Pharmacogenetic Decision Support IT System for Psychiatric Hospitalization: RCT

描述（由申请人提供）：我们提出了一项随机临床试验（RCT），以比较根据患者CYP2D6基因型状态治疗重度抑郁症（MDD）患者与经验“标准护理”精神药物治疗的结果。我们假设CYP2D6基因型和CYP2D6酶的预测功能状态，以及适合患者先天药物代谢的药物警报，将改善精神药物的选择，减少精神病院的住院时间和再入院时间。试验地点是哈特福德医院，该医院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是一家主要的研究型精神病院，在行为、精神和成瘾障碍领域以卓越、全面的病人护理、研究和教育而享誉全国。IOL已经开发并实施了临床评估和监测系统（CEMS），这是一种创新的电子信息系统，可以向住院患者的医生传递临床可操作的指导，并将其作为一种高效、快速的方式向临床医生提供基因型信息。GRC由PI G. Rua o博士领导，已成为医疗保险认证和国家许可的药物遗传学临床实验室和咨询机构的孵化器，自2005年以来已将近4000名患者转介到该实验室。IOL和GRC已经发表并提交了药理学数据和一项试点临床研究，支持RCT的基本原理。在RCT中，这个为期5年的R01项目将分配500名患者进行标准治疗（S组），其中CYP2D6遗传信息已确定，但未传递给治疗临床医生，精神药物治疗是经验确定的；1000名患者进行基因引导治疗（G组），基因分型结果和治疗建议通过CEMS在入院24小时内提供给临床医生。CYP2D6基因分型将包括检测导致酶具有亚正常或超正常功能的所有多态性。对于G组中40%的代谢不良或快速代谢的患者，主要由CYP2D6酶代谢的药物被禁止。主要终点是住院时间，次要终点是30天再入院频率。基于S组和G组遗传分层的进一步研究将调查具体的精神药物使用情况。该计划以IOL的高住院人口普查和CEMS系统为基础，由该计划的首席临床医生J.W. Goethe博士开发。T.R. Holford博士（耶鲁大学）将担任统计顾问，D. flolockhart博士（印第安纳州）将担任医学顾问。预期的好处是定量了解提供CYP2D6药物遗传信息对结果和相关成本的影响，以及为CYP2D6基因分型指导精神药物治疗的比较有效性提供客观基准。

DESCRIPTION (provided by applicant): 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 o 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.