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Systematic Review of Model-Based Economic Evaluations of Treatments for Alzheimer’s Disease

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Abstract

Background

Numerous economic evaluations using decision-analytic models have assessed the cost effectiveness of treatments for Alzheimer’s disease (AD) in the last two decades. It is important to understand the methods used in the existing models of AD and how they could impact results, as they could inform new model-based economic evaluations of treatments for AD.

Objective

The aim of this systematic review was to provide a detailed description on the relevant aspects and components of existing decision-analytic models of AD, identifying areas for improvement and future development, and to conduct a quality assessment of the included studies.

Methods

We performed a systematic and comprehensive review of cost-effectiveness studies of pharmacological treatments for AD published in the last decade (January 2005 to February 2015) that used decision-analytic models, also including studies considering patients with mild cognitive impairment (MCI). The background information of the included studies and specific information on the decision-analytic models, including their approach and components, assumptions, data sources, analyses, and results, were obtained from each study. A description of how the modeling approaches and assumptions differ across studies, identifying areas for improvement and future development, is provided. At the end, we present our own view of the potential future directions of decision-analytic models of AD and the challenges they might face.

Results

The included studies present a variety of different approaches, assumptions, and scope of decision-analytic models used in the economic evaluation of pharmacological treatments of AD. The major areas for improvement in future models of AD are to include domains of cognition, function, and behavior, rather than cognition alone; include a detailed description of how data used to model the natural course of disease progression were derived; state and justify the economic model selected and structural assumptions and limitations; provide a detailed (rather than high-level) description of the cost components included in the model; and report on the face-, internal-, and cross-validity of the model to strengthen the credibility and confidence in model results. The quality scores of most studies were rated as fair to good (average 87.5, range 69.5–100, in a scale of 0–100).

Conclusion

Despite the advancements in decision-analytic models of AD, there remain several areas of improvement that are necessary to more appropriately and realistically capture the broad nature of AD and the potential benefits of treatments in future models of AD.

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References

  1. Caro JJ, Moller J. Decision-analytic models: current methodological challenges. Pharmacoeconomics. 2014;32(10):943–50.

    Article  PubMed  Google Scholar 

  2. Pouryamout L, Dams J, Wasem J, Dodel R, Neumann A. Economic evaluation of treatment options in patients with Alzheimer’s disease: a systematic review of cost-effectiveness analyses. Drugs. 2012;72(6):789–802.

    Article  PubMed  Google Scholar 

  3. Green C, Shearer J, Ritchie CW, Zajicek JP. Model-based economic evaluation in Alzheimer’s disease: a review of the methods available to model Alzheimer’s disease progression. Value Health. 2011;14(5):621–30.

    Article  PubMed  Google Scholar 

  4. Oremus M. Systematic review of economic evaluations of Alzheimer’s disease medications. Expert Rev Pharmacoecon Outcomes Res. 2008;8(3):273–89.

    Article  PubMed  Google Scholar 

  5. Cohen JT, Neumann PJ. Decision analytic models for Alzheimer’s disease: state of the art and future directions. Alzheimers Dement. 2008;4(3):212–22.

    Article  PubMed  Google Scholar 

  6. Green C. Modelling disease progression in Alzheimer’s disease: a review of modelling methods used for cost-effectiveness analysis. Pharmacoeconomics. 2007;25(9):735–50.

    Article  PubMed  Google Scholar 

  7. Loveman E, Green C, Kirby J, Takeda A, Picot J, Payne E, et al. The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer’s disease. Health Technol Assess. 2006;10(1):iii–iv, ix–xi, 1–160.

  8. Getsios D, Blume S, Ishak KJ, Maclaine GDH. Cost effectiveness of donepezil in the treatment of mild to moderate Alzheimer’s disease: a UK evaluation using discrete-event simulation. Pharmacoeconomics. 2010;28(5):411–27.

    Article  PubMed  Google Scholar 

  9. Caro JJ, Getsios D, Migliaccio-Walle K, Raggio G, Ward A, Group AS. Assessment of health economics in Alzheimer’s disease (AHEAD) based on need for full-time care. Neurology. 2001;57(6):964–71.

    Article  CAS  PubMed  Google Scholar 

  10. Bond M, Rogers G, Peters J, Anderson R, Hoyle M, Miners A, et al. The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer’s disease (review of Technology Appraisal No. 111): a systematic review and economic model. Health Technol Assess. 2012;16(21):1–470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Morris JC, Blennow K, Froelich L, Nordberg A, Soininen H, Waldemar G, et al. Harmonized diagnostic criteria for Alzheimer’s disease: recommendations. J Intern Med. 2014;275(3):204–13.

    Article  CAS  PubMed  Google Scholar 

  12. Buckley JS, Salpeter SR. A risk-benefit assessment of dementia medications: systematic review of the evidence. Drugs Aging. 2015;32(6):453–67.

    Article  CAS  PubMed  Google Scholar 

  13. Morris JC. Revised criteria for mild cognitive impairment may compromise the diagnosis of Alzheimer disease dementia. Arch Neurol. 2012;69(6):700–8.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer Dement. 2011;7(3):280–92.

    Article  Google Scholar 

  15. Levey A, Lah J, Goldstein F, Steenland K, Bliwise D. Mild cognitive impairment: an opportunity to identify patients at high risk for progression to Alzheimer’s disease. Clin Ther. 2006;28(7):991–1001.

    Article  PubMed  Google Scholar 

  16. Cummings JL, Morstorf T, Zhong K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimer Res Ther. 2014;6(4):37.

    Article  Google Scholar 

  17. Chiou CF, Hay JW, Wallace JF, Bloom BS, Neumann PJ, Sullivan SD, et al. Development and validation of a grading system for the quality of cost-effectiveness studies. Med Care. 2003;41(1):32–44.

    Article  PubMed  Google Scholar 

  18. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Pharmacoeconomics. 2013;31(5):361–7.

    Article  PubMed  Google Scholar 

  19. Philips Z, Ginnelly L, Sculpher M, Claxton K, Golder S, Riemsma R, et al. Review of guidelines for good practice in decision-analytic modelling in health technology assessment. Health Technol Assess. 2004;8(36):iii–iv, ix–xi, 1–158.

  20. Drummond MF, Jefferson TO. Guidelines for authors and peer reviewers of economic submissions to the BMJ. The BMJ Economic Evaluation Working Party. BMJ. 1996;313(7052):275–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Green C, Picot J, Loveman E, Takeda A, Kirby J, Clegg A. Modelling the cost effectiveness of cholinesterase inhibitors in the management of mild to moderately severe Alzheimer’s disease. Pharmacoeconomics. 2005;23(12):1271–82.

    Article  CAS  PubMed  Google Scholar 

  22. Rive B, Grishchenko M, Guilhaume-Goulant C, Katona C, Livingston G, Lamure M, et al. Cost effectiveness of memantine in Alzheimer’s disease in the UK. J Med Econ. 2010;13(2):371–80. doi:10.3111/13696998.2010.491347.

    Article  CAS  PubMed  Google Scholar 

  23. Djalalov S, Yong J, Beca J, Black S, Saposnik G, Musa Z, et al. Genetic testing in combination with preventive donepezil treatment for patients with amnestic mild cognitive impairment: an exploratory economic evaluation of personalized medicine. Mol Diagn Ther. 2012;16(6):389–99.

    Article  CAS  PubMed  Google Scholar 

  24. Gagnon M, Rive B, Hux M, Guilhaume C. Cost-effectiveness of memantine compared with standard care in moderate-to-severe Alzheimer disease in Canada. Can J Psychiatry. 2007;52(8):519–26.

    PubMed  Google Scholar 

  25. Lachaine J, Beauchemin C, Legault M, Bineau S. Economic evaluation of the impact of memantine on time to nursing home admission in the treatment of Alzheimer disease. Can J Psychiatry. 2011;56(10):596–604.

    PubMed  Google Scholar 

  26. Guo S, Hernandez L, Wasiak R, Gaudig M. Modeling the clinical and economic implications of galantamine in the treatment of mild-to-moderate Alzheimer’s disease in Germany. J Med Econ. 2010;13(4):641–54.

    Article  PubMed  Google Scholar 

  27. Hartz S, Getsios D, Tao S, Blume S, Maclaine G. Evaluating the cost effectiveness of donepezil in the treatment of Alzheimer’s disease in Germany using discrete event simulation. BMC Neurol. 2012;12:2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Teipel SJ, Ewers M, Reisig V, Schweikert B, Hampel H, Happich M. Long-term cost-effectiveness of donepezil for the treatment of Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci. 2007;257(6):330–6.

    Article  PubMed  Google Scholar 

  29. Antonanzas F, Rive B, Badenas JM, Gomez-Lus S, Guilhaume C. Cost-effectiveness of memantine in community-based Alzheimer’s disease patients: an adaptation in Spain. Eur J Health Econ. 2006;7(2):137–44.

    Article  PubMed  Google Scholar 

  30. Lopez-Bastida J, Hart W, Garcia-Perez L, Linertova R. Cost-effectiveness of donepezil in the treatment of mild or moderate Alzheimer’s disease. J Alzheimers Dis. 2009;16(2):399–407.

