Unit of Neurology Department of Medicine Florence Health Authority, San Giovanni di Dio Hospital, Via Di Torregalli n 3, 50143, Florence, Italy,
J Neurol. 2015 Jun;262(6):1401-6. doi: 10.1007/s00415-014-7535-0. Epub 2014 Oct 14.
In epilepsy trials a substantial proportion of patients receiving placebo has some improvement or experience adverse events (AEs) which match those related to active drug. The characterization of factors influencing these responses is crucial for a better comprehension of study results and to improve design of new trials. Seventy-one placebo-controlled, double-blind trials in drug-resistant focal epilepsies has been selected. The effect of multiple factors on some outcome measures were explored using a meta-regression model. For subjective and objective AEs, risk difference (RD) was calculated and entered in an inverse variance-weighted linear meta-regression model as independent variable to evaluate the relationship with data reported in placebo-treated patients. The number of study arms influence the percentage of patients withdrawing because of AEs and the highest dose of the experimental drug used in each RCT correlates with withdrawal because of AEs and with subjective AEs. Higher titration speed is associated with lower percentages of responders and higher reporting of both objective and subjective AEs. The correlation between proportions of placebo-treated patients with subjective and objective neurological AEs and relative RD, was significant (P = 0.002 r = 0.364 and P < 0.001 r = 0.650, respectively). Efficacy and tolerability outcomes of the placebo groups are intrinsically tied to the trial methodology and to the outcomes observed in patients treated with the active drug. The correlation for objective and subjective AEs between RD and the placebo-treated patients suggest that investigators are influenced by factors which operate within each specific trial.
在癫痫试验中，接受安慰剂的患者中有相当一部分有一定程度的改善或经历了与活性药物相关的不良反应 (AE)。因此，对影响这些反应的因素进行特征描述对于更好地理解研究结果和改进新试验的设计至关重要。本研究纳入了 71 项药物难治性局灶性癫痫的安慰剂对照、双盲试验。采用荟萃回归模型探讨了多种因素对某些结局指标的影响。对于主观和客观 AE，计算了风险差异 (RD)，并将其作为自变量纳入逆方差加权线性荟萃回归模型中，以评估与安慰剂治疗患者报告的关系。研究臂的数量影响因 AE 而退出的患者比例，每个 RCT 中使用的实验药物的最高剂量与因 AE 而退出以及与主观 AE 相关。更高的滴定速度与反应者的比例较低和客观与主观 AE 的报告较高相关。安慰剂治疗患者中主观和客观神经 AE 的比例与相对 RD 之间存在显著相关性（P = 0.002 r = 0.364 和 P < 0.001 r = 0.650）。安慰剂组的疗效和耐受性结局与试验方法以及用活性药物治疗的患者中观察到的结局密切相关。RD 与安慰剂治疗患者之间的客观和主观 AE 的相关性表明，研究者受到每个特定试验中存在的因素的影响。
