Fisher and Bradford Hill: their personal impact

When the time came for me to leave school, there was only one subject I wanted to study: mathematics. I decided, however, for reasons that have been described elsewhere1 to read medicine instead. It was, therefore, not surprising that, as a medical student, I sought ways in which mathematics could be used in medicine and it was not long before I discovered one, when I came across Fisher’s2 book on statistical methods for research workers. Most of it was beyond me, but it led me to the χ2 test, with the result that my first publication was an article in the St Thomas’s Hospital Gazette in which I showed the poverty of the evidence that had been cited by one of my teachers in support of the belief that gonadotropic hormones would help the descent of undescended testes in young boys.3 For as big or bigger a difference between the descent rate observed in treated boys and that in the historical series with which it had been compared might have been expected to occur by chance six times out of ten. Re-reading the article now, I am struck by the obscurity of the presentation, for I was enamoured of formulae and had not yet had the benefit of Bradford Hill’s teaching of the importance of simplicity of language and the avoidance of formulae when writing for non-statistical readers. Fisher’s book did not, however, lead me to allocate treatments at random when, after qualification, I had the opportunity for testing medical beliefs and the two trials that I tried to or did undertake during the war relied on alternation to determine treated and control series. One was to test the prophylactic value of sulphonamides as an immediate treatment for wounds. This was turned down by the senior divisional medical officer on the grounds that either such treatment was useful, in which case it should be given to all wounded men, or it was not, in which case I should not waste His Majesty’s money. Unfortunately the senior medical officer could not tell me, in response to my enquiry, whether the treatment was useful or not—that was my province. The other trial, which was never completed owing to a new posting, was to see whether the standard advice to keep patients with infectious hepatitis in bed until the urine was free of bile had any justification. If, however, Fisher’s book did not lead me to use randomization in a simple trial, it did lead me, many years later, to help design a most economical trial, when Prichard and his colleagues at University College Hospital tested the effect of pronethanol (the first beta-blocker on the market) for the prevention of angina.4 For a clear benefit was shown (P 0.001) with only 12 patients, two of whom took the drug or a placebo over four periods of a fortnight in each of the six possible orders (ABAB, ABBA, AABB, BABA, BAAB, BBAA).