A REGULATORY PERSPECTIVE ON ESSENTIAL CONSIDERATIONS IN DESIGN AND ANALYSIS OF SUBGROUPS WHEN CORRECTLY CLASSIFIED

作者：Wang Sue Jane^*; Hung H M James

来源：Journal of Biopharmaceutical Statistics, 2014, 24(1): 19-41.

DOI：10.1080/10543406.2013.856022

• Biomarker
• Formation of subgroup
• Interaction-to-overall effects ratio
• Predictive of treatment effect
• Subgroup-specific treatment effect hypothesis

This regulatory research provides possible approaches for improvement to conventional subgroup analysis in a fixed design setting. The interaction-to-overall effects ratio is recommended in the planning stage for potential predictors whose prevalence is at most 50% and its observed ratio is recommended in the analysis stage for proper subgroup interpretation if sample size is only planned to target the overall effect size. We illustrate using regulatory examples and underscore the importance of striving for balance between safety and efficacy when considering a regulatory recommendation of a label restricted to a subgroup. A set of decision rules gives guidance for rigorous subgroup-specific conclusions.

• 出版日期2014-1-2