Department of Clinical Medicine (Pharmaceutical Medicine), Kitasato University Graduate School of Pharmaceutical Sciences, Shirokane-5-9-1, Minato-ku, Tokyo, Japan.
Clin Drug Investig. 2013 May;33(5):315-24. doi: 10.1007/s40261-013-0077-x.
Placebo response in clinical trials for anti-epileptic drugs (AEDs) has been examined and a recent meta-analysis revealed that East Asian trials showed unexpectedly higher placebo response. As multi-national trials have become common, it is important to understand placebo response in different settings, including regions/countries for future clinical trials.
The present meta-analysis aims to investigate the potential factors that contribute to higher placebo response in clinical trials for add-on therapy to adult patients with refractory partial epilepsy in East Asian and Western populations.
A database was established based on published clinical trials conducted in East Asian and Western countries. The relationship between the degree of placebo response and potential influencing factors was examined by logistic regression analyses.
The database included 33 trials from five AEDs: gabapentin, topiramate, levetiracetam, pregabalin, and zonisamide. Placebo response was associated with patient characteristics such as disease duration, percentage of patients with complex partial seizure (CPS) at baseline, percentage of patients treated with two AEDs, protocol-required seizure frequency at baseline, and year of publication. Logistic regression analysis demonstrated that the placebo response in East Asian trials was statistically higher than that in Western trials.
Patient characteristics such as longer disease duration and CPS at baseline contribute to a reduction in placebo response in clinical trials of AEDs for partial epilepsy. While the reasons for the geographical difference in placebo response are not clear, these and other patient characteristics contributing to placebo response should be carefully considered in the design of future clinical trials of AEDs for partial epilepsy.
抗癫痫药物（AED）临床试验中的安慰剂反应已经过研究，最近的一项荟萃分析显示，东亚试验显示出出乎意料的更高的安慰剂反应。随着多国家试验变得普遍，了解不同环境（包括地区/国家）中的安慰剂反应对于未来的临床试验非常重要。
本荟萃分析旨在研究导致东亚和西方人群中成年难治性部分性癫痫患者附加治疗临床试验中安慰剂反应较高的潜在因素。
根据在东亚和西方国家进行的已发表临床试验建立数据库。通过逻辑回归分析检查安慰剂反应程度与潜在影响因素之间的关系。
该数据库包括来自五种 AED 的 33 项试验：加巴喷丁、托吡酯、左乙拉西坦、普瑞巴林和唑尼沙胺。安慰剂反应与患者特征相关，例如疾病持续时间、基线时复杂部分性发作（CPS）患者的百分比、接受两种 AED 治疗的患者的百分比、基线时协议要求的发作频率以及发表年份。逻辑回归分析表明，东亚试验的安慰剂反应明显高于西方试验。
基线时疾病持续时间较长和 CPS 等患者特征有助于减少部分性癫痫 AED 临床试验中的安慰剂反应。虽然安慰剂反应的地理差异原因尚不清楚，但在设计未来的部分性癫痫 AED 临床试验时，应仔细考虑这些以及其他影响安慰剂反应的患者特征。
