arXiv subjects

Antony M. Overstall

Publications and source records attributed to Antony M. Overstall.

13 recordsLinked to original sources

arXiv2025

General Bayesian L2 calibration of mathematical models

A mathematical model is a function taking certain arguments and returning a theoretical prediction of a feature of a physical system. The arguments to the mathematical model can be split into two groups; (a) controllable variables of the system; and (b) calibration parameters: unknown characteristics of the physical system that cannot be controlled or directly measured. Of interest is the estimation of the calibration parameter using physical observations. Since the mathematical model will be an inexact representation of the physical system: the aim is to estimate values for the calibration parameters to make the mathematical model ``close" to the physical system. Closeness is defined as the squared $L^2$ norm of the difference between the mathematical model and the physical system. Different Bayesian and general Bayesian methods are introduced, developed and compared for this task.

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arXiv2025

A general Bayesian approach to design adaptive clinical trials with time-to-event outcomes

Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants, use resources efficiently and allow clinically meaningful conclusions to be drawn. Adaptive clinical trials (i.e. trials that can be altered based on evidence that has accrued) are often more efficient, informative and ethical than standard or non-adaptive trials because they require fewer participants, target more promising treatments, and can stop early with sufficient evidence of effectiveness or harm. The design of adaptive trials requires the pre-specification of adaptions that are permissible throughout the conduct of the trial. Proposed adaptive designs are then usually evaluated through simulation which provides indicative metrics of performance (e.g. statistical power and type-1 error) under different scenarios. Trial simulation requires assumptions about the data generating process to be specified but correctly specifying these in practice can be difficult, particularly for new and emerging diseases. To address this, we propose an approach to design adaptive clinical trials without needing to specify the complete data generating process. To facilitate this, we consider a general Bayesian framework where inference about the treatment effect on a time-to-event outcome can be performed via the partial likelihood. As a consequence, the proposed approach to evaluate trial designs is robust to the specific form of the baseline hazard function. The benefits of this approach are demonstrated through the redesign of a recent clinical trial to evaluate whether a third dose of a vaccine provides improved protection against gastroenteritis in Australian Indigenous infants.

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arXiv2025

Optimal design of dynamic experiments for scalar-on-function linear models with application to a biopharmaceutical study

A Bayesian optimal experimental design framework is developed for experiments where settings of one or more variables, referred to as profile variables, can be functions. For this type of experiment, a design consists of combinations of functions for each run of the experiment. Within a scalar-on-function linear model, profile variables are represented through basis expansions. This allows finite-dimensional representation of the profile variables and optimal designs to be found. The approach enables control over the complexity of the profile variables and model. The method is illustrated on a real application involving dynamic feeding strategies in an Ambr250 modular bioreactor system.

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arXiv2025

Gibbs optimal design of experiments

Bayesian optimal design is a well-established approach to planning experiments. A distribution for the responses, i.e. a statistical model, is assumed which is dependent on unknown parameters. A utility function is then specified giving gain in information in estimating the true values of the parameters, using the Bayesian posterior distribution. A Bayesian optimal design is given by maximising expectation of the utility with respect to the distribution implied by statistical model and prior distribution for the true parameter values. The approach accounts for the experimental aim, via specification of the utility, and of assumed sources of uncertainty. However, it is predicated on the statistical model being correct. Recently, a new type of statistical inference, known as Gibbs inference, has been proposed. This is Bayesian-like, i.e. uncertainty for unknown quantities is represented by a posterior distribution, but does not necessarily require specification of a statistical model. The resulting inference is less sensitive to misspecification of the statistical model. This paper introduces Gibbs optimal design: a framework for optimal design of experiments under Gibbs inference. A computational approach to find designs in practice is outlined and the framework is demonstrated on exemplars including linear models, and experiments with count and time-to-event responses.

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arXiv2022

Robust simulation design for generalized linear models in conditions of heteroscedasticity or correlation

A meta-model of the input-output data of a computationally expensive simulation is often employed for prediction, optimization, or sensitivity analysis purposes. Fitting is enabled by a designed experiment, and for computationally expensive simulations, the design efficiency is of importance. Heteroscedasticity in simulation output is common, and it is potentially beneficial to induce dependence through the reuse of pseudo-random number streams to reduce the variance of the meta-model parameter estimators. In this paper, we develop a computational approach to robust design for computer experiments without the need to assume independence or identical distribution of errors. Through explicit inclusion of the variance or correlation structures into the meta-model distribution, either maximum likelihood estimation or generalized estimating equations can be employed to obtain an appropriate Fisher information matrix. Robust designs can then be computationally sought which maximize some relevant summary measure of this matrix, averaged across a prior distribution of any unknown parameters.

