Merge pull request #1728 from ihmeuw/alzheimers-concept-model

Create Alzheimers concept model

Author: NathanielBlairStahn

docs/source/models/causes/alzheimers/index.rst

@@ -0,0 +1,33 @@
+..
+  Section title decorators for this document:
+
+  ==============
+  Document Title
+  ==============
+
+  Section Level 1 (#.0)
+  +++++++++++++++++++++
+
+  Section Level 2 (#.#)
+  ---------------------
+
+  Section Level 3 (#.#.#)
+  ~~~~~~~~~~~~~~~~~~~~~~~
+
+  Section Level 4
+  ^^^^^^^^^^^^^^^
+
+  Section Level 5
+  '''''''''''''''
+
+  The depth of each section level is determined by the order in which each
+  decorator is encountered below. If you need an even deeper section level, just
+  choose a new decorator symbol from the list here:
+  https://docutils.sourceforge.io/docs/ref/rst/restructuredtext.html#sections
+  And then add it to the list of decorators above.
+
+.. _2021_cause_alzheimers_disease:
+
+=====================
+Alzheimer's Disease
+=====================

docs/source/models/concept_models/index.rst

@@ -14,7 +14,8 @@ Active concept model documents can be found here:
    vivarium_us_cvd/concept_model
    vivarium_wasting_paper/concept_model
    vivarium_mncnh_portfolio/concept_model
-   vivarium_moud/concept_model   
+   vivarium_moud/concept_model
+   vivarium_alzheimers/concept_model
 
 A list of all (active and complete) concept model documents can be found here:
 

docs/source/models/concept_models/vivarium_alzheimers/concept_model.rst

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+..
+  Section title decorators for this document:
+
+  ==============
+  Document Title
+  ==============
+
+  Section Level 1 (#.0)
+  +++++++++++++++++++++
+
+  Section Level 2 (#.#)
+  ---------------------
+
+  Section Level 3 (#.#.#)
+  ~~~~~~~~~~~~~~~~~~~~~~~
+
+  Section Level 4
+  ^^^^^^^^^^^^^^^
+
+  Section Level 5
+  '''''''''''''''
+
+  The depth of each section level is determined by the order in which each
+  decorator is encountered below. If you need an even deeper section level, just
+  choose a new decorator symbol from the list here:
+  https://docutils.sourceforge.io/docs/ref/rst/restructuredtext.html#sections
+  And then add it to the list of decorators above.
+
+.. _2025_concept_model_vivarium_alzheimers:
+
+===============================================
+Alzheimer's Disease Early Detection Simulation
+===============================================
+
+.. contents::
+  :local:
+
+.. list-table:: Abbreviations
+  :header-rows: 1
+
+  * - Abbreviation
+    - Definition
+  * - AD
+    - Alzheimer's Disease
+  * - BBBM
+    - Blood-Based Biomarkers
+  * - CSF
+    - Cerebrospinal Fluid
+  * - MCI
+    - Mild Cognitive Impairment
+  * - PET
+    - Positron Emission Tomography
+  * - DALYs
+    - Disability-Adjusted Life Years
+  * - CSU
+    - Client Services Unit
+  * - FHS
+    - Future Health Scenarios
+
+1.0 Overview
+++++++++++++
+
+This project leverages IHME's simulation capabilities to quantify health
+and economic impacts associated with early detection and treatment of
+pre-clinical Alzheimer's disease (AD). The simulation evaluates scenarios
+involving blood-based biomarker (BBBM) testing and a hypothetical
+intervention that slows disease progression.
+
+**Basic Goals:**
+
+- Simulate the patient journey from identification through intervention
+  and outcomes
+- Compare health and economic impacts across reference and alternative
+  scenarios in 10 locations
+
+**Funding and collaboration:**
+
+We are designing this simulation in conjunction with IHME's Client
+Services Unit (CSU) with a focus on health and economic impact. Our team
+will focus on simulating the the health impacts of preclinical AD
+testing and the hypothetical intervention, and the Resource Tracking
+team will use our results to estimate the economic impacts. We will be
+using population forecasts from the Future Health Scenarios (FHS) team.
+
+2.0 Modeling Aims and Objectives
++++++++++++++++++++++++++++++++++
+
+The primary goal is to simulate the impact of early detection strategies
