Simultaneous Inference Using Multiple Marginal Models.

Abstract

This tutorial describes single-step low-dimensional simultaneous inference with a focus on the availability of adjusted p values and compatible confidence intervals for more than just the usual mean value comparisons. The basic idea is, first, to use the influence of correlation on the quantile of the multivariate t-distribution: the higher the less conservative. In addition, second, the estimability of the correlation matrix using the multiple marginal models approach (mmm) using multiple models in the class of linear up to generalized linear mixed models. The underlying maxT-test using mmm is discussed by means of several real data scenarios using selected R packages. Surprisingly, different features are highlighted, among them: (i) analyzing different-scaled, correlated, multiple endpoints, (ii) analyzing multiple correlated binary endpoints, (iii) modeling dose as qualitative factor and/or quantitative covariate, (iv) joint consideration of several tuning parameters within the poly-k trend test, (v) joint testing of dose and time, (vi) considering several effect sizes, (vii) joint testing of subgroups and overall population in multiarm randomized clinical trials with correlated primary endpoints, (viii) multiple linear mixed effect models, (ix) generalized estimating equations, and (x) nonlinear regression models.