How does the threshold score to enter a major depression trial influence the size of the available patient population for study?

Abstract

Background: This paper describes the relationship between entry criteria and eligible population for inclusion in Major Depression (MD) clinical trials. Inclusion criteria for a MD study typically require patients to pass a threshold score on a depression rating scale, most commonly the HAM-D or MÅDRS. A Score To Enter (STE) of ≥17 on the HAM-D 17-item scale is a typical value, although higher values (i.e. ≥22 or even ≥25 points) are often used. It is commonly supposed that patients with higher baseline scores form a more sensitive sample for discriminating active drug from placebo. Method: We present data from a sample of depressed hospital outpatients and describe their general characteristics. We then introduce a model, based upon this sample, which predicts the impact of STE on eligible trial population. Results and conclusion: A small increase in STE has a marked effect on eligible population: an increase in HAM-D (17 item) STE from 17 to 21 and 25 reduces the eligible population by 42 and 76%, respectively. These predictions are reasonably robust when our model is validated with known clinical trial data. Clinical relevance: Our findings have major implications for planning and managing Major Depression trials as higher STEs substantially restrict the proportion of patient eligible for study.