Original Article
Cost-Effectiveness and Cost-Utility Analysis of Ingenol Mebutate Versus Diclofenac 3% and Imiquimod 5% in the Treatment of Actinic Keratosis in Spain
Análisis de coste-efectividad y coste-utilidad de ingenol mebutato versus diclofenaco 3% e imiquimod 5% en el tratamiento de la queratosis actínica en España
I. Elíasa, N. Ortega-Joaquína, P. de la Cuevab, L.J. del Pozoc, D. Moreno-Ramírezd, A. Boadae, M. Aguilarf, A. Miradag, E. Mosquerag, C. Gibbonsh, I. Oyagüeza,
Autor para correspondencia
a Pharmacoeconomics & Outcomes Research Iberia, Madrid, Spain
b Departamento de Dermatología, Hospital Universitario Infanta Leonor, Madrid, Spain
c Departamento de Dermatología, Hospital Universitario Son Espases, Mallorca, Spain
d Departamento de Dermatología, Hospital Universitario Virgen de la Macarena, Sevilla, Spain
e Departamento de Dermatología, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain
f Departamento de Dermatología, Hospital Costa del Sol, Marbella, Málaga, Spain
g Laboratorios LEO Pharma, S. A., Barcelona, Spain
h LEO Pharma, Berkshire, Reino Unido
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(A) Epidermal necrosis with vesicle formation. Melanin is found dispersed into the debris and remnants of pigmented keratinocytes (black arrows). Dermal inflammation with oedema, vasodilatation and erythrocyte extravasation is shown (H&E 100×). (B) Fragments of the tubules of nematocysts are seen in the stratum corneum (yellow arrows) (H&E 200×).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L.J. del Pozo, N. Knöpfel, A. Martín-Santiago, M.M. Escudero-Góngora, C. Saus, N. Izquierdo-Herce, A. Bauzà-Alonso" "autores" => array:7 [ 0 => array:2 [ "nombre" => "L.J." "apellidos" => "del Pozo" ] 1 => array:2 [ "nombre" => "N." "apellidos" => "Knöpfel" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Martín-Santiago" ] 3 => array:2 [ "nombre" => "M.M." "apellidos" => "Escudero-Góngora" ] 4 => array:2 [ "nombre" => "C." "apellidos" => "Saus" ] 5 => array:2 [ "nombre" => "N." "apellidos" => "Izquierdo-Herce" ] 6 => array:2 [ "nombre" => "A." 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Claves en el diagnóstico dermatoscópico" ] ] "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" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1050 "Ancho" => 1400 "Tamanyo" => 200627 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Lentigo maligna. A, Flat brown symmetric lesion with a diameter of 6<span class="elsevierStyleHsp" style=""></span>mm on the right cheek of an adult. B, Dermoscopic features: asymmetric pigmented follicular openings (black arrows).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L.A. Bollea-Garlatti, G.N. Galimberti, R.L. 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"apellidos" => "Oyagüez" "email" => array:1 [ 0 => "ioyaguez@porib.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:8 [ 0 => array:3 [ "entidad" => "Pharmacoeconomics & Outcomes Research Iberia, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Universitario Infanta Leonor, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Universitario Son Espases, Mallorca, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Universitario Virgen de la Macarena, Sevilla, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Departamento de Dermatología, Hospital Costa del Sol, Marbella, Málaga, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Laboratorios LEO Pharma, S. A., Barcelona, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "LEO Pharma, Berkshire, Reino Unido" "etiqueta" => "h" "identificador" => "aff0040" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Análisis de coste-efectividad y coste-utilidad de ingenol mebutato versus diclofenaco 3% e imiquimod 5% en el tratamiento de la queratosis actínica en España" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 937 "Ancho" => 1653 "Tamanyo" => 87006 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Scatterplot of the probabilistic sensitivity analysis results for ingenol mebutate vs imiquimod 5% for actinic keratosis lesions on the face and scalp.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Actinic keratosis (AK) manifests with red or skin-colored lesions with varying degrees of hyperkeratosis making them feel rough to the touch. Because sun exposure is the main—but not the only—risk factor for AK, the lesions are usually found in exposed areas of the body.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Fifteen percent of men and 6% of women in Europe develop AK,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">2</span></a> and prevalence rates of 18% in women and 34% in men over the age of 70 years have been reported.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">3</span></a> A Spanish epidemiologic study estimated that AK affects 23.5% of the population over the age of 45 years.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The risk of progression of AK to invasive carcinoma has been estimated at about 0.75% per lesion per year; an additional 0.53% accrues if there is a history of skin cancer.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">5</span></a> Extrapolating from these data, we can say that an immunocompetent patient with no history of skin cancer who has 8 AK lesions has a 5.8% chance of developing squamous cell carcinoma within 10 years.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Given the high prevalence of AK, this condition generates a considerable economic burden. In the United States skin cancer is among the 5 most costly cancer diagnoses.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Besides the carcinogenic potential of AK, the impact of skin diseases on quality of life must be considered.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">7</span></a> Therapies available to treat AK range from minimally invasive ones (such as cryotherapy or pharmacologic approaches) to more radical ones such as shave excision, electrodesiccation and curettage, laser surgery, and chemical exfoliation.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">8</span></a> More recent approaches include the treatment of field cancerization with photodynamic therapy or topical treatments such as 5-fluorouracil (0.5% and 5%), ingenol mebutate (0.015% and 0.05%), diclofenac (3%), and imiquimod (2.5%, 3.75%, and 5%); indications vary according to the area of the body being treated. The aims of these treatments are to eliminate visible lesions (an outcome termed clearance), prevent progression to invasive carcinoma, and halt the development of new lesions. Recurrence is common among treated patients, however.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Given the budget constraints that have arisen during periods of economic difficulty and the breadth of the therapeutic arsenal at our disposal for AK, there is increased interest in information that can guide the proper selection of treatments and application of resources. Pharmacoeconomics—or the assessment of health technologies—takes the approach of rigorously analyzing the costs and heath benefits of therapeutic alternatives. This approach should be understood as a useful complement to decision-making based purely on clinical information.</p><p id="par0035" class="elsevierStylePara elsevierViewall">This study aimed to estimate the efficiency of ingenol mebutate in the treatment of patients with AK in Spain.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">We used a Markov model with 3 health states (AK, clearance, and death) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) to simulate the course of disease in a hypothetical patient cohort.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The entire cohort (mean age, 73 years) had AK lesions at the start of the simulation<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">4</span></a>; potentially they could remain in that state or transition to a state of either clearance or death.