PT  - JOURNAL ARTICLE
AU  - Moira Verbelen
AU  - David A Collier
AU  - Dan Cohen
AU  - James H MacCabe
AU  - Cathryn M Lewis
TI  - Establishing the characteristics of an effective pharmacogenetic test for clozapine induced agranulocytosis
AID  - 10.1101/010900
DP  - 2014 Jan 01
TA  - bioRxiv
PG  - 010900
4099  - http://biorxiv.org/content/early/2014/10/31/010900.short
4100  - http://biorxiv.org/content/early/2014/10/31/010900.full
AB  - Clozapine is the only evidence-based therapy for treatment resistant schizophrenia, but it induces agranulocytosis, a rare but potentially fatal haematological adverse reaction, in less than 1% of users. To improve safety, the drug is subject to mandatory haematological monitoring throughout the course of treatment, which is burdensome for the patient and one of the main reasons clozapine is underused. Therefore, a pharmacogenetic test is clinically useful if it identifies a group of patients for whom the agranulocytosis risk is low enough to alleviate monitoring requirements. Assuming a genotypic marker stratifies patients into a high risk and a low risk group, we explore the relationship between test sensitivity, group size and agranulocytosis risk. High sensitivity minimizes the agranulocytosis risk in the low risk group and is essential for clinical utility, in particular in combination with a small high risk group.