TY - JOUR
T1 - Clinical trials
T2 - the mathematics of falling vaccine efficacy with rising disease incidence
AU - Gomes, M. Gabriela M.
AU - Gordon, Stephen B.
AU - Lalloo, David G.
PY - 2016/6/8
Y1 - 2016/6/8
N2 - Reports of unexplained discrepancies in the efficacy of vaccines, as estimated from randomised controlled trials in different parts of the world, are commonplace in the literature [1], [2], [3], [4]. Moreover, there is a consistent trend for lower vaccine efficacy when measured in settings where the disease of interest has a higher incidence, leading to questions about the appropriateness of pooled estimates. Here, we examine the mathematical basis for such trends and propose a measure of efficacy that is valid across settings. The approach relies on fitting mechanistic models, which specify pathogen exposures and host responses, to global vaccine trial data stratified by local disease incidence. Such models enable the estimation of vaccine protection per exposure to the pathogen. A strategy to estimate per-exposure vaccine efficacy will enable more accurate estimates of vaccine efficacy across a range of disease incidence [5].
AB - Reports of unexplained discrepancies in the efficacy of vaccines, as estimated from randomised controlled trials in different parts of the world, are commonplace in the literature [1], [2], [3], [4]. Moreover, there is a consistent trend for lower vaccine efficacy when measured in settings where the disease of interest has a higher incidence, leading to questions about the appropriateness of pooled estimates. Here, we examine the mathematical basis for such trends and propose a measure of efficacy that is valid across settings. The approach relies on fitting mechanistic models, which specify pathogen exposures and host responses, to global vaccine trial data stratified by local disease incidence. Such models enable the estimation of vaccine protection per exposure to the pathogen. A strategy to estimate per-exposure vaccine efficacy will enable more accurate estimates of vaccine efficacy across a range of disease incidence [5].
KW - efficacy of vaccines
KW - randomised controlled trials
KW - vaccine protection per exposure
UR - http://www.scopus.com/inward/record.url?scp=84966560495&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2016.04.065
DO - 10.1016/j.vaccine.2016.04.065
M3 - Comment/debate
C2 - 27177948
AN - SCOPUS:84966560495
SN - 0264-410X
VL - 34
SP - 3007
EP - 3009
JO - Vaccine
JF - Vaccine
IS - 27
ER -