Alexander Blackrie's proposed comparison of two treatments for the 'gravel and stone' (1763): A randomised controlled non-inferiority trial?

Abstract

Alexander Blackrie (bap. 1702, d. 1772) was a Scottish Surgeon-Apothecary who attended Aberdeen's grammar school and Marischal College. He served as surgeon-general in India and practised at Bromley, Kent, England. In later life, he suffered from the 'gravel and stone' i.e., urological stones. This triggered an enquiry into the lucrative medication of Dr Chittick of Bath. Blackrie deduced it to be nothing more than soap-lye (Sodium hydroxide) and went on to formulate his own version ('Blackrie's lixivium'). Blackrie undertook comparative experiments on the efficacy of these two products at dissolving equally-sized fragments of the same urinary stone. In 1763, he published his proposal to compare the two products in patients. This called for: selection of patients 'afflicted in the same degree', randomisation by 'dividing them equally by lot', the 'experiment' to be 'repeated' and the number of participations to be 'large'. Although never implemented, Blackrie's proposal is an early model of a randomised controlled trial and may be the first description of a non-inferiority trial. His use of the term 'decisive' experiment and reference to James Jurin FRS may offer a link with Hauksbee the Younger's 1743 proposed 'experimentum crucis'. Blackrie's contribution to the development of fair comparisons of treatments deserves greater recognition.