Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
PharmacoEconomics
Published in: PharmacoEconomics 8/2016

01-08-2016 | Systematic Review

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

Authors: Catrin O. Plumpton, Daniel Roberts, Munir Pirmohamed, Dyfrig A. Hughes

Published in: PharmacoEconomics | Issue 8/2016

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Davies EC, Green CF, Taylor S, Williamson PR, Mottram DR, Pirmohamed M. Adverse drug reactions in hospital in-patients: a prospective analysis of 3695 patient-episodes. PLoS One. 2009;4:e4439.CrossRefPubMedPubMedCentral
2.
Pirmohamed M, James S, Meakin S, Green C, Scott AK, Walley T, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients. BMJ. 2004;329:15–9.CrossRefPubMedPubMedCentral
3.
Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279:1200–5.CrossRefPubMed
4.
Ingelman-Sundberg M. Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol Sci. 2004;25:193–200.CrossRefPubMed
5.
Pirmohamed M. Personalized pharmacogenomics: predicting efficacy and adverse drug reactions. Annu Rev Genomics Hum Genet. 2014;15:349–70.CrossRefPubMed
6.
7.
Yip VL, Alfirevic A, Pirmohamed M. Genetics of immune-mediated adverse drug reactions: a comprehensive and clinical review. Clin Rev Allergy Immunol. 2015;48(2–3):165–75.CrossRefPubMed
8.
Cargnin S, Jommi C, Canonico PL, Genazzani AA, Terrazzino S. Diagnostic accuracy of HLA-B*57:01 screening for the prediction of abacavir hypersensitivity and clinical utility of the test: a meta-analytic review. Pharmacogenomics. 2014;15(7):963–76.CrossRefPubMed
9.
Mallal S, Phillips E, Carosi G, Molina J-M, Workman C, Tomazic J, et al. HLA-B*5701 screening for hypersensitivity reaction. N Engl J Med. 2008;358:568–79.CrossRefPubMed
10.
Hughes DA, Vilar FJ, Ward CC, Alfirevic A, Park BK, Pirohamed M. Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity. Pharmacogenetics. 2004;14:335–42.CrossRefPubMed
11.
Schackman BR, Scott CA, Walensky RP, Losina E, Freedberg KA, Sax PE. The cost-effectiveness of HLA-B*5701 genetic screening to guide initial antiretroviral therapy for HIV. AIDS. 2008;22:2025–33.CrossRefPubMedPubMedCentral
12.
Pirmohamed M, Hughes DA. Pharmacogenetic tests: the need for a level playing field. Nat Rev Drug Discov. 2013;12:3–4.CrossRefPubMed
13.
Phillips KA, van Bebber SL. A systematic review of cost-effectiveness analyses of pharmacogenomic interventions. Pharmacogenomics. 2004;5(8):1139–49.CrossRefPubMed
14.
Beaulieu M, de Denus S, Lachaine J. Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010;11(11):1573–90.CrossRefPubMed
15.
Verhoed TI, Redekop WK, Darba J, Geitona M, Hughes DA, Siebert U, et al. A systematic review of cost-effectiveness analyses of pharmacogenetic-guided dosing in treatment with coumarin derivatives. Pharmacogenomics. 2010;11(7):989–1002.CrossRef
16.
Compagni A, Bartoli S, Buehrlen B, Fattore G, Ibarreta D, de Mesa EG. Avoiding adverse drug reactions by pharmacogenetic testing: a systematic review of the economic evidence in the case of TPMT and AZA-induced side effects. Int J Technol Assess Health Care. 2008;24(3):294–302.CrossRefPubMed
17.
18.
Moher D, Liberati A, Tetzlaff J. Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.CrossRefPubMedPubMedCentral
19.
