title: Clinical safety evaluation of combination vaccines.
abstract: The development plan for new combination vaccines should include clinical studies designed to provide an adequate safety database (as well as efficacy data) to support licensure. Ideally, randomized studies to compare the safety of the combination vaccine with the separately administered components (or already licensed combinations of components) should be performed. For new combination vaccines having components with proven efficacy, comparative immunogenicity data may provide a sufficient basis to support efficacy, precluding the need for a large efficacy study. In the absence of the safety database that would have been derived from such an efficacy study, it is important to conduct a comparative safety study with a sample size suitable for the evaluation of less common adverse events. For large safety trials, a simplified design where only a subset of subjects is assessed in detail for the more common adverse events may be appropriate.
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20852, USA.
authors.forename: K
authors.initials: K
authors.lastname: Midthun
authors.forename: A D
authors.initials: AD
authors.lastname: Horne
authors.forename: K L
authors.initials: KL
authors.lastname: Goldenthal
mesh_terms: D001699:Biometry; D017322:Clinical Trials, Phase II as Topic / Q000379:methods / Q000706:statistics & numerical data; D017326:Clinical Trials, Phase III as Topic / Q000379:methods / Q000706:statistics & numerical data; D016208:Databases, Factual; D017277:Drug Approval; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data; D012449:Safety; D018401:Sample Size; D017778:Vaccines, Combined / Q000009:adverse effects* / Q000276:immunology / Q000494:pharmacology*
chemical_list: D017778:Vaccines, Combined