Informing policy via dynamic models: Cholera in Haiti.

Public health decisions must be made about when and how to implement interventions to control an infectious disease epidemic. These decisions should be informed by data on the epidemic as well as current understanding about the transmission dynamics. Such decisions can be posed as statistical questions about scientifically motivated dynamic models. Thus, we encounter the methodological task of building credible, data-informed decisions based on stochastic, partially observed, nonlinear dynamic models. This necessitates addressing the tradeoff between biological fidelity and model simplicity, and the reality of misspecification for models at all levels of complexity. We assess current methodological approaches to these issues via a case study of the 2010-2019 cholera epidemic in Haiti. We consider three dynamic models developed by expert teams to advise on vaccination policies. We evaluate previous methods used for fitting these models, and we demonstrate modified data analysis strategies leading to improved statistical fit. Specifically, we present approaches for diagnosing model misspecification and the consequent development of improved models. Additionally, we demonstrate the utility of recent advances in likelihood maximization for high-dimensional nonlinear dynamic models, enabling likelihood-based inference for spatiotemporal incidence data using this class of models. Our workflow is reproducible and extendable, facilitating future investigations of this disease system. Author summary: Quantitative understanding of infectious disease transmission dynamics relies upon mathematical models informed by scientific knowledge and relevant data. The models aim to provide a statistical description of the trajectory of an epidemic and its uncertainty, together with a representation of the underlying biological mechanisms. Evaluation of success at these goals is necessary in order for a model to provide a reliable tool for guiding evidence-based public policy interventions. In this article, we conduct a re-analysis of the 2010–2019 cholera outbreak in Haiti. We use this case study to investigate current procedures for fitting mechanistic models to time series data, while identifying limitations of these methodologies and proposing remedies. Our analysis presents methodology for diagnosing how well a model describes observed data. Using objective measures to assess model fit ensures that our evaluation is based on quantifiable criteria. Incorporating reproducibility into this assessment results in a framework that enables the validation or refinement of model based inferences when revisiting the data, facilitating scientific discovery. Our data analysis workflow is supported by recent advances in algorithms, software and hardware, which facilitate statistical fitting of nonlinear stochastic dynamic models to observed incidence data. However, inference for high-dimensional systems remains a methodological challenge. One of the models under consideration involves spatially coupled stochastic meta-populations, and we demonstrate how a recently developed algorithm permits likelihood-based inference and model diagnostics in this setting. We contend that raising the currently accepted standards of infectious disease modeling will result in a greater ability of scientists and policy makers to understand and respond to future infectious disease outbreaks. [ABSTRACT FROM AUTHOR]