Dynamic monitoring of the effects of adherence to medication on survival in heart failure patients: A joint modeling approach exploiting time-varying covariates

Adherence to medication is the process by which patients take their drugs as prescribed, and represents an issue in pharmacoepidemiological studies. Poor adherence is often associated with adverse health conditions and outcomes, especially in case of chronic diseases such as heart failure (HF). This turns out in an increased request for health care services, and in a greater burden for the health care system. In recent years, there has been a substantial growth in pharmacotherapy research, aimed at studying effects and consequences of proper/improper adherence to medication both for the increasing awareness of the problem and for the pervasiveness of poor adherence among patients. However, the way adherence is computed and accounted for into predictive models is far from being informative as it may be. In fact, it is usually analyzed as a fixed baseline covariate, without considering its time-varying behavior. The purpose and novelty of this study is to define a new personalized monitoring tool exploiting time-varying definition of adherence to medication, within a joint modeling approach. In doing so, we are able to capture and quantify the association between the longitudinal process of dynamic adherence to medication with the long-term survival outcome. Another novelty of this approach consists of exploiting the potential of health care administrative databases in order to reconstruct the dynamics of drugs consumption through pharmaceutical administrative registries. In particular, we analyzed administrative data provided byRegione Lombardia - Healthcare Divisionrelated to patients hospitalized for HF between 2000 and 2012.