Method of modeling for drug design, evaluation and prescription in the treatment of disease

Abstract

A method implemented on at least one specifically programmed computer to improve the outcome of a drug trial. The method includes (a) generating a parameterized mathematical model of disease and immune response, (b) including in the parameterized mathematical model effects from one or more drugs with time-dependent variables that can change during a therapy, (c) creating a calibrated model using empirical data to aid in determining parameters of the parameterized mathematical model, (d) determining responses of the calibrated model to a series of time-dependent drug therapies, and (e) selecting at least one therapy based on the determined responses of the model.

1 . A method implemented on at least one specifically programmed computer to improve the outcome of a drug trial, said method comprising:
 a. generating a parameterized mathematical model of disease and immune response;   b. including in the parameterized mathematical model effects from one or more drugs with time-dependent variables that can change during a therapy;   c. creating a calibrated model using empirical data to aid in determining parameters of said parameterized mathematical model;   d. determining responses of said calibrated model to a series of time-dependent drug therapies; and   e. selecting at least one therapy based on the determined responses of the model, wherein steps a to d are performed using said at least one computer.   
     
     
         2 . The method of  claim 1 , wherein the disease is genetic, pathogenic, cancerous, antigenic, trauma, chemicals, or radiation. 
     
     
         3 . The method of  claim 2 , wherein the series of drug therapies have time-dependent dosing schedules applied over different durations of treatment. 
     
     
         4 . The method of  claim 2 , wherein the series of drug therapies have time-dependent dosing schedules which consist of different total drug dose delivered. 
     
     
         5 . The method of  claim 1 , further comprising the step of adjusting the time dependent therapy to improve the outcome of the drug trial by using a dose which is higher in a first part of the treatment than in a later part of the treatment. 
     
     
         6 . The method of  claim 1 , wherein the disease is an infection that is pathogenic, the drug targets the pathogen or its replication process, and the method further comprises improving the outcome of the drug trial by adjusting the time-dependent dose given during the therapy. 
     
     
         7 . The method of  claim 1 , wherein the disease is an infection that triggers an inflammatory process, the drug targets an immune signaling pathway including a cytokine, chemokine, hormone, or immunoglobulin, and the method further comprises improving the outcome of the drug trial by adjusting the time-dependent dose given during the therapy. 
     
     
         8 . A method implemented on at least one specifically programmed computer to improve the outcome of a drug trial, said method comprising:
 a. generating a parameterized mathematical model of disease and immune response;   b. including in the parameterized mathematical model effects from a drug with time-dependent variables that can change during a therapy;   c. creating a plurality of calibrated models using sub-populations of empirical data from a drug trial to aid in determining sub-population parameter sets;   d. determining responses of said calibrated models to a series of drug therapies; and   e. selecting at least one therapy based on the determined responses of the models, wherein steps a to d are performed using said at least one computer.   
     
     
         9 . The method of  claim 8 , wherein the disease is genetic, pathogenic, cancerous, antigenic, trauma, chemicals, or radiation. 
     
     
         10 . The method of  claim 9 , wherein the series of drug therapies have time-dependent dosing schedules applied over different durations of treatment. 
     
     
         11 . The method of  claim 9 , wherein the series of drug therapies have time-dependent dosing schedules which consist of different total drug dose delivered. 
     
     
         12 . The method of  claim 8 , further comprising the step of adjusting the time-dependent therapy to improve the outcome of the drug trial by using a dose which is higher in a first part of the treatment than in a later part of the treatment. 
     
     
         13 . The method of  claim 8 , wherein the disease is an infection that is pathogenic, the drug targets the pathogen or its replication process, and the method further comprises improving the outcome of the drug trial by adjusting the time-dependent dose given during the therapy. 
     
     
         14 . The method of  claim 8 , wherein the disease is an infection that triggers an inflammatory process, the drug targets an immune signaling pathway including a cytokine, chemokine, hormone, or immunoglobulin, and the method further comprises improving the outcome of the drug trial by adjusting the time-dependent dose given during the therapy. 
     
     
         15 . The method of  claim 1 , further comprising:
 f. administering at least one selected therapy to subjects in a drug trial.   
     
     
         16 . The method of  claim 8 , further comprising:
 f. administering at least one selected therapy to subjects in a drug trial.   
     
     
         17 . A method to improve the outcome of a drug trial, said method comprising:
 a. generating a lumped-parameter mathematical model of disease and immune response;   b. modeling one or more drugs with time-dependent variables that can change during a therapy;   c. creating a calibrated model using empirical data to aid in determining parameters of said lumped-parameter mathematical model;   d. determining responses of said calibrated model to a series of time-dependent drug therapies;   e. selecting at least one therapy based on the determined responses of the model; and   f. administering at least one selected therapy to subjects in a drug trial.