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Impact of the implementation of a protocol for the adequate and safe use of tumor markers
Impacto de la aplicación de un protocolo para el uso adecuado y seguro de marcadores tumorales
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Therefore, tools have been developed to facilitate decision-making, algorithms, recommendations or guidelines on clinical practice.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> This preventive approach is unusual. It would be desirable to have a more systemic vision of safe procedures and practices, covering risks and repercussions for the patient, as it should be in the use of tumor markers (TMs).<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2–4</span></a> Since their discovery, their number and use has evolved considerably. The easy measurement, the lower cost and their popularity have made them become routine test.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,6</span></a> However, sometimes the selection of the TMs as a diagnostic test is inadequate, implying undesirable consequences, given the existence of non-neoplastic diseases increasing TM serum levels. In addition, a negative result does not exclude the possibility of neoplasm.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5–7</span></a> It is therefore important to know the TMs and adjust their use where higher specificity and sensitivity is ensured to minimize false positives or false negatives,<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,7,8</span></a> since improper TM prescription might trigger potentially harmful tests for the patient to confirm the result.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In accordance with the European Group on Tumor Markers (EGTM) and other agencies such as the National Academy of Clinical Biochemistry and the American Society of Clinical Oncology, TMs, except for the AFP and PSA, have only one clear use for monitoring the disease, treatment monitoring and identifying relapses.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,6,7,9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In this context, an intervention strategy was decided to improve the adequacy and safe use of TMs,<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5,7–10</span></a> following 2 adverse events in hospital (intestinal perforation after colonoscopy and abnormal bleeding in liver biopsy) after additional tests performed to verify the positive result of TMs. Subsequently, it was confirmed that there was no indication of TMs or tumoral disease.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Thus the aim of this study is to analyze the impact of the intervention and assess the adequacy and reduction of TM requests.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">Prospective cohort study, pre-post intervention, in the area of influence of the Serrania Hospital. The information systems of Clinical and Anatomical Pathology Laboratory were used as data sources. The analytical requests of the 4 most common and requested TMs were analyzed from January 2010 to December 2014, included in the portfolio of services: carcinoembryonic antigen (CEA), CA15.3, CA 19.9 and CA125. Requests for oncological queries (considered appropriate) and of the Laboratory were excluded (for being quality controls).</p><p id="par0030" class="elsevierStylePara elsevierViewall">The pre-intervention period was 2010, intervention, during January–May 2011, and the post-intervention period, until December 2014.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The intervention consisted of training and protocolization. The protocol was developed by a multidisciplinary working group, as recommended by the EGTM and other scientific societies (TMs included in the study should be used only for treatment monitoring, followup and identification of disease recurrence). The implementation of the protocol was accompanied by training activities to health professionals of Primary and Hospital Care on the use of TMs, clinical significance and limitations. From the laboratory, compliance with protocol was monitored, rejecting the request in not finding prior existence of neoplastic disease (requests classified as ‘not applicable’) and informing about the reason. This protocol has been maintained over time.</p><p id="par0040" class="elsevierStylePara elsevierViewall">TM tests were performed on a Siemens Centauro<span class="elsevierStyleSup">®</span> Xp analyzer, by chemiluminescence, not varying equipment or technique during the study. For each TM, the results were classified according to the manufacturer's baseline value, serum levels above which it was considered positive.</p><p id="par0045" class="elsevierStylePara elsevierViewall">It was investigated whether or not there were pathological studies (biopsies) and the result obtained.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The data analysis was performed using descriptive study of the variables of the study population, hypothesis testing applied to the analysis of the adequacy of the evidence in 2014 compared to those in 2011 (chi-square).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">During the period 2010–2014 the overall analytical requests analyzed were 5189; 9289 TMs. Distribution was CEA and CA19.9 with 45.40 and 27.79%, respectively, followed by CA125 (16.10%) and CA15.3 (10.71%).</p><p id="par0060" class="elsevierStylePara elsevierViewall">From 2010 to 2014, the total number of requests decreased by 50.81% from 1667 to 820 requests per year, reducing the number of tests from 3112 to 1331. This has meant a “stop doing” by 57.23% of TMs. This percentage difference between requests and tests is explained with lower average tests requested by request (19.93%), the median decreasing from 2 to 1 TMs per request.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The largest reduction was in CA19.9, by 65.93%, followed by CA15.3, CEA and CA125 with a 56.01, 52.56 and 41.61%, respectively (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Considering only the cost of reagents, in the period studied, it has produced savings of 34,810<span class="elsevierStyleHsp" style=""></span>€.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Regarding the compliance with the protocol, the percentage of requests reported as ‘not applicable’ was decreasing, from 68.97% for June–December 2011 to 49.26% in 2012 (mainly due to the reduction of CA125 and CA19.9), 22.26% in 2013 and 22.09% in 2014 (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The differences reported were significant.