Accepted for/Published in: Journal of Medical Internet Research
Date Submitted: Oct 2, 2025
Date Accepted: Dec 15, 2025
Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Beyond the Black Box: Assessing the Reliability and Clinical Validity of Large Language Model-Generated Reasoning
ABSTRACT
Background:
Creating high-quality clinical Chains-of-Thought (CoTs) is crucial for explainable medical Artificial Intelligence (AI) while constrained by data scarcity. Although Large Language Models (LLMs) can synthesize medical data, their clinical reliability remains unverified.
Objective:
This study evaluates the reliability of LLM-generated CoTs and investigates prompting strategies to enhance their quality.
Methods:
In a blinded comparative study, senior clinicians in Assisted Reproductive Technology (ART) evaluated CoTs generated via three distinct strategies: Zero-shot, Random Few-shot (using shallow examples), and Selective Few-shot (using diverse, high-quality examples). These expert ratings were compared against evaluations from a state-of-the-art AI model (GPT-4o).
Results:
The Selective Few-shot strategy significantly outperformed other strategies across all human evaluation metrics (p < 0.001). Critically, the Random Few-shot strategy offered no significant improvement over the Zero-shot baseline, demonstrating that low-quality examples are as ineffective as no examples. The success of the Selective strategy is attributed to two principles: "Gold-Standard Depth" (reasoning quality) and "Representative Diversity" (generalization). Notably, the AI evaluator failed to discern these critical performance differences.
Conclusions:
The clinical reliability of synthetic CoTs is dictated by strategic prompt curation, not the mere presence of examples. We propose a "Dual Principles" framework as a foundational methodology to generate trustworthy data at scale. This work offers a validated solution to the data bottleneck and confirms the indispensable role of human expertise in evaluating high-stakes clinical AI.
Citation
