Cost-effectiveness analysis of strategies of Covid-19 vaccination in Colombia: comparison of high-risk prioritization and no prioritization strategies with the absence of a vaccination plan
Objectives Our study compares two national COVID-19 vaccination plan strategies—high-risk prioritization and no prioritization—and estimates their cost-effectiveness compared with no vaccination, to generate possible recommendations for future vaccination plans. Methods We developed a Markov discret...
- Autores:
-
Morales-Zamora, Gilberto
Espinosa Eco, Oscar
Puertas, Edwin
Fernández, Juan Carlos
Hernández, José
Zakzuk, Verónica
Cepeda, Magda
Alvis-Guzmán, Nelson
Castañeda-Orjuela, Carlos
Paternina-Caicedo, Angel
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2022
- Institución:
- Corporación Universidad de la Costa
- Repositorio:
- REDICUC - Repositorio CUC
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.cuc.edu.co:11323/9372
- Acceso en línea:
- https://hdl.handle.net/11323/9372
https://doi.org/10.1016/j.vhri.2022.04.004
https://repositorio.cuc.edu.co/
- Palabra clave:
- Colombia
Cost-effectiveness
Modeling
Severe acute respiratory syndrome coronavirus 2
Vaccination
- Rights
- embargoedAccess
- License
- © 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc.
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dc.title.eng.fl_str_mv |
Cost-effectiveness analysis of strategies of Covid-19 vaccination in Colombia: comparison of high-risk prioritization and no prioritization strategies with the absence of a vaccination plan |
title |
Cost-effectiveness analysis of strategies of Covid-19 vaccination in Colombia: comparison of high-risk prioritization and no prioritization strategies with the absence of a vaccination plan |
spellingShingle |
Cost-effectiveness analysis of strategies of Covid-19 vaccination in Colombia: comparison of high-risk prioritization and no prioritization strategies with the absence of a vaccination plan Colombia Cost-effectiveness Modeling Severe acute respiratory syndrome coronavirus 2 Vaccination |
title_short |
Cost-effectiveness analysis of strategies of Covid-19 vaccination in Colombia: comparison of high-risk prioritization and no prioritization strategies with the absence of a vaccination plan |
title_full |
Cost-effectiveness analysis of strategies of Covid-19 vaccination in Colombia: comparison of high-risk prioritization and no prioritization strategies with the absence of a vaccination plan |
title_fullStr |
Cost-effectiveness analysis of strategies of Covid-19 vaccination in Colombia: comparison of high-risk prioritization and no prioritization strategies with the absence of a vaccination plan |
title_full_unstemmed |
Cost-effectiveness analysis of strategies of Covid-19 vaccination in Colombia: comparison of high-risk prioritization and no prioritization strategies with the absence of a vaccination plan |
title_sort |
Cost-effectiveness analysis of strategies of Covid-19 vaccination in Colombia: comparison of high-risk prioritization and no prioritization strategies with the absence of a vaccination plan |
dc.creator.fl_str_mv |
Morales-Zamora, Gilberto Espinosa Eco, Oscar Puertas, Edwin Fernández, Juan Carlos Hernández, José Zakzuk, Verónica Cepeda, Magda Alvis-Guzmán, Nelson Castañeda-Orjuela, Carlos Paternina-Caicedo, Angel |
dc.contributor.author.spa.fl_str_mv |
Morales-Zamora, Gilberto Espinosa Eco, Oscar Puertas, Edwin Fernández, Juan Carlos Hernández, José Zakzuk, Verónica Cepeda, Magda Alvis-Guzmán, Nelson Castañeda-Orjuela, Carlos Paternina-Caicedo, Angel |
dc.subject.proposal.spa.fl_str_mv |
Colombia |
topic |
Colombia Cost-effectiveness Modeling Severe acute respiratory syndrome coronavirus 2 Vaccination |
dc.subject.proposal.eng.fl_str_mv |
Cost-effectiveness Modeling Severe acute respiratory syndrome coronavirus 2 Vaccination |
description |
