Design of a group-randomized Streptococcus pneumoniae vaccine trial

Lawrence H. Moulton, Katherine L. O'Brien, Robert Kohberger, Ih Chang, Raymond Reid, Robert Weatherholtz, Jill G. Hackell, George R. Siber, Mathuram Santosham

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

A group-randomized, double-masked, phase III trial of a Streptococcus pneumoniae conjugate vaccine is being conducted in American Indian populations in the southwestern United States. Approximately 9000 infants will be enrolled in the primary efficacy cohort with vaccine allocation determined by community of residence. The trial is designed to continue until 48 cases of invasive pneumococcal disease due to vaccine serotypes have accumulated. Thirty-eight geographically and socially distinct areas were randomized within blocks formed by population size and geographic location. This design affords the opportunity to capture the effects of herd immunity (indirect effects) by estimating the impact of the vaccine intervention on nonimmunized infants. Group-randomized trials have challenging design and analysis features, many of which are discussed here in the context of the first such trial designed to lead to licensure of a drug or biologic in the United States.

Original languageEnglish (US)
Pages (from-to)438-452
Number of pages15
JournalControlled clinical trials
Volume22
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Group-randomized trial
  • Streptococcus pneumoniae
  • Vaccine

ASJC Scopus subject areas

  • Pharmacology

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