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Alessandra Mattei

Publications and source records attributed to Alessandra Mattei.

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Regression-based approach for natural direct and indirect relative risk in case of multiple mediators

Mediation analysis investigates whether part of the treatment effect is channelled through one or more mediators along the causal pathway between the treatment and the primary outcome. However, the presence of multiple, potentially dependent mediators raises substantial challenges, particularly when the outcome is binary, the mediators are measured on different scales, and interactions are present. We consider on causal mediation analysis with a binary treatment and a binary outcome, defining natural direct, indirect, and total effects on the relative-risk scale, thereby avoiding the interpretational difficulties associated with non-collapsible effect measures. Under a sequential ignorability assumption, we develop a unified regression-based framework that accommodates multiple continuous, binary, or mixed mediators. The proposed framework accounts for dependence among mediators and allows for both exposure-mediator and mediator-mediator interactions. We derive closed-form expressions for the causal effects across the different mediator settings and develop a likelihood-based inference procedure for estimating the causal effects and quantifying their uncertainty. The methodology is illustrated through two empirical applications.

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Spatial vertical regression for spatial panel data: Evaluating the effect of the Florentine tramway's first line on commercial vitality

Synthetic control methods are commonly used in panel data settings to evaluate the effect of an intervention. In many of these cases, the treated and control units correspond to spatial units such as regions or neighborhoods. Our approach addresses the challenge of understanding how an intervention applied at specific locations influences the surrounding area. Traditional synthetic control applications may struggle with defining the effective area of impact, the extent of treatment propagation across space, and the variation of effects with distance from the treatment sites. To address these challenges, we introduce Spatial Vertical Regression (SVR) within the Bayesian paradigm. This innovative approach allows us to accurately predict the outcomes in varying proximities to the treatment sites, while meticulously accounting for the spatial structure inherent in the data. Specifically, rooted on the vertical regression framework of the synthetic control method, SVR employs a Gaussian process to ensure that the imputation of missing potential outcomes for areas of different distance around the treatment sites is spatially coherent, reflecting the expectation that nearby areas experience similar outcomes and have similar relationships to control areas. This approach is particularly pertinent to our study on the Florentine tramway's first line construction. We study its influence on the local commercial landscape, focusing on how business prevalence varies at different distances from the tram stops.

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Bayesian principal stratification with longitudinal data and truncation by death

In many causal studies, outcomes are censored by death, in the sense that they are neither observed nor defined for units who die. In such studies, the focus is usually on the stratum of always survivors up to a single fixed time s. Building on a recent strand of the literature, we propose an extended framework for the analysis of longitudinal studies, where units can die at different time points, and the main endpoints are observed and well defined only up to the death time. We develop a Bayesian longitudinal principal stratification framework, where units are cross classified according to the longitudinal death status. Under this framework, the focus is on causal effects for the principal strata of units that would be alive up to a time point s irrespective of their treatment assignment, where these strata may vary as a function of s. We can get precious insights into the effects of treatment by inspecting the distribution of baseline characteristics within each longitudinal principal stratum, and by investigating the time trend of both principal stratum membership and survivor-average causal effects. We illustrate our approach for the analysis of a longitudinal observational study aimed to assess, under the assumption of strong ignorability of treatment assignment, the causal effects of a policy promoting start ups on firms survival and hiring policy, where firms hiring status is censored by death.

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Evaluating causal effects on time-to-event outcomes in an RCT in Oncology with treatment discontinuation

In clinical trials, patients may discontinue treatments prematurely, breaking the initial randomization and, thus, challenging inference. Stakeholders in drug development are generally interested in going beyond the Intention-To-Treat (ITT) analysis, which provides valid causal estimates of the effect of treatment assignment but does not inform on the effect of the actual treatment receipt. Our study is motivated by an RCT in oncology, where patients assigned the investigational treatment may discontinue it due to adverse events. We propose adopting a principal stratum strategy and decomposing the overall ITT effect into principal causal effects for groups of patients defined by their potential discontinuation behavior. We first show how to implement a principal stratum strategy to assess causal effects on a survival outcome in the presence of continuous time treatment discontinuation, its advantages, and the conclusions one can draw. Our strategy deals with the time-to-event intermediate variable that may not be defined for patients who would not discontinue; moreover, discontinuation time and the primary endpoint are subject to censoring. We employ a flexible model-based Bayesian approach to tackle these complexities, providing easily interpretable results. We apply this Bayesian principal stratification framework to analyze synthetic data of the motivating oncology trial. We simulate data under different assumptions that reflect real scenarios where patients' behavior depends on critical baseline covariates. Supported by a simulation study, we shed light on the role of covariates in this framework: beyond making structural and parametric assumptions more credible, they lead to more precise inference and can be used to characterize patients' discontinuation behavior, which could help inform clinical practice and future protocols.

