Naltrexone Treatment

描述(由申请人提供)：在这项国际先导性研究中，我们使用四项海洛因依赖治疗临床试验的数据，以确定哪些患者将更好地接受纳曲酮治疗，以及受访者中哪种类型的纳曲酮制剂(口服、植入型或注射型)会导致最佳结果。尽管在美国，纳曲酮已经被FDA批准用于阿片成瘾的治疗，但它一直没有得到充分利用。在俄罗斯(替代疗法是非法的)，纳曲酮是唯一的药物治疗选择。纳曲酮有三种形式：口服型和缓释型、注射型和植入型。一种新的方法(基于模型的随机森林，mobForest)(Garge等人(2013)将扩展到海洛因治疗和制定单一的可解释的节俭模式。这些方法将被应用于过去四项纳曲酮疗效随机双盲、双模拟、安慰剂对照临床试验的组合数据，并确定哪些患者可能对不同的纳曲酮制剂有反应。这些研究是在俄罗斯圣彼得堡进行的，拥有近1000名患者的数据，涉及400多个个体水平的变量，涵盖人口统计学、临床、遗传学和心理测量学领域。我们将开发经过验证的预测模型，提供对患者反应的预测。我们将为跨文化临床实践提供与临床相关的解释，并评估在更大规模的多国研究中的潜在用途。

DESCRIPTION (provided by applicant): In this international pilot study we use data from four clinical trials of heroin dependence treatment to identify which patients will be better respondents to naltrexone treatment and among respondents which type of naltrexone formulation (oral, implantable, or injectable) leads to the best outcome. Although in the United States naltrexone has been FDA approved for treatment of opioid addiction it has been underutilized. In Russia (where substitution therapy is illegal), naltrexone is the only pharmacological treatment option. Naltrexone is available in three forms: oral and extended release, injectable, and implantable depot-formulations. A novel methodology (Model-based Random Forest, mobForest) (Garge et al. 2013) will be extended to heroin treatment and to the development of a single interpretable parsimonious model. These methods will be applied to combined data from past four naltrexone efficacy randomized double blind, double dummy, placebo- controlled clinical trials and identify which patients are likely to respond to different naltrexone formulations. These studies were conducted in St. Petersburg, Russia, have data on almost 1,000 patients with more than 400 individual-level variables spanning demographics, clinical, genetic, and psychometrics domains. We will develop validated predictive models that provide prognosis of patients' response. We will provide clinically- relevant interpretations to cross-cultural clinical practice, and assess potential use in a larger multi-country study.