A systematic review of the clinical validity of the Cologuard™ genetic test for screening colorectal cancer

array:23 ["pii" => "S2254887415000934" "issn" => "22548874" "doi" => "10.1016/j.rceng.2015.08.006" "estado" => "S300" "fechaPublicacion" => "2015-12-01" "aid" => "1188" "copyright" => "Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI)" "copyrightAnyo" => "2015" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Rev Clin Esp. 2015;215:527-36" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 37 "formatos" => array:2 [ "HTML" => 36 "PDF" => 1 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0014256515002180" "issn" => "00142565" "doi" => "10.1016/j.rce.2015.08.002" "estado" => "S300" "fechaPublicacion" => "2015-12-01" "aid" => "1188" "copyright" => "Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Rev Clin Esp. 2015;215:527-36" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 563 "formatos" => array:2 [ "HTML" => 114 "PDF" => 449 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "REVISIÓN" "titulo" => "Validez clínica de la prueba genética CologuardTM para el cribado de cáncer colorrectal: revisión sistemática" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "527" "paginaFinal" => "536" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "A systematic review of the clinical validity of the Cologuard™ genetic test for screening colorectal cancer" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1779 "Ancho" => 1650 "Tamanyo" => 197583 ] ] "descripcion" => array:1 [ "es" => "Diagrama de flujo de la selección de artículos." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.Á. Onieva-García, A. Llanos-Méndez, E. Baños-Álvarez, R. Isabel-Gómez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M.Á." "apellidos" => "Onieva-García" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Llanos-Méndez" ] 2 => array:2 [ "nombre" => "E." "apellidos" => "Baños-Álvarez" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Isabel-Gómez" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2254887415000934" "doi" => "10.1016/j.rceng.2015.08.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887415000934?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256515002180?idApp=WRCEE" "url" => "/00142565/0000021500000009/v2_201601010043/S0014256515002180/v2_201601010043/es/main.assets" ] ] "itemAnterior" => array:19 [ "pii" => "S2254887415000922" "issn" => "22548874" "doi" => "10.1016/j.rceng.2015.08.005" "estado" => "S300" "fechaPublicacion" => "2015-12-01" "aid" => "1189" "copyright" => "Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "ssu" "cita" => "Rev Clin Esp. 2015;215:515-26" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 57 "formatos" => array:2 [ "HTML" => 54 "PDF" => 3 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Clinical practice guidelines for postmenopausal, glucocorticoid-induced and male osteoporosis. Spanish Society for Research on Bone and Mineral Metabolism (3rd updated version 2014)" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "515" "paginaFinal" => "526" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Guías de práctica clínica en la osteoporosis posmenopáusica, glucocorticoidea y del varón. Sociedad Española de Investigación Ósea y del Metabolismo Mineral (3.ª versión actualizada 2014)" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2325 "Ancho" => 3295 "Tamanyo" => 420884 ] ] "descripcion" => array:1 [ "en" => "Drug selection algorithm. Abbreviations: DS, digestive system; ALN, alendronate; Dmab, denosumab; BMD, bone mineral density; FN, femoral neck; RF, renal failure; PTH 1-34, teriparatide; SR, strontium ranelate; RIS, risedronate; SERMs, selective estrogen receptor modulators; ZOLE, zoledronate." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. González-Macías, J. del Pino-Montes, J.M. Olmos, X. Nogués" "autores" => array:5 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "González-Macías" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "del Pino-Montes" ] 2 => array:2 [ "nombre" => "J.M." "apellidos" => "Olmos" ] 3 => array:2 [ "nombre" => "X." "apellidos" => "Nogués" ] 4 => array:1 [ "colaborador" => "on behalf of the Comisión de Redacción de las Guías de Osteoporosis de la SEIOMM" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0014256515002192" "doi" => "10.1016/j.rce.2015.08.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256515002192?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887415000922?idApp=WRCEE" "url" => "/22548874/0000021500000009/v2_201601010034/S2254887415000922/v2_201601010034/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "A systematic review of the clinical validity of the Cologuard™ genetic test for screening colorectal cancer" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "527" "paginaFinal" => "536" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M.Á. Onieva-García, A. Llanos-Méndez, E. Baños-Álvarez, R. Isabel-Gómez" "autores" => array:4 [ 0 => array:4 [ "nombre" => "M.Á." "apellidos" => "Onieva-García" "email" => array:1 [ 0 => "mariaa.onieva@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Llanos-Méndez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "E." "apellidos" => "Baños-Álvarez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "R." "apellidos" => "Isabel-Gómez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "UGC Interniveles de Salud Pública de Granada, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Agencia de Evaluación de Tecnologías Sanitarias de Andalucía, Consejería de Salud de la Junta de Andalucía, Sevilla, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Validez clínica de la prueba genética Cologuard™ para el cribado de cáncer colorrectal: revisión sistemática" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1657 "Ancho" => 1650 "Tamanyo" => 200381 ] ] "descripcion" => array:1 [ "en" => "Risk of bias. Applicability of each study." ] ] ] "textoCompleto" => "BackgroundColorectal cancer (CRC) is the most common malignancy in Europe and Spain and constitutes the second leading cause of overall mortality from cancer.