Daily Papers

Large language models (LLMs) have shown remarkable progress in encoding clinical knowledge and responding to complex medical queries with appropriate clinical reasoning. However, their applicability in subspecialist or complex medical settings remains underexplored. In this work, we probe the performance of AMIE, a research conversational diagnostic AI system, in the subspecialist domain of breast oncology care without specific fine-tuning to this challenging domain. To perform this evaluation, we curated a set of 50 synthetic breast cancer vignettes representing a range of treatment-naive and treatment-refractory cases and mirroring the key information available to a multidisciplinary tumor board for decision-making (openly released with this work). We developed a detailed clinical rubric for evaluating management plans, including axes such as the quality of case summarization, safety of the proposed care plan, and recommendations for chemotherapy, radiotherapy, surgery and hormonal therapy. To improve performance, we enhanced AMIE with the inference-time ability to perform web search retrieval to gather relevant and up-to-date clinical knowledge and refine its responses with a multi-stage self-critique pipeline. We compare response quality of AMIE with internal medicine trainees, oncology fellows, and general oncology attendings under both automated and specialist clinician evaluations. In our evaluations, AMIE outperformed trainees and fellows demonstrating the potential of the system in this challenging and important domain. We further demonstrate through qualitative examples, how systems such as AMIE might facilitate conversational interactions to assist clinicians in their decision making. However, AMIE's performance was overall inferior to attending oncologists suggesting that further research is needed prior to consideration of prospective uses.

Conditional Average Treatment Effects (CATE) estimation is one of the main challenges in causal inference with observational data. In addition to Machine Learning based-models, nonparametric estimators called meta-learners have been developed to estimate the CATE with the main advantage of not restraining the estimation to a specific supervised learning method. This task becomes, however, more complicated when the treatment is not binary as some limitations of the naive extensions emerge. This paper looks into meta-learners for estimating the heterogeneous effects of multi-valued treatments. We consider different meta-learners, and we carry out a theoretical analysis of their error upper bounds as functions of important parameters such as the number of treatment levels, showing that the naive extensions do not always provide satisfactory results. We introduce and discuss meta-learners that perform well as the number of treatments increases. We empirically confirm the strengths and weaknesses of those methods with synthetic and semi-synthetic datasets.

To effectively optimize and personalize treatments, it is necessary to investigate the heterogeneity of treatment effects. With the wide range of users being treated over many online controlled experiments, the typical approach of manually investigating each dimension of heterogeneity becomes overly cumbersome and prone to subjective human biases. We need an efficient way to search through thousands of experiments with hundreds of target covariates and hundreds of breakdown dimensions. In this paper, we propose a systematic paradigm for detecting, surfacing and characterizing heterogeneous treatment effects. First, we detect if treatment effect variation is present in an experiment, prior to specifying any breakdowns. Second, we surface the most relevant dimensions for heterogeneity. Finally, we characterize the heterogeneity beyond just the conditional average treatment effects (CATE) by studying the conditional distributions of the estimated individual treatment effects. We show the effectiveness of our methods using simulated data and empirical studies.

Machine learning (ML) holds great potential for accurately forecasting treatment outcomes over time, which could ultimately enable the adoption of more individualized treatment strategies in many practical applications. However, a significant challenge that has been largely overlooked by the ML literature on this topic is the presence of informative sampling in observational data. When instances are observed irregularly over time, sampling times are typically not random, but rather informative -- depending on the instance's characteristics, past outcomes, and administered treatments. In this work, we formalize informative sampling as a covariate shift problem and show that it can prohibit accurate estimation of treatment outcomes if not properly accounted for. To overcome this challenge, we present a general framework for learning treatment outcomes in the presence of informative sampling using inverse intensity-weighting, and propose a novel method, TESAR-CDE, that instantiates this framework using Neural CDEs. Using a simulation environment based on a clinical use case, we demonstrate the effectiveness of our approach in learning under informative sampling.

Dynamic treatment regimes (DTRs) are personalized, adaptive, multi-stage treatment plans that adapt treatment decisions both to an individual's initial features and to intermediate outcomes and features at each subsequent stage, which are affected by decisions in prior stages. Examples include personalized first- and second-line treatments of chronic conditions like diabetes, cancer, and depression, which adapt to patient response to first-line treatment, disease progression, and individual characteristics. While existing literature mostly focuses on estimating the optimal DTR from offline data such as from sequentially randomized trials, we study the problem of developing the optimal DTR in an online manner, where the interaction with each individual affect both our cumulative reward and our data collection for future learning. We term this the DTR bandit problem. We propose a novel algorithm that, by carefully balancing exploration and exploitation, is guaranteed to achieve rate-optimal regret when the transition and reward models are linear. We demonstrate our algorithm and its benefits both in synthetic experiments and in a case study of adaptive treatment of major depressive disorder using real-world data.

