Commentary: a burning question of subgroup analysis in pain trials.
Commentary: a burning question of subgroup analysis in pain trials.
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评论：疼痛试验中亚组分析的一个紧迫问题。
DOI：
10.1016/j.pain.2010.01.010
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发表时间：
2010
期刊：
影响因子：
7.4
通讯作者：
Gibbs,Jennifer
中科院分区：
文献类型：
--
作者：
Gibbs,Jennifer
灼口综合征（BMS）的特征是持续的浅表疼痛，通常是烧灼感。主要表现在舌头，但BMS可能涉及其他口内结构。一些证据表明，外周和中枢疼痛机制有助于这种情况。在BMS患者中观察到粘膜神经支配异常，上皮神经纤维较少，上皮中TRPV 1表达纤维数量较多，这表明外周神经系统的作用[9，13]。在BMS患者的舌头中也观察到热阈值和味觉阈值的变化[3，5，12]。与正常对照患者相比，BMS患者中观察到的眨眼反射改变支持中枢神经系统功能障碍的贡献[7]。此外，使用PET扫描的研究表明，BMS患者的壳核中多巴胺水平较低，壳核中纹状体FDOPA摄取减少[6，8]。在本期《疼痛》杂志中，Grémeau-Richard及其同事通过使用双盲交叉随机对照设计[4]评估舌神经局部麻醉阻滞对疼痛的影响，探索外周传入神经对BMS的贡献。该研究的结果非常有趣，并邀请讨论疼痛试验中亚组分析的使用。在他们的研究中，使用0-10 VAS在舌神经区域局部麻醉或盐水注射之前和之后15分钟测量疼痛。使用利多卡因治疗的个体疼痛减少2.7±3.9 cm，而使用生理盐水治疗后观察到疼痛减少2.0±2.6 cm。事实上，利多卡因与生理盐水对整个组的影响没有显著差异。然而，作者观察到对局部麻醉的反应相当不均匀，并注意到一些个体在局部麻醉后报告的疼痛显著减轻，而一组在局部麻醉后疼痛没有变化或增加。根据对利多卡因的反应，形成了亚组，称为“外周”组或“中心”组。当对这些亚组的结果进行重新分析时，作者发现局部麻醉剂与安慰剂相比在外周组（p= 0.02）中具有高度显著性影响，但在中心组中没有（p= 0.15）。由于方法中没有迹象表明作者计划进行亚组分析，因此我们必须假设进行亚组分析的决定是事后做出的。问题是在本研究中，事后亚组分析是否有效。
Burning mouth syndrome (BMS) is characterized by continuous superficial pain, often burning in nature. The primary manifestation is in the tongue but BMS may involve other intraoral structures. Several lines of evidence suggest that peripheral and central pain mechanisms contribute to this condition. A contribution of the peripheral nervous system is suggested by the observation of abnormal mucosal innervation in BMS patients with fewer epithelial nerve fibers, and greater numbers of TRPV1 expressing fibers in the epithelium [9, 13]. Alterations of the thermal and gustatory thresholds are also observed in the tongue of BMS patients [3, 5, 12]. Contributions of central nervous system dysfunction are supported by the observation of altered blink reflex in BMS patients compared to normal control patients [7]. Furthermore, studies using PET scan demonstrate lower levels of dopamine in the putamen and decreased striatal FDOPA uptake in the putamen in BMS patients [6, 8]. In this issue of Pain, Grémeau-Richard and colleagues explore the contribution of peripheral afferents to BMS by evaluating the effect of local anesthetic block of the lingual nerve on pain using a double-blind cross-over randomized controlled design [4].The results of the study are very interesting and invite a discussion of the use of subgroup analysis in pain trials. In their study, pain was measured using a 0–10 VAS both before and 15 min after local anesthetic or saline injection in the area of the lingual nerve. Individuals treated with lidocaine experienced a 2.7±3.9 cm decrease in pain while a 2.0±2.6 cm decrease was observed after saline. The effect of the lidocaine versus saline on the group as a whole was, in fact, not significantly different. However, the authors observed that the response to the local anesthetic was quite heterogeneous and noted that there were some individuals who had a significant decrease in their reported pain after the local anesthetic and a group that either had no change or an increase in pain after local anesthetic. Based on the response to lidocaine, sub-groups were formed and termed either the ‘‘peripheral” or the ‘‘central” group. When the results of these sub-groups were re-analyzed, the authors found a highly significant effect of local anesthetic versus placebo in the peripheral group (p= 0.02) but not in the central group (p= 0.15). As there is no indication in the methods that the authors planned to perform subgroup analysis we must assume the decision to perform a subgroup analysis was made post hoc. The question is whether a post hoc subgroup analysis is valid in this study.