+for Alzheimer's disease using blood-based biomarkers and subsequent
+interventions. The simulation tracks simulants through health states
+from age ~30 to 125 years (or death), capturing progression through
+preclinical AD, mild cognitive impairment (MCI) due to AD, and three
+stages of dementia due to Alzheimer's disease.
+
+2.1 Scenarios
+-------------
+
+1. **Reference Scenario:** Present-day conditions, including current
+   cerebrospinal fluid (CSF) and amyloid-positron emission tomography
+   (PET) diagnostic pathways after clinical disease develops, but with
+   no BBBM uptake or disease-modifying therapies.
+2. **Alternative Scenario 1:** Introduction of BBBM testing for at-risk
+   preclinical populations (no intervention)
+3. **Alternative Scenario 2:** BBBM testing plus hypothetical
+   intervention that prevents, delays, or slows disease progression
+
+2.2 General Modeling Strategy
+------------------------------
+
+Based on literature and GBD, we conceive of Alzheimer's disease (AD) as
+comprising a six-stage progression:
+
+  **Susceptible → Preclinical AD → MCI due to AD → Mild AD → Moderate AD
+  → Severe AD**
+
+The last three stages correspond to the three sequelae (mild, moderate,
+severe) of the GBD cause "Alzheimer's disease and other dementias." We
+will have to separate AD out from other dementias in the GBD data, and
+we will need non-GBD data sources to inform our modeling of preclinical
+AD and MCI due to AD. Furthermore, reality may be a bit more complicated
+than the simple one-directional progression depicted above, but the
+assumption of no recovery from any state might be sufficient for our
+purposes.
+
+The basic plan for the design of the simulation is as follows:
+
+- Use forecasted population estimates
+
+  - We have data on 'population', 'deaths', 'migration', and 'births'
+    from FHS that can inform the age structure in the population out to
+    year 2100; we plan to use population and deaths forecasts, but not
+    migration or births
+  - Based on GBD data, the incidence of AD within each age group is
+    pretty stable over time, so we are **not** planning on using
+    forecasted data for Alzheimer's disease
+
+- Only simulate people who will eventually get AD (and other dementias (?))
+
+  - This drastically reduces population size and hence compute resources
+  - We will need to "work backwards" from GBD's Alzheimer's estimates
+    and the population forecasts to
+    determine how many people to add on each time step
+  - We will need to do some calculations outside the simulation to
+    account for false positive tests and people who don't progress from
+    preclinical AD or MCI to dementia due to AD
+
+- On top of the population model, we will add an Alzheimer's disease
+  progression model, a testing and diagnosis model, and a treatment
+  model, as detailed in the next section
+
+- We're doing a test run with mock-ups of all components and a full
+  population (not just simulants with AD) to get an idea of the runtime
+  for simulating 80 years in 10 locations
+
+3.0 Simulation Components
+++++++++++++++++++++++++++++++++++++
+
+.. list-table:: Simulation Components
+  :header-rows: 1
+
+  * - Component
+    - Purpose
+    - Main Features
+    - Dependencies
+  * - :ref:`Population Model <other_models_alzheimers_population>`
+    - Evolution of simulant demographics over time
+    - Influx of incident cases of preclinical AD, aging of simulants,
+      all-cause mortality
+    - Forecasted population data, age-specific incidence rates of
+      preclinical AD
+  * - :ref:`Alzheimer's Disease Model <2021_cause_alzheimers_disease>`
+    - Disease progression
+    - Transition rates through 6 stages of AD, cause-specific mortality
+    - Population model
+  * - :ref:`Testing/Diagnosis Model <intervention_alzheimers_testing_diagnosis>`
+    - BBBM and existing testing pathways
+    - Multi-modal testing, correlation between testing and disease
+      progression
+    - Disease model, population model
+  * - :ref:`Treatment Model <intervention_hypothetical_alzheimers_treatment>`
