EFFECTIVENESS OF MULTI-DRUG TREATMENTS IN TOURETTE'S

这项K23提案的目的是让候选人做好准备，成为一名独立的研究人员，能够设计、获得资金并对患有神经和精神障碍的儿童进行有效的临床试验。候选人提出了一种独特且完美结合的教育经验组合：1)指导精神病学、神经病学和结果研究方面的成熟临床试验研究人员；以及2)统计和研究设计方面的严格硕士培训计划，在18个月内每月30小时的课堂时间。候选人建议将在多药治疗儿童和青少年抽动症的临床有效性试验中学到的经验教训付诸实施。抽动症是一种神经和精神症状并存的典型性障碍。多发性抽动症是一种神经精神障碍，其特征是一年以上的运动和声带痉挛，对功能或社会造成干扰。儿童和青少年经常同时患有多种神经精神病学诊断，并接受从未一起测试过的药物组合治疗。目前的临床研究通常涉及单一疗法的疗效研究，其临床相关性可能有限。这项K奖的研究建议包括一项多巴胺激动剂培高利特的随机对照临床有效性研究，允许同时治疗共病疾病。主要的假设是，培高利特的治疗将与显著的抽动抑制有关，独立于同时治疗强迫症或ADHD。这项研究将有能力确定治疗后的共病强迫症或ADHD的存在是否会导致药物治疗后抽搐症状的变化出现显著差异。赠款的另一个重点将是制定衡量这种疾病的卫生保健利用和费用的措施，并确定它们与缺乏有效症状管理的关系。

The purpose of this K23 proposal is to prepare the candidate to become an independent investigator, able to design, acquire funding for, and perform valid clinical trials in children with co-occurring neurologic and psychiatric disorders. The candidate proposes a unique and well- integrated combination of educational experiences: 1) mentorship with established clinical trials researchers in psychiatry, neurology, and outcomes research; and 2) a rigorous master's training program in statistics and research design, with 30 hours of classroom time per month over 18 months. The candidate proposes to implement the lessons learned in a clinical effectiveness trial of multi-drug treatments in children and adolescents with Tourette's Syndrome, a paradigm disorder of co-occurring neurologic and psychiatric symptoms. Tourette's Syndrome is a neuropsychiatric disorder characterized by greater than one year of motor and vocal tics that are functionally or socially disturbing. Children and adolescents frequently have multiple co-occurring neuropsychiatric diagnoses and are treated with combinations of medications that have never been tested together. Current clinical research typically involves efficacy studies of monotherapy that may have limited clinical relevance. The research proposal of this K award includes a randomized controlled clinical effectiveness study of a dopamine agonist, pergolide, allowing for concurrent treatment of comorbid disorders. The primary hypothesis is that treatment with pergolide will be associated with significant tic suppression, independent of concurrent treatment for OCD or ADHD. The study will have the power to determine whether the presence of treated co-morbid OCD or ADHD accounts for significant variance in the change in tic symptoms on medication. An additional focus of the grant will be developing measures of health care utilization and costs in this disorder and determining their relationship to the presence of absence of effective symptom management.