ESA Mortality Risk Prediction via Hemoglobin Degradation Rate

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Solution Overview

Problem

Current methods for treating anemia with Erythropoiesis Stimulating Agents (ESAs) in patients with cancer, chemotherapy, chronic kidney disease (CKD), or chronic inflammation lack the ability to accurately predict individual patient responses, leading to adverse events such as mortality and thromboembolic events due to insufficient sensitivity in baseline parameters and lack of patient-specific predictive values.

Innovation Solution

A method involving the determination of individual hemoglobin degradation rate, ESA binding sites, and ESA dose to calculate an accumulated risk factor, which stratifies patients into high or low risk groups for adverse events, using a non-linear dynamic pharmacokinetic ESA-EPO-R pathway model to assess ESA binding properties and hemoglobin production.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If linear or logistic regression models are used to predict patient responses from clinical markers, then prediction capability is provided, but sensitivity for individualized prediction is insufficient

Engineering Contradiction:
Improveprediction sensitivityVSAvoidindividualized prediction reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent changes from using standard clinical markers to using dynamic Hb degradation rate and ESA binding site number as predictive parameters. This parameter transformation enables individualized prediction by capturing patient-specific physiological responses to ESA treatment, thereby improving both prediction sensitivity and reliability for mortality risk assessment.

Inventive Principle:
Principle #35Parameter changes

2Device complexity

If baseline parameters and their combinations are used for prediction, then prediction approach is simple, but predictive sensitivity for individual patients is insufficient

Engineering Contradiction:
Improveprediction model complexityVSAvoidindividual prediction sensitivity
Core Design Contradiction:
Device complexityVSMeasurement precision

Solution Approach 1:

The patent performs preliminary determination of Hb degradation rate and ESA binding site number before risk assessment. This preliminary action captures individual patient characteristics early in treatment, enabling sensitive individualized prediction without requiring complex longitudinal modeling, thus balancing simplicity with predictive precision.

Inventive Principle:
Principle #10Preliminary action

3Duration of action of stationary object

If ESA treatment is continued without risk assessment, then anemia treatment continuity is maintained, but adverse events such as mortality and thromboembolic events occur

Engineering Contradiction:
Improvetreatment continuityVSAvoidadverse events
Core Design Contradiction:
Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent implements feedback by continuously monitoring Hb levels to calculate Hb degradation rate and ESA binding site number, then using these parameters to assess mortality risk and adjust ESA treatment accordingly. This feedback mechanism enables treatment continuity while preventing adverse events through dynamic risk-adjusted dosing decisions.

Inventive Principle:
Principle #23Feedback

Data Source

PatentEP3355061B1Prediction-method of mortality due to treatment with erythropoiesis stimulating agents
Publication Date: 2020.11.18 DEUTES KREBSFORSCHUNGSZENT STIFTUNG DES OFFENTLICHEN RECHTS
  • EP3355061B1 patent drawingFigure 1a
  • EP3355061B1 patent drawingFigure 1b
  • EP3355061B1 patent drawingFigure 1c

AI summary

The present invention pertains to the diagnosis of a high risk of mortality or other adverse events in a patient suffering from anemia, for example anemia caused by chemotherapy, cancer or chronic inflammation such as chronic kidney disease (CKD). The invention provides means to diagnose a patient who receives Erythropoiesis Stimulating Agents (ESA) and suffer from an adverse event if the treatment with the ESA is continued. Based on the herein disclosed methods, the clinician will be able to diagnose the prevalence of a fatal event and adjust the treatment of the anemia in the patient accordingly.