<a class="elsevierStyleCrossRef" href="#bib0160">1</a> It is estimated that the mortality rate from CRC has decreased by 13% in the last two decades in Spain.<a class="elsevierStyleCrossRef" href="#bib0165">2</a> However, this decrease is still well below that achieved in other European countries and the United States, and screening detection rates remain suboptimal, mainly due to the low participation of the population.<a class="elsevierStyleCrossRefs" href="#bib0165">2,3</a>Current screening methods targeted toward the population aged 50 years or more at moderate risk include annual high-sensitivity fecal occult blood tests (FOBT) (guaiac-based or immunological [FOBTi]); sigmoidoscopy every 5 years and FOBT every 3 years; or colonoscopy every 10 years.<a class="elsevierStyleCrossRefs" href="#bib0175">4,5</a> The method of choice in Spain is FOBTi every 2 years.<a class="elsevierStyleCrossRef" href="#bib0170">3</a> Although there is consensus for recommending any of these alternatives, there is still controversy regarding the cost-effectiveness of deoxyribonucleic acid (DNA) tests in feces due to the lack of data for determining the screening interval.<a class="elsevierStyleCrossRef" href="#bib0185">6</a>Stool DNA tests are designed to detect molecular abnormalities in the epithelial cells of precancerous adenomatous polyps (advanced adenoma [AA] or sessile serrated polyp [SSP]) or sloughed CRC cells into the large intestine lumen.<a class="elsevierStyleCrossRef" href="#bib0190">7</a> To date, only two DNA tests have been marketed (PreGen Plus™ and ColoSure™), none of which have been approved by the Food and Drug Administration.<a class="elsevierStyleCrossRef" href="#bib0185">6</a> The multitarget stool DNA test marketed as Cologuard™ has recently been approved by the Food and Drug Administration as a screening test for population at moderate risk of CRC and has been included as a healthcare provision in the Medicare and Medicaid services of the United States.<a class="elsevierStyleCrossRef" href="#bib0195">8</a> The main differences from its predecessors (PreGen Plus™ and ColoSure™) lies in the detected genetic markers, the incorporation of fecal occult blood (FOB) detection and the use of QuARTS technology™ for real-time DNA amplification.<a class="elsevierStyleCrossRef" href="#bib0185">6</a> This emerging technology could be an alternative noninvasive screening, which, with optimal performance and increased adherence rate, might reduce the incidence and mortality of CRC.The aim of this systematic review was to combine the available evidence to analyze the validity, diagnostic accuracy and clinical utility of the multitarget stool DNA test (Cologuard™) in CRC screening.MethodsA systematic literature review was performed by following the PRISMA recommendations.<a class="elsevierStyleCrossRef" href="#bib0200">9</a> The results were summarized in narrative form. A statistical analysis was not possible due to the heterogeneity of the studies.Information sourcesThe MedLine, EMBASE, Web of Science and PubMed databases were consulted until July 2014. In addition, we also consulted the Centre for Reviews and Dissemination, the International Information Network on New and Emerging Health Technologies (EuroScan), the Cochrane Library, the website of agencies not included in the International Network of Agencies for Health Technology Assessment, the Ministry of Health, Social Services and Equality, the platforms of Agencies and Health Technology Assessment Units, the World Health Organization, the Centers for Disease Control and Prevention, the Emergency Care Research Institute (ECRI) and the National Institute for Health and Clinical Excellence. Secondary references were also reviewed.For this purpose, both natural and controlled language was employed, using the terms: “colorectal neoplasms,” “DNA mutational analysis,” “stool DNA test,” “Cologuard,” “mass screening,” “screening,” “early detection of cancer,” “sensitivity,” “specificity,” “likelihood functions,” “reproducibility of results” and “area under the curve,” among others.Selection of studiesTwo reviewers independently selected studies that examined the validity and diagnostic accuracy of the multitarget stool DNA test, comparing it with any method for the diagnosis or screening of CRC in asymptomatic populations.Assessment reports and summaries of emerging technologies were also included, because they contain useful information for corroborating the methodological rigor of our search.Narrative reviews, letters to the editor, editorials, meeting abstracts and preclinical studies were excluded.Data extractionThe variables included the characteristics of the study (author, year of publication, country, study period, objectives, phase of the study and funding); the population (sample size, sociodemographic and clinical features, inclusion and exclusion criteria); and the intervention (screening test and reference). In addition, the results relating to diagnostic validity and accuracy (sensitivity, specificity, predictive values, likelihood ratios, ROC curve and intraobserver and interobserver variability) were extracted. When possible, 2×2 contingency tables were generated to calculate these parameters from each study's data.Assessment of risk of bias and evidence levelIn addition, two reviewers independently assessed the quality and risk of bias according to the Quality Assessment of Diagnostic Accuracy Studies-1 and Quality Assessment of Diagnostic Accuracy Studies-2 tool, respectively.<a class="elsevierStyleCrossRefs" href="#bib0205">10,11</a> Discrepancies were resolved by consensus. The level of evidence was defined according to The National Institute for Health and Clinical Excellence recommendations.