ABSTRACT

Objective

This article delineates best practices in the application of the experimental therapeutics framework for evaluating interventions within the context of randomized controlled trials (RCTs), offering a methodological primer and guiding framework for this approach. We illustrate these practices using an ongoing clinical trial conducted within the framework of a National Institute of Mental Health exploratory phased-innovation award for the development of psychosocial therapeutic interventions for mental disorders (R61/R33), describing the implementation of a novel “Facial Affect Sensitivity Training” (FAST) intervention for children with callous-unemotional (CU) traits. CU traits (e.g., lack of guilt or remorse, low empathy, shallow affect) are an established risk factor for persistent and severe youth misconduct, which reflect impairment in identified neurocognitive mechanisms that interfere with child socialization, and predict poor treatment outcomes, even with well-established treatments for disruptive behavior.

Method

We outline the stages, goals, and best practices for an experimental therapeutics framework. In the FAST trial, we assert that impaired sensitivity for emotional distress cues (fear and/or sadness) is mechanistically linked to CU traits in children, and that by targeting sensitivity to facial affect directly via a computerized automated feedback and incentive system, we can exert downstream effects on CU traits.

Results

In the context of an open pilot trial, we found preliminary support for feasibility and mechanism engagement using FAST.

Conclusions

We summarize pilot study limitations and how they are being addressed in the R61/R33 RCTs, as well as challenges and future directions for psychosocial experimental therapeutics.

中文翻译：

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对具有新兴 CU 特征的幼儿进行面部影响敏感性训练：一种实验治疗方法

摘要

客观的

本文描述了应用实验治疗框架在随机对照试验 (RCT) 背景下评估干预措施的最佳实践，为该方法提供了方法学入门和指导框架。我们使用在国家心理健康研究所探索性阶段性创新奖框架内进行的一项正在进行的临床试验来说明这些实践，该试验用于开发精神障碍的心理社会治疗干预措施（R61/R33），描述了一种新颖的“面部影响”的实施针对具有冷酷无情（CU）特征的儿童的“敏感性训练”（FAST ）干预。CU特征（例如，缺乏内疚或悔恨、低同理心、浅薄情感）是青少年持续和严重不当行为的既定风险因素，这反映了已识别的神经认知机制的损害，这些机制会干扰儿童的社会化，并预测不良的治疗结果，即使是针对破坏性行为的行之有效的治疗方法。

方法

我们概述了实验治疗框架的阶段、目标和最佳实践。在 FAST 试验中，我们断言，对情绪困扰线索（恐惧和/或悲伤）的敏感性受损在机制上与儿童的 CU 特征相关，并且通过计算机化的自动反馈和激励系统直接针对面部情感的敏感性，我们可以对 CU 性状产生下游影响。

结果

在公开试点的背景下，我们找到了使用FAST 的可行性和机制参与的初步支持。

结论

我们总结了试点研究的局限性以及 R61/R33 RCT 中如何解决这些局限性，以及心理社会实验治疗的挑战和未来方向。