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.
We preregistered a comparison of two ways to help an LLM answer questions over a small research corpus: a single-round Vector RAG system and an LLM-compiled markdown wiki. Both systems answered the same 13 questions over 24 papers using the same answer-generating model, and their answers were scored by blinded LLM judges. The wiki scored much better at connecting findings across papers, but its advantage in answer organization was not strong after judge adjustment. RAG met the preregistered test for single-fact lookup questions. The clean query-side cost result went against the expected wiki advantage: under the tested setup, the wiki used far more query tokens than RAG, so it could not recover any upfront build cost through cheaper queries. Two exploratory analyses changed how we interpret the result. First, claim-level citation checking favored the wiki: its cited pages more often supported the exact claims being made, even though RAG scored better on the overall groundedness rubric. Second, a decomposition-based RAG variant recovered most of the wiki's advantage on cross-paper synthesis at lower LLM-token cost, but it did not recover the wiki advantage in claim-by-claim citation support. The main conclusion is that grounded research synthesis is not a single capability. Systems can differ in how well they organize evidence, how well their citations support each claim, and how much they cost to run. In this study, no architecture was best on all three.
Meta-analysis synthesis highlights a fundamental challenge in knowledge-based scientific analysis: structured evidence does not by itself represent the analytical knowledge required for executable computation. Decisions about evidence assignment, analytical contrasts, outcome and time-point alignment, effect-size formulation, and methodological admissibility must be explicit before statistical execution. Existing automated approaches often embed these decisions in model outputs, generated code, or workflow traces rather than representing them as independently verifiable knowledge. We introduce the Executable Analytical Knowledge Representation (EAKR), a machine-actionable representation of the knowledge required to transform structured evidence into executable meta-analysis. An EAKR represents evidence, relations, numerical inputs, constraints, provenance, and unresolved issues. We operationalise EAKR in MetaSynDec, an agentic harness in which large language models propose structured updates and deterministic services govern schema- and contract-based validation and execution. Across 58 synthesis units, MetaSynDec constructed all EAKRs, with 57 proceeding to statistical execution. Of 56 units with sufficient information to define a reference analysis object, 38 (67.9%) achieved complete object fidelity and 42 (75.0%) exact evidence-set agreement, with a mean Jaccard similarity of 0.909. Generated and published confidence intervals overlapped in 54 of 55 units (98.2%). MetaSynDec outperformed direct LLM generation in reference synthesis-structure agreement (57/58 versus 23/58; p<0.001) and among 23 jointly completed units, exact reference-formulation agreement (23/23 versus 1/23; p<0.001). These findings provide feasibility evidence that EAKR supports formal validation, traceability, statistical execution, and improved methodological agreement relative to direct LLM generation.