Avoiding Adverse Drug Reactions by Pharmacogenetic Testing: a Systematic Review of the Economic Evidence in the Case of TPMT and AZA-induced Side-effects

Objectives The study aims at evaluating the economic evidence related to testing for genetic variants of the drug-metabolizing enzyme, thiopurine methyltransferase (TPMT), to prevent toxicity in drug therapy. 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 the assessing the reliability of data on costs of neutropenia and of performing the tests, the two main cost categories that could inform an economic evaluation of TPMT pharmacogenetic testing. Methods A systematic review of the literature was performed to gather economic 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 six articles were retrieved specifying the costs associated with the management and treatment of AZA-induced neutropenia. The majority of these studies is 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 cost per prevented case of neutropenia equals to 5,300 �. Conclusions Solid economic considerations related to this type of pharmacogenetic testing are still limited by the ADR underreporting 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, could be more reliable sources of cost data in the future.

JRC.J.5 - Agriculture and Life Sciences in the Economy