Artificial Intelligence Can Match Domain Experts in Evidence Extraction and Critical Appraisal of Microbial Oncogenesis Research Publications
Authors: Kaela Kokkas, Hairong Wang, Richard Klein, Nazir A. Ismail, Natalie Irwin, Mohammad Z. Moonsamy, Kubendran Naidoo, Jeremy Nel, +6 more
Abstract
Confirmed oncogenic microbes contribute significantly to cancer burden. Identifying novel microbial oncogenicity could yield strategies that will reduce disease burdens. However, relevant evidence is dispersed and infeasible for humans to comprehensively synthesize. LLMs may enable scalable, expert-level systematic evidence synthesis to identify microbe-cancer pairs; however, such capabilities have not yet been demonstrated. Domain experts were recruited to create a dataset to benchmark LLM performance (Gemini 2.5 Pro, Gemini 2.5 Flash, GPT-5, GPT-5 Nano) on 24 research papers using MMTV-LV and breast cancer as a case study. We devised a structured template for evidence extraction and appraisal, consisting of MCQ, Likert-scale, multi-select, and free-text question types (77 items across 24 papers). Agreement between (1) experts and (2) experts and each LLM was determined per question instance using novel metrics. LLMs were assessed by comparing inter-expert and expert-LLM agreement distributions to determine whether LLMs behaved as additional experts by increasing or maintaining inter-expert agreement. Free-text responses were further evaluated qualitatively. Across all question types, LLM responses aligned closely with experts, with GPT-5 and GPT-5 Nano achieving score distributions indistinguishable from experts. Gemini models behaved similarly but were significantly more lenient in applying microbial oncogenesis criteria. Hallucinations were rare. Methodological appraisal and identification of contradictions within full-texts were the most persistent LLM vulnerabilities. GPT-5 and GPT-5 Nano were indistinguishable from experts on structured domain research paper evaluation tasks. This supports use of LLMs for automated systematic evidence synthesis. However, methodological appraisal tasks and contradiction identification in full-texts remain weaknesses requiring strengthening.
Large language models (LLMs) have saturated standard medical benchmarks that test factual recall, yet their ability to perform higher-order reasoning, such as synthesizing evidence from multiple sources, remains critically under-explored. To address this gap, we introduce MedMeta, the first benchmark designed to evaluate an LLM's ability to generate conclusions from medical meta-analyses using only the abstracts of cited studies. MedMeta comprises 81 meta-analyses from PubMed (2018--2025) and evaluates models using two distinct workflows: a Retrieval-Augmented Generation (Golden-RAG) setting with ground-truth abstracts, and a Parametric-only approach relying on internal knowledge. Our evaluation framework is validated by a well-structured analysis showing our LLM-as-a-judge protocol strongly aligns with human expert ratings, as evidenced by high Pearson's r correlation (0.81) and Bland-Altman analysis revealing negligible systematic bias, establishing it as a reliable proxy for scalable evaluation. Our findings underscore the critical importance of information grounding: the Golden-RAG workflow consistently and significantly outperforms the Parametric-only approach across models. In contrast, the benefits of domain-specific fine-tuning are marginal and largely neutralized when external material is provided. Furthermore, stress tests show that all models, regardless of architecture, fail to identify and reject negated evidence, highlighting a critical vulnerability in current RAG systems. Notably, even under ideal RAG conditions, current LLMs achieve only slightly above-average performance (~2.7/5.0). MedMeta provides a challenging new benchmark for evidence synthesis and demonstrates that for clinical applications, developing robust RAG systems is a more promising direction than model specialization alone.
Large language models (LLMs) are increasingly being explored for clinical decision support, but their reliability in complex oncology treatment planning remains unclear. We evaluated agentic LLM systems for breast cancer treatment recommendation generation using 72 real clinical cases across stages I to IV and 1,147 case-specific rubrics generated through Asymmetric Information Rubric Generation (AIRG), in which the rubric generator had access to real clinical decisions unavailable to the evaluated models. Seven pipelines were compared, including single-LLM baselines, tool-augmented systems, and multi-agent architectures with fact checking and autonomous subagent spawning. The best-performing configuration, Claude Opus 4.8 with the D&C+SA pipeline, achieved a global score of 0.594 ± 0.025. Tool use and increased agent autonomy had mixed effects, improving performance in some settings but degrading it in others. Performance varied by clinical domain and disease stage, and oncologist-led error analysis revealed persistent clinically relevant failures, including incorrect or missing recommendations, flawed justifications, citation errors, outdated claims, and overconfidence. These findings suggest that agentic LLM systems can generate clinically relevant breast cancer recommendations, but remain insufficient for unsupervised clinical use.
Vinicius Anjos de Almeida, Nícolas Henrique Borges, Leonardo Vicenzi +5
Meta-analysis is a demanding form of evidence synthesis that combines literature retrieval, PI/ECO-guided study selection, and statistical aggregation. Its structured, verifiable workflow makes it an ideal substrate for evaluating systematic scientific reasoning, yet existing benchmarks lack ground truth across the full retrieval-screening-synthesis pipeline. We introduce MetaSyn, a dataset of 442 expert-curated meta-analyses from Nature Portfolio journals. Each entry pairs a research question with PI/ECO criteria, a retrieval corpus of 140k PubMed articles, verified positive studies, hard negatives that are topically similar but PI/ECO-ineligible, and complete search strategies and date bounds. Benchmarking twelve pipeline configurations (nine RAG variants and a protocol-driven agent) reveals a critical screening bottleneck: despite a retrieval ceiling of 90.9% recall at K=200, no system recovers more than 52.7% of ground-truth included literature. Current LLMs fail to reliably separate eligible studies from PI/ECO-failing distractors in pools of comparable topical relevance. Stage-attributed metrics capture where systems succeed and fail; a single end-to-end score does not.