Distributional Flexibility under Box-Cox Normality: A Theoretical and Empirical Evaluation of the Power-Normal Distribution

Abstract

Methods based on Box-Cox models have recently been developed for inference on clinically interpretable treatment effects in clinical trials. These methods model marginal outcome distributions using the power-normal distribution (PND), but the range of real-world data distributions that it can adequately approximate remains unclear. We evaluated PND approximations using two parameterizations of the four-parameter generalized $F$/generalized beta of the second kind family and 165 laboratory variables from the National Health and Nutrition Examination Survey. Overall distributional agreement was assessed using the overlap coefficient and Jensen-Shannon divergence, and location and spread on the original scale were evaluated using relative biases in the median and interquartile range. The PND closely approximated a broad range of smooth unimodal positive distributions in both the theoretical and empirical evaluations. Reduced agreement was associated with pronounced lower-bound accumulation, heaping or discretization, and multicomponent or peak-tail features. These features may be recognizable before fitting and provide practical guidance for assessing the suitability of the PND. We also developed the R package powerNormal for distributional calculations, parameter estimation, reparameterization, and random-number generation for the PND.