01621nas a2200169   4500000000100000000000100001008004100002260001500043100001600058700001800074245005500092856004600147300001200193490000700205520122500212022001401437       2025                            d  c2025-07-011 aLauren Hope1 aJarrod Bailey00aBreaking down the barriers to animal-free research  uhttps://doi.org/10.1177/02611929251349465  a215-2310 v533 aFor centuries, animals have been used in research due to their genetic and physiological similarities to humans. However, significant differences exist between humans and animals, which have the potential to confound results obtained from such experiments. These differences result in reduced translatability of animal data to humans, which is a major contributing factor to the 92% failure rate for novel therapies in clinical trials. Advances in scientific research have enabled the development of human-focused New Approach Methodologies (NAMs), which include in silico and 3-D in vitro models. By harnessing these novel approaches, greater predictive power for human biology, human diseases and assessment of novel therapies could be achieved. However, several obstacles remain to their wider adoption, including potential financial constraints, publication bias, and some concerns about the reliability of NAMs due to the novelty of this field, compared to animal studies. Here, we outline the differences between humans and animals used in research, discuss in detail the obstacles to the greater adoption of NAMs in research, and provide recommendations on how to accelerate a shift toward human-focused research.  a0261-1929