title: Two-part test of vaccine effect.
abstract: Vaccine benefit is usually two-folded: (i) prevent a disease or, failing that, (ii) diminish the severity of a disease. To assess vaccine effect, we propose two adaptive tests. The weighted two-part test is a combination of two statistics, one on disease incidence and one on disease severity. More weight is given to the statistic with the larger a priori effect size, and the weights are determined to maximize testing power. The randomized test applies to the scenario where the total number of infections is relatively small. It uses information on disease severity to bolster power while preserving disease incidence as the primary interest. Properties of the proposed tests are explored asymptotically and by numerical studies. Although motivated by vaccine studies, the proposed tests apply to any trials that involve both binary and continuous outcomes for evaluating treatment effect.
authors: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, U.S.A.
authors: Zonghui
authors: Z
authors: Hu
authors: Michael
authors: M
authors: Proschan
mesh_terms: D016915:AIDS Vaccines; D023381:Endpoint Determination; D015658:HIV Infections / Q000453:epidemiology* / Q000517:prevention & control*; D015497:HIV-1; D006801:Humans; D015994:Incidence; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012720:Severity of Illness Index; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines
keywords: Fisher's exact test; Lachenbruch's test; local alternative; randomization test; vaccine
references: Stat Methods Med Res. 2016 Dec;25(6):2733-2749
references: 24803511
references: J Acquir Immune Defic Syndr. 2004 Nov 1;37(3):1385-92
references: 15483468
references: Stat Methods Med Res. 2002 Aug;11(4):297-302
references: 12197297
references: Biometrics. 2003 Sep;59(3):531-41
references: 14601754
references: Biometrics. 2009 Sep;65(3):885-93
references: 19210727