Husereau D, Drummond M, Petrou S. ISPOR Health Economic Evaluation Publication Guidelines-CHEERS Good Reporting Practices Task Force Consolidated Health Economic Evaluation Reporting Standards (CHEERS)—explanation and elaboration: a report of the ISPOR Health Economic Evaluation Publication Guidelines Good Reporting Practices Task Force. Value Health. 2013;16:231–50.CrossRefPubMed
20.
Kauf TL, Farkouh RA, Earnshaw SR, Watson ME, Maroudas P, Chambers MG. Economic efficiency of genetic screening to inform the use of abacavir sulfate in the treatment of HIV. Pharmacoeconomics. 2010;28(11):1025–38.CrossRefPubMed
21.
Wolf W, Blankenburg M, Bogner JR, Becker W, Gorriahn D, Mueller MC, et al. Cost impact of prospective HLA-B*5701-screening prior to abacavir/lamivudine fixed dose combination use in Germany. Eur J Med Res. 2010;15(4):145–51.CrossRefPubMedPubMedCentral
22.
Calatravaa DN, de la Calle-Martín Ó, Iribarren-Loyartec JA, Rivero-Románd A, García-Bujalancee L, Pérez-Escolanoe I, Brosa-Riestra M. Cost-effectiveness analysis of HLA-B*5701 typing in the prevention of hypersensitivity to abacavir in HIV + patients in Spain. Enferm Infecc Microbiol Clin. 2010;28(9):590–5.CrossRef
23.
Kapoor R, Martinez-Vega R, Dong D, Tan SY, Leo YS, Lee CC, et al. Reducing hypersensitivity reactions with HLA-B*5701 genotyping before abacavir prescription: clinically useful but is it cost-effective in Singapore? Pharmacogenet Genomics. 2015;25:60–72.CrossRefPubMed
24.
Donnan JR, Ungar WJ, Mathews M, Hancock-Howard RL, Rahman P. A cost effectiveness analysis of thiopurine methyltransferase testing for guiding 6-mercaptopurine dosing in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2011;57(2):231–9.CrossRefPubMed
25.
Dubinsky MC, Reyes E, Ofman J, Chiou CF, Wade S, Sandborn WJ. A cost-effectiveness analysis of alternative disease management strategies in patients with Crohn’s disease treated with azathioprine or 6-mercaptopurine. Am J Gastroenterol. 2005;100(10):2239–47.CrossRefPubMed
26.
Hagaman JT, Kinder BW, Eckman MH. Thiopurine S-methyltransferase [corrected] testing in idiopathic pulmonary fibrosis: a pharmacogenetic cost-effectiveness analysis. Lung. 2010;188(2):125–32.CrossRefPubMed
27.
Marra CA, Esdaile JM, Anis AH. Practical pharmacogenetics: the cost effectiveness of screening for thiopurine s-methyltransferase polymorphisms in patients with rheumatological conditions treated with azathioprine. J Rheumatol. 2002;29(12):2507–12.PubMed
28.
Oh KT, Anis AH, Bae SC. Pharmacoeconomic analysis of thiopurine methyltransferase polymorphism screening by polymerase chain reaction for treatment with azathioprine in Korea. Rheumatology. 2004;43(2):156–63.CrossRefPubMed
29.
Priest VL, Begg EJ, Gardiner SJ, Frampton CM, Gearry RB, Barclay ML, et al. Pharmacoeconomic analyses of azathioprine, methotrexate and prospective pharmacogenetic testing for the management of inflammatory bowel disease. Pharmacoeconomics. 2006;24(8):767–81.CrossRefPubMed
30.
Sayani FA, Prosser C, Bailey RJ, Jacobs P, Fedorak RN. Thiopurine methyltransferase enzyme activity determination before treatment of inflammatory bowel disease with azathioprine: effect on cost and adverse events. Can J Gastroenterol. 2005;19(3):147–51.CrossRefPubMed
31.
Tavadia SM, Mydlarski PR, Reis MD, Mittmann N, Pinkerton PH, Shear N, et al. Screening for azathioprine toxicity: a pharmacoeconomic analysis based on a target case. J Am Acad Dermatol. 2000;42(4):628–32.CrossRefPubMed
32.
