Cost-utility analysis of memantine in Alzheimer’s Disease in Brazil
DOI:
https://doi.org/10.33448/rsd-v11i11.33846Keywords:
Alzheimer’s Disease; Cost-utility Analysis; Memantine; Unified health system.Abstract
Accelerated population aging has led to a progressive increase in dementia, particularly Alzheimer’s Disease (AD). The study’s objective was to perform a cost-utility analysis on the use of memantine in the severe stage of AD in Brazil compared to no specific pharmacological treatment from the perspective of the Brazilian Unified Health System (SUS). A Markov model was designed to simulate the progression of AD through five finite stages of health that considered cognitive function and a time horizon of five years. Progression probabilities were derived from clinical trials and population-based studies. Direct costs included hospitalization, medical consultation, use of additional medications, as well as laboratory tests. The measures for Quality Adjusted Life Year (QALY) were derived from the international literature. Costs and benefits were discounted by 5%. Compared to no specific pharmacological treatment, memantine was associated with gains in QALY and additional costs. The model showed that memantine resulted in a gain of 0.00308 QALY over the simulated 5 years and an increase in costs of R$351.50 per patient in already discounted values, resulting in an incremental cost-effectiveness ratio (ICER) of R$114,123.38 per QALY. The cost and effect of memantine on AD progression were the variables under the most uncertainty. Although memantine represents gains in QALY, its ICER is considered high for the Brazilian context considering its high costs and its small and limited benefit in time.
References
Agüero-Torres, H., Qiu, C., Winblad, B., & Fratiglioni, L. (2002). Dementing disorders in the elderly: evolution of disease severity over 7 years. Alzheimer Disease & Associated Disorders, 16(4), 221-227.
Albert, S. M., Costa, R., Merchant, C., et al. (1999). Hospitalization and Alzheimer's disease: Results from a community-based study. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 54(5), M267-M271.
Alves, J. E. D. (2014). Transição demográfica, transição da estrutura etária e envelhecimento. Revista portal de divulgação, (40).
Andersen, C. K., Wittrup-Jensen, K. U., Lolk, A. ,et al. (2004). Ability to perform activities of daily living is the main factor affecting quality of life in patients with dementia. Health and quality of life outcomes, 2(1), 1-7.
Andrieu, S., Reynish, E., Nourhashemi, F., et al. (2002). Predictive factors of acute hospitalization in 134 patients with Alzheimer's disease: a one year prospective study. International journal of geriatric psychiatry, 17(5), 422-426.
Antonanzas, F., Rive, B., Badenas, J. M., et al. (2006). Cost-effectiveness of memantine in community-based Alzheimer’s disease patients: an adaptation in Spain. The European Journal of Health Economics, 7(2), 137-144.
Associação Brasileira de Alzheimer (2017). Evolução da doença. http://www.abraz.org.br/sobrealzheimer/evolucao-da-doenca.
Bertram, M. Y., Lauer, J. A., De Joncheere, K., et al. (2016). Cost–effectiveness thresholds: pros and cons. Bulletin of the World Health Organization, 94(12), 925- 930.
Blanco-Silvente, L. (2018). Discontinuation, efficacy, and safety of cholinesterase inhibitors for Alzheimer’s disease: a meta-analysis and meta-regression of 43 randomized clinical trials enrolling 16 106 patients. International Journal of Neuropsychopharmacology, 20(7), 519–528.
Boff, M. S., Sekyia, F. S., & Bottino, C. M. de C. (2015). Prevalence of dementia among brazilian population: systematic review. Rev Med (São Paulo), 94 (3), 154-161.
Bond, M., Rogers, G., Peters, J., et al. (2012). 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 technology assessment (Winchester, England), 16(21), 1-470.
Brasil. (2011). Decreto n. º 7.646 de 21 de dezembro de 2011. Dispõe sobre a Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde e sobre o processo administrativo para incorporação, exclusão e alteração de tecnologias em saúde pelo Sistema Único de Saúde-SUS, e dá outras providências. Diário Oficial da União.
Brasil. (2002b). Lei nº 14.313, de 21 de março de 2022. Altera a Lei nº 8.080, de 19 de setembro de 1990 (Lei Orgânica da Saúde), para dispor sobre os processos de incorporação de tecnologias ao Sistema Único de Saúde (SUS) e sobre a utilização, pelo SUS, de medicamentos cuja indicação de uso seja distinta daquela aprovada no registro da Agência Nacional de Vigilância Sanitária (Anvisa). Diário Oficial da União.
Brasil. (2017a). Ministério da Saúde. Secretaria de Ciência e Tecnologia e Insumos Estratégicos (SCTIE). Comissão Nacional de Incorporação de Tecnologias no SUS. Relatório de recomendação: Memantina para doença de Alzheimer. Brasília: Ministério da Saúde, 2017a.