<a class="elsevierStyleCrossRef" href="#bib0215">12</a>ResultsA total of 299 references were identified. After the selection process, 5 primary studies of diagnostic tests (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) were included.<a class="elsevierStyleCrossRefs" href="#bib0220">13–17</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Likewise, a summary report published by ECRI that assessed the impact of Cologuard™ was included.<a class="elsevierStyleCrossRef" href="#bib0190">7</a> The authors predicted, regarding the current screening tests, an increase in the adherence rate and early detection of lesions that consequently results in greater health benefits but also increased costs.Characteristics of the primary studiesAll studies examined the validity of DNA biomarkers in feces, along with the FOB in the detection rate of CRC or advanced precancerous lesions.<a class="elsevierStyleCrossRefs" href="#bib0220">13–17</a> The reference test was colonoscopy,<a class="elsevierStyleCrossRefs" href="#bib0220">13–17</a> considering the index lesion the most advanced colorectal epithelial lesion<a class="elsevierStyleCrossRefs" href="#bib0220">13–17</a> or the larger among two or more similar lesions.<a class="elsevierStyleCrossRefs" href="#bib0220">13,16</a>The three studies<a class="elsevierStyleCrossRefs" href="#bib0220">13–15</a> that used the DNA Cologuard™ biomarker panel assessed aberrant methylations in the promoter region of bone morphogenetic protein 3 (BMP3) and N-Myc downstream-regulated gene 4 (NDRG4), 7-point mutations in the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene and detected FOB by quantitative FOBTi. The remaining two studies evaluated the Cologuard™ prototype,<a class="elsevierStyleCrossRefs" href="#bib0235">16,17</a> which also detects aberrant methylations in the vimentin (VIM) and tissue factor pathway inhibitor 2 (TFPI2) genes. FOB was detected by the porphyrin method.The cumulative study population for analyzing the performance of the Cologuard™ test was 14,235 participants (13,691 apparently asymptomatic and 544 with symptoms suggestive of CRC)<a class="elsevierStyleCrossRefs" href="#bib0220">13–15</a> and 825 for the prototype (including asymptomatic individuals and those with suggestive symptoms).<a class="elsevierStyleCrossRefs" href="#bib0235">16,17</a> The percentage of women ranged from 50% to 55%, and the mean age ranged from 60 to 65 years (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The excluded patients were those with syndromes at high risk for CRC (Lynch syndrome or familial adenomatous polyposis), inflammatory bowel disease,<a class="elsevierStyleCrossRefs" href="#bib0220">13,14,16</a> previous colorectal resection,<a class="elsevierStyleCrossRefs" href="#bib0220">13,14</a> recent screening test,<a class="elsevierStyleCrossRefs" href="#bib0220">13,14</a> a history of gastrointestinal neoplasia or bleeding in the past 30 days<a class="elsevierStyleCrossRef" href="#bib0220">13</a> or who underwent incomplete colonoscopy.<a class="elsevierStyleCrossRef" href="#bib0225">14</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Risk of bias in the primary studiesThe methodological quality of the prospective studies was high<a class="elsevierStyleCrossRefs" href="#bib0220">13,14</a> (or Sackett phase III<a class="elsevierStyleCrossRef" href="#bib0245">18</a>) with level Ib evidence. The rest of the studies had moderate quality<a class="elsevierStyleCrossRefs" href="#bib0230">15–17</a> and a case-control design (Sackett phase II) and level III evidence.The main risk of bias was related to the characteristics of the participants in the case-control studies (selection bias).<a class="elsevierStyleCrossRefs" href="#bib0230">15–17</a> The inclusion of patients with symptoms suggestive of the target disease could overestimate the diagnostic validity parameters (predictive values and sensitivity) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>The risk of bias in the interpretation of the study test results was low, because the positivity of the test was objectively defined with a pre-set cutoff value.<a class="elsevierStyleCrossRefs" href="#bib0220">13–17</a> In contrast, there was a risk of observer bias in three studies.<a class="elsevierStyleCrossRefs" href="#bib0230">15–17</a> The observers did not record whether the colonoscopy (a subjective test) was performed without knowing the test's positivity or negativity, which could have influenced the interpretation of the colonoscopy results and biased the results.All patients had undergone colonoscopy as the reference test.<a class="elsevierStyleCrossRefs" href="#bib0220">13–17</a> Regarding the patient classification, it was considered that there had been no errors in the diagnosis of precancerous or cancerous lesions found during the colonoscopy because, except for 9 lesions in the Heigh et al. study,<a class="elsevierStyleCrossRef" href="#bib0225">14</a> all lesions were confirmed by pathology (gold standard). Moreover, although there is some uncertainty about the correct classification of the healthy participants who did not undergo pathology, this was not considered relevant according to the colonoscopy diagnostic performance (95% sensitivity and 90% specificity).<a class="elsevierStyleCrossRef" href="#bib0250">19</a>The time interval between the colonoscopy and the study test was reported in 1 study (90 days at most).<a class="elsevierStyleCrossRef" href="#bib0220">13</a> In the remaining studies,<a class="elsevierStyleCrossRefs" href="#bib0225">14–17</a> this interval was not specified, raising doubts about the similarity of the spectrum of patients undergoing each test at two different times.Only the Imperiale et al. study suffered losses (21.8% of participants). The authors found significant differences in age and race between the participants who completed the study and were evaluated and those who did not complete it and were not included in the analysis. The magnitude of these differences was not noticeable except for the participants older than 74 years. The proportion of these participants was 9% in the evaluated group compared to 13.6% in the nonevaluated group. This could have underestimated the detection of proximal cancers, which are more common than distal cancers at the age of 70 or older.