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Vanessa Didelez

Publications and source records attributed to Vanessa Didelez.

At least 19 recordsLinked to original sources

The Generalised Kernel Covariance Measure

We consider the problem of conditional independence (CI) testing and adopt a kernel-based approach. Kernel-based CI tests embed variables in reproducing kernel Hilbert spaces, regress their embeddings on the conditioning variables, and test the resulting residuals for marginal independence. This approach yields tests that are sensitive to a broad range of conditional dependencies. Existing methods, however, rely heavily on kernel ridge regression, which is computationally expensive when properly tuned and yields poorly calibrated tests when left untuned, which limits their practical usefulness. We propose the Generalised Kernel Covariance Measure (GKCM), a regression-model-agnostic kernel-based CI test that accommodates a broad class of regression estimators. Building on the Generalised Hilbertian Covariance Measure framework (Lundborg et al., 2022), we characterise conditions under which GKCM satisfies uniform asymptotic level guarantees. In simulations, GKCM paired with tree-based regression models frequently outperforms state-of-the-art CI tests across a diverse range of data-generating processes, achieving better type I error control and competitive or superior power.

stat.ML

Bounds for causal mediation effects

Several frameworks have been proposed for studying causal mediation analysis. What these frameworks have in common is that they all make assumptions for point identifications that can be violated even when treatment is randomized. When a causal effect is not point-identified, one can sometimes derive bounds, i.e. a range of possible values that are consistent with the observed data. In this work, we study causal bounds for mediation effects under both the natural effects framework and the separable effects framework. In particular, we show that when there are unmeasured confounders for the intermediate variables(s) the sharp symbolic bounds on separable (in)direct effect coincide with existing bounds for natural (in)direct effects in the analogous setting. We compare these bounds to valid bounds for the natural direct effects when only the cross-world independence assumption does not hold. Furthermore, we demonstrate the use and compare the results of the bounds on data from a trial investigating the effect of peanut consumption on the development of peanut allergy in infants through specific pathways of measured immunological biomarkers.

stat.ME

The risks of risk assessment: causal blind spots when using prediction models for treatment decisions

Clinicians increasingly rely on prediction models to guide treatment choices. Most prediction models, however, are developed using observational data that include some patients who have already received the treatment the prediction model is meant to inform. Special attention to the causal role of those earlier treatments is required when interpreting the resulting predictions. We identify 'causal blind spots' in three common approaches to handling treatment when developing a prediction model: including treatment as a predictor, restricting to individuals taking a certain treatment, and ignoring treatment. Through several real examples, we illustrate how the risks obtained from models developed using such approaches may be misinterpreted and can lead to misinformed decision-making. Our discussion covers issues attributable to confounding, selection, mediation and changes in treatment protocols over time. We advocate for an extension of guidelines for the development, reporting and evaluation of prediction models to avoid such misinterpretations. Developers must ensure that the intended target population for the model, and the treatment conditions under which predictions hold, are clearly communicated. When prediction models are intended to inform treatment decisions, they need to provide estimates of risk under the specific treatment (or intervention) options being considered, known as 'prediction under interventions'. Next to suitable data, this requires causal reasoning and causal inference techniques during model development and evaluation. Being clear about what a given prediction model can and cannot be used for prevents misinformed treatment decisions and thereby prevents potential harm to patients.

stat.ME

Robot Pouring: Identifying Causes of Spillage and Selecting Alternative Action Parameters Using Probabilistic Actual Causation

In everyday life, we perform tasks (e.g., cooking or cleaning) that involve a large variety of objects and goals. When confronted with an unexpected or unwanted outcome, we take corrective actions and try again until achieving the desired result. The reasoning performed to identify a cause of the observed outcome and to select an appropriate corrective action is a crucial aspect of human reasoning for successful task execution. Central to this reasoning is the assumption that a factor is responsible for producing the observed outcome. In this paper, we investigate the use of probabilistic actual causation to determine whether a factor is the cause of an observed undesired outcome. Furthermore, we show how the actual causation probabilities can be used to find alternative actions to change the outcome. We apply the probabilistic actual causation analysis to a robot pouring task. When spillage occurs, the analysis indicates whether a task parameter is the cause and how it should be changed to avoid spillage. The analysis requires a causal graph of the task and the corresponding conditional probability distributions. To fulfill these requirements, we perform a complete causal modeling procedure (i.e., task analysis, definition of variables, determination of the causal graph structure, and estimation of conditional probability distributions) using data from a realistic simulation of the robot pouring task, covering a large combinatorial space of task parameters. Based on the results, we discuss the implications of the variables' representation and how the alternative actions suggested by the actual causation analysis would compare to the alternative solutions proposed by a human observer. The practical use of the analysis of probabilistic actual causation to select alternative action parameters is demonstrated.

