Department of Physical Medicine and Rehabilitation, Østfold Hospital Trust, 1714, Grålum, Norway.
Oslo Centre for Biostatistics and Epidemiology, Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Eur J Clin Pharmacol. 2022 Sep;78(9):1377-1384. doi: 10.1007/s00228-022-03355-6. Epub 2022 Jul 16.
Chronic pain trials commonly allow auxiliary pain medications such as rescue and concomitant analgesics in addition to the randomized treatment. Changes in auxiliary pain medications after randomization represent intercurrent events that may affect either the interpretation or the existence of the measurements associated with the clinical question of interest, complicating the assessment of treatment efficacy. In chronic pain trials, pain intensity typically varies and patients may take the auxiliary medications 1 day but not the next or increase and decrease the dosages temporarily while continuing their randomized study medication. This distinctive feature of auxiliary pain medications as an intercurrent event has received little attention in the literature. Further clarifications on how to manage these issues are therefore pressing. Here we provide perspectives on issues related to auxiliary pain medication-related intercurrent events in randomized controlled chronic pain trials considering the strategies suggested in the E9(R1) addendum to the ICH guideline on statistical principles for clinical trials.
慢性疼痛试验通常除了随机治疗外,还允许辅助止痛药物,如急救和伴随镇痛剂。随机分组后辅助止痛药物的变化代表了可能影响与关注的临床问题相关的测量解释或存在的并发事件,使治疗效果的评估变得复杂。在慢性疼痛试验中,疼痛强度通常会发生变化,患者可能会在某一天服用辅助药物,但下一天不会服用,或者在继续服用随机研究药物的同时临时增加或减少剂量。辅助止痛药物作为一种并发事件的这种独特特征在文献中很少受到关注。因此,如何处理这些问题需要进一步澄清。在这里,我们考虑到 ICH 临床试验统计原则指南 E9(R1)增编中建议的策略,就随机对照慢性疼痛试验中与辅助止痛药物相关的并发事件相关问题提供了一些观点。
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