Background and Aims: The methods with which prediction models are usually developed mean that neither the parameters nor the predictions should be interpreted causally. However, when prediction models are used to support decision making, there is often a need for predicting outcomes under hypothetical interventions. We aimed to identify published methods for developing and validating prediction models that enable risk estimation of outcomes under hypothetical interventions, utilizing causal inference: their main methodological approaches, underlying assumptions, targeted estimands, and potential pitfalls and challenges with using the method, and unresolved methodological challenges.
Methods: We systematically reviewed literature published by December 2019, considering papers in the health domain that used causal considerations to enable prediction models to be used for predictions under hypothetical interventions.
Results: We identified 4919 papers through database searches and a further 115 papers through manual searches, of which 13 were selected for inclusion, from both the statistical and the machine learning literature. Most of the identified methods for causal inference from observational data were based on marginal structural models and g-estimation.
Conclusions: There exist two broad methodological approaches for allowing prediction under hypothetical intervention into clinical prediction models: 1) enriching prediction models derived from observational studies with estimated causal effects from clinical trials and meta-analyses; and 2) estimating prediction models and causal effects directly from observational data. These methods require extending to dynamic treatment regimes, and consideration of multiple interventions to operationalise a clinical decision support system. Techniques for validating 'causal prediction models' are still in their infancy.
Randomised controlled trials aim to assess the impact of one (or more) health interventions relative to other standard interventions. RCTs sometimes use an ordinal outcome, which is an endpoint that comprises of multiple, monotonically ordered categories that are not necessarily separated by a quantifiable distance. Ordinal outcomes are appealing in clinical settings as disease states can represent meaningful categories that may be of clinical importance. They can also retain information and increase statistical power compared to dichotomised outcomes. Target parameters for ordinal outcomes in…
The incorporation of causal inference in mediation analysis has led to theoretical and methodological advancements -- effect definitions with causal interpretation, clarification of assumptions required for effect identification, and an expanding array of options for effect estimation. However, the literature on these results is fast-growing and complex, which may be confusing to researchers unfamiliar with causal inference or unfamiliar with mediation. The goal of this paper is to help ease the understanding and adoption of causal mediation analysis. It starts by highlighting a key difference…
For exposures $X$ like obesity, no precise and unambiguous definition exists for the hypothetical intervention $do(X = x_0)$. This has raised concerns about the relevance of causal effects estimated from observational studies for such exposures. Under the framework of structural causal models, we study how the effect of $do(X = x_0)$ relates to the effect of interventions on causes of $X$. We show that for interventions focusing on causes of $X$ that affect the outcome through $X$ only, the effect of $do(X = x_0)$ equals the effect of the considered intervention. On the other hand, for interve…
Estimating Pathway Treatment Effects in the Presence of Intermediate Events with Multi-State Data
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center（弗雷德·哈钦森癌症中心疫苗与传染病部门）；Department of Economics, University of California San Diego（加州大学圣地亚哥分校经济学系）；Department of Biostatistics, University of Michigan（密歇根大学生物统计学系）；Amazon Inc.（亚马逊公司）
Graphical models can represent a multivariate distribution in a convenient and accessible form as a graph. Causal models can be viewed as a special class of graphical models that not only represent the distribution of the observed system but also the distributions under external interventions. They hence enable predictions under hypothetical interventions, which is important for decision making. The challenging task of learning causal models from data always relies on some underlying assumptions. We discuss several recently proposed structure learning algorithms and their assumptions, and comp…
Policy interventions can spill over to units of a population that are not directly exposed to the policy but are geographically close to the units receiving the intervention. In recent work, investigations of spillover effects on neighboring regions have focused on estimating the average treatment effect of a particular policy in an observed setting. Our research question broadens this scope by asking what policy consequences would the treated units have experienced under hypothetical exposure settings. When we only observe treated unit(s) surrounded by controls -- as is common when a policy i…
Inferring the causal structure of a system typically requires interventional data, rather than just observational data. Since interventional experiments can be costly, it is preferable to select interventions that yield the maximum amount of information about a system. We propose a novel Bayesian method for optimal experimental design by sequentially selecting interventions that minimize the expected posterior entropy as rapidly as possible. A key feature is that the method can be implemented by computing simple summaries of the current posterior, avoiding the computationally burdensome task o…
InfluenceField: A Differentiable Field with Interventionally Identifiable Causal Structure for Multimodal World Modeling
Mathematical Institute, University of Oxford（牛津大学数学研究所）；Department of Computer Science, University of Oxford（牛津大学计算机科学系）；School of Mathematical Sciences, University of Nottingham Ningbo China（宁波诺丁汉大学数学科学学院）
We present new methods to estimate causal effects retrospectively from micro data with the assistance of a machine learning ensemble. This approach overcomes two important limitations in conventional methods like regression modeling or matching: (i) ambiguity about the pertinent retrospective counterfactuals and (ii) potential misspecification, overfitting, and otherwise bias-prone or inefficient use of a large identifying covariate set in the estimation of causal effects. Our method targets the analysis toward a well defined ``retrospective intervention effect'' (RIE) based on hypothetical po…