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arXiv2021

Properties of using Fisher information gain for Bayesian design of experiments

The Bayesian decision-theoretic approach to design of experiments involves specifying a design (values of all controllable variables) to maximise the expected utility function (expectation with respect to the distribution of responses and parameters). For most common utility functions, the expected utility is rarely available in closed form and requires a computationally expensive approximation which then needs to be maximised over the space of all possible designs. This hinders practical use of the Bayesian approach to find experimental designs. However, recently, a new utility called Fisher information gain has been proposed. The resulting expected Fisher information gain reduces to the prior expectation of the trace of the Fisher information matrix. Since the Fisher information is often available in closed form, this significantly simplifies approximation and subsequent identification of optimal designs. In this paper, it is shown that for exponential family models, maximising the expected Fisher information gain is equivalent to maximising an alternative objective function over a reduced-dimension space, simplifying even further the identification of optimal designs. However, if this function does not have enough global maxima, then designs that maximise the expected Fisher information gain lead to non-identifiablility.

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arXiv2021

Bayesian decision-theoretic design of experiments under an alternative model

Traditionally Bayesian decision-theoretic design of experiments proceeds by choosing a design to minimise expectation of a given loss function over the space of all designs. The loss function encapsulates the aim of the experiment, and the expectation is taken with respect to the joint distribution of all unknown quantities implied by the statistical model that will be fitted to observed responses. In this paper, an extended framework is proposed whereby the expectation of the loss is taken with respect to a joint distribution implied by an alternative statistical model. Motivation for this includes promoting robustness, ensuring computational feasibility and for allowing realistic prior specification when deriving a design. To aid in exploring the new framework, an asymptotic approximation to the expected loss under an alternative model is derived, and the properties of different loss functions are established. The framework is then demonstrated on a linear regression versus full-treatment model scenario, on estimating parameters of a non-linear model under model discrepancy and a cubic spline model under an unknown number of basis functions.

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arXiv2020

Bayesian adaptive N-of-1 trials for estimating population and individual treatment effects

This article proposes a novel adaptive design algorithm that can be used to find optimal treatment allocations in N-of-1 clinical trials. This new methodology uses two Laplace approximations to provide a computationally efficient estimate of population and individual random effects within a repeated measures, adaptive design framework. Given the efficiency of this approach, it is also adopted for treatment selection to target the collection of data for the precise estimation of treatment effects. To evaluate this approach, we consider both a simulated and motivating N-of-1 clinical trial from the literature. For each trial, our methods were compared to the multi-armed bandit approach and a randomised N-of-1 trial design in terms of identifying the best treatment for each patient and the information gained about the model parameters. The results show that our new approach selects designs that are highly efficient in achieving each of these objectives. As such, we propose our Laplace-based algorithm as an efficient approach for designing adaptive N-of-1 trials.

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arXiv2019

A synthetic likelihood-based Laplace approximation for efficient design of biological processes

Complex models used to describe biological processes in epidemiology and ecology often have computationally intractable or expensive likelihoods. This poses significant challenges in terms of Bayesian inference but more significantly in the design of experiments. Bayesian designs are found by maximising the expectation of a utility function over a design space, and typically this requires sampling from or approximating a large number of posterior distributions. This renders approaches adopted in inference computationally infeasible to implement in design. Consequently, optimal design in such fields has been limited to a small number of dimensions or a restricted range of utility functions. To overcome such limitations, we propose a synthetic likelihood-based Laplace approximation for approximating utility functions for models with intractable likelihoods. As will be seen, the proposed approximation is flexible in that a wide range of utility functions can be considered, and remains computationally efficient in high dimensions. To explore the validity of this approximation, an illustrative example from epidemiology is considered. Then, our approach is used to design experiments with a relatively large number of observations in two motivating applications from epidemiology and ecology.

