Home-based Therapeutic Drug Monitoring for Patient-Centric Precision Dosing of Immunosuppression after Solid Organ Transplantation

Abstract

The lifesaving potential of organ transplantation depends on the individualization of immunosuppressive drugs. Precision dosing is critical to prevent immune-mediated damage while minimizing toxicity. Precise dosing for these highly variable drugs requires multiple blood collections to accurately determine total exposure. Unfortunately, repeated sampling is challenging to implement in routine care. The overall objective was to develop an innovative method to enable people living with a transplant to self-collect blood microsamples for therapeutic drug monitoring (TDM) to support dosing decisions. Two aims were pursued to achieve the overall objective. In Aim 1, we developed methods for bioanalysis of immunosuppressants from volumetric absorptive microsamples (VAMS). The initial step resulted in the first analytical procedure to simultaneously quantify tacrolimus and mycophenolic acid from a novel VAMS device, the Tasso-M20. The next step was to conduct a clinical validation study that demonstrated agreement between the concentrations obtained from VAMS and traditional venipuncture samples, providing evidence that the VAMS results can be used interchangeably in clinical practice. Additionally, the Tasso-M20 device is reported to painlessly obtain capillary blood from the upper arm by pressing a button, which was hypothesized to be preferred by patients compared to the previous generation VAMS technique using a finger stick (Mitra device). To test this hypothesis, as part of the clinical validation study, participants had samples collected using both devices and completed a questionnaire using validated instruments comparing preferences, usability, acceptability, and feasibility. The findings confirm that the Tasso-M20 is preferred due to reduced pain and increased usability, and the concept of home-based TDM was considered acceptable and feasible to patients. A pilot randomized hybrid type 1 effectiveness-implementation study was completed to address aim 2. Aim two sought to quantify the performance and facilitators/barriers of a home-based TDM model incorporating adaptive text messaging delivered via mobile phone. The text message intervention was intended to support adherence and guide sample collection. Participants were randomized to unidirectional reminders or bidirectional messages. The effectiveness was evaluated by the percentage of samples returned within 48 hours of the scheduled collection. The 100% sample return rate, with 94% postmarked within 48 hours, was much higher than previous reports and suggests the value of integrating technology to support self-management. Semi-structured interviews were used to understand the implementation context from the patient’s perspective. The qualitative results identified that home-based TDM was easy to conduct with many patient-identified facilitators compared to traditional venipuncture, including enhanced flexibility and the ability to obtain additional data to optimize therapy. Patient cost-sharing was identified as the most critical barrier to implementation. Collectively, the results showed that combining VAMS with mobile health technology is acceptable and feasible to facilitate the collection of repeated samples in the comfort of home. Combining modern tools from various disciplines (analytical chemistry, pharmacometrics, and health behavior), we developed a patient-centric home-based TDM model encompassing a valid analytical approach and mobile health technology to support future precision dosing as a method to improve patient outcomes.