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Cost-effectiveness of pharmacogenetic testing to tailor smoking-cessation treatment

The Pharmacogenomics Journal volume 8, pages 391–399 (2008)Cite this article

Abstract

We evaluated the cost-effectiveness of a range of smoking cessation drug treatments, including varenicline, transdermal nicotine (TN), bupropion and the use of a genetic test to choose between TN and bupropion. We performed Monte Carlo simulation with sensitivity analysis, informing analyses with published estimates of model parameters and current prices for genetic testing and smoking-cessation therapy. The primary outcomes were discounted life-years (LY) and lifetime tobacco-cessation treatment costs. In the base case, varenicline treatment was optimal with an ICER, compared to bupropion, of $2985/LY saved. In sensitivity analyses, varenicline was in all cases (and bupropion in most cases) admissible; only under favorable assumptions was the genetically tailored approach competitive. Our data suggest that an untailored approach of treatment with either bupropion or varenicline is a cost-effective form of tobacco dependence treatment, but a tailored approach for selecting between TN and bupropion can be cost-effective under plausible assumptions.

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References

  1. Munafò MR, Shields AE, Berrettini WH, Patterson F, Lerman C . Pharmacogenetics and nicotine addiction treatment. Pharmacogenomics 2005; 6: 211–223.

    Article  PubMed  Google Scholar 

  2. Kirchheiner J, Nickchen K, Bauer M, Wong ML, Licinio J, Roots I et al. Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response. Mol Psychiatry 2004; 9: 442–473.

    Article  CAS  PubMed  Google Scholar 

  3. Schafer M, Rujescu D, Giegling I, Guntermann A, Erfurth A, Bondy B et al. Association of short-term response to haloperidol treatment with a polymorphism in the dopamine D(2) receptor gene. Am J Psychiatry 2001; 158: 802–804.

    Article  CAS  PubMed  Google Scholar 

  4. Peters EJ, Slager SL, McGrath PJ, Knowles JA, Hamilton SP . Investigation of serotonin-related genes in antidepressant response. Mol Psychiatry 2004; 9: 879–889.

    Article  CAS  PubMed  Google Scholar 

  5. Polanczyk G, Zeni C, Genro JP, Guimaraes AP, Roman T, Hutz MH et al. Association of the adrenergic alpha2A receptor gene with methylphenidate improvement of inattentive symptoms in children and adolescents with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 2007; 64: 218–224.

    Article  CAS  PubMed  Google Scholar 

  6. Oslin DW, Berrettini W, Kranzler HR, Pettinati H, Gelernter J, Volpicelli JR et al. A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology 2003; 28: 1546–1552.

    Article  CAS  PubMed  Google Scholar 

  7. Lerman C, Jepson C, Wileyto EP, Epstein LH, Rukstalis M, Patterson F et al. Role of functional genetic variation in the dopamine D2 receptor (DRD2) in response to bupropion and nicotine replacement therapy for tobacco dependence: results of two randomized clinical trials. Neuropsychopharmacology 2006; 31: 231–242.

    Article  CAS  PubMed  Google Scholar 

  8. Lerer B, Segman RH, Fangerau H, Daly AK, Basile VS, Cavallaro R et al. Pharmacogenetics of tardive dyskinesia: combined analysis of 780 patients supports association with dopamine D3 receptor gene Ser9Gly polymorphism. Neuropsychopharmacology 2002; 27: 105–119.

    Article  CAS  PubMed  Google Scholar 

  9. Reynolds GP, Zhang Z, Zhang X . Polymorphism of the promoter region of the serotonin 5-HT(2C) receptor gene and clozapine-induced weight gain. Am J Psychiatry 2003; 160: 677–679.

    Article  PubMed  Google Scholar 

  10. Corrigan OP . Pharmacogenetics, ethical issues: review of the Nuffield Council on Bioethics Report. J Med Ethics 2005; 31: 144–148.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Shields A, Lerman C, Sullivan P . Translating emerging research on the genetics of smoking into clinical practice: ethical and social considerations. Nicotine Tob Res 2004; 6: 675–688.

    Article  PubMed  Google Scholar 

  12. US Department of Health and Human Services. The Health Benefits of Smoking Cessation, USDHHS, PHS, CDC, Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; DHHS Publication No. (CDC) 90-8416 1990.

  13. American Legacy Foundation. Saving Lives, Saving Money: Why States Should Invest in a Tobacco-Free Future. American Legacy Foundation: Washington, DC, 2002.