Objectives Our study compares two national COVID-19 vaccination plan strategies—high-risk prioritization and no prioritization—and estimates their cost-effectiveness compared with no vaccination, to generate possible recommendations for future vaccination plans. Methods We developed a Markov discrete-time, compartmental, deterministic model stratified by Colombian departments, healthcare workers, comorbidities, and age groups and calibrated to seroprevalence, cases, and deaths. The model simulates three scenarios: no vaccination, no prioritization of vaccination, and prioritization of high-risk population. The study presents the perspective of the health system of Colombia, including the direct health costs financed by the government and the direct health outcomes related to the infection. We measured symptomatic cases, deaths, and costs for each of the three scenarios from the start of the vaccination rollout to February 20, 2023. Results Both for the base-case and across multiple sensitivity analyses, the high-risk prioritization proves to be the most cost-effective of the considered strategies. An increment of US$255 million results in an incremental cost-effectiveness ratio of US$3339 per disability-adjusted life-year avoided. The simulations show that prioritization of high-risk population reduces symptomatic cases by 3.4% and deaths by 20.1% compared with no vaccination. The no-prioritization strategy is still cost-effective, with an incremental cost-effectiveness ratio of US$5223.66, but the sensitivity analysis the show potential risks of losing cost-effectiveness under the cost-effectiveness threshold (one gross domestic product per averted disability-adjusted life-year). Conclusions The high-risk prioritization strategy is consistently more cost-effective than the no-prioritization strategy across multiple scenarios. High-risk prioritization is the recommended strategy in low-resource settings to reduce the burden of disease. |
publishDate |
2022 |
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2022-07-14T19:54:25Z |
dc.date.available.none.fl_str_mv |
2022-07-14T19:54:25Z 2023 |
dc.date.issued.none.fl_str_mv |
2022 |
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Artículo de revista |
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Gilberto Morales-Zamora, Oscar Espinosa, Edwin Puertas, Juan Carlos Fernández, José Hernández, Verónica Zakzuk, Magda Cepeda, Nelson Alvis-Gúzman, Carlos Castañeda-Orjuela, Angel Paternina-Caicedo, Cost-Effectiveness Analysis of Strategies of COVID-19 Vaccination in Colombia: Comparison of High-Risk Prioritization and No Prioritization Strategies With the Absence of a Vaccination Plan, Value in Health Regional Issues, Volume 31, 2022, Pages 101-110, ISSN 2212-1099, https://doi.org/10.1016/j.vhri.2022.04.004. |
dc.identifier.issn.spa.fl_str_mv |
2212-1099 |
dc.identifier.uri.spa.fl_str_mv |
https://hdl.handle.net/11323/9372 |
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https://doi.org/10.1016/j.vhri.2022.04.004 |
dc.identifier.doi.spa.fl_str_mv |
10.1016/j.vhri.2022.04.004 |
dc.identifier.eissn.spa.fl_str_mv |
2212-1102 |
dc.identifier.instname.spa.fl_str_mv |
Corporación Universidad de la Costa |
dc.identifier.reponame.spa.fl_str_mv |
REDICUC - Repositorio CUC |
dc.identifier.repourl.spa.fl_str_mv |
https://repositorio.cuc.edu.co/ |
identifier_str_mv |
Gilberto Morales-Zamora, Oscar Espinosa, Edwin Puertas, Juan Carlos Fernández, José Hernández, Verónica Zakzuk, Magda Cepeda, Nelson Alvis-Gúzman, Carlos Castañeda-Orjuela, Angel Paternina-Caicedo, Cost-Effectiveness Analysis of Strategies of COVID-19 Vaccination in Colombia: Comparison of High-Risk Prioritization and No Prioritization Strategies With the Absence of a Vaccination Plan, Value in Health Regional Issues, Volume 31, 2022, Pages 101-110, ISSN 2212-1099, https://doi.org/10.1016/j.vhri.2022.04.004. 2212-1099 10.1016/j.vhri.2022.04.004 2212-1102 Corporación Universidad de la Costa REDICUC - Repositorio CUC |
url |
https://hdl.handle.net/11323/9372 https://doi.org/10.1016/j.vhri.2022.04.004 https://repositorio.cuc.edu.co/ |
dc.language.iso.none.fl_str_mv |
eng |
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eng |
dc.relation.ispartofjournal.spa.fl_str_mv |
Value in Health Regional Issues |
dc.relation.references.spa.fl_str_mv |
1. Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020;20(5):533–534 [published correction appears in Lancet Infect Dis. 2020;20(9):e215]. 2. Davies N, Kucharski A, Eggo R, Gimma A, Edmunds W. Centre for the Mathematical Modelling of Infectious Diseases COVID-19 working group. Effects of non-pharmaceutical interventions on COVID-19 cases, deaths, and demand for hospital services in the UK: a modelling study. Lancet Public Health. 2020;5(7):e375–e385. 3. Flaxman S, Mishra S, Gandy A, et al. Estimating the effects of nonpharmaceutical interventions on COVID-19 in Europe. Nature. 2020;584(7820):257–261. 4. Voysey M, Clemens S, Madhi S, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of 4 randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99–111. 5. Baden L, El Sahly H, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403–416. 6. Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med. 2021;384(15):1412–1423. 7. Polack F, Thomas S, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603–2615. 8. Knoll M, Wonodi C. Oxford–AstraZeneca COVID-19 vaccine efficacy. Lancet. 2021;397(10269):72–74. 9. Li Q, Guan X,Wu P, et al. Early transmission dynamics inWuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020;382(13):1199–1207. 10. Global economic prospects. Resumen. https://www.bancomundial.org/es/publication/global-economic-prospects. Accessed December 23, 2020. 11. Institute for Health Metrics and Evaluation. University of Washington. Healthdata – Global Burden of Disease. University of Washington; 2021. https://vizhub.healthdata.org/gbd-results/. 12. Ministerio de Salud y Protección Social. Base de Datos Única de Afiliados (BDUA). 2012-2020;Vol 2020. https://servicios.adres.gov.co/BDUA/ConsultaAfiliados-BDUA. 13. Ministerio de Salud y Protección Social. Departamento Administrativo Nacional de Estadística. Estadísticas Vitales. 2012-2019;Vol 2020. https://www.dane.gov.co/index.php/servicios-al-ciudadano/281-demograficas/estadisticas-vitales. 14. Briggs A, Claxton K, Sculpher M. Decision modelling for health economic evaluation. Oxford, United Kingdom: Oxford University Press; 2006. 15. Ministerio de Salud y Protección Social. Base de datos de la Suficiencia del Aseguramiento en Salud. Vol. 2021; 2012-2018. 16. Ministerio de Salud y Protección Social. Base de Datos del Registro Único Nacional de Talento Humano en Salud. (ReTHUS). 2020. https://web.sispro.gov.co/THS/Cliente/ConsultasPublicas/ConsultaPublicaDeTHxIdentificacion.aspx. 17. Verity R, Okell L, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020;20(6):669–677 [published correction appears in Lancet Infect Dis. 2020;20(6):e116]. 18. Instituto Nacional de Salud. Base de datos de Casos. COVID-19 en Colombia; 2020. https://www.ins.gov.co/Noticias/Paginas/Coronavirus.aspx. 19. Prem K, Cook A, Jit M. Projecting social contact matrices in 152 countries using contact surveys and demographic data. PLoS Comput Biol. 2017;13(9): e1005697. 20. Google. COVID-19 Community Mobility Reports. https://www.google.com/covid19/mobility/. 21. Mutual Ser EPS. Mutual Ser EPS COVID-19 recorded cases. 2020. 22. Departamento Administrativo Nacional de Estadística. Producto Interno Bruto – Datos actualizados para. Vol. 2021. 2020; https://www.dane.gov.co/index.php/estadisticas-por-tema/cuentas-nacionales/cuentas-nacionalestrimestrales/pib-informacion-tecnica. 23. Departamento Administrativo Nacional de Estadística, ed. Censo Nacional de Poblacion y Vivienda 2018. Departamento Administrativo Nacional de Estadística; 2018. https://www.dane.gov.co/index.php/estadisticas-por-tema/demografia-y-poblacion/censo-nacional-de-poblacion-y-vivenda-2018. 24. Nelder J, Mead R. A simplex method for function minimization. Comput J. 1965;7(4):308–313. 25. Huang Y, McColl W. Improved simplex method for function minimization. Proc IEEE Int Conf Syst Man Cybern. 1996;3:1702–1705. 26. Davies N, Abbott S, Barnard R, et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science. 2021;372(6538). eabg3055. |
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© 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0) |
