Organizations: School of Mathematical and Computational Sciences Massey University Auckland, New Zealand
Abstract
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.
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.
While automated research systems promise to accelerate empirical analysis, they are prone to silent failures: instances in which analysis code executes successfully yet relies on invalid causal assumptions. We present the Artificial Intelligence (AI)-based Epidemiology Research Assistant (ARA), a framework that makes these failures visible by explicitly encoding causal design principles, study-specific assumptions, and methodological constraints. ARA integrates protocol construction, synthetic data generation, and adversarial validation into a unified pipeline. The framework translates natural language research questions into structured causal protocols and executable analysis code by first constructing a protocol and then generating synthetic datasets using Structural Causal Models (SCMs) with known ground-truth effects. This synthetic-data step can also support pipeline development when access to confidential data, such as medical data, is restricted. The generated analysis is then evaluated under controlled violations of identification assumptions. We evaluate ARA on the Automated Causal Reasoning Benchmark, assessing recovery of identification strategies, causal quantities, treatment and outcome variables, and consistency between generated code and approved protocol. Protocol construction and adversarial validation did not consistently improve numerical agreement with benchmark estimates compared with standard LLM-based generation. However, they changed the failure mode: instead of silently returning causal estimates, ARA often surfaced protocol concerns, diagnostic failures, incomplete inference, or downgraded non-causal interpretations. These findings suggest that validity-first automated science systems should be evaluated not only by answer accuracy, but also by whether they indicate when causal claims are unwarranted.