cs.RO

Constraint-based causal discovery with tiered background knowledge and latent variables in single or overlapping datasets

In this paper we consider the use of tiered background knowledge within constraint based causal discovery. Our focus is on settings relaxing causal sufficiency, i.e. allowing for latent variables which may arise because relevant information could not be measured at all, or not jointly, as in the case of multiple overlapping datasets. We first present novel insights into the properties of the 'tiered FCI' (tFCI) algorithm. Building on this, we introduce a new extension of the IOD (integrating overlapping datasets) algorithm incorporating tiered background knowledge, the 'tiered IOD' (tIOD) algorithm. We show that under full usage of the tiered background knowledge tFCI and tIOD are sound, while simple versions of the tIOD and tFCI are sound and complete. We further show that the tIOD algorithm can often be expected to be considerably more efficient and informative than the IOD algorithm even beyond the obvious restriction of the Markov equivalence classes. We provide a formal result on the conditions for this gain in efficiency and informativeness. Our results are accompanied by a series of examples illustrating the exact role and usefulness of tiered background knowledge.

stat.ML

Improving Finite Sample Performance of Causal Discovery by Exploiting Temporal Structure

Methods of causal discovery aim to identify causal structures in a data driven way. Existing algorithms are known to be unstable and sensitive to statistical errors, and are therefore rarely used with biomedical or epidemiological data. We present an algorithm that efficiently exploits temporal structure, so-called tiered background knowledge, for estimating causal structures. Tiered background knowledge is readily available from, e.g., cohort or registry data. When used efficiently it renders the algorithm more robust to statistical errors and ultimately increases accuracy in finite samples. We describe the algorithm and illustrate how it proceeds. Moreover, we offer formal proofs as well as examples of desirable properties of the algorithm, which we demonstrate empirically in an extensive simulation study. To illustrate its usefulness in practice, we apply the algorithm to data from a children's cohort study investigating the interplay of diet, physical activity and other lifestyle factors for health outcomes.

stat.ME

Graphical criteria for the identification of marginal causal effects in continuous-time survival and event-history analyses

We consider continuous-time survival or more general event-history settings, where the aim is to infer the causal effect of a time-dependent treatment process. This is formalised as the effect on the outcome event of a (possibly hypothetical) intervention on the intensity of the treatment process, i.e. a stochastic intervention. To establish whether valid inference about the interventional situation can be drawn from typical observational, i.e. non-experimental, data we propose graphical rules indicating whether the observed information is sufficient to identify the desired causal effect by suitable re-weighting. In analogy to the well-known causal directed acyclic graphs, the corresponding dynamic graphs combine causal semantics with local independence models for multivariate counting processes. Importantly, we highlight that causal inference from censored data requires structural assumptions on the censoring process beyond the usual independent censoring assumption, which can be represented and verified graphically. Our results establish general non-parametric identifiability and do not rely on particular survival models. We illustrate our proposal with a data example on HPV-testing for cervical cancer screening, where the desired effect is estimated by re-weighted cumulative incidence curves.

stat.ME

A practical guide to causal discovery with cohort data

In this guide, we present how to perform constraint-based causal discovery using three popular software packages: pcalg (with add-ons tpc and micd), bnlearn, and TETRAD. We focus on how these packages can be used with observational data and in the presence of mixed data (i.e., data where some variables are continuous, while others are categorical), a known time ordering between variables, and missing data. Throughout, we point out the relative strengths and limitations of each package, as well as give practical recommendations. We hope this guide helps anyone who is interested in performing constraint-based causal discovery on their data.

stat.AP

Risk-based decision making: estimands for sequential prediction under interventions

Prediction models are used amongst others to inform medical decisions on interventions. Typically, individuals with high risks of adverse outcomes are advised to undergo an intervention while those at low risk are advised to refrain from it. Standard prediction models do not always provide risks that are relevant to inform such decisions: e.g., an individual may be estimated to be at low risk because similar individuals in the past received an intervention which lowered their risk. Therefore, prediction models supporting decisions should target risks belonging to defined intervention strategies. Previous works on prediction under interventions assumed that the prediction model was used only at one time point to make an intervention decision. In clinical practice, intervention decisions are rarely made only once: they might be repeated, deferred and re-evaluated. This requires estimated risks under interventions that can be reconsidered at several potential decision moments. In the current work, we highlight key considerations for formulating estimands in sequential prediction under interventions that can inform such intervention decisions. We illustrate these considerations by giving examples of estimands for a case study about choosing between vaginal delivery and cesarean section for women giving birth. Our formalization of prediction tasks in a sequential, causal, and estimand context provides guidance for future studies to ensure that the right question is answered and appropriate causal estimation approaches are chosen to develop sequential prediction models that can inform intervention decisions.

