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. 2000 Sep 14;2(3):80–90. doi: 10.1208/ps020329

Assessing the cost-effectiveness of pharmacogenomics

David L Veenstra 1,✉, Mitchell K Higashi 1, Kathryn A Phillips 2
PMCID: PMC2761139  PMID: 11741245

Abstract

The use of pharmacogenomics to individualize drug therapy offers the potential to improve drug effectiveness, reduce adverse side effects, and provide cost-effective pharmaceutical care. However, the combinations of disease, drug, and genetic test characteristics that will provide clinically useful and economically feasible therapeutic interventions have not been clearly elucidated. The purpose of this paper was to develop a framework for evaluating the potential cost-effectiveness of pharmacogenomic strategies that will help scientists better understand the strategic implications of their research assist in the design of clinical trials, and provide a guide for health care providers making reimbursement decisions. We reviewed concepts of cost-effectiveness analysis and pharmacogenomics and identified 5 primary characteristics that will enhance the cost-effectiveness of pharmacogenomics: 1) there are severe clinical or economic consequence that are avoided through the use of pharmacogenomics, 2) monitoring drug response using current methods is difficult, 3) a well-established association between genotype and clinical phenotype exists, 4) there is a rapid and relatively inexpensive genetic test, and 5) the variant gene is relatively common. We use this framework to evaluate several examples of pharmacogenomics. We found that pharmacogenomics offers great potential to improve patients' health in a cost-effective manner. However, pharmacogenomics will not be applied to all currently marketed drugs, and careful evaluations are needed on a case-by-case basis before investing resources in research and development of pharmacogenomic-based therapeutics and making reimbursement decisions.

