Despite the overwhelming performance improvements offered by recent natural language processing (NLP) models, the decisions made by these models are largely a black box. Towards closing this gap, the field of causal NLP combines causal inference literature with modern NLP models to elucidate causal effects of text features. We replicate and extend Bansal et al's work on regularizing text classifiers to adhere to estimated effects, focusing instead on model interpretability. Specifically, we focus on developing a two-headed RieszNet-based neural network architecture which achieves better treatment effect estimation accuracy. Our framework, CausalSent, accurately predicts treatment effects in semi-synthetic IMDB movie reviews, reducing MAE of effect estimates by 2-3x compared to Bansal et al's MAE on synthetic Civil Comments data. With an ensemble of validated models, we perform an observational case study on the causal effect of the word "love" in IMDB movie reviews, finding that the presence of the word "love" causes a +2.9% increase in the probability of a positive sentiment.

Causal machine learning (CML) enables individualized estimation of treatment effects, offering critical advantages over traditional correlation-based methods. However, existing approaches for medical survival data with censoring such as causal survival forests estimate effects at fixed time points, limiting their ability to capture dynamic changes over time. We introduce Causal Analysis for Survival Trajectories (CAST), a novel framework that models treatment effects as continuous functions of time following treatment. By combining parametric and non-parametric methods, CAST overcomes the limitations of discrete time-point analysis to estimate continuous effect trajectories. Using the RADCURE dataset [1] of 2,651 patients with head and neck squamous cell carcinoma (HNSCC) as a clinically relevant example, CAST models how chemotherapy and radiotherapy effects evolve over time at the population and individual levels. By capturing the temporal dynamics of treatment response, CAST reveals how treatment effects rise, peak, and decline over the follow-up period, helping clinicians determine when and for whom treatment benefits are maximized. This framework advances the application of CML to personalized care in HNSCC and other life-threatening medical conditions. Source code/data available at: https://github.com/CAST-FW/HNSCC

Clinical decisions to treat and diagnose patients are affected by implicit biases formed by racism, ableism, sexism, and other stereotypes. These biases reflect broader systemic discrimination in healthcare and risk marginalizing already disadvantaged groups. Existing methods for measuring implicit biases require controlled randomized testing and only capture individual attitudes rather than outcomes. However, the "big-data" revolution has led to the availability of large observational medical datasets, like EHRs and biobanks, that provide the opportunity to investigate discrepancies in patient health outcomes. In this work, we propose a causal inference approach to detect the effect of clinician implicit biases on patient outcomes in large-scale medical data. Specifically, our method uses proximal mediation to disentangle pathway-specific effects of a patient's sociodemographic attribute on a clinician's diagnosis decision. We test our method on real-world data from the UK Biobank. Our work can serve as a tool that initiates conversation and brings awareness to unequal health outcomes caused by implicit biases.

The g-formula can be used to estimate causal effects of sustained treatment strategies using observational data under the identifying assumptions of consistency, positivity, and exchangeability. The non-iterative conditional expectation (NICE) estimator of the g-formula also requires correct estimation of the conditional distribution of the time-varying treatment, confounders, and outcome. Parametric models, which have been traditionally used for this purpose, are subject to model misspecification, which may result in biased causal estimates. Here, we propose a unified deep learning framework for the NICE g-formula estimator that uses multitask recurrent neural networks for estimation of the joint conditional distributions. Using simulated data, we evaluated our model's bias and compared it with that of the parametric g-formula estimator. We found lower bias in the estimates of the causal effect of sustained treatment strategies on a survival outcome when using the deep learning estimator compared with the parametric NICE estimator in settings with simple and complex temporal dependencies between covariates. These findings suggest that our Deep Learning g-formula estimator may be less sensitive to model misspecification than the classical parametric NICE estimator when estimating the causal effect of sustained treatment strategies from complex observational data.

As language technologies become widespread, it is important to understand how variations in language affect reader perceptions -- formalized as the isolated causal effect of some focal language-encoded intervention on an external outcome. A core challenge of estimating isolated effects is the need to approximate all non-focal language outside of the intervention. In this paper, we introduce a formal estimation framework for isolated causal effects and explore how different approximations of non-focal language impact effect estimates. Drawing on the principle of omitted variable bias, we present metrics for evaluating the quality of isolated effect estimation and non-focal language approximation along the axes of fidelity and overlap. In experiments on semi-synthetic and real-world data, we validate the ability of our framework to recover ground truth isolated effects, and we demonstrate the utility of our proposed metrics as measures of quality for both isolated effect estimates and non-focal language approximations.

