Bayesian Pharmacokinetic Model for Hemophilia Dosing

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Solution Overview

Problem

Current treatment regimens for patients with low levels of clotting factor VIII, such as those with hemophilia A, require frequent infusions of therapeutic plasma protein to maintain adequate levels, which can be stressful for patients and healthcare facilities, and often involve multiple blood draws to determine individual pharmacokinetic profiles, leading to variability in dosing and potential bleeding risks.

Innovation Solution

A system and method using a Bayesian model to determine a therapeutic plasma protein dosing regime based on pharmacokinetic profiles of sampled patients, incorporating patient-specific characteristics like age and body weight, to optimize dosing intervals and levels, reducing the need for frequent blood draws and infusions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If frequent infusions of therapeutic plasma protein are administered to maintain adequate clotting factor levels, then patient safety and reliability of treatment are improved, but patient stress and healthcare facility burden increase

Engineering Contradiction:
Improvemaintenance of adequate clotting factor levelsVSAvoidpatient stress and facility burden
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent applies parameter changes by using population pharmacokinetic data to determine individualized dosing parameters (dose amount, dosing interval) based on patient characteristics such as body weight, age, and gender. This allows optimization of treatment parameters to maintain adequate clotting factor levels while minimizing infusion frequency, thereby reducing patient stress and facility burden while preserving treatment reliability

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If multiple blood draws are performed to determine individual pharmacokinetic profiles, then dosing precision is improved, but patient stress and time requirements increase

Engineering Contradiction:
Improvedetermination of individual pharmacokinetic profileVSAvoidtime for multiple blood draws and facility visits
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent applies partial action by using a reduced number of blood draws (as few as one or two) combined with population pharmacokinetic data to estimate individual pharmacokinetic parameters. This partial measurement approach, supplemented by computational modeling, achieves sufficient dosing precision without requiring extensive blood sampling, thereby reducing time loss and patient burden

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The patent uses population pharmacokinetic data and computational models as intermediaries to bridge the gap between limited individual patient data and accurate dosing recommendations. These intermediaries allow derivation of individualized pharmacokinetic profiles from minimal patient-specific measurements, reducing the need for multiple blood draws while maintaining dosing precision

Inventive Principle:
Principle #24Intermediary (Mediator)

3Ease of operation

If standardized dosing regimens are used for all patients, then ease of administration is improved, but dosing accuracy and individual patient optimization deteriorate

Engineering Contradiction:
Improvesimplicity of dosing regimenVSAvoiddosing accuracy
Core Design Contradiction:
Ease of operationVSManufacturing precision

Solution Approach 1:

The patent applies dynamics by creating adaptable dosing regimens that are customized for each patient based on their specific pharmacokinetic parameters derived from population data and individual measurements. The system dynamically adjusts dosing recommendations according to patient characteristics, metabolism rate, and desired trough levels, providing both simplicity through algorithmic calculation and precision through individualization

Inventive Principle:
Principle #15Dynamics

Data Source

PatentEP3879534A1Providing a pharmacokinetic drug dosing regime
Publication Date: 2021.09.15 TAKEDA PHARMA CO LTD
  • EP3879534A1 patent drawingFigure 1
  • EP3879534A1 patent drawingFigure 2
  • EP3879534A1 patent drawingFigure 3

AI summary

A system and method for providing a therapeutic plasma protein dosing regime includes determining a pharmacokinetic profile of a patient using a Bayesian model of pharmacokinetic profiles of sampled patients. The example system and method also include determining a first dosing regime for a first specified dosing interval including (i) a first dosage and (ii) a first therapeutic plasma protein level in the patient over a time period based at least upon the pharmacokinetic profile and determining a second dosing regime for a second specified dosing interval including (i) a second dosage and (ii) a second therapeutic plasma protein level in the patient over the time period based at least upon the pharmacokinetic profile. The example system and method further include displaying the first dosing regime and the second dosing regime on a client device such that the first dosing regime is displayed in conjunction with the second dosing regime.