Cost-Effectiveness of Pharmacogenomics-Guided Drug Therapy

  • Zhijia Tang
  • Weimin CaiEmail author


In healthcare settings, whether the added benefit of a new medical intervention is worth its added cost has long been a sophisticated question for clinicians, researchers, and decision makers. All healthcare professionals are expected to understand the philosophy of pharmacoeconomics in order to ensure the appropriate use of medical resources. Using pharmacogenomics-guided treatment, unreasonable medical expenses are avoided as dose being optimized, drug efficacy being enhanced, and side effects being reduced with the aim of personalizing treatment. This chapter identifies key aspects of pharmacoeconomics, including different elements and different types of pharmacoeconomic analyses, and discusses the situation why pharmacoeconomics is essential when utilizing pharmacogenomics in clinical practice.


Pharmacoeconomics Pharmacogenomics Pharmacogenetics Personalized medicine 


  1. 1.
    Rascati KL, Drummond MF, Annemans L, Davey PG (2004) Education in pharmacoeconomics: an international multidisciplinary view. PharmacoEconomics 22(3):139–147. Scholar
  2. 2.
    Townsend MC, Schirmer WJ, Schirmer JM, Fry DE (1987) Low-dose dopamine improves effective hepatic blood flow in murine peritonitis. Circ Shock 21(2):149–153PubMedGoogle Scholar
  3. 3.
    Drummond MF, Smith GT, Wells N (1988) Economic evaluation in the development of medicines. Office of Health Economics, LondonGoogle Scholar
  4. 4.
    Bertino JS (2013) Pharmacogenomics: an introduction and clinical perspective. McGraw-Hill, New YorkGoogle Scholar
  5. 5.
    Jayanthi MK, Sushma NV (2014) Drug utilization pattern and pharmacoeconomic study in paediatric dentistry at a tertiary hospital. Int J Pharm Pharm Sci 6(2):70–72Google Scholar
  6. 6.
    Lee JT, Sanchez LA (1991) Interpretation of “cost-effective” and soundness of economic evaluations in the pharmacy literature. Am J Hosp Pharm 48(12):2622–2627PubMedGoogle Scholar
  7. 7.
    Eisenberg JM (1989) Clinical economics. A guide to the economic analysis of clinical practices. JAMA 262(20):2879–2886. Scholar
  8. 8.
    Glossary of terms used in pharmacoeconomic and quality of life analysis (1992). Pharmacoeconomics 1:151Google Scholar
  9. 9.
    Yeh J, Goldman M (2009) Encyclopedia of medical decision making. SAGE, Thousand Oaks. Scholar
  10. 10.
    Kozma CM, Reeder CE, Schulz RM (1993) Economic, clinical, and humanistic outcomes: a planning model for pharmacoeconomic research. Clin Ther 15(6):1121–1132; discussion 1120PubMedGoogle Scholar
  11. 11.
    Reeder CE (1995) Overview of pharmacoeconomics and pharmaceutical outcomes evaluations. Am J Health Syst Pharm 52(19 Suppl 4):S5–S8. Scholar
  12. 12.
    Trask LS (2011) Pharmacoeconomics: principles, methods, and applications. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM (eds) Pharmacotherapy: a pathophysiologic approach, 8th edn. McGraw-Hill, New YorkGoogle Scholar
  13. 13.
    Rascati KL (2009) Introduction. In: Essentials of pharmacoeconomics, 2nd edn. Lippincott Williams & Wilkins, Philadelphia, pp 1–8Google Scholar
  14. 14.
    Ngorsuraches S (2008) Defining types of economic evaluation. J Med Assoc Thail 91(Suppl 2):S21–S27Google Scholar
  15. 15.
    Gift TL, Marrazzo J (2007) Cost-effectiveness analysis. In: Aral SO, Douglas JMJ (eds) Behavioral interventions for prevention and control of sexually transmitted diseases. Springer, New York, pp 482–499CrossRefGoogle Scholar
  16. 16.
