PK/PD Model for ESA Dosing Stability

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Solution Overview

Problem

Maintaining stable haemoglobin levels in patients receiving erythropoiesis stimulating agents (ESAs) is challenging due to the oscillation of haemoglobin values outside target ranges when dose adjustments are made before achieving a steady state, leading to inefficient clinical resource utilization and suboptimal treatment outcomes.

Innovation Solution

A computer-implemented method and device for predicting haemoglobin concentration or mass at a later time point after ESA administration, which corrects for overhydration and considers various physiological factors to determine optimal ESA and iron dosing, thereby stabilizing haemoglobin levels within target ranges.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If EPO dose is adjusted monthly based on Hb measurements, then Hb levels can be monitored and controlled, but Hb values oscillate outside target ranges and clinical resources are inefficiently utilized

Engineering Contradiction:
ImproveHb level stabilityVSAvoidResponse time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by using a pharmacokinetic/pharmacodynamic (PK/PD) model to predict future Hb levels before the next measurement point. The model extrapolates Hb concentration trends based on previous measurements and EPO dosing history, allowing clinicians to anticipate Hb levels at the next monitoring point and adjust doses proactively rather than reactively, thereby preventing oscillations and reducing unnecessary dose adjustments.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If EPO dose is changed before achieving steady state, then Hb monitoring can be responsive, but Hb oscillates to values outside target range

Engineering Contradiction:
ImproveTreatment efficiencyVSAvoidHb concentration stability
Core Design Contradiction:
ProductivityVSStability of the object's composition

Solution Approach 1:

The patent implements feedback control by using the PK/PD model to continuously predict Hb levels based on actual measurements and dosing history. The predicted Hb values feed back into the dosing decision process, allowing the system to optimize EPO dosing to maintain Hb within target ranges. This closed-loop approach prevents oscillations by adjusting doses based on predicted rather than just historical data.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent applies parameter changes by utilizing the PK/PD model to transform raw Hb measurement data and dosing history into predicted future Hb levels. This parameter transformation allows clinicians to see the projected impact of current dosing decisions and adjust dosing parameters (dose amount, frequency) to achieve desired Hb stability, converting reactive dose adjustments into proactive optimized dosing.

Inventive Principle:
Principle #35Parameter changes

3Measurement precision

If frequent Hb monitoring is performed, then Hb levels can be closely tracked, but clinical resources are continuously consumed

Engineering Contradiction:
ImproveHb level monitoring accuracyVSAvoidClinical resource consumption
Core Design Contradiction:
Measurement precisionVSLoss of energy

Solution Approach 1:

The patent applies copying by creating a virtual representation of the patient's Hb level trajectory through the PK/PD model. Instead of relying solely on physical blood measurements, the model generates a predicted Hb concentration curve that copies and extrapolates the actual Hb behavior. This virtual copy allows clinicians to monitor Hb trends continuously without performing frequent physical measurements, reducing resource consumption while maintaining monitoring precision.

Inventive Principle:
Principle #26Copying

Data Source

PatentEP2550531B1Methods and apparatuses for predicting the effects of erythropoesis stimulating agents (ESA), and for determining a dose to be administered
Publication Date: 2017.05.31 FRESENIUS MEDICAL CARE DEUTSCHLAND GMBH
  • EP2550531B1 patent drawingFigure 1
  • EP2550531B1 patent drawingFigure 2
  • EP2550531B1 patent drawingFigure 3

AI summary

The present invention relates to a method for predicting the concentration or the mass of haemoglobin or an approximation thereof, respectively, in a body fluid and/or an extracorporeal sample thereof of a patient at a later, second point of time, the patient having theoretically or in reality been administered a certain dose of an erythropoesis stimulating agent at an earlier, first point of time. It relates further to a method for determining the dose of an erythropoesis stimulating agent to be administered to a patient, to a method for determining whether a patient is affected by circumstances leading to the loss of haemoglobin, to corresponding devices and to an erythropoesis stimulating medicament for use in the treatment of anemia. Finally the present invention relates to corresponding means, digital storage means, a computer program product, and a computer program.