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dc.contributor.authorGreene, Garrett
dc.contributor.authorCostello, Richard W.
dc.contributor.authorCushen, Breda
dc.contributor.authorSulaiman, Imran
dc.contributor.authorMac Hale, Elaine
dc.contributor.authorConroy, Ronan M.
dc.contributor.authorDoyle, Frank
dc.date.accessioned2018-12-19T17:09:53Z
dc.date.available2018-12-19T17:09:53Z
dc.date.issued2018-04-20
dc.identifier.citationGreene G, Costello RW, Cushen B, Sulaiman I, Mac Hale E, Conroy RM, et al. (2018) A novel statistical method for assessing effective adherence to medication and calculating optimal drug dosages. PLoS ONE 13(4): e0195663. https://doi.org/10.1371/journal.pone.0195663en_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0195663
dc.identifier.urihttp://hdl.handle.net/10147/623978
dc.descriptionObjective: We derive a novel model-based metric for effective adherence to medication, and validate it using data from the INhaler Compliance Assessment device (INCATM). This technique employs dose timing data to estimate the threshold drug concentration needed to maintain optimal health. Methods: The parameters of the model are optimised against patient outcome data using maximum likelihood methods. The model is fitted and validated by secondary analysis of two independent datasets from two remote-monitoring studies of adherence, conducted through clinical research centres of 5 Irish hospitals. Training data came from a cohort of asthma patients (~ 47,000 samples from 218 patients). Validation data is from a cohort of 204 patients with COPD recorded between 2014 and 2016. Results: The time above threshold measure is strongly predictive of adverse events (exacerbations) in COPD patients (Odds Ratio of exacerbation = 0.52 per SD increase in adherence, 95% Confidence Interval [0.34–0.79]). This compares well with the best known previous method, the Area Under the dose-time Curve (AUC) (Odds Ratio = 0.69, 95% Confidence Interval [0.48–0.99]). In addition, the fitted value of the dose threshold (0.56 of prescribed dosage) suggests that prescribed doses may be unnecessarily high given good adherence. Conclusions: The resulting metric accounts for missed doses, dose-timing errors, and errors in inhaler technique, and provides enhanced predictive validity in comparison to previously used measures. In addition, the method allows us to estimate the correct dosage required to achieve the effect of the medication using the patients’ own adherence data and outcomes. The adherence score does depend not on sex or other demographic factors suggesting that effective adherence is driven by individual behavioural factors.en_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectMEDICINES MANAGEMENTen_US
dc.subjectCHRONIC OBSTRUCTIVE PULMONARY DISEASEen_US
dc.subjectDRUG ADMINISTRATIONen_US
dc.subject.otherDRUG DOSAGEen_US
dc.titleA novel statistical method for assessing effective adherence to medication and calculating optimal drug dosagesen_US
dc.typeArticleen_US
dc.contributor.departmentRoyal College of Surgeons in Ireland, Clinical Research Centre, Beaumont Hospitalen_US
dc.identifier.journalPlos Oneen_US
refterms.dateFOA2018-12-19T17:09:53Z


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