Yale Center for Analytical Sciences, Yale University, New Haven, Connecticut 06511, USA.
J Pain. 2013 Aug;14(8):767-77.e8. doi: 10.1016/j.jpain.2013.04.004. Epub 2013 Jun 3.
In pain clinical trials, the rescue analgesic medication such as patient-controlled analgesia morphine is often made available for patients for breakthrough pain. The patient-controlled analgesia morphine usage decreases the study agent's effect on pain relative to placebo and introduces greater variability in attainment of pain scores. For assessment of analgesic efficacy, the isolated statistical analysis of pain score or morphine consumption as a surrogate marker for pain not only loses statistical efficiency but also may incur increased false-positive findings because of multiple testing. The aim of this article is to review the research to date for choices of statistical tests for pain or morphine consumption outcome, with a focus on systematically evaluating a means for collective analgesic assessment of pain and morphine consumption using an integrated outcome. A case example is illustrated for data visualization, statistical comparison, and effect size estimation using the new endpoint. Some implications for clinical practice and further research are discussed.
This article provides statistical evidence to conclude that an integrated outcome of pain score and morphine consumption provides an efficient means for integrated analgesic assessment.
在疼痛临床试验中，常为患者提供解救镇痛药物，如患者自控镇痛吗啡，以缓解爆发性疼痛。与安慰剂相比，患者自控镇痛吗啡的使用降低了研究药物对疼痛的作用，并增加了达到疼痛评分的变异性。为了评估镇痛疗效，仅对疼痛评分或吗啡消耗的单独统计分析作为疼痛的替代标志物，不仅会降低统计效率，而且由于多次检验，还可能导致更多的假阳性发现。本文的目的是回顾迄今为止有关疼痛或吗啡消耗结果的统计检验选择的研究，重点是系统地评估使用综合结果对疼痛和吗啡消耗进行集体镇痛评估的方法。通过一个案例示例说明了使用新的终点进行数据可视化、统计比较和效应量估计的方法。讨论了对临床实践和进一步研究的一些影响。
本文提供了统计证据，得出结论认为疼痛评分和吗啡消耗的综合结果为综合镇痛评估提供了一种有效的方法。
