Optimal design of studies of influenza transmission in households. II: comparison between cohort and case-ascertained studies.

Both case-ascertained household studies, in which households are recruited after an 'index case' is identified, and household cohort studies, where a household is enrolled before the start of the epidemic, may be used to test and estimate the protective effect of interventions used to prevent influenza transmission. A simulation approach parameterized with empirical data from household studies was used to evaluate and compare the statistical power of four study designs: a cohort study with routine virological testing of household contacts of infected index case, a cohort study where only household contacts with acute respiratory illness (ARI) are sampled for virological testing, a case-ascertained study with routine virological testing of household contacts, and a case-ascertained study where only household contacts with ARI are sampled for virological testing. We found that a case-ascertained study with ARI-triggered testing would be the most powerful design while a cohort design only testing household contacts with ARI was the least powerful. Sensitivity analysis demonstrated that these conclusions varied by model parameters including the serial interval and the risk of influenza virus infection from outside the household.