Erythropoietic stimulating agent (esa) dosage determination

Abstract

An Erythropoietic Stimulating Agent (ESA) dosing system/method determines patient-specific ESA therapies for patients affected by insufficient hemoglobin production that may benefit from ESA treatment. The ESA dosing system includes a model that represents a process by which red blood cells are produced in humans. The model may include one or more parameters, the values of which are patient-specific. The model takes into account patient-specific historical hemoglobin (Hgb) data and corresponding historical ESA dosage data to estimate the patient-specific values of the model parameters, and determines a target therapeutic dose of the ESA that may maintain the patient's Hgb within a target range.

1 . A system, comprising:
 a biophysical simulation engine that represents a process by which red blood cells are produced in humans, wherein the biophysical simulation engine includes a plurality of parameters the values of which are patient-specific; and   a processing unit that receives patient-specific historical hemoglobin (Hgb) data and corresponding historical erythropoietic stimulating agent (ESA) dosage data, applies the Hgb data and the ESA dosage data to the biophysical simulation engine to estimate the patient-specific values of the plurality of parameters, and determines a therapeutic dose of the ESA based on the patient-specific values of the plurality of parameters.   
     
     
         2 . The system of  claim 1 , wherein the processing unit further identifies, based on the therapeutic dose, an equivalent dosing regimen titrated to available commercial doses. 
     
     
         3 . The system of  claim 1 , wherein the parameters include one or more of an Erythroblast Production Rate, a Blast Mortality Fraction, a Reticulocyte Mortality Fraction, a Hepatic EPO, a RBC Avg Lifespan, an EC50, and a setup EPO. 
     
     
         4 . The system of  claim 1 , wherein the parameters include one or more of a Blast Forming Unit Input, a Colony Forming Unit Survival, a Recticulocyte Survival, an Erythropoietin Receptor Multiplier, a Red Blood Cell Lifespan, and an Erythropoietin Setup Rate. 
     
     
         5 . The system of  claim 1 , wherein the processing unit applies an optimization algorithm to estimate the patient-specific values of the plurality of parameters. 
     
     
         6 . The system of  claim 1 , further comprising a user interface that displays a graph of the patient-specific historical hemoglobin (Hgb) data and the corresponding historical erythropoietic stimulating agent (ESA) dosage data during a descriptive phase. 
     
     
         7 . The system of  claim 1 , wherein the user interface further displays a graph of patient-specific simulated hemoglobin data and the therapeutic dose of the ESA during a prescriptive phase. 
     
     
         8 . A method comprising:
 receiving patient-specific historical hemoglobin (Hgb) and corresponding patient-specific historical erythropoietic stimulating agent (ESA) dosage data;   estimating patient-specific values for each of a plurality of parameters of a biophysical simulation model that represents a process by which red blood cells are produced in humans based on the patient-specific historical Hgb and corresponding patient-specific historical ESA dosage data; and   determining a therapeutic dose that results in a predicted Hgb level stabilized within a target range based on the patient-specific values for each of the plurality of parameters.   
     
     
         9 . The method of  claim 8 , wherein estimating patient-specific values for each of the plurality of parameters comprises applying Monte Carlo methods to estimate the patient specific values. 
     
     
         10 . The method of  claim 8 , further comprising identifying one or more dosing regimens that deliver the equivalent of the therapeutic dose. 
     
     
         11 . The method of  claim 8 , further comprising:
 receiving patient response data concerning actual Hgb levels of the patient under the identified dosing regimen;   comparing the actual Hgb levels of the patient under the identified dosing regimen to the predicted, stabilized Hgb level;   identifying variations from the predicted, stabilized Hgb level; and   re-estimating the patient-specific values for each of the plurality of parameters of the biophysical simulation model to obtain an updated therapeutic dose based on the identified variations.   
     
     
         12 . The method of  claim 8 , wherein determining the therapeutic dose comprises:
 receiving a target Hgb level; and   iteratively applying the patient-specific values for each of the parameters to a series of proposed therapeutic dosages until the target Hgb is obtained.   
     
     
         13 . A method comprising:
 receiving patient-specific historical hemoglobin (Hgb) and corresponding patient-specific historical erythropoietic stimulating agent (ESA) dosage data obtained during a descriptive period;   estimating patient-specific values for each of a plurality of parameters of a model that represents a process by which red blood cells are produced in humans based on the patient-specific historical Hgb and corresponding patient-specific historical ESA dosage data;   simulating patient-specific Hgb values for a prescriptive period based on the patient-specific values; and   identifying a therapeutic dose of the ESA that maintains the patient-specific simulated Hgb values in a target range during the prescriptive phase.   
     
     
         14 . The system of  claim 1 , wherein the parameters include one or more of a Blast Forming Unit Input, a Colony Forming Unit Survival, a Recticulocyte Survival, an Erythropoietin Receptor Multiplier, a Red Blood Cell Lifespan, and an Erythropoietin Setup Rate. 
     
     
         15 . A method comprising:
 receiving patient-specific historical hemoglobin (Hgb) and corresponding patient-specific historical erythropoietic stimulating agent (ESA) dosage data;   optimizing patient-specific values for each of a plurality of parameters of a model that represents a process by which red blood cells are produced in humans to determine a best fit with the patient-specific historical Hgb and corresponding patient-specific historical ESA dosage data; and   determining a therapeutic dose of the ESA that maintains a patient-specific simulated Hgb values in a target range.