Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop.

BACKGROUND: Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities. OBJECTIVE: This report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment. METHODS: The National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs. RESULTS: Advances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them. CONCLUSIONS: These recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders.

Integrating statistical and clinical research elements in intervention-related grant applications: summary from an NIMH workshop.

OBJECTIVE: The authors summarize points for consideration generated in a National Institute of Mental Health (NIMH) workshop convened to provide an opportunity for reviewers from different disciplines-specifically clinical researchers and statisticians-to discuss how their differing and complementary expertise can be well integrated in the review of intervention-related grant applications. METHODS: A 1-day workshop was convened in October, 2004. The workshop featured panel presentations on key topics followed by interactive discussion. This article summarizes the workshop and subsequent discussions, which centered on topics including weighting the statistics/data analysis elements of an application in the assessment of the application's overall merit; the level of statistical sophistication appropriate to different stages of research and for different funding mechanisms; some key considerations in the design and analysis portions of applications; appropriate statistical methods for addressing essential questions posed by an application; and the role of the statistician in the application's development, study conduct, and interpretation and dissemination of results. RESULTS: A number of key elements crucial to the construction and review of grant applications were identified. It was acknowledged that intervention-related studies unavoidably involve trade-offs. Reviewers are helped when applications acknowledge such trade-offs and provide good rationale for their choices. Clear linkage among the design, aims, hypotheses, and data analysis plan and avoidance of disconnections among these elements also strengthens applications. CONCLUSION: The authors identify multiple points to consider when constructing intervention-related grant applications. The points are presented here as questions and do not reflect institute policy or comprise a list of best practices, but rather represent points for consideration.

Psychosocial intervention development for the prevention and treatment of depression: promoting innovation and increasing access.

Great strides have been made in developing psychosocial interventions for the treatment of depression and bipolar disorder over the last three decades, but more remains to be done. The National Institute of Mental Health Psychosocial Intervention Development Workgroup recommends three priorities for future innovation: 1) development of new and more effective interventions that address both symptom change and functional capacity, 2) development of interventions that prevent onset and recurrence of clinical episodes in at-risk populations, and 3) development of user-friendly interventions and nontraditional delivery methods to increase access to evidence-based interventions. In each of these areas, the Workgroup recommends systematic study of the mediating mechanisms that drive the process of change and the moderators that influence their effects. This information will highlight the elements of psychosocial interventions that most contribute to the prevention and treatment of mood disorders across diagnostic groups, populations served, and community settings. The process of developing innovative interventions should have as its goal a mental health service delivery system that prevents the onset and recurrence of the mood disorders, furnishes increasingly effective treatment for those who seek it, and provides access to evidence-based psychosocial interventions via all feasible means.