Cost-effectiveness of pharmacogenetic-guided treatment: are we there yet?

Pharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene-drug associations have been discovered, but PGx-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health-care. We reviewed economic evaluations for PGx associations listed in the US Food and Drug Administration (FDA) Table of Pharmacogenomic Biomarkers in Drug Labeling. We determined the proportion of evaluations that found PGx-guided treatment to be cost-effective or dominant over the alternative strategies, and estimated the impact on this proportion of removing the cost of genetic testing. Of the 137 PGx associations in the FDA table, 44 economic evaluations, relating to 10 drugs, were identified. Of these evaluations, 57% drew conclusions in favour of PGx testing, of which 30% were cost-effective and 27% were dominant (cost-saving). If genetic information was freely available, 75% of economic evaluations would support PGx-guided treatment, of which 25% would be cost-effective and 50% would be dominant. Thus, PGx-guided treatment can be a cost-effective and even a cost-saving strategy. Having genetic information readily available in the clinical health record is a realistic future prospect, and would make more genetic tests economically worthwhile.

Establishing the characteristics of an effective pharmacogenetic test for clozapine-induced agranulocytosis.

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.