Recommended Citation
Pandey A, Raja R, Estepp JH, Ramkrishna D. Leveraging mathematical modeling to analyze nonadherence for hydroxyurea therapy in sickle cell disease. CPT Pharmacometrics Syst Pharmacol. 2023; 12: 748-757. doi:10.1002/psp4.12945
DOI
https://doi.org/10.1002/psp4.12945
Date of this Version
5-16-2023
Abstract
Nonadherence is common in individuals with sickle cell disease (SCD) on hydroxyurea therapy and can be observed with waning improvements in hematologic parameters or biomarkers like mean cell volume and fetal hemoglobin level over time. We modeled the impact of hydroxyurea nonadherence on longitudinal biomarker profiles. We estimated the potential nonadherent days in individuals exhibiting a drop in biomarker levels by modifying the dosing profile using a probabilistic approach. Incorporating additional nonadherence using our approach besides existing ones in the dosing profile improves the model fits. We also studied how different patterns in adherence give rise to various physiological profiles of biomarkers. The key finding is consecutive days of nonadherence are less favorable than when nonadherence is interspersed. These findings improve our understanding of nonadherence and how appropriate intervention strategies can be applied for individuals with SCD susceptible to the severe impacts of nonadherence.
Comments
This is the published version of the Pandey A, Raja R, Estepp JH, Ramkrishna D. Leveraging mathematical modeling to analyze nonadherence for hydroxyurea therapy in sickle cell disease. CPT Pharmacometrics Syst Pharmacol. 2023; 12: 748-757. doi:10.1002/psp4.12945