Advertisement

PharmacoEconomics

, Volume 28, Issue 5, pp 411–427 | Cite as

Cost Effectiveness of Donepezil in the Treatment of Mild to Moderate Alzheimer’s Disease

A UK Evaluation Using Discrete-Event Simulation
  • Denis GetsiosEmail author
  • Steve Blume
  • K. Jack Ishak
  • Grant D. H. Maclaine
Original Research Article

Abstract

Background: Recommendations in the UK suggest restricting treatment of Alzheimer’s disease with cholinesterase inhibitors, on cost-effectiveness grounds, to patients with moderate cognitive decline. As the economic analyses that informed these recommendations have been the subject of debate, we sought to address the potential limitations of existing models and produce estimates of donepezil treatment cost effectiveness in the UK using the most recent available data and simulation techniques.

Methods: A discrete-event simulation was developed that predicts progression of Alzheimer’s disease through correlated changes in cognition, behavioural disturbance and function. Patient-level data from seven randomized, placebo-controlled donepezil trials and a 7-year follow-up registry provided the basis for modeling longitudinal outcomes. Individuals in the simulation were assigned unique demographic and clinical characteristics and then followed for 10 years, with severity of disease tracked on continuous scales. Patient mix and costs were developed from UK-specific literature. Analyses were run for severity subgroups to evaluate outcomes for sub-populations with disease of mild versus moderate severity from both a healthcare payer and societal perspective. All costs are reported in £, year 2007 values, and all outcomes are discounted at 3.5% per annum.

Results: Over 10 years, treatment of all patients with mild to moderate disease reduces overall direct medical costs by an average of over £2300 per patient. When unpaid caregiver time is also taken into consideration, savings increase to over £4700 per patient. Compared with untreated patients, patients receiving donepezil experience a discounted gain in QALYs averaging 0.11, with their caregivers gaining, on average, 0.01 QALYs. For the subset of patients starting treatment with more severe disease, savings are more modest, averaging about £1600 and £3750 from healthcare and societal perspectives, respectively. In probabilistic sensitivity analyses, donepezil dominated no treatment between 57% and 62% of replications when only medical costs were considered, and between 74% and 79% of replications when indirect costs were included, with results more favourable for treatment initiation in the mild versus moderate severity stages of the disease.

Conclusions: Although the simulation results are not definitive, they suggest that donepezil leads to health benefits and cost savings when used to treat mild to moderately severe Alzheimer’s disease in the UK. They also indicate that both benefits and savings may be greatest when treatment is started while patients are still in the mild stages of Alzheimer’s disease.

Keywords

Cholinesterase Inhibitor Probabilistic Sensitivity Analysis Supplemental Digital Content Patient Care Cost Discrete Health State 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

All authors participated in the conception and design of the economic model and analyses, and in the writing of the manuscript. Denis Getsios was the lead investigator and provided the detailed specifications on the model design, directed implementation and oversaw the programming. Steve Blume assisted with design of the model, data analyses and development of the model inputs and directed the analyses. Jack Ishak directed the design and implementation of the data analyses for development of model input data. Grant Maclaine assisted in the design of the model, review and collection of the model input data, and specification of the analyses. This work was supported by an unrestricted grant from Eisai Ltd.

The authors thank Ye Tan for biostatistical support, Luis Hernandez for his involvement in programming the model and Sunning Tao for running the economic analyses and assisting in the production of the manuscript.

Grant Maclaine is an employee of Eisai Europe Limited, the sponsor of the research. The remaining authors are employees of United BioSource Corporation, a firm consulting to Eisai and other pharmaceutical manufacturers who market medications for treating Alzheimer’s disease.

Supplementary material

40273_2012_28050411_MOESM1_ESM.pdf (188 kb)
Supplementary material, approximately 193 KB.

