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A Receiver Operating Characteristic Framework for Non-adherence Detection Using Drug Concentration
Carlos Pérez-Ruixo1, Bart Remmerie2, Juan José Peréz-Ruixo2
1Janssen Research & Development, Clinical Pharmacology & Pharmacometrics, Beerse, Belgium. cperezru@ITS.JNJ.com.
The AAPS Journal
|March 16, 2019
Summary
Plasma risperidone levels can predict schizophrenia treatment adherence. Three trough concentration measurements are recommended for accurate assessment of medication adherence in patients.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Psychiatric Pharmacology
- Clinical Trial Simulation
Background:
- Non-adherence to antipsychotic medication is a major cause of relapse in schizophrenia.
- Predicting treatment adherence is crucial for effective schizophrenia management.
Purpose of the Study:
- To evaluate plasma risperidone concentrations as a predictor of treatment adherence.
- To identify the optimal plasma concentration threshold for distinguishing adherent from non-adherent patients.
Main Methods:
- Population pharmacokinetic modeling to simulate risperidone steady-state trough concentrations.
- Receiver operating characteristic (ROC) analysis to assess adherence probability.
- Evaluation of single versus multiple trough concentration measurements.
Main Results:
- A single trough concentration measurement yielded an area under the ROC curve (AUC_ROC) of 0.71, with an optimal threshold of 11.9 ng/mL.
- Three trough concentration measurements improved the AUC_ROC to 0.85.
- An optimal probability threshold of 0.51 was estimated for reliable discrimination.
Conclusions:
- Three consecutive steady-state trough concentration measurements of risperidone are necessary for an accurate diagnostic test of treatment adherence.
- This approach can reliably differentiate between adherent and non-adherent patients with schizophrenia.
Keywords:
ROC analysisdiagnostic testdrug adherencedrug plasma concentrationspopulation PK model–based simulationMore Related Videos
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