Linking Systems Models of Pharmacology with Behavioural Models of Adherence : A Feasibility Study

Abstract: Pharmacokinetic (PK)- and pharmacodynamic (PD) modeling are useful tools whenassessing treatment effect. A patient’s adherence can potentially be rate-limiting, since it isthe first process in a chain of processes that determines treatment effect. Therefore agreater system taking into consideration PKPD as well as adherence models couldpotentially unlock a greater system understanding. This study focuses on investigating thefeasibility of combining models concerning adherence, PK and PD. An extensive mapping of previously made work on the topics of PKPD model developmentand adherence models concerning type 2 diabetes was conducted. Results concluded thatthere are gaps in research regarding adequate adherence-scoring methods that easily can belinked to dosing regimens. Furthermore, there is lacking research regarding feedback fromexposure-response to adherence. A simple model was implemented to provide a proposedlinkage inhowthe connection could be made between adherence and a PKPD-model.Sensitivity analysis showed that the adherence scoring used (Summary of DiabetesSelf-Care Activities measure, SDSCA) had a moderate correlation to the final response onfasting plasma glucose (Spearman ρ=−0.478∗∗∗). This result suggests that adherenceshould be considered as a relatively important factor to weave in to systems models ofpharmacology and future research should be made on further developing modelsimplementing both social factors, such as adherence, as well as pharmacologic response. Apossible way could be linking dose regimen to adherence scoring.