A Receiver Operating Characteristic Framework for Non-adherence Detection Using Drug Concentration Thresholds —Application to Simulated Risperidone Data in Schizophrenic Patients

AbstractNon-adherence to antipsychotic medication is a primary factor in disease relapse in schizophrenic patients. We sought to evaluate if plasma concentrations of the antipsychotic risperidone can be used as a predictor of treatment adherence and to identify the optimal plasma concentration threshold to reliably distinguish between adherent and non-adherent patients. A population pharmacokinetic model was used to simulate plasma risperidone steady-state trough concentrations in 1000 virtual patients, where 60% of the patients were 100% adherent to their medication, while 40% of the patients were non-adherent to their medication. The probability of adherence was assessed by receiver operating characteristic (ROC) analysis onCtrough. The area under the ROC curve (AUCROC) was used to identify the optimalCtrough threshold. Singlevs multipleCtrough at steady state was also evaluated. After a single risperidoneCtrough measurement, the AUCROC (95% CI) was estimated to be 0.71 (0.69 –0.72) and the optimalCtrough threshold accounting for the lowest number of adherent and non-adherent misclassifications was estimated to be 11.9  ng/mL. After multipleCtrough measurements, the AUCROC (95% CI) increased up to 0.85 (0.84 –0.87) for threeCtrough measurements. The optimal probability threshold to reliably discriminate between adherent and non-adherent patients was estimated to be 0.51. Using this model which is reflective of typical adherence to antipsychotic medication, we found tha...
Source: The AAPS Journal - Category: Drugs & Pharmacology Source Type: research