Uyttendaele UDickson JLShaw, GeoffDesaive TChase, Geoff2018-01-112018-01-112017Uyttendaele U, Dickson JL, Shaw GM, Desaive T, Chase JG (2017). Virtual Trials of the NICE-SUGAR Protocol: The Impact on Performance of Protocol and Protocol Compliance. Toulouse, France: IFAC (International Fedaration of Automated Control) 20th World Congress. 09/07/2017-14/07/2017.http://hdl.handle.net/10092/14944Hypoglycaemia, hyperglycaemia and blood glucose (BG) variability are associated with worsened outcomes in critical care. However, NICE-SUGAR trial showed no clinical benefit from intensive insulin therapy. This study compares the table-based NICE-SUGAR and model-based STAR protocols to assess their relative capability to achieve safe, effective control for all patients. Validated virtual patients (n=443) were used to simulate glycemic outcomes of the NICE-SUGAR and STAR protocols. Key outcomes evaluate tightness and safety of control for all patients: %BG in 80–144 mg/dL range (PTR); Per-Patient Mean BG (PPM_BG); and Incidence of Hypoglycaemia (BG<40 mg/dL). These metrics determine performance overall, for each patient, and safety. Results are assessed for NICE-SUGAR measuring per-protocol (~24/day) and at reported average rate (~3-hourly; ~8/day). STAR measures 1-3-hourly, averaging 12/day. Per-protocol, STAR provided tight control, with higher PTR (90.7% vs. 78.3%) and tighter median [IQR] PPM_BG (112[106-119] vs. 117[106–137] mg/dL), and greater safety from hypoglycaemia (5 (1%) vs. 10 patients (2.5%)) compared to NICE-SUGAR simulations as per protocol. The 5-95th percentile range PPM_BG for NICE-SUGAR (97–185 mg/dL) showed ~5% of NICE-SUGAR patients had mean BG above 180mg/dL matching clinically reported performance. STAR’s 5th-90th PPM_BG percentile range was (97–146 mg/dL). Measuring as recorded clinically, NICE-SUGAR had PTR of 77%, PPM_BG of 122 [110-140] mg/dL and 24(6%) of patients experienced hypoglycaemia. These results match clinically reported values well (mean BG 115 vs. 118 mg/dL clinically vs. simulation, clinically 7% of patients had a hypoglycemic event). Glycaemic control protocols need to be both safe and effective for all patients before potential clinical benefits can be assessed. NICE-SUGAR clinical results do not match results expected from their protocol, and show reduced safety and performance in comparison to STAR.enCreative Commons Attribution Non-Commercial No Derivatives Licenseglucosehyperglycaemiaglycaemic controlinsulin sensitivityConference Contributions - Published2017-08-07Fields of Research::40 - Engineering::4003 - Biomedical engineering::400303 - Biomechanical engineeringFields of Research::32 - Biomedical and clinical sciences::3202 - Clinical sciences::320208 - Endocrinologyhttps://doi.org/10.1016/j.ifacol.2017.08.1159