</p><p id="par0050" class="elsevierStylePara elsevierViewall">By allowing for changes between the states of clearance and AK, the model recognizes the possibility of recurrence, or the reappearance of lesions. Available evidence estimates an annual recurrence rate of 20%,<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">10</span></a> regardless of treatment received.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In this analysis the possibility of death refers not to death caused by AK per se but rather death from any cause occurring in the general population.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">11</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Death was included as a health state in the interest of estimating the efficiency of therapy not only in terms of cost-effectiveness but also cost-utility, which estimates the cost per quality-adjusted life-years (QALY) gained.</p><p id="par0065" class="elsevierStylePara elsevierViewall">This analytical approach was developed with the help of a panel of experts consisting of 5 dermatologists from hospitals in different areas of Spain; these experts are authors of this article. The Delphi method was used to achieve consensus. Questionnaires to collect the information and data needed to execute the model were drafted in Word and Excel and piloted. Responses were compared and discussed at a meeting at which the participants came to agreement about the parameters to include.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Available Therapies</span><p id="par0070" class="elsevierStylePara elsevierViewall">The comparators were the pharmacologic treatments authorized (in addition to ingenol mebutate) for treating AK on the face and scalp and/or the trunk and extremities: diclofenac 3% and imiquimod 5%.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Given that not all the therapies included are indicated for application on all locations, we posed 3 scenarios: one comparing ingenol mebutate to diclofenac 3% to treat face and scalp lesions, another comparing ingenol mebutate to diclofenac 3% to treat lesions on the trunk and extremities, and another comparing ingenol mebutate to imiquimod 5% for lesions on the face and scalp.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Perspective, Time Horizon, and Discount Rate</span><p id="par0080" class="elsevierStylePara elsevierViewall">The perspective adopted was that of the Spanish National Health Service (NHS); therefore, we took only direct health costs into consideration. The time horizon of 5 years was considered sufficient to identify and quantify changes in patients’ conditions, taking into consideration not only the initial treatment but also possible medium-term recurrences. A discount rate of 3% was applied to costs and outcomes.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Health Outcomes</span><p id="par0085" class="elsevierStylePara elsevierViewall">The measure of treatment effectiveness was total clearances gained. Because no direct comparisons (head-to-head trials) were available, we obtained data from indirect comparisons (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) using Bucher's method.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Clinical trials of AK treatments that used clearance rates as the outcome measure were identified by a search of the literature. Specific trials found for the ingenol mebutate vs diclofenac 3% scenario<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">13–15</span></a> were grouped according to part of the body treated (face and scalp or trunk and extremities). In contrast, the trials we found for the scenario comparing ingenol mebutate to imiquimod 5%<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">16,17</span></a> only treated the face and scalp because the summary of product characteristics for imiquimod<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a> does not recognize its use on the trunk and extremities.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The panel of experts consulted during the development process for this study estimated an adherence-to-treatment rate of 90% for ingenol mebutate and 60% for the other treatments; their opinion was that lack of adherence reduced treatment efficacy by 50%.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Measurement of Results Obtained</span><p id="par0100" class="elsevierStylePara elsevierViewall">The incremental cost-effectiveness and cost-utility ratios (ICER and ICUR, respectively) were calculated as the cost differentials between ingenol mebutate and each comparator divided by the difference in health outcomes between the compared treatments. The denominators for the ICER and ICUR were clearances and QALY gained (ingenol mebutate vs each comparator).</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Utility Values</span><p id="par0105" class="elsevierStylePara elsevierViewall">QALY values were estimated by multiplying life-years gained by a factor termed utility, which represents patients’ preferences for certain states of health. The utility variable was expressed on a scale from 0 to 1, where 1 corresponds to perfect health and 0 represents death.</p><p id="par0110" class="elsevierStylePara elsevierViewall">For this analysis we considered that a value of 0.986 indicated that a treatment was useful for patients with AK; a value of 1 was assigned if complete clearance was observed.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Resource Use and Associated Costs</span><p id="par0115" class="elsevierStylePara elsevierViewall">Different doses were entered into the analysis of costs according to part of the body being treated (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">The estimated total cost for using each treatment included the retail price of the drug itself plus the cost of visits to a dermatologist for adverse events and follow-up. All costs were expressed in euro values for 2015 (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><p id="par0125" class="elsevierStylePara elsevierViewall">Drug costs were calculated on the basis of the retail price,<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a> to which we applied the deduction established by Royal Decree-Law 8/2010.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">21</span></a> Resources used (number of visits to the dermatologist during the follow-up period) were identified and their cost estimated based on the judgment of the expert panel (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Unit costs of the resources used were obtained from published NHS databases.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">22</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Sensitivity Analyses</span><p id="par0130" class="elsevierStylePara elsevierViewall">Deterministic and probabilistic sensitivity analyses were used to study the influence of different parameters on the robutness of the results.</p><p id="par0135" class="elsevierStylePara elsevierViewall">In the deterministic sensitivity analysis the effects of the following parameter modifications were explored: discount rate (0% and 5%), time horizon (30 years), treatment adherence rate (setting the rate of nonadherence set to 10% for all treatments), efficacy (decreasing the value for nonadherence to 33.3%), emergency visits related to adverse events (setting additional emergency visits required to 5% of patients using ingenol mebutate, 2% of those using diclofenac, and 10% of those using imiquimod), additional use of an antibiotic (for patients requiring an additional dermatology visit in 30% of those on ingenol mebutate, 5% of those on diclofenac, and 100% of those on imiquimod), and the use of generic imiquimod and imiquimod 3.75% (including the price differences) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">In the probabilistic sensitivity analysis the values for the parameters were modified simultaneously according to the beta, log-normal, and gamma distributions by means of 1000 Monte Carlo simulations.