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.

Keywords

initial severity clinical trials response

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