Brasil (2022a). Ministério da Saúde. Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Departamento de Assistência Farmacêutica e Insumos Estratégicos. (2022). Relação nacional de medicamentos essenciais: Rename. Ministério da Saúde.
Brasil. (2014). Ministério da Saúde. Secretaria de Ciência, Tecnologia e Insumos Estratégicos. Departamento de Ciência e Tecnologia. Diretrizes metodológicas: diretriz de avaliação econômica: (2ª. ed.): Ministério da Saúde, 2014.
Brasil (2017b). Ministério da Saúde. Secretaria de Atenção à Saúde (SAS). Portaria Conjunta nº 13, de 28 de novembro de 2017. Aprova o Protocolo Clínico e Diretrizes Terapêuticas da Doença de Alzheimer. Brasília: Ministério da Saúde, 2017b.
Brasil (2018). Ministério da Saúde. Conselho Nacional de Secretários de Saúde. Conselho Nacional de Secretarias Municipais de Saúde. 10ª 10ª Reunião ordinária da comissão intergestores tripartite. Pauta. Brasília: Ministério da Saúde, 2018.
Bremenkamp, M. G., Rodrigues, L. R., Lage, R. R., et al. (2014). Sintomas neuropsiquiátricos na doença de Alzheimer: frequência, correlação e ansiedade do cuidador. Revista Brasileira de Geriatria e Gerontologia, 17, 763-773.
Brookmeyer, R., Corrada, M. M., Curriero, F. C., & Kawas, C. (2002). Survival following a diagnosis of Alzheimer disease. Arch Neurol., 59(11), 1764-1767.
Budd, D., Burns, L. C., Guo, Z., et al. (2011). Impact of early intervention and disease modification in patients with predementia Alzheimer’s disease: a Markov model simulation. Clinico Economics and outcomes research: CEOR, 3, 189.
Castro, D. M., Dillon, C., Machnicki, G., & Allegri, R. F. (2010). The economic cost of Alzheimer’s disease. Dement Neuropsychol, 4(4), 262-267.
Ekman, M., Berg, J., Wimo, A., et al. (2007). Health utilities in mild cognitive impairment and dementia: a population study in Sweden. International Journal of Geriatric Psychiatry: A journal of the psychiatry of late life and allied sciences, 22(7), 649-655.
Feng, Z., et al. (2017). Hospital and emergency department use by people with alzheimers disease and related disorders: final report. OFFICE OF THE ASSISTANT SECRETARY FOR PLANNING AND EVALUATION. https://aspe.hhs.gov/basic-report/hospital-and-emergency-department-use-people-alzheimer’s-disease-and-related-disorders-final-report#execsum.
Findling, R. L., McNamara, N. K., Stansbrey, R. J., et al. (2007). A pilot evaluation of the safety, tolerability, pharmacokinetics, and effectiveness of memantine in pediatric patients with attention-deficit/hyperactivity disorder combined type. Journal of child and adolescent psychopharmacology, 17(1), 19-33.
Forlenza, O. V. (2005). Tratamento farmacológico da doença de Alzheimer. Rev.Psiq. Clin, 32(3), 137-148.
Francois, C., Sintonen, H., Sulkava, R., & Rive, B. (2004). Cost effectiveness of memantine in moderately severe to severe Alzheimer’s disease. Clinical drug investigation, 24(7), 373-384.
Frytak, J. R., Henk, H. J., Zhao, Y., et al. (2008). Health service utilization among Alzheimer's disease patients: evidence from managed care. Alzheimer's & Dementia, 4(5), 361-367.
Gagnon, M., Rive, B., Hux, M., & Guilhaume, C. (2007). Cost-effectiveness of memantine compared with standard care in moderate-to-severe Alzheimer disease in Canada. The Canadian Journal of Psychiatry, 52(8), 519-526.
Geldmacher, D. S. (2008). Cost-effectiveness of drug therapies for Alzheimer’s disease: A brief review. Neuropsychiatr Dis Treat, 4(3), 549–555
Gilligan, A. M., Malone, D. C., Warholak, T. L., & Armstrong, E. P. (2013). Predictors of hospitalization and institutionalization in Medicaid patient populations with Alzheimer’s disease. Advances in Alzheimer's Disease, 2(3), 74-82.
Gutierrez, B. A. O., Silva, H. S. D., Guimarães, C., & Campino, A. C. (2014). Impacto econômico da doença de Alzheimer no Brasil: é possível melhorar a assistência e reduzir custos? Ciência & Saúde Coletiva, 19, 4479-4486.
Hartz, S., et al. (2012). Evaluating the cost effectiveness of donepezil in the treatment of Alzheimer’s disease in Germany using discrete event simulation. BMC Neurol., 12(1), 1-12.
Howard, R. (2012). Donepezil and memantine for moderate-to-severe Alzheimer’s disease. N Engl J Med, 366, 893-903.
Jiang, J., & Jiang, H. (2015). Efficacy and adverse effects of memantine treatment for Alzheimer’s disease from randomized controlled trials. Neurological Sciences, 36(9), 1633-1641.
Jones, R. W., McCrone, P., & Guilhaume, C. (2004). Cost effectiveness of memantine in Alzheimer’s disease. Drugs & aging, 21(9), 607-620.
Jönsson, L. (2005). Cost-effectiveness of memantine for moderate to severe Alzheimer's disease in Sweden. The American journal of geriatric pharmacotherapy, 3(2), 77-86.
Jönsson, L., Andreasen, N., Kilander, L., et al. (2006). Patient-and proxy-reported utility in Alzheimer disease using the EuroQoL. Alzheimer Disease & Associated Disorders, 20(1), 49-55.
Knapp, M., King, D., Romeo, R., et al. (2017). Cost‐effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO‐AD trial). International Journal of Geriatric Psychiatry, 32(12), 1205-1216.
Lachaine, J., Beauchemin, C., Legault, M., & Bineau, S. (2011). Economic evaluation of the impact of memantine on time to nursing home admission in the treatment of Alzheimer disease. The Canadian Journal of Psychiatry, 56(10), 596-604.
Laitinen, M. L., Bell, J. S., Lavikainen, P., et al. (2011). Nationwide study of antipsychotic use among community-dwelling persons with Alzheimer's disease in Finland. International psychogeriatrics, 23(10), 1623-1631.
Laitinen, M. L., Lönnroos, E., Bell, J. S., et al. (2015). Use of antidepressants among community-dwelling persons with Alzheimer's disease: a nationwide register-based study. International psychogeriatrics, 27(4), 669-672.
Larson, E. B., et al. (2006). Exercise is associated with reduced risk for incident dementia among persons 65 Years of age and older. Annals of Internal Medicine, 144 (2), 73-82.
Lebrão, M. L. (2007). O envelhecimento no Brasil: aspectos da transição demográfica e epidemiológica. Saúde coletiva, 4(17), 135-140.
Lima, D. (2008). O tratamento farmacológico para Doença de Alzheimer. Revista HUPE, 7 (1), 79-87.
Livingston, G., Sommerlad, A., Orgeta, V., et al. (2017). Dementia prevention, intervention, and care. The Lancet, 390(10113), 2673-2734. http://dx.doi.org/10.1016/S0140-6736(17)31363-6.
Lopez-Bastida, J., Serrano-Aguilar, P., Perestelo-Perez, L., & Oliva-Moreno, J. (2006). Social-economic costs and quality of life of Alzheimer disease in the Canary Islands, Spain. Neurology, 67(12), 2186-2191.
Martinez, C., Jones, R. W., & Rietbrock, S. (2013). Trends in the prevalence of antipsychotic drug use among patients with Alzheimer's disease and other dementias including those treated with antidementia drugs in the community in the UK: a cohort study. BMJ open, 3(1).
Mendez, M. F., Martin, R. J., Smyth, K. A., & Whitehouse, P. J. (1990). Psychiatric symptoms associated with Alzheimer's disease. The Journal of Neuropsychiatry and Clinical Neurosciences, 2 (1), 28-33.
Miranda, G. M. D., Mendes, A. D. C. G., & Silva, A. L. A. D. (2016). O envelhecimento populacional brasileiro: desafios e consequências sociais atuais e futuras. Revista brasileira de geriatria e gerontologia, 19, 507-519.
Motzek, T., Werblow, A., Tesch, F., Marquardt, G., & Schmitt, J. (2018). Determinants of hospitalization and length of stay among people with dementia–An analysis of statutory health insurance claims data. Archives of Gerontology and Geriatrics, 76, 227-233.
Neumann, P. J., Kuntz, K. M., Leon, J., Araki, S. S., Hermann, R. C., Hsu, M. A., & Weinstein, M. C. (1999). Health utilities in Alzheimer's disease: a cross-sectional study of patients and caregivers. Medical Care, 27-32.
Nitrini, R., Bottino, C. M., Albala, C., et al. (2009). Prevalence of dementia in Latin America: a collaborative study of population-based cohorts. International Psychogeriatrics, 21(4), 622-630.
Nitrini, R., Caramelli, P., Bottino, C. M. D. C., et al. (2005). Diagnóstico de doença de Alzheimer no Brasil: avaliação cognitiva e funcional. Recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia. Arquivos de Neuro-psiquiatria, 63, 720-727.