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arXiv2019

Bayesian design of experiments for intractable likelihood models using coupled auxiliary models and multivariate emulation

A Bayesian design is given by maximising an expected utility over a design space. The utility is chosen to represent the aim of the experiment and its expectation is taken with respect to all unknowns: responses, parameters and/or models. Although straightforward in principle, there are several challenges to finding Bayesian designs in practice. Firstly, the utility and expected utility are rarely available in closed form and require approximation. Secondly, the design space can be of high-dimensionality. In the case of intractable likelihood models, these problems are compounded by the fact that the likelihood function, whose evaluation is required to approximate the expected utility, is not available in closed form. A strategy is proposed to find Bayesian designs for intractable likelihood models. It relies on the development of an automatic, auxiliary modelling approach, using multivariate Gaussian process emulators, to approximate the likelihood function. This is then combined with a copula-based approach to approximate the marginal likelihood (a quantity commonly required to evaluate many utility functions). These approximations are demonstrated on examples of stochastic process models involving experimental aims of both parameter estimation and model comparison.

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arXiv2018

Quantifying Uncertainty in Transdimensional Markov Chain Monte Carlo Using Discrete Markov Models

Bayesian analysis often concerns an evaluation of models with different dimensionality as is necessary in, for example, model selection or mixture models. To facilitate this evaluation, transdimensional Markov chain Monte Carlo (MCMC) relies on sampling a discrete indexing variable to estimate the posterior model probabilities. However, little attention has been paid to the precision of these estimates. If only few switches occur between the models in the transdimensional MCMC output, precision may be low and assessment based on the assumption of independent samples misleading. Here, we propose a new method to estimate the precision based on the observed transition matrix of the model-indexing variable. Assuming a first order Markov model, the method samples from the posterior of the stationary distribution. This allows assessment of the uncertainty in the estimated posterior model probabilities, model ranks, and Bayes factors. Moreover, the method provides an estimate for the effective sample size of the MCMC output. In two model-selection examples, we show that the proposed approach provides a good assessment of the uncertainty associated with the estimated posterior model probabilities.

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arXiv2017

An approach for finding fully Bayesian optimal designs using normal-based approximations to loss functions

The generation of decision-theoretic Bayesian optimal designs is complicated by the significant computational challenge of minimising an analytically intractable expected loss function over a, potentially, high-dimensional design space. A new general approach for approximately finding Bayesian optimal designs is proposed which uses computationally efficient normal-based approximations to posterior summaries to aid in approximating the expected loss. This new approach is demonstrated on illustrative, yet challenging, examples including hierarchical models for blocked experiments, and experimental aims of parameter estimation and model discrimination. Where possible, the results of the proposed methodology are compared, both in terms of performance and computing time, to results from using computationally more expensive, but potentially more accurate, Monte Carlo approximations. Moreover the methodology is also applied to problems where the use of Monte Carlo approximations is computationally infeasible.

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arXiv2016

Bayesian design of experiments for generalised linear models and dimensional analysis with industrial and scientific application

The design of an experiment can be always be considered at least implicitly Bayesian, with prior knowledge used informally to aid decisions such as the variables to be studied and the choice of a plausible relationship between the explanatory variables and measured responses. Bayesian methods allow uncertainty in these decisions to be incorporated into design selection through prior distributions that encapsulate information available from scientific knowledge or previous experimentation. Further, a design may be explicitly tailored to the aim of the experiment through a decision-theoretic approach using an appropriate loss function. We review the area of decision-theoretic Bayesian design, with particular emphasis on recent advances in computational methods. For many problems arising in industry and science, experiments result in a discrete response that is well described by a member of the class of generalised linear models. We describe how Gaussian process emulation, commonly used in computer experiments, can play an important role in facilitating Bayesian design for realistic problems. A main focus is the combination of Gaussian process regression to approximate the expected loss with cyclic descent (coordinate exchange) optimisation algorithms to allow optimal designs to be found for previously infeasible problems. We also present the first optimal design results for statistical models formed from dimensional analysis, a methodology widely employed in the engineering and physical sciences to produce parsimonious and interpretable models. Using the famous paper helicopter experiment, we show the potential for the combination of Bayesian design, generalised linear models and dimensional analysis to produce small but informative experiments.

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