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Regarding the number of TMs whose serum levels tested positive (mainly CA15.3 and CA 19.9), they varied from 14.3% in 2010 to 10.6% in 2011, remaining constant until 2014, with 10.84%.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The analysis of biopsies requested of patients with positive MTs showed a significant variation from 21.6% of positive biopsies in 2010 to 40.6% in 2011, constant percentage until 2014 (42.9%).</p><p id="par0085" class="elsevierStylePara elsevierViewall">The anatomical pathology examination of the 708 patients for 2012, 2013 and 2014, respectively, with requests classified as ‘not applicable’, showed that in no case it had been positive.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">Protocol training and implementation activities have improved awareness among professionals about the appropriate use of the TMs, so that the assumable risk inherent to examination or diagnostic test is properly justified.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5–7</span></a> Requests have been aimed at a safer and more effective implementation in daily practice,<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> increasing performance and efficiency.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,8,9</span></a> The certainty of professionals in the request of TMs has also improved, being minimized both physical risks (due to additional testing)<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and psychological risks (anxiety produced by communicating a positive result) in patients.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The belief of professionals on the use of TMs as screening test, observed during training, favored the high use and low performance of these tests during the years prior to the intervention.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,5</span></a> However, training and protocols have managed to reverse the trend, favoring patient's safety.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–4,9</span></a> This realization and adjustment effort was mainly in primary care, where TM training was more deeply addressed. During the first months of intervention its impact was already seen in the reduction of requests. This has been accompanied by increased tests following the protocol. This has been understood as adherence of the professionals to protocol and greater awareness about the clinical usefulness of the TMs.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,7</span></a> Nevertheless, we should reflect about the stabilization (2013, 2014) of the requests qualified as ‘applicable’. This might be due to a continuous and high turnover of doctors in the units. Therefore, it is necessary to disseminate the protocol and continue training. The optimal target would be the confluence of the number of requests and applicable testing. The number of anatomical pathological studies has also decreased, resulting in increased performance.</p><p id="par0100" class="elsevierStylePara elsevierViewall">One of the concerns when addressing this project was to track patients whose requests were rejected, hence their pathological examination, proving that in no patient undergoing a biopsy the result was positive. Thus, it is worth noting that the number of registered tumors in the hospital tumor registry remained constant.</p><p id="par0105" class="elsevierStylePara elsevierViewall">This confirms that the TMs are useful and important depending on the patient's circumstances and disease.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,9</span></a> However their use following the protocol provides the clinician invaluable data when monitoring treatment and disease, especially in relapses, minimizing confusion about whether the positive result might be due to other conditions or biological variability in the patient, rather than the neoplastic disease.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4,8,9</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interests</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors report no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres635241" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec647750" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres635240" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Fundamento y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec647749" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-03-31" "fechaAceptado" => "2015-04-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec647750" "palabras" => array:4 [ 0 => "Tumor markers" 1 => "Patient safety" 2 => "Guideline" 3 => "Monitoring" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec647749" "palabras" => array:4 [ 0 => "Marcador tumoral" 1 => "Seguridad del paciente" 2 => "Protocolo" 3 => "Monitorización" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Improper clinical use of tumor markers (TM) may cause unnecessary additional studies to confirm or refute a positive result. After observing 2 adverse events due to a wrong use of TM, a protocol for improving their use was implemented. The objective of this study was to determine the impact of the implementation of the protocol.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This was a pre-postintervention study, where analytical requests of carcinoembryonic antigen, CA15.3, CA19.9 and CA125 were analyzed during one year in patients not undergoing checking of neoplasia. A protocol was implemented and physicians were trained as recommended by the European Group on Tumor Markers, limiting its use to monitor the disease and its treatment. The study period was 2010–2014.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The total number of requests dropped 50.81% and the percentage of adequacy of TM increased, each year, from 31.03 to 77.91%.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The implementation of a protocol for the proper use of TM contributes to a safer use, avoiding incorrect studies and unnecessary and harmful tests for the patient.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and method" ] 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">Fundamento y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Los marcadores tumorales (MT) son pruebas accesibles para la actividad clínica. Su uso inadecuado puede provocar pruebas complementarias innecesarias para confirmar o refutar un resultado positivo. Tras 2 acontecimientos adversos por un uso incorrecto de MT, se implementó un protocolo para el uso adecuado y seguro de estos. El objetivo de este trabajo fue determinar el impacto de la implementación de dicho protocolo.