Budget Impact Analysis of Brivaracetam Adjunctive Therapy for Partial-Onset Epileptic Seizures in Valencia Community, Spain

[EN] Background and Objective More than 30% of patients with epilepsy have inadequate control of seizures with drug therapy. The goal of this study is to determine the budget impact (BI) of the introduction of brivaracetam to the portfolio of approved drugs in Spain as adjunctive therapy for the treatment of partial-onset epilepsy in patients over 16 years old with a 5-year time horizon in the Valencia Community, a Spanish region with a population of 5 million. Methods The BI model compares the pharmaceutical expenditure on antiepileptics in two scenarios: with and without brivaracetam. It assumes that the introduction and increased use of brivaracetam will lead to a proportional decrease in consumption of coexisting adjunctive antiepileptics and calculates the evolution of the consumption of brivaracetam over 5 years (2016-2020). The model was designed from the perspective of the Spanish National Health System. Data on the candidate population, consumption of antiepileptics, market share and pharmaceutical expenditure were obtained from real-world data. Finally, a sensitivity analysis was carried out on the set of variables involved in the evolution of costs using a Monte-Carlo simulation. Results The model estimates that the target population eligible for adjunctive antiepileptics will hold at around 2352 between 2016 and 2020. Annual expenditure on antiepileptics is approximately a,notsign3.6 million. The number of patients eligible for treatment with brivaracetam would increase from 42 to 179 and annual savings of 0.09-0.37% would be created, representing a,notsign 41,873 over 5 years (0.23% of the total budget). The sensitivity analysis corroborates that the probability of achieving savings with brivaracetam is around 84%. Conclusions Brivaracetam is a therapeutic alternative that allows savings for the health system in patients with non-controlled epilepsy in monotherapy, having a fixed, predictable annual cost (independent of dose) from the first day of treatment as the lack of need for titration means the patient is within a range of therapeutic doses from the first dose.This work was supported partially by the Instituto de Salud Carlos III-Ministerio de Economia y Competitividad and the European Union (FEDER [Fonds Europeen de Developpement Economique et Regional (European Fund for Economic and Regional Development)] funds)-FIS PI12/00037.Barrachina Martínez, I.; Vivas-Consuelo, D.; Piera-Balbastre, A. (2018). Budget Impact Analysis of Brivaracetam Adjunctive Therapy for Partial-Onset Epileptic Seizures in Valencia Community, Spain. Clinical Drug Investigation. 38(4):353-363. https://doi.org/10.1007/s40261-017-0615-zS353363384World Health Organization (2017). Epilepsy fact sheet. http://www.who.int/mediacentre/factsheets/fs999/en/. Accessed 12 Jan 2016.Fiest KM, Sauro KM, Wiebe S, Patten SB, Kwon CS, Dykeman J, et al. Prevalence and incidence of epilepsy. Neurology. 2017;88:296–303.Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005–2009. Epilepsia. 2010;51:676–85.García-Ramos R, Pastor AG, Masjuan J, Sánchez C, Gil A. FEEN report on epilepsy in Spain [in Spanish]. Neurologia. 2011;26:548–55.Brodie MJ. Practical use of newer antiepileptic drugs as adjunctive therapy in focal epilepsy. CNS Drugs. 2015;29:893–904.Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342:314–9.Sánchez-álvarez JC, Gil-Nagel A, Casas-Fernández C, Mauri-Llerda JA, Salas-Puig J, Sancho-Rieger J. Drug-resistant epilepsy: current recommendations for diagnosis and treatment in Spain. Neurologia. 2012;27:575–84.Fazel S, Wolf A, Långström N, Newton CR, Lichtenstein P. Premature mortality in epilepsy and the role of psychiatric comorbidity: a total population study. Lancet. 2013;382(9905):1646–54. https://doi.org/10.1016/S0140-6736(13)60899-5.Villanueva V, Girón JM, Martín J, Lahuerta J, Dolz M, Cuesta M. Quality of life and economic impact of refractory epilepsy in Spain: the ESPERA study. Neurologia. 2013;28:195–204.Sancho J, Pena P, Rufo M, Palacios G, Masramon X, Rejas J, LINCE Study Collaborative Group. Health and non-health care resources use in the management of adult outpatients with drug-resistant epilepsy in Spain: a cost-of-illness study (LINCE study). Epilepsy Res. 2008;81:176–187.Laxer KD, Trinka E, Hirsch LJ, Cendes F, Langfitt J, Delanty N, et al. The consequences of refractory epilepsy and its treatment. Epilepsy Behav. 2014;37:59–70.Duncan JS, Duncan JS, Sander JW, Sisodiya SM, Walker MC. Adult epilepsy. Lancet. 2006;367:1087–100.European Medicines Agency (EMA). EPARs for authorised medicinal products for human use—Stelara. 2016. http://www.emea.europa.eu/humandocs/Humans/EPAR/stelara/stelara.htm. Accessed 29 Nov 2017.Biton V, Berkovic SF, Abou-Khalil B, Sperling MR, Johnson ME, Lu S. Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: a phase III randomized, double-blind, placebo-controlled trial. Epilepsia. 2014;55:57–66.Ferlazzo E, Russo E, Mumoli L, Sueri C, Gasparini S, Palleria C, et al. Profile of brivaracetam and its potential in the treatment of epilepsy. Neuropsychiatr Dis Treat. 2015;11:2967–73.Sullivan SD, Mauskopf JA, Augustovski F, Caro JJ, Lee KM, Minchin M, et al. Budget impact analysis—principles of good practice: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force. Value Health. 2014;17:5–14.European Medicines Agency. Vimpat. Summary of product characteristics. 2016. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000863/WC500050338.pdf. Accessed 27 Nov 2017.European Medicines Agency. Eslicarbazepine. Summary of product characteristics. 2017. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000988/WC500047225.pdf. Accessed 27 Nov 2017.European Medicines Agency. Perampanel. Summary of product characteristics. 2012. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/002434/WC500130840.pdf. Accessed 29 Nov 2017.European Medicines Agency. Retigabine. Summary of product characteristics. 2016;1–26. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001245/WC500104835.pdf. Accessed 29 Nov 2017.European Medicines Agency Zonisamide. Summary of product characteristics. 2017. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/004127/WC500204305.pdf. Accessed 29 Nov 2017.BOE (2010) Real Decreto-Ley 8/2010, de 20 de mayo, por el que se adoptan medidas extraordinarias para la reducción del déficit público. Boe 20/5/2010:45070–45128. https://www.boe.es/diario_boe/txt.php?id=BOE-A-2010-8228. Accessed 29 Nov 2017.Farmacéuticos CG de CO de BOTfarma. BOT Base de datos del medicamento. https://botplusweb.portalfarma.com/. Accessed 29 Nov 2017.AEMPS. Informe de Posicionamiento Terapéutico de brivaracetam (Briviact®) en epilepsia. 2017;1–7. https://www.aemps.gob.es/medicamentosUsoHumano/informesPublicos/docs/IPT-brivaracetam-Briviact-epilepsia.pdf. Accessed 29 Nov 2017.Belén Ferro-Rey M, Roca-Cusachs A, Sicras-Mainar A, Álvarez-Martín C, de Salas-Cansado M. Fixed drug combinations in hypertension: a budget impact analysis for the spanish health system on the marketing of a fixed combination of olmesartan/amlodipine [in Spanish]. Aten Primaria. 2011;43:345–55.Simoens S. Pharmacoeconomics of anti-epileptic drugs as adjunctive therapy for refractory epilepsy. Expert Rev Pharmacoecon Outcomes Res. 2010;10(3):309–15.Borghs S, Thieffry S, Noack-Rink M, Dedeken P, Hong LS, Byram L, et al. Health care cost associated with the use of enzyme-inducing and non-enzyme-active antiepileptic drugs in the UK: a long-term retrospective matched cohort study. BMC Neurol. 2017;17:59

