PDA (Privacy-Preserving Distributed Algorithms) in action: ten principles for high-quality multi-site clinical evidence generation

BACKGROUND: Distributed Research Networks (DRNs) offer significant opportunities for collaborative multi-site research and have significantly advanced healthcare research based on clinical observational data. However, generating high-quality real-world evidence using fit-for-use data from multi-site studies faces important challenges, including biases associated with various types of heterogeneity within and across sites and data sharing difficulties. Over the last 10 years, Privacy-Preserving Distributed Algorithms (PDA) have been developed and utilized in numerous national and international real-world studies spanning diverse domains, from comparative effectiveness research, target trial emulation, to healthcare delivery, policy evaluation, and system performance assessment. Despite these advances, there remains a lack of comprehensive and clear guiding principles for generating high-quality real-world evidence through collaborative studies leveraging the methods under PDA. OBJECTIVE: The paper aims to establish 10 principles of best practice for conducting high-quality multi-site studies using PDA. These principles cover all phases of research, including study preparation, protocol development, analysis, and final reporting. DISCUSSION: The 10 principles for conducting a PDA study outline a principled, efficient, and transparent framework for employing distributed learning algorithms within DRNs to generate reliable and reproducible real-world evidence.