References

  1. 1.
    Knapp M, Prince M, Albanese E, et al., for Kings’ College London and London School of Economics. Dementia UK 2007. London: Alzheimer’s Society, 2007 [online]. Available from URL: http://www.alzheimers.org.uk/site/scripts/download_info.php?fileID=2 [Accessed 2008 Dec 9]Google Scholar
  2. 2.
    Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev 2006; (1): CD005593Google Scholar
  3. 3.
    Hansen RA, Gartlehner G, Webb AP, et al. Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. Clin Interv Aging 2008; 3 (2): 211–25PubMedGoogle Scholar
  4. 4.
    Cohen JT, Neumann PJ. Decision analytic models for Alzheimer’s disease: state of the art and future directions. Alzheimers Dement 2008; 4: 212–22PubMedCrossRefGoogle Scholar
  5. 5.
    Green C. Modelling disease progression in Alzheimer’s disease: a review of modelling methods used for costeffectiveness analysis. Pharmacoeconomics 2007; 25 (9): 735–50PubMedCrossRefGoogle Scholar
  6. 6.
    Oremus M. Systematic review of economic evaluations of Alzheimer’s disease medications. Expert Rev Pharmacoecon Outcomes Res 2008; 8 (3): 273–89PubMedCrossRefGoogle Scholar
  7. 7.
    National Institute for Health and Clinical Excellence (NICE). Donepezil, galantamine, rivastigmine (review) and memantine for the treatment of Alzheimer’s disease. London: NICE, 2006 Nov [online]. Available from URL:http://guidance.nice.org.uk/TA111 [Accessed 2008 Dec 9]Google Scholar
  8. 8.
    Caro JJ, Getsios D, Migliaccio-Walle K, et al., for the ASG. Assessment of health economics in Alzheimer’s disease (AHEAD) based on need for full-time care. Neurology 2001; 57: 964–71PubMedCrossRefGoogle Scholar
  9. 9.
    Getsios D, Migliaccio-Walle K, Caro JJ. NICE cost-effectiveness appraisal of cholinesterase inhibitors: was the right question posed? Were the best tools used? Pharmacoeconomics 2007; 25 (12): 997–1006PubMedCrossRefGoogle Scholar
  10. 10.
    Pelosi AJ, McNulty SJ, Jackson GA. Role of cholinesterase inhibitors in dementia care needs rethinking. BMJ 2006; 333: 491–3PubMedCrossRefGoogle Scholar
  11. 11.
    Dyer C. Appeal Court rules that NICE procedure was unfair. BMJ 2008 May 10; 336 (7652): 1035PubMedCrossRefGoogle Scholar
  12. 12.
    Bosanquet N, Yeates A. Modelling the cost-effectiveness of cholinesterase inhibitors in the management of mild to moderately severe Alzheimer’s disease. Pharmacoeconomics 2006; 24 (6): 623–5PubMedCrossRefGoogle Scholar
  13. 13.
    Iliffe S. The National Institute for Health and Clinical Excellence (NICE) and drug treatment for Alzheimer’s disease. CNS Drugs 2007; 21 (3): 177–84PubMedCrossRefGoogle Scholar
  14. 14.
    Mohs RC, Doody RS, Morris JC, et al. A 1-year, placebocontrolled preservation of function survival study of donepezil in AD patients. Neurology 2001; 57 (3): 481–8PubMedCrossRefGoogle Scholar
  15. 15.
    Winblad B, Engedal K, Soininen H, et al. A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology 2001; 57 (3): 489–95PubMedCrossRefGoogle Scholar
  16. 16.
    Feldman H, Gauthier S, Hecker J, et al. A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer’s disease. Neurology 2001; 57 (4): 613–20PubMedCrossRefGoogle Scholar
  17. 17.
    CERAD: Consortium to Establish a Registry for Alzheimer’s Disease [online]. Available from URL: http://cerad.mc.duke.edu/Default.htm [Accessed 2009 Mar 6]
  18. 18.
    Rogers SL, Farlow MR, Doody RS, et al. A 24-week, doubleblind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Donepezil Study Group. Neurology 1998; 50 (1): 136–45PubMedCrossRefGoogle Scholar
  19. 19.
    Rogers SL, Doody RS, Mohs RC, et al. Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Arch Intern Med 1998; 158 (9): 1021–31PubMedCrossRefGoogle Scholar
  20. 20.