stat.ME

Parameterizing and Simulating from Causal Models

Many statistical problems in causal inference involve a probability distribution other than the one from which data are actually observed; as an additional complication, the object of interest is often a marginal quantity of this other probability distribution. This creates many practical complications for statistical inference, even where the problem is non-parametrically identified. In particular, it is difficult to perform likelihood-based inference, or even to simulate from the model in a general way. We introduce the `frugal parameterization', which places the causal effect of interest at its centre, and then builds the rest of the model around it. We do this in a way that provides a recipe for constructing a regular, non-redundant parameterization using causal quantities of interest. In the case of discrete variables we can use odds ratios to complete the parameterization, while in the continuous case copulas are the natural choice; other possibilities are also discussed. Our methods allow us to construct and simulate from models with parametrically specified causal distributions, and fit them using likelihood-based methods, including fully Bayesian approaches. Our proposal includes parameterizations for the average causal effect and effect of treatment on the treated, as well as other causal quantities of interest.

stat.ME

Do we become wiser with time? On causal equivalence with tiered background knowledge

Equivalence classes of DAGs (represented by CPDAGs) may be too large to provide useful causal information. Here, we address incorporating tiered background knowledge yielding restricted equivalence classes represented by 'tiered MPDAGs'. Tiered knowledge leads to considerable gains in informativeness and computational efficiency: We show that construction of tiered MPDAGs only requires application of Meek's 1st rule, and that tiered MPDAGs (unlike general MPDAGs) are chain graphs with chordal components. This entails simplifications e.g. of determining valid adjustment sets for causal effect estimation. Further, we characterise when one tiered ordering is more informative than another, providing insights into useful aspects of background knowledge.

stat.ML

Variable selection in linear regression models: choosing the best subset is not always the best choice

Variable selection in linear regression settings is a much discussed problem. Best subset selection (BSS) is often considered the intuitive 'gold standard', with its use being restricted only by its NP-hard nature. Alternatives such as the least absolute shrinkage and selection operator (Lasso) or the elastic net (Enet) have become methods of choice in high-dimensional settings. A recent proposal represents BSS as a mixed integer optimization problem so that much larger problems have become feasible in reasonable computation time. We present an extensive neutral comparison assessing the variable selection performance, in linear regressions, of BSS compared to forward stepwise selection (FSS), Lasso and Enet. The simulation study considers a wide range of settings that are challenging with regard to dimensionality (with respect to the number of observations and variables), signal-to-noise ratios and correlations between predictors. As main measure of performance, we used the best possible F1-score for each method to ensure a fair comparison irrespective of any criterion for choosing the tuning parameters, and results were confirmed by alternative performance measures. Somewhat surprisingly, it was only in settings where the signal-to-noise ratio was high and the variables were (nearly) uncorrelated that BSS reliably outperformed the other methods, even in low-dimensional settings. Further, the FSS's performance was nearly identical to BSS. Our results shed new light on the usual presumption of BSS being, in principle, the best choice for variable selection. Especially for correlated variables, alternatives like Enet are faster and appear to perform better in practical settings.

stat.ME

Multiple imputation and test-wise deletion for causal discovery with incomplete cohort data

Causal discovery algorithms estimate causal graphs from observational data. This can provide a valuable complement to analyses focussing on the causal relation between individual treatment-outcome pairs. Constraint-based causal discovery algorithms rely on conditional independence testing when building the graph. Until recently, these algorithms have been unable to handle missing values. In this paper, we investigate two alternative solutions: Test-wise deletion and multiple imputation. We establish necessary and sufficient conditions for the recoverability of causal structures under test-wise deletion, and argue that multiple imputation is more challenging in the context of causal discovery than for estimation. We conduct an extensive comparison by simulating from benchmark causal graphs: As one might expect, we find that test-wise deletion and multiple imputation both clearly outperform list-wise deletion and single imputation. Crucially, our results further suggest that multiple imputation is especially useful in settings with a small number of either Gaussian or discrete variables, but when the dataset contains a mix of both neither method is uniformly best. The methods we compare include random forest imputation and a hybrid procedure combining test-wise deletion and multiple imputation. An application to data from the IDEFICS cohort study on diet- and lifestyle-related diseases in European children serves as an illustrating example.

stat.ME

Time-dependent mediators in survival analysis: Modelling direct and indirect effects with the additive hazards model

