Clinical trials often evaluate multiple outcome variables to form a comprehensive picture of the effects of a new treatment. The resulting multidimensional insight contributes to clinically relevant and efficient decision-making about treatment superiority. Common statistical procedures to make these superiority decisions with multiple outcomes have two important shortcomings, however: (1) Outcome variables are often modeled individually, and consequently fail to consider the relation between outcomes; and (2) superiority is often defined as a relevant difference on a single, on any, or on all outcome(s); and lacks a compensatory mechanism that allows large positive effects on one or multiple outcome(s) to outweigh small negative effects on other outcomes. To address these shortcomings, this paper proposes (1) a Bayesian model for the analysis of correlated binary outcomes based on the multivariate Bernoulli distribution; and (2) a flexible decision criterion with a compensatory mechanism that captures the relative importance of the outcomes. A simulation study demonstrates that efficient and unbiased decisions can be made while Type I error rates are properly controlled. The performance of the framework is illustrated for (1) fixed, group sequential, and adaptive designs; and (2) non-informative and informative prior distributions.
Multiple imputation is a recommended technique to deal with missing data. We study the problem where the investigator has already created imputations before the arrival of the next wave of data. The newly arriving data contain missing values that need to be imputed. The standard method (RE-IMPUTE) is to combine the new and old data before imputation, and re-impute all missing values in the combined data. We study the properties of two methods that impute the missing data in the new part only, thus preserving the historic imputations. Method NEST multiply imputes the new data conditional on each filled-in old data m 2 > 1 times. Method APPEND is the special case of NEST with m 2 ¼ 1, thus appending each filled-in data by single imputation. We found that NEST and APPEND have the same validity as RE-IMPUTE for monotone missing data-patterns. NEST and APPEND also work well when relations within waves are stronger than between waves and for moderate percentages of missing data. We do not recommend the use of NEST or APPEND when relations within time points are weak and when associations between time points are strong.
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