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><p id="par0145" class="elsevierStylePara elsevierViewall">At the end of the 5-year simulation, ingenol mebutate had demonstrated more effectiveness than diclofenac 3%. In face and scalp treatments, ingenol mebutate gained 0.192 more clearances and 0.011 QALY more than diclofenac 3%; in trunk and extremity treatments, ingenol mebutate led to 0.129 more clearances than diclofenac 3% and 0.007 additional QALY (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">The total 5-year costs were lower with ingenol mebutate than with diclofenac 3%; the incremental costs, and hence savings, were–€297.60 in the treatment of face and scalp AKs and −€222.66 in the treatment of trunk and extremity lesions.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Ingenol mebutate provided better health outcomes in terms of clearances and QALY at lower costs than diclofenac 3% for the treatment of AK on both locations studied.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Ingenol mebutate was also more effective than imiquimod 5%, based on 0.032 additional clearances and 0.002 additional QALY in the treatment of face and scalp AK. The total cost per patient of treatment was €551.50 with ingenol mebutate and €527.89 with imiquimod 5%.</p><p id="par0165" class="elsevierStylePara elsevierViewall">The resulting ICER and ICUR were €728.64/clearance gained and €10<span class="elsevierStyleHsp" style=""></span>906/QALY gained with ingenol mebutate vs imiquimod 5%.</p><p id="par0170" class="elsevierStylePara elsevierViewall">Assuming a-willingness-to-pay threshold of €30<span class="elsevierStyleHsp" style=""></span>000/QALY,<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">23</span></a> which is used as a reference value in most economic evaluations of health technologies in Spain,<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">24</span></a> treatment with ingenol mebutate would be considered an efficient strategy in comparison with diclofenac 3% or imiquimod 5%.</p><p id="par0175" class="elsevierStylePara elsevierViewall">The deterministic sensitivity analyses confirmed the model's consistency in the 3 scenarios studied. Ingenol mebutate emerged as a dominant option vs diclofenac 3% in all the sensitivity analyses regardless of body site being treated (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> and <a class="elsevierStyleCrossRef" href="#sec0090">Appendix BS1, online supplementary material</a>). Our findings also show that treatment of face and scalp AK with ingenol mebutate could be considered a cost-effective strategy in comparison with imiquimod 5%, given that it proved efficient in 80% of the sensitivity analysis (applying an efficiency threshold of €30<span class="elsevierStyleHsp" style=""></span>000/QALY<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a>). The ICUR exceeded that efficiency threshold in 2 situations: when a 33% (vs 50%) decrease in efficacy was assumed to be associated with nonadherence and when the cost of generic imiquimod 5% was used rather than the price of the brand-name product (<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a> and <a class="elsevierStyleCrossRef" href="#sec0090">Appendix BS2, online supplementary material</a>).</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">The results of the probabilistic sensitivity analysis are shown grafically using a scatterplot, where each point represents an ICUR for one of the 1000 simulations performed (<a class="elsevierStyleCrossRefs" href="#fig0010">Figs. 2 and 3</a>). Thus, when ingenol mebutate was compared with diclofenac 3%, 96% of the simulations of face and scalp and 91% of trunk and extremity treatments had ICURs under the €30<span class="elsevierStyleHsp" style=""></span>000/QALY threshold<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). In the scenario comparing ingenol mebutate to imiquimod 5%, 80% of the simulations were cost-effective (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0185" class="elsevierStylePara elsevierViewall">The high population prevalence of AK has led to a substantial economic burden for health systems. It is therefore important to find more effective treatment alternatives that can reduce the duration of disease and frequency of recurrences, thereby lowering treatment-associated costs and contributing to NHS sustainability.</p><p id="par0190" class="elsevierStylePara elsevierViewall">The patient profile in this disease, which appears in persons of advanced age, makes it difficult to choose the best therapeutic alternative. An indicator like the ICER, which brings together information on costs and health outcomes in addition to treatment durations, can be very helpful horizons, given that shorter treatments increase patient adherence<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">25</span></a> and play a direct role in increasing efficacy. Even though the 3 treatments we evaluated (ingenol mebutate, diclofenac 3%, and imiquimod 5%) give the expected skin responses, quality of life improvements are evident in AK patients treated with ingenol mebutate because they are not affected by side effects that diminish that quality or satisfaction.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">26</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">A strength of this study is that it is the only cost-effectiveness analysis of AK treatments used currently in Spain (with the exception of photodynamic therapy) that has been validated by a panel of experts. One other pharmacoeconomic analysis of AK treatment in Spain appeared recently,<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">27</span></a> but the alternatives considered were not those of the present analysis. Two studies done in Scotland<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">28</span></a> and Finland<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">29</span></a> compared ingenol mebutate to diclofenac 3% and imiquimod 5%. Both studies looked at treatment from their NHS perspectives and both concluded that ingenol mebutate was a cost-effective choice<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">22</span></a> (higher costs and better health outcomes) and dominant<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">23</span></a> (lower costs and better health outcomes) vs diclofenac 3%, and also cost-effective vs imiquimod 5%.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">23</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">The present study also reviewed data from the various clinical trials of the treatments studied, grouping them according to the body sites where they are applied. This approach meant that we assessed efficacy as conservatively as possible in a situation requiring indirect comparisons between treatments.</p><p id="par0205" class="elsevierStylePara elsevierViewall">The consistency of the model was supported by sensitivity analyses applying modifications of parameters that might have compromised the analysis: in spite of the numerous permutations considered, the results still showed that ingenol mebutate is a dominant treatment option in comparison with diclofenac 3% (i.e., ingenol mebutate offers greater efficacy at a lower incremental cost) and cost-effective in comparison with imiquimod 5%. These results were consistent across all the analyses except the 2 mentioned previously. The parameter modifications that had the greatest impact on sensitivity analyses were the decrease in assumed level of efficacy in nonadherent patients and the lower cost of using the generic formulation of imiquimod. With those modifications the ICUR exceeded the threshold of €30<span class="elsevierStyleHsp" style=""></span>000/QALY<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a> (and €2500/clearance).