<a class="elsevierStyleCrossRef" href="#bib0220">13</a>Results of the primary studiesDiagnostic accuracy and overall performance of the Cologuard™ testThe sensitivity ranged from 92.3% to 97.8% for CRC and from 42.4% to 57% for AA.<a class="elsevierStyleCrossRefs" href="#bib0220">13,14</a> The sensitivity for SSP was 55.2%.<a class="elsevierStyleCrossRef" href="#bib0225">14</a> The specificity for advanced colorectal neoplasia (including CRC and AA) achieved a range between 86.6% and 90%. The positive likelihood ratio (LR+) ranged from 5.9 to 9.8 for CRC and from 3.2 to 5.7 for AA,<a class="elsevierStyleCrossRefs" href="#bib0220">13,14</a> indicating the number of times more likely the test will be positive for a sick patient than for a healthy one. Therefore, a positive test result provides strong diagnostic evidence for CRC, while it is less useful for detecting AA, although its detection could be considered clinically relevant (values above 10 indicate conclusive diagnostic evidence; between 5 and 10 indicates strong evidence; and between 1 and 2 indicates low evidence).<a class="elsevierStyleCrossRef" href="#bib0255">20</a> Furthermore, the negative likelihood ratio (LR−) ranged from 0.02 to 0.09 for CRC and from 0.5 to 0.7 for AA,<a class="elsevierStyleCrossRefs" href="#bib0220">13,14</a> indicating the number of times more likely the test will be negative for a sick patient than for a healthy one. Thus, a negative test result provides conclusive diagnostic evidence against CRC, in other words, it is an excellent test for ruling out CRC. A negative test result also provides low evidence for ruling out AA (values below 0.1 indicate conclusive diagnostic evidence; lower than 0.2 indicates strong evidence; and between 0.6 and 1 indicates low evidence).<a class="elsevierStyleCrossRef" href="#bib0255">20</a> The overall test performance was higher for CRC (area under the curve: 0.94) than for advanced colorectal neoplasia (0.73).<a class="elsevierStyleCrossRef" href="#bib0220">13</a> Heigh et al.<a class="elsevierStyleCrossRef" href="#bib0225">14</a> measured the discriminative ability of each marker and found statistically significant values for BMP3, NDRG4 and KRAS (0.87 [95% CI 0.80–0.95], p<.0001; 0.79 [95% CI 0.70–0.88], p<.0001; 0.64 [95% CI 0.53–0.75], p=.0068, respectively) but not for occult hemoglobin (0.50 [95% CI 0.40–0.61], p=.47)<a class="elsevierStyleCrossRefs" href="#bib0220">13,14</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Diagnostic validity and overall performance of Cologuard™ prototypeThe sensitivity ranged from 84.9% to 86.7% for CRC and from 54.1% to 81.8% for AA. The specificity for advanced colorectal neoplasia was 89.1%. This test provided strong diagnostic evidence to detect and rule out CRC (LR+, 7.7; LR−, 0.2) and was less useful for AA (LR+, 4.9; LR−, 0.5).<a class="elsevierStyleCrossRefs" href="#bib0235">16,17</a>Ahlquist et al.<a class="elsevierStyleCrossRef" href="#bib0235">16</a> found an area under the curve of 0.90 (95% CI 0.86–0.93) for the full marker panel (BMP3, NDRG4, KRAS, TFPI2, VIM and hemoglobin) versus 0.88 (95% CI 0.84–0.91) for the panel without hemoglobin. The relative contribution of TFPI2 and VIM was minimal, increasing the sensitivity from 1 to 3 percentage points. In contrast, BMP3, NDRG4 and KRAS significantly contributed to the test's discriminative ability (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).AccuracyAhlquist et al.<a class="elsevierStyleCrossRef" href="#bib0235">16</a> found a high degree of agreement in the results among the various laboratories (correlation coefficient of 0.978–0.996).<a class="elsevierStyleCrossRef" href="#bib0255">20</a>Comparison with other screening tests<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Comparison of Cologuard™ with quantitative FOBTi (OC-FIT CHEK, Polymedco). In the study by Heigh et al.,<a class="elsevierStyleCrossRef" href="#bib0225">14</a> the detection rate for SSP≥1cm using the Cologuard™ BMP3 test was 66% and 63% for the predetermined specificities of 91% and 95%, respectively, compared to the 10% and 0% achieved with FOBTi. These differences were statistically significant (p=.003; p<.001, respectively). In the Imperiale et al. study,<a class="elsevierStyleCrossRef" href="#bib0220">13</a> Cologuard™ was more sensitive for detecting CRC in any stage (stages I–III) and for both locations (proximal and distal), with values of approximately 90% or higher. The absolute differences of 24 percentage points for stages I and II, and the proximal location stand out. Although the sensitivity of Cologuard™ achieved lower values (approximately 50%) for AA detection, the sensitivity was also greater, with absolute differences ranging from 16 to 26 percentage points and up to 37 points for SSP detection. However, the specificity of FOBTi (94.9–96.4%) was higher than that of Cologuard™ (86.6–89.8%), with false positive rates of 3.6–5.1% and 10.2–13.4%, respectively<a class="elsevierStyleCrossRef" href="#bib0220">13</a> (<a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3 and 4</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0010">•Comparison of the Cologuard™ prototype with methylated SEPT9 gene in plasma (Septin 9). The sensitivity for detecting CRC and large AA with the Cologuard™ prototype was higher than that of Septin 9 (85% vs. 40%, p=.0001). The same occurred with the isolated sensitivity for detecting large AA (82% vs. 14%, p=.0001), CRC (87% vs. 60%, p=.046), stages I–III of CRC (95% vs. 50%, p=.013) and proximal CRC (92% vs. 46%, p=.034).