Development and Validation of the Michigan Chronic Disease Simulation Model (MICROSIM)

Abstract

Strategies to prevent or delay Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) are urgently needed. Blood pressure (BP) management is a promising strategy for AD/ADRD prevention and the key element in the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet the effects of different population level BP control strategies across the life course on AD/ADRD are not known. Large-scale randomized controlled trials are the least biased approach to identifying the effect of BP control on AD/ADRD, yet trials may be infeasible due to the need for prolonged follow-up and very large sample sizes. Thus, simulation analyses leveraging the best available observational data may be the best and most practical approach to answering these questions. In this manuscript, we describe the design principles, implementation details, and population-level validation of a novel population health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP COG) study of the effect of BP levels over the life course on cognitive decline and dementia. MICROSIM was designed by applying computer programming best practices to create a novel simulation model. The initial purpose of this extensible, open-source framework is to explore a series of questions related to the impact of different blood pressure management strategies on late-life cognition and all-cause dementia, as well as the effects on race differences in all-cause dementia incidence. Ultimately, though, the framework is designed to be extensible such that a variety of different clinical conditions could be added to the framework.

Effect of Population-Level Blood Pressure Treatment Strategies on Cardiovascular and Cognitive Outcomes

“…12 Michigan Chronic Disease Simulation Model's design is summarized in the Supplemental Methods and detailed elsewhere. 13 We evaluated 2 separate BP treatment strategies compared with usual care, one based on universal implementation of the Eighth Joint National Committee (JNC-8) guidelines and another based on universal implementation of SPRINT (Systolic Blood Pressure Intervention Trial), both compared with usual care. Details of both algorithms are summarized in the Supplemental Methods.…”

Development and validation of the Michigan Chronic Disease Simulation Model (MICROSIM)

“…Transparency-the mere possibility that other groups will assess one's codebase incentivizes coders to program carefully and ensure the code is readable and coherent. The entire MICROSIM codebase [12], including the notebooks used to develop MICROSIM's inputs and the notebooks used for the validation analyses [13] presented in this manuscript, are all publicly available on GitHub [12]. Opening the repository to other investigators also broadens the user base and thereby increases the likelihood of identifying errors in the simulation and improving the rigor and reproducibility of the simulation.…”

“…MICROSIM is a population and individual-based Monte Carlo simulation using varying regression-based models (e.g., logistic regression for binary outcomes, Cox regression for time-to-event data) to model annual transition probabilities in risk factors and outcomes [12]. MICROSIM is designed to enable the direct application of data from common clinical and epidemiological data sources to disentangle the complex interaction, at the individual level, between competing forces across heterogeneous individuals and understand population-level effects by aggregating across individuals.…”