</p><p id="par0210" class="elsevierStylePara elsevierViewall">This study has certain limitations that should be taken into account when interpreting the results. Among them is the theoretical nature inherent to any modeling study, as projections may not faithfully represent the reality of routine clinical practice. We chose to use a Markov model that allowed us to incorporate repeated events such as the possibility of recurrent AK episodes in a single patient. However, other approaches to economic evaluation of interventions in this disease have used decision trees, which can be easier to interpret intuitively. The possibility of transitioning to a state of death may seem farfetched in a disease that is not associated with high mortality, but it was considered necessary for estimating QALY (providing a survival endpoint for the cost-utility threshold). In any case, the model and the determination of the states of health contemplated were constrained by the availability of clinical data for carrying out the simulation.</p><p id="par0215" class="elsevierStylePara elsevierViewall">Another possible limitation concerns the method used to designate efficacy variables. Given the absence of clinical trials directly comparing the treatment alternatives we studied, we used indirect methods to infer levels of efficacy. Indirect comparisons, can be more biased than direct ones and may overestimate an intervention's efficacy.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">30</span></a> However, the use of indirect treatment comparisons has become a standard, widely recognized approach to use when direct evidence from randomized trials is unavailable or inadequate. Indirect comparisons can provide useful, complementary information about the relative efficacy of interventions if and only if they have high internal and external validity and the clinical trials are similar.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">31</span></a> They also provide useful evidence for judiciously selecting the best treatment.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">32</span></a> Nevertheless, the comparisons made in this study should ideally be repeated using data from direct treatment comparisons.</p><p id="par0220" class="elsevierStylePara elsevierViewall">Another limitation stems from our use of data from studies performed in other countries; this decision was necessary because this type of study has not been done in Spain. The utility values used in the model were derived from a study done in the United Kingdom.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">13</span></a> They were validated by our panel of experts, who considered these values to be representative of the population of patients with AK in Spain. They are also those defined for the EuroQol 5-dimensions questionnaire and do not vary across different European countries.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">In spite of these limitations, this economic evaluation can facilitate prescribing physicians’ decisions given that ingenol mebutate is a dominant therapy with lower costs for the NHS and leads to more effective health outcomes for patients in comparison with diclofenac 3%. In addition, if €30<span class="elsevierStyleHsp" style=""></span>000/QALY is accepted as a valid threshold of efficiency,<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a> ingenol mebutate can be considered a cost-effective alternative compared to imiquimod 5% for treating AK lesions on the face and scalp in Spain.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Ethical Disclosures</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Protection of human and animal subjects</span><p id="par0230" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Data confidentiality</span><p id="par0235" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data are disclosed in this article.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Right to privacy and informed consent</span><p id="par0240" class="elsevierStylePara elsevierViewall">The authors declare that no private patient data are disclosed in this article.</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conflicts of Interest</span><p id="par0245" class="elsevierStylePara elsevierViewall">I. Elías, N. Ortega-Joaquín, and I. Oyagüez, who are employed by PORIB, a consultancy firm specializing in cost-effectiveness analyses of health care technologies, received an unconditional grant from LEO-Pharma to carry out the analyses for this paper.</p><p id="par0250" class="elsevierStylePara elsevierViewall">A. Miranda, E. Mosquera, and C. Gibbons are employees of LEO-Pharma.</p><p id="par0255" class="elsevierStylePara elsevierViewall">P. de la Cueva, L. J. del Pozo, D. Moreno-Ramírez, A. Boada, and M. Aguilar participated as expert consultants to validate the parameters used for this analysis; the unconditional grant they received from LEO-Pharma for their participation at no time influenced their opinions or the conclusions they drew.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:18 [ 0 => array:3 [ "identificador" => "xres824820" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec821295" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres824819" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec821296" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Available Therapies" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Perspective, Time Horizon, and Discount Rate" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Health Outcomes" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Measurement of Results Obtained" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Utility Values" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Resource Use and Associated Costs" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Sensitivity Analyses" ] 13 => array:2 [ "identificador" => "sec0050" "titulo" => "Results" ] 14 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 15 => array:3 [ "identificador" => "sec0060" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "Right to privacy and informed consent" ] ] ] 16 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflicts of Interest" ] 17 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-11-20" "fechaAceptado" => "2016-03-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec821295" "palabras" => array:3 [ 0 => "Ingenol mebutate" 1 => "Cost-effectiveness analysis" 2 => "Actinic keratosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec821296" "palabras" => array:3 [ 0 => "Ingenol mebutato" 1 => "Análisis coste-efectividad" 2 => "Queratosis actínica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To perform a cost-effectiveness and cost-utility analysis of ingenol mebutate in the treatment of actinic keratosis in Spain.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We used an adapted Markov model to simulate evolution of a cohort of patients (mean age, 73 years) with actinic keratosis over a 5-year period. The comparators were diclofenac 3% and imiquimod 5%. The analysis was performed from the perspective of the Spanish National Health System based on direct costs (2015 retail price plus value added tax less the mandatory discount). A panel of experts estimated resources, taking unit costs from national databases. An annual discount rate of 3% was applied. Deterministic and probabilistic sensitivity analyses were performed.