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array:24 [ "pii" => "S2387020616301851" "issn" => "23870206" "doi" => "10.1016/j.medcle.2015.09.005" "estado" => "S300" "fechaPublicacion" => "2016-01-15" "aid" => "3406" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2015" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2016;146:61-4" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0025775315005709" "issn" => "00257753" "doi" => "10.1016/j.medcli.2015.09.019" "estado" => "S300" "fechaPublicacion" => "2016-01-15" "aid" => "3406" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2016;146:61-4" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 41 "formatos" => array:2 [ "HTML" => 18 "PDF" => 23 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original breve</span>" "titulo" => "Análisis coste-efectividad del tratamiento de la hepatitis C crónica con sofosbuvir-simeprevir en pacientes con genotipo 1 y fibrosis avanzada" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "61" "paginaFinal" => "64" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Cost-effectiveness analysis of sofosbuvir-simeprevir regimens for chronic hepatitis C genotype 1 patients with advanced fibrosis" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2028 "Ancho" => 1632 "Tamanyo" => 136490 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Modelo conceptual de la historia natural de la enfermedad hepática asociada al virus de la hepatitis C.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Javier Mar, Lorea Mar-Barrutia, Vicente Gimeno-Ballester, Ramón San Miguel" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Javier" "apellidos" => "Mar" ] 1 => array:2 [ "nombre" => "Lorea" "apellidos" => "Mar-Barrutia" ] 2 => array:2 [ "nombre" => "Vicente" "apellidos" => "Gimeno-Ballester" ] 3 => array:2 [ "nombre" => "Ramón" "apellidos" => "San Miguel" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020616301851" "doi" => "10.1016/j.medcle.2015.09.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616301851?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315005709?idApp=UINPBA00004N" "url" => "/00257753/0000014600000002/v1_201601130113/S0025775315005709/v1_201601130113/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020616301425" "issn" => "23870206" "doi" => "10.1016/j.medcle.2015.07.003" "estado" => "S300" "fechaPublicacion" => "2016-01-15" "aid" => "3372" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2016;146:65-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial article</span>" "titulo" => "Post-thrombotic syndrome: A pending issue" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "65" "paginaFinal" => "66" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome postrombótico: una asignatura pendiente" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Francisco Gabriel Botella" "autores" => array:1 [ 0 => array:2 [ "nombre" => "Francisco" "apellidos" => "Gabriel Botella" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775315004522" "doi" => "10.1016/j.medcli.2015.07.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315004522?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616301425?idApp=UINPBA00004N" "url" => "/23870206/0000014600000002/v1_201605240650/S2387020616301425/v1_201605240650/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2387020616300560" "issn" => "23870206" "doi" => "10.1016/j.medcle.2015.05.048" "estado" => "S300" "fechaPublicacion" => "2016-01-15" "aid" => "3359" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2016;146:55-60" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Early intensive treatment improves outcomes in patients with glomerular hyperfiltration and type 2 diabetes" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "55" "paginaFinal" => "60" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "El tratamiento intensivo precoz mejora los resultados en pacientes con hiperfiltración glomerular y diabetes tipo 2" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1633 "Ancho" => 1606 "Tamanyo" => 157593 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Kaplan•Meier survival analysis of the risk of doubling creatinine according to baseline isotopic GFR and UAE over a mean of 17 years of follow-up. The only difference was observed between baseline isotopic GFR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>120<span class="elsevierStyleHsp" style=""></span>mL/min/1.73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span> and baseline UAE<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h and the other three groups (LogRank 0.004). Isotopic GFR, isotopic glomerular filtration rate; UAE, urinary albumin excretion.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Maria-Isabel Troya, Josep Bonet, Isabel Salinas, Ferran Torres, Jordi Bonal, Anna Sanmartí, Ramón Romero" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Maria-Isabel" "apellidos" => "Troya" ] 1 => array:2 [ "nombre" => "Josep" "apellidos" => "Bonet" ] 2 => array:2 [ "nombre" => "Isabel" "apellidos" => "Salinas" ] 3 => array:2 [ "nombre" => "Ferran" "apellidos" => "Torres" ] 4 => array:2 [ "nombre" => "Jordi" "apellidos" => "Bonal" ] 5 => array:2 [ "nombre" => "Anna" "apellidos" => "Sanmartí" ] 6 => array:2 [ "nombre" => "Ramón" "apellidos" => "Romero" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0025775315004017" "doi" => "10.1016/j.medcli.2015.05.016" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315004017?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616300560?idApp=UINPBA00004N" "url" => "/23870206/0000014600000002/v1_201605240650/S2387020616300560/v1_201605240650/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Brief report</span>" "titulo" => "Cost-effectiveness analysis of sofosbuvir-simeprevir regimens for chronic hepatitis C genotype 1 patients with advanced fibrosis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "61" "paginaFinal" => "64" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Javier Mar, Lorea Mar-Barrutia, Vicente Gimeno-Ballester, Ramón San Miguel" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Javier" "apellidos" => "Mar" "email" => array:1 [ 0 => "javier.marmedina@osakidetza.net" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Lorea" "apellidos" => "Mar-Barrutia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "Vicente" "apellidos" => "Gimeno-Ballester" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 3 => array:3 [ "nombre" => "Ramón" "apellidos" => "San Miguel" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Unidad de Gestión Sanitaria, Hospital Alto Deba, Mondragón, Guipúzcoa, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Bilbao, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Farmacia, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Facultad de Farmacia, Universidad de Granada, Granada, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Farmacia, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Análisis coste-efectividad del tratamiento de la hepatitis C crónica con sofosbuvir-simeprevir en pacientes con genotipo 1 y fibrosis avanzada" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2026 "Ancho" => 1628 "Tamanyo" => 141636 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Conceptual model of the natural history of liver disease associated with hepatitis C virus.