Historically, research ethics committees (RECs) have been guided by ethical principles regarding human experimentation intended to protect participants from physical harms and to provide assurance as to their interests and welfare. But research that analyzes large aggregate data sets, possibly including detailed clinical and genomic information of individuals, may require different assessment. At the same time, growth in international data-sharing collaborations adds stress to a system already under fire for subjecting multisite research to replicate ethics reviews, which can inhibit research without improving the quality of human subjects' protections ( 1 , 2 ). “Top-down” national regulatory approaches exist for ethics review across multiple sites in domestic research projects [e.g., United States ( 3 , 4 ), Canada ( 5 ), United Kingdom, ( 6 ), Australia ( 7 )], but their applicability for data-intensive international research has not been considered. Stakeholders around the world have thus been developing “bottom-up” solutions. We scrutinize five such ef orts involving multiple countries around the world, including resource-poor settings (table S1), to identify models that could inform a framework for mutual recognition of international ethics review (i.e., the acceptance by RECs of the outcome of each other's review).