There are ~680,000 adolescent and young adult cancer survivors (AYACS) in the U.S., and this number is likely to grow as the incidence of cancer in this age-group is rising. AYACS experience significant disruptions to achieving normative developmental milestones (e.g. completion of education, developing a career, dating, marriage, child birth), which often results in elevated rates of depressive symptoms compared to healthy peers and other cancer survivors. Among cancer survivors, depressive symptoms associated with poorer quality of life, lower adherence to medical recommendations, increased healthcare utilization/costs, and elevated mortality risk. Though psychosocial interventions for depression are efficacious in the general population, few have been adapted for use with AYACS. Additionally, interventions to improve depressive symptoms have typically been provided in-person, which has resulted in many barriers to participation (e.g., distance, limited clinician availability “after hours”) that are problematic for AYACS who tend to have many competing commitments wuch as school, work, and parenting. Therefore, it is critical to develop AYACS-targeted interventions that can be delivered remotely and on-demand such as mobile health applications (mHealth apps). The objective of this proposal is to prepare and optimize a mHealth app to promote self-management of depressive symptoms among AYACS (iManageAYA), guided by the Multiphase Optimization Strategy (MOST) framework. MOST is a framework adapted from engineering that uses highly efficient factorial experiments to evaluate individual and combined effects of intervention components to determine which ones can be reduced, eliminated, or replaced to improve efficiency. During the K99 phase, I propose using an iterative user-centered design process to prepare a prototype of iManageAYA that is usable, acceptable, and feasible for AYACS. This intervention will consist of a core application and four evidence-based components: 1) behavioral activation; 2) cognitive restructuring; 3) mindfulness training; and 4) peer support. During the R00 phase, I will determine which intervention components reduce depressive symptoms using a full factorial experiment. I will use the results of this experiment to develop an intervention that only includes components that significantly contributed to reductions in depressive symptoms among AYACS, minimizing participant burden. I plan to propose future studies will test the efficacy of this optimized intervention, as well as strategies for its dissemination and implementation. In addition to the proposed research, I will extend my knowledge and skills in: 1) user-centered design; 2) the MOST approach; 3) the conduct of clinical trials with AYACS; 4) dissemination and implementation science and 5) professional development. This K99/R00 award will enable my transition to an independent career conducting innovative research to develop, evaluate, implement, and disseminate psychosocial interventions that address the unique needs of AYACS. My mentoring team and collaborators have the necessary skills and resources to assist me in achieving my goals and will ensure that I successfully transition to an independent investigator.

PROJECT NARRATIVE The public health significance in this study lies in its potential to develop an improved understanding of how to efficiently improve depressive symptoms among adolescent and young adult cancer survivors (AYACS). The findings from this study could result in a scalable and low-cost intervention that enhances self-management of depressive symptoms in this population. Ultimately, this could lead to improved quality of life, increased adherence to medical recommendations, and reductions in healthcare costs associated with cancer recurrence, comorbidities, and premature death among AYACS.