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Morales-Zamora, GilbertoEspinosa Eco, OscarPuertas, EdwinFernández, Juan CarlosHernández, JoséZakzuk, VerónicaCepeda, MagdaAlvis-Guzmán, NelsonCastañeda-Orjuela, CarlosPaternina-Caicedo, Angel2022-07-14T19:54:25Z20232022-07-14T19:54:25Z2022Gilberto Morales-Zamora, Oscar Espinosa, Edwin Puertas, Juan Carlos Fernández, José Hernández, Verónica Zakzuk, Magda Cepeda, Nelson Alvis-Gúzman, Carlos Castañeda-Orjuela, Angel Paternina-Caicedo, Cost-Effectiveness Analysis of Strategies of COVID-19 Vaccination in Colombia: Comparison of High-Risk Prioritization and No Prioritization Strategies With the Absence of a Vaccination Plan, Value in Health Regional Issues, Volume 31, 2022, Pages 101-110, ISSN 2212-1099, https://doi.org/10.1016/j.vhri.2022.04.004.2212-1099https://hdl.handle.net/11323/9372https://doi.org/10.1016/j.vhri.2022.04.00410.1016/j.vhri.2022.04.0042212-1102Corporación Universidad de la CostaREDICUC - Repositorio CUChttps://repositorio.cuc.edu.co/Objectives Our study compares two national COVID-19 vaccination plan strategies—high-risk prioritization and no prioritization—and estimates their cost-effectiveness compared with no vaccination, to generate possible recommendations for future vaccination plans. Methods We developed a Markov discrete-time, compartmental, deterministic model stratified by Colombian departments, healthcare workers, comorbidities, and age groups and calibrated to seroprevalence, cases, and deaths. The model simulates three scenarios: no vaccination, no prioritization of vaccination, and prioritization of high-risk population. The study presents the perspective of the health system of Colombia, including the direct health costs financed by the government and the direct health outcomes related to the infection. We measured symptomatic cases, deaths, and costs for each of the three scenarios from the start of the vaccination rollout to February 20, 2023. Results Both for the base-case and across multiple sensitivity analyses, the high-risk prioritization proves to be the most cost-effective of the considered strategies. An increment of US$255 million results in an incremental cost-effectiveness ratio of US$3339 per disability-adjusted life-year avoided. The simulations show that prioritization of high-risk population reduces symptomatic cases by 3.4% and deaths by 20.1% compared with no vaccination. The no-prioritization strategy is still cost-effective, with an incremental cost-effectiveness ratio of US$5223.66, but the sensitivity analysis the show potential risks of losing cost-effectiveness under the cost-effectiveness threshold (one gross domestic product per averted disability-adjusted life-year). Conclusions The high-risk prioritization strategy is consistently more cost-effective than the no-prioritization strategy across multiple scenarios. High-risk prioritization is the recommended strategy in low-resource settings to reduce the burden of disease.10 páginasapplication/pdfengElsevier USAUnited States© 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc.Atribución-NoComercial-SinDerivadas 4.0 Internacional (CC BY-NC-ND 4.0)https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/embargoedAccesshttp://purl.org/coar/access_right/c_f1cfCost-effectiveness analysis of strategies of Covid-19 vaccination in Colombia: comparison of high-risk prioritization and no prioritization strategies with the absence of a vaccination planArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85https://www.valuehealthregionalissues.com/article/S2212-1099(22)00110-8/fulltext#relatedArticlesColombiaValue in Health Regional Issues1. Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020;20(5):533–534 [published correction appears in Lancet Infect Dis. 2020;20(9):e215].2. Davies N, Kucharski A, Eggo R, Gimma A, Edmunds W. Centre for the Mathematical Modelling of Infectious Diseases COVID-19 working group. Effects of non-pharmaceutical interventions on COVID-19 cases, deaths, and demand for hospital services in the UK: a modelling study. Lancet Public Health. 2020;5(7):e375–e385.3. Flaxman S, Mishra S, Gandy A, et al. Estimating the effects of nonpharmaceutical interventions on COVID-19 in Europe. Nature. 2020;584(7820):257–261.4. Voysey M, Clemens S, Madhi S, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of 4 randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021;397(10269):99–111.5. Baden L, El Sahly H, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403–416.6. Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med. 2021;384(15):1412–1423.7. Polack F, Thomas S, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603–2615.8. Knoll M, Wonodi C. Oxford–AstraZeneca COVID-19 vaccine efficacy. Lancet. 