Pharmacogenetic Decision Support IT System for Psychiatric Hospitalization: RCT

项目总结 我们提出了一项随机临床试验(RCT)来比较重度抑郁症患者的结果 精神障碍(MDD)根据患者的CYP2D6基因状态与经验性“标准”进行治疗 CARE“精神药物治疗。我们假设CYP2D6基因和预测的功能状态 带有与患者先天药物代谢相适应的药物警报的CYP2D6酶将得到提炼 选择精神药物，减少精神科住院时间和再入院时间。 试验地点是哈特福德医院，它提供两个关键的机构资源：生活研究所(IOL) 和遗传学研究中心(GRC)。IOL是一家以研究为基础的大型精神病院，拥有 在以下领域以卓越、全面的患者护理、研究和教育而享誉全国 行为、精神和成瘾障碍。人工晶状体已经开发并实施了临床 评估和监测系统(CEMS)，一种创新的电子报文传送系统 对住院患者的医生的临床可操作指导，并将在这里用作 向临床医生提供高效、快速的基因分型信息。GRC由PI G.Ruaéo博士领导， 曾作为联邦医疗保险认证和国家许可的药物遗传学临床实验室的孵化器 自2005年以来，已转诊了近4000名患者。IOL和GRC已经发布了 并提供了药物遗传学数据和一项试验性临床研究，支持RCT的理论基础。 在随机对照试验中，这个为期5年的R01计划将500名患者分配到标准治疗(S组)， 确定了CYP2D6遗传信息，但不会将其传递给治疗的临床医生和精神药物 治疗是由经验决定的，1000到基因引导治疗(G组)，其中基因分型 结果和治疗建议通过CEMS在入院后24小时内提供给临床医生。 CYP2D6基因分型将包括检测导致酶低于正常或低于正常的所有多态 超常函数。对于G组中40%的代谢率较低或代谢较快的患者，药物 主要由CYP2D6酶代谢的是被禁止的。主要终点是医院长度为 住院时间和次要终点、再住院30天的频率。基于其他研究的 关于遗传分层S组和G组都将调查具体的精神药物使用情况。 该计划的基础是IOL的高住院患者普查和CEMS系统，由该公司开发 该项目的首席临床医生J.W.歌德博士。T.R.Holford博士(耶鲁)将担任统计顾问和 D.Flockhart博士(印第安纳州)将担任医学顾问。预期收益是数量上的。 了解提供CYP2D6药物遗传学信息对预后和相关因素的影响 指导CYP2D6基因分型比较有效性的成本和客观基准 精神药物疗法。

PROJECT SUMMARY We propose a Randomized Clinical Trial (RCT) to compare outcomes in patients with major depressive disorder (MDD) treated according to the patient's CYP2D6 genotype status versus empiric "standard-of- care" psychotropic therapy. We hypothesize that CYP2D6 genotype and predicted functional status of the CYP2D6 enzyme with medication alerts suited to the patient's innate drug metabolism will refine psychotropic medication selection and decrease both psychiatric hospital length of stay and re-admission. The trial setting is Hartford Hospital, which offers 2 key institutional resources: the Institute of Living (IOL) and the Genetics Research Center (GRC). The IOL is a major research-based psychiatric hospital with a national reputation for excellence, comprehensive patient care, research and education in the fields of behavioral, psychiatric and addiction disorders. The IOL has developed and implemented the Clinical Evaluation and Monitoring System (CEMS), an innovative electronic messaging system that transmits clinically actionable guidance to the physician on hospitalized patients, and which will be utilized here as an efficient, rapid way to advance genotype information to clinicians. The GRC, led by the PI, Dr. G. Rua¿o, has served as incubator for a Medicare-certified and State-licensed pharmacogenetic clinical laboratory and consultation, to which nearly 4000 patients have been referred since 2005. IOL and GRC have published and presented pharmacogenetic data and a pilot clinical study supporting the rationale for the RCT. In the RCT, this 5-year R01 Program will assign 500 patients to standard therapy (Group S) for whom CYP2D6 genetic information is determined but not transmitted to the treating clinician and psychotropic therapy is empirically determined, and 1000 to genetically guided therapy (Group G) where genotyping result and treatment recommendations are furnished via CEMS to the clinician within 24 hours of admission. CYP2D6 genotyping will consist of testing for all polymorphisms that result in an enzyme with sub-normal or supra-normal function. For the 40% of patients in Group G who are poor or rapid metabolizers, medications primarily metabolized by the CYP2D6 enzyme are proscribed. The primary endpoint is hospital length of stay and the secondary endpoint, the frequency of 30 day hospital readmission. Additional research based on genetic stratification of both Group S and Group G will investigate specific psychotropic usage. The Program is anchored by the high inpatient census and CEMS system at IOL, developed by this Program's lead clinician, Dr. J.W. Goethe. Dr. T.R. Holford (Yale) will serve as a statistical consultant and Dr. D. Flockhart (Indiana) will serve as a medical consultant. The expected benefits are quantitative understanding of the effect of providing CYP2D6 pharmacogenetic information on outcomes and associated costs and objective benchmarking for the comparative effectiveness of CYP2D6 genotyping for guiding psychotropic therapy.