title: Sensitivity analysis for missing dichotomous outcome data in multi-visit randomized clinical trial with randomization-based covariance adjustment.
abstract: Dichotomous endpoints in clinical trials have only two possible outcomes, either directly or via categorization of an ordinal or continuous observation. It is common to have missing data for one or more visits during a multi-visit study. This paper presents a closed form method for sensitivity analysis of a randomized multi-visit clinical trial that possibly has missing not at random (MNAR) dichotomous data. Counts of missing data are redistributed to the favorable and unfavorable outcomes mathematically to address possibly informative missing data. Adjusted proportion estimates and their closed form covariance matrix estimates are provided. Treatment comparisons over time are addressed with Mantel-Haenszel adjustment for a stratification factor and/or randomization-based adjustment for baseline covariables. The application of such sensitivity analyses is illustrated with an example. An appendix outlines an extension of the methodology to ordinal endpoints.
authors.affiliation: a University of North Carolina , Department of Biostatistics , Chapel Hill , North Carolina , USA.
authors.forename: Siying
authors.initials: S
authors.lastname: Li
authors.affiliation: a University of North Carolina , Department of Biostatistics , Chapel Hill , North Carolina , USA.
authors.forename: Gary G
authors.initials: GG
authors.lastname: Koch
authors.affiliation: a University of North Carolina , Department of Biostatistics , Chapel Hill , North Carolina , USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Preisser
authors.affiliation: a University of North Carolina , Department of Biostatistics , Chapel Hill , North Carolina , USA.|b University of Maryland , School of Medicine , Baltimore , Maryland , USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Lam
authors.affiliation: c SanchezKam , LLC , Alexandria , Virginia , USA.
authors.forename: Matilde
authors.initials: M
authors.lastname: Sanchez-Kam
mesh_terms: D000068598:Data Accuracy; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012680:Sensitivity and Specificity
keywords: Covariance matrix estimation for functions involving ratios; Mantel-Haenszel methods; imputation for missing ordinal outcomes; mathematical imputation via redistribution; tipping point analysis