Factors determining placebo response in drug-resistant focal epilepsy

决定耐药局灶性癫痫安慰剂反应的因素

基本信息

批准号：
8583010
负责人：
Emilia Bagiella
金额：
$ 8.48万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-15 至 2015-05-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8583010
关键词：
Adult Adverse event Affect Agreement Antiepileptic Agents Categories Characteristics Child Clinical Treatment Clinical Trials Clinical Trials Design Collaborations Conduct Clinical Trials Data Drug Approval Processes Drug resistance Enrollment Epilepsy Failure Goals Gold Individual International Lead Meta-Analysis Monitor National Institute of Neurological Disorders and Stroke Outcome Study Partial Epilepsies Patients Pharmaceutical Preparations Pharmacologic Substance Phase Placebo Control Placebo Effect Placebos Play Randomized Randomized Clinical Trials Randomized Controlled Trials Refractory Research Research Design Research Infrastructure Role Sample Size Seizures Site Target Populations Time base demographics design disease characteristic dosage drug abuser effective therapy interest patient population public health relevance response success treatment center treatment effect trend willingness

项目摘要

DESCRIPTION (provided by applicant): Clinical trials constitute the gold standard of research that informs treatment of epilepsy as well as the drug approval process. Improper trial design or a design based on incorrect assumptions could lead to the wrong conclusions and, potentially, to a misuse of the drug. The context in which adjunctive-therapy AED trials are designed and conducted has profoundly changed over the past 20 years. Associated with these changes is an observed increased variability in the responder rate both across and within studies and, in particular, an observed increased response to placebo with peaks as high as 40%. Recent analysis of randomized controlled trials of adjunctive AEDs showed that response to placebo has increased significantly over time. Higher than hypothesized placebo response rates can confound the true treatment effect size potentially resulting in failure of investigational AEDs to show efficacy. The goal of this project is to determine factors associated with response in patients randomized to placebo in adjunctive randomized clinical trials of AEDs in adults and children with focal epilepsy. In collaboration with the NINDS, the International League against Epilepsy has reached an agreement with a number of pharmaceutical companies who have expressed interest in this project and willingness to share information about their trials. Previou meta-analysis have suggested that multiple factors may be responsible for the increasing placebo response rates. These factors contribute at different levels. We will be exploring three major categories of variables. In Aim 1 we will be looking at patient-related factors, in Aim 2 we will focus on trial-specific factors and in Aim 3 we will be looking at site- related factors. The context in which clinical trials in epilepsy are conducted has changed over time. In order to design the most efficient and most successful trials it is essential to understand what factors need to be taken into consideration during the design phase and the conduct of the trial. The proposed study will help understand these factors and will inform the design of new studies in patients with drug resistant epilepsy.

描述（由申请人提供）：临床试验构成了研究的黄金标准，该标准为癫痫的治疗以及药物批准过程提供了信息。试验设计不当或基于错误假设的设计可能会导致错误的结论，并可能导致滥用该药物。在过去的20年中，设计和进行辅助治疗AED试验的背景已发生了深刻的变化。与这些变化相关的是，跨研究和内部的响应者速率的变异性增加，尤其是观察到对安慰剂的反应增加，峰值高达40％。最近对辅助AED的随机对照试验的分析表明，随着时间的推移，对安慰剂的反应显着增加。高于假设的安慰剂反应率可能会混淆真正的治疗效果的大小，可能导致研究AED失败显示功效。该项目的目的是确定与成人和局灶性癫痫儿童AED的辅助随机临床试验中随机分配安慰剂的反应相关的因素。与Ninds合作，国际反对癫痫联盟已与许多对该项目表示兴趣的制药公司达成协议，并愿意分享有关其试验的信息。 PREVIOU荟萃分析表明，多个因素可能导致安慰剂应答率提高。这些因素在不同级别的贡献。我们将探索三个主要变量类别。在AIM 1中，我们将研究与患者相关的因素，在AIM 2中，我们将专注于特定于试验的因素，在AIM 3中，我们将研究与现场相关的因素。这进行癫痫中临床试验的背景随着时间的流逝而发生了变化。为了设计最有效，最成功的试验，必须了解在设计阶段和试验的行为中需要考虑哪些因素。拟议的研究将有助于理解这些因素，并将为具有耐药性癫痫患者的新研究设计。