<a class="elsevierStyleCrossRef" href="#bib0240">17</a> The false positive rate of Septin 9 was higher than that of the prototype (21% vs. 7%) (<a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3 and 4</a>).</li></ul>DiscussionSpain has recently approved the inclusion of CRC screening in the National Health System's basic portfolio of services, using FOBTi (performed every 2 years) for the population aged 50–69 years.<a class="elsevierStyleCrossRef" href="#bib0170">3</a> Although FOBTi has proven to be cost-effective,<a class="elsevierStyleCrossRefs" href="#bib0260">21–23</a> the low participation rate (approximately 35%) has led to suboptimal results.<a class="elsevierStyleCrossRefs" href="#bib0170">3,24,25</a> The acceptance rate is even lower when colonoscopy is the screening test of choice (approximately 25%).<a class="elsevierStyleCrossRefs" href="#bib0275">24,25</a> New genetic tests, such as Cologuard™, represent an alternative screening that could improve the program's performance as a whole.<a class="elsevierStyleCrossRef" href="#bib0180">5</a>Considering that sensitivity is the most important attribute of a diagnostic test designed for mass screening, one could conclude that Cologuard™ is a valid test for detecting CRC at any stage, including early stages and both proximal and distal locations, with sensitivities of over 90%. An LR− lower than 0.1 also makes it an excellent test for ruling out CRC. However, its utility in detecting AA is lower, with sensitivities of approximately 40%,<a class="elsevierStyleCrossRefs" href="#bib0220">13–15</a> although always higher than those obtained by FOBTi.<a class="elsevierStyleCrossRef" href="#bib0220">13</a> The results for the prototype were similar but with slightly lower LR− and sensitivity values.<a class="elsevierStyleCrossRefs" href="#bib0235">16,17</a>There are two remarkable findings that could play a major role in clinical practice. One of these findings is the increased sensitivity of Cologuard™ for serrated polyps compared with FOBTi, given that the polyp-cancer sequence appears fastest in the serrated pathway.<a class="elsevierStyleCrossRef" href="#bib0285">26</a> The other important aspect is that proximal cancer detection with Cologuard™ was substantially higher than with FOBTi. This finding is particularly relevant because of the lower diagnostic performance when detecting proximal malignancies (when compared with distal malignancies) reported for FOBT and lower endoscopy.<a class="elsevierStyleCrossRef" href="#bib0290">27</a>The articles included in this review could be considered a compendium of consecutive studies of increasing complexity that gradually control the various biases that can affect the validation process, seeking more pragmatic goals that are applicable to clinical practice. Thus, we can see that the Ahlquist et al.<a class="elsevierStyleCrossRefs" href="#bib0235">16,17</a> and Lidgard et al.<a class="elsevierStyleCrossRef" href="#bib0230">15</a> (case-control design) studies have methodological deficits (mainly related to the spectrum of patients) to a greater degree than the Heigh et al.<a class="elsevierStyleCrossRef" href="#bib0225">14</a> and Imperiale et al.<a class="elsevierStyleCrossRef" href="#bib0220">13</a> (prospective design) studies. As previously mentioned, the inclusion of patients with similar symptoms to those of the target disease in the Alhquist et al.<a class="elsevierStyleCrossRefs" href="#bib0235">16,17</a> and Lidgard et al.<a class="elsevierStyleCrossRef" href="#bib0230">15</a> studies would theoretically increase the prevalence of the disease, overestimating the diagnostic validity parameters related to the post-test probability (predictive values). Thus, an increase in the number of patients would indirectly increase the test sensitivity. For this reason and given that the case-control design is the most critical aspect in the introduction of risk of bias,<a class="elsevierStyleCrossRef" href="#bib0295">28</a> we have assigned more importance to the prospective studies in the conclusions of this systematic review. These studies were able to minimize the risk of bias in each assessed aspect: adequate spectrum of patients, blind interpretation of results, appropriate reference test and adequate reporting of losses.The external validity was limited by the heterogeneity in the test's maturity, as a number of studies used the marketed test (Cologuard™)<a class="elsevierStyleCrossRefs" href="#bib0220">13–15</a> while others used the prototype.<a class="elsevierStyleCrossRefs" href="#bib0235">16,17</a> Another aspect of the external validity was the study setting, which was focused primarily on North America. However, the extrapolation of results to a hypothetical Spanish population does not imply, in theory, a lower diagnostic validity for the test (in terms of post-test probability), given that the prevalence of CRC in Spain is higher than in North America.<a class="elsevierStyleCrossRef" href="#bib0160">1</a> It is also noteworthy that the funding for most of the studies came from the company that developed and distributed the test, which could represent a conflict of interest.It has already been stated that Cologuard™ is a valid test, a prerequisite for any screening or diagnostic test, but it is not sufficient. Its success in a screening program, measured in terms of health benefits, will depend on many other factors that have yet to be analyzed. Thus, the possibility of including Cologuard™ in the National Health System's portfolio of services depends on ethical, social and organizational aspects.First, we should assess the acceptance of the screening test by the population. The authors of the summary report from the ECRI<a class="elsevierStyleCrossRef" href="#bib0190">7</a> measured greater adherence compared with the current screening tests. However, there are limiting factors. For example, 36g of feces are required for the proper processing of Cologuard™, which could hinder both population recruitment and laboratory handling. Moreover, Cologuard™ and FOBT share the same sample collection procedure; therefore, from the patient's point of view, both tests would be similar. In our opinion, these issues could lessen the hypothetical increase in adherence with the use of Cologuard™. We should be aware that the higher adherence mentioned by the ECRI authors was based on expert forecasts and opinions.Second, the rate at which Cologuard™ should be performed to ensure lesion detection is not yet known. The company that marketed the test has proposed a 3-year interval between two consecutive screenings,<a class="elsevierStyleCrossRef" href="#bib0300">29</a> but the studies included in this review do not provide sufficient data on this issue. It is essential to determine this interval to measure the effects of Cologuard™ in reducing CRC incidence and mortality and to compare it with other screening methods, given that the literature shows that periodicity determines, along with other factors, the achievement (or not) of optimum results.<a class="elsevierStyleCrossRef" href="#bib0305">30</a> It would therefore be advisable to have studies that compare the frequency of the test to that of current tests and compare the overall performance of the screening program for various strategies.Third, the specificity of the test should be considered. Although the sensitivity is necessary for the screening tests, it is not sufficient. The lower specificity found for Cologuard™ compared with FOBT increases the probability of finding false positives, thereby resulting in the need for confirmation by colonoscopy. Therefore, although Cologuard™ is a valid test in terms of efficiency, it might be inefficient for most patients who end up needing a colonoscopy, with the resulting consumption of resources (cost increase) and side effects such as overdiagnosis, anxiety and risk of complications from invasive tests such as colonoscopy. The estimated cost for Cologuard™ is also 30 times higher than that of FOBT,<a class="elsevierStyleCrossRef" href="#bib0310">31</a> which significantly increases the cost of the screening program.In conclusion, this systematic review shows that the multitarget stool DNA test Cologuard™ is an effective (and valid) screening test for ruling out cancerous lesions and, to a lesser extent, precancerous lesions. However, there are no data for determining whether the Cologuard™ screening program could obtain greater health benefits compared with current programs; that is, whether it would be more effective in terms of reducing CRC incidence and mortality. To determine to what extent this test could provide improvements, future studies should delve deeper into issues such as the impact on population participation (adherence), the time interval between two consecutive screenings to ensure early lesion detection and test efficiency through cost-effectiveness studies.FundingThis document was developed under the collaboration agreement signed by the Institute of Health Carlos III, an autonomous body of the Ministry of Economy and Competitiveness and the Department of Equality, Health and Social Policy of the Andalusian Government as part of the development of activities of the Spanish Network of Agencies for Health Technology Assessment and Services of the NHS, funded by the Ministry of Health, Social Services and Equality.Conflict of interestsThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres594218" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec609140" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres594217" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec609141" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Information sources" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Selection of studies" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Data extraction" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Assessment of risk of bias and evidence level" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Characteristics of the primary studies" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Risk of bias in the primary studies" ] 2 => array:3 [ "identificador" => "sec0050" "titulo" => "Results of the primary studies" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Diagnostic accuracy and overall performance of the Cologuard™ test" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Diagnostic validity and overall performance of Cologuard™ prototype" ] ] ] 3 => array:2 [ "identificador" => "sec0065" "titulo" => "Accuracy" ] 4 => array:2 [ "identificador" => "sec0070" "titulo" => "Comparison with other screening tests" ] ] ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interests" ] 10 => array:2 [ "identificador" => "xack199860" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-04-09" "fechaAceptado" => "2015-08-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec609140" "palabras" => array:5 [ 0 => "Systematic review" 1 => "Colorectal cancer" 2 => "Screening" 3 => "Analysis of DNA mutations" 4 => "Feces" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec609141" "palabras" => array:5 [ 0 => "Revisión sistemática" 1 => "Cáncer colorrectal" 2 => "Cribado" 3 => "Análisis de mutaciones de ADN" 4 => "Heces" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectivesThe aim of this study was to assess the available evidence on the validity, diagnostic accuracy and clinical utility of the multitarget DNA test in feces (Cologuard™) for screening for colorectal cancer (CRC). Material and methodsA systematic review was performed by consulting MedLine, EMBASE and Web of Science to July 2014. Studies on diagnostic tests were selected that evaluated the test in asymptomatic adults who underwent CRC screening. The quality and risk of bias were assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. The level of evidence was defined according to the National Institute for Health and Clinical Excellence. A qualitative synthesis was conducted. ResultsA total of 299 literature references were identified, including 1 synthesis report and 5 diagnostic test studies. Three of the five studies had a case-control design in Sackett phase II and were of moderate quality, and two had a prospective design in Sacket phase III and were of high quality. The sensitivity for detecting CRC was greater than 90%, but only 40% for detecting advanced adenomas. The test provided conclusive diagnostic evidence to rule out CRC (negative likelihood ratio, LR−: 0.02–0.09), although it was not useful for ruling out advanced adenoma (LR−: 0.5–0.7). ConclusionsThe Cologuard™ test is a valid screening test for ruling out cancerous lesions but is suboptimal for ruling out precancerous lesions. There is no evidence in terms of mortality, survival or cost-effectiveness." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivosEl objetivo fue evaluar la evidencia disponible sobre la validez, precisión diagnóstica y utilidad clínica del test multidiana de ADN en heces (Cologuard™) en el cribado de cáncer colorrectal (CCR). Material y métodosSe realizó una revisión sistemática consultando MedLine, EMBASE y Web of Science hasta julio de 2014. Se seleccionaron estudios de pruebas diagnósticas que evaluaran el test en adultos asintomáticos sometidos a cribado de CCR. La calidad y el riesgo de sesgo se evaluaron mediante la herramienta Quality Assessment of Diagnostic Accuracy Studies. El nivel de evidencia se definió según The National Institute for Healthand Clinical Excellence. Se realizó una síntesis cualitativa. ResultadosSe identificaron 299 referencias bibliográficas, incluyéndose un informe de síntesis y cinco estudios de pruebas diagnósticas, tres de ellos con diseño caso-control en fase II de Sackett y de moderada calidad, y dos con diseño prospectivo en fase III de Sacket y de alta calidad. La sensibilidad para detectar CCR fue superior al 90%, pero solo del 40% para la detección de adenoma avanzado. El test proporcionó evidencia diagnóstica concluyente para descartar CCR (cociente de probabilidad negativo, CPN: 0,02-0,09), aunque no fue útil para descartar adenoma avanzado (CPN: 0,5-0,7). ConclusionesEl test Cologuard™ es una prueba de cribado válida para descartar lesiones cancerosas, resultando subóptima para descartar lesiones precancerosas. No hay evidencia sobre resultados en términos de mortalidad o supervivencia, ni sobre coste-efectividad." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Onieva-García MÁ, Llanos-Méndez A, Baños-Álvarez E, Isabel-Gómez R. Validez clínica de la prueba genética Cologuard™ para el cribado de cáncer colorrectal: revisión sistemática. Rev Clin Esp. 2015;215:527–536." ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1779 "Ancho" => 1650 "Tamanyo" => 187791 ] ] "descripcion" => array:1 [ "en" => "Flow diagram for the selection of articles." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1657 "Ancho" => 1650 "Tamanyo" => 200381 ] ] "descripcion" => array:1 [ "en" => "Risk of bias. Applicability of each study." ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "Abbreviations: N, population size; NA, not applicable; NC, not specified." "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">Test \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Author and 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">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">Type of patient, n \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">Women, n (%)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a></th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Mean age, years (range)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a></th><th class="td" title="table-head " align="left" valign="top" scope="col">Race, n (%)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \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">CRC stage, n (%)<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a></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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" 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">Overall \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">Without lesions \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">With lesions \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">Overall \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">Without lesions \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">With lesions \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">I–III \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">IV \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">Cologuard™ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Imperiale 2014<a class="elsevierStyleCrossRef" href="#bib0220">13</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12,776 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asymptomatic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5364 (54) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">64 (NC) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">White, 8392 (84)African-American, 1068 (11)Other, 523 (5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Heigh 2014<a class="elsevierStyleCrossRef" href="#bib0225">14</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">456 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asymptomatic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">138<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (53)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">61<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (52–77)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Lidgard 2013<a class="elsevierStyleCrossRef" href="#bib0230">15</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asymptomatic, 459Symptomatic, 544 