Inferring unbiased treatment effects has received widespread attention in the machine learning community. In recent years, our community has proposed numerous solutions in standard settings, high-dimensional treatment settings, and even longitudinal settings. While very diverse, the solution has mostly relied on neural networks for inference and simultaneous correction of assignment bias. New approaches typically build on top of previous approaches by proposing new (or refined) architectures and learning algorithms. However, the end result -- a neural-network-based inference machine -- remains unchallenged. In this paper, we introduce a different type of solution in the longitudinal setting: a closed-form ordinary differential equation (ODE). While we still rely on continuous optimization to learn an ODE, the resulting inference machine is no longer a neural network. Doing so yields several advantages such as interpretability, irregular sampling, and a different set of identification assumptions. Above all, we consider the introduction of a completely new type of solution to be our most important contribution as it may spark entirely new innovations in treatment effects in general. We facilitate this by formulating our contribution as a framework that can transform any ODE discovery method into a treatment effects method.

In the pharmaceutical industry, the use of artificial intelligence (AI) has seen consistent growth over the past decade. This rise is attributed to major advancements in statistical machine learning methodologies, computational capabilities and the increased availability of large datasets. AI techniques are applied throughout different stages of drug development, ranging from drug discovery to post-marketing benefit-risk assessment. Kolluri et al. provided a review of several case studies that span these stages, featuring key applications such as protein structure prediction, success probability estimation, subgroup identification, and AI-assisted clinical trial monitoring. From a regulatory standpoint, there was a notable uptick in submissions incorporating AI components in 2021. The most prevalent therapeutic areas leveraging AI were oncology (27%), psychiatry (15%), gastroenterology (12%), and neurology (11%). The paradigm of personalized or precision medicine has gained significant traction in recent research, partly due to advancements in AI techniques hamburg2010path. This shift has had a transformative impact on the pharmaceutical industry. Departing from the traditional "one-size-fits-all" model, personalized medicine incorporates various individual factors, such as environmental conditions, lifestyle choices, and health histories, to formulate customized treatment plans. By utilizing sophisticated machine learning algorithms, clinicians and researchers are better equipped to make informed decisions in areas such as disease prevention, diagnosis, and treatment selection, thereby optimizing health outcomes for each individual.

Objective: Using natural language processing (NLP) to find sentences that state treatment plans in a clinical note, would automate plan extraction and would further enable their use in tools that help providers and care managers. However, as in the most NLP tasks on clinical text, creating gold standard to train and test NLP models is tedious and expensive. Fortuitously, sometimes but not always clinical notes contain sections with a heading that identifies the section as a plan. Leveraging contents of such labeled sections as a noisy training data, we assessed accuracy of NLP models trained with the data. Methods: We used common variations of plan headings and rule-based heuristics to find plan sections with headings in clinical notes, and we extracted sentences from them and formed a noisy training data of plan sentences. We trained Support Vector Machine (SVM) and Convolutional Neural Network (CNN) models with the data. We measured accuracy of the trained models on the noisy dataset using ten-fold cross validation and separately on a set-aside manually annotated dataset. Results: About 13% of 117,730 clinical notes contained treatment plans sections with recognizable headings in the 1001 longitudinal patient records that were obtained from Cleveland Clinic under an IRB approval. We were able to extract and create a noisy training data of 13,492 plan sentences from the clinical notes. CNN achieved best F measures, 0.91 and 0.97 in the cross-validation and set-aside evaluation experiments respectively. SVM slightly underperformed with F measures of 0.89 and 0.96 in the same experiments. Conclusion: Our study showed that the training supervised learning models using noisy plan sentences was effective in identifying them in all clinical notes. More broadly, sections with informal headings in clinical notes can be a good source for generating effective training data.

Combination therapies have become the standard of care for diseases such as cancer, tuberculosis, malaria and HIV. However, the combinatorial set of available multi-drug treatments creates a challenge in identifying effective combination therapies available in a situation. To assist medical professionals in identifying beneficial drug-combinations, we construct an expert-annotated dataset for extracting information about the efficacy of drug combinations from the scientific literature. Beyond its practical utility, the dataset also presents a unique NLP challenge, as the first relation extraction dataset consisting of variable-length relations. Furthermore, the relations in this dataset predominantly require language understanding beyond the sentence level, adding to the challenge of this task. We provide a promising baseline model and identify clear areas for further improvement. We release our dataset, code, and baseline models publicly to encourage the NLP community to participate in this task.

Recent work has explored how to train machine learning models which do not discriminate against any subgroup of the population as determined by sensitive attributes such as gender or race. To avoid disparate treatment, sensitive attributes should not be considered. On the other hand, in order to avoid disparate impact, sensitive attributes must be examined, e.g., in order to learn a fair model, or to check if a given model is fair. We introduce methods from secure multi-party computation which allow us to avoid both. By encrypting sensitive attributes, we show how an outcome-based fair model may be learned, checked, or have its outputs verified and held to account, without users revealing their sensitive attributes.