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y método</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio pre-postintervención. Se analizó el uso, durante un año, de peticiones de MT (antígeno carcinoembrionario, CA15.3, CA19.9, CA125) de pacientes no sometidos a revisión oncológica. Se implementó un protocolo, formándose a los facultativos según las recomendaciones del Grupo Europeo de Marcadores Tumorales, limitando su uso al seguimiento de la enfermedad y monitorización de tratamientos. Período estudiado: 2010-2014.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El número total de peticiones descendió un 50,81%, y el porcentaje de adecuación de los MT aumentó anualmente desde un 31,03 hasta un 77,91%.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La implantación de un protocolo del uso adecuado de MT contribuye a un uso seguro, evitando estudios no indicados y evitando pruebas complementarias innecesarias y lesivas para el paciente.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Fundamento y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Mérida de la Torre FJ, Moreno Campoy EE, Martos Crespo F. Impacto de la aplicación de un protocolo para el uso adecuado y seguro de marcadores tumorales. Med Clin (Barc). 2015;145:526–528.</p>" ] ] "multimedia" => array:2 [ 0 => 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:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Period \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CEA</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CA15.3</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CA125</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">CA19.9</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">n \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">% Var. \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">n \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">% Var. \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">n \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">% Var. \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">n \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">% Var. \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">n \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">% Var. \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">2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1667 \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="char" valign="top">1423 \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="char" valign="top">286 \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="char" valign="top">449 \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="char" valign="top">954 \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">2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1210 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−27.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">994 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−30.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">237 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−17.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">413 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−8.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">659 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−30.92 \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">2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">718 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−40.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">566 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−43.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">134 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−43.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">203 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−50.85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">313 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−52.50 \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">2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">774 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">599 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">169 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">214 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">325 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.83 \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">2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">820 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">626 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">167 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">213 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">325 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.00 \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">2010–2014 \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="char" valign="top">−50.81 \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="char" valign="top">−56.01 \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="char" valign="top">−41.61 \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="char" valign="top">−52.56 \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="char" valign="top">−65.93 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1042190.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Number of total requests and by type of tumor marker and percentages of inter-annual and global variation.</p>" ] ] 1 => 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:1 [ "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">Year \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 \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">CEA \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">CA15.3 \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">CA19.9 \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">CA125 \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 " align="char" valign="top">2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28.82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.99 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63.43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43.84 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">77.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">77.85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70.56 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">77.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71.83 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1042189.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Annual percentage of total requests classified as “applicable” and by type of tumor marker.</p>" ] ] 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