Explanatory Clinical Trial of a Novel Parent Intervention for Childhood Anxiety

描述（由申请人提供）：这份K23申请寻求对我作为一名能够设计、执行和评估理论驱动的解释性随机临床试验（rct）的以患者为导向的临床研究者的发展至关重要的支持。我正在建立一个多方法的研究项目，研究父母是如何适应孩子的焦虑的，并通过改变这些纠缠的模式来进行干预。我进行了小型临床试验，并检查了关键的生物学和行为标记。我需要在三个核心领域发展我的技能和专业知识：1)设计和执行解释性随机对照试验~ 2)在解释性随机对照试验中整合生物行为标记物~ 3)应用统计方法检验解释性随机对照试验中的中介和调节假设。为了实现这些目标，我制定了一个培训计划，包括与所有赞助商定期会面、参观其他实验室、课程研讨会和讲习班、独立阅读和科学会议。一流和敬业的导师团队确保我接受强大的，最先进的培训。他们的指导，培训活动，以及耶鲁儿童研究中心优秀的学术环境，将为我提供开始独立研究生涯的技能，从我的第一个R01开始。父母在治疗儿童焦虑症中的作用仍未得到解决。与个体认知行为疗法（ICBT）相比，将父母纳入治疗过程并没有产生更好的效果。从这些数据中得出的一个合理的结论是，父母工作不能增强治疗效果。本K23着重于另一种似是而非的结论：父母干预需要通过父母特定的改变机制的理论工作模型来提供信息，而这不是ICBT的目标，父母干预需要在解释性临床试验中进行评估，而不仅仅是问“治疗是否有效？”以及“治疗如何起作用，对谁起作用？”形成父母对儿童焦虑反应的潜在系统为这种针对父母的干预目标提供了线索，并指出了治疗反应的潜在中介和调节者。确定父母干预反应的中介和调节因子可以提高儿童焦虑结果，并推进个性化心理治疗的目标。SPACE项目（支持童年焦虑情绪的养育）是一种以父母为基础的干预，目标是家庭调节（FA），儿童焦虑。我建议以ICBT作为基线比较条件，对SPACE进行综合解释性临床试验。该试验提出了3个主要问题：1)与ICBT相比，SPACE是否会显著降低FA水平？2)减少FA会导致积极的儿童结局吗？3)关键的生物学和行为标记（即母体催产素、自主授予、过度参与、敏感性）是否会影响儿童的预后？患有原发性焦虑症的7-14岁儿童（n=120）将被随机分为ICBT组或SPACE组。该试验的结果将指导R01的准备，并有可能提高对高度流行的儿童焦虑症的治疗效果。

DESCRIPTION (provided by applicant): This K23 application seeks support essential to my development as a patient oriented clinical investigator able to design, execute, and evaluate, theory-driven explanatory randomized clinical trials (RCTs). I am building a multi-method program of research to study how parents are drawn into accommodating their child's anxiety, and to intervene by modifying these patterns of enmeshment. I have conducted small clinical trials and have examined key biological and behavioral parent markers. I need to develop my skill and expertise in three core areas: 1) Designing and executing explanatory RCTs~ 2) Integrating bio-behavioral markers in explanatory RCTs~ 3) Applying statistical methods to test hypotheses of mediation and moderation in explanatory RCTs. To achieve these goals I have developed a training plan including regular meetings with all my sponsors, visits to other laboratories, courses seminars and workshops, independent reading, and scientific meetings. The superb and dedicated mentorship team ensures I receive strong, state of the art training. Their mentorship, the training activities, and the outstanding academic environment at the Yale Child Study Center, will provide me with the skills to launch an independent research career, starting with my first R01. The role of parents in the treatment of childhood anxiety remains unresolved. Including parents in the treatment process has not yielded superior effects compared to individual cognitive behavioral therapy (ICBT). One plausible conclusion from these data is that parent work cannot enhance effects treatment effects. This K23 focuses on an alternative plausible conclusion: That parent interventions need to be informed by theoretical working models of parent-specific mechanisms of change that are not targeted in ICBT~ and that parent interventions need to be evaluated in explanatory clinical trials asking not only 'doe treatment work?' but also 'how and for whom does treatment work?' Underlying systems that shape parents' responses to child anxiety provide clues to such parent-specific targets for intervention, and point to potential mediators and moderators of treatment response. Identifying mediators and moderators of response to parent interventions can enhance child anxiety outcomes and advance the goal of personalized psychotherapy. The SPACE Program (Supportive Parenting For Anxious Childhood Emotions) is a parent-based intervention that targets family accommodation (FA), of child anxiety. I propose an integrated explanatory clinical trial of SPACE, with ICBT as baseline comparison condition. The trial asks 3 main questions: 1) Will SPACE lead to significantly lower levels of FA compared to ICBT? 2) Will reducing FA lead to positive child outcomes? 3) Will key biological and behavioral markers (i.e., maternal oxytocin, autonomy granting, over involvement, sensitivity) moderate child outcomes? Children aged 7-14 (n=120), with primary anxiety disorders, will be randomized to either ICBT or SPACE. Results of this trial will guide the preparation of an R01 and have the potential to enhance treatment outcomes for the highly prevalent child anxiety disorders.