arXiv subjects

Daniela De Angelis

Publications and source records attributed to Daniela De Angelis.

33 records · Page 2Linked to original sources

arXiv2019

Implications for HIV elimination by 2030 of recent trends in undiagnosed infection in England: an evidence synthesis

A target to eliminate Human Immuno-deficiency Virus (HIV) transmission in England by 2030 was set in early 2019. Estimates of recent trends in HIV prevalence, particularly the number of people living with undiagnosed HIV, by exposure group, ethnicity, gender, age group and region, are essential to monitor progress towards elimination. A Bayesian synthesis of evidence from multiple surveillance, demographic and survey datasets relevant to HIV in England is employed to estimate trends in: the number of people living with HIV (PLWH); the proportion of these people unaware of their HIV infection; and the corresponding prevalence of undiagnosed HIV. All estimates are stratified by exposure group, ethnicity, gender, age group (15-34, 35-44, 45-59, 60-74), region (London, outside London) and year (2012-2017). The total number of PLWH aged 15-74 in England increased from 82,400 (95% credible interval, CrI, 78,700 to 89,100) in 2012 to 89,500 (95% CrI 87,400 to 93,300) in 2017. The proportion diagnosed steadily increased from 84% (95% CrI 77 to 88%) to 92% (95% CrI 89 to 94%) over the same time period, corresponding to a halving in the number of undiagnosed infections from 13,500 (95% CrI 9,800 to 20,200) to 6,900 (95% CrI 4,900 to 10,700). This decrease is equivalent to a halving in prevalence of undiagnosed infection and is reflected in all sub-groups of gay, bisexual and other men who have sex with men and most sub-groups of black African heterosexuals. However, decreases were not detected for some sub-groups of other ethnicity heterosexuals, particularly outside London. In 2016, the Joint United Nations Programme on HIV/ AIDS target of diagnosing 90% of people living with HIV was reached in England. To achieve HIV elimination by 2030, current testing efforts should be enhanced to address the numbers of heterosexuals living with undiagnosed HIV, especially outside London.

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arXiv2019

Efficient real-time monitoring of an emerging influenza epidemic: how feasible?

A prompt public health response to a new epidemic relies on the ability to monitor and predict its evolution in real time as data accumulate. The 2009 A/H1N1 outbreak in the UK revealed pandemic data as noisy, contaminated, potentially biased, and originating from multiple sources. This seriously challenges the capacity for real-time monitoring. Here we assess the feasibility of real-time inference based on such data by constructing an analytic tool combining an age-stratified SEIR transmission model with various observation models describing the data generation mechanisms. As batches of data become available, a sequential Monte Carlo (SMC) algorithm is developed to synthesise multiple imperfect data streams, iterate epidemic inferences and assess model adequacy amidst a rapidly evolving epidemic environment, substantially reducing computation time in comparison to standard MCMC, to ensure timely delivery of real-time epidemic assessments. In application to simulated data designed to mimic the 2009 A/H1N1 epidemic, SMC is shown to have additional benefits in terms of assessing predictive performance and coping with parameter non-identifiability.

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arXiv2018

MultiBUGS: A parallel implementation of the BUGS modelling framework for faster Bayesian inference

MultiBUGS (https://www.multibugs.org) is a new version of the general-purpose Bayesian modelling software BUGS that implements a generic algorithm for parallelising Markov chain Monte Carlo (MCMC) algorithms to speed up posterior inference of Bayesian models. The algorithm parallelises evaluation of the product-form likelihoods formed when a parameter has many children in the directed acyclic graph (DAG) representation; and parallelises sampling of conditionally-independent sets of parameters. A heuristic algorithm is used to decide which approach to use for each parameter and to apportion computation across computational cores. This enables MultiBUGS to automatically parallelise the broad range of statistical models that can be fitted using BUGS-language software, making the dramatic speed-ups of modern multi-core computing accessible to applied statisticians, without requiring any experience of parallel programming. We demonstrate the use of MultiBUGS on simulated data designed to mimic a hierarchical e-health linked-data study of methadone prescriptions including 425,112 observations and 20,426 random effects. Posterior inference for the e-health model takes several hours in existing software, but MultiBUGS can perform inference in only 28 minutes using 48 computational cores.

