Constructing Executable Analytical Knowledge Representations for Meta-Analysis Synthesis Using an Agentic Harness

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.

Transforming Evidence Synthesis: A Systematic Review of the Evolution of Automated Meta-Analysis in the Age of AI

Exponential growth in scientific literature has heightened the demand for efficient evidence-based synthesis, driving the rise of the field of Automated Meta-analysis (AMA) powered by natural language processing and machine learning. This PRISMA systematic review introduces a structured framework for assessing the current state of AMA, based on screening 978 papers from 2006 to 2024, and analyzing 54 studies across diverse domains. Findings reveal a predominant focus on automating data processing (57%), such as extraction and statistical modeling, while only 17% address advanced synthesis stages. Just one study (2%) explored preliminary full-process automation, highlighting a critical gap that limits AMA's capacity for comprehensive synthesis. Despite recent breakthroughs in large language models (LLMs) and advanced AI, their integration into statistical modeling and higher-order synthesis, such as heterogeneity assessment and bias evaluation, remains underdeveloped. This has constrained AMA's potential for fully autonomous meta-analysis. From our dataset spanning medical (67%) and non-medical (33%) applications, we found that AMA has exhibited distinct implementation patterns and varying degrees of effectiveness in actually improving efficiency, scalability, and reproducibility. While automation has enhanced specific meta-analytic tasks, achieving seamless, end-to-end automation remains an open challenge. As AI systems advance in reasoning and contextual understanding, addressing these gaps is now imperative. Future efforts must focus on bridging automation across all meta-analysis stages, refining interpretability, and ensuring methodological robustness to fully realize AMA's potential for scalable, domain-agnostic synthesis.