A Bayesian approach for the estimation of patient compliance based on the last sampling information

Poor adherence to a drug prescription significantly impacts on the efficacy and safety of a planned therapy. The relationship between drug intake and pharmacokinetics (PK) is only partially known. In this work, we focus on the so-called "inverse problem", concerned with the issue of retracing the patient compliance scenario using limited clinical knowledge. Using a reported Pop-PK model of imatinib, and accounting for the variability around its PK parameters, we were able to simulate a whole range of drug concentration values at a specific sampling point for a population of patients with all possible drug compliance profiles. Using a Bayesian decision rule, we developed a methodology for the determination of the associated compliance profile prior to a given sampling value. The adopted approach allows, for the first time, to quantitatively acquire knowledge about the compliance patterns having a causal effect on a given PK. Moreover, using a simulation approach, we were able to evaluate the evolution of success rate of the retracing process in terms of the considered time period before sampling as well as the model-inherited variability. In conclusion, this work allows, from a probability viewpoint, to propose a solution for this inverse problem of compliance determination.