A confidence interval approach for difference and ratio of normal means in self-designing clinical trials
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Date
2009-02-02T10:39:48Z
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Abstract
In self-designing clinical trials, confidence intervals are derived for
the difference and the ratio of normal means, where the results of the independent study stages are
combined using the weighted inverse normal method.
The confidence intervals always hold the predefined nominal confidence level.
During the course of the Self-designing trial, the sample sizes
as well as the number of study stages can be determined simultaneously in a completely adaptive way.
Self-designing may be considered as the limit case of adaptive group sequential designing of
O'Brien and Fleming type when the full significance level is shifted to the last stage.
We consider the effect measures difference and ratio of normal means, where the latter has not yet been considered
in group sequential trials so far.
Concrete rules are derived for updating sample sizes and assigning weights to the stages of the trial.
The clinical trial may be originally designed either to show non-inferiority or superiority.
But, in each interim analysis, it is possible to change the planning from showing non-inferiority to
showing superiority or vice versa.
The performance of the Self-designing and the resulting confidence intervals are demonstrated in real-data examples
for both considered effect measures showing both kinds of switching during an ongoing trial.
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Keywords
adaptive planning, confidence interval, learning rule, ratio of means, self-designing, switching between non-inferiority and superiority, weighted inverse normal method