James Lind Library, James Lind Initiative, Summertown Pavilion, Middle Way, Oxford OX2 7LG, UK. E-mail: ichalmers{at}jameslindlibrary.org
Accepted 9 July 2003
During the 1930s, RA Fisher showed how randomization provided the theoretical underpinning for tests of statistical significance.1 Because of this, it is often assumed that Fisher must have played a key role in the evolution of randomized trials in medicine during the 1930s and 1940s. Randomization was adopted by Austin Bradford Hill for Medical Research Council (MRC) trials for a more pragmatic reason, however. Bradford Hill was aware that an alternate allocation scheme had not been strictly observed in a MRC trial done in the early 1930s2 and that selection bias had thus probably undermined the validity of the comparisons made in the study. In designing MRC trials a decade later, he therefore used allocation schedules based on random numbers. If properly concealed, these made it more difficult for those recruiting participants to know which allocations were next in line, and, thus less likely to introduce bias in assembling therapeutic comparison groups.3
The papers in this issue of the International Journal of Epidemiologyby Peter Armitage and Richard Doll (formerly colleagues of Bradford Hill), Walter Bodmer (formerly a student of Fisher), and Harry Marks (author of a history of clinical trials4)were commissioned to reflect on this characterization of Fisher the theoretician and Bradford Hill the pragmatist. This is obviously a simplificationFisher was interested in practical problems, and Bradford Hill was aware of statistical theorybut it does help to emphasize the very different contributions made by the two men.
Fisher left a wealth of personal papers, which have been archived very helpfully at the University of Adelaide, in Australia, and an excellent biography exists.5 By contrast, very few of Bradford Hills personal papers have survived (his daughter has told me that he threw everything away) and no one has yet taken up the challenge of writing a biography.
I obtained copies of correspondence between Bradford Hill and Fisher from the Fisher Archive, and the authors of the four papers that follow were able to draw on this. However, none of them has used any material from an unpublished hand-written memoir that Bradford Hill prepared in 1988 for the Librarian at the London School of Hygiene and Tropical Medicine.6 I want to take this opportunity to bring some of this material to a wider readership.
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Passages in this memoir make clear that Bradford Hill recognized his limitations as a mathematical statistician, declaring that, having no mathematical knowledge he needed first class statisticians to work with him (ref. 6, p. 5). This acknowledgement did not prevent him criticizing statisticians who were out of touch with practical realities, however. Commenting on some American statisticians who had criticized a US trial establishing the efficacy of Salks polio vaccine, Bradford Hill wrote:
(They) knew all about statistical methods and mathematical formulae and nothing about medicine and the problems involved in making trials in human populations. They were ignorant of the fact that one often had to be content with far from perfect evidence and draw on the most likely explanation. (ref. 6, p. 30)
Hill was also intolerant of statisticians who were unprepared to make the effort to try to communicate effectively with non-statisticians. In 1960, the director of an Australian institution asked Hill about the success of his approach to teaching statistics to non-statisticians. A doctor at the Australian institution had been teaching statistics and blinding (his students) with algebra. Bradford Hill agreed to the directors proposal that a young Australian statistician should spend some time at the London School of Hygiene to learn how to use simple teaching methods.
He showed me a paper he had written. Where do you want to publish it?, I asked him. He named some medical journal. Then I said you must rewrite it more simply. I cant understand it and your proposed readers certainly wont. He was a prima donna, stormed about, said I could teach him nothing and he would go to RA Fisher the leading statistician of the day at Rothamstead. The sooner you go the better I said, get out of my department and dont come back. Of course in that situation (and I was then a friend of Fisher) Fisher would not take him. (ref. 6, p. 19)
By contrast with his intolerance of some statisticians, Bradford Hill was very indulgent of people who had difficulty understanding statistics. Indeed, he had a policy of never failing a candidate who was hopeless on medical statistics.
When I got on to the subject of statistical tests of significance I started by stating that these were based on the laws of probability over which statisticians quarrelled violently. I was entirely ignorant of them but I knew more than the lady who congratulated her friend on the birth of triplets. It is remarkable said the mother it happens only one in 8000 times. Good gracious said her friend. However did you find time for the housework? (ref. 6, p. 12)
His light-hearted lectures were very carefully planned.
