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We consider parameter estimation of ordinary differential equation (ODE) models from noisy observations. For this problem, one conventional approach is to fit numerical solutions (e.g., Euler, Runge--Kutta) of ODEs to data. However, such a method does not account for the discretization error in numerical solutions and has limited estimation accuracy. In this study, we develop an estimation method that quantifies the discretization error based on data. The key idea is to model the discretization error as random variables and estimate their variance simultaneously with the ODE parameter. The proposed method has the form of iteratively reweighted least squares, where the discretization error variance is updated with the isotonic regression algorithm and the ODE parameter is updated by solving a weighted least squares problem using the adjoint system. Experimental results demonstrate that the proposed method attains robust estimation with at least comparable accuracy to the conventional method by successfully quantifying the reliability of the numerical solutions.
We propose a time-implicit, finite-element based space-time discretization of the necessary and sufficient optimality conditions for the stochastic linear-quadratic optimal control problem with the stochastic heat equation driven by linear noise of type $[X(t)+sigma(t)]dW(t)$, and prove optimal convergence w.r.t. both, space and time discretization parameters. In particular, we employ the stochastic Riccati equation as a proper analytical tool to handle the linear noise, and thus extend the applicability of the earlier work [16], where the error analysis was restricted to additive noise.
We present a parameter estimation method for nonlinear mixed effect models based on ordinary differential equations (NLME-ODEs). The method presented here aims at regularizing the estimation problem in presence of model misspecifications, practical identifiability issues and unknown initial conditions. For doing so, we define our estimator as the minimizer of a cost function which incorporates a possible gap between the assumed model at the population level and the specific individual dynamic. The cost function computation leads to formulate and solve optimal control problems at the subject level. This control theory approach allows to bypass the need to know or estimate initial conditions for each subject and it regularizes the estimation problem in presence of poorly identifiable parameters. Comparing to maximum likelihood, we show on simulation examples that our method improves estimation accuracy in possibly partially observed systems with unknown initial conditions or poorly identifiable parameters with or without model error. We conclude this work with a real application on antibody concentration data after vaccination against Ebola virus coming from phase 1 trials. We use the estimated model discrepancy at the subject level to analyze the presence of model misspecification.
We propose a forecasting method for predicting epidemiological health series on a two-week horizon at the regional and interregional resolution. The approach is based on model order reduction of parametric compartmental models, and is designed to accommodate small amount of sanitary data. The efficiency of the method is shown in the case of the prediction of the number of infected and removed people during the two pandemic waves of COVID-19 in France, which have taken place approximately between February and November 2020. Numerical results illustrate the promising potential of the approach.
Classical a posteriori error analysis for differential equations quantifies the error in a Quantity of Interest (QoI) which is represented as a bounded linear functional of the solution. In this work we consider a posteriori error estimates of a quantity of interest that cannot be represented in this fashion, namely the time at which a threshold is crossed for the first time. We derive two representations for such errors and use an adjoint-based a posteriori approach to estimate unknown terms that appear in our representation. The first representation is based on linearizations using Taylors Theorem. The second representation is obtained by implementing standard root-finding techniques. We provide several examples which demonstrate the accuracy of the methods. We then embed these error estimates within a framework to provide error bounds on a cumulative distribution function when parameters of the differential equations are uncertain.
This paper introduces a general framework for survival analysis based on ordinary differential equations (ODE). Specifically, this framework unifies many existing survival models, including proportional hazards models, linear transformation models, accelerated failure time models, and time-varying coefficient models as special cases. Such a unified framework provides a novel perspective on modeling censored data and offers opportunities for designing new and more flexible survival model structures. Further, the aforementioned existing survival models are traditionally estimated by procedures that suffer from lack of scalability, statistical inefficiency, or implementation difficulty. Based on well-established numerical solvers and sensitivity analysis tools for ODEs, we propose a novel, scalable, and easy-to-implement general estimation procedure that is applicable to a wide range of models. In particular, we develop a sieve maximum likelihood estimator for a general semi-parametric class of ODE models as an illustrative example. We also establish a general sieve M-theorem for bundled parameters and show that the proposed sieve estimator is consistent and asymptotically normal, and achieves the semi-parametric efficiency bound. The finite sample performance of the proposed estimator is examined in simulation studies and a real-world data example.