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Randomised by (your) god: robust inference from an observational study design
  1. George Davey Smith
  1. Correspondence to:
 Professor G Davey Smith
 Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol BS8 2PR, UK; zetkin{at}

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In 1954 Archie Cochrane, then aged 45, was diagnosed as having an acute attack of polio. He was sceptical of the diagnosis at the time, but evidently thought little more about it.1 Eleven years later he was informed that his sister, Helen (fig 1), was acutely ill in a psychiatric hospital in Glasgow, said to be suffering from senile psychosis. Unhappy with this diagnosis, and hearing that she was potentially terminally ill, he enlisted the help of a physician friend to visit her in hospital. There it was determined that she was suffering from an acute attack of porphyria, precipitated by the use of barbiturates. Archie remembered back to his supposed polio attack and recalled that he had been prescribed a sleeping table before it. It looked as though he, too, had suffered an attack of porphyria.

Figure 1

 Archie Cochrane and his sister Helen (source: Bosch FX. Archie Cochrane: Back to the Front, Barcelona, 2003).

As variegate porphyria is an autosomal dominant condition Archie reasoned that informing family members of their possible propensity could avoid future episodes, through avoidance of triggering agents, as well as mitigate against potentially serious misdiagnoses. He therefore contacted family members and obtained urine or faecal samples, to trace transmission through the family. As a man convinced of the necessity of high response rates he was justifiably proud of the fact that samples were obtained from 152 of 153 living descendents of his maternal great grandfather. Indeed the relevant family tree, framed and hanging on the wall, was among the first items discussed when I visited him in Rhoose Farm House in 1985. In his report of the investigation of familial distribution of variegate porphyria tendency Archie calculated mortality rates among the maternal side of his family and, although very imprecisely estimated, a hint of excess …

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