Interim analysis multiplicity

Second, Tukey and Bonferroni multiple comparisons are done at the same point in time, i.e., immediately following a significant omnibus ANOVA result, and, more relevantly, are done with essentially the same amount of data in each case. The actual numbers of subjects in each dose treatment group may be slightly different, but the amounts of data used in each comparison will be very comparable. In contrast, the number of data used in each interim analysis increases linearly from the number used in the previous interim analysis. In our example, the number of... 

Essentially, there are two separate issues involved in performing an interim analysis a statistical issue, and an administrative or trial management issue. The statistical issue is very similar to the multiplicity issue discussed in the previous paragraph, and it applies to the reasons (1), (2) and (3) above. If we perform an interim inferential test, the overall error probability is inflated. Therefore, if one contem-... 

A group sequential approach was planned to discharge the 1.3 threshold. The significance levels for the multiple analyses were based on the Lan-DeMets spending function with an O Brien-Fleming boundary. The first analysis to discharge it would be conducted at the time when the meta-analysis to discharge the 1.8 threshold was performed. The next planned interim meta-analysis would be conducted when approximately 500 MACE-plus events had accrued, and a final interim analysis was planned to occur after approximately 700 events had accumulated, if the E3... 

Also, the analysis plan should identify the statistical methods that will be used and how hypotheses will be tested (e.g., a p value cutoff or a confidence interval for the difference that excludes 0). And the plan should prespecify whether interim analyses are planned, indicate how issues of multiple testing will be addressed, and predefine any subgroup analyses that will be conducted. Finally, the analysis plan should include the results of power and sample size calculations. 

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