The Reference Model for Disease Progression | Interagency Modeling and Analysis Group

What is being modeled?

Disease progression, currently COVID-19 or Diabetic Cardiovascular

Description & purpose of resource

The Reference Model is:

COVID-19 model for US states and territories
The Most Validated Cardiovascular (CVD) Diabetes Model known
A validation model that includes human interpretation
An ensemble model assembling multiple other models
A medical knowledge accumulator
United States Patent 9,858,390

The Reference Model can now:

Estimate COVID-19 parameters for US states and territories
Figure out best fitting infectiousness and mortality profiles for COVID-19
Determine CVD models that significantly behave better on several diabetic populations
Deduce that CVD probability halves every 5 years due to medicine improving - according to information from the last 3 decades
Calculate life tables for diabetics
Include human interpretation of potentially ambiguous outcome definitions
Interface with ClinicalTrials.Gov
Create an interactive map of our cumulative computational knowledge gap

Spatial scales

group/society

Temporal scales

days

weeks to months

human lifetime

This resource is currently

mature and useful in ongoing research

a demonstration or a framework to be built upon (perhaps with a sample implementation)

likely to require significant study prior to effective reuse

likely to be usable without detailed knowledge of its internals

Has this resource been validated?

Yes

How has the resource been validated?

The Reference Model is actually a validation tool that validates many other models - it is an ensemble model that optimizes multiple models and merges information to fit outcomes, interpretation, and other assumptions.

At the time of initially writing these words (March 2020) it is the most validated diabetes cardiovascular model known worldwide validating its results against 30 / 123 cohorts containing 471 validations - this number increased through the years and will continue increasing periodically when more data is added to ClinicalTrials.Gov.

The Reference Model was since then used to model COVID-19 and on July 29th, a preliminary version of the model was published validating against infection information of US states and territories. The work continued to include an ensemble of models including infectiousness, transmission, response, and mortality. The work was published as an interactive paper and as a webinar .

Link to Resource Credibility Assessment

The Reference Model for Disease Progression

Can this resource be associated with other resources? (e.g.: modular models, linked tools and platforms)

Yes

Which resources?

The model currently contains the following elements that are externally add to it:

- Risk equations: equations that predict the probability of reaching an outcome depending on multiple biomarkers such as age, male, blood pressure, cholesterol levels, A1c , etc...

- Observed Outcomes: This empirical data collected from multiple clinical trials is used as validation information. It includes value such as mortality, stroke, MI and composite endpoints such as CVD. Those numbers are either extracted manually from publications, or extracted via an interface from ClinicalTrials.Gov

The model uses the MIcro Simulation Tool (MIST) as its engine that enables it to run in High Performance Environments and it used the Amazon cloud for simulations in the past.

The Reference Model uses the Inpyred python library that enables population generation through Evolutionary Computation

The COVID-19 model uses an ensemble of models that include those:

Infectiousness Models [Link1] , [Link2] , [Link3]
Mortality models [Link1] , [Link2] , [Link3]

Most models were re-implemented in in python and publicly available in: [github repository]

It uses data from the multiple sources including:

The Covid Tracking project [link] for initialization adn validation
Age and state/territory statistics from US Census [link1],[link2].
Number of Interaction per individual according to [link1],[link2].
Apple mobility data [link] for response/behavior models

Key publications (e.g. describing or using resource)

There are over two dozen publications of the model, many as posters at the MSM-IMAG meeting starting in 2012.

The most recent publication is an interactive paper:

Jacob Barhak, The Reference Model is a Multi-Scale Ensemble Model of COVID-19. Self Published Interactive Manuscript. Publication Date: 27-May-2021 http://doi.org/10.34235/b7eaa32b-1a6b-444f-9848-76f83f5a733c

Another recent publication was uploaded to this page and provides an overview. It is an interactive poster that can be accessed through this link.

When loading interactive content, please use a strong computer/smartphone. Some interactive features require use of a mouse and will take above a minute to load on some machines. So please be patient.

Also, please visit the model portal on SimTK: https://simtk.org/projects/therefmodel

Here is a full list of publications in reverse chronological order: