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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Heterogeneity in Cost-Effectiveness Analysis of Vaccination for Mild and Moderate Alzheimer’s Disease

Author(s): Chung-Hsien Lin, Jean Ching-Yuan Fann, Sam Li-Sheng Chen, Hsiu-Hsi Chen and Kuen-Cheh Yang*

Volume 16, Issue 6, 2019

Page: [495 - 504] Pages: 10

DOI: 10.2174/1567205016666190612162121


Background: Immunotherapy for Alzheimer’s disease(AD) has gained momentum in recent years. One of the concerns over its application pertains to Cost-Effectiveness Analysis (CEA) from population average and specific subgroup differences, as such a therapy is imperative for health decisionmakers to allocate limited resources. However, this sort of CEA model considering heterogeneous population with risk factors adjustment has been rarely addressed.

Methods: We aimed to show the heterogeneity of CEA in immunotherapy for AD in comparison with the comparator without intervention. Economic evaluation was performed via incremental Cost- Effectiveness Ratio (ICER) and Cost-Effectiveness Acceptability Curve (CEAC) in terms of the Quality- Adjusted Life Years (QALY). First, population-average CEA was performed with and without adjustment for age and gender. Secondly, sub-group CEA was performed with the stratification of gender and age based on Markov process.

Results: Given the threshold of $20,000 of willingness to pay, the results of ICER without and with adjustment for age and gender revealed similar results ($14,691/QALY and $17,604/QALY). The subgroup ICER results by different age groups and gender showed substantial differences. The CEAC showed that the probability of being cost-effective was only 48.8%-53.3% in terms of QALY at population level but varied from 83.5% in women aged 50-64 years, following women aged 65-74 years and decreased to 0.2% in men≥ 75 years.

Conclusion: There were considerable heterogeneities observed in the CEA of vaccination for AD. As with the development of personalized medicine, the CEA results assessed by health decision-maker should not only be considered by population-average level but also specific sub-group levels.

Keywords: Alzheimer's disease, immunotherapy, vaccination, cost-effectiveness analysis, heterogeneity, personalized medicine.

Wimo A, Jonsson L, Bond J, Prince M, Winblad B. Alzheimer Disease I. The worldwide economic impact of dementia 2010; Alzheimers Dement. 9(1): 1-11. e3 (2013)
Salomone S, Caraci F, Leggio GM, Fedotova J, Drago F. New pharmacological strategies for treatment of Alzheimer’s disease: focus on disease modifying drugs. Br J Clin Pharmacol 73(4): 504-17. (2012)
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 72(6): 789-802. (2012)
Wisniewski T, Goni F. Immunotherapeutic approaches for Alzheimer’s disease. Neuron 85(6): 1162-76. (2015)
Yang KC, Chen HH. Probabilistic Cost-effectiveness analysis of vaccination for mild or moderate Alzheimer’s disease. Curr Alzheimer Res 13(7): 809-16. (2016)
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 14(5): 621-30. (2011)
Jameson JL, Longo DL. Precision medicine--personalized, problematic, and promising. N Engl J Med 372(23): 2229-34. (2015)
Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, et al. Alzheimer’s disease. Lancet 388(10043): 505-17. (2016)
Lord J, Cruchaga C. The epigenetic landscape of Alzheimer’s disease. Nat Neurosci 17(9): 1138-40. (2014)
Ritchie K, Ritchie CW, Yaffe K, Skoog I, Scarmeas N. Is late-onset Alzheimer’s disease really a disease of midlife? Alzheimers Dement 1(2): 122-30. (2015)
Lambracht-Washington D, Rosenberg RN. Advances in the development of vaccines for Alzheimer’s disease. Discov Med 15(84): 319-26. (2013)
Kohyama K, Matsumoto Y. Alzheimer’s disease and immunotherapy: what is wrong with clinical trials? ImmunoTargets Ther 4: 27-34. (2015)
Wimo A, Ballard C, Brayne C, Gauthier S, Handels R, Jones RW, et al. Health economic evaluation of treatments for Alzheimer’s disease: impact of new diagnostic criteria. J Intern Med 275(3): 304-16. (2014)
Golde TE, DeKosky ST, Galasko D. Alzheimer’s disease: the right drug, the right time. Science 362(6420): 1250-1. (2018)
Neumann PJ, Araki SS, Arcelus A, Longo A, Papadopoulos G, Kosik KS, et al. Measuring Alzheimer’s disease progression with transition probabilities: estimates from CERAD. Neurology 57(6): 957-64. (2001)
Fuh JL, Wang SJ. Cost-effectiveness analysis of donepezil for mild to moderate Alzheimer’s disease in Taiwan. Int J Geriatr Psychiatry 23(1): 73-8. (2008)
Neumann PJ, Hermann RC, Kuntz KM, Araki SS, Duff SB, Leon J, et al. Cost-effectiveness of donepezil in the treatment of mild or moderate Alzheimer’s disease. Neurology 52(6): 1138-45. (1999)
Hsieh HJ, Chen TH, Chang SH. Assessing chronic disease progression using non-homogeneous exponential regression Markov models: an illustration using a selective breast cancer screening in Taiwan. Stat Med 21(22): 3369-82. (2002)
Zhao L, Woody SK, Chhibber A. Estrogen receptor beta in Alzheimer's disease: from mechanisms to therapeutics. Ageing Res Rev 24Pt B. : 178-90. (2015)
Mielke MM, Vemuri P, Rocca WA. Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences. Clin Epidemiol 6: 37-48. (2014)
Lin KA, Choudhury KR, Rathakrishnan BG, Marks DM, Petrella JR, Doraiswamy PM, et al. Marked gender differences in progression of mild cognitive impairment over 8 years. Alzheimers Dement 1(2): 103-10. (2015)
Mendez MF. Early-onset Alzheimer’s disease: nonamnestic subtypes and type 2 AD. Arch Med Res 43(8): 677-85. (2012)
Panegyres PK, Chen HY. Differences between early and late onset Alzheimer’s disease. Am J Neurodegener Dis 2(4): 300-6. (2013)
Koss E, Edland S, Fillenbaum G, Mohs R, Clark C, Galasko D, et al. Clinical and neuropsychological differences between patients with earlier and later onset of Alzheimer’s disease: a CERAD analysis, Part XII. Neurology 46(1): 136-41. (1996)
Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278(16): 1349-56. (1997)
Ferretti MT, Iulita MF, Cavedo E, Chiesa PA, Schumacher Dimech A, Santuccione Chadha A, et al. Sex differences in Alzheimer disease - the gateway to precision medicine. Nat Rev Neurol 14(8): 457-69. (2018)
Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, et al. Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization. Neurology 61(1): 46-54. (2003)
Sperling RA, Jack CR Jr, Black SE, Frosch MP, Greenberg SM, Hyman BT, et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimers Dement 7(4): 367-85. (2011)
Sperling R, Salloway S, Brooks DJ, Tampieri D, Barakos J, Fox NC, et al. Amyloid-related imaging abnormalities in patients with Alzheimer’s disease treated with bapineuzumab: a retrospective analysis. Lancet Neurol 11(3): 241-9. (2012)
Salloway S, Sperling R, Fox NC, Blennow K, Klunk W, Raskind M, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med 370(4): 322-33. (2014)
Patterson CE, Todd SA, Passmore AP. Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer’s disease. Pharmacogenomics J 11(6): 444-50. (2011)
Wang L, Day J, Roe CM, Brier MR, Thomas JB, Benzinger TL, et al. The effect of APOE epsilon4 allele on cholinesterase inhibitors in patients with Alzheimer disease: evaluation of the feasibility of resting state functional connectivity magnetic resonance imaging. Alzheimer Dis Assoc Disord 28(2): 122-7. (2014)
Braga IL, Silva PN, Furuya TK, Santos LC, Pires BC, Mazzotti DR, et al. Effect of APOE and CHRNA7 genotypes on the cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer’s disease. Am J Alzheimers Dis Other Demen 30(2): 139-44. (2015)
Lahiri DK, Ray B. Intravenous immunoglobulin treatment preserves and protects primary rat hippocampal neurons and primary human brain cultures against oxidative insults. Curr Alzheimer Res 11(7): 645-54. (2014)
Counts SE, Lahiri DK. Overview of immunotherapy in Alzheimer’s disease (AD) and mechanisms of IVIG neuroprotection in preclinical models of AD. Curr Alzheimer Res 11(7): 623-5. (2014)
Relkin NR, Thomas RG, Rissman RA, Brewer JB, Rafii MS, van Dyck CH, et al. A phase 3 trial of IV immunoglobulin for Alzheimer disease. Neurology 88(18): 1768-75. (2017)
Counts SE, Ray B, Mufson EJ, Perez SE, He B, Lahiri DK. Intravenous immunoglobulin (IVIG) treatment exerts antioxidant and neuropreservatory effects in preclinical models of Alzheimer’s disease. J Clin Immunol 34(Suppl. 1): S80-5. (2014)
Farlow MR, Andreasen N, Riviere ME, Vostiar I, Vitaliti A, Sovago J, et al. Long-term treatment with active Abeta immunotherapy with CAD106 in mild Alzheimer’s disease. Alzheimers Res Ther 7(1): 23. (2015)
Winblad B, Andreasen N, Minthon L, Floesser A, Imbert G, Dumortier T, et al. Safety, tolerability, and antibody response of active Abeta immunotherapy with CAD106 in patients with Alzheimer’s disease: randomised, double-blind, placebo-controlled, first-in-human study. Lancet Neurol 11(7): 597-604. (2012)
Mandler M, Santic R, Gruber P, Cinar Y, Pichler D, Funke SA, et al. Tailoring the antibody response to aggregated Ass using novel Alzheimer-vaccines. PLoS One 10(1)e0115237 (2015)

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