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Principal stratification with continuous treatments and continuous post-treatment variables

Principal stratification (PS) is a commonly used approach for understanding the mechanisms through which a treatment affects an outcome. The goal of this work is to extend the PS framework to studies with continuous treatments, which introduces a number of both challenges and opportunities in terms of defining causal effects and performing inference. This manuscript provides multiple key methodological contributions: 1) we introduce principal causal estimands for continuous treatments that provide insights into different causal mechanisms, 2) we show that nonparametric identification is possible under a principal ignorability assumption, but only under a restrictive assumption on the joint distribution of potential mediators, which can be dropped under mild parametric assumptions, 3) we utilize nonparametric Bayesian models for the joint distribution of the potential mediating variables to ensure our approach is robust to model misspecification, and 4) we provide theoretical justification for utilizing an outcome model to identify the joint distribution of the potential mediating variables, and show that this is only possible if a principal ignorability assumption is violated. Lastly, we apply our methodology to a novel study of the relationship between the economy and arrest rates, and how this is potentially mediated by police capacity.

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Selecting Subpopulations for Causal Inference in Regression Discontinuity Designs

The Brazil Bolsa Familia (BF) program is a conditional cash transfer program aimed to reduce short-term poverty by direct cash transfers and to fight long-term poverty by increasing human capital among poor Brazilian people. Eligibility for Bolsa Familia benefits depends on a cutoff rule, which classifies the BF study as a regression discontinuity (RD) design. Extracting causal information from RD studies is challenging. Following Li et al (2015) and Branson and Mealli (2019), we formally describe the BF RD design as a local randomized experiment within the potential outcome approach. Under this framework, causal effects can be identified and estimated on a subpopulation where a local overlap assumption, a local SUTVA and a local ignorability assumption hold. We first discuss the potential advantages of this framework over local regression methods based on continuity assumptions, which concern the definition of the causal estimands, the design and the analysis of the study, and the interpretation and generalizability of the results. A critical issue of this local randomization approach is how to choose subpopulations for which we can draw valid causal inference. We propose a Bayesian model-based finite mixture approach to clustering to classify observations into subpopulations where the RD assumptions hold and do not hold. This approach has important advantages: a) it allows to account for the uncertainty in the subpopulation membership, which is typically neglected; b) it does not impose any constraint on the shape of the subpopulation; c) it is scalable to high-dimensional settings; e) it allows to target alternative causal estimands than the average treatment effect (ATE); and f) it is robust to a certain degree of manipulation/selection of the running variable. We apply our proposed approach to assess causal effects of the Bolsa Familia program on leprosy incidence in 2009.

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Exploiting network information to disentangle spillover effects in a field experiment on teens' museum attendance

A key element in the education of youths is their sensitization to historical and artistic heritage. We analyze a field experiment conducted in Florence (Italy) to assess how appropriate incentives assigned to high-school classes may induce teens to visit museums in their free time. Non-compliance and spillover effects make the impact evaluation of this clustered encouragement design challenging. We propose to blend principal stratification and causal mediation, by defining sub-populations of units according to their compliance behavior and using the information on their friendship networks as mediator. We formally define principal natural direct and indirect effects and principal controlled direct and spillover effects, and use them to disentangle spillovers from other causal channels. We adopt a Bayesian approach for inference.

