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Novel Targets Discovery and Psychosocial Intervention Development Workshop


February 24–25, 2020




The National Institute of Mental Health (NIMH) Division of Translational Research convened a workshop to provide a forum for NIMH-funded interdisciplinary research teams to illustrate how collaborations between basic, translational, and clinical researchers have led to the identification of novel targets for psychosocial/behavioral interventions.

Despite tremendous advances in basic neuroscience and behavioral science that drive our understanding of the neural circuitry and neurobiological mechanisms underlying mental disorders, our best interventions are still only effective for a portion of those with mental illnesses who receive them. This has led to efforts to develop interventions that target specific underlying mechanisms of mental illness in order to better align an intervention with characteristics of the individual being treated. To encourage the translation of mechanistic findings into novel, mechanism-informed interventions, it is important to make explicit the types of scientific evidence about a mechanism/process that would provide convincing evidence of its potential as an intervention target.

For non-pharmaceutical interventions, a target may be a manipulable interpersonal or contextual factor, a key cognitive operation, or a neural pathway involved in the onset or maintenance of a specific mental illness. The experimental evidence approach to intervention development requires evidence that, when a target is manipulated by an intervention, it mediates the intervention’s ability to reduce the incidence of a negative outcome or the presence/severity of troublesome distressing/impairing symptoms. It follows that the efficacy of an intervention depends on finding viable targets.

Despite the many benefits of the experimental therapeutics/translational pipeline approach to intervention development and testing, it has challenged the field in many ways. The workshop provided a forum for interdisciplinary research teams to share their experience in developing strategies, overcoming challenges, and building collaborative teams when using this approach to identify and evaluate novel targets. Key ideas addressed during the workshop included target selection (rationale/properties); target measures (validity/reliability/suitability for the intervention or disorder under study); cross-disciplinary collaborations; and, the experimental therapeutics framework (challenges of implementing and how these could be addressed).

The workshop consisted of presentations by six interdisciplinary teams, all in the early stages of developing psychosocial interventions. The teams presented their approaches and rationales for identifying novel target mechanisms, the strategies they used, and the challenges they overcame in the process. Workshop participants discussed each presentation and provided feedback about the research process, highlighting successful approaches, common challenges, and suggestions for improvement.

The discussion touched on six major themes: 1) Target and Measure Selection, 2) Specificity versus Generalizability, 3) Intervention Design, 4) Technology, 5) Multidisciplinary Teams, and 6) Feedback from Participants:

Target identification and measurement

During the meeting participants discussed the importance of identifying the best available target and the methods used to measure it prior to submitting an application for early phase testing of the target. Investigations into the mechanisms associated with mental disorders can incorporate the work needed to demonstrate and evaluate the properties of a mechanism that would make it a viable target for an intervention. For instance, demonstration that the value of the mechanism differs with severity of symptoms, or changes with improvement, or is mutable with an experimental manipulation might point to its potential with a target. Demonstrating that the mechanism can be reliably and validly measured would be important if one were to consider testing the impact of an intervention on the mechanism. NIMH staff participated in the discussion to clarify distinctions between early stage and mechanistic clinical trials, and emphasized the need to consult with Program Staff when beginning the process of preparing an application for submission to the National Institutes of Health (NIH) for funding.

Specificity versus Generalizability

Workshop participants discussed the need to weigh the specificity of targets selected for psychosocial intervention development versus the generalizability of each to larger trial designs and patient populations. Issues discussed included: the need to consider whether targets can stratify patients into diagnostic subgroups and if this stratification is necessary; the use of temporal analyses to measure change; whether to measure interactions of multiple targets; and the approaches to adapt and adjust measures to suit the study population, not just the target.

Intervention Design

Participants discussed the need to ensure that designs are human-centered, with careful attention to the target population. Issues to consider included: understanding specific needs and preferences; barriers to participation; designing engaging but challenging technology-based tasks; and facilitating compliance with practice/tasks that can be completed at home and in real-world settings.

The discussion also included a consideration of dosing in psychosocial intervention development and the need for researchers to refer to the literature to guide dose and dose-response, develop novel approaches to assess dose including those that assess management and patient fidelity, and quantify dose for future replication efforts. Challenges in addressing dosing concerns were outlined, including the nature of some psychosocial interventions where dosing remains relatively intangible.


Technology-based interventions and assessments were also discussed. Related issues included: the need to select the technology based on the needs of each patient population (e.g., an intervention for young children should not use heavy, cumbersome equipment); the need for training and technical support; adaptive designs to moderate game difficulty based on player competence; the need to couple technology-based interventions with in-person therapeutic support particularly among vulnerable populations; and the need to align behavioral and physiological data collection, where relevant. The lengthy, labor- and time-intensive process of software development was also discussed.

Multidisciplinary Teams

The teams agreed regarding the need and advantage of having multidisciplinary expertise when identifying and testing a novel target for psychosocial interventions. A key point brought out was the need to involve implementation scientists early in the process to ensure that interventions are scalable, sustainable, and can ultimately improve clinical practice. Since early phase testing of target engagement includes go/no-go milestones, the participants also agreed that it was important to involve statisticians or mathematical modelers to inform go/no-go criteria, effect size, or design strategies.

The participants agreed that it was important to facilitate interdisciplinary workflow by holding regular meetings, providing written standardized protocols, and acknowledging individuals (e.g., research assistants) and their contributions. Managing some multi-disciplinary teams requires innovative strategies; for instance, understanding the needs of different disciplines (e.g. engineering) when setting up project management and communication strategies is essential for seamless work across multi-disciplinary teams.

Technology-based intervention development presents unique challenges. Since technological development is expensive in terms of time and costs, it helps when team members with this expertise have a personal interest in the mental health field or have a professional stake in the project. Ways forward here include considering ways to engage the technology industry as a community rather than placing the burden of technology development on an individual partner.

Feedback from Participants

Part of the final discussion focused on receiving feedback from participants on difficulties when applying for and scientific review of early stage clinical trial grant applications. Participants agreed on the need to clarify some aspects of some Funding Opportunity Announcements (FOA) for early stage clinical trials. Some participants suggested the need to disambiguate terminology by providing specific definitions and concrete examples in the FOA.

The possibility was raised of developing guidance materials to help applicants understand requirements for validity and reliability of target measurements, including potential parameters by which a target or intervention is considered novel.

Participants also expressed a need for clarification of the differences between grant mechanisms, specifically R34 versus R33, and the degree of evidence required for each funding mechanism.

Participants thought it would be important to recognize inconsistencies in the review process and work to overcome them. For instance, could refresher training for reviewers prior to the review session ensure that both the applicant and reviewer are using the same definitions and parameters? This could be particularly helpful for reviewers so that they are familiarized with study design that includes multiple diagnostic groups.

NIMH staff encouraged the participants to interact with Program staff to answer questions specific to their applications.