We propose an algorithm for meta-learning that is model-agnostic, in the sense that it is compatible with any model trained with gradient descent and applicable to a variety of different learning problems, including classification, regression, and reinforcement learning. The goal of meta-learning is to train a model on a variety of learning tasks, such that it can solve new learning tasks using only a small number of training samples. In our approach, the parameters of the model are explicitly trained such that a small number of gradient steps with a small amount of training data from a new task will produce good generalization performance on that task. In effect, our method trains the model to be easy to fine-tune. We demonstrate that this approach leads to state-of-the-art performance on two few-shot image classification benchmarks, produces good results on few-shot regression, and accelerates fine-tuning for policy gradient reinforcement learning with neural network policies.

Inspire therapy is an FDA-approved internal neurostimulation treatment for obstructive sleep apnea. However, not all patients respond to this therapy, posing a challenge even for experienced otolaryngologists to determine candidacy. This paper makes the first attempt to leverage both machine learning and deep learning techniques in discerning patient responsiveness to Inspire therapy using medical data and videos captured through Drug-Induced Sleep Endoscopy (DISE), an essential procedure for Inspire therapy. To achieve this, we gathered and annotated three datasets from 127 patients. Two of these datasets comprise endoscopic videos focused on the Base of the Tongue and Velopharynx. The third dataset composes the patient's clinical information. By utilizing these datasets, we benchmarked and compared the performance of six deep learning models and five classical machine learning algorithms. The results demonstrate the potential of employing machine learning and deep learning techniques to determine a patient's eligibility for Inspire therapy, paving the way for future advancements in this field.

Machine learning has successfully framed many sequential decision making problems as either supervised prediction, or optimal decision-making policy identification via reinforcement learning. In data-constrained offline settings, both approaches may fail as they assume fully optimal behavior or rely on exploring alternatives that may not exist. We introduce an inherently different approach that identifies possible "dead-ends" of a state space. We focus on the condition of patients in the intensive care unit, where a "medical dead-end" indicates that a patient will expire, regardless of all potential future treatment sequences. We postulate "treatment security" as avoiding treatments with probability proportional to their chance of leading to dead-ends, present a formal proof, and frame discovery as an RL problem. We then train three independent deep neural models for automated state construction, dead-end discovery and confirmation. Our empirical results discover that dead-ends exist in real clinical data among septic patients, and further reveal gaps between secure treatments and those that were administered.

In semi-supervised learning, unlabeled samples can be utilized through augmentation and consistency regularization. However, we observed certain samples, even undergoing strong augmentation, are still correctly classified with high confidence, resulting in a loss close to zero. It indicates that these samples have been already learned well and do not provide any additional optimization benefits to the model. We refer to these samples as ``naive samples". Unfortunately, existing SSL models overlook the characteristics of naive samples, and they just apply the same learning strategy to all samples. To further optimize the SSL model, we emphasize the importance of giving attention to naive samples and augmenting them in a more diverse manner. Sample adaptive augmentation (SAA) is proposed for this stated purpose and consists of two modules: 1) sample selection module; 2) sample augmentation module. Specifically, the sample selection module picks out {naive samples} based on historical training information at each epoch, then the naive samples will be augmented in a more diverse manner in the sample augmentation module. Thanks to the extreme ease of implementation of the above modules, SAA is advantageous for being simple and lightweight. We add SAA on top of FixMatch and FlexMatch respectively, and experiments demonstrate SAA can significantly improve the models. For example, SAA helped improve the accuracy of FixMatch from 92.50% to 94.76% and that of FlexMatch from 95.01% to 95.31% on CIFAR-10 with 40 labels.

Within the field of causal inference, we consider the problem of estimating heterogeneous treatment effects from data. We propose and validate a novel approach for learning feature representations to aid the estimation of the conditional average treatment effect or CATE. Our method focuses on an intermediate layer in a neural network trained to predict the outcome from the features. In contrast to previous approaches that encourage the distribution of representations to be treatment-invariant, we leverage a genetic algorithm that optimizes over representations useful for predicting the outcome to select those less useful for predicting the treatment. This allows us to retain information within the features useful for predicting outcome even if that information may be related to treatment assignment. We validate our method on synthetic examples and illustrate its use on a real life dataset.

