Leveraging Technology to Improve Medication Adherence in Adolescent and Young Adult Kidney or Liver Transplant Recipients

Over 1/3 of adolescents and young adults (AYAs) who have undergone kidney or liver transplantation are nonadherent to immunosuppressant medicine, a leading cause of organ rejection, graft failure, and death. Despite the American Society of Transplantation's calls for real-time approaches to address immunosuppressant

nonadherence, there are no validated metrics using real-time adherence data (e.g., electronic pillboxes) to identify those at risk for rejection and no efficacious interventions that leverage these data to improve adherence. Hence, we will fill these critical gaps in nonadherence management by validating the new “Real-Time Adherence

Measure,” a novel instrument that could revolutionize how nonadherence is detected by linking the precision of non-invasive, easily downloaded, timestamped electronic pillbox data to tacrolimus blood level standard deviations (biological index of drug ingestion) to direct in the moment when immunosuppressant nonadherence

leads to rejection. We will harness this real-time daily dosing information in an adherence-promoting just-in-time adaptive intervention (JITAI), a cutting-edge mobile health approach capable of fully incorporating AYAs' daily electronically-monitored adherence to deliver tailored intervention content exactly when the AYA needs it most.

Currently, there are no JITAIs for this purpose. We will conduct this vital research, which involves using a micro- randomized trial, a state-of-the-art experimental design for creating successful JITAIs. To develop our JITAI, we will modify a promising existing intervention for promoting AYA adherence (sent adherence support messages

when dose was due) by triggering adherence support messages only when medicine is missed and providing praise messages when medicine is taken. A JITAI-version of this intervention will be piloted with AYA kidney or liver transplant recipients in a 12-week micro-randomized trial to identify intervention content and timing that

maximize the JITAI's impact on adherence. AYAs will be randomized after each electronically-monitored missed tacrolimus dose to receive (1) an adherence support message or (2) no message. After each on time dose, AYAs will be randomized to receive (1) a praise message or (2) no message. AYAs' engagement in the JITAI will be

qualitatively characterized to support long-term uptake. Our findings will address significant knowledge gaps in how to optimally leverage technology to effectively measure and improve medication adherence for AYA kidney or liver transplant recipients, reduce nonadherence-related rejection, graft loss, and death, and improve people's

health and quality of life. Dr. Eaton's study and training activities will prepare her to use advanced methodologies to validate novel clinical metrics, design JITAIs, conduct micro-randomized trials, and improve mobile health engagement. It is critical for Dr. Eaton to have support from this K23 to attain expertise in these innovative

methods and to achieve her important scientific aims. Dr. Eaton's career development activities will occur at Johns Hopkins. Results of this study will provide essential preliminary data for Dr. Eaton's R01-supported full- scale RCT of her JITAI and support her successful transition to become an independent investigator.