Unlocking efficiency in real-world collaborative studies: a multi-site international study with one-shot lossless GLMM algorithm

The widespread adoption of real-world data has given rise to numerous healthcare-distributed research networks, but multi-site analyses still face administrative burdens and data privacy challenges. In response, we developed a Collaborative One-shot Lossless Algorithm for Generalized Linear Mixed Models (COLA-GLMM), the first-ever algorithm that achieves both lossless and one-shot properties. COLA-GLMM ensures accuracy against the gold standard of pooled data while requiring only summary statistics and completes within a single communication round, eliminating the usual back-and-forth overhead. We further introduced an enhanced version that employs homomorphic encryption to reduce the risks of summary statistics misuse at the coordinating center. The simulation studies showed near-exact agreement with the gold standard in parameter estimation, with relative differences of 7.8 × 10⁻⁶%–3.0% under various cell suppression settings. We also validated COLA‑GLMM on eight international decentralized databases to identify risk factors for COVID‑19 mortality. Together, these results show that COLA‑GLMM enables accurate, low‑burden, and privacy-preserving multi‑site research.