Nonadherence to prescribed medication is a\ncommon barrier to effective treatment, and current options\nto determine adherence are limited. This study describes\ndevelopment of an aggregate adherence measure based on\npopulation pharmacokinetics (PK), and its comparison to a\nsubjective questionnaire, the Morisky 8-item medication\nadherence scale (MMAS8), in a trial of psychiatric patients\non stable doses of oral aripiprazole. A comprehensive\nmodel was first built using plasma drug concentration data\nfrom 24 clinical studies comprising 448 patients with over\n13,500 observations. Application of this model to independent\npatient profiles for a given drug-dosing regimen\nwere used to generate the primary aggregate adherence\nmetric, a ratio of observed versus expected plasma exposures\nat steady-state. Although the metric is capable of\ncomparing relative adherence across groups, simulations\nshowed that the metric is not sufficiently sensitive as an\nindividual diagnostic in all cases. There were no trends\nobserved between results from calculated aggregate adherence\nmetrics and total scores from MMAS8 in a single visit\nclinical trial of 47 patients with bipolar 1 disorder or\nschizophrenia who were on stable doses of aripiprazole,\nalthough a strong association was observed for one\nMMAS8 question. The range of the metric calculated for\npatients was between 0.16 and 3.15. The described\napproach of a novel ââ?¬Ë?ââ?¬Ë?reverseââ?¬â?¢Ã¢â?¬â?¢ application of population\nPK to quantify relative adherence with an aggregate measure\nmay be influential for both clinical and pharmacometric\ncommunities.
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