COVID-19, Fake News, and Vaccines: Should Regulation Be Implemented?

[EN] We analysed issues concerning the establishment of compulsory vaccination against COVID-19, as well as the role of misinformation as a disincentive-especially when published by health professionals-and citizen acceptance of measures in this regard. Data from different surveys revealed a high degree of hesitation rather than outright opposition to vaccines. The most frequent complaint related to the COVID-19 vaccination was the fear of side effects. Within the Spanish and European legislative framework, both compulsory vaccination and government regulation of FN (Fake News) appear to be feasible options, counting on sufficient legal support, which could be reinforced by additional amendment. However, following current trends of good governance, policymakers must have public legitimation. Rather than compulsory COVID-19 vaccination, an approach based on education and truthful information, persuading the population of the benefits of a vaccine on a voluntary basis, is recommended. Disagreements between health professionals are positive, but they should be resolved following good practice and the procedures of the code of ethics. Furthermore, citizens do not support the involvement of government authorities in the direct control of news. Collaboration with the media and other organizations should be used instead.Marco-Franco, JE.; Pita-Barros, P.; Vivas-Orts, D.; González-De Julián, S.; Vivas-Consuelo, D. (2021). COVID-19, Fake News, and Vaccines: Should Regulation Be Implemented?. International Journal of Environmental research and Public Health (Online). 18(2):1-11. https://doi.org/10.3390/ijerph18020744S111182Reuters Institute Digital News Report 2020https://reutersinstitute.politics.ox.ac.uk/sites/default/files/2020-06/DNR_2020_FINAL.pdfMerck CEO Ken Frazier Discusses a COVID Cure, Racism, and Why Leaders Need to Walk the Talkhttps://hbswk.hbs.edu/item/merck-ceo-ken-frazier-speaks-about-a-covid-cure-racism-and-why-leaders-need-to-walk-the-talkDe las Heras-Pedrosa, C., Rando-Cueto, D., Jambrino-Maldonado, C., & Paniagua-Rojano, F. J. (2020). Exploring the Social Media on the Communication Professionals in Public Health. Spanish Official Medical Colleges Case Study. International Journal of Environmental Research and Public Health, 17(13), 4859. doi:10.3390/ijerph17134859Page, B. I., & Shapiro, R. Y. (1983). Effects of Public Opinion on Policy. American Political Science Review, 77(1), 175-190. doi:10.2307/1956018Public Opinion Surveys as Input to Administrative Reformhttp://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=CCNM/SIGMA/PUMA(98)48&docLanguage=EnJacobs, L. R. (1992). The Recoil Effect: Public Opinion and Policymaking in the U.S. and Britain. Comparative Politics, 24(2), 199. doi:10.2307/422278The Statistics Portal for Market Data, Market Research and Market Studieshttps://www.statista.com/Flash Eurobarometer 464: Fake News and Disinformation Onlinehttps://op.europa.eu/en/publication-detail/-/publication/2d79b85a-4cea-11e8-be1d-01aa75ed71a1/language-enState of Vaccine Confidence in the EU 2018https://ec.europa.eu/health/sites/health/files/vaccination/docs/2018_vaccine_confidence_en.pdfGlobal Attitudes on a COVID-19 Vaccine, 2020https://www.ipsos.com/sites/default/files/ct/news/documents/2020-09/global-attitudes-on-a-covid-19-vaccine-ipsos-survey-for-wef-2020.pdfEffects and Consequences of the Coronavirus (II): Advance Results. Tabulation by Sociodemographic Variableshttp://datos.cis.es/pdf/Es3302marMT_A.pdfNeumann-Böhme, S., Varghese, N. E., Sabat, I., Barros, P. P., Brouwer, W., van Exel, J., … Stargardt, T. (2020). Once we have it, will we use it? A European survey on willingness to be vaccinated against COVID-19. The European Journal of Health Economics, 21(7), 977-982. doi:10.1007/s10198-020-01208-6Gallup-Knight Foundation: Americans see Media As Key to Democracy But Increasingly Don’t Trust Ithttps://knightfoundation.org/press/releases/gallup-knight-foundation-report-americans-see-media-as-key-to-democracy-but-increasingly-don-t-trust-it/“Fake News” Threat to Media; Editorial Decisions, Outside Actors at Faulthttps://www.monmouth.edu/polling-institute/reports/monmouthpoll_us_040218/Insider NJ Monmouth National—America Takes Sides in Social Media Warhttps://www.insidernj.com/press-release/monmouth-national-america-takes-sides-social-media-war/International Study of Valueshttps://www.fbbva.es/wp-content/uploads/2019/09/Presentacion_Estudio_Valores_2019.pdfCoronavirus Special Reportshttps://www.agcom.it/osservatorio-sulla-disinformazione-onlineWhich Media Are Responsible for Spreading False or Inaccurate Information Regarding the Coronavirus (COVID-19) and Its