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Treatment of hepatitis C virus (HCV) infection is experiencing continuing progress in recent years, obtaining sustained viral responses over 90%.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> However, its high price limits its widespread use. Therefore, the economic evaluation of all clinical scenarios is becoming a determining factor in the incorporation process into clinical practice.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In HCV infected patients with high degree of fibrosis, the use of free-interferon schemes with direct acting antivirals (DAAs), such as Simeprevir (SIM) and sofosbuvir (SOF), is recommended. Given the limited resources, treatment has been prioritized for patients with higher risk of morbidity and mortality (patients with advanced fibrosis or compensated cirrhosis, transplant recipients and those with severe extrahepatic manifestations of HCV infection), since they obtain greater benefit in the short term.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The SIM-SOF combination is indicated in patients with HCV genotype 1 with high levels of fibrosis (F3-F4), providing high efficiency and preventing from adverse effects associated with interferon treatment. The regimen used has varied depending on the duration (12 or 24 weeks) and the addition or not of ribavirin.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of the study was to measure the cost-effectiveness of SOF-SIM treatment in patients with HCV genotype 1 and levels of F3-F4 fibrosis according to COSMOS clinical trial results.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methodology</span><p id="par0025" class="elsevierStylePara elsevierViewall">A cost-effectiveness analysis was conducted to calculate the incremental cost-effectiveness ratio, which is a measure of contrast between increased costs and increased effectiveness among the different therapeutic alternatives compared.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The basis of the study was COSMOS clinical trial, in which the effectiveness of the SIM-SOF combination was analyzed.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> It included patients with genotype 1 and with advanced fibrosis (F3-F4).<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Patients in each cohort were randomized to receive SIM-SOF with or without ribavirin for 12 or 24 weeks.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Markov model<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> was used, previously described and validated<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6,7</span></a> to estimate the costs and clinical outcomes from the start of treatment. In this model, the natural history of hepatitis C was simulated, including death from liver disease or any other causes (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), using the TreeAge Pro 2014 software. The patient's life was used as time horizon to estimate quality-adjusted life years (QALY) and costs. The treatment cohort population was defined in accordance with the average characteristics of patients in the clinical trials, 50 years old, and assuming a distribution of 50% of patients in F3 and another 50% in F4. The discount rate applied was 3%.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> The perspective applied was that of the Spanish National Health System assuming an effectiveness threshold in €40,000<span class="elsevierStyleHsp" style=""></span>per QALY.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">4,8</span></a> This model is fully described in the technical annex attached, available online.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Given the absence of comparator arm in the COSMOS study, the standard of care was used as an alternative for genotype 1 with F3-F4 fibrosis consisting of triple therapy with peginterferon, ribavirin and a generic protease inhibitor resulting from combining boceprevir with telaprevir.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">7,9</span></a> This treatment provided a 72% sustained viral response with an overall laboratory sale price of €33,000<span class="elsevierStyleHsp" style=""></span>.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Drug costs were estimated depending on the dosage and treatment regimen included in the clinical trial and the data sheet from the laboratory sale price (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Since the acquisition of both drugs in our environment is subject to considerable discount compared to the official price due to the competition among the therapeutic alternatives, a sensitivity analysis reduced the price by 50%. Cost estimates considered a SOF regimen 400<span class="elsevierStyleHsp" style=""></span>mg/day, SIM 150<span class="elsevierStyleHsp" style=""></span>mg/day, and ribavirin dosage depending on body weight. Health resources costs associated to disease progression were obtained from hospitals in the Basque Health Service in 2013.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The model included health-related adjustment for quality of life<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6,7</span></a> for the various stages of chronic liver disease (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). This model also considered the loss of quality of life associated with treatment (disutility) as a result of the adverse effects.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6,7</span></a> To analyze the uncertainty of results the following was conducted: (a) sensitivity analysis by varying the discount (0–5%), (b) effectiveness of the SOF-SIM (−5%) combination and (c) the baseline cohort (100% F3 and 100% F4) and probabilistic sensitivity analysis (ASP), which is the method recommended by the NICE. All of this was conducted with pharmacy costs reduced by 50%.