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

• 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
• 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

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，为癫痫的治疗和药物审批过程提供信息。不正确的试验设计或基于不正确假设的设计可能导致错误的结论，并可能导致药物滥用。在过去的20年里，连续治疗AED试验的设计和实施背景发生了深刻的变化。与这些变化相关的是观察到的研究间和研究内应答率的变异性增加，特别是观察到的对安慰剂的应答增加，峰值高达40%。最近对连续性AED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。高于假设的安慰剂应答率可能混淆真实的治疗效应量，可能导致试验性AED未能 显示功效。 本项目的目的是确定在成人和儿童局灶性癫痫的连续随机临床试验中，随机接受安慰剂治疗的患者的反应相关因素。国际抗癫痫联盟与NINDS合作，与一些制药公司达成协议，这些公司表示对该项目感兴趣并愿意分享有关其试验的信息。先前的荟萃分析表明，多种因素可能是导致安慰剂应答率增加的原因。这些因素在不同层面上起作用。我们将探讨三大类变量。在目标1中，我们将关注患者相关因素，在目标2中，我们将关注试验特定因素，在目标3中，我们将关注研究中心相关因素。 的 癫痫临床试验的背景随着时间的推移而改变。为了设计最有效和最成功的试验，必须了解在设计阶段和试验进行期间需要考虑哪些因素。这项拟议的研究将有助于了解这些因素，并将为耐药性癫痫患者的新研究设计提供信息。