Previous works on Treatment Effect Estimation (TEE) are not in widespread use because they are predominantly theoretical, where strong parametric assumptions are made but untractable for practical application. Recent work uses multilayer perceptron (MLP) for modeling casual relationships, however, MLPs lag far behind recent advances in ML methodology, which limits their applicability and generalizability. To extend beyond the single domain formulation and towards more realistic learning scenarios, we explore model design spaces beyond MLPs, i.e., transformer backbones, which provide flexibility where attention layers govern interactions among treatments and covariates to exploit structural similarities of potential outcomes for confounding control. Through careful model design, Transformers as Treatment Effect Estimators (TransTEE) is proposed. We show empirically that TransTEE can: (1) serve as a general purpose treatment effect estimator that significantly outperforms competitive baselines in a variety of challenging TEE problems (e.g., discrete, continuous, structured, or dosage-associated treatments) and is applicable to both when covariates are tabular and when they consist of structural data (e.g., texts, graphs); (2) yield multiple advantages: compatibility with propensity score modeling, parameter efficiency, robustness to continuous treatment value distribution shifts, explainable in covariate adjustment, and real-world utility in auditing pre-trained language models

Predicting how different interventions will causally affect a specific individual is important in a variety of domains such as personalized medicine, public policy, and online marketing. There are a large number of methods to predict the effect of an existing intervention based on historical data from individuals who received it. However, in many settings it is important to predict the effects of novel interventions (e.g., a newly invented drug), which these methods do not address. Here, we consider zero-shot causal learning: predicting the personalized effects of a novel intervention. We propose CaML, a causal meta-learning framework which formulates the personalized prediction of each intervention's effect as a task. CaML trains a single meta-model across thousands of tasks, each constructed by sampling an intervention, along with its recipients and nonrecipients. By leveraging both intervention information (e.g., a drug's attributes) and individual features~(e.g., a patient's history), CaML is able to predict the personalized effects of novel interventions that do not exist at the time of training. Experimental results on real world datasets in large-scale medical claims and cell-line perturbations demonstrate the effectiveness of our approach. Most strikingly, CaML's zero-shot predictions outperform even strong baselines trained directly on data from the test interventions.

Randomized controlled trials (RCTs) are considered the gold standard for estimating the average treatment effect (ATE) of interventions. One use of RCTs is to study the causes of global poverty -- a subject explicitly cited in the 2019 Nobel Memorial Prize awarded to Duflo, Banerjee, and Kremer "for their experimental approach to alleviating global poverty." Because the ATE is a population summary, anti-poverty experiments often seek to unpack the effect variation around the ATE by conditioning (CATE) on tabular variables such as age and ethnicity that were measured during the RCT data collection. Although such variables are key to unpacking CATE, using only such variables may fail to capture historical, geographical, or neighborhood-specific contributors to effect variation, as tabular RCT data are often only observed near the time of the experiment. In global poverty research, when the location of the experiment units is approximately known, satellite imagery can provide a window into such factors important for understanding heterogeneity. However, there is no method that specifically enables applied researchers to analyze CATE from images. In this paper, using a deep probabilistic modeling framework, we develop such a method that estimates latent clusters of images by identifying images with similar treatment effects distributions. Our interpretable image CATE model also includes a sensitivity factor that quantifies the importance of image segments contributing to the effect cluster prediction. We compare the proposed methods against alternatives in simulation; also, we show how the model works in an actual RCT, estimating the effects of an anti-poverty intervention in northern Uganda and obtaining a posterior predictive distribution over effects for the rest of the country where no experimental data was collected. We make all models available in open-source software.

How do we most effectively treat a disease or condition? Ideally, we could consult a database of evidence gleaned from clinical trials to answer such questions. Unfortunately, no such database exists; clinical trial results are instead disseminated primarily via lengthy natural language articles. Perusing all such articles would be prohibitively time-consuming for healthcare practitioners; they instead tend to depend on manually compiled systematic reviews of medical literature to inform care. NLP may speed this process up, and eventually facilitate immediate consult of published evidence. The Evidence Inference dataset was recently released to facilitate research toward this end. This task entails inferring the comparative performance of two treatments, with respect to a given outcome, from a particular article (describing a clinical trial) and identifying supporting evidence. For instance: Does this article report that chemotherapy performed better than surgery for five-year survival rates of operable cancers? In this paper, we collect additional annotations to expand the Evidence Inference dataset by 25\%, provide stronger baseline models, systematically inspect the errors that these make, and probe dataset quality. We also release an abstract only (as opposed to full-texts) version of the task for rapid model prototyping. The updated corpus, documentation, and code for new baselines and evaluations are available at http://evidence-inference.ebm-nlp.com/.