Thompson AJ, Newman WG, Elliott RA, Roberts SA, Tricker K, Payne K. The cost-effectiveness of a pharmacogenetic test: a trial-based evaluation of TPMT genotyping for azathioprine. Value Health. 2014;17(1):22–33.CrossRefPubMed
33.
van den Akker-van Marle ME. Gurwitz D, Detmar SB, Enzing CM, Hopkins MM, de Mesa E, Ibarreta DG. Cost-effectiveness of pharmacogenomics in clinical practice: a case study of thiopurine methyltransferase genotyping in acute lymphoblastic leukemia in Europe. Pharmacogenomics. 2006;7(5):783–92.CrossRefPubMed
34.
Winter J, Walker A, Shapiro D, Gaffney D, Spooner RJ, Mills PR. Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease. Aliment Pharmacol Ther. 2004;20(6):593–9.CrossRefPubMed
35.
Saokaew S, Tassaneeyakul W, Maenthaisong R, Chaiyakunapruk N. Cost-Effectiveness Analysis of HLA-B*5801 Testing in Preventing Allopurinol-Induced SJS/TEN in Thai Population. PLoS One. 2014;9(4):e94294.CrossRefPubMedPubMedCentral
36.
Park DJ, Kang JH, Lee JW, Lee KE, Wen L, Kim TJ, et al. Cost-effectiveness analysis of HLA-B5801 genotyping in the treatment of gout patients with chronic renal insufficiency in Korea. Arthritis Care Res (Hoboken). 2015;67(2):280–7.CrossRef
37.
Dong D, Sung C, Finkelstein EA. Cost-effectiveness of HLA-B*1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore. Neurology. 2012;79(12):1259–67.CrossRefPubMed
38.
Rattanavipapong W, Koopitakkajorn T, Praditsitthikorn N, Mahasirimongkol S, Teerawattananon Y. Economic evaluation of HLA-B*15:02 screening for carbamazepine-induced severe adverse drug reactions in Thailand. Epilepsia. 2013;54(9):1628–38.CrossRefPubMed
39.
Tiamkao S, Jitpimolmard J, Sawanyawisuth K, Jitpimolmard S. Cost minimization of HLA-B*1502 screening before prescribing carbamazepine in Thailand. Int J Clin Pharm. 2013;35(4):608–12.CrossRefPubMed
40.
Plumpton CO, Yip VLM, Alfirevic A, Marson AG, Pirmohamed M, Hughes DA. Cost effectiveness of screening for HLA-A*31:01 prior to initiation of Carbamazepine in epilepsy. Epilepsia. 2015;56(4):556–63.CrossRefPubMed
41.
Gold HT, Hall MJ, Blinder V, Schackman BR. Cost effectiveness of pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 before irinotecan administration for metastatic colorectal cancer. Cancer. 2009;115(17):3858–67.CrossRefPubMedPubMedCentral
42.
Pichereau S, Louarn A, Lecomte T, Blasco H, Guellec C, Bourgoin H. Cost-effectiveness of UGT1A1*28 genotyping in preventing severe neutropenia following FOLFIRI therapy in colorectal cancer. J Pharm Pharm Sci. 2010;13(4):615–25.CrossRefPubMed
43.
Obradovic M, Mrhar A, Kos M. Cost–effectiveness of UGT1A1 genotyping in second-line, high-dose, once every 3 weeks irinotecan monotherapy treatment of colorectal cancer. Pharmacogenomics. 2008;9(5):539–49.CrossRefPubMed
44.
Eckman MH, Rosand J, Greenberg SM, Gage BF. Cost-effectiveness of using pharmacogenetic information in warfarin dosing for patients with nonvalvular atrial fibrillation. Ann Intern Med. 2009;150(2):73–83.CrossRefPubMed
45.
Leey JA, McCabe S, Koch JA, Miles TP. Cost-effectiveness of genotype-guided warfarin therapy for anticoagulation in elderly patients with atrial fibrillation. Am J Geriatr Pharmacother. 2009;7(4):197–203.CrossRefPubMed
46.
Patrick AR, Avorn J, Choudhry NK. Cost-effectiveness of genotype-guided warfarin dosing for patients with atrial fibrillation. Circ Cardiovasc Qual Outcomes. 2009;2(5):429–36.CrossRefPubMed
47.
You JH, Tsui KK, Wong RS, Cheng G. Potential clinical and economic outcomes of CYP2C9 and VKORC1 genotype-guided dosing in patients starting warfarin therapy. Clin Pharmacol Ther. 2009;86(5):540–7.CrossRefPubMed
