With more than 13% of adolescents diagnosed with depressive disorders each year, prevention of depressive
disorders has become a key priority for the NIMH. Unfortunately, we have no widely available interventions to
reduce morbidity and mortality (e.g. public health impact). To address this need, we developed a multi-health
system “collaboratory” to develop and evaluate the primary care based-technology “behavioral vaccine,”
Competent Adulthood Transition with Cognitive-Behavioral Humanistic and Interpersonal Therapy (CATCH-IT)
(14 adolescent, 4 parent modules). Using this health-system collaboratory model, CATCH-IT demonstrated
evidence of efficacy in prevention of depressive episodes in phase-three clinical trials in the United States and
China. However, like many “package” interventions, CATCH-IT became larger and more complex across efficacy
trials. Thus, adolescents and parents were less willing to complete all 18 modules, suggesting adolescent dose
“tolerability” issues (e.g. satisfaction, acceptability and resource use, “time as cost”). Similarly, primary care
practices have “scalability” challenges (acceptability, feasibility, resource use, cost), resulting in declining
REACH (percent of at-risk youth who complete intervention). To prepare for implementation studies and
dissemination, we need to address adolescent tolerability and practice/health system scalability, while preserving
efficacy. Multiphase Optimization Strategy (MOST) uses a systematic analytic approach and a factorial
randomized clinical trial design to address efficacy, tolerability, and scalability, simultaneously. We will use a
MOST approach to optimize CATCH-IT for the prevention of depression (indicated prevention, i.e., elevated
symptoms of depression) in practices and health systems representative of US geography and population. The
theoretically grounded components of CATCH-IT selected for study and optimization are: behavioral activation,
cognitive therapy, interpersonal psychotherapy, and parent program. We will use a 4-factor (2x2x2x2) fully
crossed factorial design with N=16 cells (20 per cell, 15% dropout) to evaluate the contribution of each
component. We propose to randomize N=378 (N=189) from each health system site. The at-risk youth will be
high school students 13 through 18 years old, not currently experiencing a mood disorder, but with subsyndromal
symptoms of depression (moderate to high risk). Using the efficient factorial design, we can assess the
contribution to prevention efficacy of each component. Thus, the MOST study design will enable us to eliminate
non-contributing components while preserving efficacy and to optimize CATCH-IT by strengthening tolerability
and scalability by reducing “resource use.” By reducing resource use, we anticipate satisfaction and acceptability
will also increase, preparing the way for an implementation trial and eventual US Preventive Services Task Force
endorsement to support dissemination. Thus, our primary question is whether one component, or perhaps
two, can demonstrate an equivalent effect to combinations of other components in terms of efficacy, whilst also
demonstrating superior adolescent/family tolerability scalability over a 12-month follow-up.