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">4–7</span></a> The PSA analyzes simultaneously the impact on the results of parametric uncertainty associated with the evidence available on effectiveness, utilities, hospital costs and the transition probabilities among different stages.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the results for the four branches of the COSMOS clinical trial. The 12-week regimens are below €40.000<span class="elsevierStyleHsp" style=""></span>per QALY threshold with the official price, and even cheaper with the price calculated using a 50% discount over the price of drugs. Probabilistic analysis showed consistent results, and in the 12-week regimens the percentage of efficient simulations or below the €40.000<span class="elsevierStyleHsp" style=""></span>per QALY threshold ranged from 95 to 99%. As in other studies, the variable with the greatest impact in the univariate analysis was the discount.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">The main contribution of our paper is to establish the cost-effectiveness ratio of the 12-week SIM-SOF combination, which is below €40.000<span class="elsevierStyleHsp" style=""></span>per QALY, considered as the efficiency threshold in our environment.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> Despite the difficulty to know the actual cost of medicines for the health services of the autonomous communities, we can state that they are well below official prices as a result of the discount policies of pharmaceutical companies. Thus, the calculation with a 50% discount can be used as a reference of the effectiveness level. On the contrary, and despite the 50% discount, the 24-week regimen shows a value in the limit of the willingness to pay used in the Spanish medical literature.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> This last data would justify to use the same cost for the 12 and 24-week treatment, as it would ensure that a 24-week treatment would be effective.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The clinical profile of the study patients is consistent with the indication of the strategic plan for hepatitis C released by the Ministry of Health, Social Services and Equality, as it includes patients with METAVIR F3 and F4 fibrosis. In addition, these indications are consistent with the data collected by GeSIDA guidelines released in February 2015.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">This study is consistent with other papers published in international medical literature in which treating hepatitis C with new DAAs, including SOF-SIM combination, is considered cost-effective.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">10,11</span></a> The real problem from the economic point of view is the impact on the budget, as expressed in the Strategic Plan for addressing hepatitis C approved by the National Health System. Discovering DAAs has provided a treatment as significant as penicillin in addressing bacterial infection. The problem is that their high prices do not allow to treat all patients when diagnosed. Therefore, the criterion of priority applied has been the severity of chronic liver disease associated.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Funding</span><p id="par0075" class="elsevierStylePara elsevierViewall">This study has been conducted with the resources of the services involved and it has not received funding from any public or private entity.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interests</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors report no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres644388" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec657456" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres644387" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec657457" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methodology" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-05-04" "fechaAceptado" => "2015-09-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec657456" "palabras" => array:4 [ 0 => "Hepatitis C" 1 => "Sofosbuvir" 2 => "Simeprevir" 3 => "Cost-effectiveness" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec657457" "palabras" => array:4 [ 0 => "Hepatitis C" 1 => "Sofosbuvir" 2 => "Simeprevir" 3 => "Coste-efectividad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The aim of this study was to measure the cost-effectiveness of the treatment with simeprevir and sofosbuvir in chronic hepatitis C genotype 1 patients with F3-F4 levels of fibrosis, according to the results of the COSMOS trial.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A Markov model was used to estimate the costs and clinical outcomes from the start of therapy. In the model, the progression was simulated alongside the different health states of the chronic liver disease associated with chronic hepatitis C using whole life as time-horizon.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The 12-weeks treatment schemes was below the threshold of €40,000 per quality-adjusted life year. On the contrary, despite the 50% cost reduction, the 24-weeks regimen demonstrated a limited level of efficiency when compared with the willingness to pay used in the Spanish medical literature.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This finding would support the introduction of a flat rate in the price of drugs without taking into account the duration of treatment to ensure that treatment with 24 weeks was efficient.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este estudio fue medir la relación coste-efectividad del tratamiento con simeprevir y sofosbuvir en pacientes con hepatitis C crónica genotipo 1 y grados de fibrosis F3-F4, de acuerdo con los resultados del ensayo clínico COSMOS.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se utilizó un modelo de Markov para estimar los costes y los resultados clínicos desde el comienzo del tratamiento. Usando como horizonte temporal toda la vida del paciente, en el modelo se simuló la progresión de la enfermedad entre los diferentes estados de salud de la enfermedad hepática crónica asociada a la hepatitis C.