  14. US Department of Health and Human Services. Healthy People 2010, 2nd edn. USDHHS: Washington, DC, 2000.

  15. Esson KM, Leeder SR . The Millennium Development Goals and Tobacco Control: An Opportunity for Global Partnership. World Health Organization: Geneva, Switzerland, 2004.

    Google Scholar 

  16. Hughes J, Stead L, Lancaster T . Antidepressants for smoking cessation. Cochrane Database Syst Rev 2007; 1: CD000031.

    Google Scholar 

  17. Etter JF, Stapleton JA . Nicotine replacement therapy for long-term smoking cessation: a meta-analysis. Tob Control 2006; 15: 280–285.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wu P, Wilson K, Dimoulas P, Mills EJ . Effectiveness of smoking cessation therapies: a systematic review and meta-analysis. BMC Public Health 2006; 6: 300.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Nides M, Oncken C, Gonzales D, Rennard S, Watsky EJ, Anziano R et al. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med 2006; 166: 1561–1568.

    Article  PubMed  Google Scholar 

  20. Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 2006; 296: 47–55.

    Article  CAS  PubMed  Google Scholar 

  21. Schnoll RA, Lerman C . Current and emerging pharmacotherapies for treating tobacco dependence. Expert Opin Emerg Drugs 2006; 11: 429–444.

    Article  CAS  PubMed  Google Scholar 

  22. Rutter JL . Symbiotic relationship of pharmacogenetics and drugs of abuse. AAPS J 2006; 8: E174–E184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lerman C, Wileyto EP, Patterson F, Rukstalis M, Audrain-McGovern J, Restine S et al. The functional mu opioid receptor (OPRM1) Asn40Asp variant predicts short-term response to nicotine replacement therapy in a clinical trial. Pharmacogenomics J 2004; 4: 184–192.

    Article  CAS  PubMed  Google Scholar 

  24. Lee AM, Jepson C, Hoffmann E, Epstein L, Hawk LW, Lerman C et al. CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial. Biol Psychiatry 2007; 62: 635–641.

    Article  CAS  PubMed  Google Scholar 

  25. Lerman C, Tyndale R, Patterson F, Wileyto EP, Shields PG, Pinto A et al. Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation. Clin Pharmacol Ther 2006; 79: 600–608.

    Article  CAS  PubMed  Google Scholar 

  26. Malaiyandi V, Lerman C, Benowitz NL, Jepson C, Patterson F, Tyndale RF . Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy. Mol Psychiatry 2006; 11: 400–409.

    Article  CAS  PubMed  Google Scholar 

  27. Hughes DA, Vilar FJ, Ward CC, Alfirevic A, Park BK, Pirmohamed M . Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity. Pharmacogenetics 2004; 14: 335–342.

    Article  PubMed  Google Scholar 

  28. Flowers CR, Veenstra D . The role of cost-effectiveness analysis in the era of pharmacogenomics. Pharmacoeconomics 2004; 22: 481–493.

    Article  PubMed  Google Scholar 

  29. Roden DM, Altman RB, Benowitz NL, Flockhart DA, Giacomini KM, Johnson JA et al. Pharmacogenomics: challenges and opportunities. Ann Intern Med 2006; 145: 749–757.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Fiscella K, Franks P . Cost-effectiveness of the transdermal nicotine patch as an adjunct to physicians’ smoking cessation counseling. JAMA 1996; 275: 1247–1251.

    Article  CAS  PubMed  Google Scholar 

  31. Wasley MA, McNagny SE, Phillips VL, Ahluwalia JS . The cost-effectiveness of the nicotine transdermal patch for smoking cessation. Prev Med 1997; 26: 264–270.

    Article  CAS  PubMed  Google Scholar 

  32. Croghan IT, Offord KP, Evans RW, Schmidt S, Gomez-Dahl LC, Schroeder DR et al. Cost-effectiveness of treating nicotine dependence: the Mayo Clinic experience. Mayo Clin Proc 1997; 72: 917–924.

    Article  CAS  PubMed  Google Scholar 

  33. Curry SJ, Grothaus LC, McAfee T, Pabiniak C . Use and cost effectiveness of smoking-cessation services under four insurance plans in a health maintenance organization. N Engl J Med 1998; 339: 673–679.

    Article  CAS  PubMed  Google Scholar 

  34. Stapleton JA, Lowin A, Russell MA . Prescription of transdermal nicotine patches for smoking cessation in general practice: evaluation of cost-effectiveness. Lancet 1999; 354: 210–215.