References

  • 1.Collins FS. Genetics: An explosion of knowledge is transforming clinical practice. Geriatrics. 1999;54:41–47. [PubMed] [Google Scholar]
  • 2.Friend SH. How DNA microarrays and expression profiling will affect clinical practice. BMJ. 1999;319:1–2. doi: 10.1136/bmj.319.7220.1306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Evans WE, Relling MV. Pharmacogenomics: translating functional genomics into rational therapeutics. Science. 1999;286:487–491. doi: 10.1126/science.286.5439.487. [DOI] [PubMed] [Google Scholar]
  • 4.Brookes AJ. The essence of SNPs. Gene. 1999;234:177–186. doi: 10.1016/S0378-1119(99)00219-X. [DOI] [PubMed] [Google Scholar]
  • 5.Gelehrter TD, Collins FS, Ginsburg D. Principles of Medical Genetics. 2nd ed. Baltimore, Md: Williams & Wilkins; 1998. [Google Scholar]
  • 6.McCarthy JJ, Hilfiker R. The use of single-nucleotide polymorphism maps in pharmacogenomics. Nat Biotechnol. 2000;18:505–508. doi: 10.1038/75360. [DOI] [PubMed] [Google Scholar]
  • 7.Veenstra DL, Kollman PA. Modeling protein stability a theoretical analysis of the stability of T4 lysozyme mutants. Protein Eng. 1997;10:789–807. doi: 10.1093/protein/10.7.789. [DOI] [PubMed] [Google Scholar]
  • 8.Sadee W.Pharmacogenomics BMJ 19993191–4.10390429 [Google Scholar]
  • 9.Marshall A. Getting the right drug into the right patient. Nat Biotechnol. 1997;15:1249–1252. doi: 10.1038/nbt1197-1249. [DOI] [PubMed] [Google Scholar]
  • 10.Kleyn PW, Vesell ES. Genetic variation as a guide to drug development. Science. 1998;281:1820–1821. doi: 10.1126/science.281.5384.1820. [DOI] [PubMed] [Google Scholar]
  • 11.Hodgson J, Marshall A. Pharmacogenomics: will the regulators approve? Nat Biotechnol. 1998;16:243–246. doi: 10.1038/nbt0398-243. [DOI] [PubMed] [Google Scholar]
  • 12.Regalado A. Inventing the pharmacogenomics busines. Am J Health Syst Pharm. 1999;56:40–50. doi: 10.1093/ajhp/56.1.40. [DOI] [PubMed] [Google Scholar]
  • 13.Persidis A. The business of pharmacogenomics. Nat Biotechnol. 1998;16:209–210. doi: 10.1038/nbt0298-209. [DOI] [PubMed] [Google Scholar]
  • 14.Garber AM, Phelps CE. Economic foundations of cost-effectiveness analysis. J Health Econ. 1997;16:1–31. doi: 10.1016/S0167-6296(96)00506-1. [DOI] [PubMed] [Google Scholar]
  • 15.Weinstein MC, Siegel JE, Gold MR, Kamlet MS, Russell LB. Recommendations of the Panel on Cost-effectiveness in Health and Medicine. JAMA. 1996;276:1253–1258. doi: 10.1001/jama.276.15.1253. [DOI] [PubMed] [Google Scholar]
  • 16.Drummond M, Dubois D, Garattini L, et al. Current trends in the use of pharmacoecoinomics and outcomes research in Europe. Value in Health. 1999;2:323–332. doi: 10.1046/j.1524-4733.1999.25003.x. [DOI] [PubMed] [Google Scholar]
  • 17.CCOHTA. Canadian Coordinating Office for Health Technology Assessment Guidelines for economic evaluations of pharmacoenticals. Canada. 2nd ed. 1997 (http://www.ccohta.ca/main-e.html).
  • 18.Mather DB, Sullivan SD, Augenstein D, Fullerton DS, Athlerly D. Incorporating clinical outcomes and economic consequences into drug formulary decisions: a practical approach. Am J Manag Care. 1999;5:277–285. [PubMed] [Google Scholar]
  • 19.Kuivenhoven JA, Jukema JW, Zwinderman AH, Knijf P, McPherson R, Bruschke AV, Lie KI, Kastelein JJ. The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. N Engl J Med. 1998;338:86–93. doi: 10.1056/NEJM199801083380203. [DOI] [PubMed] [Google Scholar]
  • 20.McHutchinson JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustigi VK, Goodman ZD, Ling M, Cort S, Albrecht JK. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitic C. N Engl J Med. 1998;339(21):1485–1492. doi: 10.1056/NEJM199811193392101. [DOI] [PubMed] [Google Scholar]
  • 21.Younossi ZM, Singer ME, McHutchison JG, Shermock KM. Costeffectiveness of interferon alpha2b combined with ribavirin for the treatment of chronic hepatitis C. Hepatology. 1999;30(5):1318–1324. doi: 10.1002/hep.510300518. [DOI] [PubMed] [Google Scholar]
  • 22.Veenstra DL, Tran C, Lum B, Cheung R. The cost-effectiveness of genetic screening and combination theapy for hepatitis C. Paper presented at: Drug Information Association 2nd Annual Workshop on Pharmacentical Outcomes Research. May 11–12. 2000: Seattle, Wash.
  • 23.Weinstein MC, Goldie SJ, Cohen C, Losian H, Zhang HJ, Kimmel AD. Resistance testing to guide the choice of second-line. antitretroviral therapy in HIV: clinical impact and cost-effectiveness [abstract]. In: Program and Abstracts of the meeting of the Sciety for Medical Decision Making: October 3–6, 1999: Reno. Nev.