48.
Pink J, Pirmohamed M, Lane S, Hughes DA. Cost-Effectiveness of Pharmacogenetics-Guided Warfarin Therapy vs. Alternative Anticoagulation in Atrial Fibrillation. Clin Pharmacol Ther. 2014;95(2):199–207.CrossRefPubMed
49.
McWilliam A, Lutter R, Nardinelli C. Healthcare impact of personalized medicine using genetic testing: an exploratory analysis for warfarin. Per Med. 2008;5(3):279–84.CrossRef
50.
Schalekamp T, Boink GJJ, Visser LE, Stricker BHCh, de Boer A, Klungel OH. CYP2C9 genotyping in acenocoumarol treatment: is it a cost-effective addition to international normalized ratio monitoring? Clin Pharmacol Ther. 2006;79(6):511–20.CrossRefPubMed
51.
You JHS, Tsui KKN, Wong RSM, Cheng G. Cost-effectiveness of dabigatran versus genotype-guided management of warfarin therapy for stroke prevention in patients with atrial fibrillation. PLoS One. 2012;7(6):e39640.CrossRefPubMedPubMedCentral
52.
Meckley LM, Gudgeon JM, Anderson JL, Williams MS, Veenstra DL. A policy model to evaluate the benefits, risks and costs of warfarin pharmacogenomic testing. Pharmacoeconomics. 2010;28(1):61–74.CrossRefPubMed
53.
You JH, Chan FW, Wong RS, Cheng G. The potential clinical and economic outcomes of pharmacogenetics-oriented management of warfarin therapy: a decision analysis. Thromb Haemost. 2004;92(3):590–7.PubMed
54.
Verhoef TI, Redekop WK, Veenstra DL, Thariani R, Beltman PA, van Schie RMF, de Boer A, Maitland-van der Zee AH and Members of the EU-PACT group. Cost-effectiveness of pharmacogenetic-guided dosing of phenprocoumon in atrial fibrillation. Pharmacogenomics. 2013;14(8):869–83.CrossRefPubMed
55.
Lala A, Berger JS, Sharma G, Hochman JS, Braithwaite RS, Ladapo JA. Genetic testing in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cost-effectiveness analysis. J Thromb Haemost. 2013;11(1):81–91.CrossRefPubMed
56.
Panattoni L, Brown PM, Te Ao B, Webster M, Gladding P. The cost effectiveness of genetic testing for CYP2C19 variants to guide thienopyridine treatment in patients with acute coronary syndromes: a New Zealand evaluation. Pharmacoeconomics. 2012;30(11):1067–84.CrossRefPubMed
57.
Reese ES, Mullins CD, Beitelshees AL, Onukwugha E. Cost-effectiveness of cytochrome P450 2C19 genotype screening for selection of antiplatelet therapy with clopidogrel or prasugrel. Pharmacotherapy. 2012;32(4):323–32.CrossRefPubMedPubMedCentral
58.
Sorich MJ, Horowitz JD, Sorich W, Wiese MD, Pekarsky B, Karnon JD. Cost-effectiveness of using CYP2C19 genotype to guide selection of clopidogrel or ticagrelor in Australia. Pharmacogenomics. 2013;14(16):2013–21.CrossRefPubMed
59.
Veenstra DL, Harris J, Gibson RL, Rosenfeld M, Burke W, Watts C. Pharmacogenomic testing to prevent aminoglycoside-induced hearing loss in cystic fibrosis patients: potential impact on clinical, patient, and economic outcomes. Genet Med. 2007;9(10):695–704.CrossRefPubMed
60.
Dionne F, Mitton C, Rassekh R, Brooks B, Ross C, Hayden M, et al. Economic impact of a genetic test for cisplatin-induced ototoxicity. Pharmacogenomics J. 2012;12(3):205–13.CrossRefPubMed
61.
Kim SK, Jun JB, El-Sohemy S, Bae SC. Cost-effectiveness analysis of MTHFR polymorphism screening by polymerase chain reaction in Korean patients with rheumatoid arthritis receiving methotrexate. J Rheumatol. 2006;33(7):1266–74.PubMed
62.
