Pharmacogenetic testing for adverse drug reaction prevention: systematic review of economic evaluations and the appraisal of quality matters for clinical practice and implementation

Abstract

Background Genetic testing has potential roles in identifying whether an individual would have risk of adverse drug reactions (ADRs) from a particular medicine. Robust cost-effectiveness results on genetic testing would be useful for clinical practice and policy decision-making on allocating resources effectively. This study aimed to update a systematic review on economic evaluations of pharmacogenetic testing to prevent ADRs and critically appraise the quality of reporting and sources of evidence for model input parameters. Methods We searched studies through Medline via PubMed, Scopus and CRD’s NHS Economic Evaluation up to October 2019. Studies investigating polymorphism-based pharmacogenetic testing, which guided drug therapies to prevent ADRs, using economic evaluation methods were included. Two reviewers independently performed data extraction and assessed the quality of reporting using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines and the quality of data sources using the hierarchy of evidence developed by Cooper et al. Results Fifty-nine economic evaluations of pharmacogenetic testing to avoid drug-induced ADRs were found between 2002 and 2018. Cost-utility and cost-effectiveness analyses were the most common methods of economic evaluation of pharmacogenetic testing. Most studies complied with the CHEERS checklist, except for single study-based economic evaluations which did not report uncertainty analysis (78%). There was a lack of high-quality evidence not only for estimating the clinical effectiveness of pharmacogenetic testing, but also baseline clinical data. About 14% of the studies obtained clinical effectiveness data of testing from a meta-analysis of case-control studies with direct comparison, which was not listed in the hierarchy of evidence used. Conclusions Our review suggested that future single study-based economic evaluations of pharmacogenetic testing should report uncertainty analysis, as this could significantly affect the robustness of economic evaluation results. A specific ranking system for the quality of evidence is needed for the economic evaluation of pharmacogenetic testing of ADRs. Differences in parameters, methods and outcomes across studies, as well as population-level and system-level differences, may lead to the difficulty of comparing cost-effectiveness results across countries.

PRECISE-Value: An interactive web application that estimates the value of implementing a clinical decision support system for a pharmacogenomic testing program

“…That is not the focus of our work. To estimate the costs of testing, we encourage the reader to access other publications, in which PGx testing has been studied and modeled at a population scale (7)(8)(9)(10)(11)27). Rather, our goal in this project was to complement the existing data by incorporating a novel aspect to the analysis: understanding how patient population, demographics, structure of the testing program, and IT costs impact the cost-effectiveness of PGx-CDS.…”

“…Clinical decision support (CDS) is a critical component for integrating PGx data into the prescribing process, as a provider placing a medication order may not be trained in the interpretation of PGx results (6) and is also unlikely to be aware of a patient's genotype unless they have intentionally sought out that information (4). Multiple studies have examined the cost-effectiveness of PGx for various drug-gene pairs (7)(8)(9)(10)(11), but these studies generally focus on testing and/or medication costs and do not take into account the contribution of CDS to these programs' costs and bene ts (12).…”

Cardiovascular precision medicine – A pharmacogenomic perspective

“…Most of the cost-effectiveness studies have been conducted separate from implementation initiatives and they indicate that PGx testing results in a reduction in per-patient treatment cost (Winner et al, 2015 ; Deenen et al, 2016 ), lower cost-per-QALY (Mitropoulou et al, 2015 ) and cost savings in long-term care (Saldivar et al, 2016 ). A recent systematic appraisal of economic evaluations of PGx testing to prevent ADRs found a number of deficiencies in the quality of data used in cost-effectiveness and cost-utility analyses (Turongkaravee et al, 2021 ). Of the 14 economic evaluation studies of CYP2C9 and VKORC1 testing, 10 studies showed that CYP2C9 and VKORC1 testing would be a variably cost-effective and four studies suggested otherwise (Turongkaravee et al, 2021 ).…”

“…A recent systematic appraisal of economic evaluations of PGx testing to prevent ADRs found a number of deficiencies in the quality of data used in cost-effectiveness and cost-utility analyses (Turongkaravee et al, 2021 ). Of the 14 economic evaluation studies of CYP2C9 and VKORC1 testing, 10 studies showed that CYP2C9 and VKORC1 testing would be a variably cost-effective and four studies suggested otherwise (Turongkaravee et al, 2021 ). In contrast, all nine economic evaluation studies of CYP2C19 testing before prescription of clopidogrel ACS patients undergoing PCI showed that CYP2C19 testing would be a potentially cost-effective treatment strategy for avoiding MACE.…”

Direct Oral Anticoagulants (DOAC): Are We Ready for a Pharmacogenetic Approach?

“…As widely demonstrated by recent studies, the individual response to drugs is a multifactorial condition, depending on the interaction between environmental and genetic factors. An insufficient response to drug treatment can cause a partial or total failure of the current therapy, while an excessive response can cause serious and sometimes fatal side effects and adverse reactions [7].…”