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The effectiveness of ingenol mebutate—with 0.192 and 0.129 more clearances gained in treatments for face and scalp lesions and trunk and extremity lesions, respectively—was superior to diclofenac's. The total costs of treatment with ingenol mebutate were lower at € 551.50 (face and scalp) and € 622.27 (trunk and extremities) than the respective costs with diclofenac (€ 849.11 and € 844.93). The incremental cost-effectiveness and cost-utility ratios showed that ingenol mebutate was a dominant strategy vs diclofenac. Ingenol mebutate also proved to be more effective than imiquimod, based on 0.535 and 0.503 clearances, and total costs of € 551.50 and € 527.89 for the two drugs, respectively. The resulting incremental cost-effectiveness ratio was € 728.64 per clearance gained with ingenol mebutate vs imiquimod.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Ingenol mebutate was a dominant treatment option vs diclofenac and was efficient vs imiquimod (i.e., more effective at a higher cost, achieving an incremental cost-utility ratio of<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>€<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>000/quality-adjusted life-years).</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "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">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Realizar un análisis coste-efectividad y coste-utilidad de ingenol mebutato en el tratamiento de la queratosis actínica en España.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realizó la adaptación de un modelo de Markov que simuló una cohorte de pacientes (73 años de media) con queratosis actínica en un horizonte temporal de 5 años. Los comparadores fueron diclofenaco 3% e imiquimod 5%. El análisis se desarrolló desde la perspectiva del Sistema Nacional de Salud, incluyendo costes directos sanitarios (PVP<span class="elsevierStyleInf">IVA</span> con la deducción obligatoria, € 2015). La estimación de recursos se llevó a cabo por un panel de expertos y los costes unitarios se obtuvieron de bases de datos de costes nacionales. La tasa de descuento considerada fue del 3% anual. Se realizaron análisis de sensibilidad determinísticos y probabilísticos.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Ingenol mebutato fue más eficiente frente a diclofenaco, con 0,192 aclaramientos incrementales en la cara y el cuero cabelludo y 0,129 en el tronco y las extremidades. Los costes totales fueron de 551,50<span class="elsevierStyleHsp" style=""></span>€ y 622,27<span class="elsevierStyleHsp" style=""></span>€ comparados con 849,11<span class="elsevierStyleHsp" style=""></span>€ y 844,93<span class="elsevierStyleHsp" style=""></span>€ en diclofenaco (cara y cuero cabelludo y tronco y extremidades, respectivamente). Es decir, ingenol mebutato es una alternativa de tratamiento dominante frente a diclofenaco 3%. Ingenol mebutato también mostró una mayor eficacia frente a imiquimod 5%, con 0,535 vs 0,503 aclaramientos ganados, y unos costes totales de 551,50<span class="elsevierStyleHsp" style=""></span>€ vs 527,89<span class="elsevierStyleHsp" style=""></span>€, siendo la relación coste-efectividad incremental resultante de 728,64<span class="elsevierStyleHsp" style=""></span>€/aclaramiento adicional.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Ingenol mebutato resultó ser una estrategia dominante vs diclofenaco, y eficiente, es decir, presentó mayor efectividad y mayores costes (relación coste-utilidad incremental inferior a 30.000<span class="elsevierStyleHsp" style=""></span>€/AVAC) vs imiquimod.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "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="npar0020">Please cite this article as: Elías I, Ortega-Joaquín N, de la Cueva P, del Pozo LJ, Moreno-Ramírez D, Boada A, et al. Análisis de coste-efectividad y coste-utilidad de ingenol mebutato versus diclofenaco 3% e imiquimod 5% en el tratamiento de la queratosis actínica en España. Actas Dermosifiliogr. 2016;107:498–508.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0265" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0090" ] ] ] ] "multimedia" => array:10 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1712 "Ancho" => 2545 "Tamanyo" => 123953 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Markov model.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1212 "Ancho" => 1628 "Tamanyo" => 148450 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Scatterplot of the probabilistic sensitivity analysis results for ingenol mebutate vs diclofenac 3% for actinic keratosis lesions on the face and scalp and the trunk and extremities. QALY refers to quality-adjusted life-years.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 937 "Ancho" => 1653 "Tamanyo" => 87006 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Scatterplot of the probabilistic sensitivity analysis results for ingenol mebutate vs imiquimod 5% for actinic keratosis lesions on the face and scalp.</p>" ] ] 3 => 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="spar0065" class="elsevierStyleSimplePara elsevierViewall">Abbreviation: CI, confidence interval; RD, risk difference.</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" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical Trial \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">Ingenol Mebutate vs Placebo, RD (95% CI) \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">Diclofenac 3% vs Placebo, RD (95% CI) \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">Indirect RD (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Indirect comparison of ingenol mebutate vs diclofenac 3% on the face and scalp</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PEP005-016 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">34.8 (26.3–43.3) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PEP005-025 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42.0 (33.0–51.0) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rivers et al.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">13</span></a> (2002) \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="left" valign="top">23.1 (7.9–38.3) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Stockfleth et al.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">14</span></a> (2011) \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="left" valign="top">16.6 (6.8–26.4) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Wolf et al.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">15</span></a> (2001) \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="left" valign="top">28.3 (12.4–44.3) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Grouped \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">34.8 (29.5–46.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.6 (13.2–27.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17.6 (6.18–29.01) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Indirect comparison of ingenol mebutate vs diclofenac 3% on the trunk and extremities</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PEP005-014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23.1 (14.5–31.8) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PEP005-028 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37.1 (26.6–47.7) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Rivers et al.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">13</span></a> (2002) \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="left" valign="top">23.1 (7.9–38.3) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Stockfleth et al.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">14</span></a> (2011) \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="left" valign="top">16.6 (6.8–26.4) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Wolf et al.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">15</span></a> (2001) \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="left" valign="top">28.3 (12.4–44.3) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Grouped \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29.6 (20.1–39.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.6 (13.2–27.