Biostatistics Advance Access originally published online on November 16, 2008
Biostatistics 2009 10(2):310-323; doi:10.1093/biostatistics/kxn037
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Statistical monitoring of clinical trials with multivariate response and/or multiple arms: a flexible approach
Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada joanh{at}stat.sfu.ca
Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA
1 To whom correspondence should be addressed.
Randomized clinical trials with a multivariate response and/or multiple treatment arms are increasingly common, in part because of their efficiency and a greater concern about balancing risks with benefits. In some trials, the specific types and magnitudes of treatment group differences that would warrant early termination cannot easily be specified prior to the onset of the trial and/or could change as the trial progresses. This underscores the need for more flexible monitoring methods than traditional approaches. This paper extends the repeated confidence bands approach for interim monitoring to more general settings where there can be a multivariate response and/or multiple treatment arms and where the metrics for comparing treatment groups can change during the conduct of the trial. We illustrate the approach using the results of a recent AIDS clinical trial and examine its efficiency and robustness via simulation.
Keywords: Group sequential analysis; Interim review; Multiple comparisons; Multiple end points; Nonparametric inference; Repeated confidence bands
Received October 9, 2007; revised May 27, 2008; revised September 29, 2008; accepted for publication October 13, 2008.