Bayesian population modeling of drug dosing adherence

Verfasser / Beitragende:
[Kelly Fellows, Colin Stoneking, Murali Ramanathan]
Ort, Verlag, Jahr:
2015
Enthalten in:
Journal of Pharmacokinetics and Pharmacodynamics, 42/5(2015-10-01), 515-525
Format:
Artikel (online)
ID: 605534071
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024 7 0 |a 10.1007/s10928-015-9439-8  |2 doi 
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245 0 0 |a Bayesian population modeling of drug dosing adherence  |h [Elektronische Daten]  |c [Kelly Fellows, Colin Stoneking, Murali Ramanathan] 
520 3 |a Adherence is a frequent contributing factor to variations in drug concentrations and efficacy. The purpose of this work was to develop an integrated population model to describe variation in adherence, dose-timing deviations, overdosing and persistence to dosing regimens. The hybrid Markov chain-von Mises method for modeling adherence in individual subjects was extended to the population setting using a Bayesian approach. Four integrated population models for overall adherence, the two-state Markov chain transition parameters, dose-timing deviations, overdosing and persistence were formulated and critically compared. The Markov chain-Monte Carlo algorithm was used for identifying distribution parameters and for simulations. The model was challenged with medication event monitoring system data for 207 hypertension patients. The four Bayesian models demonstrated good mixing and convergence characteristics. The distributions of adherence, dose-timing deviations, overdosing and persistence were markedly non-normal and diverse. The models varied in complexity and the method used to incorporate inter-dependence with the preceding dose in the two-state Markov chain. The model that incorporated a cooperativity term for inter-dependence and a hyperbolic parameterization of the transition matrix probabilities was identified as the preferred model over the alternatives. The simulated probability densities from the model satisfactorily fit the observed probability distributions of adherence, dose-timing deviations, overdosing and persistence parameters in the sample patients. The model also adequately described the median and observed quartiles for these parameters. The Bayesian model for adherence provides a parsimonious, yet integrated, description of adherence in populations. It may find potential applications in clinical trial simulations and pharmacokinetic-pharmacodynamic modeling. 
540 |a Springer Science+Business Media New York, 2015 
690 7 |a Adherence  |2 nationallicence 
690 7 |a Compliance  |2 nationallicence 
690 7 |a Dosing patterns  |2 nationallicence 
690 7 |a Runs  |2 nationallicence 
690 7 |a Circular distribution  |2 nationallicence 
700 1 |a Fellows  |D Kelly  |u Department of Pharmaceutical Sciences and Neurology, State University of New York, 355 Kapoor Hall, 14214-8033, Buffalo, NY, USA  |4 aut 
700 1 |a Stoneking  |D Colin  |u Seminar for Statistics, Department of Mathematics, ETH Zurich, Zurich, Switzerland  |4 aut 
700 1 |a Ramanathan  |D Murali  |u Department of Pharmaceutical Sciences and Neurology, State University of New York, 355 Kapoor Hall, 14214-8033, Buffalo, NY, USA  |4 aut 
773 0 |t Journal of Pharmacokinetics and Pharmacodynamics  |d Springer US; http://www.springer-ny.com  |g 42/5(2015-10-01), 515-525  |x 1567-567X  |q 42:5<515  |1 2015  |2 42  |o 10928 
856 4 0 |u https://doi.org/10.1007/s10928-015-9439-8  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s10928-015-9439-8  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Fellows  |D Kelly  |u Department of Pharmaceutical Sciences and Neurology, State University of New York, 355 Kapoor Hall, 14214-8033, Buffalo, NY, USA  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Stoneking  |D Colin  |u Seminar for Statistics, Department of Mathematics, ETH Zurich, Zurich, Switzerland  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Ramanathan  |D Murali  |u Department of Pharmaceutical Sciences and Neurology, State University of New York, 355 Kapoor Hall, 14214-8033, Buffalo, NY, USA  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Journal of Pharmacokinetics and Pharmacodynamics  |d Springer US; http://www.springer-ny.com  |g 42/5(2015-10-01), 515-525  |x 1567-567X  |q 42:5<515  |1 2015  |2 42  |o 10928