Ethics, Medicine and Public Health 34 ( 101311). 2026Background: In the United States, federally funded clinical research is often required to collect, analyze, and report ethno-racial data. While the collection of such data may serve important purposes related to inclusion, hypothesis generation, and evidence synthesis, routine analysis and reporting raise important methodological and conceptual concerns. In particular, these practices may reinforce misconceptions about race as a biological category and distort scientific inference. Methodology: This paper critically examines U.S. regulatory requirements and research practices concerning ethno-racial data, focusing on their epistemic and statistical implications. It analyzes fairness-based and epistemic justifications for subgroup analyses, the use of post hoc subgroup comparisons, and recent policy frameworks governing race- and ethnicity-based reporting. Results / discussion: Regulatory expectations surrounding race- and ethnicity-based analyses may encourage exploratory subgroup comparisons without adequate prior justification, increasing the risk of false-positive findings and misleading conclusions. Such practices may also promote unwarranted assumptions about biological differences and influence clinical tools and guidelines. Similar approaches have increasingly appeared outside the United States despite limited scientific justification. Conclusion / perspectives: A shift toward hypothesis-driven research is needed. Race and ethnicity should not be treated as default variables for subgroup analysis and reporting. Instead, race- and ethnicity-based analyses should ordinarily require prospective scientific justification, pre-specified analytical plans, and clear distinction between exploratory and confirmatory findings. Such an approach would strengthen scientific validity while reducing the risk of reinforcing problematic assumptions about race.