A central question in human immunology is how a patient's repertoire of T cells impacts disease. Here, we introduce a method to infer the causal effects of T cell receptor (TCR) sequences on patient outcomes using observational TCR repertoire sequencing data and clinical outcomes data. Our approach corrects for unobserved confounders, such as a patient's environment and life history, by using the patient's immature, pre-selection TCR repertoire. The pre-selection repertoire can be estimated from nonproductive TCR data, which is widely available. It is generated by a randomized mutational process, V(D)J recombination, which provides a natural experiment. We show formally how to use the pre-selection repertoire to draw causal inferences, and develop a scalable neural-network estimator for our identification formula. Our method produces an estimate of the effect of interventions that add a specific TCR sequence to patient repertoires. As a demonstration, we use it to analyze the effects of TCRs on COVID-19 severity, uncovering potentially therapeutic TCRs that are (1) observed in patients, (2) bind SARS-CoV-2 antigens in vitro and (3) have strong positive effects on clinical outcomes.

Supervised machine learning (ML) and deep learning (DL) algorithms excel at predictive tasks, but it is commonly assumed that they often do so by exploiting non-causal correlations, which may limit both interpretability and generalizability. Here, we show that this trade-off between explanation and prediction is not as deep and fundamental as expected. Whereas ML and DL algorithms will indeed tend to use non-causal features for prediction when fed indiscriminately with all data, it is possible to constrain the learning process of any ML and DL algorithm by selecting features according to Pearl's backdoor adjustment criterion. In such a situation, some algorithms, in particular deep neural networks, can provide near unbiased effect estimates under feature collinearity. Remaining biases are explained by the specific algorithmic structures as well as hyperparameter choice. Consequently, optimal hyperparameter settings are different when tuned for prediction or inference, confirming the general expectation of a trade-off between prediction and explanation. However, the effect of this trade-off is small compared to the effect of a causally constrained feature selection. Thus, once the causal relationship between the features is accounted for, the difference between prediction and explanation may be much smaller than commonly assumed. We also show that such causally constrained models generalize better to new data with altered collinearity structures, suggesting generalization failure may often be due to a lack of causal learning. Our results not only provide a perspective for using ML for inference of (causal) effects but also help to improve the generalizability of fitted ML and DL models to new data.

TSCI implements treatment effect estimation from observational data under invalid instruments in the R statistical computing environment. Existing instrumental variable approaches rely on arguably strong and untestable identification assumptions, which limits their practical application. TSCI does not require the classical instrumental variable identification conditions and is effective even if all instruments are invalid. TSCI implements a two-stage algorithm. In the first stage, machine learning is used to cope with nonlinearities and interactions in the treatment model. In the second stage, a space to capture the instrument violations is selected in a data-adaptive way. These violations are then projected out to estimate the treatment effect.

In biomarker studies it is popular to perform an unsupervised clustering of high-dimensional variables like genome wide screens of SNPs, gene expressions, and protein data and regress for example treatment response, patient recorded outcome measures, time to disease progression, or overall survival on these potentially mislabelled clusters. It is well-known from the statistical literature that errors in continuous and categorical covariates can lead to loss of important information about effects on outcome (Carroll et al., 2006). However, to our surprise this is often ignored when regressing outcome on classes identified by unsupervised learning, which might lead to important clinical effect measures being overlooked (Alizadeh et al., 2000; Veer et al., 2002; Guinney et al., 2015; Zhan et al., 2006; Broyl et al., 2010). We suggest to cast the problem as a covariate misclassification problem. This leaves us with a concourse of possible modelling and analysis options, see for example the book by Carroll et al. (2006) or the recent review by Brakenhoff et al. (2018).

Non-linear machine learning models often trade off a great predictive performance for a lack of interpretability. However, model agnostic interpretation techniques now allow us to estimate the effect and importance of features for any predictive model. Different notations and terminology have complicated their understanding and how they are related. A unified view on these methods has been missing. We present the generalized SIPA (Sampling, Intervention, Prediction, Aggregation) framework of work stages for model agnostic interpretation techniques and demonstrate how several prominent methods for feature effects can be embedded into the proposed framework. We also formally introduce pre-existing marginal effects to describe feature effects for black box models. Furthermore, we extend the framework to feature importance computations by pointing out how variance-based and performance-based importance measures are based on the same work stages. The generalized framework may serve as a guideline to conduct model agnostic interpretations in machine learning.