Robert Gallo

Thomas Savage, Ashwin Nayak, Robert Gallo et al.

One of the major barriers to using large language models (LLMs) in medicine is the perception they use uninterpretable methods to make clinical decisions that are inherently different from the cognitive processes of clinicians. In this manuscript we develop novel diagnostic reasoning prompts to study whether LLMs can perform clinical reasoning to accurately form a diagnosis. We find that GPT4 can be prompted to mimic the common clinical reasoning processes of clinicians without sacrificing diagnostic accuracy. This is significant because an LLM that can use clinical reasoning to provide an interpretable rationale offers physicians a means to evaluate whether LLMs can be trusted for patient care. Novel prompting methods have the potential to expose the black box of LLMs, bringing them one step closer to safe and effective use in medicine.

Patrick Vossler, Jean Feng, Venkat Sivaraman et al.

Hospital Quality Improvement (QI) plays a critical role in optimizing healthcare delivery by translating high-level hospital goals into actionable solutions. A critical step of QI is to identify the key modifiable contributing factors, a process we call QI factor discovery, typically through expert-driven semi-structured qualitative tools like fishbone diagrams, chart reviews, and Lean Healthcare methods. AI has the potential to transform and accelerate QI factor discovery, which is traditionally time- and resource-intensive and limited in reproducibility and auditability. Nevertheless, current AI alignment methods assume the task is well-defined, whereas QI factor discovery is an exploratory, fuzzy, and iterative sense-making process that relies on complex implicit expert judgments. To design an AI pipeline that formalizes the QI process while preserving its exploratory components, we propose viewing the task as learning not only LLM prompts but also the overarching natural-language specifications. In particular, we map QI factor discovery to steps of the classical AI/ML development process (problem formalization, model learning, and model validation) where the specifications are tunable hyperparameters. Domain experts and AI agents iteratively refine both the overarching specifications and AI pipeline until AI extractions are concordant with expert annotations and aligned with clinical objectives. We applied this "Human-AI Spec-Solution Co-optimization" framework at an urban safety-net hospital to identify factors driving prolonged length of stay and unplanned 30-day readmissions. The resulting AI-for-QI pipelines achieved $\ge 70\%$ concordance with expert annotations. Compared to prior manual Lean analyses, the AI pipeline was substantially more efficient, recovered previous findings, surfaced new modifiable factors, and produced auditable reasoning traces.

Maia Kotelanski, Robert Gallo, Ashwin Nayak et al.

Large Language Models have difficulty communicating uncertainty, which is a significant obstacle to applying LLMs to complex medical tasks. This study evaluates methods to measure LLM confidence when suggesting a diagnosis for challenging clinical vignettes. GPT4 was asked a series of challenging case questions using Chain of Thought and Self Consistency prompting. Multiple methods were investigated to assess model confidence and evaluated on their ability to predict the models observed accuracy. The methods evaluated were Intrinsic Confidence, SC Agreement Frequency and CoT Response Length. SC Agreement Frequency correlated with observed accuracy, yielding a higher Area under the Receiver Operating Characteristic Curve compared to Intrinsic Confidence and CoT Length analysis. SC agreement is the most useful proxy for model confidence, especially for medical diagnosis. Model Intrinsic Confidence and CoT Response Length exhibit a weaker ability to differentiate between correct and incorrect answers, preventing them from being reliable and interpretable markers for model confidence. We conclude GPT4 has a limited ability to assess its own diagnostic accuracy. SC Agreement Frequency is the most useful method to measure GPT4 confidence.

Peter G. Brodeur, Thomas A. Buckley, Zahir Kanjee et al.

A seminal paper published by Ledley and Lusted in 1959 introduced complex clinical diagnostic reasoning cases as the gold standard for the evaluation of expert medical computing systems, a standard that has held ever since. Here, we report the results of a physician evaluation of a large language model (LLM) on challenging clinical cases against a baseline of hundreds of physicians. We conduct five experiments to measure clinical reasoning across differential diagnosis generation, display of diagnostic reasoning, triage differential diagnosis, probabilistic reasoning, and management reasoning, all adjudicated by physician experts with validated psychometrics. We then report a real-world study comparing human expert and AI second opinions in randomly-selected patients in the emergency room of a major tertiary academic medical center in Boston, MA. We compared LLMs and board-certified physicians at three predefined diagnostic touchpoints: triage in the emergency room, initial evaluation by a physician, and admission to the hospital or intensive care unit. In all experiments--both vignettes and emergency room second opinions--the LLM displayed superhuman diagnostic and reasoning abilities, as well as continued improvement from prior generations of AI clinical decision support. Our study suggests that LLMs have achieved superhuman performance on general medical diagnostic and management reasoning, fulfilling the vision put forth by Ledley and Lusted, and motivating the urgent need for prospective trials.