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.0 (−3.0–21.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Indirect comparison of ingenol mebutate vs imiquimod 5% on the face and scalp</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PEP005-016 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">34.8 (26.3–43.3) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PEP005-025 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42.0 (33.0–51.0) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Jorizzo et al.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">16</span></a> (2007) \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="left" valign="top">39.0 (28.2–49.8) \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Korman et al.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a> (2005) \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="left" valign="top">41.1 (34.1–48.2) \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></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Grouped \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38.2 (29.5–46.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40.5 (34.6–46.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−2.3 (−12.8–8.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Treatment comparisons</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Efficacy</span></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ingenol mebutate vs diclofenac 3% (face and scalp)</td><td class="td" title="table-entry " align="left" valign="top">Ingenol mebutate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diclofenac 3% \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">42.24% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24.64% \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><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ingenol mebutate vs diclofenac 3% (trunk and extremities)</td><td class="td" title="table-entry " align="left" valign="top">Ingenol mebutate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diclofenac 3% \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">34.07% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25.07% \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><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ingenol mebutate vs imiquimod 5% (face and scalp)</td><td class="td" title="table-entry " align="left" valign="top">Ingenol mebutate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Imiquimod 5% \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">42.24% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44.54% \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 => "xTab1386712.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Results of Indirect Comparisons of Ingenol Mebutate vs Diclofenac 3% and Imiquimod 5%.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "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" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Active Ingredient \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">Presentation \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">Retail Price (With VAT) \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">Retail Price (With VAT and Deduction) \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">Dosing \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Drug costs</span></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ingenol mebutate</td><td class="td" title="table-entry " align="left" valign="top">Picato<span class="elsevierStyleSup">®</span> 150<span class="elsevierStyleHsp" style=""></span>μg/g gel, 3 single-dose tubes of 0.47<span class="elsevierStyleHsp" style=""></span>g \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€105.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€97.33<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 tube/d for 3 consecutive days once a year \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">Picato<span class="elsevierStyleSup">®</span> 500<span class="elsevierStyleHsp" style=""></span>μg/g gel, 2 single-dose tubes of 0.47<span class="elsevierStyleHsp" style=""></span>g \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€109.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€101.24<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 tube/d for 2 consecutive days once a year \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diclofenac 3%</td><td class="td" title="table-entry " align="left" valign="top">Solaraze<span class="elsevierStyleSup">®</span> 30<span class="elsevierStyleHsp" style=""></span>mg/g gel, 1 tube of 25<span class="elsevierStyleHsp" style=""></span>g \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€30.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€28.28<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>g/d for 90 consecutive days once a year \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">Solaraze<span class="elsevierStyleSup">®</span> 30<span class="elsevierStyleHsp" style=""></span>mg/g gel, 1 tube of 60<span class="elsevierStyleHsp" style=""></span>g \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€73.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€67.87<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Imiquimod 5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Aldara<span class="elsevierStyleSup">®</span> 50<span class="elsevierStyleHsp" style=""></span>mg/g cream, 24 packets of 250<span class="elsevierStyleHsp" style=""></span>mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€125.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€116.49<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 packet/d for 12 consecutive days once a year \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Resources</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Specialist visits \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Number \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unit Cost \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">Total Visits</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dermatologist, first visit \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€57.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="left" valign="top">3 (regardless of treatment)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dermatologist, follow-up visit \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€31.43 \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 => "xTab1386711.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Deduction, 7.5%.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Deduction, 15.0%.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Use of Resources and Spending in Base Cases.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "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" title="table-head " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Drug Costs</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Active Ingredient \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">Presentation \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">Retail Price (Plus VAT) \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">Retail Price (Plus VAT and Deduction<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> \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">Fusidic acid \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fusidic acid ISDIN<span class="elsevierStyleSup">®</span> (20<span class="elsevierStyleHsp" style=""></span>mg/g cream 15<span class="elsevierStyleHsp" style=""></span>g) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€2.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€2.56 \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">Imiquimod 3.75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Zyclara<span class="elsevierStyleSup">®</span> 3.75%, 37.5<span class="elsevierStyleHsp" style=""></span>mg/g cream, 28 packets of 250<span class="elsevierStyleHsp" style=""></span>mg each \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€134.