title: Can we reduce the dose of a vaccine?
abstract: This paper describes the planning, implementation, and analysis of a clinical trial to develop a pediatric vaccine against the tick-borne encephalitis virus. The trial was primarily a dose-finding study with the following objectives: the protein content of the vaccine should be lower than that of the vaccine for adults (which was already approved) in order to reduce reactogenicity, especially the rate of fever reactions, in children. At the same time, the protein content had to be high enough so that the immunogenicity of the pediatric vaccine would be at least equivalent to that of the vaccine for adults. We discuss in detail the definition of the equivalence criterion and the considerations concerning sample size calculation. The methods described in this paper are also useful for designing clinical trials for the development of combined vaccines.
authors.affiliation: Behringwerke AG, Liederbach, FRG.
authors.forename: G
authors.initials: G
authors.lastname: Rosenkranz
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D000956:Antigens, Viral / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D004675:Encephalitis, Tick-Borne / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D018401:Sample Size; D013810:Therapeutic Equivalency; D014765:Viral Vaccines / Q000494:pharmacology*
chemical_list: D000956:Antigens, Viral; D014765:Viral Vaccines