Park's story and Winters' tale: alternate allocation clinical trials in turn of the century America.

Abstract

In 1898, Johannes Fibiger of Copenhagen, in the setting of scepticism about the efficacy of diphtheria antitoxin, famously allocated 484 patients admitted to his hospital on alternate days to either receive or not receive antitoxin in order to test its utility.1–3 Over the subsequent half-century before the Medical Research Council's randomized control study of streptomycin for pulmonary tuberculosis, alternate allocation would emerge as an increasingly utilized and respected methodological tool for determining therapeutic efficacy.4–6 Yet the advent and early dissemination of this methodology – and the resistance to its wider application – is only now beginning to be seriously researched. William H Park (1863–1939), the longstanding director of the laboratories of the New York Board of Health, has been justifiably honoured for having saved countless lives through the use of diphtheria antitoxin and immunization in New York City at the end of the 19th century and beginning of the 20th century.7 During those same years, Park was closely associated with some of the most sophisticated and visible therapeutic trials in America (and the world). In addition to using alternate allocation of patients to treatment comparison groups, they used double-blinding,8 multisite collaboration, and statistically compared treatment groups, including the use of statistical synthesis (meta-analysis).9 Park would claim, like Fibiger, to have first conducted such an alternate allocation study in the 1890s in the setting of scepticism regarding the utility of diphtheria antitoxin. Yet a deeper investigation of the context of Park's apparent study reveals not only a surprise twist, but important insights into the advent of, and resistance to, the alternate allocation method in the United States, and possibly further afield.