Oliveira, I. A. G. D., Caetano, R., Steffen, R. E., & Biz, A. N. (2019). A systematic review of economic evaluations of the use of memantine alone or combined with donepezil for moderate to severe Alzheimer’s disease. Revista Brasileira de Geriatria e Gerontologia, 22.
Pinto, M., Santos, M., & Trajman, A. Limiar de custo-efetividade: uma necessidade para o Brasil? J Bras Econ Saúde, 8(1), 58-60.
Prescrire Rédaction (2018). Médicaments de lamaladie d'Alzheimer: enfin non remboursables en France.Rev Prescrire, 38 (416).
Reisberg, B., Doody, R., Stöffler, A., et al. (2003). Memantine in moderate-to-severe Alzheimer's disease. New England Journal of Medicine, 348(14), 1333-1341.
Rhee, Y., Csernansky, J. G., Emanuel, L. L., et al. (2011). Psychotropic medication burden and factors associated with antipsychotic use: An analysis of a population‐based sample of community‐dwelling older persons with dementia. Journal of the American Geriatrics Society, 59(11), 2100-2107.
Rive, B., Aarsland, D., Grishchenko, M., et al. (2012). Cost‐effectiveness of memantine in moderate and severe Alzheimer's disease in Norway. International journal of geriatric psychiatry, 27(6), 573-582.
Rive, B., Grishchenko, M., Guilhaume–Goulant, C., et al. (2010). Cost effectiveness of memantine in Alzheimer's disease in the UK. Journal of medical economics, 13(2), 371-380.
Robinson, L. A., Hammitt, J. K., Chang, A. Y., & Resch, S. (2017). Understanding and improving the one and three times GDP per capita cost-effectiveness thresholds. Health Policy and Planning, 32(1), 141-145.
Russ, T. C., Parra, M. A., Lim, A. E., et al. (2015). Prediction of general hospital admission in people with dementia: cohort study. The British Journal of Psychiatry, 206(2), 153-159.
Saad, R., Lemmer, T., & Clark, O. (2017). Limiar de eficiência em avaliações de tecnologias em saúde. J Bras Econ Saude, 9(Supl1), 115-122.
Saint-Laurent Thibault, C., Özer Stillman, I., Chen, S., et al. (2015). Cost-utility analysis of memantine extended release added to cholinesterase inhibitors compared to cholinesterase inhibitor monotherapy for the treatment of moderate-to-severe dementia of the Alzheimer’s type in the US. Journal of medical economics, 18(11), 930-943.
Santos, M. D. S., Pinto, M., & Trajman, A. (2017). Contradições e o limiar de custo-efetividade. Cadernos de Saúde Pública, 33(8).
Selbæk, G., Engedal, K., & Bergh, S. (2013). The prevalence and course of neuropsychiatric symptoms in nursing home patients with dementia: a systematic review. Journal of the American Medical Directors Association, 14(3), 161-169.
Suthers, K., Kim, J. K., & Crimmins, E. (2003). Life expectancy with cognitive impairment in the older population of the United States. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 58(3), S179-S186.
Taipale, H., Koponen, M., Tanskanen, A., et al. (2016). Drug use in persons with and without Alzheimer's disease aged 90 years or more. Age and ageing, 45(6), 900-904.
Taipale, H., Koponen, M., Tanskanen, A., et al. (2015). Long-term use of benzodiazepines and related drugs among community-dwelling individuals with and without Alzheimer’s disease. International Clinical Psychopharmacology, 30(4), 202-208.
Veras, R. P., & Oliveira, M. (2018). Envelhecer no Brasil: a construção de um modelo de cuidado. Ciência & saúde coletiva, 23, 1929-1936.
Veras, R. P., Caldas, C. P., Dantas, S. B., Sancho, L. G., et al. (2007). Avaliação dos gastos com o cuidado do idoso com demência. Arch. Clin. Psychiatry (São Paulo), 34 (1).
Wang, G., Cheng, Q., Zhang, S., Bai, L., et al. (2008). Economic impact of dementia in developing countries: an evaluation of Alzheimer-type dementia in Shanghai, China. Journal of Alzheimer's Disease, 15(1), 109-115.
Wimo, A., Guerchet, M., Ali, G. C., Wu, Y., et al. (2017). The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimers Dement, 13 (1), 1–7.
Wlodarczyk, J. H., Brodaty, H., & Hawthorne, G. (2004). The relationship between quality of life, Mini-Mental State Examination, and the Instrumental Activities of Daily Living in patients with Alzheimer’s disease. Archives of gerontology and geriatrics, 39(1), 25-33.
Zanetti, O., Solerte, S. B., & Cantoni, F. (2009). Life expectancy in Alzheimer's disease (AD). Archives of gerontology and geriatrics, 49, 237-243.
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