AI Case Study

University of California Los Angeles researchers maintain patient drug levels within target range using personally calibrated treatment



Healthcare Providers And Services

Project Overview

From the research paper: "According to most liver transplant immunosuppression protocols, only the tacrolimus dose is adjusted on the basis of a patient’s daily tacrolimus whole-blood trough concentration (or trough level). Dosing of other immunosuppressants follows established protocols. Patient-specific target ranges are based on clinical context, including
ethnicity, age, liver disease, disease severity, kidney function, comorbidities, concern for rejection, and use of other immunosuppressants. Despite the multiple drugs coadministered with tacrolimus, PPD optimization of the single tacrolimus input ensures that the patient’s drug levels are maintained in a target range. Patient-specific coefficients that define the PPD are determined by calibrating the input doses to the phenotypic outputs, which can include trough levels of drugs or biomarkers
as indicators of efficacy and safety."

Reported Results

The patients given the PPD optimised dosage had "significantly less variability in tacrolimus trough levels" compared to the control group.


From the research paper: "We discovered that treatment efficacy for a given patient can be related to drug dosing through a “response surface” represented by a parabola; we called this mathematical phenotype–dose relationship “parabolic personalized dosing” (PPD). PPD is a second-order algebraic equation based on coefficients specific to the application (in this case, the patient) and initially unknown as treatment commences. This approach adaptively individualizes an input on the basis of these specific coefficients. As a foundation for this clinical study, we have used the PPD platform in vitro and in vivo preclinically for applications in drug development. These studies showed that the parabolic response can identify optimal drug administration conditions across a broad spectrum of indications, from metabolic inhibitors to optimal combinations of antiangiogenic medicines in cancer and stem cells. We hypothesized that PPD could be extended to the clinic, specifically in the context of posttransplant regimens, where patients respond variably and a “one-size-fits-all” therapeutic paradigm is not desired. Patient-specific coefficients that define the PPD are determined by calibrating the input doses to the phenotypic outputs, which can include trough levels of drugs or bio- markers as indicators of efficacy and safety. PPD is disease mechanism–independent and disease indication–agnostic. Additionally, because experimental data are needed to construct this response surface by calibrating the coefficients, PPD is not a model-based algorithm."



General Operations


According to the research article: "Posttransplant immunosuppressive drugs such as tacrolimus have narrow therapeutic ranges. Inter- and intraindividual variability in dosing requirements conventionally use physician-guided titrated drug administration, which results in frequent deviations from the target trough ranges, particularly during the critical postoperative phase. There is a clear need for personalized management of posttransplant regimens to prevent adverse events and allow the patient to be discharged sooner.

The standard of care is for a provider to adjust the dose of an immunosuppressant drug in response to a whole-blood trough concentration,making an educated guess about factors causing deviation from the target range and the amount by which to adjust the dose in response. These decisions are made largely on the basis of clinical experience, and patients frequently deviate from the target range, running the alternate risks of toxicity or graft rejection."



4 liver transplant patients were given the treatment optimised by the researchers while 4 other liver transplant patients received the standard care as a control group.