Optimal design of studies of influenza transmission in households. I: Case-ascertained studies

Case-ascertained household transmission studies, in which households including an 'index case' are recruited and followed up, are invaluable to understanding the epidemiology of influenza. We used a simulation approach parameterized with data from household transmission studies to evaluate alternative study designs. We compared studies that relied on self-reported illness in household contacts vs. studies that used home visits to collect swab specimens for virological confirmation of secondary infections, allowing for the trade-off between sample size vs. intensity of follow-up given a fixed budget. For studies estimating the secondary attack proportion, 2-3 follow-up visits with specimens collected from all members regardless of illness were optimal. However, for studies comparing secondary attack proportions between two or more groups, such as controlled intervention studies, designs with reactive home visits following illness reports in contacts were most powerful, while a design with one home visit optimally timed also performed well.