10779/rcsi.10784408.v1 Garrett Greene Garrett Greene Richard W. Costello Richard W. Costello Breda Cushen Breda Cushen Imran Sulaiman Imran Sulaiman Elaine MacHale Elaine MacHale Ronan M. Conroy Professor Ronan M. Conroy Professor Frank Doyle Frank Doyle A novel statistical method for assessing effective adherence to medication and calculating optimal drug dosages. Royal College of Surgeons in Ireland 2019 Aged Anti-Asthmatic Agents Area Under Curve Asthma Bronchodilator Agents Cohort Studies Drug Dosage Calculations Female Humans Male Medication Adherence Middle Aged Models Statistical Nebulizers and Vaporizers Pulmonary Disease Chronic Obstructive Self Report Sex Factors Medicine 2019-11-22 16:29:41 Journal contribution https://repository.rcsi.com/articles/journal_contribution/A_novel_statistical_method_for_assessing_effective_adherence_to_medication_and_calculating_optimal_drug_dosages_/10784408 <p><strong>OBJECTIVE:</strong> 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.</p> <p><strong>METHODS:</strong> 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.</p> <p><strong>RESULTS:</strong> 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.</p> <p><strong>CONCLUSIONS:</strong> 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.</p>