Pharmacogenetic Decision Support IT System for Psychiatric Hospitalization: RCT

精神病院住院药物遗传学决策支持 IT 系统：RCT

• 批准号: 8725079
• 负责人: GUALBERTO RUANO
• 金额: $ 24.95万
• 依托单位: HARTFORD HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8725079
• 关键词: Pharmacogenetic; Decision; Support; System; Psychiatric

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.

描述（由申请人提供）：我们提出一项随机临床试验（RCT），以比较根据患者 CYP2D6 基因型状态进行治疗的重度抑郁症（MDD）患者与经验性“标准护理”精神治疗的结果。我们假设 CYP2D6 基因型和预测 CYP2D6 酶的功能状态以及适合患者先天药物代谢的药物警报将完善精神药物的选择，并减少精神病医院的住院时间和再次入院时间。试验地点是哈特福德医院，该医院提供 2 个关键机构资源：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医院，在行为、精神和成瘾障碍领域提供卓越的患者护理、研究和教育，在全国享有盛誉。 IOL 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，可以向医生传输有关住院患者的临床可行指导，并将在这里用作向临床医生提供基因型信息的有效、快速的方式。 GRC 由 PI G. Rua¿ 博士领导，一直是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的孵化器，自 2005 年以来已转诊近 4000 名患者。IOL 和 GRC 已发表并提供了药物遗传学数据和支持 RCT 基本原理的试点临床研究。在 RCT 中，这项为期 5 年的 R01 计划将分配 500 名患者接受标准治疗（S 组），其中 CYP2D6 遗传信息已确定，但不会传递给治疗临床医生，精神药物治疗根据经验确定；1000 名患者接受基因引导治疗（G 组），其中基因分型结果和治疗建议在入院 24 小时内通过 CEMS 向临床医生提供。 CYP2D6 基因分型将包括测试所有导致酶功能低于正常或超正常功能的多态性。对于 G 组中 40% 代谢较差或代谢较快的患者，主要由 CYP2D6 酶代谢的药物被禁用。主要终点是住院时间，次要终点是 30 天再入院的频率。基于 S 组和 G 组遗传分层的其他研究将调查特定的精神药物用途。该计划以 IOL 的高住院患者普查和 CEMS 系统为基础，由该计划的首席临床医生 J.W.歌德。 T.R.博士Holford（耶鲁大学）将担任统计顾问，D. Flockhart 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 药物遗传学信息对结果和相关成本的影响，以及对 CYP2D6 基因分型指导精神治疗的比较有效性进行客观基准评估。