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los regímenes de 12 semanas se situaron por debajo del umbral de 40.000<span class="elsevierStyleHsp" style=""></span>€/año de vida ajustado por calidad. Por el contrario, aun con una reducción del 50% del coste de adquisición, el régimen de 24 semanas demostró un nivel de eficiencia en el límite del requerido por la disponibilidad a pagar utilizada en la literatura médica española.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este último dato justificaría la introducción de un coste igual para la duración de 12 y 24 semanas, asegurando la eficiencia del tratamiento de duración prolongada.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Mar J, Mar-Barrutia L, Gimeno-Ballester V, San Miguel R. Análisis coste-efectividad del tratamiento de la hepatitis C crónica con sofosbuvir-simeprevir en pacientes con genotipo 1 y fibrosis avanzada. Med Clin (Barc). 2016;146:61–64.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0090" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0040" ] ] ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2026 "Ancho" => 1628 "Tamanyo" => 141636 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Conceptual model of the natural history of liver disease associated with hepatitis C virus.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">PSA: probabilistic sensitivity analysis (percentage of simulations below the €40.000 per QALY threshold); QALY: quality-adjusted life year; Comparator: triple therapy; Cosmos 1: 24 weeks<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ribavirin regimen; Cosmos 2: 24 weeks; Cosmos 3: 12 weeks<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>ribavirin; Cosmos 4: 12 weeks ICER: incremental cost-effectiveness ratio; SVR: sustained viral response.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Alternative \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Drug cost \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">SVR \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Disutility \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Overall cost \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Effectiveness \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">ICER \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">PSA \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="6" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">ICER sensitivity analysis in euro/QALY with -50% cost</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Unit \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Euros \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Euros \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">QALY \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Euro/QALY \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cost<span class="elsevierStyleHsp" style=""></span>−<span class="elsevierStyleHsp" style=""></span>50% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Discount 0% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Discount 5% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Effectiveness<span class="elsevierStyleHsp" style=""></span>−<span class="elsevierStyleHsp" style=""></span>5% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">F3 100% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">F4 100% \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cosmos 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">139,296 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.028 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">151,276 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">111,778 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52,681 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23,962 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">78,334 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59,657 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46,688 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60,263 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cosmos 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">138,996 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.028 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">149,178 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83,825 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">89% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38,686 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17,336 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59,106 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42,499 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34,779 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44,556 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cosmos 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69,648 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">81,628 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33,849 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">99% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13,729 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5909 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24,945 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18,404 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13,991 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16,945 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cosmos 4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69,498 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">81,478 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33,682 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13,645 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5870 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24,831 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18,316 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13,921 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16,852 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Comparator \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33,483 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.115 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51,207 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1062185.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Results and sensitivity analysis of cost-effectiveness analysis in accordance with the alternative to Cosmos clinical trial and drug prices.</p>" ] ] 2 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 616854 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.P. 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