Learning study similarity to investigate heterogeneity in meta-analysis using LLMs and triplet loss

Abstract

Meta-analyses of observational studies often show substantial between-study heterogeneity, limiting the interpretability of pooled estimates. Meta-regression can be used to explore heterogeneity, but it is often underpowered to handle multiple effect modifiers. We propose a novel framework that integrates large language models (LLMs) with deep metric learning to infer study-level similarity prior to meta-analysis. Study-level clinical and methodological characteristics were processed by an LLM to generate study triplets (anchor, similar, dissimilar). These triplets were constructed by treating each study as an anchor and comparing it with pairs of other studies to identify, in each instance, the study most similar to the anchor. Then, the triplets were used into an embedding model trained with triplet loss; a deep learning approach that learns an embedding space where clinically and methodologically similar studies are clustered together. We apply our framework to a meta-analysis dataset of 58 observational studies comparing cognitive outcomes between preterm- and term-born children. Subsequently, we fit meta-analysis models within the identified study clusters and compare the results with those of the overall analysis. Results suggested three clusters two of which retained considerable between-study heterogeneity. The remaining cluster comprised the most homogeneous group of studies and exhibited a more extreme pooled effect estimate together with a narrower prediction interval compared with the overall analysis. This work presents a novel approach for exploring heterogeneity in meta-analysis by incorporating study characteristics prior to model fitting. By transforming study information into a similarity space, the framework identifies coherent subgroups and supports more precise inference in heterogeneous real-world evidence.