Causal machine learning for predicting treatment outcomes

Causal machine learning (ML) offers flexible, data-driven methods for predicting treatment outcomes including efficacy and toxicity, thereby supporting the assessment and safety of drugs. A key benefit of causal ML is that it allows for estimating individualized treatment effects, so that clinical decision-making can be personalized to individual patient profiles. Causal ML can be used in combination with both clinical trial data and real-world data, such as clinical registries and electronic health records, but caution is needed to avoid biased or incorrect predictions. In this Perspective, we discuss the benefits of causal ML (relative to traditional statistical or ML approaches) and outline the key components and steps. Finally, we provide recommendations for the reliable use of causal ML and effective translation into the clinic.

Stabilized Neural Prediction of Potential Outcomes in Continuous Time

Patient trajectories from electronic health records are widely used to predict potential outcomes of treatments over time, which then allows to personalize care. Yet, existing neural methods for this purpose have a key limitation: while some adjust for time-varying confounding, these methods assume that the time series are recorded in discrete time. In other words, they are constrained to settings where measurements and treatments are conducted at fixed time steps, even though this is unrealistic in medical practice. In this work, we aim to predict potential outcomes in continuous time. The latter is of direct practical relevance because it allows for modeling patient trajectories where measurements and treatments take place at arbitrary, irregular timestamps. We thus propose a new method called stabilized continuous time inverse propensity network (SCIP-Net). For this, we further derive stabilized inverse propensity weights for robust prediction of the potential outcomes. To the best of our knowledge, our SCIP-Net is the first neural method that performs proper adjustments for time-varying confounding in continuous time.

Automated Knowledge Concept Annotation and Question Representation Learning for Knowledge Tracing

Knowledge tracing (KT) is a popular approach for modeling students' learning progress over time, which can enable more personalized and adaptive learning. However, existing KT approaches face two major limitations: (1) they rely heavily on expert-defined knowledge concepts (KCs) in questions, which is time-consuming and prone to errors; and (2) KT methods tend to overlook the semantics of both questions and the given KCs. In this work, we address these challenges and present KCQRL, a framework for automated knowledge concept annotation and question representation learning that can improve the effectiveness of any existing KT model. First, we propose an automated KC annotation process using large language models (LLMs), which generates question solutions and then annotates KCs in each solution step of the questions. Second, we introduce a contrastive learning approach to generate semantically rich embeddings for questions and solution steps, aligning them with their associated KCs via a tailored false negative elimination approach. These embeddings can be readily integrated into existing KT models, replacing their randomly initialized embeddings. We demonstrate the effectiveness of KCQRL across 15 KT algorithms on two large real-world Math learning datasets, where we achieve consistent performance improvements.

A Fused Large Language Model for Predicting Startup Success

Investors are continuously seeking profitable investment opportunities in startups and, hence, for effective decision-making, need to predict a startup's probability of success. Nowadays, investors can use not only various fundamental information about a startup (e.g., the age of the startup, the number of founders, and the business sector) but also textual description of a startup's innovation and business model, which is widely available through online venture capital (VC) platforms such as Crunchbase. To support the decision-making of investors, we develop a machine learning approach with the aim of locating successful startups on VC platforms. Specifically, we develop, train, and evaluate a tailored, fused large language model to predict startup success. Thereby, we assess to what extent self-descriptions on VC platforms are predictive of startup success. Using 20,172 online profiles from Crunchbase, we find that our fused large language model can predict startup success, with textual self-descriptions being responsible for a significant part of the predictive power. Our work provides a decision support tool for investors to find profitable investment opportunities.

Model-agnostic meta-learners for estimating heterogeneous treatment effects over time

Estimating heterogeneous treatment effects (HTEs) over time is crucial in many disciplines such as personalized medicine. For example, electronic health records are commonly collected over several time periods and then used to personalize treatment decisions. Existing works for this task have mostly focused on model-based learners (i.e., learners that adapt specific machine-learning models). In contrast, model-agnostic learners -- so-called meta-learners -- are largely unexplored. In our paper, we propose several meta-learners that are model-agnostic and thus can be used in combination with arbitrary machine learning models (e.g., transformers) to estimate HTEs over time. Here, our focus is on learners that can be obtained via weighted pseudo-outcome regressions, which allows for efficient estimation by targeting the treatment effect directly. We then provide a comprehensive theoretical analysis that characterizes the different learners and that allows us to offer insights into when specific learners are preferable. Finally, we confirm our theoretical insights through numerical experiments. In sum, while meta-learners are already state-of-the-art for the static setting, we are the first to propose a comprehensive set of meta-learners for estimating HTEs in the time-varying setting.

