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Avoiding adverse drug reactions by pharmacogenetic testing: A systematic review of the economic evidence in the case of TPMT and AZA-induced side effects

Published online by Cambridge University Press:  04 July 2008

Amelia Compagni
Università Bocconi
Simona Bartoli
Università Bocconi
Bernhard Buehrlen
Fraunhofer Institute for Systems and Innovation Research
Giovanni Fattore
Università Bocconi
Dolores Ibarreta
Institute for Prospective Technological Studies
Emma Gutierrez de Mesa
European Centre for Disease Prevention and Control


Objectives: The study aims at evaluating the economic evidence related to testing for genetic variants of the drug-metabolizing enzyme, TPMT. Detecting TPMT genetic variants before the administration of azathioprine (AZA) has the potential to prevent serious and costly adverse drug reactions (ADRs), such as neutropenia. In particular, our analysis concentrated on assessing the reliability of data on costs of neutropenia and performing the tests, the two main cost categories that could inform an economic evaluation of TPMT pharmacogenetic testing.

Methods: A systematic literature review was performed to gather evidence on the costs of testing and neutropenia. Articles were critically appraised for their comprehensiveness and quality. To better estimate costs of TPMT tests, a small-scale survey of European diagnostic laboratories was conducted.

Results: Only seven articles were retrieved specifying the costs associated with the management and treatment of AZA-induced neutropenia. Most of these studies are based on theoretical modeling reconstructed with key-informants or on very few cases of ADRs, and either the methodology for cost calculation is not specified or costs are based on national cost databases and tariffs. After critical appraisal of these studies, we considered €2,116 as the most reliable estimate for the cost of a case of neutropenia. Literature review accompanied by the survey of several diagnostic laboratories also provided an estimate (€68) for TPMT testing. Based on these values, the net cost per prevented case of neutropenia equals to €5,300.

Conclusions: Solid economic considerations related to TPMT pharmacogenetic testing are still limited by underreporting of ADRs and high level of approximation related to cost data. Ad hoc observational studies and the ADR recording process embedded in pharmacovigilance systems, established across Europe, should represent more reliable sources of cost data in the future.

Copyright © Cambridge University Press 2008

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