Ontology-constrained multi-LLM scoring of hypothesis support in the predictive processing literature

Large language models (LLMs) excel at answering pre-specified questions, yet their ability to navigate the open-ended, pre-conclusion stage of discovery remains largely unmeasured. We introduce Prospective Hypothesis Discovery (PHD), which asks models to autonomously construct grounded, discriminative, and testable hypothesis spaces from inconclusive evidence, including anomalous observations and fragmented records, to guide subsequent investigation. To evaluate this capability, we introduce HypoArena, comprising HypoData, a benchmark of 988 cases across six scientific and analytical domains, and HypoEval, an evaluation framework for open-ended hypothesis sets. To construct HypoData at scale, we propose Retrospective Context Regression, a Forge--Audit pipeline that reconstructs pre-conclusion contexts from completed expert documents by removing explicit conclusions, target hypotheses, and retrospective causal attributions while preserving the factual substrate. Because PHD admits multiple valid outputs, HypoEval combines bidirectional pairwise judgments with Bradley--Terry--Davidson aggregation for ranking and six-dimensional rubric scoring for diagnosis. Experiments on 15 frontier LLMs reveal clear capability stratification and model-dependent effects of structured analytical skills, with gains for several lower-performing models on HypoArena but regressions for other systems, including a top-performing model. Compared with absolute rubric scoring, arena evaluation resolves finer-grained differences among models, with aggregated rankings showing strong agreement with human experts and an independent judge. Together, these results support treating PHD as a distinct target for evaluating how LLMs formulate investigative directions when final conclusions are withheld. Our code and data are publicly available at github.com/SKYLENAGE-AI/HypoArena and github.com/SKYLENAGE-AI/HypoArena.

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.

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.