The misleading concept of initial severity in depression clinical trials: development and results from a mathematical model

Abstract

Objective: Recently, meta-analytic studies have suggested a positive relationship between initial severity and magnitude of treatment efficacy. The aim of the current study was to develop a mathematical model to test the assumption concerning the role of initial severity in treatment response. Methods: A number of experimental artificial datasets were developed on the basis of three different scenarios which reflect a pre-determined effect of initial severity. They were used to test for correlations at the patient level as well as at the meta-analysis level (trial level). Results: The results suggested that in all scenarios and analyses the correlations were so high that a ceiling effect was obvious. The testing concerned changes from baseline, but not differences between arms. Conclusions: Overall the data suggest that the question concerning the role of initial severity cannot be answered. Any allegations on such a role are based on flawed methodology and do not take into consideration the true nature of data.