A graphical approach to assess the goodness-of-fit of random-effects linear models when the goal is to measure individual benefits of medical treatments in severely ill patients

摘要

Two-dimensional personalized medicine (2-PM) models are tools for measuring individual benefits of medical treatments for chronic diseases which have potential applications in personalized medicine. These models assume normality for the distribution of random effects. It is necessary to examine the appropriateness of this assumption. Here, we propose a graphical approach to assessing the goodness-of-fit of 2-PM models with continuous responses. We propose benefit quantile-quantile (BQQ) plots which compare the empirical quantiles of individual benefits from a patient sample predicted through an empirical Bayes (EB) approach versus the quantiles of the theoretical distribution of individual benefits derived from the assumption of normality for the random effects. We examine the performance of the approach by conducting a simulation study that compared 2-PM models with non-normal distributions for the random effects versus models with comparable normal distributions. Cramer-von Mises discrepancies were used to quantify the performance of the approach. The approach was illustrated with data from a clinical trial of imipramine for patients with depression. Simulations showed that BQQ plots were able to capture deviations from the normality assumption for the random effects and did not show any asymmetric deviations from the y?=?x line when the random effects were normally distributed. For the depression data, the points of the BQQ plot were scattered around closely to the y?=?x line, without presenting any asymmetric deviations. This implied the adequacy of the normality assumption for the random effects and the goodness-of-fit of the 2-PM model for the imipramine data. BQQ plots are sensitive to violations of the normality assumption for the random effects, suggesting that the approach is a useful tool for examining the goodness-of-fit of random-effects linear models when the goal is to measure individual treatment benefits.