Method, system and computer simulation environment for testing of monitoring and control strategies in diabetes

Patent metadata

Field	Value
Publication number	US-10546659-B2
Application number	US-66444408-A
Country	US
Kind code	B2
Filing date	Jun 20, 2008
Priority date	Jun 21, 2007
Publication date	Jan 28, 2020
Grant date	Jan 28, 2020

Abstract

A simulation environment for in silico testing of monitoring methods, open-loop and closed-loop treatment strategies in type 1 diabetes. Some exemplary principal components of the simulation environment comprise, but not limited thereto, the following: 1) a “population” of in silico “subjects” with type 1 diabetes in three age groups; 2) a simulator of CGM sensor errors; 3) a simulator of insulin pumps and discrete insulin delivery; 4) an interface allowing the input of user-specified treatment scenarios; and 5) a set of standardized outcome measures and graphs evaluating the quality of the tested treatment strategies. These components can be used separately or in combination for the preclinical evaluation of open-loop or closed-loop control treatments of diabetes.

First claim

We claim:

1. An interactive computer-implemented method for testing of monitoring and treatment strategies for diabetes in an individual patient, comprising:
providing a computer-executable model of the human glucose-insulin metabolic system;
providing a database of a population of simulated diabetic human subjects representative of the general diabetic population, the simulated population being derived from real patient data and collectively having a set of metabolic parameters with values encompassing a distribution of parameters observed in vivo across the population of diabetic subjects;
receiving a user input defining a treatment strategy for said individual patient and selected simulated subjects from said database on which to run the defined treatment strategy;
running said defined treatment strategy in a computer processor on said selected simulated subjects using said human glucose-insulin model and determining glucose levels of said selected simulated subjects during running of said treatment strategy using a simulated glucose monitoring sensor;
evaluating effects on metabolic parameters of said selected simulated subjects by said treatment strategy based on said determined glucose levels from said simulated glucose monitoring sensor; and
outputting said evaluated effects to said user.

2. The method of claim 1 , further comprising providing a model of errors of said simulated continuous glucose monitoring sensor due to errors in calibration and blood-to-interstitial glucose delays.

3. The method of claim 1 , further comprising providing a model of subcutaneous insulin delivery via insulin pump.

4. The method of claim 1 , wherein said user interacts with said testing method through an interactive module to implement said testing method.

5. An interactive computer simulation system for evaluation of monitoring and treatment strategies for diabetes in an individual patient, comprising:
a computer-executable module including a model of the human glucose-insulin metabolic system;
a database of a population of simulated diabetic human subjects representative of the general diabetic population, the simulated population being derived from real patient data and collectively having a set of metabolic parameters with values encompassing a distribution of parameters observed in vivo across the population of diabetic subjects;
an interactive module configured to receive user input defining a treatment strategy for said individual patient and selected simulated subjects from said database on which to run the defined treatment strategy;
a simulated glucose monitoring sensor for determining glucose levels of said selected simulated subjects;
a computer processor configured to run said defined treatment strategy on said selected simulated subjects using said human glucose-insulin model, to determine glucose levels of said selected simulated subjects during running of said treatment strategy using said simulated glucose monitoring sensor, to determine the effects on metabolic parameters of said selected simulated subjects by said treatment strategy, and to output said evaluated effects to said user.

6. The system of claim 5 , wherein said said simulated glucose monitoring sensor includes a representation of errors of a continuous glucose monitoring sensor due to errors in calibration and blood-to-interstitial glucose delays.

7. The system of claim 5 , wherein said computer simulation system further comprises:
a computer module simulating an insulin pump, said simulated insulin pump including a representation of subcutaneous insulin delivery via an insulin pump.

8. The system of claim 5 ,
wherein said interactive module further allows a user to interact with said computer simulation system for implementing said testing.

9. The system of claim 5 , whereby the interactive module allows a user to interact with the simulated subjects at intervals of about every 10 minutes.

10. The system of claim 5 , wherein the interactive module is run by executing software that allows a user to:
a) input a testing scenario,
b) select simulated subjects for running the scenario, and
c) select a set of outcome metrics to evaluate the scenario.

11. The system of claim 10 , wherein the software allows a user to select a set of glucose control outcome metrics representing or indicating average glycemia, temporal glucose variability, and associated risks for hypoglycemia and hyperglycemia.

12. The system of claim 5 , wherein the user input includes a schedule of meals with corresponding carbohydrate amounts.

13. The system of claim 5 , wherein the interactive module allows a user to evaluate the effect of a pre-clinical treatment method on selected simulated subjects as a substitute for testing of the treatment method in live animals.

14. The system of claim 5 , wherein the interactive module allows a user to evaluate the effect of a treatment method associated with a clinical protocol on selected simulated subjects.

15. The system of claim 5 , further comprising a simulated insulin delivery device for delivering a continuous or scheduled dosing of a discrete amount of insulin to the simulated subjects.

16. The system of claim 15 , wherein the simulated delivery device is a subcutaneous insulin pump.

17. The system of claim 5 , wherein the simulated population comprises about 300 simulated subjects.

18. The system of claim 5 , wherein the simulated population comprises about 200 simulated subjects.

19. The system of claim 5 , wherein the simulated population comprises about 100 simulated subjects.

20. An interactive computer simulation system for evaluation of monitoring and treatment methods for diabetes in an individual patient, comprising:
a processor configured to apply a model of the human metabolic system and provide a population of simulated human subjects representative of the general diabetic population, the simulated population derived from real patient data and collectively having a set of metabolic parameters with values encompassing a distribution of the parameters observed in vivo across the population of diabetic subjects,
a simulated glucose monitoring sensor for continuously determining glucose levels of the simulated subjects, and
software that allows a user to:
a) input a testing scenario,
b) select simulated subjects for running the scenario, and
c) select a set of outcome metrics to evaluate the scenario.

Assignees

• Kovatchev Boris P
• Breton Marc D
• Cobelli Claudio
• Dalla Man Chiara
• Univ Virginia Patent Foundation

Inventors

• Kovatchev Boris P
• Breton Marc D
• Cobelli Claudio
• Dalla Man Chiara

Classifications

• G16H20/10

  relating to drugs or medications, e.g. for ensuring correct administration to patients · CPC title

• G16H50/50 Primary

  for simulation or modelling of medical disorders · CPC title

• G16H20/17

  delivered via infusion or injection · CPC title