RT Journal Article
SR Electronic
T1 Competing effects of indirect protection and clustering on the power of cluster-randomized controlled vaccine trials
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 191163
DO 10.1101/191163
A1 Matt D.T. Hitchings
A1 Marc Lipsitch
A1 Rui Wang
A1 Steven E. Bellan
YR 2017
UL http://biorxiv.org/content/early/2017/12/09/191163.abstract
AB Power considerations for trials evaluating vaccines against infectious diseases are complicated by indirect protective effects of vaccination. While cluster-randomized trials (cRCTs) are less statistically efficient than individually randomized trials (iRCT), a cRCT’s ability to measure direct and indirect vaccine effects may mitigate the loss of efficiency due to clustering. Within cRCTs, the number and size of clusters affects three determinants of power: the effect size being measured, disease incidence, and intra-cluster correlation. We simulate trials conducted in a collection of small communities to assess how indirect protection and clustering affect the power of cRCTs and iRCTs during an emerging epidemic. Across diverse parameters, we find that within the same trial population, cRCTs are never more powerful than iRCTs, although the difference can be small. We also identify two effects that attenuate the loss of cRCT power traditionally associated with increased cluster size. First, if enrollment of fewer, larger clusters is performed to achieve higher vaccine coverage within vaccinated communities, this increases the effect to be measured and, consequently, power. Second, the greater rate of imported transmission in larger communities may increase the attack rate and similarly mitigate loss of power relative to a trial in many, smaller communities.