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arXiv2018

Analysing Multiple Epidemic Data Sources

Evidence-based knowledge of infectious disease burden, including prevalence, incidence, severity and transmission, in different population strata and locations, and possibly in real time, is crucial to the planning and evaluation of public health policies. Direct observation of a disease process is rarely possible. However, latent characteristics of an epidemic and its evolution can often be inferred from the synthesis of indirect information from various routine data sources, as well as expert opinion. The simultaneous synthesis of multiple data sources, often conveniently carried out in a Bayesian framework, poses a number of statistical and computational challenges: the heterogeneity in type, relevance and granularity of the data, together with selection and informative observation biases, lead to complex probabilistic models that are difficult to build and fit, and challenging to criticize. Using motivating case studies of influenza, this chapter illustrates the cycle of model development and criticism in the context of Bayesian evidence synthesis, highlighting the challenges of complex model building, computationally efficient inference, and conflicting evidence.

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arXiv2017

Exploiting routinely collected severe case data to monitor and predict influenza outbreaks

Influenza remains a significant burden on health systems. Effective responses rely on the timely understanding of the magnitude and the evolution of an outbreak. For monitoring purposes, data on severe cases of influenza in England are reported weekly to Public Health England. These data are both readily available and have the potential to provide valuable information to estimate and predict the key transmission features of seasonal and pandemic influenza. We propose an epidemic model that links the underlying unobserved influenza transmission process to data on severe influenza cases. Within a Bayesian framework, we infer retrospectively the parameters of the epidemic model for each seasonal outbreak from 2012 to 2015, including: the effective reproduction number; the initial susceptibility; the probability of admission to intensive care given infection; and the effect of school closure on transmission. The model is also implemented in real time to assess whether early forecasting of the number of admission to intensive care is possible. Our model of admissions data allows reconstruction of the underlying transmission dynamics revealing: increased transmission during the season 2013/14 and a noticeable effect of Christmas school holiday on disease spread during season 2012/13 and 2014/15. When information on the initial immunity of the population is available, forecasts of the number of admissions to intensive care can be substantially improved. Readily available severe case data can be effectively used to estimate epidemiological characteristics and to predict the evolution of an epidemic, crucially allowing real-time monitoring of the transmission and severity of the outbreak.

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arXiv2017

Conflict diagnostics for evidence synthesis in a multiple testing framework

Evidence synthesis models that combine multiple datasets of varying design, to estimate quantities that cannot be directly observed, require the formulation of complex probabilistic models that can be expressed as graphical models. An assessment of whether the different datasets synthesised contribute information that is consistent with each other, and in a Bayesian context, with the prior distribution, is a crucial component of the model criticism process. However, a systematic assessment of conflict suffers from the multiple testing problem, through testing for conflict at multiple locations in a model. We demonstrate the systematic use of conflict diagnostics, while accounting for the multiple hypothesis tests of no conflict at each location in the graphical model. The method is illustrated by a network meta-analysis to estimate treatment effects in smoking cessation programs and an evidence synthesis to estimate HIV prevalence in Poland.

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arXiv2017

Joining and splitting models with Markov melding

Analysing multiple evidence sources is often feasible only via a modular approach, with separate submodels specified for smaller components of the available evidence. Here we introduce a generic framework that enables fully Bayesian analysis in this setting. We propose a generic method for forming a suitable joint model when joining submodels, and a convenient computational algorithm for fitting this joint model in stages, rather than as a single, monolithic model. The approach also enables splitting of large joint models into smaller submodels, allowing inference for the original joint model to be conducted via our multi-stage algorithm. We motivate and demonstrate our approach through two examples: joining components of an evidence synthesis of A/H1N1 influenza, and splitting a large ecology model.

