Statistical analysis
infection
SARS-COV-2 INFECTION, ASYMPTOMATIC COVID-19, INFECTION, SECONDARY, REGRESSION, EVENTS
We assumed a 5% secondary attack rate of symptomatic COVID-19 cases in the placebo group during our study period, and a true efficacy of 70% (equating to an attack rate of 1.5% with SA58). Allowing for a dropout rate of 10%, we calculated that a study population of approximately 2300 participants randomized in a 3:1 ratio to treatment or placebo would be sufficient to provide approximately 80% power to demonstrate the lower bound of the two-sided 95% confidence interval (CI) for efficacy to be >0.3.The incidence rates of symptomatic COVID-19 per 100 person-days were calculated for the SA58 and placebo groups during the case monitoring period, by dividing the number of events with the total number of follow-up days. Crude incidence rate ratios (IRRs) comparing the SA58 and placebo groups were calculated. For the adjusted analysis, a Poisson regression model was used, with robust variance using the log of the follow-up days as an offset to estimate IRR of symptomatic COVID-19 cases with SA58 vs. placebo. Efficacy of treatment was calculated as 1 minus IRR and was presented with a two-sided 95% confidence interval (95%CI). In the final efficacy analysis, we excluded participants who tested positive for SARS-CoV-2 within 24 h by RT–PCR at the visit on Day one to account for people with early and undetectable infection when SA58 was administered and for an expected time lag between administration and RT–PCR screening assay. Kaplan–Meier curves were also presented for SA58 and placebo groups, with hazard ratios (HR) calculated by using Cox proportional hazard models. We also calculated the efficacy of SA58 against other outcomes, e.g. SARS-CoV-2 infection (SARS-CoV-2 RT–PCR positive during follow-up) and severe COVID-19 following the same methodology as for the primary efficacy end point. The robustness of our results was tested by performing separate analyses of efficacy among participants with different duration of follow-up days (namely <5 days vs. ≥5 days), by including participants who tested positive for SARS-CoV-2 by RT–PCR within 24 h of the first drug administration, and by restricting efficacy analyses to participants who had continuous exposure to COVID-19. For the comparison of individual-level variables at baseline, we used Student’s 