+    - Hypothetical disease-modifying therapy
+    - Reduction in progression rate, adherence
+    - Disease model, testing model
+  * - Economic Impact model
+    - Cost-effectiveness analysis
+    - Comprehensive cost modeling, ICER calculations
+    - All other modules
+
+4.0 Specifications
+++++++++++++++++++
+
+4.1 Default Parameter Specifications
+------------------------------------
+
+.. list-table:: Default Simulation Parameter Specifications
+  :header-rows: 1
+
+  * - Parameter
+    - Value
+    - Note
+  * - Locations
+    - Sweden, US, China, Japan, Brazil, UK, Germany, France, Italy,
+      Spain
+    - 10 locations of interest
+  * - Simulation start date
+    - 2025-01-01
+    -
+  * - Simulation end date
+    - 2100-12-31
+    - 76-year simulation period (forecasted data goes through year 2100)
+  * - Observation start date
+    - 2025-01-01
+    - No burn-in period
+  * - Cohort type
+    - Open
+    - Cohort consists of simulants who are in any of the 5 stages of
+      Alzheimer's disease
+  * - Sex
+    - Males & Females
+    -
+  * - Age start (Initialization)
+    - Age at which preclinical AD starts (~30 years or later)
+    - Age start is simulant-dependent
+  * - Age end (Initialization)
+    - 125 years
+    - End of oldest age group
+  * - Age start (Observation)
+    - Age at which preclinical AD starts (~30 years or later)
+    - All simulants are observed since all have AD or its precursors
+  * - Age end (Observation)
+    - 125 years or death
+    -
+  * - Population size per draw
+    - 100,000 simulants
+    -
+  * - Number of Draws
+    - 25 draws
+    -
+  * - Timestep
+    - 6 months
+    - Twice a year is sufficient to capture frequency of testing and
+      disease progression
+  * - Randomness key columns
+    - ['entrance_time', 'age', 'sex']
+    - There should be no need to modify the standard key columns
+
+4.2 Scenario Details
+------------------------
+
+.. list-table:: Scenario details
+  :header-rows: 1
+
+  * - Scenario
+    - Columns with more details go here
+    - Note
+  * - 0. Reference
+    -
+    -
+  * - 1. Testing scale-up (Alternative 1)
+    -
+    -
+  * - 2. Treatment scale-up (Alternative 2)
+    -
+    -
+
+4.3 Outputs and Observers
+--------------------------
+
+.. list-table:: Outputs of simulation observers
+  :header-rows: 1
+
+  * - Observation
+    - Default stratifications
+    - Note
+  * -
+    -
+    -
+
+5.0 Model Runs and Verification & Validation
++++++++++++++++++++++++++++++++++++++++++++++
+
+5.1 Model Runs
+------------------------
+
+.. list-table:: Model run requests
+  :header-rows: 1
+
+  * - Number
+    - Description
+    - Scenarios
+    - Directory
+    - Specification mods
+    - Stratification mods
+    - Observer mods
+  * - 0.0
+    - Mock-up run with full population and fake data to test runtime
+    -
+    -
+    -
+    -
+    -
+
+5.2 V & V Tracking
+------------------------
+
+.. list-table:: V&V Tracking
+  :header-rows: 1
+
+  * - Model number
+    - V&V plan
+    - V&V summary
+    - Link to notebook
+  * -
+    -
+    -
+    -

docs/source/models/intervention_models/alzheimers/hypothetical_treatment.rst

@@ -0,0 +1,33 @@
+..
+  Section title decorators for this document:
+
+  ==============
+  Document Title
+  ==============
+
+  Section Level 1 (#.0)
+  +++++++++++++++++++++
+
+  Section Level 2 (#.#)
+  ---------------------
+
+  Section Level 3 (#.#.#)
+  ~~~~~~~~~~~~~~~~~~~~~~~
+
+  Section Level 4
+  ^^^^^^^^^^^^^^^
+
+  Section Level 5
+  '''''''''''''''
+
+  The depth of each section level is determined by the order in which each
+  decorator is encountered below. If you need an even deeper section level, just
+  choose a new decorator symbol from the list here:
+  https://docutils.sourceforge.io/docs/ref/rst/restructuredtext.html#sections
+  And then add it to the list of decorators above.
+
+.. _intervention_hypothetical_alzheimers_treatment:
+
+========================================
+Hypothetical Alzheimer's Treatment
+========================================