Healthy Growth

Rena Eudy-Byrne
Aug 15, 2018

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Thanks!


Gates Team

  • Mike Morimoto
  • Lyn Powell
  • Thomas Peyret
Bill & Melinda Gates Foundation Healthy birth, growth and development knowledge integration (HBGDki) project provided access to data and also funded this work.


Metrum Team

  • Tim Knab
  • Kyle Baron
  • Eric Anderson
  • Matt Riggs

Systems Pharmacology

Definition: Combine knowlege of pharmacology and a physiological system to build a model with math.
Can be used to:

  • Generate hypotheses
  • Evaluate a mechanism of action or effectiveness of a new drug
  • Identify new biomarkers
  • Identify individual phenotypes that cause an [drug] intervention to work more or less well

    – eg. growth dynamics of child in Mali or Peru

Health Issue



Questions:

  • when to intervene to protect growth? Rescue growth?
  • Which individuals are more or less likely to respond to intervention?
  • What are the relative contributions of infection and nutrition to growth impairment?

Technical Issue

Problem: Existing commercial platform was mathematically robust but slow

  • Physiologically-based mathematical model was large
    • 26 differential equations & 155 parameters took 226 seconds to simulate [2 years in child with infection]
    • lacked access to high-performace computing grid
  • No user-interface
    • primary audience is clinician

Solution in R

Workflow

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\( ^{1} \) Kyle T Baron (2018). mrgsolve: Simulate from ODE-Based Population PK/PD and Systems Pharmacology Models. R package version 0.8.12. https://CRAN.R-project.org/package=mrgsolve

  • Translate model into R using mrgsolve \( ^1 \)

    • Use of Rcpp and BH Packages
    • Use of boost [c++ library]

  • http://mrgsolve.github.io

  • Reduced runtime by 96%

  • Development of Shiny App


When to treat?

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Who to treat?
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{{drawing}} Relative effects of Nutrition and Pathogen on growth?

Translation to R was a win!

  • Huge efficiency gain
    • important for optimization and shiny app
    • easy access to high performace computing
  • Streamlined the addition of UI


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BONUS!

  • Open Science Initiatives

    • Pave the way for future model development


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Gut Growth App