Impact?https://www.statista.com/statistics/1111877/opinions-on-fake-news-sources-about-the-coronavirus-by-macro-region-italy/Covid-19 News and Information: Consumption and Attitudeshttps://www.ofcom.org.uk/research-and-data/tv-radio-and-on-demand/news-media/coronavirus-news-consumption-attitudes-behaviourHow to Report Misinformation Onlinehttps://www.who.int/campaigns/connecting-the-world-to-combat-coronavirus/how-to-report-misinformation-online?gclid=EAIaIQobChMIj_bv-tqx7QIV5hoGAB1REwetEAAYASAAEgLpjPD_BwECovid-19 Pandemichttps://www.ecdc.europa.eu/en/covid-19-pandemicFighting Disinformationhttps://ec.europa.eu/info/live-work-travel-eu/coronavirus-response/fighting-disinformation_enTackling Online Disinformationhttps://ec.europa.eu/digital-single-market/en/tackling-online-disinformationFunded Projects in the Fight against Disinformationhttps://ec.europa.eu/info/live-work-travel-eu/coronavirus-response/fighting-disinformation/funded-projects-fight-against-disinformation_enSocial Observatory for Disinformation and Social Media Analysishttps://cordis.europa.eu/project/id/825469European Court of Human Rights European Convention on Human Rights; 1950 with Ammendshttps://www.echr.coe.int/documents/convention_eng.pdfThe Legal Framework to Address “Fake News”: Possible Policy Actions at the EU Levelhttps://www.europarl.europa.eu/RegData/etudes/IDAN/2018/619013/IPOL_IDA(2018)619013_EN.pdfCoronavirus: EU Strengthens Action to Tackle Disinformationhttps://ec.europa.eu/commission/presscorner/detail/en/ip_20_1006EEAS Special Report Update: Short Assessment of Narratives and Disinformation around the Covid-19 Pandemic (Update May–November)https://euvsdisinfo.eu/eeas-special-report-update-short-assessment-of-narratives-and-disinformation-around-the-covid-19-pandemic-update-may-november/Fighting Disinformation—COVID-19 Vaccineshttps://www.consilium.europa.eu/en/policies/coronavirus/fighting-disinformation/Calling of an International Conference on Freedom of Informationhttps://digitallibrary.un.org/record/209774?ln=esUniversal Declaration of Human Rightshttps://www.un.org/en/ga/search/view_doc.asp?symbol=A/RES/217(III)WMA Declaration of Genevahttps://www.wma.net/policies-post/wma-declaration-of-geneva/Hendriks. (1997). Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine. European Journal of Health Law, 4(1), 89-100. doi:10.1163/15718099720521896Code of Medical Ethics Guide to Medical Ethicshttps://www.cgcom.es/sites/default/files/codigo_deontologia_medica.pdfCase-law STS 1639/2016—ECLI: ES:TS:2016:1639http://www.poderjudicial.es/search/AN/openCDocument/f9caf3b37c843044ddaedeee43551672cfe231e21f03965aCharter of Fundamental Rights of the European Unionhttps://eur-lex.europa.eu/eli/treaty/char_2012/ojRoope, L. S. J., Buckell, J., Becker, F., Candio, P., Violato, M., Sindelar, J. L., … Clarke, P. M. (2020). How Should a Safe and Effective COVID-19 Vaccine be Allocated? Health Economists Need to be Ready to Take the Baton. PharmacoEconomics - Open, 4(4), 557-561. doi:10.1007/s41669-020-00228-5Ding, Y., Du, X., Li, Q., Zhang, M., Zhang, Q., Tan, X., & Liu, Q. (2020). Risk perception of coronavirus disease 2019 (COVID-19) and its related factors among college students in China during quarantine. PLOS ONE, 15(8), e0237626. doi:10.1371/journal.pone.0237626Dryhurst, S., Schneider, C. R., Kerr, J., Freeman, A. L. J., Recchia, G., van der Bles, A. M., … van der Linden, S. (2020). Risk perceptions of COVID-19 around the world. Journal of Risk Research, 23(7-8), 994-1006. doi:10.1080/13669877.2020.1758193Wise, T., Zbozinek, T. D., Michelini, G., Hagan, C. C., & Mobbs, D. (2020). Changes in risk perception and self-reported protective behaviour during the first week of the COVID-19 pandemic in the United States. Royal Society Open Science, 7(9), 200742. doi:10.1098/rsos.200742Olivares-Delgado, F., Iglesias-Sánchez, P. P., Benlloch-Osuna, M. T., Heras-Pedrosa, C. de las, & Jambrino-Maldonado, C. (2020). Resilience and Anti-Stress during COVID-19 Isolation in Spain: An Analysis through Audiovisual Spots. International Journal of Environmental Research and Public Health, 17(23), 8876. doi:10.3390/ijerph17238876Bavel, J. J. V., Baicker, K., Boggio, P. S., Capraro, V., Cichocka, A., Cikara, M., … Willer, R. (2020). Using social and behavioural science to support COVID-19 pandemic response. Nature Human Behaviour, 4(5), 460-471. doi:10.1038/s41562-020-0884-zBaldassarre, A., Giorgi, G., Alessio, F., Lulli, L., Arcangeli, G., & Mucci, N. (2020). Stigma and Discrimination (SAD) at the Time of the SARS-CoV-2 Pandemic. International Journal of Environmental Research and Public Health, 17(17), 6341. doi:10.3390/ijerph17176341Betsch, C. (2020). How behavioural science data helps mitigate the COVID-19 crisis. Nature Human Behaviour, 4(5), 438-438. doi:10.1038/s41562-020-0866-