2021;397(10269):72–74.9. Li Q, Guan X,Wu P, et al. Early transmission dynamics inWuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020;382(13):1199–1207.10. Global economic prospects. Resumen. https://www.bancomundial.org/es/publication/global-economic-prospects. Accessed December 23, 2020.11. Institute for Health Metrics and Evaluation. University of Washington. Healthdata – Global Burden of Disease. University of Washington; 2021. https://vizhub.healthdata.org/gbd-results/.12. Ministerio de Salud y Protección Social. Base de Datos Única de Afiliados (BDUA). 2012-2020;Vol 2020. https://servicios.adres.gov.co/BDUA/ConsultaAfiliados-BDUA.13. Ministerio de Salud y Protección Social. Departamento Administrativo Nacional de Estadística. Estadísticas Vitales. 2012-2019;Vol 2020. https://www.dane.gov.co/index.php/servicios-al-ciudadano/281-demograficas/estadisticas-vitales.14. Briggs A, Claxton K, Sculpher M. Decision modelling for health economic evaluation. Oxford, United Kingdom: Oxford University Press; 2006.15. Ministerio de Salud y Protección Social. Base de datos de la Suficiencia del Aseguramiento en Salud. Vol. 2021; 2012-2018.16. Ministerio de Salud y Protección Social. Base de Datos del Registro Único Nacional de Talento Humano en Salud. (ReTHUS). 2020. https://web.sispro.gov.co/THS/Cliente/ConsultasPublicas/ConsultaPublicaDeTHxIdentificacion.aspx.17. Verity R, Okell L, Dorigatti I, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020;20(6):669–677 [published correction appears in Lancet Infect Dis. 2020;20(6):e116].18. Instituto Nacional de Salud. Base de datos de Casos. COVID-19 en Colombia; 2020. https://www.ins.gov.co/Noticias/Paginas/Coronavirus.aspx.19. Prem K, Cook A, Jit M. Projecting social contact matrices in 152 countries using contact surveys and demographic data. PLoS Comput Biol. 2017;13(9): e1005697.20. Google. COVID-19 Community Mobility Reports. https://www.google.com/covid19/mobility/.21. Mutual Ser EPS. Mutual Ser EPS COVID-19 recorded cases. 2020.22. Departamento Administrativo Nacional de Estadística. Producto Interno Bruto – Datos actualizados para. Vol. 2021. 2020; https://www.dane.gov.co/index.php/estadisticas-por-tema/cuentas-nacionales/cuentas-nacionalestrimestrales/pib-informacion-tecnica.23. Departamento Administrativo Nacional de Estadística, ed. Censo Nacional de Poblacion y Vivienda 2018. Departamento Administrativo Nacional de Estadística; 2018. https://www.dane.gov.co/index.php/estadisticas-por-tema/demografia-y-poblacion/censo-nacional-de-poblacion-y-vivenda-2018.24. Nelder J, Mead R. A simplex method for function minimization. Comput J. 1965;7(4):308–313.25. Huang Y, McColl W. Improved simplex method for function minimization. Proc IEEE Int Conf Syst Man Cybern. 1996;3:1702–1705.26. Davies N, Abbott S, Barnard R, et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Science. 2021;372(6538). eabg3055.11010131ColombiaCost-effectivenessModelingSevere acute respiratory syndrome coronavirus 2VaccinationPublicationORIGINALCost-Effectiveness Analysis of Strategies of COVID-19 Vaccination in Colombia.pdfCost-Effectiveness Analysis of Strategies of COVID-19 Vaccination in Colombia.pdfapplication/pdf1777340https://repositorio.cuc.edu.co/bitstreams/ee03a872-df72-4f06-b18c-fdb02a054941/downloada052d7960637160b7f14677d5e6f1294MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-83196https://repositorio.cuc.edu.co/bitstreams/4f9767b4-a8e1-4842-bc87-bf423f431d88/downloade30e9215131d99561d40d6b0abbe9badMD52TEXTCost-Effectiveness Analysis of Strategies of COVID-19 Vaccination in Colombia.pdf.txtCost-Effectiveness Analysis of Strategies of COVID-19 Vaccination in Colombia.pdf.txttext/plain43003https://repositorio.cuc.edu.co/bitstreams/9e99e340-d537-413f-9b34-7396cacc81dd/download35e245328de3b8507de3e9b74d18cdb3MD53THUMBNAILCost-Effectiveness Analysis of Strategies of COVID-19 Vaccination in Colombia.pdf.jpgCost-Effectiveness Analysis of Strategies of COVID-19 Vaccination in Colombia.pdf.jpgimage/jpeg15353https://repositorio.cuc.edu.co/bitstreams/1bb19640-40d4-4ab8-8433-6bc8b97cc7da/downloadf8bfe39288891873d80821282c6a23e4MD5411323/9372oai:repositorio.cuc.edu.co:11323/93722024-09-16 16:50:17.417https://creativecommons.org/licenses/by-nc-nd/4.0/© 2022 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc.open.accesshttps://repositorio.cuc.edu.coRepositorio de la Universidad de la Costa CUCrepdigital@cuc.edu.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 |