    CAS  PubMed  Google Scholar 

  31. Fuh JL, Wang SJ. Cost-effectiveness analysis of donepezil for mild to moderate Alzheimer’s disease in Taiwan. Int J Geriatr Psychiatry. 2008;23(1):73–8.

    Article  PubMed  Google Scholar 

  32. Hoogveldt B, Rive B, Severens J, Maman K, Guilhaume C. Cost-effectiveness analysis of memantine for moderate-to-severe Alzheimer’s disease in the Netherlands. Neuropsychiatr Dis Treat. 2011;7:313–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Jonsson L. Cost-effectiveness of memantine for moderate to severe Alzheimer’s disease in Sweden. Am J Geriatr Pharmacother. 2005;3(2):77–86.

    Article  PubMed  Google Scholar 

  34. Kasuya M, Meguro K. Health economic effect of donepezil treatment for CDR 0.5 converters to Alzheimer’s disease as shown by the Markov model. Arch Gerontol Geriatr. 2010;50(3):295–9.

    Article  CAS  PubMed  Google Scholar 

  35. Pfeil AM, Kressig RW, Szucs TD. Alzheimer’s dementia: budget impact and cost-utility analysis of a combination treatment with a cholinesterase inhibitor and memantine in Switzerland. Swiss Med Wkly. 2012;142:w13676.

    PubMed  Google Scholar 

  36. Rive B, Aarsland D, Grishchenko M, Cochran J, Lamure M, Toumi M. Cost-effectiveness of memantine in moderate and severe Alzheimer’s disease in Norway. Int J Geriatr Psychiatry. 2012;27(6):573–82.

    Article  CAS  PubMed  Google Scholar 

  37. Suh GH. Modeling the cost-effectiveness of galantamine for mild to moderately severe Alzheimer’s disease in Korea. Value Health. 2009;12(Suppl 3):S49–54.

    Article  PubMed  Google Scholar 

  38. Touchon J, Lachaine J, Beauchemin C, Granghaud A, Rive B, Bineau S. The impact of memantine in combination with acetylcholinesterase inhibitors on admission of patients with Alzheimer’s disease to nursing homes: cost-effectiveness analysis in France. Eur J Health Econ. 2014;15(8):791–800.

    Article  PubMed  Google Scholar 

  39. Weycker D, Taneja C, Edelsberg J, Erder MH, Schmitt FA, Setyawan J, et al. Cost-effectiveness of memantine in moderate-to-severe Alzheimer’s disease patients receiving donepezil. Curr Med Res Opin. 2007;23(5):1187–97.

    Article  CAS  PubMed  Google Scholar 

  40. Kurz X, Scuvee-Moreau J, Rive B, Dresse A. A new approach to the qualitative evaluation of functional disability in dementia. Int J Geriatr Psychiatry. 2003;18(11):1050–5.

    Article  CAS  PubMed  Google Scholar 

  41. Wilson RS, Aggarwal NT, Barnes LL, Bienias JL, Mendes de Leon CF, Evans DA. Biracial population study of mortality in mild cognitive impairment and Alzheimer disease. Arch Neurol. 2009;66(6):767–72.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Neumann PJ, Sandberg EA, Araki SS, Kuntz KM, Feeny D, Weinstein MC. A comparison of HUI2 and HUI3 utility scores in Alzheimer’s disease. Med Decis Mak. 2000;20(4):413–22.

    Article  CAS  Google Scholar 

  43. Eddy DM, Hollingworth W, Caro JJ, Tsevat J, McDonald KM, Wong JB, et al. Model transparency and validation: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-7. Value Health. 2012;15(6):843–50.

    Article  PubMed  Google Scholar 

  44. Briggs AH, Weinstein MC, Fenwick EA, Karnon J, Sculpher MJ, Paltiel AD, et al. Model parameter estimation and uncertainty: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-6. Value Health. 2012;15(6):835–42.

    Article  PubMed  Google Scholar 

  45. Stern Y, Tang MX, Albert MS, Brandt J, Jacobs DM, Bell K, et al. Predicting time to nursing home care and death in individuals with Alzheimer disease. JAMA. 1997;277(10):806–12.

    Article  CAS  PubMed  Google Scholar 

  46. Stern Y, Albert M, Brandt J, Jacobs DM, Tang MX, Marder K, et al. Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer’s disease: prospective analyses from the Predictors Study. Neurology. 1994;44(12):2300–7.

