arXiv subjects

Andrea Gabrio

Publications and source records attributed to Andrea Gabrio.

12 recordsLinked to original sources

arXiv2026

A Bayesian Longitudinal Model for Imputing Item-Level Missing Data in Trial-Based Economic Evaluations

Trial-based economic evaluations are widely used to assess the cost-effectiveness of healthcare interventions and inform decision-making. Cost and effectiveness outcomes are typically collected using multi-item questionnaires administered at multiple time points, and are often subject to item-level missingness. In principle, imputation (i.e., replacing missing value with estimated or substituted values) should be performed at the item level to fully exploit available information. However, this is rarely implemented in practice due to several statistical challenges, including the longitudinal data structure, cross-item dependence, heterogeneous missingness patterns, and the mixture of skewed cost and count data. In this paper, we develop a Bayesian longitudinal model for imputing item-level missing data in trial-based economic evaluations that accommodates these complexities within a unified framework. The approach combines a transition-model formulation for longitudinal dependence with flexible distributional assumptions and explicit modelling of cross-item relationships, allowing item-level responses of different types to be coherently modelled over time. Motivated by a real-world trial, we demonstrate the flexibility and practical applicability of the proposed approach. We further discuss how the model can be extended to settings where data may be missing not at random.

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arXiv2026

Value-of-Information Analysis for External Validation of Risk Prediction Models in Multicenter Studies and Systematic Reviews

External validation studies have finite sample sizes, creating uncertainty about whether a prediction model's Net Benefit (NB) exceeds default strategies' NB. The expected value of perfect information (EVPI) quantifies consequences of uncertainty. Current EVPI methods focus on single studies, ignoring between-center heterogeneity. We extend EVPI and expected value of partial perfect information (EVPPI) to account for between-cluster heterogeneity in multicenter studies and meta-analyses. We distinguish between the global and local optimal strategy and between observed and unobserved clusters. We define EVPIglobal, EVPIcluster_j, EVPIcluster, and EVPPIcluster,prevalence, implemented in the MetaNB R package, and illustrate them using a systematic review across 36 centers of the ADNEX model for ovarian cancer diagnosis. Assuming one global decision regarding ADNEX adoption, there is no need for further data to confirm ADNEX is superior overall (EVPIglobal 0). Meta-analysis borrows information across observed clusters, resulting in consistent local superiority of ADNEX and nonzero but typically lower EVPIcluster_j than when considering local data alone. There is 0.03 probability default strategies are superior in unobserved centers. Eliminating uncertainty on performance and prevalence in each (EVPIcluster) would gain 1134 net avoided false positives (FP) per year, assuming 350000 tumors annually with 20% malignancies. Determining only local prevalence with certainty (EVPPIcluster, prevalence) would gain net 158 avoided FP per year. EVPI extensions disentangle sources of uncertainty and quantify the need for further validation to determine the global or locally optimal strategy. Considering uncertainty and heterogeneity in clinical utility across clusters is essential to decide whether additional validation studies are warranted.

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arXiv2026

A Bayesian Approach for Nonignorable Dropout in Bivariate Longitudinal Models

Longitudinal data collected in clinical trials are almost always incomplete due to some of the participants dropping out from the study during the planned follow-up. A common strategy to handle nonresponse expresses missingness in terms of a dropout process, which is jointly analysed with the outcome process to facilitate the formulation of the missingness assumptions. However, when the outcome is multivariate, the identification of the dropout process becomes problematic, especially when individuals have different dropout times for each type of response, and sensitivity analysis is difficult. The modelling task may be also be complicated by data complexities (e.g. skewness and spikes) which are difficult to capture through standard parametric methods. An example of this analysis framework occurs in trial-based economic evaluations, where a longitudinal bivariate response, formed by suitably-defined measures of effectiveness and costs, is analysed to inform policymakers about the cost-effectiveness of alternative interventions. We present a novel Bayesian nonparametric approach to handle a missing bivariate longitudinal outcome by jointly modelling the dropout process associated with each type of response while also taking into account the complexities of the data. We specify a flexible nonparametric model for the observed data and partially identify the distribution of the missing data with identifying restrictions conditional on the dropout indicators and sensitivity parameters. We explore alternative nonignorable scenarios through different priors for the sensitivity parameters. Our approach is motivated by, and applied to, data from a trial assessing the cost-effectiveness of a new treatment for intellectual disability and challenging behaviour.

