The first randomised controlled trial
The Dutch trials of paludrine in malaria and the MRC’s first trial of streptomycin in pulmonary tuberculosis are usually cited as the first publications of the results of randomised controlled trials (RCT). They were both published in the late 1940s. They indeed are probably the first reports of RCTs with a positive outcome. However, negative trials are equally important and results of trials of patulin as a treatment for the common cold were published as a letter in 19431 and a full paper in 19442by Stansfeld and colleagues. Jim Stansfeld who died in 1998 was later to become the first paediatrician in the City of Durham from 1950–82. In his self written obituary he wrote “Later posted to Bovington Camp, Dorset, in order to investigate a supposed cure for common colds—which proved useless.” With this he dismissed, or did not recognise, his major contribution to medical science.
Patulin was isolated in 1941 as part of a search for antibacterial substances produced by molds. It was sent to Dr W E Gye who was investigating anticancer agents. He had a severe cold at the time and tested patulin on himself with encouraging results. Further tests on other staff members were equally positive. A supply was made available to the army in March 1943 and over the next six months 100 soldiers with severe colds were given either patulin or a placebo on an alternate basis. The subjects improved equally quickly and they concluded that patulin had no demonstrable effect on the course of the disease.
Patulin was useless, but this first randomised trial probably saved a huge number of people the indignity of a useless treatment.
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