Calculated Forecast for Technical Obsolescence in Computerised Tomography Equipment

Elsevier user license: Permitted: For non-commercial purposes: Read, print & download Text & data mine Translate the article Not Permitted: Reuse portions or extracts from the article in other works Redistribute or republish the final article Sell or re-use for commercial purposesTo estimate the useful life of Computerised Tomography Equipment (CT)Reyes Santias, F.; Vivas Consuelo, DJJ.; Ramos, M. (2012). Calculated Forecast for Technical Obsolescence in Computerised Tomography Equipment. Value in Health. 15(7):A318-A318. doi:10.1016/j.jval.2012.08.710SA318A31815

Predicting healthcare expenditure by multimorbidity groups

[EN] Objectives: This article has two main purposes. Firstly, to model the integrated healthcare expenditure for the entire population of a health district in Spain, according to multimorbidity, using Clinical Risk Groups (CRG). Secondly, to show how the predictive model is applied to the allocation of health budgets. Methods: The database used contains the information of 156,811 inhabitants in a Valencian Community health district in 2013. The variables were: age, sex, CRG's main health statuses, severity level, and healthcare expenditure. The two-part models were used for predicting healthcare expenditure. From the coefficients of the selected model, the relative weights of each group were calculated to set a case-mix in each health district. Results: Models based on multimorbidity-related variables better explained integrated healthcare expenditure. In the first part of the two-part models, a logit model was used, while the positive costs were modelled with a log-linear OLS regression. An adjusted R-2 of 46-49% between actual and predicted values was obtained. With the weights obtained by CRG, the differences found with the case-mix of each health district proved most useful for budgetary purposes. Conclusions: The expenditure models allowed improved budget allocations between health districts by taking into account morbidity, as opposed to budgeting based solely on population size.This work was supported by "Instituto de Salud Carlos III - Ministerio de Economia y Competitividad" and the European Union (FEDER funds) - FIS PI12/00037.Caballer-Tarazona, V.; Guadalajara Olmeda, MN.; Vivas-Consuelo, D. (2019). Predicting healthcare expenditure by multimorbidity groups. Health Policy. 123(4):427-434. https://doi.org/10.1016/j.healthpol.2019.02.002S427434123

