In silico preclinical trials: methodology and engineering guide to closed-loop control in type 1 diabetes mellitus.
This article sets forth guidelines for in silico (simulation-based) proof-of-concept testing of artificial pancreas control algorithms. The goal was to design a test procedure that can facilitate regulatory approval [e.g., Food and Drug Administration Investigational Device Exemption] for General Clinical Research Center experiments without preliminary testing on animals. The methodology is designed around a software package, based on a recent meal simulation model of the glucose-insulin system. Putting a premium on generality, this document starts by specifying a generic, rather abstract, meta-algorithm for control. The meta-algorithm has two main components: (1) patient assessment and tuning of control parameters, i.e., algorithmic processes for collection and processing patient data prior to closed-loop operation, and (2) controller warm-up and run-time operation, i.e., algorithmic processes for initializing controller states and managing blood glucose. The simulation-based testing methodology is designed to reveal the conceptual/mathematical operation of both main components, as applied to a large population of in silico patients with type 1 diabetes mellitus.
Patek
Stephen D
SD
Department of Systems and Information Engineering, University of Virginia, Charlottesville, Virginia, USA. patek@virginia.edu
Bequette
B Wayne
BW
Breton
Marc
M
Buckingham
Bruce A
BA
Dassau
Eyal
E
Doyle
Francis J
FJ
Lum
John
J
Magni
Lalo
L
Zisser
Howard
H
D000465:Algorithms; D001786:Blood Glucose / Q000502:physiology*; D003198:Computer Simulation; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000628:therapy*; D005502:Food; D006801:Humans; D007328:Insulin / Q000502:physiology; D007332:Insulin Infusion Systems; D019397:Pancreas, Artificial
D001786:Blood Glucose; D007328:Insulin