We discuss causal mediation analyses for survival data and propose a new approach based on the additive hazards model. The emphasis is on a dynamic point of view, that is, understanding how the direct and indirect effects develop over time. Hence, importantly, we allow for a time varying mediator. To define direct and indirect effects in such a longitudinal survival setting we take an interventional approach (Didelez (2018)) where treatment is separated into one aspect affecting the mediator and a different aspect affecting survival. In general, this leads to a version of the non-parametric g-formula (Robins (1986)). In the present paper, we demonstrate that combining the g-formula with the additive hazards model and a sequential linear model for the mediator process results in simple and interpretable expressions for direct and indirect effects in terms of relative survival as well as cumulative hazards. Our results generalise and formalise the method of dynamic path analysis (Fosen et al. (2006), Strohmaier et al. (2015)). An application to data from a clinical trial on blood pressure medication is given.

stat.ME

On efficient adjustment in causal graphs

We consider estimation of a total causal effect from observational data via covariate adjustment. Ideally, adjustment sets are selected based on a given causal graph, reflecting knowledge of the underlying causal structure. Valid adjustment sets are, however, not unique. Recent research has introduced a graphical criterion for an 'optimal' valid adjustment set (O-set). For a given graph, adjustment by the O-set yields the smallest asymptotic variance compared to other adjustment sets in certain parametric and non-parametric models. In this paper, we provide three new results on the O-set. First, we give a novel, more intuitive graphical characterisation: We show that the O-set is the parent set of the outcome node(s) in a suitable latent projection graph, which we call the forbidden projection. An important property is that the forbidden projection preserves all information relevant to total causal effect estimation via covariate adjustment, making it a useful methodological tool in its own right. Second, we extend the existing IDA algorithm to use the O-set, and argue that the algorithm remains semi-local. This is implemented in the R-package pcalg. Third, we present assumptions under which the O-set can be viewed as the target set of popular non-graphical variable selection algorithms such as stepwise backward selection.

math.ST

Insights into the "cross-world" independence assumption of causal mediation analysis

Causal mediation analysis is a useful tool for epidemiological research, but it has been criticized for relying on a "cross-world" independence assumption that is empirically difficult to verify and problematic to justify based on background knowledge. In the present article we aim to assist the applied researcher in understanding this assumption. Synthesizing what is known about the cross-world independence assumption, we discuss the relationship between assumptions for causal mediation analyses, causal models, and non-parametric identification of natural direct and indirect effects. In particular we give a practical example of an applied setting where the cross-world independence assumption is violated even without any post-treatment confounding. Further, we review possible alternatives to the cross-world independence assumption, including the use of computation of bounds that avoid the assumption altogether. Finally, we carry out a numerical study in which the cross-world independence assumption is violated to assess the ensuing bias in estimating natural direct and indirect effects. We conclude with recommendations for carrying out causal mediation analyses.

stat.ME

Generalized interpretation and identification of separable effects in competing event settings

In competing event settings, a counterfactual contrast of cause-specific cumulative incidences quantifies the total causal effect of a treatment on the event of interest. However, effects of treatment on the competing event may indirectly contribute to this total effect, complicating its interpretation. We previously proposed the separable effects (Stensrud et al, 2019) to define direct and indirect effects of the treatment on the event of interest. This definition presupposes a treatment decomposition into two components acting along two separate causal pathways, one exclusively outside of the competing event and the other exclusively through it. Unlike previous definitions of direct and indirect effects, the separable effects can be subject to empirical scrutiny in a study where separate interventions on the treatment components are available. Here we extend and generalize the notion of the separable effects in several ways, allowing for interpretation, identification and estimation under considerably weaker assumptions. We propose and discuss a definition of separable effects that is applicable to general time-varying structures, where the separable effects can still be meaningfully interpreted, even when they cannot be regarded as direct and indirect effects. We further derive weaker conditions for identification of separable effects in observational studies where decomposed treatments are not yet available; in particular, these conditions allow for time-varying common causes of the event of interest, the competing events and loss to follow-up. For these general settings, we propose semi-parametric weighted estimators that are straightforward to implement. As an illustration, we apply the estimators to study the separable effects of intensive blood pressure therapy on acute kidney injury, using data from a randomized clinical trial.

stat.ME

Separable Effects for Causal Inference in the Presence of Competing Events

In time-to-event settings, the presence of competing events complicates the definition of causal effects. Here we propose the new separable effects to study the causal effect of a treatment on an event of interest. The separable direct effect is the treatment effect on the event of interest not mediated by its effect on the competing event. The separable indirect effect is the treatment effect on the event of interest only through its effect on the competing event. Similar to Robins and Richardson's extended graphical approach for mediation analysis, the separable effects can only be identified under the assumption that the treatment can be decomposed into two distinct components that exert their effects through distinct causal pathways. Unlike existing definitions of causal effects in the presence of competing events, our estimands do not require cross-world contrasts or hypothetical interventions to prevent death. As an illustration, we apply our approach to a randomized clinical trial on estrogen therapy in individuals with prostate cancer.

stat.ME