    Article  CAS  PubMed  Google Scholar 

  47. Stern RG, Mohs RC, Davidson M, Schmeidler J, Silverman J, Kramer-Ginsberg E, et al. A longitudinal study of Alzheimer’s disease: measurement, rate, and predictors of cognitive deterioration. Am J Psychiatry. 1994;151(3):390–6.

    Article  CAS  PubMed  Google Scholar 

  48. Heyman A, Peterson B, Fillenbaum G, Pieper C. Predictors of time to institutionalization of patients with Alzheimer’s disease: the CERAD experience, part XVII. Neurology. 1997;48(5):1304–9.

    Article  CAS  PubMed  Google Scholar 

  49. Lopez OL, Wisniewski SR, Becker JT, Boller F, DeKosky ST. Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease. Arch Neurol. 1999;56(10):1266–72.

    Article  CAS  PubMed  Google Scholar 

  50. Lopez OL, Wisnieski SR, Becker JT, Boller F, DeKosky ST. Extrapyramidal signs in patients with probable Alzheimer disease. Arch Neurol. 1997;54(8):969–75.

    Article  CAS  PubMed  Google Scholar 

  51. Brennan A, Chick SE, Davies R. A taxonomy of model structures for economic evaluation of health technologies. Health Econ. 2006;15(12):1295–310.

    Article  PubMed  Google Scholar 

  52. Roberts M, Russell LB, Paltiel AD, Chambers M, McEwan P, Krahn M, et al. Conceptualizing a model: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force-2. Value Health. 2012;15(6):804–11.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1):CD005593.

  54. McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006;(2):CD003154.

  55. Resnick SM. Preclinical biomarkers in Alzheimer disease: a sum greater than the parts. JAMA Neurol. 2014;71(11):1357–8.

    Article  PubMed  Google Scholar 

  56. Mendiondo MS, Ashford JW, Kryscio RJ, Schmitt FA. Modelling mini mental state examination changes in Alzheimer’s disease. Stat Med. 2000;19(11–12):1607–16.

    Article  CAS  PubMed  Google Scholar 

  57. Hendrix SB. Measuring clinical progression in MCI and pre-MCI populations: enrichment and optimizing clinical outcomes over time. Alzheimers Res Ther. 2012;4(4):24.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12(2):207–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Jansen WJ, Ossenkoppele R, Knol DL, Tijms BM, Scheltens P, Verhey FR, et al. Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis. JAMA. 2015;313(19):1924–38.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367(9):795–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Delacourte A, Sergeant N, Champain D, Wattez A, Maurage CA, Lebert F, et al. Nonoverlapping but synergetic tau and APP pathologies in sporadic Alzheimer’s disease. Neurology. 2002;59(3):398–407.

    Article  CAS  PubMed  Google Scholar 

  62. Handels RL, Joore MA, Tran-Duy A, Wimo A, Wolfs CA, Verhey FR, et al. Early cost-utility analysis of general and cerebrospinal fluid-specific Alzheimer’s disease biomarkers for hypothetical disease-modifying treatment decision in mild cognitive impairment. Alzheimers Dement. 2015;11(8):896–905.

    Article  PubMed  Google Scholar 

  63. Guo S, Getsios D, Revankar N, Xu P, Thompson G, Bobula J, et al. Evaluating disease-modifying agents: a simulation framework for Alzheimer’s disease. Pharmacoeconomics. 2014;32(11):1129–39.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Malinda O’Donnell, Principal Market Access Writer at Evidera, for her review and feedback on the manuscript.

Author contributions

Luis Hernandez was the leading author who conducted the study design, literature search, data extraction, and writing of the manuscript, and will serve as guarantor for the content of the manuscript. Asli Ozen and Rodrigo DosSantos participated in the literature search, data extraction, and writing of the manuscript. Denis Getsios participated in the study design and review of the manuscript.

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Authors and Affiliations

  1. Evidera, 430 Bedford St #300, Lexington, MA, 02420, USA

    Luis Hernandez & Denis Getsios

  2. Evidera, Bethesda, MD, USA

    Asli Ozen & Rodrigo DosSantos

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  1. Luis Hernandez
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  2. Asli Ozen
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  4. Denis Getsios
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Correspondence to Luis Hernandez.

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Funding

This study was fully sponsored by Evidera.

Conflict of interest

Luis Hernandez, Asli Ozen, Rodrigo DosSantos, and Denis Getsios are employees of Evidera, a company that provides consulting and other research services to pharmaceutical, device, government, and non-government organizations.

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Hernandez, L., Ozen, A., DosSantos, R. et al. Systematic Review of Model-Based Economic Evaluations of Treatments for Alzheimer’s Disease. PharmacoEconomics 34, 681–707 (2016). https://doi.org/10.1007/s40273-016-0392-1

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