There has been slow progress in the development of interventions that prevent and/or reduce mental-health morbidity and mortality. The National Institute of Mental Health (NIMH) launched an experimental-therapeutics initiative with the goal of accelerating the development of effective interventions. The emphasis is on interventions designed to engage a target mechanism. A target mechanism is a process (e.g., behavioral, neurobiological) proposed to underlie change in a defined clinical endpoint and through change in which an intervention exerts its effect. This article is based on discussions from an NIMH workshop conducted in February 2020 and subsequent conversations among researchers using this approach. We discuss the components of an experimental-therapeutics approach such as clinical-outcome selection, target definition and measurement, intervention design and selection, and implementation of a team-science strategy. We emphasize the important contributions of different constituencies (e.g., patients, caregivers, providers) in deriving hypotheses about novel target mechanisms. We highlight strategies for target-mechanism identification using published and hypothetical examples. We consider the decision-making dilemmas that arise with different patterns of results in purported mechanisms and clinical outcomes. We end with considerations of the practical challenges of this approach and the implications for future directions of this initiative.

中文翻译：

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实验治疗：来自国家心理健康研究所新目标发现和心理社会干预开发研讨会的机遇和挑战。


预防和/或减少心理健康发病率和死亡率的干预措施的制定进展缓慢。美国国家心理健康研究所 (NIMH) 发起了一项实验治疗计划，旨在加速开发有效的干预措施。重点是旨在参与目标机制的干预措施。目标机制是一个过程（例如，行为的、神经生物学的），被提议作为定义的临床终点变化的基础，并通过干预发挥其作用的变化。本文基于 2020 年 2 月举行的 NIMH 研讨会的讨论以及使用此方法的研究人员之间的后续对话。我们讨论实验治疗方法的组成部分，例如临床结果选择、目标定义和测量、干预设计和选择以及团队科学策略的实施。我们强调不同群体（例如患者、护理人员、提供者）在得出有关新目标机制的假设方面的重要贡献。我们使用已发表的和假设的例子来强调目标机制识别的策略。我们考虑了由于所谓的机制和临床结果的不同结果模式而出现的决策困境。最后，我们考虑了这种方法的实际挑战以及该倡议对未来方向的影响。