    Black SE, Doody R, Li H, et al. Donepezil preserves cognition and global function in patients with severe Alzheimer disease. Neurology 2007; 69 (5): 459–69PubMedCrossRefGoogle Scholar
  21. 21.
    Winblad B, Kilander L, Eriksson S, et al. Donepezil in patients with severe Alzheimer’s disease: double-blind, parallelgroup, placebo-controlled study. Lancet 2006; 367 (9516): 1057–65PubMedCrossRefGoogle Scholar
  22. 22.
    Doody RS, Geldmacher DS, Gordon B, et al. Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease. Arch Neurol 2001; 58 (3): 427–33PubMedCrossRefGoogle Scholar
  23. 23.
    Winblad B, Wimo A, Engedal K, et al. 3-year study of donepezil therapy in Alzheimer’s disease: effects of early and continuous therapy. Dement Geriatr Cogn Disord 2006; 21 (5-6): 353–63PubMedCrossRefGoogle Scholar
  24. 24.
    Stern RG, Mohs RC, Davidson M, et al. A longitudinal study of Alzheimer’s disease: measurement, rate, and predictors of cognitive deterioration. Am J Psychiatry 1994; 151: 390–6PubMedGoogle Scholar
  25. 25.
    Mendiondo MS, Ashford JW, Kryscio RJ, et al. Modelling Mini Mental State Examination changes in Alzheimer’s disease. Stat Med 2000; 19: 1607–16PubMedCrossRefGoogle Scholar
  26. 26.
    Mohs RC, Schmeidler J, Aryan M. Longitudinal studies of cognitive, functional and behavioural change in patients with Alzheimer’s disease. Stat Med 2000; 19: 1401–9PubMedCrossRefGoogle Scholar
  27. 27.
    Doody R, Geldmacher D, Gordon B, et al., for the Donepezil Study G. Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer’s disease. Arch Neurol 2001; 58: 427–33PubMedCrossRefGoogle Scholar
  28. 28.
    Lyle S, Grizzell M, Willmott S, et al. Treatment of a whole population sample of Alzheimer’s disease with donepezil over a 4-year period: lessons learned. Dement Geriatr Cogn Disord 2008; 25: 226–31PubMedCrossRefGoogle Scholar
  29. 29.
    Xie J, Brayne C, and the Medical Research Council Cognitive Function and Ageing Study Collaborators. Survival time in people with dementia: analysis from population based cohort study with 14 year follow-up. BMJ 2008; 336: 258–62PubMedCrossRefGoogle Scholar
  30. 30.
    Curtis L. Unit costs of health and social care. London: Personal Social Services Research Unit, 2007 [online]. Available from URL: http://www.pssru.ac.uk/pdf/uc/uc2007/uc2007.pdf [Accessed 2008 Dec 9]Google Scholar
  31. 31.
    Macdonald A, Cooper B. Long-term care dementia services: an impending crisis. Age Ageing 2007; 36: 16–22PubMedCrossRefGoogle Scholar
  32. 32.
    HM Revenue and Customs. National minimum wage: archived rates [online]. Available from URL: http://www.hmrc.gov.uk/nmw/archived_rates.htm [Accessed 2010 Feb 6]
  33. 33.
    Jonsson L, Andreasen N, Kilander L, et al. Patient- and proxy-reported utility in Alzheimer disease using the EuroQoL. Alzheimer Dis Assoc Disord 2006; 20 (1): 49–55PubMedCrossRefGoogle Scholar
  34. 34.
    Brazier J, Roberts J, Deverill M. The estimation of a preference-based measure of health from the SF-36. J Health Econ 2002; 21: 271–92PubMedCrossRefGoogle Scholar
  35. 35.
    Tun S, Murman D, Long H, et al. Predictive validity of neuropsychiatric subgroups on nursing home placement and survival in patients with Alzheimer disease. Am J Geriatr Psychiatry 2007; 15 (4): 314–27PubMedCrossRefGoogle Scholar
  36. 36.
    Ward A, Caro JJ, Getsios D, et al. Asessment of health economics in Alzheimer’s disease (AHEAD): treatment with galantamine in the UK. Int J Geriat Psychiatry 2003; 18: 740–7CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Denis Getsios
    • 1
    Email author
  • Steve Blume
    • 2
  • K. Jack Ishak
    • 3
  • Grant D. H. Maclaine
    • 4
  1. 1.United BioSource CorporationLexingtonUSA
  2. 2.United BioSource CorporationBethesdaUSA
  3. 3.United BioSource CorporationMontrealCanada
  4. 4.Eisai Ltd. HatfieldHertfordshireUK

Personalised recommendations