    Article  CAS  PubMed  Google Scholar 

  35. Woolacott NF, Jones L, Forbes CA, Mather LC, Sowden AJ, Song FJ et al. The clinical effectiveness and cost-effectiveness of bupropion and nicotine replacement therapy for smoking cessation: a systematic review and economic evaluation. Health Technol Assess 2002; 6: 1–245.

    Article  CAS  PubMed  Google Scholar 

  36. Song F, Raftery J, Aveyard P, Hyde C, Barton P, Woolacott N . Cost-effectiveness of pharmacological interventions for smoking cessation: a literature review and a decision analytic analysis. Med Decis Making 2002; 22S5: S26–S37.

    Article  Google Scholar 

  37. Cornuz J, Pinget C, Gilbert A, Paccaud F . Cost-effectiveness analysis of the first-line therapies for nicotine dependence. Eur J Clin Pharmacol 2003; 59: 201–206.

    Article  PubMed  Google Scholar 

  38. Centers for Disease Control and Prevention. Cigarette smoking among adults—United States 2000. MMWR 2002; 51: 642–645.

    Google Scholar 

  39. Hymowitz N, Cummings KM, Hyland A, Lynn WR, Pechacek TF, Hartwell TDK . Predictors of smoking cessation in a cohort of adult smokers followed for five years. Tob Control 1997; 6: S57–S62.

    Article  PubMed  PubMed Central  Google Scholar 

  40. West R, Gilsenan A, Coste F, Zhou X, Brouard R, Nonnemaker J et al. The ATTEMPT cohort: a multi-national longitudinal study of predictors, patterns and consequences of smoking cessation; introduction and evaluation of internet recruitment and data collection methods [erratum appears in Addiction 2006 Oct;101:1528]. Addiction 2006; 101: 1352–1361.

    Article  PubMed  Google Scholar 

  41. Hyland A, Li Q, Bauer JE, Giovino GA, Steger C . Predictors of cessation in a cohort of current and former smokers followed over 13 years. Nicotine Tob Res 2004; 6S3: S363–S369.

    Article  Google Scholar 

  42. Killen JD, Fortmann SP, Murphy Jr GM, Hayward C, Arredondo C, Cromp D et al. Extended treatment with bupropion SR for cigarette smoking cessation. J Consult Clin Psychol 2006; 74: 286–294.

    Article  PubMed  Google Scholar 

  43. Jamerson BD, Nides M, Jorensby DE, Donahue R, Garrett P, Johnston JA et al. Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo. Clin Ther 2001; 23: 744–752.

    Article  CAS  PubMed  Google Scholar 

  44. Hall SM, Humfleet GL, Reus VI, Muñoz RF, Cullen J . Extended nortriptyline and psychological treatment for cigarette smoking. Am J Psychiatry 2004; 161: 2100–2107.

    Article  PubMed  Google Scholar 

  45. Han ES, Foulds J, Steinberg B, Gandhi KK, West B, Richardson DL et al. Characteristics and smoking cessation outcomes of patients returning for repeat tobacco dependence treatment. Int J Clin Pract 2006; 60: 1068–1074.

    Article  CAS  PubMed  Google Scholar 

  46. Partin MR, An LC, Nelson DB, Nugent S, Snyder A, Fu SS et al. Randomized trial of an intervention to facilitate recycling for relapsed smokers. Am J Prev Med 2006; 31: 293–299.

    Article  PubMed  Google Scholar 

  47. Cinciripini P, Wetter D, Tomlinson G, Tsoh J, De Moor C, Cinciripini L et al. The effects of the DRD2 polymorphism on smoking cessation and negative affect: evidence for a pharmacogenetic effect on mood. Nicotine Tob Res 2004; 6: 229–239.

    Article  CAS  PubMed  Google Scholar 

  48. Liu QR, Drgon T, Walther D, Johnson C, Poleskaya O, Hess J et al. Pooled association genome scanning: validation and use to identify addiction vulnerability loci in two samples. Proc Natl Acad Sci USA 2005; 102: 11864–11869.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Barendregt JJ, Bonneux L, van der Maas PJ . The health care costs of smoking. N Engl J Med 1997; 337: 1052–1057.

    Article  CAS  PubMed  Google Scholar 

  50. Carlsten C, Burke W . Potential for genetics to promote public health: genetics research on smoking suggests caution about expectations. JAMA 2006; 296: 2480–2482.

