(published in Statistics in Medicine, Volume 29, issue 26, p.2698-2708, 2010.)
Description
The evaluation of vaccine safety involves pre-clinical animal studies, pre-licensure randomized clinical trials and post-licensure safety studies. Sequential design and analysis are of particular interest because they allow early termination of the trial or quick detection that the vaccine exceeds a prescribed bound on the adverse event rate. After a review of recent developments in this area, we propose a new class of sequential generalized likelihood ratio tests for evaluating adverse event rates in two-armed pre-licensure clinical trials and single-armed post-licensure studies. The proposed approach is illustrated using data from the Rotavirus Efficacy and Safety Trial (REST). Simulation studies of the performance of the proposed approach and other methods are also given.
Research and Software reported here was supported in part by the U.S. National Science Foundation under grant number DMS-0805879 and in part by Stanford NIH/NCRR CTSA award number UL1 RR025744.
Software
Section 4.2 of the paper describes the computation of the GLR boundaries for designing pre-licensure vaccine trials. The boundary depends on four fundamental parameters of the model.
The package includes a Shiny webapp that can be run with
library(sglr)
runApp(“webapp”, package=”sglr”)
Install the package as usual on R from your favorite CRAN repository by selecting the package sglr. Or in an R session, type
install.packages(“sglr”)
Once the package is installed, typing example(glrSearch) will run a search example. You can plot the boundary for the REST trial with plotBoundary(b0=2.8, b1=2.4, p=c(0.5, 10/11), textXOffset=1, textYSkip=1)