Markov Models for Economic Evaluation in Osteoporosis Treatment

[EN] Osteoporosis is frequent in elderly people, causing bone fractures and lowering their quality of life. The costs incurred by these fractures constitute a problem for public health. Markov chains were used to carry out an incremental cost-utility analysis of the four main drugs used in Spain to treat osteoporosis (alendronate, risedronate, denosumab and teriparatide). We considered 14 clinical transition states, from starting osteoporotic treatment at the age of 50 until death or the age of 100. Cost-effectiveness was measured by quality adjusted life years (QALYs). The values used in the Markov model were obtained from the literature. Teriparatide is the cost-effective alternative in the treatment of osteoporosis in patients with fractures from the age of 50, establishing a payment threshold of 20,000 EUR/QALY. However, it is the most expensive therapy, not appearing cost-effective in cases that do not present fracture and in ages over 80 years with fracture. Alendronate and denosumab therapies are presented as cost-effective osteoporosis treatment alternatives depending on the age of onset and duration of treatment. From the perspective of cost-effectiveness, establishing a payment threshold of 20,000 EUR/QALY, teriparatide is the cost-effective alternative in patients with fracture from the age of 50 to 70 years old in Spain.Osca Guadalajara, M.; Díaz-Carnicero, J.; González-De Julián, S.; Vivas-Consuelo, D. (2021). Markov Models for Economic Evaluation in Osteoporosis Treatment. Mathematics. 9(18):1-20. https://doi.org/10.3390/math9182331S12091

COVID-19 Healthcare Planning: Predicting Mortality and the Role of the Herd Immunity Barrier in the General Population

