Empirical Shrinkage Estimation Research Articles

Considerations for pediatric trial designs and analyses

ABSTRACTThere are challenges in designing pediatric trials arising from special ethical issues and the relatively small accessible patient population. The application of conventional phase 3 trial designs to pediatrics is not realistic in some therapeutic areas. To address this issue, we propose various approaches for designing pediatric trials that incorporate data available from adult studies using James–Stein shrinkage estimation, empirical shrinkage estimation, and Bayesian methods. We also apply the concept of consistency used in multi-regional trials to pediatric trials. The performance of these methods is assessed through representative scenarios and an example using actual Type 2 diabetes mellitus (T2DM) trials.

Multi-regional clinical trial design and consistency assessment of treatment effects

We can apply both fixed and random effects models to multi-regional clinical trial (MRCT) design and data analysis. Thoroughly, understanding the features of these models in an MRCT setting will help assessing their applicability to an MRCT. In this paper, we discuss the interpretations of trial results from these models. We also evaluate the impact of the number of regions and the sample size configuration across the regions on the required total sample size for the overall treatment effect assessment. For quantifying treatment effects of individual regions, the empirical shrinkage estimator and the James-Stein type shrinkage estimator associate with smaller variability compared with the regular sample estimator. We conduct computation and simulation to compare the performance of these estimators when they are applied to assess consistency of treatment effects across regions. We use a multinational trial example to illustrate the application of these methods.