Eligibility-Aware Evidence Synthesis: An Agentic Framework for Clinical Trial Meta-Analysis

Abstract

Clinical evidence synthesis requires identifying relevant trials from large registries and aggregating results that account for population differences. While recent LLM-based approaches have automated components of systematic review, they do not support end-to-end evidence synthesis. Moreover, conventional meta-analysis weights studies by statistical precision without considering clinical compatibility reflected in eligibility criteria. We propose EligMeta, an agentic framework that integrates automated trial discovery with eligibility-aware meta-analysis, translating natural-language queries into reproducible trial selection and incorporating eligibility alignment into study weighting to produce cohort-specific pooled estimates. EligMeta employs a hybrid architecture separating LLM-based reasoning from deterministic execution: LLMs generate interpretable rules from natural-language queries and perform schema-constrained parsing of trial metadata, while all logical operations, weight computations, and statistical pooling are executed deterministically to ensure reproducibility. The framework structures eligibility criteria and computes similarity-based study weights reflecting population alignment between target and comparator trials. In a gastric cancer landscape analysis, EligMeta reduced 4,044 candidate trials to 39 clinically relevant studies through rule-based filtering, recovering all 13 guideline-cited trials. In an olaparib adverse events meta-analysis across four trials, eligibility-aware weighting shifted the pooled risk ratio from 2.18 (95% CI: 1.71-2.79) under conventional Mantel-Haenszel estimation to 1.97 (95% CI: 1.76-2.20), demonstrating quantifiable impact of incorporating eligibility alignment. EligMeta bridges automated trial discovery with eligibility-aware meta-analysis, providing a scalable and reproducible framework for evidence synthesis in precision medicine.

Figures (5)

• Figure 1: Overview of the EligMeta framework for clinical trial evidence synthesis. A free-text clinical query is translated into structured, auditable rule sets defining study selection criteria and a target eligibility profile. These rules are applied through deterministic evaluation to retrieve and filter relevant trials from public registries, with all intermediate artifacts available for expert review. The resulting studies support downstream landscape analysis and eligibility-aware meta-analysis, in which each study's contribution to the pooled estimate is weighted by its population similarity to the target trial.
• Figure 2: Trial selection and structuring workflow. Left: A free-text clinical query is translated into a reviewed set of structured rules defining study selection criteria and target conditions. Each rule is transformed to a function plan via LLM reasoning. Right: The function plans are applied to trial records using format-constrained parsing and deterministic evaluation, producing a filtered set of trials and structured summaries. LLM usage is restricted to rule specification and parsing, while all selection operations are deterministic and auditable.
• Figure 3: Eligibility-aware meta-analysis workflow. Left: Free-text eligibility criteria, together with a target disease specification, are translated into explicit, human-readable penalty rules that capture clinically meaningful differences between trial populations and the target scenario. These rules are evaluated on a structured representation of eligibility criteria to produce trial-level penalty scores through deterministic operations. Right: Penalty scores are transformed into eligibility weights, which are then incorporated into weighted meta-analysis to produce population-aligned effect estimates. LLM usage is restricted to penalty rule specification and schema-constrained parsing, while penalty evaluation, score transformation, and statistical estimation are deterministic and auditable.
• Figure 4: Stepwise filtering results for the gastric cancer use case. The diagram follows the six rules described in the text, showing the number of clinical trials remaining and excluded at each filtering step.
• Figure 5: Comparison of pooled risk ratio estimates for all-grade vomiting under classical precision-based weighting (left) and eligibility-aware weighting (right), for olaparib maintenance versus placebo.

Theorems & Definitions (4)

• Proposition 1: First-order unbiasedness
• proof
• Proposition 2: Large-sample variance
• proof