Detection of Behavioral Anomalies in Medication Adherence Patterns Among Patients With Serious Mental Illness Engaged With a Digital Medicine System
Authors: Knights Jonathan , Heidary Zahra , Cochran Jeffrey M 
Published: July 2020

Background
Adherence to medication is often represented in the form of a success percentage over a period of time. Although noticeable changes to aggregate adherence levels may be indicative of unstable medication behavior, a lack of noticeable changes in aggregate levels over time does not necessarily indicate stability. The ability to detect developing changes in medication-taking behavior under such conditions in real time would allow patients and care teams to make more timely and informed decisions.

Objective
This study aims to develop a method capable of identifying shifts in behavioral (medication) patterns at the individual level and subsequently assess the presence of such shifts in retrospective clinical trial data from patients with serious mental illness.

Methods
We defined the term adherence volatility as “the degree to which medication ingestion behavior fits expected behavior based on historically observed data” and defined a contextual anomaly system around this concept, leveraging the empirical entropy rate of a stochastic process as the basis for formulating anomaly detection. For the presented methodology, each patient’s evolving behavior is used to dynamically construct the expectation bounds for each future interval, eliminating the need to rely on model training or a static reference sequence.

Results
Simulations demonstrated that the presented methodology identifies anomalous behavior patterns even when aggregate adherence levels remain constant and highlight the temporal dependence inherent in these anomalies. Although a given sequence of events may present as anomalous during one period, that sequence should subsequently contribute to future expectations and may not be considered anomalous at a later period—this feature was demonstrated in retrospective clinical trial data. In the same clinical trial data, anomalous behavioral shifts were identified at both high- and low-adherence levels and were spread across the whole treatment regimen, with 77.1% (81/105) of the population demonstrating at least one behavioral anomaly at some point in their treatment.

Conclusions
Digital medicine systems offer new opportunities to inform treatment decisions and provide complementary information about medication adherence. This paper introduces the concept of adherence volatility and develops a new type of contextual anomaly detection, which does not require an a priori definition of normal and allows expectations to evolve with shifting behavior, removing the need to rely on training data or static reference sequences. Retrospective analysis from clinical trial data highlights that such an approach could provide new opportunities to meaningfully engage patients about potential shifts in their ingestion behavior; however, this framework is not intended to replace clinical judgment, rather to highlight elements of data that warrant attention. The evidence provided here identifies new areas for research and seems to justify additional explorations in this area.