[EN] Using a mathematical model for COVID-19 incorporating data on excess of mortality compared to the corresponding period of the previous year obtained from the daily monitoring of mortality in Spain (MoMo), the prediction of total number of casualties in Spain for the first outbreak has been computed. From this figure, and following a stepwise meta-analysis of available reports, the case fatality rate (CFR) and the infectious case fatality rate (IFR) for the outbreak have been estimated. As the impact of age on these rates is notable, it is proposed to include an age-related adjusted fatality ratio in future comparative analyses between studies, calculated by adjusting the results by risk ratio to a reference age band (e.g., 60-69). From the casualty figures, and the corresponding CFR and IFR ratios, the forecast of serologically positive cases in the general Spanish population has been estimated at approximately 1% (0.87-1.3%) of the samples. If the data are confirmed by the ongoing study of the Carlos III Institute, until a vaccine is found, the immunity acquired in the general population after the infectious outbreak is far from the 65-70% herd immunity required as a barrier for COVID-19.Marco-Franco, JE.; Guadalajara Olmeda, MN.; González-De Julián, S.; Vivas-Consuelo, D. (2020). COVID-19 Healthcare Planning: Predicting Mortality and the Role of the Herd Immunity Barrier in the General Population. Sustainability. 12(13):1-10. https://doi.org/10.3390/su12135228S1101213Mathematical modeling draws more accurate picture of coronavirus cases 2020https://www.eurekalert.org/pub_releases/2020-04/mcog-mmd041020.phpRed Nacional de Vigilancia Epidemiológica-[Spanish epidemiological surveillance network]https://www.isciii.es/QueHacemos/Servicios/VigilanciaSaludPublicaRENAVE/EnfermedadesTransmisibles/Documents/INFORMES/Informes%20COVID-19/Informe%20nº%2022.%20Situación%20de%20COVID-19%20en%20España%20a%2013%20de%20abril%20de%202020.pdfJung, S., Akhmetzhanov, A. R., Hayashi, K., Linton, N. M., Yang, Y., Yuan, B., … Nishiura, H. (2020). Real-Time Estimation of the Risk of Death from Novel Coronavirus (COVID-19) Infection: Inference Using Exported Cases. Journal of Clinical Medicine, 9(2), 523. doi:10.3390/jcm9020523Linton, N., Kobayashi, T., Yang, Y., Hayashi, K., Akhmetzhanov, A., Jung, S., … Nishiura, H. (2020). Incubation Period and Other Epidemiological Characteristics of 2019 Novel Coronavirus Infections with Right Truncation: A Statistical Analysis of Publicly Available Case Data. Journal of Clinical Medicine, 9(2), 538. doi:10.3390/jcm9020538Rajgor, D. D., Lee, M. H., Archuleta, S., Bagdasarian, N., & Quek, S. C. (2020). The many estimates of the COVID-19 case fatality rate. The Lancet Infectious Diseases, 20(7), 776-777. doi:10.1016/s1473-3099(20)30244-9Mizumoto, K., Kagaya, K., Zarebski, A., & Chowell, G. (2020). Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Eurosurveillance, 25(10). doi:10.2807/1560-7917.es.2020.25.10.2000180Wu, J. T., Leung, K., Bushman, M., Kishore, N., Niehus, R., de Salazar, P. M., … Leung, G. M. (2020). Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China. Nature Medicine, 26(4), 506-510. doi:10.1038/s41591-020-0822-7Hauser, A., Counotte, M. J., Margossian, C. C., Konstantinoudis, G., Low, N., Althaus, C. L., & Riou, J. (2020). Estimation of SARS-CoV-2 mortality during the early stages of an epidemic: a modeling study in Hubei, China, and six regions in Europe. doi:10.1101/2020.03.04.20031104Russell, T. W., Hellewell, J., Jarvis, C. I., van Zandvoort, K., Abbott, S., … Ratnayake, R. (2020). Estimating the infection and case fatality ratio for coronavirus disease (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess cruise ship, February 2020. Eurosurveillance, 25(12). doi:10.2807/1560-7917.es.2020.25.12.2000256Wu, Z., & McGoogan, J. M. (2020). Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China. JAMA, 323(13), 1239. doi:10.1001/jama.2020.2648Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., … Zhang, L. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet, 395(10223), 507-513. doi:10.1016/s0140-6736(20)30211-7Wang, X., Ma, Z., Ning, Y., Chen, C., Chen, R., Chen, Q., … Zhao, H. (2020). Estimating the case fatality ratio of the COVID-19 epidemic in China. doi:10.1101/2020.02.17.20023630Italian Task Force COVID-19. Epidemia COVID-19 [Covid-19 epidemic]https://www.epicentro.iss.it/coronavirus/bollettino/Bollettino-sorveglianza-integrata-COVID-19_26-marzo%202020.pdfUK coronavirus death toll reaches 1,789 amid data reporting concerns |World news| The Guardianhttps://www.theguardian.com/world/2020/mar/31/uk-coronavirus-death-toll-reaches-1789-amid-data-reporting-concernsCoronavirus-missing-deathshttps://www.nytimes.com/interactive/2020/04/21/world/coronavirus-missing-deaths.htmlLipsitch, M., Cohen, T., Cooper, B., Robins, J. M., Ma, S., James, L., … Murray, M. (2003). Transmission Dynamics and Control of Severe Acute Respiratory Syndrome. Science, 300(5627), 1966-1970. doi:10.1126/science.1086616Sanche, S., Lin, Y. T., Xu, C., Romero-Severson, E., Hengartner, N., & Ke, R. (2020). High Contagiousness and Rapid Spread of Severe Acute Respiratory Syndrome Coronavirus 2. Emerging Infectious Diseases, 26(7), 1470-1477. doi:10.3201/eid2607.200282WHO warns that few have developed antibodies to Covid-19https://www.theguardian.com/society/2020/apr/20/studies-suggest-very-few-have-had-covid-19-without-symptomsVerity, R., Okell, L. C., Dorigatti, I., Winskill, P., Whittaker, C., Imai, N., … Ferguson, N. M. (2020). Estimates of the severity of COVID-19 disease. doi:10.1101/2020.03.09.20033357Wong, J. Y., Kelly, H., Ip, D. K. M., Wu, J. T., Leung, G. M., & Cowling, B. J. (2013). Case Fatality Risk of Influenza A (H1N1pdm09). Epidemiology, 24(6), 830-841. doi:10.1097/ede.0b013e3182a67448Bendavid, E., Mulaney, B., Sood, N., Shah, S., Ling, E., Bromley-Dulfano, R., … Bhattacharya, J. (2020). COVID-19 Antibody Seroprevalence in Santa Clara County, California. doi:10.1101/2020.04.14.2006246

Impact of age and gender in the pharmaceutical expenditure of anxiolytics in primary health care

Elsevier user license: Permitted: For non-commercial purposes: Read, print & download Text & data mine Translate the article Not Permitted: Reuse portions or extracts from the article in other works Redistribute or republish the final article Sell or re-use for commercial purposesStudy the prescription of anxiolytics in Primary Health Care measured by the number of daily doses prescribed (DDD) to each patient (adjusting for age and gender) in order to quantify the pharmaceutical expenditure of anxiolytics.Guadalajara Olmeda, MN.; De La Poza, E.; Barrachina Martínez, I.; Vivas Consuelo, DJJ. (2011). Impact of age and gender in the pharmaceutical expenditure of anxiolytics in primary health care. Value in Health. 14(7):A300-A300. https://doi.org/10.1016/j.jval.2011.08.373SA300A30014

Simplified Mathematical Modeling of Uncertainty: Cost-Effectiveness of COVID-19 Vaccines in Spain