I firstly replaced You can prove anything by statistics by you can prove nothing by statistics. You can prove anything by the misuse of statistics, and politicians, advertisers do just that, and unless you know something about them you will be misled. In the strict sense of the word proven you can prove nothing, but you can make one interpretation of the data more probable than any other (e.g. smoking and cancer of the lung). My lectures may have appeared spontaneous. They were anything but that. I put long hours of thought into them and wrote them with care. (ref. 6, p. 11)
In addition to his substantial contributions to the design and interpretation of controlled trials and epidemiological studies, Bradford Hill deserves to be remembered for his skills as a communicatorin his writings as well as his lectures. Indeed, his talents as a communicator may go some way to explaining why the MRCs randomized trial of streptomycin appears to have been so influential in the adoption of new methodological standards for therapeutic evaluation. One manifestation of Bradford Hills concern to communicate successfully with clinicians was his diligence in informing himself about clinical matters: during a lecture tour of the US in 1951 he had to explain to his audiences that he was not medically qualified, which came as a surprise to many (ref. 6, p. 18).
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After rereading Bradford Hills 1950s papers on the clinical trial7,8 when I was drafting the methodology chapter for a book in which I was involved,9 I sent him a postcard reiterating just how much pleasure his writings always gave meand how frustrated I felt that I was having such difficulty in producing clear, readable prose myself. He responded in a typically modest style:
I am glad that you enjoyed re-reading my papers on CTs of the 1950s. I believe I wrote clearly because I had a simple mind and had to try hard to make things clear to myself. And of course I must have gained by all the reading I did when I was bed-bound thro 1917/18pretty well all the worlds classics in fictionin English and in translationsand I deliberately studied the art of writing (Quiller Couch, Ernest Gowers, Fowler & so on). And I always enjoyed writingsome nice white sheets of paper & a fountain pen & away one can wander.10
The following year, when I felt that I had produced a reasonable draft of my chapter, I asked him if he would look over it.
You told me that I should overlook the style and point out bad logic or other errors. You ask the impossible. I have spent a lifes time on MSSmy own, my staffs or as editor of this or thatseeking a short word in place of a long one, cutting the length of sentences, deleting adjectives and double negatives ... I was floundering out of my depth immediately in your introductionwhat in Gods name is a conceptual frameworkjust one, let alone a variety! And the sentence spans close on 50 words. I made an attempt to shorten and simplify but it cant be done. I beg you Iain, rewrite that introduction. There is so much to come that is clear and goodyou may at the outset scare away the reader (simple-minded ones like me).11
Fishers seminal contribution to the design of experiments is uncontestable. The nature of Bradford Hills distinctive contribution to the history of randomized clinical trials as a communicator as well as a scientist is less well recognized. Twenty years after the report of the MRC streptomycin trial, Professor John Crofton was introducing Bradford Hill for an honorary Doctorate in Medicine at the University of Edinburgh. Unsurprisingly, Crofton had a good deal to say about Bradford Hills role in the evolution of controlled trials. A passage in Bradford Hills unpublished memoir is revealing:
John, I said, you know I did not invent the controlled trial. It goes back at least to Lind who tried lime juice in scurvy compared with the usual nauseating mixtures of the day. I know that, Crofton replied, but you persuaded an extremely conservative profession which regarded change with suspicion, to accept and use them. That was, and is, I think a fair judgement. (ref. 6, p. 29)
In the year that sees the 250th anniversary of the publication of Linds Treatise of the Scurvy (www.jameslindlibrary.org), Austin Bradford Hills concurrence with Croftons judgement helps to clarify one of the several reasons that he has a special place in the history of controlled trials.
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2 Chalmers I. MRC Therapeutic Trials Committees report on serum treatment of lobar pneumonia, BMJ 1934. In: Chalmers I, Milne I, Tröhler U, Vandenbroucke J (eds). The James Lind Library (www.jameslindlibrary.org). Accessed Tuesday 7 January 2003.
3 Chalmers I. Comparing like with like: some historical milestones in the evolution of methods to create unbiased comparison groups in therapeutic experiments. Int J Epidemiol 2001;30:117078.
4 Marks HM. The Progress of Experiment: Science and Therapeutic Reform in the United States, 19001990. Cambridge: Cambridge University Press, 2000.
5 Fisher-Box J. RA Fisher: The Life of a Scientist. New York, Chichester, Brisbane, Toronto: John Wiley & Sons, 1978.
6 Bradford Hill A. Some memories of A.B.H. Manuscript dated January 1988, held in the Archive at the London School of Hygiene and Tropical Medicine.
7 Bradford Hill A. The clinical trial. Brit Med Bull 1951;7:27882.[ISI]
8 Bradford Hill A. The clinical trial. N Engl J Med 1952;247:11319.[ISI]
9 Chalmers I. Evaluating the effects of care during pregnancy and childbirth. In: Chalmers I, Enkin M, Keirse MJNC (eds). Effective Care in Pregnancy and Childbirth. Oxford: Oxford University Press, 1989, pp. 338.
10 Bradford Hill A. Letter to Iain Chalmers, 7 June 1987.
11 Bradford Hill A. Letter to Iain Chalmers, 15 June 1988.
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