Table 1.

Lost in Translation—Some Potential Reasons Why Clinical Stroke Trials Were Unable to Replicate Bench Findings

Complexity of ischemic pathophysiology underestimated

Low quality of preclinical studies, underpowered, effect sizes overestimated, results not robust (low internal validity)

Stroke models do not match with patient characteristics (age, sex, comorbidities, polypharmacology; low external validity)

Negative publication bias (particularly in preclinical research)

Heterogeneity of stroke patients, therapies not matched to individual pathophysiology

Super systemic effects (on immune, cardiovascular system, etc) attributable to a substantial fraction of stroke morbidity and mortality, but little understood and under-researched

Timing of therapy wrong or clinically irrelevant, clinical trial design not matched to preclinical findings

Significant species differences