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Direct and spillover effects of a new tramway line on the commercial vitality of peripheral streets. A synthetic-control approach

In cities, the creation of public transport infrastructure such as light rails can cause changes on a very detailed spatial scale, with different stories unfolding next to each other within a same urban neighborhood. We study the direct effect of a light rail line built in Florence (Italy) on the retail density of the street where it was built and and its spillover effect on other streets in the treated street's neighborhood. To this aim, we investigate the use of the Synthetic Control Group (SCG) methods in panel comparative case studies where interference between the treated and the untreated units is plausible, an issue still little researched in the SCG methodological literature. We frame our discussion in the potential outcomes approach. Under a partial interference assumption, we formally define relevant direct and spillover causal effects. We also consider the ``unrealized'' spillover effect on the treated street in the hypothetical scenario that another street in the treated unit's neighborhood had been assigned to the intervention.

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Assessing causal effects in the presence of treatment switching through principal stratification

Clinical trials often allow patients in the control arm to switch to the treatment arm if their physical conditions are worse than certain tolerance levels. For instance, treatment switching arises in the Concorde clinical trial, which aims to assess causal effects on the time-to-disease progression or death of immediate versus deferred treatment with zidovudine among patients with asymptomatic HIV infection. The Intention-To-Treat analysis does not measure the effect of the actual receipt of the treatment and ignores the information on treatment switching. Other existing methods reconstruct the outcome a patient would have had if they had not switched under strong assumptions. Departing from the literature, we re-define the problem of treatment switching using principal stratification and focus on causal effects for patients belonging to subpopulations defined by the switching behavior under control. We use a Bayesian approach to inference, taking into account that (i) switching happens in continuous time; (ii) switching time is not defined for patients who never switch in a particular experiment; and (iii) survival time and switching time are subject to censoring. We apply this framework to analyze synthetic data based on the Concorde study. Our data analysis reveals that immediate treatment with zidovudine increases survival time for never switcher and that treatment effects are highly heterogeneous across different types of patients defined by the switching behavior.

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Causal inference for binary non-independent outcomes

Causal inference on multiple non-independent outcomes raises serious challenges, because multivariate techniques that properly account for the outcome's dependence structure need to be considered. We focus on the case of binary outcomes framing our discussion in the potential outcome approach to causal inference. We define causal effects of treatment on joint outcomes introducing the notion of product outcomes. We also discuss a decomposition of the causal effect on product outcomes into intrinsic and extrinsic causal effects, which respectively provide information on treatment effect on the intrinsic (product) structure of the product outcomes and on the outcomes' dependence structure. We propose a log-mean linear regression approach for modeling the distribution of the potential outcomes, which is particularly appealing because all the causal estimands of interest and the decomposition into intrinsic and extrinsic causal effects can be easily derived by model parameters. The method is illustrated in two randomized experiments concerning (i) the effect of the administration of oral pre-surgery morphine on pain intensity after surgery; and (ii) the effect of honey on nocturnal cough and sleep difficulty associated with childhood upper respiratory tract infections.

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A novel quantile-based decomposition of the indirect effect in mediation analysis with an application to infant mortality in the US population

In mediation analysis, the effect of an exposure (or treatment) on an outcome variable is decomposed into two components: a direct effect, which pertains to an immediate influence of the exposure on the outcome, and an indirect effect, which the exposure exerts on the outcome through a third variable called mediator. Our motivating example concerns the relationship between maternal smoking (the exposure, $X$), birthweight (the mediator, $M$), and infant mortality (the outcome, $Y$), which has attracted the interest of epidemiologists and statisticians for many years. We introduce new causal estimands, named $u$-specific direct and indirect effects, which describe the direct and indirect effects of the exposure on the outcome at a specific quantile $u$ of the mediator, $0 < u < 1$. Under sequential ignorability we derive an interesting and novel decomposition of $u$-specific indirect effects. The components of this decomposition have a straightforward interpretation and can provide new insights into the complexity of the mechanisms underlying the indirect effect. We illustrate the proposed methods using data on infant mortality in the US population. We provide analytical evidence that supports the hypothesis that the risk of sudden infant death syndrome is not predicted by changes in the birthweight distribution.

