Isabel Chien

Isabel Chien, Nina Deliu, Richard E. Turner et al. · cambridge

While interest in the application of machine learning to improve healthcare has grown tremendously in recent years, a number of barriers prevent deployment in medical practice. A notable concern is the potential to exacerbate entrenched biases and existing health disparities in society. The area of fairness in machine learning seeks to address these issues of equity; however, appropriate approaches are context-dependent, necessitating domain-specific consideration. We focus on clinical trials, i.e., research studies conducted on humans to evaluate medical treatments. Clinical trials are a relatively under-explored application in machine learning for healthcare, in part due to complex ethical, legal, and regulatory requirements and high costs. Our aim is to provide a multi-disciplinary assessment of how fairness for machine learning fits into the context of clinical trials research and practice. We start by reviewing the current ethical considerations and guidelines for clinical trials and examine their relationship with common definitions of fairness in machine learning. We examine potential sources of unfairness in clinical trials, providing concrete examples, and discuss the role machine learning might play in either mitigating potential biases or exacerbating them when applied without care. Particular focus is given to adaptive clinical trials, which may employ machine learning. Finally, we highlight concepts that require further investigation and development, and emphasize new approaches to fairness that may be relevant to the design of clinical trials.

Javier González, Risa Ueno, Cliff Wong et al.

The rapid digitization of real-world data presents an unprecedented opportunity to optimize healthcare delivery and accelerate biomedical discovery. However, these data are often found in unstructured forms such as clinical notes in electronic medical records (EMRs), and is typically plagued by confounders, making it challenging to generate robust real-world evidence (RWE). Therefore, we present TRIALSCOPE, a framework designed to distil RWE from population level observational data at scale. TRIALSCOPE leverages biomedical language models to structure clinical text at scale, employs advanced probabilistic modeling for denoising and imputation, and incorporates state-of-the-art causal inference techniques to address common confounders in treatment effect estimation. Extensive experiments were conducted on a large-scale dataset of over one million cancer patients from a single large healthcare network in the United States. TRIALSCOPE was shown to automatically curate high-quality structured patient data, expanding the dataset and incorporating key patient attributes only available in unstructured form. The framework reduces confounding in treatment effect estimation, generating comparable results to randomized controlled lung cancer trials. Additionally, we demonstrate simulations of unconducted clinical trials - including a pancreatic cancer trial with varying eligibility criteria - using a suite of validation tests to ensure robustness. Thorough ablation studies were conducted to better understand key components of TRIALSCOPE and establish best practices for RWE generation from EMRs. TRIALSCOPE was able to extract data cancer treatment data from EMRs, overcoming limitations of manual curation. We were also able to show that TRIALSCOPE could reproduce results of lung and pancreatic cancer clinical trials from the extracted real world data.

Umang Bhatt, Isabel Chien, Muhammad Bilal Zafar et al.

As the complexity of machine learning (ML) models increases, resulting in a lack of prediction explainability, several methods have been developed to explain a model's behavior in terms of the training data points that most influence the model. However, these methods tend to mark outliers as highly influential points, limiting the insights that practitioners can draw from points that are not representative of the training data. In this work, we take a step towards finding influential training points that also represent the training data well. We first review methods for assigning importance scores to training points. Given importance scores, we propose a method to select a set of DIVerse INfluEntial (DIVINE) training points as a useful explanation of model behavior. As practitioners might not only be interested in finding data points influential with respect to model accuracy, but also with respect to other important metrics, we show how to evaluate training data points on the basis of group fairness. Our method can identify unfairness-inducing training points, which can be removed to improve fairness outcomes. Our quantitative experiments and user studies show that visualizing DIVINE points helps practitioners understand and explain model behavior better than earlier approaches.