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arXiv2017

Quantifying the recency of HIV infection using multiple longitudinal biomarkers

Knowledge of the time at which an HIV-infected individual seroconverts, when the immune system starts responding to HIV infection, plays a vital role in the design and implementation of interventions to reduce the impact of the HIV epidemic. A number of biomarkers have been developed to distinguish between recent and long-term HIV infection, based on the antibody response to HIV. To quantify the recency of infection at an individual level, we propose characterising the growth of such biomarkers from observations from a panel of individuals with known seroconversion time, using Bayesian mixed effect models. We combine this knowledge of the growth patterns with observations from a newly diagnosed individual, to estimate the probability seroconversion occurred in the X months prior to diagnosis. We explore, through a simulation study, the characteristics of different biomarkers that affect our ability to estimate recency, such as the growth rate. In particular, we find that predictive ability is improved by using joint models of two biomarkers, accounting for their correlation, rather than univariate models of single biomarkers.

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arXiv2017

Evidence synthesis for stochastic epidemic models

In recent years the role of epidemic models in informing public health policies has progressively grown. Models have become increasingly realistic and more complex, requiring the use of multiple data sources to estimate all quantities of interest. This review summarises the different types of stochastic epidemic models that use evidence synthesis and highlights current challenges.

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arXiv2017

Value of Information: Sensitivity Analysis and Research Design in Bayesian Evidence Synthesis

Suppose we have a Bayesian model which combines evidence from several different sources. We want to know which model parameters most affect the estimate or decision from the model, or which of the parameter uncertainties drive the decision uncertainty. Furthermore we want to prioritise what further data should be collected. These questions can be addressed by Value of Information (VoI) analysis, in which we estimate expected reductions in loss from learning specific parameters or collecting data of a given design. We describe the theory and practice of VoI for Bayesian evidence synthesis, using and extending ideas from health economics, computer modelling and Bayesian design. The methods are general to a range of decision problems including point estimation and choices between discrete actions. We apply them to a model for estimating prevalence of HIV infection, combining indirect information from several surveys, registers and expert beliefs. This analysis shows which parameters contribute most of the uncertainty about each prevalence estimate, and provides the expected improvements in precision from collecting specific amounts of additional data.

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arXiv2015

Reconstructing transmission trees for communicable diseases using densely sampled genetic data

Whole genome sequencing of pathogens from multiple hosts in an epidemic offers the potential to investigate who infected whom with unparalleled resolution, potentially yielding important insights into disease dynamics and the impact of control measures. We considered disease outbreaks in a setting with dense genomic sampling, and formulated stochastic epidemic models to investigate person-to-person transmission, based on observed genomic and epidemiological data. We constructed models in which the genetic distance between sampled genotypes depends on the epidemiological relationship between the hosts. A data augmented Markov chain Monte Carlo algorithm was used to sample over the transmission trees, providing a posterior probability for any given transmission route. We investigated the predictive performance of our methodology using simulated data, demonstrating high sensitivity and specificity, particularly for rapidly mutating pathogens with low transmissibility. We then analyzed data collected during an outbreak of methicillin-resistant Staphylococcus aureus in a hospital, identifying probable transmission routes and estimating epidemiological parameters. Our approach overcomes limitations of previous methods, providing a framework with the flexibility to allow for unobserved infection times, multiple independent introductions of the pathogen, and within-host genetic diversity, as well as allowing forward simulation.

