Immunomodulators and primary prevention of respiratory infections: methodological considerations.

Immunomodulators have been evaluated mainly for their efficacy as a secondary preventive treatment to protect sick children from the recurrence of infections. We investigated the efficacy of one such product, IMOCURR, as a primary preventive treatment in children attending daycare, who face a very high risk of recurrent infections. EPICUR is a double-blind trial which was designed to study the efficacy of IMOCURR versus placebo. In order to have sufficient statistical power, data collection was based on a daily follow-up procedure and all important concomitant risk factors, such as age, environment and season, were controlled at the study design stage. The sample size required was calculated to be at least 400 children and a total of 423 were actually included. The results obtained for the total follow-up period and those obtained for the treatment period only were very different. This finding raises important questions which have methodological implications. This paper discusses these implications.