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Anne M. Presanis

Publications and source records attributed to Anne M. Presanis.

13 recordsLinked to original sources

Detecting Conflicts in Evidence Synthesis Models Using Score Discrepancies

Evidence synthesis models combine multiple data sources to estimate latent quantities of interest, enabling reliable inference on parameters that are difficult to measure directly. However, shared parameters across data sources can induce conflicts both among the data and with the assumed model structure. Detecting and quantifying such conflicts remains a challenge in model criticism. Here we propose a general framework for conflict detection in evidence synthesis models based on score discrepancies, extending prior-data conflict diagnostics to more general conflict checks in the latent space of hierarchical models. Simulation studies in an exchangeable model demonstrate that the proposed approach effectively detects between-data inconsistencies. Application to an influenza severity model illustrates its use, complementary to traditional deviance-based diagnostics, in complex real-world hierarchical settings. The proposed framework thus provides a flexible and broadly applicable tool for consistency assessment in Bayesian evidence synthesis.

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The Lifebelt Particle Filter for robust estimation from low-valued count data

Particle filtering methods can be applied to estimation problems in discrete spaces on bounded domains, to sample from and marginalise over unknown hidden states. As in continuous settings, problems such as particle degradation can arise: proposed particles can be incompatible with the data, lying in low probability regions or outside the boundary constraints, and the discrete system could result in all particles having weights of zero. In this paper we introduce the Lifebelt Particle Filter (LBPF), a novel method for robust likelihood estimation in low-valued count problems. The LBPF combines a standard particle filter with one (or more) lifebelt particles which, by construction, lie within the boundaries of the discrete random variables, and therefore are compatible with the data. A mixture of resampled and non-resampled particles allows for the preservation of the lifebelt particle, which, together with the remaining particle swarm, provides samples from the filtering distribution, and can be used to generate unbiased estimates of the likelihood. The main benefit of the LBPF is that only one or few, wisely chosen, particles are sufficient to prevent particle collapse. Differently from other methods, there is no need to increase the number of particles, and therefore the computational effort, in regions of the parameter space that generate less likely hidden states. The LBPF can be used within a pseudo-marginal scheme to draw inferences on static parameters, $ \boldsymbolθ $, governing the system. We address here the estimation of a parameter governing probabilities of deaths and recoveries of hospitalised patients during an epidemic.

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Hospitalisation risk for COVID-19 patients infected with SARS-CoV-2 variant B.1.1.7: cohort analysis

Objective: To evaluate the relationship between coronavirus disease 2019 (COVID-19) diagnosis with SARS-CoV-2 variant B.1.1.7 (also known as Variant of Concern 202012/01) and the risk of hospitalisation compared to diagnosis with wildtype SARS-CoV-2 variants. Design: Retrospective cohort, analysed using stratified Cox regression. Setting: Community-based SARS-CoV-2 testing in England, individually linked with hospitalisation data. Participants: 839,278 laboratory-confirmed COVID-19 patients, of whom 36,233 had been hospitalised within 14 days, tested between 23rd November 2020 and 31st January 2021 and analysed at a laboratory with an available TaqPath assay that enables assessment of S-gene target failure (SGTF). SGTF is a proxy test for the B.1.1.7 variant. Patient data were stratified by age, sex, ethnicity, deprivation, region of residence, and date of positive test. Main outcome measures: Hospitalisation between 1 and 14 days after the first positive SARS-CoV-2 test. Results: 27,710 of 592,409 SGTF patients (4.7%) and 8,523 of 246,869 non-SGTF patients (3.5%) had been hospitalised within 1-14 days. The stratum-adjusted hazard ratio (HR) of hospitalisation was 1.52 (95% confidence interval [CI] 1.47 to 1.57) for COVID-19 patients infected with SGTF variants, compared to those infected with non-SGTF variants. The effect was modified by age (P<0.001), with HRs of 0.93-1.21 for SGTF compared to non-SGTF patients below age 20 years, 1.29 in those aged 20-29, and 1.45-1.65 in age groups 30 years or older. Conclusions: The results suggest that the risk of hospitalisation is higher for individuals infected with the B.1.1.7 variant compared to wildtype SARS-CoV-2, likely reflecting a more severe disease. The higher severity may be specific to adults above the age of 30.

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Trends in risks of severe events and lengths of stay for COVID-19 hospitalisations in England over the pre-vaccination era: results from the Public Health England SARI-Watch surveillance scheme

Background: Trends in hospitalised case-fatality risk (HFR), risk of intensive care unit (ICU) admission and lengths of stay for patients hospitalised for COVID-19 in England over the pre-vaccination era are unknown. Methods: Data on hospital and ICU admissions with COVID-19 at 31 NHS trusts in England were collected by Public Health England's Severe Acute Respiratory Infections surveillance system and linked to death information. We applied parametric multi-state mixture models, accounting for censored outcomes and regressing risks and times between events on month of admission, geography, and baseline characteristics. Findings: 20,785 adults were admitted with COVID-19 in 2020. Between March and June/July/August estimated HFR reduced from 31.9% (95% confidence interval 30.3-33.5%) to 10.9% (9.4-12.7%), then rose steadily from 21.6% (18.4-25.5%) in September to 25.7% (23.0-29.2%) in December, with steeper increases among older patients, those with multi-morbidity and outside London/South of England. ICU admission risk reduced from 13.9% (12.8-15.2%) in March to 6.2% (5.3-7.1%) in May, rising to a high of 14.2% (11.1-17.2%) in September. Median length of stay in non-critical care increased during 2020, from 6.6 to 12.3 days for those dying, and from 6.1 to 9.3 days for those discharged. Interpretation: Initial improvements in patient outcomes, corresponding to developments in clinical practice, were not sustained throughout 2020, with HFR in December approaching the levels seen at the start of the pandemic, whilst median hospital stays have lengthened. The role of increased transmission, new variants, case-mix and hospital pressures in increasing COVID-19 severity requires urgent further investigation.

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Assessing the causal effect of binary interventions from observational panel data with few treated units

Researchers are often challenged with assessing the impact of an intervention on an outcome of interest in situations where the intervention is non-randomised, the intervention is only applied to one or few units, the intervention is binary, and outcome measurements are available at multiple time points. In this paper, we review existing methods for causal inference in these situations. We detail the assumptions underlying each method, emphasize connections between the different approaches and provide guidelines regarding their practical implementation. Several open problems are identified thus highlighting the need for future research.

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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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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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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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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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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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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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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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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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