[EN] When exceptional situations such as the COVID-19 pandemic arise and reliable data is not available at decision-making times, estimation using mathematical models can provide a reasonable reckoning for health planning. We present a simplified model (static but with two-time references) for estimating the cost-effectiveness of the Covid-19 vaccine. A simplified model provides quick assessment of the upper bound of cost-effectiveness, as we illustrated with data from Spain, and allows for easy comparisons between countries. It may also provide useful comparisons among different vaccines at the marketplace, from the perspective of the buyer. From analysis of this information, key epidemiological figures, and costs of the disease for Spain have been estimated, based on mortality. The fatality value is a robust data that can alternatively be obtained from death registers, funeral homes, cemeteries, and crematoria. Our model estimates the cost-effectiveness ratio (ICER) to be 5,132 € (4,926 ¿ 5,276) as of 17 February 2021, based on the following assumptions/inputs: an estimated cost of 30 euros per dose (plus transport, storing, and administration), two doses per person, efficacy of 70% and coverage of 70% of the population. Even considering the possibility of some bias, this simplified model provides confirmation that vaccination against COVID-19 is highly cost-effective.Marco-Franco, JE.; Pita-Barros, P.; González-De Julián, S.; Sabat, I.; Vivas-Consuelo, D. (2021). Simplified Mathematical Modeling of Uncertainty: Cost-Effectiveness of COVID-19 Vaccines in Spain. Mathematics. 9(5):1-15. https://doi.org/10.3390/math90505661159

Data Envelopment Analysis Applications on Primary Health Care Using Exogenous Variables and Health Outcomes

[EN] A data envelopment analysis was used to evaluate the efficiency of 18 primary healthcare centres in a health district of the Valencian Community, Spain. Factor analysis was used as a first step in order to identify the most explanatory variables to be incorporated in the models. Included as variable inputs were the ratios of general practitioners, nurses, and costs; as output variables, those included were consultations, emergencies, avoidable hospitalisations, and prescription efficiency; as exogenous variables, those included were the percentage of population over 65 and a multimorbidity index. Confidence intervals were calculated using bootstrapping to correct possible biases. Efficient organisations within the set were identified, although the results depend on the models used and the introduction of exogenous variables. Pharmaceutical expenditure showed the greatest slack and room for improvement in its management. Data envelopment analysis allows an evaluation of efficiency that is focussed on achieving better results and a proper distribution and use of healthcare resources, although it needs the desired goals of the healthcare managers to be clearly identified, as the perspective of the analysis influences the results, as does including variables that measure the achievements and outcomes of the healthcare services.This research was funded by "Conselleria de Hacienda y Modelo Economico de la Comunitat Valenciana (Spain)", file number HIECPU/2019/1, in the context of the Project "Desarrollo de un Modelo para el analisis de la eficiencia en las Unidades Basicas de Salud de atencion primaria en un departamento de Salud perteneciente al mapa sanitario de la Comunidad Valenciana".González-De Julián, S.; Barrachina Martínez, I.; Vivas-Consuelo, D.; Bonet-Pla, Á.; Usó-Talamantes, R. (2021). Data Envelopment Analysis Applications on Primary Health Care Using Exogenous Variables and Health Outcomes. Sustainability. 13(3):1-18. https://doi.org/10.3390/su1303133711813

Probabilistic study of the effect of anti-epileptic drugs under uncertainty: Cost-effectiveness analysis

