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Brief report
Cost-effectiveness analysis of sofosbuvir-simeprevir regimens for chronic hepatitis C genotype 1 patients with advanced fibrosis
Análisis coste-efectividad del tratamiento de la hepatitis C crónica con sofosbuvir-simeprevir en pacientes con genotipo 1 y fibrosis avanzada
Javier Mara,b,
Corresponding author
javier.marmedina@osakidetza.net

Corresponding author.
, Lorea Mar-Barrutiac, Vicente Gimeno-Ballesterd,e, Ramón San Miguele,f
a Unidad de Gestión Sanitaria, Hospital Alto Deba, Mondragón, Guipúzcoa, Spain
b Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Bilbao, Spain
c Facultad de Medicina, Universidad de Barcelona, Barcelona, Spain
d Servicio de Farmacia, Hospital Universitario Miguel Servet, Zaragoza, Spain
e Facultad de Farmacia, Universidad de Granada, Granada, Spain
f Servicio de Farmacia, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain
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Given the limited resources&#44; treatment has been prioritized for patients with higher risk of morbidity and mortality &#40;patients with advanced fibrosis or compensated cirrhosis&#44; transplant recipients and those with severe extrahepatic manifestations of HCV infection&#41;&#44; since they obtain greater benefit in the short term&#46;<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 &#40;F3-F4&#41;&#44; providing high efficiency and preventing from adverse effects associated with interferon treatment&#46; The regimen used has varied depending on the duration &#40;12 or 24 weeks&#41; and the addition or not of ribavirin&#46;<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&#46;<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&#44; which is a measure of contrast between increased costs and increased effectiveness among the different therapeutic alternatives compared&#46;<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&#44; in which the effectiveness of the SIM-SOF combination was analyzed&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> It included patients with genotype 1 and with advanced fibrosis &#40;F3-F4&#41;&#46;<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&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Markov model<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> was used&#44; previously described and validated<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6&#44;7</span></a> to estimate the costs and clinical outcomes from the start of treatment&#46; In this model&#44; the natural history of hepatitis C was simulated&#44; including death from liver disease or any other causes &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; using the TreeAge Pro 2014 software&#46; The patient&#39;s life was used as time horizon to estimate quality-adjusted life years &#40;QALY&#41; and costs&#46; The treatment cohort population was defined in accordance with the average characteristics of patients in the clinical trials&#44; 50 years old&#44; and assuming a distribution of 50&#37; of patients in F3 and another 50&#37; in F4&#46; The discount rate applied was 3&#37;&#46;<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 &#8364;40&#44;000<span class="elsevierStyleHsp" style=""></span>per QALY&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">4&#44;8</span></a> This model is fully described in the technical annex attached&#44; available online&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Given the absence of comparator arm in the COSMOS study&#44; the standard of care was used as an alternative for genotype 1 with F3-F4 fibrosis consisting of triple therapy with peginterferon&#44; ribavirin and a generic protease inhibitor resulting from combining boceprevir with telaprevir&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">7&#44;9</span></a> This treatment provided a 72&#37; sustained viral response with an overall laboratory sale price of &#8364;33&#44;000<span class="elsevierStyleHsp" style=""></span>&#46;</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 &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; 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&#44; a sensitivity analysis reduced the price by 50&#37;&#46; Cost estimates considered a SOF regimen 400<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; SIM 150<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; and ribavirin dosage depending on body weight&#46; Health resources costs associated to disease progression were obtained from hospitals in the Basque Health Service in 2013&#46;</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&#44;7</span></a> for the various stages of chronic liver disease &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; This model also considered the loss of quality of life associated with treatment &#40;disutility&#41; as a result of the adverse effects&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">6&#44;7</span></a> To analyze the uncertainty of results the following was conducted&#58; &#40;a&#41; sensitivity analysis by varying the discount &#40;0&#8211;5&#37;&#41;&#44; &#40;b&#41; effectiveness of the SOF-SIM &#40;&#8722;5&#37;&#41; combination and &#40;c&#41; the baseline cohort &#40;100&#37; F3 and 100&#37; F4&#41; and probabilistic sensitivity analysis &#40;ASP&#41;&#44; which is the method recommended by the NICE&#46; All of this was conducted with pharmacy costs reduced by 50&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">4&#8211;7</span></a> The PSA analyzes simultaneously the impact on the results of parametric uncertainty associated with the evidence available on effectiveness&#44; utilities&#44; hospital costs and the transition probabilities among different stages&#46;</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&#46; The 12-week regimens are below &#8364;40&#46;000<span class="elsevierStyleHsp" style=""></span>per QALY threshold with the official price&#44; and even cheaper with the price calculated using a 50&#37; discount over the price of drugs&#46; Probabilistic analysis showed consistent results&#44; and in the 12-week regimens the percentage of efficient simulations or below the &#8364;40&#46;000<span class="elsevierStyleHsp" style=""></span>per QALY threshold ranged from 95 to 99&#37;&#46; As in other studies&#44; the variable with the greatest impact in the univariate analysis was the discount&#46;</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&#44; which is below &#8364;40&#46;000<span class="elsevierStyleHsp" style=""></span>per QALY&#44; considered as the efficiency threshold in our environment&#46;<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&#44; we can state that they are well below official prices as a result of the discount policies of pharmaceutical companies&#46; Thus&#44; the calculation with a 50&#37; discount can be used as a reference of the effectiveness level&#46; On the contrary&#44; and despite the 50&#37; discount&#44; the 24-week regimen shows a value in the limit of the willingness to pay used in the Spanish medical literature&#46;<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&#44; as it would ensure that a 24-week treatment would be effective&#46;</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&#44; Social Services and Equality&#44; as it includes patients with METAVIR F3 and F4 fibrosis&#46; In addition&#44; these indications are consistent with the data collected by GeSIDA guidelines released in February 2015&#46;<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&#44; including SOF-SIM combination&#44; is considered cost-effective&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">10&#44;11</span></a> The real problem from the economic point of view is the impact on the budget&#44; as expressed in the Strategic Plan for addressing hepatitis C approved by the National Health System&#46; Discovering DAAs has provided a treatment as significant as penicillin in addressing bacterial infection&#46; The problem is that their high prices do not allow to treat all patients when diagnosed&#46; Therefore&#44; the criterion of priority applied has been the severity of chronic liver disease associated&#46;</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&#46;</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&#46;</p></span></span>"
