ABSTRACT
Meta-Analysis ....................................................................66 6.5 Impact of Defining Region on Regional Sample Size Estimation .........68 6.6 Conclusion .................................................................................................... 71 6.7 Discussion .....................................................................................................72 6.8 Limitations .................................................................................................... 73 References ............................................................................................................... 74
or pathological factors as well as extrinsic factors such as medical practice. The increasing use of data from MRCTs to meet the disparate evidentiary standards for product registration in different countries and regions provides an imperative to find a systematic approach for defining region when planning, reviewing, and conducting MRCTs as well as analyzing data generated from such studies. This chapter describes a systematic approach to defining region in MRCTs; in fact, the approach goes beyond drawing lines on a map by recommending a standardized approach for the sponsor to think through carefully, prespecify, and justify any regional definition as well as to obtain regulatory concurrence prior to study conduct. Adequate justification of the definition should take into consideration factors such as race or ethnicity, disease epidemiology, medical practice, and geographic proximity, among others. Heterogeneity of any factor across region may lead to inconsistency in trial results. Identifying these factors in the planning stage can help to anticipate, plan for, and provide proper perspectives in trial results across regions.
