The misleading concept of initial severity in depression clinical trials: development and results from a mathematical model.
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.
Associate Professor of Psychiatry, School of Medicine, 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Greece, and Chair, Research Methods in Psychiatry, World Psychiatric Association, Geneva, Switzerland.
Konstantinos N
KN
Fountoulakis
D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D003866:Depressive Disorder / Q000628:therapy*; D006801:Humans; D008962:Models, Theoretical; D012720:Severity of Illness Index; D016896:Treatment Outcome
clinical trials; initial severity; response