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Potential outcome approach to causal inference in assessing the short term impact of air pollution on mortality

The opportunity to assess short term impact of air pollution relies on the causal interpretation of the exposure-outcome association, but up to now few studies explicitly faced this issue within a causal inference framework. In this paper, we reformulated the problem of assessing the short term impact of air pollution on health using the potential outcome approach to causal inference. We focused on the impact of high daily levels of PM10 on mortality within two days from the exposure in the metropolitan area of Milan (Italy), during the period 2003-2006. After defining the number of attributable deaths in terms of difference between potential outcomes, we used the estimated propensity score to match each high exposure-day with a day with similar background characteristics but lower PM10 level. Then, we estimated the impact by comparing mortality between matched days. We found that during the study period daily exposures larger than 40 microgram per cubic meter were responsible of 1079 deaths (116; 2042). The impact was more evident among the elderly than in the younger classes of age. The propensity score matching turned out to be an appealing method to assess historical impacts in this field.

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Bayesian Inference for Sequential Treatments under Latent Sequential Ignorability

We focus on causal inference for longitudinal treatments, where units are assigned to treatments at multiple time points, aiming to assess the effect of different treatment sequences on an outcome observed at a final point. A common assumption in similar studies is Sequential Ignorability (SI): treatment assignment at each time point is assumed independent of future potential outcomes given past observed outcomes and covariates. SI is questionable when treatment participation depends on individual choices, and treatment assignment may depend on unobservable quantities associated with future outcomes. We rely on Principal Stratification to formulate a relaxed version of SI: Latent Sequential Ignorability (LSI) assumes that treatment assignment is conditionally independent on future potential outcomes given past treatments, covariates and principal stratum membership, a latent variable defined by the joint value of observed and missing intermediate outcomes. We evaluate SI and LSI, using theoretical arguments and simulation studies to investigate the performance of the two assumptions when one holds and inference is conducted under both. Simulations show that when SI does not hold, inference performed under SI leads to misleading conclusions. Conversely, LSI generally leads to correct posterior distributions, irrespective of which assumption holds.

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Evaluating the Causal Effect of University Grants on Student Dropout: Evidence from a Regression Discontinuity Design Using Principal Stratification

Regression discontinuity (RD) designs are often interpreted as local randomized experiments: a RD design can be considered as a randomized experiment for units with a realized value of a so-called forcing variable falling around a pre-fixed threshold. Motivated by the evaluation of Italian university grants, we consider a fuzzy RD design where the receipt of the treatment is based on both eligibility criteria and a voluntary application status. Resting on the fact that grant application and grant receipt statuses are post-assignment (post-eligibility) intermediate variables, we use the principal stratification framework to define causal estimands within the Rubin Causal Model. We propose a probabilistic formulation of the assignment mechanism underlying RD designs, by re-formulating the Stable Unit Treatment Value Assumption (SUTVA) and making an explicit local overlap assumption for a subpopulation around the threshold. A local randomization assumption is invoked instead of more standard continuity assumptions. We also develop a model-based Bayesian approach to select the target subpopulation(s) with adjustment for multiple comparisons, and to draw inference for the target causal estimands in this framework. Applying the method to the data from two Italian universities, we find evidence that university grants are effective in preventing students from low-income families from dropping out of higher education.

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Exploiting multiple outcomes in Bayesian principal stratification analysis with application to the evaluation of a job training program

The causal effect of a randomized job training program, the JOBS II study, on trainees' depression is evaluated. Principal stratification is used to deal with noncompliance to the assigned treatment. Due to the latent nature of the principal strata, strong structural assumptions are often invoked to identify principal causal effects. Alternatively, distributional assumptions may be invoked using a model-based approach. These often lead to weakly identified models with substantial regions of flatness in the posterior distribution of the causal effects. Information on multiple outcomes is routinely collected in practice, but is rarely used to improve inference. This article develops a Bayesian approach to exploit multivariate outcomes to sharpen inferences in weakly identified principal stratification models. We show that inference for the causal effect on depression is significantly improved by using the re-employment status as a secondary outcome in the JOBS II study. Simulation studies are also performed to illustrate the potential gains in the estimation of principal causal effects from jointly modeling more than one outcome. This approach can also be used to assess plausibility of structural assumptions and sensitivity to deviations from these structural assumptions. Two model checking procedures via posterior predictive checks are also discussed.

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