Intercurrent (post-treatment) events occur frequently in randomized trials, and investigators often express interest in treatment effects that suitably take account of these events. A naive conditioning on intercurrent events does not have a straight-forward causal interpretation, and the practical relevance of other commonly used approaches is debated. In this work, we discuss how to formulate and choose an estimand, beyond the marginal intention to treat effect, from the point of view of a decision maker and drug developer. In particular, we argue that careful articulation of a practically useful research question should either reflect decision making at this point in time or future drug development. Indeed, a substantially interesting estimand is a formalization of the (plain English) description of a research question. A common feature of estimands that are practically useful is that they correspond to possibly hypothetical but well-defined interventions in identifiable (sub)populations. To illustrate our points, we consider five examples that were recently used to motivate consideration of principal stratum estimands in clinical trials. In all of these examples, we propose alternative causal estimands, such as conditional effects, sequential regime effects and separable effects, that correspond to explicit research questions of substantial interest. Certain questions require stronger assumptions for identification. However, we highlight that our proposed estimands require less stringent assumptions than estimands commonly targeted in these settings, including principal stratum effects.
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Continuous determinantal point processes (DPPs) are a class of repulsive point processes on $\mathbb{R}^d$ with many statistical applications. Although an explicit expression of their density is known, it is too complicated to be used directly for maximum likelihood estimation. In the stationary case, an approximation using Fourier series has been suggested, but it is limited to rectangular observation windows and no theoretical results support it. In this contribution, we investigate a different way to approximate the likelihood by looking at its asymptotic behaviour when the observation window grows towards $\mathbb{R}^d$. This new approximation is not limited to rectangular windows, is faster to compute than the previous one, does not require any tuning parameter, and some theoretical justifications are provided. It moreover provides an explicit formula for estimating the asymptotic variance of the associated estimator. The performances are assessed in a simulation study on standard parametric models on $\mathbb{R}^d$ and compare favourably to common alternative estimation methods for continuous DPPs.
A central obstacle in the objective assessment of treatment effect (TE) estimators in randomized control trials (RCTs) is the lack of ground truth (or validation set) to test their performance. In this paper, we provide a novel cross-validation-like methodology to address this challenge. The key insight of our procedure is that the noisy (but unbiased) difference-of-means estimate can be used as a ground truth "label" on a portion of the RCT, to test the performance of an estimator trained on the other portion. We combine this insight with an aggregation scheme, which borrows statistical strength across a large collection of RCTs, to present an end-to-end methodology for judging an estimator's ability to recover the underlying treatment effect. We evaluate our methodology across 709 RCTs implemented in the Amazon supply chain. In the corpus of AB tests at Amazon, we highlight the unique difficulties associated with recovering the treatment effect due to the heavy-tailed nature of the response variables. In this heavy-tailed setting, our methodology suggests that procedures that aggressively downweight or truncate large values, while introducing bias, lower the variance enough to ensure that the treatment effect is more accurately estimated.
Medical professionals evaluating alternative treatment plans for a patient often encounter time varying confounders, or covariates that affect both the future treatment assignment and the patient outcome. The recently proposed Counterfactual Recurrent Network (CRN) accounts for time varying confounders by using adversarial training to balance recurrent historical representations of patient data. However, this work assumes that all time varying covariates are confounding and thus attempts to balance the full state representation. Given that the actual subset of covariates that may in fact be confounding is in general unknown, recent work on counterfactual evaluation in the static, non-temporal setting has suggested that disentangling the covariate representation into separate factors, where each either influence treatment selection, patient outcome or both can help isolate selection bias and restrict balancing efforts to factors that influence outcome, allowing the remaining factors which predict treatment without needlessly being balanced.
Randomized controlled trials (RCTs) are considered as the gold standard for testing causal hypotheses in the clinical domain. However, the investigation of prognostic variables of patient outcome in a hypothesized cause-effect route is not feasible using standard statistical methods. Here, we propose a new automated causal inference method (AutoCI) built upon the invariant causal prediction (ICP) framework for the causal re-interpretation of clinical trial data. Compared to existing methods, we show that the proposed AutoCI allows to efficiently determine the causal variables with a clear differentiation on two real-world RCTs of endometrial cancer patients with mature outcome and extensive clinicopathological and molecular data. This is achieved via suppressing the causal probability of non-causal variables by a wide margin. In ablation studies, we further demonstrate that the assignment of causal probabilities by AutoCI remain consistent in the presence of confounders. In conclusion, these results confirm the robustness and feasibility of AutoCI for future applications in real-world clinical analysis.
