Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). We explored this hypothesis using data from 3 previously published trials testing treatments for IC/BPS, which suggested modest benefits but did not meet a priori primary outcome statistical significance criteria. Importantly, these studies also collected symptom questionnaire data that allowed us to retrospectively identify participants with and without widespread pain. Analyzing the treatment by the degree of widespread pain revealed a difference in outcome and statistical significance level for each trial. Participants with predominately local pain (ie, limited widespread pain symptoms) responded to therapy targeting local symptoms, whereas those with widespread pain did not. Alternatively, participants with widespread pain beyond their local pelvic pain responded to more centrally acting treatments. Our results suggest that differentiating patients based on widespread vs more localized pain is a key consideration for designing future clinical trials for conditions with variable pain profiles, such as IC/BPS and potentially other pain-based syndromic disorders.

中文翻译：

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广泛的疼痛表型影响间质性膀胱炎/膀胱疼痛综合征随机临床试验的治疗效果结果：慢性盆腔疼痛网络研究的多学科方法。


众所周知，疼痛临床试验非常复杂，而且在证明疗效方面往往效率低下，即使对于已知的有效治疗方法也是如此。一个主要问题是难以先验地识别要包含在研究人群中的特定表型。最近的工作已经确定广泛疼痛的程度是对治疗反应可能性的重要决定因素，但尚未在治疗间质性膀胱炎/膀胱疼痛综合征 （IC/BPS） 的临床试验中进行测试。我们使用 3 项先前发表的测试 IC/BPS 治疗试验的数据来探讨这一假设，这些试验表明有适度的益处，但不符合先验的主要结局统计显着性标准。重要的是，这些研究还收集了症状问卷数据，使我们能够回顾性地识别有和没有广泛疼痛的参与者。根据广泛疼痛的程度分析治疗，揭示了每项试验的结果和统计学显着性水平的差异。以局部疼痛为主的受试者（即，局限性广泛疼痛症状）的受试者对针对局部症状的治疗有反应，而那些具有广泛疼痛的受试者则没有反应。或者，除了局部盆腔疼痛之外，具有广泛疼痛的参与者对更集中作用的治疗有反应。我们的结果表明，根据广泛与更局部的疼痛来区分患者是针对具有不同疼痛特征的疾病（例如 IC/BPS 和可能的其他基于疼痛的综合征疾病）设计未来临床试验的关键考虑因素。