There is a lot of confusion about the first use of randomization in an experiment and the first use of randomization in medicine. Some writers think that the great statistician R A Fisher carried out the first randomized trial (in agriculture)¹ and published the results in 1923.^2–5 Others think that the first medical trial was carried out by the British National Research Council in the 1940s.^6,7 But there are earlier examples and we think we have found the oldest.

Readers of this series will know that controlled trials are as old as Biblical Daniel,⁸ the evaluation of smallpox inoculation in 1721,⁹ the evaluation of Mesmerism in 1784,¹⁰ and Semmelweiss’s trials to reduce hospital infections.¹¹ To resolve this debate we have to be precise in our definition of randomization in experiments.

The word “randomization” does not exist in the Oxford English Dictionary or its supplement.^12,13 It has two frequent uses in social science and clinical research. The first is a “random sample” from a larger population. Here randomization is used to ensure that the sample is representative of the population as a whole. The second use of randomization in experimental design is our focus here. There is an experiment, purposefully and prospectively designed; there are control and experimental interventions on patients purposefully designed to eliminate every observable and unobservable difference between the two except for the experimental intervention; and there is a method of assignment which is out …