Ecological fallacy as a novel risk factor for poor translation in neuroscience research: A systematic review and simulation study.

BACKGROUND: Translational neuroscience is largely concerned with establishing causal links between biological processes and functional outcomes. Exciting new methods have emerged and top-tier biomedical journals are placing increasingly high demand for experiments that link outcomes. One pitfall to making these connections is the "ecological fallacy"-establishing a relationship between outcomes based on aggregate (averaged) results (a distinct issue from correlation vs causation).

METHODS: To showcase the ecological fallacy, we first used simulated data to define and demonstrate the problem. Next, we performed a systematic review to determine the prevalence of the fallacy in top-tier biomedical journals (Science, Nature Medicine, Neuron, Nature, Nature Neuroscience, Cell). Based on our own research interests and specializations, we specifically focused on recent publications in the area of spinal cord injury and regenerative medicine.

RESULTS: Of the articles reviewed which examined a relationship between central nervous system regeneration and a behavioural outcome, 100% (21/21) were subject to possible ecological fallacy.

CONCLUSIONS: Ecological fallacy is highly prevalent in neuroscience research and could partially account for translation failures in this field. Reporting guidelines for in vivo experiments should include subject-level correlation analyses for the primary outcomes.