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arXiv2015

Synthesising evidence to estimate pandemic (2009) A/H1N1 influenza severity in 2009-2011

Knowledge of the severity of an influenza outbreak is crucial for informing and monitoring appropriate public health responses, both during and after an epidemic. However, case-fatality, case-intensive care admission and case-hospitalisation risks are difficult to measure directly. Bayesian evidence synthesis methods have previously been employed to combine fragmented, under-ascertained and biased surveillance data coherently and consistently, to estimate case-severity risks in the first two waves of the 2009 A/H1N1 influenza pandemic experienced in England. We present in detail the complex probabilistic model underlying this evidence synthesis, and extend the analysis to also estimate severity in the third wave of the pandemic strain during the 2010/2011 influenza season. We adapt the model to account for changes in the surveillance data available over the three waves. We consider two approaches: (a) a two-stage approach using posterior distributions from the model for the first two waves to inform priors for the third wave model; and (b) a one-stage approach modelling all three waves simultaneously. Both approaches result in the same key conclusions: (1) that the age-distribution of the case-severity risks is "u"-shaped, with children and older adults having the highest severity; (2) that the age-distribution of the infection attack rate changes over waves, school-age children being most affected in the first two waves and the attack rate in adults over 25 increasing from the second to third waves; and (3) that when averaged over all age groups, case-severity appears to increase over the three waves. The extent to which the final conclusion is driven by the change in age-distribution of those infected over time is subject to discussion.

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arXiv2014

Estimation of HIV Burden through Bayesian Evidence Synthesis

Planning, implementation and evaluation of public health policies to control the human immunodeficiency virus (HIV) epidemic require regular monitoring of disease burden. This includes the proportion living with HIV, whether diagnosed or not, and the rate of new infections in the general population and in specific risk groups and regions. Estimation of these quantities is not straightforward: data informing them directly are not typically available, but a wealth of indirect information from surveillance systems and ad hoc studies can inform functions of these quantities. In this paper we show how the estimation problem can be successfully solved through a Bayesian evidence synthesis approach, relaxing the focus on "best available" data to which classical methods are typically restricted. This more comprehensive and flexible use of evidence has led to the adoption of our proposed approach as the official method to estimate HIV prevalence in the United Kingdom since 2005.

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arXiv2013

Conflict Diagnostics in Directed Acyclic Graphs, with Applications in Bayesian Evidence Synthesis

Complex stochastic models represented by directed acyclic graphs (DAGs) are increasingly employed to synthesise multiple, imperfect and disparate sources of evidence, to estimate quantities that are difficult to measure directly. The various data sources are dependent on shared parameters and hence have the potential to conflict with each other, as well as with the model. In a Bayesian framework, the model consists of three components: the prior distribution, the assumed form of the likelihood and structural assumptions. Any of these components may be incompatible with the observed data. The detection and quantification of such conflict and of data sources that are inconsistent with each other is therefore a crucial component of the model criticism process. We first review Bayesian model criticism, with a focus on conflict detection, before describing a general diagnostic for detecting and quantifying conflict between the evidence in different partitions of a DAG. The diagnostic is a p-value based on splitting the information contributing to inference about a "separator" node or group of nodes into two independent groups and testing whether the two groups result in the same inference about the separator node(s). We illustrate the method with three comprehensive examples: an evidence synthesis to estimate HIV prevalence; an evidence synthesis to estimate influenza case-severity; and a hierarchical growth model for rat weights.

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arXiv2012

Modeling of the HIV infection epidemic in the Netherlands: A multi-parameter evidence synthesis approach

Multi-parameter evidence synthesis (MPES) is receiving growing attention from the epidemiological community as a coherent and flexible analytical framework to accommodate a disparate body of evidence available to inform disease incidence and prevalence estimation. MPES is the statistical methodology adopted by the Health Protection Agency in the UK for its annual national assessment of the HIV epidemic, and is acknowledged by the World Health Organization and UNAIDS as a valuable technique for the estimation of adult HIV prevalence from surveillance data. This paper describes the results of utilizing a Bayesian MPES approach to model HIV prevalence in the Netherlands at the end of 2007, using an array of field data from different study designs on various population risk subgroups and with a varying degree of regional coverage. Auxiliary data and expert opinion were additionally incorporated to resolve issues arising from biased, insufficient or inconsistent evidence. This case study offers a demonstration of the ability of MPES to naturally integrate and critically reconcile disparate and heterogeneous sources of evidence, while producing reliable estimates of HIV prevalence used to support public health decision-making.

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