Alzheimer's disease (AD) is a degenerative brain disease impairing a person's ability to perform day to day activities. The clinical manifestations of Alzheimer's disease are characterized by heterogeneity in age, disease span, progression rate, impairment of memory and cognitive abilities. Due to these variabilities, personalized care and treatment planning, as well as patient counseling about their individual progression is limited. Recent developments in machine learning to detect hidden patterns in complex, multi-dimensional datasets provides significant opportunities to address this critical need. In this work, we use unsupervised and supervised machine learning approaches for subtype identification and prediction. We apply machine learning methods to the extensive clinical observations available at the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set to identify patient subtypes and to predict disease progression. Our analysis depicts the progression space for the Alzheimer's disease into low, moderate and high disease progression zones. The proposed work will enable early detection and characterization of distinct disease subtypes based on clinical heterogeneity. We anticipate that our models will enable patient counseling, clinical trial design, and ultimately individualized clinical care.

Advances in large language models (LLMs) provide new opportunities in healthcare for improved patient care, clinical decision-making, and enhancement of physician and administrator workflows. However, the potential of these models importantly depends on their ability to generalize effectively across clinical environments and populations, a challenge often underestimated in early development. To better understand reasons for these challenges and inform mitigation approaches, we evaluated ClinicLLM, an LLM trained on [HOSPITAL]'s clinical notes, analyzing its performance on 30-day all-cause readmission prediction focusing on variability across hospitals and patient characteristics. We found poorer generalization particularly in hospitals with fewer samples, among patients with government and unspecified insurance, the elderly, and those with high comorbidities. To understand reasons for lack of generalization, we investigated sample sizes for fine-tuning, note content (number of words per note), patient characteristics (comorbidity level, age, insurance type, borough), and health system aspects (hospital, all-cause 30-day readmission, and mortality rates). We used descriptive statistics and supervised classification to identify features. We found that, along with sample size, patient age, number of comorbidities, and the number of words in notes are all important factors related to generalization. Finally, we compared local fine-tuning (hospital specific), instance-based augmented fine-tuning and cluster-based fine-tuning for improving generalization. Among these, local fine-tuning proved most effective, increasing AUC by 0.25% to 11.74% (most helpful in settings with limited data). Overall, this study provides new insights for enhancing the deployment of large language models in the societally important domain of healthcare, and improving their performance for broader populations.

Instrumental variable (IV) methods are used to estimate causal effects in settings with unobserved confounding, where we cannot directly experiment on the treatment variable. Instruments are variables which only affect the outcome indirectly via the treatment variable(s). Most IV applications focus on low-dimensional treatments and crucially require at least as many instruments as treatments. This assumption is restrictive: in the natural sciences we often seek to infer causal effects of high-dimensional treatments (e.g., the effect of gene expressions or microbiota on health and disease), but can only run few experiments with a limited number of instruments (e.g., drugs or antibiotics). In such underspecified problems, the full treatment effect is not identifiable in a single experiment even in the linear case. We show that one can still reliably recover the projection of the treatment effect onto the instrumented subspace and develop techniques to consistently combine such partial estimates from different sets of instruments. We then leverage our combined estimators in an algorithm that iteratively proposes the most informative instruments at each round of experimentation to maximize the overall information about the full causal effect.

Synthesizing clinical evidence largely relies on systematic reviews of clinical trials and retrospective analyses from medical literature. However, the rapid expansion of publications presents challenges in efficiently identifying, summarizing, and updating clinical evidence. Here, we introduce TrialMind, a generative artificial intelligence (AI) pipeline for facilitating human-AI collaboration in three crucial tasks for evidence synthesis: study search, screening, and data extraction. To assess its performance, we chose published systematic reviews to build the benchmark dataset, named TrialReviewBench, which contains 100 systematic reviews and the associated 2,220 clinical studies. Our results show that TrialMind excels across all three tasks. In study search, it generates diverse and comprehensive search queries to achieve high recall rates (Ours 0.711-0.834 v.s. Human baseline 0.138-0.232). For study screening, TrialMind surpasses traditional embedding-based methods by 30% to 160%. In data extraction, it outperforms a GPT-4 baseline by 29.6% to 61.5%. We further conducted user studies to confirm its practical utility. Compared to manual efforts, human-AI collaboration using TrialMind yielded a 71.4% recall lift and 44.2% time savings in study screening and a 23.5% accuracy lift and 63.4% time savings in data extraction. Additionally, when comparing synthesized clinical evidence presented in forest plots, medical experts favored TrialMind's outputs over GPT-4's outputs in 62.5% to 100% of cases. These findings show the promise of LLM-based approaches like TrialMind to accelerate clinical evidence synthesis via streamlining study search, screening, and data extraction from medical literature, with exceptional performance improvement when working with human experts.

