Its first mention as a methodological principle in a textbook may have been in 1952, in the first edition of Elementary Medical Statistics authored by clinical epidemiologist Donald Mainland. In a section of the book entitled ‘On Planning a Simple Experiment’, a subsection entitled ‘Intercurrent events’ addressed the problem resulting from unforeseen events that may occur during any treatment. This may happen after random allocation and be known or suspected to influence the outcome of a clinical trial. Mainland listed five events to illustrate the challenge (Mainland 1952a, p 109):