A Markov Model of Gap Occurrence in Continuous Glucose Monitoring Data for Realistic in Silico Clinical Trials.

BACKGROUND AND OBJECTIVE: Continuous glucose monitoring (CGM) sensors measure interstitial glucose concentration every 1-5 min for days or weeks. New CGM-based diabetes therapies are often tested in in silico clinical trials (ISCTs) using diabetes simulators. Accurate models of CGM sensor inaccuracies and failures could help improve the realism of ISCTs. However, the modeling of CGM failures has not yet been fully addressed in the literature. This work aims to develop a mathematical model of CGM gaps, i.e., occasional portions of missing data generated by temporary sensor errors (e.g., excessive noise or artifacts). METHODS: Two datasets containing CGM traces collected in 167 adults and 205 children, respectively, using the Dexcom G6 sensor (Dexcom Inc., San Diego, CA) were used. Four Markov models, of increasing complexity, were designed to describe three main characteristics: number of gaps for each sensor, gap distribution in the monitoring days, and gap duration. Each model was identified on a portion of each dataset (training set). The remaining portion of each dataset (real test set) was used to evaluate model performance through a Monte Carlo simulation approach. Each model was used to generate 100 simulated test sets with the same size as the real test set. The distributions of gap characteristics on the simulated test sets were compared with those observed on the real test set, using the two-sample Kolmogorov-Smirnov test and the Jensen-Shannon divergence. RESULTS: A six-state Markov model, having two states to describe normal sensor operation and four states to describe gap occurrence, achieved the best results. For this model, the Kolmogorov-Smirnov test found no significant differences between the distribution of simulated and real gap characteristics. Moreover, this model obtained significantly lower Jensen-Shannon divergence values than the other models. CONCLUSIONS: A Markov model describing CGM gaps was developed and validated on two real datasets. The model describes well the number of gaps for each sensor, the gap distribution over monitoring days, and the gap durations. Such a model can be integrated into existing diabetes simulators to realistically simulate CGM gaps in ISCTs and thus enable the development of more effective and robust diabetes management strategies.