Developing Methods to Estimate Mediation Effects in Adaptive Interventions

项目总结 拟议的K01指导研究科学家发展奖将为Ahnalee Brincks博士准备 领导开发新的定量方法，通过这些方法来了解 以人为中心的适应性干预影响药物使用和成瘾，包括海洛因和其他阿片类药物 使用障碍(OUD)。Brincks博士，密歇根州立大学学院生物统计学助理教授 人类医学部将受益于NIDA资助的MSU药物依赖流行病学的建立 培训计划和国家拉美裔科学网络指导计划，继续得到大学的支持 在经验丰富的NIDA Pi的指导下，Jim Anthony博士担任HERE K01的首席赞助商。 以人为中心的适应性干预(Ais)是临床医生根据以下情况对治疗进行适应性调整的手段。 观察治疗开始前后的受试者特征。作为有希望的新方法 DUA和OUD，AIs的临床和预防干预为从业者提供了循证工具来调整 随着这些需求的发展，进行干预以满足每个患者的需求，以便在 理想的时间和最佳的剂量。目前存在的统计方法可以评估AIS是否工作，以及 谁的人工智能是有效的。然而，目前尚无统计工具可用来了解认可机构在这方面的运作方式。 通过临床研究的超分子机制和中介途径 和预防研究背景。需要新的调解方法，通过更多的了解来改善认可机构 穿插在中间的路径。识别干预途径可导致发现新的干预靶点 将在随后的OUD和DUA干预的现场驱动人工智能试验中受到挑战或确认。 K01的支持将加强布林克斯博士的职业发展。除了学习乌德/杜瓦自然历史 以及临床课程、诊断和病人护理服务，她还将学习1)应用于DUA的流行病学， 其决定因素和并发症，定义为包括艾滋病毒/艾滋病、丙型肝炎病毒和其他传染病，2) 当前DUA干预措施及其假设的介体，3)用于建立适应性的实验设计 干预措施(例如，序贯多重分配随机试验)，以及4)科学状况因果关系 NIDA研究中中介途径的方法。在她的K01研究中，她的主要目标是开发 新的定量方法，以更好地了解AIs减少OUD和其他DUA的机制。一个 第二个目标是应用这些方法来评估人工智能试验数据中的中介假设。她将发射 一个专注于OUD/DUA中介途径的独立项目，将当前的人工智能方法扩展到 临床干预评估，重点是降低社区、学校和社区的OUD/DUA发病率 目标人群。因此，这项工作应该对NIDA的战略目标产生深远的影响。

PROJECT SUMMARY The proposed K01 Mentored Research Scientist Development Award will prepare Ahnalee Brincks, Ph.D. to lead the development of novel quantitative methods needed to understand the mechanisms through which person-focused adaptive interventions affect drug use and addiction (DUA), including heroin and other opioid use disorders (OUD). Dr. Brincks, Assistant Professor of Biostatistics at the Michigan State University College of Human Medicine, will benefit from the NIDA-funded establishment of MSU's Drug Dependence Epidemiology Training Program and National Hispanic Science Network Mentoring Program, continued with university support under the direction of an experienced NIDA PI, Dr. Jim Anthony, who serves as here lead K01 sponsor. Person-focused adaptive interventions (AIs) are used by clinicians make adaptations to treatment based on participant characteristics that are observed before and after treatment starts. As promising new approaches for clinical and preventive interventions in DUA and OUD, AIs give practitioners evidence-based tools to adjust an intervention to fit each patient's needs as these needs evolve, to deliver the most effective intervention at the ideal time and in the optimal dose. Current statistical approaches exist to evaluate whether AIs work and for whom AIs are effective. However, there are no statistical tools for understanding how the AIs work at the level of the person's experience, via supra-molecular mechanisms and mediational pathways investigated in clinical and prevention researchcontexts. New mediation methods are needed to improve AIs via greater understanding of intervening pathways. Identification of intervening pathways can lead to discover of new intervention targets to be challenged or confirmed in subsequent field-driving AI trials of OUD and DUA interventions. K01 support will strengthen Dr. Brincks' career development. In addition to studying OUD/DUA natural history and clinical course, diagnosis and patient care services, she also will learn 1) epidemiology as applied to DUA, their determinants and complications, defined to encompass HIV/AIDS, HCV, and other infectious diseases, 2) current DUA interventions and their hypothesized mediators, 3) experimental designs used to build adaptive interventions (e.g., Sequential Multiple Assignment Randomized Trials), and 4) state-of-the-science causal approaches to mediational pathways in NIDA research. In her K01 research, her primary aim is development of new quantitative methods to better understand mechanisms through which AIs reduce OUD and other DUA. A second aim involves applying these methods to evaluate mediation hypotheses in AI trial data. She will launch an independent program focused on OUD/DUA mediational pathways, extending current AI approaches beyond clinical intervention evaluations to focus on reducing OUD/DUA incidence rates in communities, schools, and target populations. As such, this work should have far-reaching implications for NIDA strategic goals.