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

Merck Research Laboratories, West Point, PA 19486, USA, joseph_heyse{at}merck.com

Barbara J Kuter

Merck Research Laboratories, West Point, PA 19486, USA

Michael J Dallas

Merck Research Laboratories, West Point, PA 19486, USA

Penny Heaton, for the REST study team

Novavax, Rockville, MD 20850, USA

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. Clinical Trials 2008; 5: 131—139. http:// ctj.sagepub.com

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Clinical Trials, Vol. 5, No. 2, 131-139 (2008)
DOI: 10.1177/1740774508090507


SAGE Open article

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This Article Immediate free access via SAGE Open OA Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Heyse, J. F Articles by Heaton, P. Search for Related Content PubMed PubMed Citation Articles by Heyse, J. F Articles by Heaton, P., for the RE Social Bookmarking                         What's this?