    Kaplan RM (1993) Quality of life assessment for cost/utility studies in cancer. Cancer Treat Rev 19(Suppl A):85–96CrossRefGoogle Scholar
  17. 17.
    Sanchez LA, Lee J (1994) Use and misuse of pharmacoeconomic terms: a definitions primer. Top Hosp Pharm Manag 13(4):11–22Google Scholar
  18. 18.
    Cox E (2003) Cost-minimization analysis. In: Grauer D, Lee J, Odom T et al (eds) Pharmacoeconomics and outcomes, 2nd edn. American College of Clinical Pharmacy, Kansas City, pp 103–114Google Scholar
  19. 19.
    Plothner M, Ribbentrop D, Hartman JP, Frank M (2016) Cost-effectiveness of pharmacogenomic and pharmacogenetic test-guided personalized therapies: a systematic review of the approved active substances for personalized medicine in Germany. Adv Ther 33(9):1461–1480. Scholar
  20. 20.
    Table of pharmacogenomic biomarkers in drug labeling (2019). Accessed 10 Jan 2020
  21. 21.
    Diphoorn J, Cazzaniga S, Gamba C, Schroeder J, Citterio A, Rivolta AL, Vighi GD, Naldi L, Group RE-Ls (2016) Incidence, causative factors and mortality rates of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in northern Italy: data from the REACT registry. Pharmacoepidemiol Drug Saf 25(2):196–203. Scholar
  22. 22.
    Frey N, Jossi J, Bodmer M, Bircher A, Jick SS, Meier CR, Spoendlin J (2017) The epidemiology of Stevens-Johnson syndrome and toxic epidermal necrolysis in the UK. J Invest Dermatol 137(6):1240–1247. Scholar
  23. 23.
    Man CB, Kwan P, Baum L, Yu E, Lau KM, Cheng AS, Ng MH (2007) Association between HLA-B∗1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia 48(5):1015–1018. Scholar
  24. 24.
    European Medicines Agency (2012) PhVWP monthly report on safety concerns, guidelines and general matters. EMA, LondonGoogle Scholar
  25. 25.
    Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT (2004) Medical genetics: a marker for Stevens-Johnson syndrome. Nature 428(6982):486. Scholar
  26. 26.
    Dong D, Sung C, Finkelstein EA (2012) Cost-effectiveness of HLA-B∗1502 genotyping in adult patients with newly diagnosed epilepsy in Singapore. Neurology 79(12):1259–1267. Scholar
  27. 27.
    Ferrell PB Jr, McLeod HL (2008) Carbamazepine, HLA-B∗1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics 9(10):1543–1546. Scholar
  28. 28.
    ESA practice alert: on HLA testing for risk of Stevens–Johnson syndrome prior to commencing AEDs in patients of Asian ethnicity (2009). Accessed 10 Jan 2020
  29. 29.
    Plumpton CO, Yip VL, Alfirevic A, Marson AG, Pirmohamed M, Hughes DA (2015) Cost-effectiveness of screening for HLA-A∗31:01 prior to initiation of carbamazepine in epilepsy. Epilepsia 56(4):556–563. Scholar
  30. 30.
    Gonzalez-Galarza FF, McCabe A, Melo Dos Santos EJ, Takeshita L, Ghattaoraya G, Jones AR, Middleton D (2018) Allele frequency net database. Methods Mol Biol 1802:49–62. Scholar
  31. 31.
    Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, Lin YL, Lan JL, Yang LC, Hong HS, Chen MJ, Lai PC, Wu MS, Chu CY, Wang KH, Chen CH, Fann CS, Wu JY, Chen YT (2005) HLA-B∗5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci U S A 102(11):4134–4139. Scholar
  32. 32.
