Maarten J Bijlsma1, Fanny Janssen2,3, Eelko Hak1. 1. Unit PharmacoEpidemiology & PharmacoEconomics (PE2), Department of Pharmacy, University of Groningen, Groningen, The Netherlands. 2. Population Research Centre (PRC), Faculty of Spatial Sciences, University of Groningen, Groningen, The Netherlands. 3. Netherlands Interdisciplinary Demographic Institute, Hague, The Netherlands.
Abstract
PURPOSE: Accurate measurement of drug adherence is essential for valid risk-benefit assessments of pharmacologic interventions. To date, measures of drug adherence have almost exclusively been applied for a fixed-time interval and without considering changes over time. However, patients with irregular dosing behaviour commonly have a different prognosis than patients with stable dosing behaviour. METHODS: We propose a method, based on the proportion of days covered (PDC) method, to measure time-varying drug adherence and drug dosage using electronic records. We compare a time-fixed PDC method with the time-varying PDC method through detailed examples and through summary statistics of 100 randomly selected patients on statin therapy. RESULTS: We demonstrate that time-varying PDC method better distinguishes an irregularly dosing patient from a stably dosing patient and demonstrate how the time-fixed method can result in a biassed estimate of drug adherence. Furthermore, the time-varying PDC method may be better used to reduce certain types of confounding and misclassification of exposure. CONCLUSIONS: The time-varying PDC method may improve longitudinal and time-to-event studies that associate adherence with a clinical outcome or (intervention) studies that seek to describe changes in adherence over time.
PURPOSE: Accurate measurement of drug adherence is essential for valid risk-benefit assessments of pharmacologic interventions. To date, measures of drug adherence have almost exclusively been applied for a fixed-time interval and without considering changes over time. However, patients with irregular dosing behaviour commonly have a different prognosis than patients with stable dosing behaviour. METHODS: We propose a method, based on the proportion of days covered (PDC) method, to measure time-varying drug adherence and drug dosage using electronic records. We compare a time-fixed PDC method with the time-varying PDC method through detailed examples and through summary statistics of 100 randomly selected patients on statin therapy. RESULTS: We demonstrate that time-varying PDC method better distinguishes an irregularly dosing patient from a stably dosing patient and demonstrate how the time-fixed method can result in a biassed estimate of drug adherence. Furthermore, the time-varying PDC method may be better used to reduce certain types of confounding and misclassification of exposure. CONCLUSIONS: The time-varying PDC method may improve longitudinal and time-to-event studies that associate adherence with a clinical outcome or (intervention) studies that seek to describe changes in adherence over time.
Authors: Carlton Christian; Brittany A Borden; Keith Danahey; Kiang-Teck J Yeo; Xander M R van Wijk; Mark J Ratain; Peter H O'Donnell Journal: Clin Pharmacol Ther Date: 2020-05-25 Impact factor: 6.875
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