The controlled clinical trial turns 100 years: Fibiger's trial of serum treatment of diphtheria

The British Medical Research Council's trial of streptomycin for pulmonary tuberculosis, published in 1948,1 has been proposed as the first randomised trial in which random numbers were used and allocation of patients was effectively concealed. Before 1948 several randomised trials had been reported,2 but the method of randomisation was either not stated3 or was open to selection bias—for example, randomisation with use of a deck of cards.4

The earliest of these trials was published in 1898.5 It investigated the effect of serum treatment on diphtheria and was conducted by the Danish Nobel laureate, Johannes Fibiger. It was the first clinical trial in which random allocation was used and emphasised as a pivotal methodological principle. This pioneering improvement in methodology, combined with a large number of patients and rigorous planning, conduct, and reporting, makes the trial a milestone in the history of clinical trials.

Fibiger's trial was published in Danish and its method of randomisation has often been quoted incorrectly. We have translated central passages into English (available on the BMJwebsite at www.bmj.com) and discussed its methodological merit.