Identify and systematically study elements of personalized mental health care.
An implicit goal of comparative effectiveness research (CER) is to generate information for patients, clinicians, and policy makers regarding which interventions are most effective for which patients under given circumstances. Thus, CER is most useful when it has potential for impact (i.e., addresses a condition that has substantial public health significance in terms of prevalence and burden, and has the potential to inform practice or policy decisions); is conducted in diverse, representative populations; and assesses a broad array of stakeholder-relevant outcomes. Given the emphasis on diverse populations and the potential for subgroup analyses, CER represents a potential platform for informing personalized medicine, whereby assessment of relevant moderators (e.g., clinical characteristics, biomarker/biosignature data) can facilitate identification of subgroups that are differentially responsive. In turn, information regarding differential responses can inform more prescriptive, personalized approaches for matching individuals to interventions or suggest subgroups for whom alternative or optimized interventions are needed.
NIMH encourages research necessary to determine whether efficacious interventions work under usual conditions, and generalize to the full range of relevant patients and service settings. Given the resources necessary to launch large-scale trials and conduct intervention research in community/practice settings, studies must be justified in terms of potential impact; use innovative platforms and designs (e.g., time and cost efficiencies for enrolling representative patient samples via networks or other existing infrastructure); and, further treatment personalization. NIMH will give lower priority to large scale trials designed to detect incremental gains; expensive trials of on-patent medications without demonstrated superiority over off-patent medications; and trials adapting currently available treatments for new subpopulations, without strong empirical justification (see Objective 3.4.B)
- Support CER and practical or pragmatic trials conducted under “real world” conditions.
Priority areas include:
- Performing effectiveness studies that systematically examine heterogeneity in representative patient populations to identify moderators of intervention response and inform more prescriptive, personalized approaches.
- Conducting trials that incorporate measures of putative mechanisms of action and address relevant mechanistic hypotheses in secondary or exploratory analyses.
- Conducting trials that utilize existing infrastructure (e.g., electronic medical records, administrative data bases, patient registries) to increase the efficiency of participant recruitment and to facilitate the collection of moderator data (e.g., clinical characteristics, biomarkers), longer-term follow-up data, and broader, stakeholder-relevant outcomes (e.g., mental health and general health care utilization, costs).
- Designing studies with large representative samples that incorporate collection of core data or specimens (e.g., genetic, epigenetic, hormonal, neuropsychiatric assessments) in a manner that is standardized, readily integrated with data from other sources (e.g., in repositories), and promotes sharing and dissemination for pooled analysis.
- Carrying out effectiveness studies that go beyond examining the effect of interventions on symptomatic /functional outcomes and also address questions regarding how patient-, provider-, and organizational-level factors impact clinical outcomes as well as the implementation of research- generated interventions.
- Optimize interventions, adapt or augment them for refractory groups, and facilitate implementation by providers. Adaptation or extension of proven interventions should only be undertaken if there is a compelling rationale, supported by empirical evidence, that can be justified in terms of: (a) theoretical and empirical support for the adaptation target (e.g., changes a factor that has been associated with non-response, partial response, patient non-engagement, or relapse); (b) clear explication of the mechanism by which that moderator variable functions to disadvantage or advantage a subgroup (ideally, with behavioral and/or biological data that support the mechanism hypothesis); and (c) evidence to suggest that the adapted intervention will result in a substantial improvement in response rate, speed of response, an aspect of care, or uptake in community/practice settings when compared to existing intervention approaches.
Priority areas include:
- Developing and testing theoretically and empirically supported adaptations of existing approaches for new indications to address disorders or conditions for which efficacious interventions are lacking.
- Developing and testing theoretically and empirically supported adaptations or augmentations of evidence-supported interventions, when research suggests that a moderator or negative prognostic factor can be targeted to substantially improve response and personalize treatment for a readily-identifiable refractory subgroup.
- Conducting research on targeted adaptations to improve the fit of evidence-supported interventions for use in representative community/practice settings, especially studies that systematically measure provider/setting capacity and incorporate stakeholder input in the adaptation process.