Across research disciplines, cluster randomized trials (CRTs) are commonly implemented to evaluate interventions delivered to groups of participants, such as communities and clinics. Despite advances in the design and analysis of CRTs, several challenges remain. First, there are many possible ways to specify the intervention effect (e.g., at the individual-level or at the cluster-level). Second, the theoretical and practical performance of common methods for CRT analysis remain poorly understood. Here, we use causal models to formally define an array of causal effects as summary measures of counterfactual outcomes. Next, we provide a comprehensive overview of well-known CRT estimators, including the t-test and generalized estimating equations (GEE), as well as less known methods, including augmented-GEE and targeted maximum likelihood estimation (TMLE). In finite sample simulations, we illustrate the performance of these estimators and the importance of effect specification, especially when cluster size varies. Finally, our application to data from the Preterm Birth Initiative (PTBi) study demonstrates the real-world importance of selecting an analytic approach corresponding to the research question. Given its flexibility to estimate a variety of effects and ability to adaptively adjust for covariates for precision gains while maintaining Type-I error control, we conclude TMLE is a promising tool for CRT analysis.
Inspired by the success of BERT, several multimodal representation learning approaches have been proposed that jointly represent image and text. These approaches achieve superior performance by capturing high-level semantic information from large-scale multimodal pretraining. In particular, LXMERT and UNITER adopt visual region feature regression and label classification as pretext tasks. However, they tend to suffer from the problems of noisy labels and sparse semantic annotations, based on the visual features having been pretrained on a crowdsourced dataset with limited and inconsistent semantic labeling. To overcome these issues, we propose unbiased Dense Contrastive Visual-Linguistic Pretraining (DCVLP), which replaces the region regression and classification with cross-modality region contrastive learning that requires no annotations. Two data augmentation strategies (Mask Perturbation and Intra-/Inter-Adversarial Perturbation) are developed to improve the quality of negative samples used in contrastive learning. Overall, DCVLP allows cross-modality dense region contrastive learning in a self-supervised setting independent of any object annotations. We compare our method against prior visual-linguistic pretraining frameworks to validate the superiority of dense contrastive learning on multimodal representation learning.
Feature attribution is often loosely presented as the process of selecting a subset of relevant features as a rationale of a prediction. This lack of clarity stems from the fact that we usually do not have access to any notion of ground-truth attribution and from a more general debate on what good interpretations are. In this paper we propose to formalise feature selection/attribution based on the concept of relaxed functional dependence. In particular, we extend our notions to the instance-wise setting and derive necessary properties for candidate selection solutions, while leaving room for task-dependence. By computing ground-truth attributions on synthetic datasets, we evaluate many state-of-the-art attribution methods and show that, even when optimised, some fail to verify the proposed properties and provide wrong solutions.
This paper focuses on the expected difference in borrower's repayment when there is a change in the lender's credit decisions. Classical estimators overlook the confounding effects and hence the estimation error can be magnificent. As such, we propose another approach to construct the estimators such that the error can be greatly reduced. The proposed estimators are shown to be unbiased, consistent, and robust through a combination of theoretical analysis and numerical testing. Moreover, we compare the power of estimating the causal quantities between the classical estimators and the proposed estimators. The comparison is tested across a wide range of models, including linear regression models, tree-based models, and neural network-based models, under different simulated datasets that exhibit different levels of causality, different degrees of nonlinearity, and different distributional properties. Most importantly, we apply our approaches to a large observational dataset provided by a global technology firm that operates in both the e-commerce and the lending business. We find that the relative reduction of estimation error is strikingly substantial if the causal effects are accounted for correctly.
BERT-based architectures currently give state-of-the-art performance on many NLP tasks, but little is known about the exact mechanisms that contribute to its success. In the current work, we focus on the interpretation of self-attention, which is one of the fundamental underlying components of BERT. Using a subset of GLUE tasks and a set of handcrafted features-of-interest, we propose the methodology and carry out a qualitative and quantitative analysis of the information encoded by the individual BERT's heads. Our findings suggest that there is a limited set of attention patterns that are repeated across different heads, indicating the overall model overparametrization. While different heads consistently use the same attention patterns, they have varying impact on performance across different tasks. We show that manually disabling attention in certain heads leads to a performance improvement over the regular fine-tuned BERT models.
Clustering is an essential data mining tool that aims to discover inherent cluster structure in data. For most applications, applying clustering is only appropriate when cluster structure is present. As such, the study of clusterability, which evaluates whether data possesses such structure, is an integral part of cluster analysis. However, methods for evaluating clusterability vary radically, making it challenging to select a suitable measure. In this paper, we perform an extensive comparison of measures of clusterability and provide guidelines that clustering users can reference to select suitable measures for their applications.
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