We study the problem of adaptively identifying patient subpopulations that benefit from a given treatment during a confirmatory clinical trial. This type of adaptive clinical trial has been thoroughly studied in biostatistics, but has been allowed only limited adaptivity so far. Here, we aim to relax classical restrictions on such designs and investigate how to incorporate ideas from the recent machine learning literature on adaptive and online experimentation to make trials more flexible and efficient. We find that the unique characteristics of the subpopulation selection problem -- most importantly that (i) one is usually interested in finding subpopulations with any treatment benefit (and not necessarily the single subgroup with largest effect) given a limited budget and that (ii) effectiveness only has to be demonstrated across the subpopulation on average -- give rise to interesting challenges and new desiderata when designing algorithmic solutions. Building on these findings, we propose AdaGGI and AdaGCPI, two meta-algorithms for subpopulation construction. We empirically investigate their performance across a range of simulation scenarios and derive insights into their (dis)advantages across different settings.

Decision-makers are often experts of their domain and take actions based on their domain knowledge. Doctors, for instance, may prescribe treatments by predicting the likely outcome of each available treatment. Actions of an expert thus naturally encode part of their domain knowledge, and can help make inferences within the same domain: Knowing doctors try to prescribe the best treatment for their patients, we can tell treatments prescribed more frequently are likely to be more effective. Yet in machine learning, the fact that most decision-makers are experts is often overlooked, and "expertise" is seldom leveraged as an inductive bias. This is especially true for the literature on treatment effect estimation, where often the only assumption made about actions is that of overlap. In this paper, we argue that expertise - particularly the type of expertise the decision-makers of a domain are likely to have - can be informative in designing and selecting methods for treatment effect estimation. We formally define two types of expertise, predictive and prognostic, and demonstrate empirically that: (i) the prominent type of expertise in a domain significantly influences the performance of different methods in treatment effect estimation, and (ii) it is possible to predict the type of expertise present in a dataset, which can provide a quantitative basis for model selection.

The recommendation of medication is a vital aspect of intelligent healthcare systems, as it involves prescribing the most suitable drugs based on a patient's specific health needs. Unfortunately, many sophisticated models currently in use tend to overlook the nuanced semantics of medical data, while only relying heavily on identities. Furthermore, these models face significant challenges in handling cases involving patients who are visiting the hospital for the first time, as they lack prior prescription histories to draw upon. To tackle these issues, we harness the powerful semantic comprehension and input-agnostic characteristics of Large Language Models (LLMs). Our research aims to transform existing medication recommendation methodologies using LLMs. In this paper, we introduce a novel approach called Large Language Model Distilling Medication Recommendation (LEADER). We begin by creating appropriate prompt templates that enable LLMs to suggest medications effectively. However, the straightforward integration of LLMs into recommender systems leads to an out-of-corpus issue specific to drugs. We handle it by adapting the LLMs with a novel output layer and a refined tuning loss function. Although LLM-based models exhibit remarkable capabilities, they are plagued by high computational costs during inference, which is impractical for the healthcare sector. To mitigate this, we have developed a feature-level knowledge distillation technique, which transfers the LLM's proficiency to a more compact model. Extensive experiments conducted on two real-world datasets, MIMIC-III and MIMIC-IV, demonstrate that our proposed model not only delivers effective results but also is efficient. To ease the reproducibility of our experiments, we release the implementation code online.

Providing high quality explanations for AI predictions based on machine learning is a challenging and complex task. To work well it requires, among other factors: selecting a proper level of generality/specificity of the explanation; considering assumptions about the familiarity of the explanation beneficiary with the AI task under consideration; referring to specific elements that have contributed to the decision; making use of additional knowledge (e.g. expert evidence) which might not be part of the prediction process; and providing evidence supporting negative hypothesis. Finally, the system needs to formulate the explanation in a clearly interpretable, and possibly convincing, way. Given these considerations, ANTIDOTE fosters an integrated vision of explainable AI, where low-level characteristics of the deep learning process are combined with higher level schemes proper of the human argumentation capacity. ANTIDOTE will exploit cross-disciplinary competences in deep learning and argumentation to support a broader and innovative view of explainable AI, where the need for high-quality explanations for clinical cases deliberation is critical. As a first result of the project, we publish the Antidote CasiMedicos dataset to facilitate research on explainable AI in general, and argumentation in the medical domain in particular.

This paper presents our team's participation in the MEDIQA-ClinicalNLP2024 shared task B. We present a novel approach to diagnosing clinical dermatology cases by integrating large multimodal models, specifically leveraging the capabilities of GPT-4V under a retriever and a re-ranker framework. Our investigation reveals that GPT-4V, when used as a retrieval agent, can accurately retrieve the correct skin condition 85% of the time using dermatological images and brief patient histories. Additionally, we empirically show that Naive Chain-of-Thought (CoT) works well for retrieval while Medical Guidelines Grounded CoT is required for accurate dermatological diagnosis. Further, we introduce a Multi-Agent Conversation (MAC) framework and show its superior performance and potential over the best CoT strategy. The experiments suggest that using naive CoT for retrieval and multi-agent conversation for critique-based diagnosis, GPT-4V can lead to an early and accurate diagnosis of dermatological conditions. The implications of this work extend to improving diagnostic workflows, supporting dermatological education, and enhancing patient care by providing a scalable, accessible, and accurate diagnostic tool.