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    "fechaRecibido" => "2015-05-04"
    "fechaAceptado" => "2015-09-03"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
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          "palabras" => array:4 [
            0 => "Hepatitis C"
            1 => "Sofosbuvir"
            2 => "Simeprevir"
            3 => "Cost-effectiveness"
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          "clase" => "keyword"
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          "identificador" => "xpalclavsec657457"
          "palabras" => array:4 [
            0 => "Hepatitis C"
            1 => "Sofosbuvir"
            2 => "Simeprevir"
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        "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&#44; according to the results of the COSMOS trial&#46;</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&#46; In the model&#44; 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&#46;</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 &#8364;40&#44;000 per quality-adjusted life year&#46; On the contrary&#44; despite the 50&#37; cost reduction&#44; the 24-weeks regimen demonstrated a limited level of efficiency when compared with the willingness to pay used in the Spanish medical literature&#46;</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&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este estudio fue medir la relaci&#243;n coste-efectividad del tratamiento con simeprevir y sofosbuvir en pacientes con hepatitis C cr&#243;nica genotipo 1 y grados de fibrosis F3-F4&#44; de acuerdo con los resultados del ensayo cl&#237;nico COSMOS&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se utiliz&#243; un modelo de Markov para estimar los costes y los resultados cl&#237;nicos desde el comienzo del tratamiento&#46; Usando como horizonte temporal toda la vida del paciente&#44; en el modelo se simul&#243; la progresi&#243;n de la enfermedad entre los diferentes estados de salud de la enfermedad hep&#225;tica cr&#243;nica asociada a la hepatitis C&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los reg&#237;menes de 12 semanas se situaron por debajo del umbral de 40&#46;000<span class="elsevierStyleHsp" style=""></span>&#8364;&#47;a&#241;o de vida ajustado por calidad&#46; Por el contrario&#44; aun con una reducci&#243;n del 50&#37; del coste de adquisici&#243;n&#44; el r&#233;gimen de 24 semanas demostr&#243; un nivel de eficiencia en el l&#237;mite del requerido por la disponibilidad a pagar utilizada en la literatura m&#233;dica espa&#241;ola&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este &#250;ltimo dato justificar&#237;a la introducci&#243;n de un coste igual para la duraci&#243;n de 12 y 24 semanas&#44; asegurando la eficiencia del tratamiento de duraci&#243;n prolongada&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Mar J&#44; Mar-Barrutia L&#44; Gimeno-Ballester V&#44; San Miguel R&#46; An&#225;lisis coste-efectividad del tratamiento de la hepatitis C cr&#243;nica con sofosbuvir-simeprevir en pacientes con genotipo 1 y fibrosis avanzada&#46; Med Clin &#40;Barc&#41;&#46; 2016&#59;146&#58;61&#8211;64&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">PSA&#58; probabilistic sensitivity analysis &#40;percentage of simulations below the &#8364;40&#46;000 per QALY threshold&#41;&#59; QALY&#58; quality-adjusted life year&#59; Comparator&#58; triple therapy&#59; Cosmos 1&#58; 24 weeks<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>ribavirin regimen&#59; Cosmos 2&#58; 24 weeks&#59; Cosmos 3&#58; 12 weeks<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>ribavirin&#59; Cosmos 4&#58; 12 weeks ICER&#58; incremental cost-effectiveness ratio&#59; SVR&#58; sustained viral response&#46;</p>"
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                  <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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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&#47;QALY with -50&#37; 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&nbsp;\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&nbsp;\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">&#37;&nbsp;\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">&nbsp;\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&nbsp;\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&nbsp;\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&#47;QALY&nbsp;\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">&#37;&nbsp;\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>&#8722;<span class="elsevierStyleHsp" style=""></span>50&#37;&nbsp;\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&#37;&nbsp;\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&#37;&nbsp;\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>&#8722;<span class="elsevierStyleHsp" style=""></span>5&#37;&nbsp;\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&#37;&nbsp;\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&#37;&nbsp;\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&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">139&#44;296&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;028&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">151&#44;276&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">111&#44;778&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&#44;681&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&#44;962&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">78&#44;334&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&#44;657&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&#44;688&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#44;263&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">149&#44;178&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83&#44;825&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">89&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&#44;686&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#44;336&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&#44;106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&#44;499&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&#44;779&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&#44;556&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81&#44;628&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&#44;849&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">99&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#44;729&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5909&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&#44;945&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&#44;404&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#44;991&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#44;945&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">81&#44;478&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&#44;682&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#44;645&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5870&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#44;852&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;115&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&#44;207&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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Article information
ISSN: 23870206
Original language: English
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

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