ABSTRACT

As introduced in Chapters 7 and 16, there has been substantial progress in the development of statistical methodology that addresses the rapidly growing needs for multiregional clinical trial (MRCT) designs recently. This chapter summarizes the numerical programs that are developed with R software to implement an MRCT design. Major functions of the programs include

CONTENTS

11.1 Introduction .............................................................................................. 131 11.2 Methodology ............................................................................................. 132

11.2.1 Model Settings and Definitions ............................................... 132 11.2.2 Estimator of Treatment Effects for Individual Regions ........ 133 11.2.3 Local Consistency Assessment for One Specific Region ...... 134 11.2.4 Simultaneous Consistency Assessment for All Regions ...... 135

11.2.4.1 Definition 1: Exceeding a Proportion of the Observed Overall Effect ........................................... 135

11.2.4.2 Definition 2: Exceeding a Prespecified Effect Size ..... 136 11.2.4.3 Definition 3: Significantly Exceeding a

Proportion of the Overall Effect .............................. 136 11.2.4.4 Definition 4: Absence of Significant Treatment-

by-Region Interaction ................................................ 136 11.2.4.5 Definition 5: Lack of Significant Difference for

Any Regions from the Overall ................................ 137 11.3 Computations and Programs ................................................................. 137

11.3.1 Objectives .................................................................................... 137 11.3.2 R function samplesize.ran() ............................................... 138 11.3.3 R function pow.loc.ran() and pow.sim.ran() ................. 139 11.3.4 R function prob.def1() ........................................................... 139

Appendix: R Program Codes............................................................................. 140 References ............................................................................................................. 147

calculating the sample size, computing the assurance probability for local or simultaneous consistency, and evaluating the impacts of regional treatment effect estimators, definitions of consistency, total region numbers, and sample size configuration on the required total sample size and consistency assessments. Section 11.2 briefly summarizes the methods to be realized; Section 11.3 introduces the R functions in terms of their main goals, as well as the input and output values, respectively; the corresponding R codes can be found in the appendix.