    Ke CH, Chung WH, Wen YH, Huang YB, Chuang HY, Tain YL, Wang YL, Wu CC, Hsu CN (2017) Cost-effectiveness analysis for genotyping before allopurinol treatment to prevent severe cutaneous adverse drug reactions. J Rheumatol 44(6):835–843. Scholar
  33. 33.
    Park DJ, Kang JH, Lee JW, Lee KE, Wen L, Kim TJ, Park YW, Park SH, Lee SS (2015) Cost-effectiveness analysis of HLA-B5801 genotyping in the treatment of gout patients with chronic renal insufficiency in Korea. Arthritis Care Res (Hoboken) 67(2):280–287. Scholar
  34. 34.
    Cheng H, Yan D, Zuo X, Liu J, Liu W, Zhang Y (2018) A retrospective investigation of HLA-B∗5801 in hyperuricemia patients in a Han population of China. Pharmacogenet Genomics 28(5):117–124. Scholar
  35. 35.
    Chong HY, Lim YH, Prawjaeng J, Tassaneeyakul W, Mohamed Z, Chaiyakunapruk N (2018) Cost-effectiveness analysis of HLA-B∗58: 01 genetic testing before initiation of allopurinol therapy to prevent allopurinol-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in a Malaysian population. Pharmacogenet Genomics 28(2):56–67. Scholar
  36. 36.
    Jutkowitz E, Dubreuil M, Lu N, Kuntz KM, Choi HK (2017) The cost-effectiveness of HLA-B∗5801 screening to guide initial urate-lowering therapy for gout in the United States. Semin Arthritis Rheum 46(5):594–600. Scholar
  37. 37.
    Khanna D, Fitzgerald JD, Khanna PP, Bae S, Singh MK, Neogi T, Pillinger MH, Merill J, Lee S, Prakash S, Kaldas M, Gogia M, Perez-Ruiz F, Taylor W, Liote F, Choi H, Singh JA, Dalbeth N, Kaplan S, Niyyar V, Jones D, Yarows SA, Roessler B, Kerr G, King C, Levy G, Furst DE, Edwards NL, Mandell B, Schumacher HR, Robbins M, Wenger N, Terkeltaub R, American College of R (2012) 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken) 64 (10):1431–1446 2012. doi:
  38. 38.
    Tan-Koi WC, Sung C, Chong YY, Lateef A, Pang SM, Vasudevan A, Aw D, Lui NL, Lee SX, Ren EC, Koay ES, Tay YK, Lim YL, Lee HY, Dong D, Loke C, Tan L, Limenta M, Lee EJ, Toh D, Chan CL (2017) Tailoring of recommendations to reduce serious cutaneous adverse drug reactions: a pharmacogenomics approach. Pharmacogenomics 18(9):881–890. Scholar
  39. 39.
    Dong D, Tan-Koi WC, Teng GG, Finkelstein E, Sung C (2015) Cost-effectiveness analysis of genotyping for HLA-B∗5801 and an enhanced safety program in gout patients starting allopurinol in Singapore. Pharmacogenomics 16(16):1781–1793. Scholar
  40. 40.
    Shimizu T, Ochiai H, Asell F, Shimizu H, Saitoh R, Hama Y, Katada J, Hashimoto M, Matsui H, Taki K, Kaminuma T, Yamamoto M, Aida Y, Ohashi A, Ozawa N (2003) Bioinformatics research on inter-racial difference in drug metabolism I. Analysis on frequencies of mutant alleles and poor metabolizers on CYP2D6 and CYP2C19. Drug Metab Pharmacokinet 18(1):48–70CrossRefGoogle Scholar
  41. 41.
    Blaisdell J, Mohrenweiser H, Jackson J, Ferguson S, Coulter S, Chanas B, Xi T, Ghanayem B, Goldstein JA (2002) Identification and functional characterization of new potentially defective alleles of human CYP2C19. Pharmacogenetics 12(9):703–711CrossRefGoogle Scholar
  42. 42.
