This submission uses the NIDDK's planning (U34) grant mechanism. It is submitted by leading pediatric transplant centers as the next step of a multicenter effort to validate a marker for nonadherence to immunosuppressant medications post-transplant (the Medication Adherence after Liver Transplant, MALT, multisite study). Nonadherence to immunosupressants is the leading cause of organ rejection in adolescent transplant recipients. The present proposal's aim is to plan a multisite study that will investigate a tailored telemetric intervention to improve transplant outcomes (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 target 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. Nonadherent at-risk adolescent liver transplant recipients will be identified using the MLVI (MLVI>2 denotes clinically significant nonadherence). The telemetric intervention (administered via telephone, FaceTime or Skype interfaces) will enable experienced interventionists to address nonadherence from a remote location, using a structured, tailored approach that accommodates specific patient needs. This approach includes addressing psychological avoidance associated with self-care, and further includes reminders and problem- solving of identified barriers to adherence. The resulting study ? a randomized controlled trial ? will engage at-risk patients only, 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 investigate an innovative ?personalized medicine? approach to target a remote intervention effort. Substantial preliminary work has been done including intervention pilots; the planning grant period will be used to finalize protocol elements, outcome measures definitions, regulatory and human subjects study documents and approvals, and training of personnel at all sites.
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 will develop a multisite trial to investigate 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 can be generalized to other populations.
| Shneider, Caitlin; Dunphy, Claire; Shemesh, Eyal et al. (2018) Assessment and Treatment of Nonadherence in Transplant Recipients. Gastroenterol Clin North Am 47:939-948 |
| Duncan, S; Annunziato, R A; Dunphy, C et al. (2018) A systematic review of immunosuppressant adherence interventions in transplant recipients: Decoding the streetlight effect. Pediatr Transplant 22: |
