title: Multistage designs for vaccine safety studies.
abstract: In a placebo-controlled vaccine safety trial, the primary interest is to demonstrate that the vaccine is sufficiently safe, rejecting the null hypothesis that the relative risk of an adverse event attributable to the vaccine is above a prespecified value, greater than one. We develop sequential as well as multistage designs for such trials where the interim analyses are conducted not after a given number of subjects but rather after a given number of events observed. We show that these designs achieve significant improvement over single-stage conditional test in terms of both the required number of events to be observed and the required number of subjects to be enrolled.
authors.affiliation: Research Statistics Unit, GlaxoSmithKline, Collegeville, Pennsylvania 19426-0989, USA. Vladimir.2.Dragalin@gsk.com
authors.forename: V
authors.initials: V
authors.lastname: Dragalin
authors.forename: V
authors.initials: V
authors.lastname: Fedorov
mesh_terms: D006801:Humans; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data; D012107:Research Design / Q000706:statistics & numerical data; D012401:Rotavirus / Q000276:immunology; D012400:Rotavirus Infections / Q000517:prevention & control; D022243:Rotavirus Vaccines / Q000009:adverse effects; D014612:Vaccines / Q000009:adverse effects*; D014613:Vaccines, Attenuated / Q000009:adverse effects
chemical_list: C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; D014612:Vaccines; D014613:Vaccines, Attenuated