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arXiv2024

A Bayesian modelling framework for health care resource use and costs in trial-based economic evaluations

Individual-level effectiveness and healthcare resource use (HRU) data are routinely collected in trial-based economic evaluations. While effectiveness is often expressed in terms of utility scores derived from some health-related quality of life instruments (e.g.~EQ-5D questionnaires), different types of HRU may be included. Costs are usually generated by applying unit prices to HRU data and statistical methods have been traditionally implemented to analyse costs and utilities or after combining them into aggregated variables (e.g. Quality-Adjusted Life Years). When outcome data are not fully observed, e.g. some patients drop out or only provided partial information, the validity of the results may be hindered both in terms of efficiency and bias. Often, partially-complete HRU data are handled using "ad-hoc" methods, implicitly relying on some assumptions (e.g. fill-in a zero) which are hard to justify beside the practical convenience of increasing the completion rate. We present a general Bayesian framework for the modelling of partially-observed HRUs which allows a flexible model specification to accommodate the typical complexities of the data and to quantify the impact of different types of uncertainty on the results. We show the benefits of using our approach using a motivating example and compare the results to those from traditional analyses focussed on the modelling of cost variables after adopting some ad-hoc imputation strategy for HRU data.

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arXiv2022

Linear mixed models to handle missing at random data in trial-based economic evaluations

Trial-based cost-effectiveness analyses (CEAs) are an important source of evidence in the assessment of health interventions. In these studies, cost and effectiveness outcomes are commonly measured at multiple time points, but some observations may be missing. Restricting the analysis to the participants with complete data can lead to biased and inefficient estimates. Methods, such as multiple imputation, have been recommended as they make better use of the data available and are valid under less restrictive Missing At Random (MAR) assumption. Linear mixed effects models (LMMs) offer a simple alternative to handle missing data under MAR without requiring imputations, and have not been very well explored in the CEA context. In this manuscript, we aim to familiarise readers with LMMs and demonstrate their implementation in CEA. We illustrate the approach on a randomised trial of antidepressant, and provide the implementation code in R and Stata. We hope that the more familiar statistical framework associated with LMMs, compared to other missing data approaches, will encourage their implementation and move practitioners away from inadequate methods.

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arXiv2022

A review of heath economic evaluation practice in the Netherlands: are we moving forward?

In 2016, the Dutch National Health Care Institute issued new guidelines that aggregated and updated previous recommendations on key elements for conducting economic evaluation. However, the impact on standard practice after the introduction of the guidelines in terms of design, methodology and reporting choices, is still uncertain. To assess this impact, we examine and compare key analysis components of economic evaluations conducted in the Netherlands before (2010-2015) and after (2016-2020) the introduction of the guidelines. We specifically focus on two aspects of the analysis that are crucial in determining the plausibility of the results: statistical methodology and missing data handling. Our review shows how many components of economic evaluations have changed in accordance with the new recommendations towards more transparent and advanced analytic approaches. However, potential limitations are identified in terms of the statistical software and information provided to support the choice of missing data methods.

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arXiv2020

A Bayesian framework for patient-level partitioned survival cost-utility analysis

Patient-level health economic data collected alongside clinical trials are an important component of the process of technology appraisal, with a view to informing resource allocation decisions. For end of life treatments, such as cancer treatments, modelling of cost-effectiveness/utility data may involve some form of partitioned survival analysis, where measures of health-related quality of life and survival time for both pre- and post-progression periods are combined to generate some aggregate measure of clinical benefits (e.g. quality-adjusted survival). In addition, resource use data are often collected from health records on different services from which different cost components are obtained (e.g. treatment, hospital or adverse events costs). A critical problem in these analyses is that both effectiveness and cost data present some complexities, including non-normality, spikes, and missingness, that should be addressed using appropriate methods. Bayesian modelling provides a powerful tool which has become more and more popular in the recent health economics and statistical literature to jointly handle these issues in a relatively easy way. This paper presents a general Bayesian framework that takes into account the complex relationships of trial-based partitioned survival cost-utility data, potentially providing a more adequate evidence for policymakers to inform the decision-making process. Our approach is motivated by, and applied to, a working example based on data from a trial assessing the cost-effectiveness of a new treatment for patients with advanced non-small-cell lung cancer.

