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. 2008;5(2):131-9.
doi: 10.1177/1740774508090507.

Evaluating the safety of a rotavirus vaccine: the REST of the story

Joseph F Heyse  1 , Barbara J Kuter, Michael J Dallas, Penny Heaton; REST Study Team
Affiliations

Evaluating the safety of a rotavirus vaccine: the REST of the story

Joseph F Heyse et al. Clin Trials. 2008.

Abstract

The Rotavirus Efficacy and Safety Trial (REST) was a blinded, placebo-controlled study of the live pentavalent human-bovine vaccine, RotaTeq (Merck & Co. Inc., West Point, PA). REST was noteworthy because its primary objective was to evaluate the safety of RotaTeq with regard to intussusception, a rare intestinal illness that occurs with a background incidence of approximately 50 cases per 100 000 infant years. The study involved approximately 70 000 infants at over 500 study sites in 11 countries. The study demonstrated that the risk of intussusception was similar in vaccine and placebo recipients and that the vaccine prevented rotavirus gastroenteritis, ameliorated the severity of disease in those who had any disease, and substantially reduced rotavirus-associated hospitalizations and other health care contacts. This report provides an in-depth review of the background, statistical and regulatory considerations, and execution of REST. We describe the rationale and methods used for sample size, continuous safety monitoring, group sequential design, and detailed study execution. The results of the study have been reported elsewhere. The design and conduct of this study may serve as a useful model for planning other future large-scale clinical trials, especially those evaluating uncommon adverse events.

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Figures

Figure 1
Figure 1
Predefined safety boundaries for the 42 and 7 day ranges after any dose: (a) 42-day period after any dose, (b) 7-day period after any dose
Figure 2
Figure 2
Criteria for stopping enrollment (based on primary hypothesis)
Figure 3
Figure 3
Statistical operating characteristics for REST study design
See this image and copyright information in PMC

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