Instituto de Ciencias Matemáticas, CSIC（西班牙科学研究所数学科学研究所）；Departamento de Matemáticas, Universidad Autónoma de Madrid（马德里自治大学数学系）；Division of Biostatistics, University of California, Berkeley（加州大学伯克利分校生物统计学部）
Living forwards or understanding backwards? A comparison of Inverse Probability of Treatment Weighting and G-estimation methods for targeting hypothetical full adherence estimands in longitudinal cohort studies
University of Exeter（埃克塞特大学）；Royal Devon University Healthcare NHS Foundation Trust（皇家德文郡大学医疗保健NHS基金会信托）；Novo Nordisk Research Centre (NNRCO)（诺和诺德研究中心）
Graphical causal models led to the development of complete non-parametric identification theory in arbitrary structured systems, and general approaches to efficient inference. Nevertheless, graphical approaches to causal inference have not been embraced by the statistics and public health communities. In those communities causal assumptions are instead expressed in terms of potential outcomes, or responses to hypothetical interventions. Such interventions are generally conceptualized only on a limited set of variables, where the corresponding experiment could, in principle, be performed. By co…
Despite substantial progress in deep learning approaches to time-series reconstruction, no existing methods are designed to uncover local activities with minute signal strength due to their negligible contribution to the optimization loss. Such local activities however can signify important abnormal events in physiological systems, such as an extra foci triggering an abnormal propagation of electrical waves in the heart. We discuss a novel technique for reconstructing such local activity that, while small in signal strength, is the cause of subsequent global activities that have larger signal …
Amazon Research（亚马逊研究院）；Max Planck Institute for Intelligent Systems（马克斯·普朗克智能系统研究所）
Discussions on causal relations in real life often consider variables for which the definition of causality is unclear since the notion of interventions on the respective variables is obscure. Asking 'what qualifies an action for being an intervention on the variable X' raises the question whether the action impacted all other variables only through X or directly, which implicitly refers to a causal model. To avoid this known circularity, we instead suggest a notion of 'phenomenological causality' whose basic concept is a set of elementary actions. Then the causal structure is defined such tha…
When engagement with a randomized trial is driven by factors that affect the outcome or when trial engagement directly affects the outcome independent of treatment, the average treatment effect among trial participants is unlikely to generalize to a target population. In this paper, we use counterfactual and graphical causal models to examine under what conditions we can generalize causal inferences from a randomized trial to the target population of trial-eligible individuals. We offer an interpretation of generalizability analyses using the notion of a hypothetical intervention to "scale-up"…
Marginal structural models were introduced in order to provide estimates of causal effects from interventions based on observational studies in epidemiological research. The key point is that this can be understood in terms of Girsanov's change of measure. This offers a mathematical interpretation of marginal structural models that has not been available before. We consider both a model of an observational study and a model of a hypothetical randomized trial. These models correspond to different martingale measures -- the observational measure and the randomized trial measure -- on some underl…
An important problem in many domains is to predict how a system will respond to interventions. This task is inherently linked to estimating the system's underlying causal structure. To this end, Invariant Causal Prediction (ICP) (Peters et al., 2016) has been proposed which learns a causal model exploiting the invariance of causal relations using data from different environments. When considering linear models, the implementation of ICP is relatively straightforward. However, the nonlinear case is more challenging due to the difficulty of performing nonparametric tests for conditional independ…
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 identifie…
Diagrams-to-Dynamics (D2D): Exploring Causal Loop Diagram Leverage Points under Uncertainty
University of Copenhagen（哥本哈根大学）；Amsterdam UMC University of Amsterdam（阿姆斯特丹大学阿姆斯特丹医学中心）；University of Amsterdam（阿姆斯特丹大学）；TNO - The Netherlands Organization for Applied Scientific Research（荷兰应用科学研究组织）；Radboud University（拉德堡德大学）
Causal decomposition analyses can help build the evidence base for interventions that address health disparities (inequities). They ask how disparities in outcomes may change under hypothetical intervention. Through study design and assumptions, they can rule out alternate explanations such as confounding, selection-bias, and measurement error, thereby identifying potential targets for intervention. Unfortunately, the literature on causal decomposition analysis and related methods have largely ignored equity concerns that actual interventionists would respect, limiting their relevance and prac…
MSCT: Addressing Time-Varying Confounding with Marginal Structural Causal Transformer for Counterfactual Post-Crash Traffic Prediction
School of Transportation, Southeast University（东南大学交通学院）；Department of Civil and Environmental Engineering, Imperial College London（帝国理工学院土木与环境工程系）；School of Mathematics, Southeast University（东南大学数学学院）；School of Cyber Science and Engineering, Southeast University（东南大学网络空间科学与工程学院）；Department of Civil and Environmental Engineering, University of Washington（华盛顿大学土木与环境工程系）
Machine learning is the science of discovering statistical dependencies in data, and the use of those dependencies to perform predictions. During the last decade, machine learning has made spectacular progress, surpassing human performance in complex tasks such as object recognition, car driving, and computer gaming. However, the central role of prediction in machine learning avoids progress towards general-purpose artificial intelligence. As one way forward, we argue that causal inference is a fundamental component of human intelligence, yet ignored by learning algorithms. Causal inference is…
Causal Inference with Missing Exposures and Missing Outcomes
University of California Berkeley（加州大学伯克利分校）；University of California San Francisco（加州大学旧金山分校）；Infectious Diseases Research Collaboration（传染病研究协作组织）；Makerere University（马凯雷雷大学）
Estimating the Complier Average Causal Effect in Randomised Controlled Trials with Non-Compliance: A Comparative Simulation Study of the Instrumental Variables and Per-Protocol Analyses
