Abstract:Imagine a world where clinical trials need far fewer patients to achieve the same statistical power, thanks to the knowledge encoded in large language models (LLMs). We present a novel framework for hierarchical Bayesian modeling of adverse events in multi-center clinical trials, leveraging LLM-informed prior distributions. Unlike data augmentation approaches that generate synthetic data points, our methodology directly obtains parametric priors from the model. Our approach systematically elicits informative priors for hyperparameters in hierarchical Bayesian models using a pre-trained LLM, enabling the incorporation of external clinical expertise directly into Bayesian safety modeling. Through comprehensive temperature sensitivity analysis and rigorous cross-validation on real-world clinical trial data, we demonstrate that LLM-derived priors consistently improve predictive performance compared to traditional meta-analytical approaches. This methodology paves the way for more efficient and expert-informed clinical trial design, enabling substantial reductions in the number of patients required to achieve robust safety assessment and with the potential to transform drug safety monitoring and regulatory decision making.
Abstract:Data preprocessing is a critical yet frequently neglected aspect of machine learning, often paid little attention despite its potentially significant impact on model performance. While automated machine learning pipelines are starting to recognize and integrate data preprocessing into their solutions for classification and regression tasks, this integration is lacking for more specialized tasks like survival or time-to-event models. As a result, survival analysis not only faces the general challenges of data preprocessing but also suffers from the lack of tailored, automated solutions in this area. To address this gap, this paper presents 'CleanSurvival', a reinforcement-learning-based solution for optimizing preprocessing pipelines, extended specifically for survival analysis. The framework can handle continuous and categorical variables, using Q-learning to select which combination of data imputation, outlier detection and feature extraction techniques achieves optimal performance for a Cox, random forest, neural network or user-supplied time-to-event model. The package is available on GitHub: https://github.com/datasciapps/CleanSurvival Experimental benchmarks on real-world datasets show that the Q-learning-based data preprocessing results in superior predictive performance to standard approaches, finding such a model up to 10 times faster than undirected random grid search. Furthermore, a simulation study demonstrates the effectiveness in different types and levels of missingness and noise in the data.
Abstract:Large language models (LLMs) have been extensively studied for their abilities to generate convincing natural language sequences, however their utility for quantitative information retrieval is less well understood. In this paper we explore the feasibility of LLMs as a mechanism for quantitative knowledge retrieval to aid data analysis tasks such as elicitation of prior distributions for Bayesian models and imputation of missing data. We present a prompt engineering framework, treating an LLM as an interface to a latent space of scientific literature, comparing responses in different contexts and domains against more established approaches. Implications and challenges of using LLMs as 'experts' are discussed.
Abstract:Explainable AI (XAI) and interpretable machine learning methods help to build trust in model predictions and derived insights, yet also present a perverse incentive for analysts to manipulate XAI metrics to support pre-specified conclusions. This paper introduces the concept of X-hacking, a form of p-hacking applied to XAI metrics such as Shap values. We show how an automated machine learning pipeline can be used to search for 'defensible' models that produce a desired explanation while maintaining superior predictive performance to a common baseline. We formulate the trade-off between explanation and accuracy as a multi-objective optimization problem and illustrate the feasibility and severity of X-hacking empirically on familiar real-world datasets. Finally, we suggest possible methods for detection and prevention, and discuss ethical implications for the credibility and reproducibility of XAI research.