分组设计各自独立地与更高的安慰剂反应率相关。结论：研究结果表明，研究特征可能有助于神经病理性疼痛治疗的临床试验的结果，并为研究降低安慰剂反应率的策略提供动力，从而可能增加有效治疗试验中阳性结果的可能性。
Background: Several recent randomized clinical trials have found that the medications being evaluated for neuropathic pain did not significantly differ from placebo for the primary efficacy endpoint, despite encouraging results from prior preclinical and clinical studies. It is unclear whether these trials were unsuccessful because the medications truly lack efficacy or whether characteristics of the trials compromised the demonstration of treatment benefits.Objective: To identify factors associated with positive (i.e., favors medication) vs negative outcomes of placebo-controlled neuropathic pain trials. Methods: We examined study characteristics associated with positive vs negative clinical trial outcomes for neuropathic pain treatments using the information provided in a comprehensive meta-analysis and additional ratings for 106 clinical trials.Results: Univariate analyses indicated that the results of medication vs placebo comparisons were more likely to be positive when medication response rates were greater, placebo response rates were lower, and studies were published earlier. In a multivariate analysis performed to identify independent contributions of study characteristics to trial outcomes, greater medication response, reduced placebo response, and larger sample sizes were each uniquely associated with positive outcomes. In addition, greater medication response rates and parallel groups designs were each independently associated with greater placebo response rates.Conclusions: The results suggest that study characteristics may contribute to the outcomes of clinical trials of treatments for neuropathic pain and provide an impetus for investigating strategies for decreasing placebo response rates and thereby possibly increasing the likelihood of positive outcomes in trials of efficacious treatments.