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€125.09 \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">Imiquimod 5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Imunocare<span class="elsevierStyleSup">®</span> 50<span class="elsevierStyleHsp" style=""></span>mg/g cream, 12 packets of 250<span class="elsevierStyleHsp" style=""></span>mg each \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€50.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€46.60 \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">Mupirocin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mupirocin ISDIN<span class="elsevierStyleSup">®</span> 20<span class="elsevierStyleHsp" style=""></span>mg/g ointment, 15<span class="elsevierStyleHsp" style=""></span>g \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€3.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€3.76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Adverse-event-related costs</span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="center" valign="top">Emergency care</td><td class="td" title="table-entry " colspan="2" align="center" valign="top">€132.04</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1386709.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">7.5% deduction according to Royal Decree–Law 8/2010.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Costs Applied in the Sensitivity Analyses.</p>" ] ] 6 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: ICER, incremental cost-effectiveness ratio; ICUR, incremental cost-utility ratio; QALY, quality-adjusted life-years.</p>" "tablatextoimagen" => array:2 [ 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" title="table-head " colspan="7" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Ingenol Mebutate vs Diclofenac 3%</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Face and Scalp</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Trunk and Extremities</th></tr><tr title="table-row"><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">Total Costs \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">Total Clearances \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">Total 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">Total Costs \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">Total Clearances \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">Total QALY \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">Ingenol mebutate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€551.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.536 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.451 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€622.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.477 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.447 \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">Diclofenac 3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€849.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.343 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.440 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€844.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.347 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.440 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1386708.png" ] ] 1 => 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" title="table-head " colspan="6" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Ingenol Mebutate vs Imiquimod 5%</th></tr><tr title="table-row"><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">Total Costs \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">Total Clearances \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">Total 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">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" style="border-bottom: 2px solid black">ICUR \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">Ingenol mebutate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€551.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.536 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.451 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">€728.64/clearance</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">€10<span class="elsevierStyleHsp" style=""></span>906/QALY</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Imiquimod 5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€527.89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.503 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.449 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1386713.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Results for Base Case.</p>" ] ] 7 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: ICER, incremental cost-effectiveness ratio; ICUR, incremental cost-utility ratio.</p>" "tablatextoimagen" => array:2 [ 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" title="table-head " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Face and Scalp</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Parameters \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">Base Case \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">Sensitivity Analysis \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">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" style="border-bottom: 2px solid black">ICUR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Base case, ingenol mebutate vs diclofenac 3% (face and scalp)</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Emergency department visits for adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="center" valign="top">Ingenol mebutate: 5%; diclofenac 3%: 2%</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Antibiotic treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="center" valign="top">Ingenol mebutate: 30%; diclofenac 3%: 5%</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Efficacy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ingenol mebutate: 42.24%; diclofenac 3%: 24.64% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">33% less effective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Discount rate on costs and health outcomes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0%<br>5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Time horizon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Adherence to treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ingenol mebutate nonadherence: 10%;<br>Diclofenac 3% nonadherence: 40% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Both treatments nonadherence: 10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1386710.png" ] ] 1 => 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" title="table-head " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Trunk and Extremities</th></tr><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Results \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">Base Case \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">Sensitivity Analysis \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">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" style="border-bottom: 2px solid black">ICUR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Base case, ingenol mebutate vs diclofenac 3% (trunk and extremities)</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Emergency department visits for adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="center" valign="top">Ingenol mebutate: 5%; diclofenac 3%: 5%</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Antibiotic treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="center" valign="top">Ingenol mebutate: 30%; diclofenac 3%: 5%</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Efficacy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ingenol mebutate: 34.07%; diclofenac 3%: 25.07% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">33% less effective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Discount rate on costs and health outcomes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0%<br>5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Time horizon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \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">Adherence to treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ingenol mebutate nonadherence: 10%;<br>Diclofenac 3% nonadherence: 40% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Both treatments nonadherence: 10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1386707.