Wider access to therapeutic care is one of the biggest challenges in mental health treatment. Due to institutional barriers, some people seeking mental health support have turned to large language models (LLMs) for personalized therapy, even though these models are largely unsanctioned and untested. We investigate the potential and limitations of using LLMs as providers of evidence-based therapy by using mixed methods clinical metrics. Using HELPERT, a prompt run on a large language model using the same process and training as a comparative group of peer counselors, we replicated publicly accessible mental health conversations rooted in Cognitive Behavioral Therapy (CBT) to compare session dynamics and counselor's CBT-based behaviors between original peer support sessions and their reconstructed HELPERT sessions. Two licensed, CBT-trained clinical psychologists evaluated the sessions using the Cognitive Therapy Rating Scale and provided qualitative feedback. Our findings show that the peer sessions are characterized by empathy, small talk, therapeutic alliance, and shared experiences but often exhibit therapist drift. Conversely, HELPERT reconstructed sessions exhibit minimal therapist drift and higher adherence to CBT methods but display a lack of collaboration, empathy, and cultural understanding. Through CTRS ratings and psychologists' feedback, we highlight the importance of human-AI collaboration for scalable mental health. Our work outlines the ethical implication of imparting human-like subjective qualities to LLMs in therapeutic settings, particularly the risk of deceptive empathy, which may lead to unrealistic patient expectations and potential harm.

Recent work has shown promising results in causal discovery by leveraging interventional data with gradient-based methods, even when the intervened variables are unknown. However, previous work assumes that the correspondence between samples and interventions is known, which is often unrealistic. We envision a scenario with an extensive dataset sampled from multiple intervention distributions and one observation distribution, but where we do not know which distribution originated each sample and how the intervention affected the system, i.e., interventions are entirely latent. We propose a method based on neural networks and variational inference that addresses this scenario by framing it as learning a shared causal graph among an infinite mixture (under a Dirichlet process prior) of intervention structural causal models. Experiments with synthetic and real data show that our approach and its semi-supervised variant are able to discover causal relations in this challenging scenario.

Mental health disorders are one of the most serious diseases in the world. Most people with such a disease lack access to adequate care, which highlights the importance of training models for the diagnosis and treatment of mental health disorders. However, in the mental health domain, privacy concerns limit the accessibility of personalized treatment data, making it challenging to build powerful models. In this paper, we introduce MentalArena, a self-play framework to train language models by generating domain-specific personalized data, where we obtain a better model capable of making a personalized diagnosis and treatment (as a therapist) and providing information (as a patient). To accurately model human-like mental health patients, we devise Symptom Encoder, which simulates a real patient from both cognition and behavior perspectives. To address intent bias during patient-therapist interactions, we propose Symptom Decoder to compare diagnosed symptoms with encoded symptoms, and dynamically manage the dialogue between patient and therapist according to the identified deviations. We evaluated MentalArena against 6 benchmarks, including biomedicalQA and mental health tasks, compared to 6 advanced models. Our models, fine-tuned on both GPT-3.5 and Llama-3-8b, significantly outperform their counterparts, including GPT-4o. We hope that our work can inspire future research on personalized care. Code is available in https://github.com/Scarelette/MentalArena/tree/main

Treatment effect estimation in continuous time is crucial for personalized medicine. However, existing methods for this task are limited to point estimates of the potential outcomes, whereas uncertainty estimates have been ignored. Needless to say, uncertainty quantification is crucial for reliable decision-making in medical applications. To fill this gap, we propose a novel Bayesian neural controlled differential equation (BNCDE) for treatment effect estimation in continuous time. In our BNCDE, the time dimension is modeled through a coupled system of neural controlled differential equations and neural stochastic differential equations, where the neural stochastic differential equations allow for tractable variational Bayesian inference. Thereby, for an assigned sequence of treatments, our BNCDE provides meaningful posterior predictive distributions of the potential outcomes. To the best of our knowledge, ours is the first tailored neural method to provide uncertainty estimates of treatment effects in continuous time. As such, our method is of direct practical value for promoting reliable decision-making in medicine.

Understanding causality should be a core requirement of any attempt to build real impact through AI. Due to the inherent unobservability of counterfactuals, large randomised trials (RCTs) are the standard for causal inference. But large experiments are generically expensive, and randomisation carries its own costs, e.g. when suboptimal decisions are trialed. Recent work has proposed more sample-efficient alternatives to RCTs, but these are not adaptable to the downstream application for which the causal effect is sought. In this work, we develop a task-specific approach to experimental design and derive sampling strategies customised to particular downstream applications. Across a range of important tasks, real-world datasets, and sample sizes, our method outperforms other benchmarks, e.g. requiring an order-of-magnitude less data to match RCT performance on targeted marketing tasks.