    Zhu Y, Swanson KM, Rojas RL, Wang Z, St Sauver JL, Visscher SL, Prokop LJ, Bielinski SJ, Wang L, Weinshilboum R, Borah BJ (2019) Systematic review of the evidence on the cost-effectiveness of pharmacogenomics-guided treatment for cardiovascular diseases. Genet Med.
  43. 43.
    Wang Y, Yan BP, Liew D, Lee VWY (2018) Cost-effectiveness of cytochrome P450 2C19 ∗2 genotype-guided selection of clopidogrel or ticagrelor in Chinese patients with acute coronary syndrome. Pharmacogenomics J 18(1):113–120. Scholar
  44. 44.
    Jiang M, You JH (2016) Cost-effectiveness analysis of personalized antiplatelet therapy in patients with acute coronary syndrome. Pharmacogenomics 17(7):701–713. Scholar
  45. 45.
    Kim K, Touchette DR, Cavallari LH, Ardati AK, DiDomenico RJ (2019) Cost-effectiveness of strategies to personalize the selection of P2Y12 inhibitors in patients with acute coronary syndrome. Cardiovasc Drugs Ther 33:533–546. Scholar
  46. 46.
    Borse MS, Dong OM, Polasek MJ, Farley JF, Stouffer GA, Lee CR (2017) CYP2C19-guided antiplatelet therapy: a cost-effectiveness analysis of 30-day and 1-year outcomes following percutaneous coronary intervention. Pharmacogenomics 18(12):1155–1166. Scholar
  47. 47.
    IMURAN® (azathioprine) (2018) Sebela Pharmaceuticals Inc. FDA website: Accessed 01 Oct 2019
  48. 48.
    Wang HH, He Y, Wang HX, Liao CL, Peng Y, Tao LJ, Zhang W, Yang HX (2018) Comparison of TPMT and NUDT15 polymorphisms in Chinese patients with inflammatory bowel disease. World J Gastroenterol 24(8):941–948. Scholar
  49. 49.
    Dubinsky MC, Reyes E, Ofman J, Chiou CF, Wade S, Sandborn WJ (2005) A cost-effectiveness analysis of alternative disease management strategies in patients with Crohn’s disease treated with azathioprine or 6-mercaptopurine. Am J Gastroenterol 100(10):2239–2247. Scholar
  50. 50.
    Priest VL, Begg EJ, Gardiner SJ, Frampton CM, Gearry RB, Barclay ML, Clark DW, Hansen P (2006) Pharmacoeconomic analyses of azathioprine, methotrexate and prospective pharmacogenetic testing for the management of inflammatory bowel disease. PharmacoEconomics 24(8):767–781. Scholar
  51. 51.
    Marra CA, Esdaile JM, Anis AH (2002) Practical pharmacogenetics: the cost effectiveness of screening for thiopurine s-methyltransferase polymorphisms in patients with rheumatological conditions treated with azathioprine. J Rheumatol 29(12):2507–2512PubMedGoogle Scholar
  52. 52.
    Compagni A, Bartoli S, Buehrlen B, Fattore G, Ibarreta D, de Mesa EG (2008) 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 24(3):294–302. Scholar
  53. 53.
    Medical Advisory S (2010) KRAS testing for anti-EGFR therapy in advanced colorectal Cancer: an evidence-based and economic analysis. Ont Health Technol Assess Ser 10(25):1–49Google Scholar
  54. 54.
    Staudacher JJ, Yazici C, Bul V, Zeidan J, Khalid A, Xia Y, Krett N, Jung B (2017) Increased frequency of KRAS mutations in African Americans compared with Caucasians in sporadic colorectal cancer. Clin Transl Gastroenterol 8(10):e124. Scholar
  55. 55.
    Yoon HH, Shi Q, Alberts SR, Goldberg RM, Thibodeau SN, Sargent DJ, Sinicrope FA, Alliance for Clinical Trials in Oncology (2015) Racial differences in BRAF/KRAS mutation rates and survival in stage III colon cancer patients. J Natl Cancer Inst 107(10):djv186. Scholar
  56. 56.