Creinin MD, Lisman R, Strickler RC. Screening for factor V Leiden mutation before prescribing combination oral contraceptives. Fertil Steril. 1999;72(4):646–51.CrossRefPubMed
63.
Smith KJ, Monsef BS, Ragni MV. Should female relatives of factor V Leiden carriers be screened prior to oral contraceptive use? A cost-effectiveness analysis. Thromb Haemost. 2008;100(3):447–52.PubMed
64.
Olgiati P, Bajo E, Bigelli M, Ronchi D, Serretti A. Should pharmacogenetics be incorporated in major depression treatment? Economic evaluation in high- and middle-income European countries. Prog Neuropsychopharmacol Biol Psychiatry. 2012;36(1):147–54.CrossRefPubMed
65.
Chantratita W, Chantarangsu S, Kiertiburanakul S, Sungkanuparph S, Charoenyingwattana A, Mahasirimongkol S. Integrating HIV-1 Pharmacogenomics into the Universal Coverage Health-Care System in Thailand: from scientific evidence to policy. J Pharmacogenom Pharmacoproteomics. 2011;S6:001.
66.
Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008;358(6):568–79.CrossRefPubMed
67.
Newman WG, Payne K, Tricker K, Roberts SA, Fargher E, Pushpakom S, et al. A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study. Pharmacogenomics. 2011;12(6):815–26.CrossRefPubMed
68.
Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013;369(24):2283–93.CrossRefPubMedPubMedCentral
69.
Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, et al. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013;369(24):2294–303.CrossRefPubMed
70.
Roberts JD, Wells GA, Le May MR, Labinaz M, Glover C, Froeschl M, et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. Lancet. 2012;379(9827):1705–11.CrossRefPubMed
71.
Wong WB, Carlson JJ, Thariani R, Veenstra DL. Cost effectiveness of pharmacogenomics: a critical and systematic review. Pharmacoeconomics. 2010;28(11):1001–13.CrossRefPubMed
72.
Payne K, Shabaruddin FH. Cost-effectiveness analysis in pharmacogenomics. Pharmacogenomics. 2010;11(5):643–6.CrossRefPubMed
73.
Flowers CR, Veenstra D. The role of cost-effectiveness analysis in the era of pharmacogenomics. Pharmacoeconomics. 2004;22(8):481–93.CrossRefPubMed
Metadata
Title
A Systematic Review of Economic Evaluations of Pharmacogenetic Testing for Prevention of Adverse Drug Reactions
Authors
Catrin O. Plumpton
Daniel Roberts
Munir Pirmohamed
Dyfrig A. Hughes
Publication date
01-08-2016
Publisher
Springer International Publishing
Published in
PharmacoEconomics / Issue 8/2016
Print ISSN: 1170-7690
Electronic ISSN: 1179-2027
DOI
https://doi.org/10.1007/s40273-016-0397-9

Other articles of this Issue 8/2016

PharmacoEconomics 8/2016 Go to the issue

Original Research Article

Cost Utility of Omalizumab Compared with Standard of Care for the Treatment of Chronic Spontaneous Urticaria

Systematic Review

Systematic Review of Health-Related Quality of Life in Patients with Pulmonary Arterial Hypertension

Leading Article

Economic Evaluation of Childhood Obesity Interventions: Reflections and Suggestions

Original Research Article

Cost Effectiveness of Protease Inhibitor Monotherapy Versus Standard Triple Therapy in the Long-Term Management of HIV Patients: Analysis Using Evidence from the PIVOT Trial

Current Opinion

Economic Evaluation of Vaccination Programmes in Older Adults and the Elderly: Important Issues and Challenges

Review Article

Ledipasvir-Sofosbuvir for Treating Chronic Hepatitis C: A NICE Single Technology Appraisal—An Evidence Review Group Perspective