Integrating the clinical and engineering aspects of closed-loop control: the Virginia experience

Abstract

Abstract To be ultimately established and accepted as a viable treatment of diabetes, artificial pancreas (AP) systems need to prove their safety and efficacy in large clinical trials in patient s natural environment. Here, we follow the 10-year evolution of one system, the UVA AP, through inpatient studies, short-term outpatient feasibility trials, and long-term free-living safety tests. To date, this system has logged at least 15,000 days of outpatient use by more than 450 people with type 1 diabetes. Many studies were multicenter, including research sites in the U.S., Europe, Israel, and Argentina. The same control algorithm was used with four sensors (Dexcom SEVEN, G4, G5, G6), two insulin pumps (Roche, Tandem), Mobile AP based on a smart phone (TypeZero s inControl) and was built in an insulin pump (t:slim X2 with Control-IQ). The algorithm has three distinct features: (i) dedicated safety module preventing hypoglycaemia; (ii) fully automated correction boluses, and (iii) gradually intensified control overnight to achieve near normoglycaemia at wakeup. Virtually, all trials included in this review used sensor-augmented pump (SAP) therapy as a control group. Despite hardware differences, the control performance remained stable and effective across studies and system configurations. Overall, the AP was superior to SAP in terms of frequency of CGM readings below 70 mg / dl (1.4% vs. 3.4%) and time within the target range of 70 – 180 mg / dl (75% vs. 67%). These differences were particularly prominent overnight. Aggregate data from 10 years of research driven by the integration of engineering and clinical efforts support the use of the UVA AP system in large-scale clinical trials aiming regulatory acceptance of this system.