    Benson AB 3rd, Venook AP, Cederquist L, Chan E, Chen YJ, Cooper HS, Deming D, Engstrom PF, Enzinger PC, Fichera A, Grem JL, Grothey A, Hochster HS, Hoffe S, Hunt S, Kamel A, Kirilcuk N, Krishnamurthi S, Messersmith WA, Mulcahy MF, Murphy JD, Nurkin S, Saltz L, Sharma S, Shibata D, Skibber JM, Sofocleous CT, Stoffel EM, Stotsky-Himelfarb E, Willett CG, Wu CS, Gregory KM, Freedman-Cass D (2017) Colon cancer, version 1.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 15(3):370–398. Scholar
  57. 57.
    Vijayaraghavan A, Efrusy MB, Goke B, Kirchner T, Santas CC, Goldberg RM (2012) Cost-effectiveness of KRAS testing in metastatic colorectal cancer patients in the United States and Germany. Int J Cancer 131(2):438–445. Scholar
  58. 58.
    Shiroiwa T, Motoo Y, Tsutani K (2010) Cost-effectiveness analysis of KRAS testing and cetuximab as last-line therapy for colorectal cancer. Mol Diagn Ther 14(6):375–384. Scholar
  59. 59.
    Chen CH, Lu YS, Cheng AL, Huang CS, Kuo WH, Wang MY, Chao M, Chen IC, Kuo CW, Lu TP, Lin CH (2019) Disparity in tumor immune microenvironment of breast cancer and prognostic impact: Asian versus western populations. Oncologist 25(1):e16–e23. Scholar
  60. 60.
    Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, American Society of Clinical Oncology/College of American Pathologists (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25(1):118–145. Scholar
  61. 61.
    Carlson RW, Moench SJ, Hammond ME, Perez EA, Burstein HJ, Allred DC, Vogel CL, Goldstein LJ, Somlo G, Gradishar WJ, Hudis CA, Jahanzeb M, Stark A, Wolff AC, Press MF, Winer EP, Paik S, Ljung BM, Force NHTiBCT (2006) HER2 testing in breast cancer: NCCN Task Force report and recommendations. J Natl Compr Canc Netw 4(Suppl 3):S1–S22; quiz S23–S24PubMedGoogle Scholar
  62. 62.
    Elkin EB, Weinstein MC, Winer EP, Kuntz KM, Schnitt SJ, Weeks JC (2004) HER-2 testing and trastuzumab therapy for metastatic breast cancer: a cost-effectiveness analysis. J Clin Oncol 22(5):854–863. Scholar
  63. 63.
    Lidgren M, Wilking N, Jonsson B, Rehnberg C (2008) Cost-effectiveness of HER2 testing and trastuzumab therapy for metastatic breast cancer. Acta Oncol 47(6):1018–1028. Scholar
  64. 64.
    Norum J, Risberg T, Olsen JA (2005) A monoclonal antibody against HER-2 (trastuzumab) for metastatic breast cancer: a model-based cost-effectiveness analysis. Ann Oncol 16(6):909–914. Scholar
  65. 65.
    Garrison LP Jr, Lubeck D, Lalla D, Paton V, Dueck A, Perez EA (2007) Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer. Cancer 110(3):489–498. Scholar
  66. 66.
    Chen W, Jiang Z, Shao Z, Sun Q, Shen K (2009) An economic evaluation of adjuvant trastuzumab therapy in HER2-positive early breast cancer. Value Health 12(Suppl 3):S82–S84. Scholar
  67. 67.
    Lang HC, Chen HW, Chiou TJ, Chan AL (2016) The real-world cost-effectiveness of adjuvant trastuzumab in HER-2/neu-positive early breast cancer in Taiwan. J Med Econ 19(10):923–927. Scholar

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© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of Clinical Pharmacy and Drug Administration, School of PharmacyFudan UniversityShanghaiChina

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