National Institutes of Health, NINDS, United States; Beth Israel Deaconess Medical Center, Department of Neurology, United States.
Centers for Disease Control, United States.
Seizure. 2017 Dec;53:31-36. doi: 10.1016/j.seizure.2017.10.016. Epub 2017 Oct 23.
Clinical epilepsy drug trials have been measuring increasingly high placebo response rates, up to 40%. This study was designed to examine the relationship between the natural variability in epilepsy, and the placebo response seen in trials. We tested the hypothesis that 'reversing' trial direction, with the baseline period as the treatment observation phase, would reveal effects of natural variability.
Clinical trial simulations were run with time running forward and in reverse. Data sources were: SeizureTracker.com (patient reported diaries), a randomized sham-controlled TMS trial, and chronically implanted intracranial EEG electrodes. Outcomes were 50%-responder rates (RR50) and median percentage change (MPC).
The RR50 results showed evidence that temporal reversal does not prevent large responder rates across datasets. The MPC results negative in the TMS dataset, and positive in the other two.
Typical RR50s of clinical trials can be reproduced using the natural variability of epilepsy as a substrate across multiple datasets. Therefore, the placebo response in epilepsy clinical trials may be attributable almost entirely to this variability, rather than the "placebo effect".
临床癫痫药物试验的安慰剂反应率不断升高，高达 40%。本研究旨在探讨癫痫的自然变异性与试验中所见安慰剂反应之间的关系。我们检验了这样一个假设，即“反转”试验方向，以基线期作为治疗观察期，将揭示自然变异性的影响。
采用正向和反向时间运行进行临床试验模拟。数据来源为：SeizureTracker.com（患者报告日记）、一项随机假手术对照 TMS 试验和慢性植入颅内 EEG 电极。结果是 50%反应率（RR50）和中位数百分比变化（MPC）。
RR50 结果表明，时间反转并不能阻止各数据集的高反应率。TMS 数据集的 MPC 结果为阴性，而其他两个数据集的 MPC 结果为阳性。
可以使用癫痫的自然变异性作为多个数据集的基础，重现典型的临床试验 RR50。因此，癫痫临床试验中的安慰剂反应可能几乎完全归因于这种变异性，而不是“安慰剂效应”。