  • 24.Anis AH, Wang X, Harrigan R. Hogg RS, Yin B. O'Shaghnessy MV, Schlechter MT, Montaner JSG. Optimizing drug treatment cost-effectiveness analysis of HIV/AIDS drug resistance testing [abstract]. In: Program and Abstracts of the Meeting of the Society. for Medical Decision Making. October 3–6, 1999; Reno. Nev
  • 25.Shak S, the Herceptin Multinational Investigator Study Group Overview of the trastuzumab Herceptin) anti-HER2 monoclonal antibody clinical program in HER2-overexpressing metastatic breast cancer. Semin Oncol. 1999;26(4 suppl 12):71–77. [PubMed] [Google Scholar]
  • 26.Motulsky AG. Drug reactions, enzymes and biochemical genetics. JAMA. 1957;165:835–837. doi: 10.1001/jama.1957.72980250010016. [DOI] [PubMed] [Google Scholar]
  • 27.Rettie AE, Wienkers LC, Gonzalez FJ, Trager WF, Korzekwa KR. Impaired (S)-warfarin metabolism catalysed by the R144C allelic variant of CYP2C9. Pharmacogenetics. 1994;4:39–42. doi: 10.1097/00008571-199402000-00005. [DOI] [PubMed] [Google Scholar]
  • 28.Aithal GP, Day CP, Kesteven PJ, Daly AK. Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet. 1999;353:717–719. doi: 10.1016/S0140-6736(98)04474-2. [DOI] [PubMed] [Google Scholar]
  • 29.Krynetski EY, Evans WE. Pharmacogenetics as a molecular basis for individualized drug therapy: the thiopurine S-methyltransferase paradigm. Pharm Res. 1999;16(3):342–349. doi: 10.1023/A:1011909315614. [DOI] [PubMed] [Google Scholar]
  • 30.Evans WE, Horner M, Chu YQ, Kalwinsky D, Roberts WM. Altered mercaptopurine metabolism, toxic effects, and dosage requirement in a thiopurine methyltransferase-deficient child with acute lymphocytic leukemia. J. Pediatr. 1991;119:985–989. doi: 10.1016/S0022-3476(05)83063-X. [DOI] [PubMed] [Google Scholar]
  • 31.Lennard L, Gibson BE, Nicole T, Lilleyman JS. Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia. Arch Dis Child. 1993;69:577–579. doi: 10.1136/adc.69.5.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Lennard L, Loon JA, Weinshilboum RM. Pharmacogenetics of acute azathioprine toxicity: relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther. 1989;46:149–154. doi: 10.1038/clpt.1989.119. [DOI] [PubMed] [Google Scholar]
  • 33.Detsky AS, Naglie G, Krahn MD, Naimark D, Redelmeier DA. Primer on medical decision analysis: Part 1—Getting started. Med Decis Making. 1997;17:123–125. doi: 10.1177/0272989X9701700201. [DOI] [PubMed] [Google Scholar]
  • 34.Steinbach G, Lynch PM, Phillips RKS. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med. 2000;342:1946–1952. doi: 10.1056/NEJM200006293422603. [DOI] [PubMed] [Google Scholar]
  • 35.Perrin L, Telenti A. HIV treatment failure: testing for HIV resistance in clinical practice. Science. 1998;280:1871–1873. doi: 10.1126/science.280.5371.1871. [DOI] [PubMed] [Google Scholar]
  • 36.Richman DD. Principles of HIV resistance testing and overview of assay performance characteristics. Antivir Ther. 2000;5:27–31. [PubMed] [Google Scholar]
  • 37.Liggett SB. Phamacogenetics of relevant targets in asthma. Clin Exp Allergy. 1998;28(suppl 1):77–79. doi: 10.1046/j.1365-2222.1998.0280s1077.x. [DOI] [PubMed] [Google Scholar]
  • 38.Israel E, Drazen JM, Ligget SB, et al. The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med. 2000;162:75–80. doi: 10.1164/ajrccm.162.1.9907092. [DOI] [PubMed] [Google Scholar]
  • 39.Richard F, Helbecque N, Neuman E, Guez D, Levy R, Amouyel P. APOE genotyping and response to drug treatment in Alzheimer's disease. Lancet. 1997;349:539–539. doi: 10.1016/S0140-6736(97)80089-X. [DOI] [PubMed] [Google Scholar]
  • 40.Farlow MR, Lahiri DK, Poirier J, Davignon J, Hui S. Apolipoprotein E genotype and gender influence response to tacrine therapy. Ann N Y Acad Sci. 1996;802:101–110. doi: 10.1111/j.1749-6632.1996.tb32603.x. [DOI] [PubMed] [Google Scholar]
  • 41.Jonsson EG, Nothen MM, Gustavsson JP, Neidt H, Bunzel R, Propping P, Sedvall GC. Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers. Psychiatry Res. 1998;79:1–9. doi: 10.1016/S0165-1781(98)00027-4. [DOI] [PubMed] [Google Scholar]
  • 42.Temple R. Are surrogate markers adequate to assess cardiovascular disease drugs? JAMA. 1999;282:790–795. doi: 10.1001/jama.282.8.790. [DOI] [PubMed] [Google Scholar]
  • 43.Lichter JB, Kuith JH. The impact of pharmacogenetics on the future of healthcare. Curr Opin Biotechnol. 1997;8:692–695. doi: 10.1016/S0958-1669(97)80121-8. [DOI] [PubMed] [Google Scholar]
  • 44.Rioux PP. Clinical trials in pharmacogenetics and pharmacogenomics methods and applications. Am J Health Syst Pharm. 2000;57:887–898. doi: 10.1093/ajhp/57.9.887. [DOI] [PubMed] [Google Scholar]

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