The attrition of novel analgesic drugs in the clinic can be attributed in the main to two factors: failure of preclinical research findings translating into human pain conditions, and a drop-off of efficacy between proof-of-concept (i.e., Phase II trials) and pivotal, confirmatory (Phase III trials) testing. In order to enhance the efficiency of the clinical drug evaluation process and determine rapidly whether a potential therapeutic candidate gives pain relief, by modulating central pain neurobiology, we propose a 'pre-proof-of-concept' approach, in which an efficacy assessment is performed in a single individual (N-of-1) using subjective clinical pain assessments supported by objective validated functional neuroimaging measures. Using an N-of-1 + i methodology, clinical- and neuroimaging-based metrics can be quantified under conditions of drug versus placebo or drug versus current standard of care conditions.

中文翻译：

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加强慢性疼痛治疗试验的选择和结果：N-of-1 + 成像 (+ i)。

临床上新型镇痛药的流失主要归因于两个因素：临床前研究结果未能转化为人类疼痛状况，以及概念验证（即 II 期试验）之间的疗效下降和关键的确认性（第三阶段试验）测试。为了提高临床药物评估过程的效率并快速确定潜在的候选治疗药物是否能缓解疼痛，通过调节中枢疼痛神经生物学，我们提出了一种“概念前验证”方法，其中疗效评估是使用客观验证的功能神经影像学测量支持的主观临床疼痛评估在单个个体（N-of-1）中进行。使用 N-of-1 + i 方法，