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arXiv2020

Joint longitudinal models for dealing with missing at random data in trial-based economic evaluations

Health economic evaluations based on patient-level data collected alongside clinical trials~(e.g. health related quality of life and resource use measures) are an important component of the process which informs resource allocation decisions. Almost inevitably, the analysis is complicated by the fact that some individuals drop out from the study, which causes their data to be unobserved at some time point. Current practice performs the evaluation by handling the missing data at the level of aggregated variables (e.g. QALYs), which are obtained by combining the economic data over the duration of the study, and are often conducted under a missing at random (MAR) assumption. However, this approach may lead to incorrect inferences since it ignores the longitudinal nature of the data and may end up discarding a considerable amount of observations from the analysis. We propose the use of joint longitudinal models to extend standard cost-effectiveness analysis methods by taking into account the longitudinal structure and incorporate all available data to improve the estimation of the targeted quantities under MAR. Our approach is compared to popular missingness approaches in trial-based analyses, motivated by an exploratory simulation study, and applied to data from two real case studies.

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arXiv2019

Bayesian Hierarchical Models for the Prediction of Volleyball Results

Statistical modelling of sports data has become more and more popular in the recent years and different types of models have been proposed to achieve a variety of objectives: from identifying the key characteristics which lead a team to win or lose to predicting the outcome of a game or the team rankings in national leagues. Although not as popular as football or basketball, volleyball is a team sport with both national and international level competitions in almost every country. However, there is almost no study investigating the prediction of volleyball game outcomes and team rankings in national leagues. We propose a Bayesian hierarchical model for the prediction of the rankings of volleyball national teams, which also allows to estimate the results of each match in the league. We consider two alternative model specifications of different complexity which are validated using data from the women's volleyball Italian Serie A1 2017-2018 season.

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arXiv2018

A Bayesian Parametric Approach to Handle Missing Longitudinal Outcome Data in Trial-Based Health Economic Evaluations

Trial-based economic evaluations are typically performed on cross-sectional variables, derived from the responses for only the completers in the study, using methods that ignore the complexities of utility and cost data (e.g. skewness and spikes). We present an alternative and more efficient Bayesian parametric approach to handle missing longitudinal outcomes in economic evaluations, while accounting for the complexities of the data. We specify a flexible parametric model for the observed data and partially identify the distribution of the missing data with partial identifying restrictions and sensitivity parameters. We explore alternative nonignorable scenarios through different priors for the sensitivity parameters, calibrated on the observed data. Our approach is motivated by, and applied to, data from a trial assessing the cost-effectiveness of a new treatment for intellectual disability and challenging behaviour.

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arXiv2018

A Full Bayesian Model to Handle Structural Ones and Missingness in Economic Evaluations from Individual-Level Data

Economic evaluations from individual-level data are an important component of the process of technology appraisal, with a view to informing resource allocation decisions. A critical problem in these analyses is that both effectiveness and cost data typically present some complexity (e.g. non normality, spikes and missingness) that should be addressed using appropriate methods. However, in routine analyses, simple standardised approaches are typically used, possibly leading to biased inferences. We present a general Bayesian framework that can handle the complexity. We show the benefits of using our approach with a motivating example, the MenSS trial, for which there are spikes at one in the effectiveness and missingness in both outcomes. We contrast a set of increasingly complex models and perform sensitivity analysis to assess the robustness of the conclusions to a range of plausible missingness assumptions. This paper highlights the importance of adopting a comprehensive modelling approach to economic evaluations and the strategic advantages of building these complex models within a Bayesian framework.

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arXiv2016

Handling Missing Data in Within-Trial Cost-Effectiveness Analysis: a Review with Future Guidelines

Cost-Effectiveness Analyses (CEAs) alongside randomised controlled trials (RCTs) are increasingly often designed to collect resource use and preference-based health status data for the purpose of healthcare technology assessment. However, because of the way these measures are collected, they are prone to missing data, which can ultimately affect the decision of whether an intervention is good value for money. We examine how missing cost and effect outcome data are handled in RCT-based CEAs, complementing a previous review (covering 2003-2009, 88 articles) with a new systematic review (2009-2015, 81 articles) focussing on two different perspectives. First, we review the description of the missing data, the statistical methods used to deal with them, and the quality of the judgement underpinning the choice of these methods. Second, we provide guidelines on how the information about missingness and related methods should be presented to improve the reporting and handling of missing data. Our review shows that missing data in within-RCT CEAs are still often inadequately handled and the overall level of information provided to support the chosen methods is rarely satisfactory.

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