Skill-Augmented AI Agents for Medical Research Analysis: An Exploratory Multi-Model Human Evaluation in an NSCLC Transcriptomic Biomarker Task
Authors: Qianyu Yao, Fei Sun, Bocheng Huang, Wei Chen, Jiarui Jiang, Shu Quan, Yifei Chen, Wenjie Xu, +5 more
Abstract
Background. Large language models and AI agents are increasingly used to support biomedical research, but native model outputs may omit key analytical steps, misuse methods, or overstate conclusions. We evaluated whether autonomous access to a medical research skill package was associated with higher-quality AI-generated transcriptomic research-analysis outputs compared with native AI without skills. Methods. We conducted an exploratory multi-model human evaluation using a non-small cell lung cancer immunotherapy biomarker task. Six model backbones were tested. The evaluation included 21 anonymized outputs: 9 native-AI outputs and 12 skill-augmented outputs generated through an AI agent implementation represented by OpenClaw. Four non-expert biomedical reviewers and two blinded experts evaluated each output, with two ratings from each reviewer type. The primary outcome was expert-rated overall quality. Results. Skill-augmented outputs showed directionally higher expert overall quality than native-AI outputs (mean 5.50 vs 5.11; difference=0.39; bootstrap 95% CI, -0.04 to 0.90; Welch p=0.156). Non-expert reviewer quality showed the same direction (mean 4.72 vs 4.47; difference=0.26; bootstrap 95% CI, -0.25 to 0.80; Welch p=0.373). Expert agreement was limited (single-rating ICC=-0.15), and model-specific effects were descriptive and heterogeneous. Conclusions. Autonomous skill access showed a directional quality signal in this exploratory sample, but the signal was smaller than expert-rating noise and should not be interpreted as confirmatory evidence. The findings primarily motivate larger evaluations of skill-augmented AI agents with stronger reliability controls, platform replication, and biological-validity assessment.
Background: Agent skills are increasingly deployed as modular, reusable capability units in AI agent systems. Medical research agent skills require safeguards beyond general-purpose evaluation, including scientific integrity, methodological validity, reproducibility, and boundary safety. This study developed and preliminarily evaluated a domain-specific audit framework for medical research agent skills, with a focus on reliability against expert review. Methods: We developed MedSkillAudit (skill-auditor@1.0), a layered framework assessing skill release readiness before deployment. We evaluated 75 skills across five medical research categories (15 per category). Two experts independently assigned a quality score (0-100), an ordinal release disposition (Production Ready / Limited Release / Beta Only / Reject), and a high-risk failure flag. System-expert agreement was quantified using ICC(2,1) and linearly weighted Cohen's kappa, benchmarked against the human inter-rater baseline. Results: The mean consensus quality score was 72.4 (SD = 13.0); 57.3% of skills fell below the Limited Release threshold. MedSkillAudit achieved ICC(2,1) = 0.449 (95% CI: 0.250-0.610), exceeding the human inter-rater ICC of 0.300. System-consensus score divergence (SD = 9.5) was smaller than inter-expert divergence (SD = 12.4), with no directional bias (Wilcoxon p = 0.613). Protocol Design showed the strongest category-level agreement (ICC = 0.551); Academic Writing showed a negative ICC (-0.567), reflecting a structural rubric-expert mismatch. Conclusions: Domain-specific pre-deployment audit may provide a practical foundation for governing medical research agent skills, complementing general-purpose quality checks with structured audit workflows tailored to scientific use cases.
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
Introduction. Clinical and Translational Science Award (CTSA) programs must document their scholars' research impact, but assembling each scholar's record by hand takes staff an estimated 15 hours and does not scale to a full cohort. An artificial intelligence (AI) agent could serve as a tool to gather scholar data across platforms and disciplines. Methods. We built a human-in-the-loop AI agent that assembles a dossier of sourced evidence for each scholar and drafts one-sentence Translational Science Benefits Model (TSBM) impact summaries for staff review. We evaluated it in the impact-reporting workflow of one CTSA hub across 10 career-development (KL2/K12) scholars. Two evaluation staff independently coded all 507 findings as accept, edit, or reject; the primary measure was the unanimous usable rate, defined as the share both accepted or edited. Results. Both reviewers accepted or edited 81.7% of the agent's findings. Reviewers each spent a median of 14 minutes per scholar, replacing an estimated 15 hours of manual assembly. Inter-rater agreement was moderate (Cohen's kappa 0.43 on the usable-versus-reject decision). A profile discovery study found the agent's recall close to human search. The agent's impact evidence spanned all four TSBM domains, and about a third of the reviewed findings fell in non-scholarly categories that routine processes tend to miss. Reviewers rated synthesis accuracy 4.5 and usefulness 4.8 on a 5-point scale. Conclusions. A human-in-the-loop AI agent can serve as the first-pass author of a scholar's impact record, shifting staff from collecting and writing to reviewing, and making cohort-scale impact reporting feasible.