OPTIMAL VACCINE TRIAL DESIGN WHEN ESTIMATING VACCINE EFFICACY FOR SUSCEPTIBILITY AND INFECTIOUSNESS FROM MULTIPLE POPULATIONS

Vaccination can have important indirect effects on the spread of an in fectious agent by reducing the level of infectiousness of vaccinees wh o become infected. To estimate the effect of vaccination on infectious ness, one typically requires data on the contacts between susceptible and infected vaccinated and unvaccinated people. As an alternative, we propose a trial design that involves multiple independent and interch angeable populations. By varying the fraction of susceptible people va ccinated across populations, we obtain an estimate of the reduction in infectiousness that depends only on incidence data from the vaccine a nd control groups of the multiple populations. One can also obtain fro m these data an estimate of the reduction of susceptibility to infecti on, We propose a vaccination strategy that is a trade-off between opti mal estimation of vaccine efficacy for susceptibility and of vaccine e fficacy for infectiousness. We show that the optimal choice depends on the anticipated efficacy of the vaccine as well as the basic reproduc tion number of the underlying infectious disease process. Smaller vacc ination fractions appear desirable when vaccine efficacy is likely hig h and the basic reproduction number is not large. This strategy avoids the potential for too few infections to occur to estimate vaccine eff icacy parameters reliably. (C) 1998 John Wiley & Sons, Ltd.