Pharmacogenetic Decision Support IT System for Psychiatric Hospitalization: RCT

项目摘要 我们提出了一项随机临床试验（RCT），以比较重度抑郁症患者的结局， 根据患者的CYP 2D 6基因型状态与经验性“标准- 护理”精神治疗。我们假设CYP 2D 6基因型和预测的功能状态， CYP 2D 6酶与药物警报适合患者的先天药物代谢将细化 精神病药物的选择，并减少精神病医院的住院时间和再次入院。 试验环境是哈特福德医院，该医院提供2个关键的机构资源：生活研究所（IOL） 遗传学研究中心（GRC）IOL是一家主要的研究型精神病医院， 卓越的国家声誉，全面的病人护理，研究和教育领域， 行为、精神和成瘾障碍。IOL开发并实施了临床 评价和监测系统（CEMS），一个创新的电子信息系统， 为住院患者的医生提供临床可操作的指导，并将在此用作 这是一种高效、快速的方式，可以将基因型信息提供给临床医生。由PI G博士领导的GRC。鲁阿奥， 曾担任Medicare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，已有近4 000名患者接受了咨询。IOL和GRC已发布 并提供了支持RCT原理的药物遗传学数据和初步临床研究。 在RCT中，该5年R 01项目将分配500例患者接受标准治疗（S组）， 确定CYP 2D 6遗传信息，但不将其传递给治疗临床医生和精神科医生。 治疗是凭经验确定的，1000例为遗传指导治疗（G组），其中基因分型 结果和治疗建议在入院后24小时内通过CEMS提供给临床医生。 CYP 2D 6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性。 超常功能对于G组中40%的代谢不良或快速代谢的患者， 主要由CYP 2D 6酶代谢。主要终点是住院时间， 住院时间和次要终点，30天内再次住院的频率。更多研究基于 对S组和G组的遗传分层将调查特定的精神药物使用情况。 该计划由IOL的高住院人口普查和CEMS系统锚定，由该公司开发， 该项目的首席临床医生J. W.歌德T.R.医生霍尔福德（耶鲁）将担任统计顾问， 博士D.弗洛克哈特（印第安纳州）将担任医疗顾问。预期收益是量化的 了解提供CYP 2D 6药物遗传学信息对结局的影响， CYP 2D 6基因分型的比较有效性的成本和客观基准， 精神治疗

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.