    Article  CAS  PubMed  Google Scholar 

  51. Lerman C, Kaufmann V, Rukstalis M, Patterson F, Perkins K, Audrain-McGovern J et al. Individualizing nicotine replacement therapy for the treatment of tobacco dependence: a randomized trial. Ann Intern Med 2004; 140: 426–433.

    Article  CAS  PubMed  Google Scholar 

  52. Fiore MC, Novotny TE, Pierce JP, Giovino GA, Hatzaiandreu EJ, Newcomb PA et al. Methods used to quit smoking in the United States. Do cessation programs help? JAMA 1990; 263: 2760–2765.

    Article  CAS  PubMed  Google Scholar 

  53. Hughes JR, Keely J, Naud S . Shape of the relapse curve and long-term abstinence among untreated smokers. Addiction 2004; 99: 29–38.

    Article  PubMed  Google Scholar 

  54. Arias E . United States life tables, 2002. Nat Vital Stat Rep 2004; 53: 1–38.

    Google Scholar 

  55. Doll R, Peto R, Boreham J, Sutherland I . Mortality in relation to smoking: 50 year's observations on male British doctors. BMJ 2004; 328: 1519–1527.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Foody JM, Cole CR, Blackstone EH, Lauer MS . A propensity analysis of cigarette smoking and mortality with consideration of the effects of alcohol. Am J Cardiol 2001; 87: 706–711.

    Article  CAS  PubMed  Google Scholar 

  57. Gotfredsen NS, Holst C, Prescott E, Vestbo J, Osler M . Smoking reduction, smoking cessation, and mortality: a 16-year follow-up of 19, 732 men and women from the Copenhagen centre for prospective population studies. Am J Epidemiol 2002; 156: 994–1001.

    Article  Google Scholar 

  58. McCarron P, Davey Smith G, Okasha M, McEwen J . Smoking in adolescence and young adulthood and mortality in later life: prospective observational study. J Epidemiol Community Health 2001; 55: 334–335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Qiao Q, Tervahauta M, Nissinen A, Tuomilehto J . Mortality from all causes and from coronary heart disease related to smoking and changes in smoking during a 35-year follow-up of middle-aged Finnish men. Eur Heart J 2000; 21: 1621–1626.

    Article  CAS  PubMed  Google Scholar 

  60. US Department of Health and Human Services. Publication 100–04 Center for Medicare & Medicaid Manual System, Transmittal 562. USDHHS: Washington, DC, 2005.

  61. Gold MR, Siegel JE, Russell LB, Weinstein MC (eds) Cost-Effectiveness in Health and Medicine. Oxford University Press: New York, 1996.

    Google Scholar 

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Acknowledgements

We acknowledge the contributions of the following investigators to the pharmacogenetic studies on which this analysis was based: Wade H Berrettini, Susan Crystal-Mansour, Leonard Epstein, Larry Hawk, Vyga Kaufmann, David Main, Ray Niaura, Angela Pinto, Peter Shields, Susan Ware and E Paul Wileyto. We also thank Steven Siegel for helpful comments on an earlier draft.

Sources of funding: This study was supported by Grants P50 CA084718 from the National Cancer Institute and National Institutes on Drug Abuse and R01 CA063562 from the National Cancer Institute, which had no role in its design, conduct or reporting.

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Authors and Affiliations

  1. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA

    D F Heitjan

  2. The Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    D F Heitjan, D A Asch & C Lerman

  3. Center for Health Equity Research and Promotion, Philadelphia Veterans Administration Medical Center, Philadelphia, PA, USA

    D F Heitjan, D A Asch, Riju Ray, Margaret Rukstalis, Freda Patterson & C Lerman

  4. The Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, PA, USA

    D A Asch & C Lerman

  5. The Transdisciplinary Tobacco Use Research Center, University of Pennsylvania, Philadelphia, PA, USA

    D A Asch

  6. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA

    Riju Ray

  7. Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, USA

    Margaret Rukstalis, Freda Patterson & C Lerman

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  1. D F Heitjan
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  2. D A Asch
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  6. C Lerman
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Correspondence to D F Heitjan.

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Duality of interest and financial disclosures

Dr Lerman has served as a consultant to Glaxo Smith-Kline, who provided bupropion and placebo for the studies described. She has also served as a consultant for Pfizer and has received funding for a project unrelated to the data presented in this paper. The other authors have no conflicts of interest to disclose.

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Heitjan, D., Asch, D., Ray, R. et al. Cost-effectiveness of pharmacogenetic testing to tailor smoking-cessation treatment. Pharmacogenomics J 8, 391–399 (2008). https://doi.org/10.1038/sj.tpj.6500492

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