Andrew J. Larner, Sarah Cooper, Max Cooper
The Charcot Journal. 2026;2(2):25–34.
Abstract
A critical step along the path of evolution of clinical trial design, the blinding of research subjects to administered medications, was pioneered by William Rivers (1864-1922). Although best known for his work with survivors of “shell-shock” during the First World War, Rivers initially trained as a neurologist. His investigation of the effects on fatigue, both muscular and mental, of various substances, particularly caffeine and alcohol, was reported in his Croonian Lectures delivered at the Royal College of Physicians of London in 1906. Key to these controlled studies was Rivers’ method “to exclude the influence of interest, sensory stimulation, and suggestion” on the results. This article examines the setting, the study, the methodology and the aftermath of Rivers’ study. Rivers’ work is found to anticipate several key factors in controlled trial methodology, including: the need for a prolonged initial washout period; the possible confounding effect of craving; the need for placebos to be fully disguised; and the relevance and value of dramatic effects as strong evidence for an intervention.
Keywords: blinding; clinical trials; fatigue; history of neuroscience; William Rivers