Conformal Prediction for Causal Effects of Continuous Treatments

Uncertainty quantification of causal effects is crucial for safety-critical applications such as personalized medicine. A powerful approach for this is conformal prediction, which has several practical benefits due to model-agnostic finite-sample guarantees. Yet, existing methods for conformal prediction of causal effects are limited to binary/discrete treatments and make highly restrictive assumptions such as known propensity scores. In this work, we provide a novel conformal prediction method for potential outcomes of continuous treatments. We account for the additional uncertainty introduced through propensity estimation so that our conformal prediction intervals are valid even if the propensity score is unknown. Our contributions are three-fold: (1) We derive finite-sample prediction intervals for potential outcomes of continuous treatments. (2) We provide an algorithm for calculating the derived intervals. (3) We demonstrate the effectiveness of the conformal prediction intervals in experiments on synthetic and real-world datasets. To the best of our knowledge, we are the first to propose conformal prediction for continuous treatments when the propensity score is unknown and must be estimated from data.

Meta-Learners for Partially-Identified Treatment Effects Across Multiple Environments

Estimating the conditional average treatment effect (CATE) from observational data is relevant for many applications such as personalized medicine. Here, we focus on the widespread setting where the observational data come from multiple environments, such as different hospitals, physicians, or countries. Furthermore, we allow for violations of standard causal assumptions, namely, overlap within the environments and unconfoundedness. To this end, we move away from point identification and focus on partial identification. Specifically, we show that current assumptions from the literature on multiple environments allow us to interpret the environment as an instrumental variable (IV). This allows us to adapt bounds from the IV literature for partial identification of CATE by leveraging treatment assignment mechanisms across environments. Then, we propose different model-agnostic learners (so-called meta-learners) to estimate the bounds that can be used in combination with arbitrary machine learning models. We further demonstrate the effectiveness of our meta-learners across various experiments using both simulated and real-world data. Finally, we discuss the applicability of our meta-learners to partial identification in instrumental variable settings, such as randomized controlled trials with non-compliance.

G-Transformer for Conditional Average Potential Outcome Estimation over Time

Estimating potential outcomes for treatments over time based on observational data is important for personalized decision-making in medicine. Yet, existing neural methods for this task suffer from either (a) bias or (b) large variance. In order to address both limitations, we introduce the G-transformer (GT). Our GT is a novel, neural end-to-end model designed for unbiased, low-variance estimation of conditional average potential outcomes (CAPOs) over time. Specifically, our GT is the first neural model to perform regression-based iterative G-computation for CAPOs in the time-varying setting. We evaluate the effectiveness of our GT across various experiments. In sum, this work represents a significant step towards personalized decision-making from electronic health records.

Data-driven subgrouping of patient trajectories with chronic diseases: Evidence from low back pain

Clinical data informs the personalization of health care with a potential for more effective disease management. In practice, this is achieved by subgrouping, whereby clusters with similar patient characteristics are identified and then receive customized treatment plans with the goal of targeting subgroup-specific disease dynamics. In this paper, we propose a novel mixture hidden Markov model for subgrouping patient trajectories from chronic diseases. Our model is probabilistic and carefully designed to capture different trajectory phases of chronic diseases (i.e., "severe", "moderate", and "mild") through tailored latent states. We demonstrate our subgrouping framework based on a longitudinal study across 847 patients with non-specific low back pain. Here, our subgrouping framework identifies 8 subgroups. Further, we show that our subgrouping framework outperforms common baselines in terms of cluster validity indices. Finally, we discuss the applicability of the model to other chronic and long-lasting diseases.

Causal Machine Learning for Cost-Effective Allocation of Development Aid

The Sustainable Development Goals (SDGs) of the United Nations provide a blueprint of a better future by 'leaving no one behind', and, to achieve the SDGs by 2030, poor countries require immense volumes of development aid. In this paper, we develop a causal machine learning framework for predicting heterogeneous treatment effects of aid disbursements to inform effective aid allocation. Specifically, our framework comprises three components: (i) a balancing autoencoder that uses representation learning to embed high-dimensional country characteristics while addressing treatment selection bias; (ii) a counterfactual generator to compute counterfactual outcomes for varying aid volumes to address small sample-size settings; and (iii) an inference model that is used to predict heterogeneous treatment-response curves. We demonstrate the effectiveness of our framework using data with official development aid earmarked to end HIV/AIDS in 105 countries, amounting to more than USD 5.2 billion. For this, we first show that our framework successfully computes heterogeneous treatment-response curves using semi-synthetic data. Then, we demonstrate our framework using real-world HIV data. Our framework points to large opportunities for a more effective aid allocation, suggesting that the total number of new HIV infections could be reduced by up to 3.3% (~50,000 cases) compared to the current allocation practice.