Expand and deepen the focus to personalize intervention research.
Clinical trials have traditionally focused on diagnostic status and symptom severity. Inattention to the complex topography of treatment targets and to the ramifications of treatment effects for health and quality of life can limit the explanatory value of findings and their uptake in routine clinical practice. Therefore, more comprehensive measures are necessary for personalized intervention strategies to succeed. NIMH encourages applications aimed at developing broader and more thorough assessment of clinical outcomes—particularly those that can enrich understanding of treatment efficacy and individual variation in response. Assessments could include biological measures and markers, behavioral measures, and psychometric instruments. Priority will be given to studies that address particular domains of functioning that may cut across traditional diagnostic categories. Applications that characterize subjects solely according to diagnostic status or symptom severity, without also assessing individual variables that presumably moderate treatment response, would not be considered responsive to this objective.
Develop innovative quantitative assessment approaches that reflect domains of functioning and dimensions of psychopathology that lend themselves to study across multiple levels of analysis—behavioral, neural systems, molecular, and genetic. For example, dysfunction of fear circuitry or deficits in working memory, rather than prevailing psychiatric categories, might serve as a focus of inquiry rather than prevailing psychiatric categories. Priorities areas include:
- Developing psychometrically sophisticated assessments for use in treatment research that tap specific domains of function (e.g., cognitive, affective) and/or their underlying circuitry to provide sensitive, quantitative measures that provide valid measurement across the full range (normal to disordered) of the dimension. This may include translation of measures originally developed for basic studies.
- Developing and validating early-response markers and surrogate endpoints (biomarkers and other indicators) for use in treatment research.
- Designing multi-modal assessments that provide a practicable but more comprehensive measurement of overall treatment response.
- Developing validated markers that are relatively brief and inexpensive for use in multi-modal assessments in outcomes research.
Develop innovative assessment approaches that extend beyond symptomatic relief to the effects of treatment on functioning, general health, and quality of life. Priorities areas include:
- Developing standard measures of functional outcomes across a range of disorders and diverse populations (varying in age, sex, and ethnicity/race, educational and socioeconomic backgrounds).
- Developing measures based on validated laboratory tests that demonstrate real-world functional significance (e.g., co-primary measures of cognitive functioning).
- Developing assessments sensitive to improved cognitive, affective, or behavioral functioning (e.g., remediation of negative symptoms/deficits) as opposed to decreases in positive symptoms (e.g., overt psychopathology) in psychotic disorders.
- Developing assessments geared toward the specific phase of the trajectory of illness (e.g., prodromal phase). For pre-emptive interventions, these assessments might include neurobiological and cognitive or behavioral measures.