[EN] Epilepsy is one of the most ancient diseases. Despite the efforts of scientists and doctors to improve the quality of live of epileptic patients, the disease is still a mystery in many senses. Anti-epileptic drugs are fundamental to reduce epileptic seizures but it have some adverse effects, which influence the quality of life outcomes of the patients. In this paper, we study the effectiveness of anti-epileptic drugs taking into account the inherent uncertainty. We establish a model, which allows to represent the natural history of epilepsy, using Markov chains. After randomizing the mathematical model, we compute the first probability density function of the solution stochastic process applying the random variable transformation technique.We also take advantage of this method to determine the distribution of some key quantities in medical decision, such as the time until a certain proportion of the population remains in each state and the incremental cost-effectiveness ratio. The study is completed computing all these quantities using data available in the literature. In addition, regarding the incremental cost-effectiveness ratio, different third generation anti-epileptic treatments are compared with the Brivaracetam, a new third generation anti-epileptic drug.This work has been supported by the Spanish Ministerio de Economia, Industria y Competitividad (MINECO), the Agencia Estatal de Investigacion (AEI) and Fondo Europeo de Desarrollo Regional (FEDER UE) grant MTM2017-89664-P. Computations have been carried thanks to the collaboration of Raul San Julian Garces and Elena Lopez Navarro granted by European Union through the Operational Program of the European Regional Development Fund (ERDF)/European Social Fund (ESF) of the Valencian Community 2014-2020, grants GJIDI/2018/A/009 and GJIDI/2018/A/010, respectively.Barrachina Martínez, I.; Navarro-Quiles, A.; Ramos, M.; Romero, J.; Roselló, M.; Vivas-Consuelo, D. (2020). Probabilistic study of the effect of anti-epileptic drugs under uncertainty: Cost-effectiveness analysis. Mathematics. 8(7):1-19. https://doi.org/10.3390/math8071120S11987García-Ramos, R., García Pastor, A., Masjuan, J., Sánchez, C., & Gil, A. (2011). FEEN report on epilepsy in Spain. Neurología (English Edition), 26(9), 548-555. doi:10.1016/j.nrleng.2011.03.004Epilepsy http://www.who.int/mediacentre/factsheets/fs999/en/Población Estimada en España http://www.ine.es/inebaseDYN/cp30321Duncan, J. S., Sander, J. W., Sisodiya, S. M., & Walker, M. C. (2006). Adult epilepsy. The Lancet, 367(9516), 1087-1100. doi:10.1016/s0140-6736(06)68477-8Brodie, M. J. (2015). Practical Use of Newer Antiepileptic Drugs as Adjunctive Therapy in Focal Epilepsy. CNS Drugs, 29(11), 893-904. doi:10.1007/s40263-015-0285-4EPARs for Authorised Medicinal Products for Human Use Stelara http://www.emea.europa.eu/humandocs/Humans/EPAR/stelara/stelara.htmKristian, B., Wachtmeister, K., Stefan, F., & Forsgren, L. (2013). Retigabine as add-on treatment of refractory epilepsy - a cost-utility study in a Swedish setting. Acta Neurologica Scandinavica, 127(6), 419-426. doi:10.1111/ane.12077Martyn-St James, M., Glanville, J., McCool, R., Duffy, S., Cooper, J., Hugel, P., & Lane, P. W. (2012). The efficacy and safety of retigabine and other adjunctive treatments for refractory partial epilepsy: A systematic review and indirect comparison. Seizure, 21(9), 665-678. doi:10.1016/j.seizure.2012.07.011Cortés, J.-C., Navarro-Quiles, A., Romero, J.-V., & Roselló, M.-D. (2017). Randomizing the parameters of a Markov chain to model the stroke disease: A technical generalization of established computational methodologies towards improving real applications. Journal of Computational and Applied Mathematics, 324, 225-240. doi:10.1016/j.cam.2017.04.040Sonnenberg, F. A., & Beck, J. R. (1993). Markov Models in Medical Decision Making. Medical Decision Making, 13(4), 322-338. doi:10.1177/0272989x9301300409Barrachina-Martínez, I., Vivas-Consuelo, D., & Piera-Balbastre, A. (2017). Budget Impact Analysis of Brivaracetam Adjunctive Therapy for Partial-Onset Epileptic Seizures in Valencia Community, Spain. Clinical Drug Investigation, 38(4), 353-363. doi:10.1007/s40261-017-0615-zSullivan, S. D., Mauskopf, J. A., Augustovski, F., Jaime Caro, J., Lee, K. M., Minchin, M., … Shau, W.-Y. (2014). Budget Impact Analysis—Principles of Good Practice: Report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force. Value in Health, 17(1), 5-14. doi:10.1016/j.jval.2013.08.2291Cortés, J.-C., Navarro-Quiles, A., Romero, J.-V., & Roselló, M.-D. (2018). Some results about randomized binary Markov chains: theory, computing and applications. International Journal of Computer Mathematics, 97(1-2), 141-156. doi:10.1080/00207160.2018.1440290Prieto, L., Sacristán, J. A., Antoñanzas, F., Rubio-Terrés, C., Pinto, J. L., & Rovira, J. (2004). Análisis coste-efectividad en la evaluación económica de intervenciones sanitarias. Medicina Clínica, 122(13), 505-510. doi:10.1016/s0025-7753(04)74288-8Karlsson, G., & Johannesson, M. (1996). The Decision Rules of Cost-Effectiveness Analysis. PharmacoEconomics, 9(2), 113-120. doi:10.2165/00019053-199609020-00003Mulhern, B., Rowen, D., Snape, D., Jacoby, A., Marson, T., Hughes, D., … Brazier, J. (2014). Valuations of epilepsy-specific health states: a comparison of patients with epilepsy and the general population. Epilepsy & Behavior, 36, 12-17. doi:10.1016/j.yebeh.2014.04.011BOT Base de Datos del Medicamento https://botplusweb.portalfarma.com/Informe de Posicionamiento Terapéutico de Brivaracetam (Briviact) en Epilepsia https://www.aemps.gob.es/medicamentosUsoHumano/informesPublicos/docs/IPTbrivaracetam-Briviact-epilepsia.pdfSacristán, J. A., Oliva, J., Del Llano, J., Prieto, L., & Pinto, J. L. (2002). ¿Qué es una tecnología sanitaria eficiente en España? Gaceta Sanitaria, 16(4), 334-343. doi:10.1016/s0213-9111(02)71933-xBertram, M. Y., Lauer, J. A., De Joncheere, K., Edejer, T., Hutubessy, R., Kieny, M.-P., & Hill, S. R. (2016). Cost–effectiveness thresholds: pros and cons. Bulletin of the World Health Organization, 94(12), 925-930. doi:10.2471/blt.15.16441