This submission brings together leading pediatric transplant centers, using the NIDDK's collaborative multisite trial (U01) grant mechanism, to investigate an innovative strategy to improve transplant outcomes by improving adherence to medication regimens. Nonadherence to immunosuppressant medications is the leading cause of organ rejection in adolescent transplant recipients. We will investigate a tailored telemetric intervention reduce the number of patients who have a rejection by improving adherence to medications in adolescents who had a liver transplant. This study will use the Medication Level Variability Index (MLVI) to inform the intervention. The MLVI is an innovative biomarker of adherence which calculates the degree of variability between immunosuppressant medication blood levels over time (higher variability = worse adherence). It is a robust predictor of organ rejection (MLVI>2 denotes clinically significant nonadherence, leading to higher rejection risk). At-risk adolescent liver transplant recipients (MLVI>2) will be enrolled in a randomized controlled trial across several transplant centers. In the active telemetric intervention arm (administered via telephone, FaceTime or Skype interfaces), experienced interventionists will remotely communicate with patients using a standardized but flexible intervention strategy. The intervention includes addressing psychological avoidance associated with self-care, and further includes reminders and problem- solving of identified barriers to adherence. Control arm participants will continue to receive standard-of-care at the site. The study will exclusively enroll at-risk patients, will continually monitor their progress through the MLVI marker, and will tailor the intervention to the adherence monitoring findings throughout the 2 year trial period. This study will thus investigate an innovative ?personalized medicine? approach to target a remote intervention effort.
Nonadherence to medications (not taking them as prescribed) is common in children who had a liver transplant, and leads to dire consequences including organ loss and death. This proposal is a multisite trial that investigates a scalable telemetric intervention to improve adherence in patients whose nonadherence is verified by an innovative biomarker. The public health benefit is large, as nonadherence is one of the most important determinants of transplant outcomes, and as the intervention may well be generalizable to other populations.
