Zero-shot interpretable biomedical literature appraisal with generative large language models.

Objective: This study aims to apply 2 decoder-based Generative Pre-trained Transformer (GPT) models (GPT-4o and GPT-o3-mini) in automating the methodological appraisal of randomized controlled trials (RCTs), under a variety of prompt designs, and to compare their performance to a fine-tuned encoder-only BioLinkBERT model. Materials and Methods: A stratified random sample of 800 articles from the McMaster Premium LiteratUre Service and Clinical Hedges databases was appraised using 2 prompting schemes: (1) classifier (independent assessment) and (2) verifier (validation of BioLinkBERT) considering either the title and abstract (TIAB) or the full text of an article. Performance was primarily evaluated against human assessments using Matthews correlation coefficient (MCC). Bootstrapping over 1000 iterations was used to estimate 95% CIs. Results: GPT-4o as a classifier with full text demonstrated comparable performance (MCC 0.429; 95% CI, 0.387-0.470) to BioLinkBERT (MCC, 0.466; 95% CI, 0.409-0.519), drastically outperforming the best GPT-o3-mini scheme (MCC, 0.272; 95% CI, 0.211-0.334). GPT-4o as a verifier with full text showed similar performance (MCC, 0.391; 95% CI, 0.335-0.444). GPT models provided transparent criterion-specific justifications. Performance using TIAB alone markedly decreased for GPT models (MCC, ≤0.100), highlighting dependency on detailed methodological information. Discussion: GPT-4o effectively automates RCT critical appraisal with comparable performance to specialized fine-tuned models when provided full text, enhancing interpretability and transparency through explicit justifications. Limitations in abstract-level detail suggest complementary roles for fine-tuned models when full texts are unavailable. Future studies should optimize goal-specific prompting to further facilitate adoption in clinical knowledge translation workflows.