Tiwari Siddharth R, Vigotsky Andrew D, Apkarian A Vania
Illinois Mathematics and Science Academy, Aurora, IL, United States.
Center for Translational Pain Research, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Front Pain Res (Lausanne). 2022 Apr 8;3:844309. doi: 10.3389/fpain.2022.844309. eCollection 2022.
Previous research reports suggest greater baseline variability is associated with greater pain relief in those who receive a placebo. However, studies that evidence this association do not control for confounding effects from regression to the mean and natural history. In this report, we analyzed data from two randomized clinical trials (Placebo I and Placebo II, total = 139) while adjusting for the effects of natural history and regression to the mean a no treatment group. Results agree between the two placebo groups in each study: both placebo groups showed negligible semi-partial correlations between baseline variability and adjusted response [ (CI) = 0.22 (0.03, 0.42) and 0 (-0.07, 0.07) for Placebo I and II, respectively]. The no treatment group in Placebo I showed a negative correlation [-0.22 (-0.43, -0.02)], but the no treatment and drug groups in Placebo II's correlations were negligible [-0.02 (-0.08, 0.02) and 0.00 (-0.10, 0.12) for the no treatment and drug groups, respectively]. When modeled as a linear covariate, baseline pain variability accounted for <1% of the variance in post-intervention pain across both studies. Even after adjusting for baseline pain and natural history, the inability of baseline pain variability to account for substantial variance in pain response highlights that previous results concerning pain variability and treatment response may be inconsistent. Indeed, the relationship appears to be neither consistently specific nor sensitive to improvements in the placebo group. More work is needed to understand and establish the prognostic value of baseline pain variability-especially its placebo specificity and generalizability across patient populations.
先前的研究报告表明，在接受安慰剂治疗的人群中，更大的基线变异性与更大程度的疼痛缓解相关。然而，证明这种关联的研究并未控制均值回归和自然病程的混杂效应。在本报告中，我们分析了两项随机临床试验（安慰剂试验I和安慰剂试验II，共139例）的数据，同时调整了自然病程和均值回归的效应（设立了一个无治疗组）。两项研究中两个安慰剂组的结果一致：两个安慰剂组在基线变异性和调整后的反应之间均显示出可忽略不计的半偏相关系数[安慰剂试验I和II分别为(CI)=0.22(0.03,0.42)和0(-0.07,0.07)]。安慰剂试验I中的无治疗组显示出负相关[-0.22(-0.43,-0.02)]，但安慰剂试验II中的无治疗组和药物组的相关性可忽略不计[无治疗组和药物组分别为-0.02(-0.08,0.02)和0.00(-0.10,0.12)]。当将基线疼痛变异性作为线性协变量进行建模时，在两项研究中，基线疼痛变异性在干预后疼痛方差中所占比例均小于1%。即使在调整了基线疼痛和自然病程之后，基线疼痛变异性仍无法解释疼痛反应中的大量方差，这突出表明先前有关疼痛变异性和治疗反应的结果可能并不一致。事实上，这种关系似乎既不是始终具有特异性，也不是对安慰剂组的改善具有敏感性。需要开展更多工作来理解和确定基线疼痛变异性的预后价值，尤其是其安慰剂特异性以及在不同患者群体中的普遍性。