In causal inference, estimating heterogeneous treatment effects (HTE) is critical for identifying how different subgroups respond to interventions, with broad applications in fields such as precision medicine and personalized advertising. Although HTE estimation methods aim to improve accuracy, how to provide explicit subgroup descriptions remains unclear, hindering data interpretation and strategic intervention management. In this paper, we propose CURLS, a novel rule learning method leveraging HTE, which can effectively describe subgroups with significant treatment effects. Specifically, we frame causal rule learning as a discrete optimization problem, finely balancing treatment effect with variance and considering the rule interpretability. We design an iterative procedure based on the minorize-maximization algorithm and solve a submodular lower bound as an approximation for the original. Quantitative experiments and qualitative case studies verify that compared with state-of-the-art methods, CURLS can find subgroups where the estimated and true effects are 16.1% and 13.8% higher and the variance is 12.0% smaller, while maintaining similar or better estimation accuracy and rule interpretability. Code is available at https://osf.io/zwp2k/.

The recent advancements in artificial intelligence highlight the potential of language models in psychological health support. While models trained on data from mental health service platform have achieved preliminary success, challenges persist in areas such as data scarcity, quality, and ensuring a solid foundation in psychological techniques. To address these challenges, this study introduces a novel approach to enhance the precision and efficacy of psychological support through large language models. Specifically, we design a specific prompt derived from principles of Cognitive Behavioral Therapy (CBT) and have generated the CBT QA dataset, specifically for Chinese psychological health Q&A based on CBT structured intervention strategies. Unlike previous methods, our dataset emphasizes professional and structured response. Utilizing this dataset, we fine-tuned the large language model, giving birth to CBT-LLM, the large-scale language model specifically designed for Cognitive Behavioral Therapy techniques. Empirical evaluations demonstrate that CBT-LLM excels in generating structured, professional, and highly relevant responses in psychological health support tasks, showcasing its practicality and quality. The model is available on Hugging Face: https://huggingface.co/Hongbin37/CBT-LLM.

Literature-Based Discovery (LBD) aims to discover new scientific knowledge by mining papers and generating hypotheses. Standard LBD is limited to predicting pairwise relations between discrete concepts (e.g., drug-disease links), and ignores critical contexts like experimental settings (e.g., a specific patient population where a drug is evaluated) and background motivations (e.g., to find drugs without specific side effects). We address these limitations with a novel formulation of contextualized-LBD (C-LBD): generating scientific hypotheses in natural language, while grounding them in a context that controls the hypothesis search space. We present a modeling framework using retrieval of ``inspirations'' from past scientific papers. Our evaluations reveal that GPT-4 tends to generate ideas with overall low technical depth and novelty, while our inspiration prompting approaches partially mitigate this issue. Our work represents a first step toward building language models that generate new ideas derived from scientific literature.

We consider the task of evaluating policies of algorithmic resource allocation through randomized controlled trials (RCTs). Such policies are tasked with optimizing the utilization of limited intervention resources, with the goal of maximizing the benefits derived. Evaluation of such allocation policies through RCTs proves difficult, notwithstanding the scale of the trial, because the individuals' outcomes are inextricably interlinked through resource constraints controlling the policy decisions. Our key contribution is to present a new estimator leveraging our proposed novel concept, that involves retrospective reshuffling of participants across experimental arms at the end of an RCT. We identify conditions under which such reassignments are permissible and can be leveraged to construct counterfactual trials, whose outcomes can be accurately ascertained, for free. We prove theoretically that such an estimator is more accurate than common estimators based on sample means -- we show that it returns an unbiased estimate and simultaneously reduces variance. We demonstrate the value of our approach through empirical experiments on synthetic, semi-synthetic as well as real case study data and show improved estimation accuracy across the board.

Adversarial training improves the robustness of neural networks against adversarial attacks, albeit at the expense of the trade-off between standard and robust generalization. To unveil the underlying factors driving this phenomenon, we examine the layer-wise learning capabilities of neural networks during the transition from a standard to an adversarial setting. Our empirical findings demonstrate that selectively updating specific layers while preserving others can substantially enhance the network's learning capacity. We therefore propose CURE, a novel training framework that leverages a gradient prominence criterion to perform selective conservation, updating, and revision of weights. Importantly, CURE is designed to be dataset- and architecture-agnostic, ensuring its applicability across various scenarios. It effectively tackles both memorization and overfitting issues, thus enhancing the trade-off between robustness and generalization and additionally, this training approach also aids in mitigating "robust overfitting". Furthermore, our study provides valuable insights into the mechanisms of selective adversarial training and offers a promising avenue for future research.