Analysis Group, Inc., 111 Huntington Ave, Floor 14, Boston, MA, USA.
UCB Pharma, Allee de la Recherche 60, 1070, Brussels, Belgium.
CNS Drugs. 2017 Oct;31(10):899-910. doi: 10.1007/s40263-017-0462-8.
Patients with focal seizures recruited into adjunctive antiepileptic drug (AED) trials have become more refractory and severe over time; concurrently, placebo responses have increased. To attempt to account for heterogeneity among trials, propensity-score weighted patient-level data were used to indirectly compare placebo responses reported in brivaracetam and levetiracetam trials.
Patient-level data from randomised, placebo-controlled brivaracetam (recruited 2007-2014) and levetiracetam (1993-1998) trials were pooled. Consistent inclusion/exclusion criteria were applied and outcomes were defined consistently. Potentially confounding baseline characteristics were adjusted for using propensity score weighting. Weighting success was assessed using placebo response.
In total, 707 and 473 active drug and 399 and 253 placebo patients comprised the brivaracetam and levetiracetam groups, respectively. Before weighting, several baseline variables were significantly different between groups; after weighting, prior vagal nerve stimulation, co-morbid depression and co-morbid anxiety remained different. Before weighting, median seizure frequency reduction was 21.7 and 3.9% in the brivaracetam and levetiracetam placebo arms, respectively; after weighting, median reduction was 15.0 and 6.0%. The comparison of non-randomised groups could be biased by unobserved confounding factors and region of residence. Lifetime AED history was unavailable in the brivaracetam trials and excluded from analysis.
Placebo responses remained different between brivaracetam and levetiracetam trials after propensity score weighting, indicating the presence of residual confounding factors associated with placebo response in these trials. It therefore remains problematic to conduct reliable indirect comparisons of brivaracetam and levetiracetam given the current evidence base, which may apply to comparisons between other AED trials.
随着时间的推移，招募到辅助抗癫痫药物（AED）试验中的局灶性癫痫患者变得更加难治和严重；同时，安慰剂反应也增加了。为了尝试解释试验之间的异质性，使用倾向评分加权患者水平数据来间接比较布里瓦仑特和左乙拉西坦试验中报告的安慰剂反应。
汇总了随机、安慰剂对照的布里瓦仑特（2007-2014 年招募）和左乙拉西坦（1993-1998 年）试验的患者水平数据。应用一致的纳入/排除标准并一致定义结局。使用倾向评分加权调整潜在混杂的基线特征。通过安慰剂反应评估加权成功。
共有 707 名和 473 名活性药物以及 399 名和 253 名安慰剂患者分别组成了布里瓦仑特和左乙拉西坦组。在加权之前，两组之间的几个基线变量存在显著差异；加权后，先前的迷走神经刺激、合并的抑郁和合并的焦虑仍然不同。在加权之前，布里瓦仑特和左乙拉西坦安慰剂组的中位癫痫发作频率降低分别为 21.7%和 3.9%；加权后，中位数降低分别为 15.0%和 6.0%。非随机分组的比较可能受到未观察到的混杂因素和居住地区的影响。布里瓦仑特试验中缺乏终身 AED 史，因此未纳入分析。
尽管进行了倾向评分加权，但布里瓦仑特和左乙拉西坦试验之间的安慰剂反应仍然存在差异，表明这些试验中与安慰剂反应相关的残留混杂因素仍然存在。因此，鉴于当前的证据基础，对布里瓦仑特和左乙拉西坦进行可靠的间接比较仍然存在问题，这可能适用于其他 AED 试验之间的比较。
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