The advent of fair treatment allocation schedules in clinical trials during the 19th and early 20th centuries

Methods to ensure that like will be compared with like in fair treatment comparisons were proposed at least as early as the 17th century. Reflecting a time-honoured device for ensuring fairness,13 Van Helmont14 and Starkey15 proposed casting lots to decide which patients should be assigned to orthodox physicians (to be bled and purged), and which to their own, alternative treatments. A century later, Anton Mesmer challenged his orthodox physician detractors to cast lots to decide which patients should be treated by them, and which by him, using ‘animal magnetizm’: In order to avoid any later argument and all the questions that could be raised about differences in age, in temperament, in diseases, in their symptoms etc. the assignment of the patients shall be made by the method of lots.16 emphasis added Casting lots is just one of several potentially unbiased methods that can be used to ensure that like will be compared with like in treatment comparisons. Alternation (or rotation) of successive patients to different treatments is an easily understood way of generating patient groups for fair treatment comparisons. As long as the underlying order of the patients' presentation has not been predetermined in some way that introduces bias, strict alternation ensures that no conscious or unconscious bias results in patients with better or worse prognoses being allocated to one of the treatment comparison groups. Other methods that have been used to ensure that like will be compared with like include patients' dates of birth, or the terminal digits of their case record numbers.