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A Systematic Review of Economic Evaluations of Pharmacogenetic Testing for Prevention of Adverse Drug Reactions

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Abstract

Background

Pharmacogenetics offers the potential to improve health outcomes by identifying individuals who are at greater risk of harm from certain medicines. Routine adoption of pharmacogenetic tests requires evidence of their cost effectiveness.

Objective

The present review aims to systematically review published economic evaluations of pharmacogenetic tests that aim to prevent or reduce the incidence of ADRs.

Methods

We conducted a systematic literature review of economic evaluations of pharmacogenetic tests aimed to reduce the incidence of adverse drug reactions. Literature was searched using Embase, MEDLINE and the NHS Economic Evaluation Database with search terms relating to pharmacogenetic testing, adverse drug reactions, economic evaluations and pharmaceuticals. Titles were screened independently by two reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts reviewed.

Results

We identified 852 articles, of which 47 met the inclusion criteria. There was evidence supporting the cost effectiveness of testing for HLA-B*57:01 (prior to abacavir), HLA-B*15:02 and HLA-A*31:01 (prior to carbamazepine), HLA-B*58:01 (prior to allopurinol) and CYP2C19 (prior to clopidogrel treatment). Economic evidence was inconclusive with respect to TPMT (prior to 6-mercaptoputine, azathioprine and cisplatin therapy), CYP2C9 and VKORC1 (to inform genotype-guided dosing of coumarin derivatives), MTHFR (prior to methotrexate treatment) and factor V Leiden testing (prior to oral contraception). Testing for A1555G is not cost effective before prescribing aminoglycosides.

Conclusions

Our systematic review identified robust evidence of the cost effectiveness of genotyping prior to treatment with a number of common drugs. However, further analyses and (or) availability of robust clinical evidence is necessary to make recommendations for others.

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Acknowledgments

This report is independent research funded by the National Institute for Health Research Invention for Innovation Programme (A biomarker panel to predict, diagnose and prevent HLA-mediated ADRs; reference number II-LB-0313-20008). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. The authors wish to thank Dr Colin Ridyard for acting as a third independent reviewer.

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Authors and Affiliations

  1. Centre for Health Economics and Medicines Evaluation, Bangor University, Ardudwy, Holyhead Road, Bangor, Wales, LL57 2PZ, UK

    Catrin O. Plumpton, Daniel Roberts & Dyfrig A. Hughes

  2. Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, L69 3GL, UK

    Munir Pirmohamed & Dyfrig A. Hughes

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  1. Catrin O. Plumpton
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Correspondence to Dyfrig A. Hughes.

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CP, DR, MP and DH declare that they have no conflict of interest.

Author Contributions

CP, DR and DH contributed substantially to the conception and design of the work. All authors made contributions to the acquisition, analysis, or interpretation of data. CP drafted the paper, and all authors revised it critically for important intellectual content, and gave their final approval of the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Appendix 1: Search Terms

Appendix 1: Search Terms

Search strategy for Embase and MEDLINE via Ovid

1

(Pharmacogenomic* or pharmacogenetic* or genomic* or genotype* or genetic* or single nucleotide polymorphism* or SNP)

2

(Cost?effective* or cost?utility or cost?benefit or cost?minimization or economic* or pharmacoeconomic*)

3

(Adverse or side?effect* or harm* or ADR? or toxic*)

4

(Drug* or medicine* or medication* or pharmaceutical*)

5

(1 AND 2 AND 3 AND 4).af.

6

5 NOT (editorial or letter or historical article or review or abstract).pt.

7

Limit 6 to English language and human subjects

Search strategy for NHS EED

1

(Pharmacogenomic* or pharmacogenetic* or genomic* or genotype* or genetic* or “single nucleotide polymorphism*” or SNP)

2

(Cost?effective* or cost?utility or cost?benefit or cost?minimization or economic* or pharmacoeconomic*)

3

(Adverse or side?effect* or harm* or ADR? or toxic*)

4

(Drug* or medicine* or medication* or pharmaceutical*)

5

(1 AND 2 AND 3 AND 4)

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Plumpton, C.O., Roberts, D., Pirmohamed, M. et al. A Systematic Review of Economic Evaluations of Pharmacogenetic Testing for Prevention of Adverse Drug Reactions. PharmacoEconomics 34, 771–793 (2016). https://doi.org/10.1007/s40273-016-0397-9

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