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Deterministic Sensitivity Analysis Results for Ingenol Mebutate vs Diclofenac 3% (Face and Scalp and Trunk and Extremities).</p>" ] ] 8 => array:8 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at6" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: ICER, incremental cost-effectiveness ratio; ICUR, incremental cost-utility ratio; QALY, quality-adjusted life-years.</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" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Results \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">Base Case \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">Sensitivity Analysis \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">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" style="border-bottom: 2px solid black">ICUR \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top">Base case, ingenol mebutate vs imiquimod 5% (face and scalp)</td><td class="td" title="table-entry " align="left" valign="top">€728.65/clearance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€10 906/QALY \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">Emergency department visits for adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="center" valign="top">Ingenol mebutate: 5%<br>Imiquimod 5%: 10%</td><td class="td" title="table-entry " align="left" valign="top">€148.56/clearance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€2224/QALY \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">Antibiotic treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="center" valign="top">Ingenol mebutate: 30%<br>Imiquimod 5%: 100%</td><td class="td" title="table-entry " align="left" valign="top">€667.43/clearance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€9990/QALY \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">Efficacy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ingenol mebutate: 42.24%<br>Imiquimod 5%: 44.54% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">33% less effective<br>Considering equal efficacy for both treatments \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€2567.73/clearance<br>€222.57/clearance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€37<span class="elsevierStyleHsp" style=""></span>428/QALY<br>€3377/QALY \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">Price \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Imiquimod 5% (Aldara<span class="elsevierStyleSup">®</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Considering the cost of Imunocare<span class="elsevierStyleSup">®</span> but not of Aldara<span class="elsevierStyleSup">®</span><br>Considering the cost of Zyclara<span class="elsevierStyleSup">®</span> but not Aldara<span class="elsevierStyleSup">®</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€2786.33/clearance<br>Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€41<span class="elsevierStyleHsp" style=""></span>706/QALY<br>Dominant \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">Discount rate on costs and health outcomes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0%<br>5% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€745.61/clearance (0%)<br>€718.27/clearance (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€10<span class="elsevierStyleHsp" style=""></span>475/QALY (0%)<br>€11<span class="elsevierStyleHsp" style=""></span>195/QALY (5%) \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">Time horizon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€1242.93/clearance \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">€7997/QALY \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">Adherence to treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ingenol mebutate nonadherence: 10%;<br>Diclofenac 3% nonadherence: 40% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Both treatments nonadherence: 10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dominant \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1386706.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Deterministic Sensitivity Analysis Results for Ingenol Mebutate vs Imiquimod 5% (Face and Scalp).</p>" ] ] 9 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 134377 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:33 [ 0 => array:3 [ "identificador" => "bib0170" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of actinic keratoses" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A.C. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 9 | 10 | 19 |
| 2024 Octubre | 76 | 40 | 116 |
| 2024 Septiembre | 63 | 23 | 86 |
| 2024 Agosto | 105 | 47 | 152 |
| 2024 Julio | 106 | 32 | 138 |
| 2024 Junio | 95 | 33 | 128 |
| 2024 Mayo | 90 | 33 | 123 |
| 2024 Abril | 101 | 31 | 132 |
| 2024 Marzo | 98 | 27 | 125 |
| 2024 Febrero | 83 | 30 | 113 |
| 2024 Enero | 81 | 35 | 116 |
| 2023 Diciembre | 74 | 15 | 89 |
| 2023 Noviembre | 81 | 26 | 107 |
| 2023 Octubre | 123 | 23 | 146 |
| 2023 Septiembre | 71 | 26 | 97 |
| 2023 Agosto | 33 | 12 | 45 |
| 2023 Julio | 41 | 46 | 87 |
| 2023 Junio | 27 | 13 | 40 |
| 2023 Mayo | 47 | 23 | 70 |
| 2023 Abril | 38 | 29 | 67 |
| 2023 Marzo | 50 | 23 | 73 |
| 2023 Febrero | 35 | 28 | 63 |
| 2023 Enero | 40 | 24 | 64 |
| 2022 Diciembre | 69 | 33 | 102 |
| 2022 Noviembre | 44 | 24 | 68 |
| 2022 Octubre | 27 | 33 | 60 |
| 2022 Septiembre | 29 | 42 | 71 |
| 2022 Agosto | 24 | 32 | 56 |
| 2022 Julio | 28 | 56 | 84 |
| 2022 Junio | 20 | 26 | 46 |
| 2022 Mayo | 51 | 35 | 86 |
| 2022 Abril | 47 | 35 | 82 |
| 2022 Marzo | 53 | 65 | 118 |
| 2022 Febrero | 44 | 64 | 108 |
| 2022 Enero | 34 | 60 | 94 |
| 2021 Diciembre | 41 | 48 | 89 |
| 2021 Noviembre | 49 | 47 | 96 |
| 2021 Octubre | 60 | 57 | 117 |
| 2021 Septiembre | 41 | 42 | 83 |
| 2021 Agosto | 51 | 32 | 83 |
| 2021 Julio | 34 | 36 | 70 |
| 2021 Junio | 67 | 42 | 109 |
| 2021 Mayo | 40 | 56 | 96 |
| 2021 Abril | 114 | 80 | 194 |
| 2021 Marzo | 68 | 33 | 101 |
| 2021 Febrero | 43 | 37 | 80 |
| 2021 Enero | 35 | 21 | 56 |
| 2020 Diciembre | 62 | 21 | 83 |
| 2020 Noviembre | 24 | 32 | 56 |
| 2020 Octubre | 31 | 15 | 46 |
| 2020 Septiembre | 40 | 17 | 57 |
| 2020 Agosto | 20 | 23 | 43 |
| 2020 Julio | 26 | 20 | 46 |
| 2020 Junio | 41 | 41 | 82 |
| 2020 Mayo | 36 | 16 | 52 |
| 2020 Abril | 22 | 21 | 43 |
| 2020 Marzo | 27 | 23 | 50 |
| 2020 Febrero | 5 | 0 | 5 |
| 2019 Abril | 5 | 8 | 13 |
| 2019 Marzo | 0 | 4 | 4 |
| 2019 Febrero | 1 | 0 | 1 |
| 2019 Enero | 1 | 0 | 1 |
| 2018 Diciembre | 3 | 0 | 3 |
| 2018 Noviembre | 1 | 0 | 1 |
| 2018 Octubre | 1 | 0 | 1 |
| 2018 Septiembre | 5 | 0 | 5 |
| 2018 Febrero | 23 | 5 | 28 |
| 2018 Enero | 40 | 12 | 52 |
| 2017 Diciembre | 41 | 10 | 51 |
| 2017 Noviembre | 46 | 12 | 58 |
| 2017 Octubre | 35 | 12 | 47 |
| 2017 Septiembre | 32 | 15 | 47 |
| 2017 Agosto | 30 | 15 | 45 |
| 2017 Julio | 26 | 9 | 35 |
| 2017 Junio | 47 | 11 | 58 |
| 2017 Mayo | 34 | 18 | 52 |
| 2017 Abril | 39 | 14 | 53 |
| 2017 Marzo | 28 | 14 | 42 |
| 2017 Febrero | 15 | 19 | 34 |
| 2017 Enero | 22 | 8 | 30 |
| 2016 Diciembre | 55 | 19 | 74 |
| 2016 Noviembre | 48 | 23 | 71 |
| 2016 Octubre | 33 | 22 | 55 |
| 2016 Julio | 3 | 4 | 7 |
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