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">549<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (55)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">462<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (58) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">87<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (42) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (38–87)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65 (50–84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65 (38–87) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">76 (92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (8) \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">Cologuard™ prototype \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0240">17</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">147 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (51)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a> (57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 (46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">64<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (51–75)<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a> (51–66) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">69 (61–75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 (73) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (27) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0235">16</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">678 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">AsymptomaticSymptomatic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">339<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">164<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (56) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">173<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> (45) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60 (39–92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">57 (41–87) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">63 (39–92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Blanca, 549 (81) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">225 (89) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27 (11) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab971648.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Data referring to the assessed population." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Data calculated by the authors of the review based on data from the studies." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "Controls paired by age and sex for feces sample (does not include the controls paired by age and sex for plasma sample)." ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of the study population." ] ] 3 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "Abbreviations: LR−, negative likelihood ratio; LR+, positive likelihood ratio; 95% CI, 95% confidence interval; NC, not calculated; ND, no data; NPV, negative predictive value; PPV, positive predictive value." "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">Type of lesion \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">Author and 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">Phase \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 (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">Specificity (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">PPV (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">NPV (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">LR+ (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">LR− (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="9" align="left" valign="top">Cologuard™</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Colorectal cancer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Imperiale 2014<a class="elsevierStyleCrossRef" href="#bib0220">13</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.923 (0.832–0.967) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.844 (0.836–0.851) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.037 (0.029–0.048) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.999 (0.998–0.999) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.902<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (5.428–6.418)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.091<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.039–0.212)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Lidgard 2013<a class="elsevierStyleCrossRef" href="#bib0230">15</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.978 (0.924–0.997)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.900 (0.879–0.919)<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.785<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> (8.033–11.918)<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.024<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> (0.006–0.094)<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \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">Advanced adenoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Imperiale 2014<a class="elsevierStyleCrossRef" href="#bib0220">13</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.424 (0.389–0.460) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.866<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.859–0.872)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.207<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.187–0.228)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.8657<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.859–0.872)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.158<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (2.863–3.483)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.665<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.626–0.708)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Lidgard 2013<a class="elsevierStyleCrossRef" href="#bib0230">15</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.570 (0.474–0.663)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.900 (0.879–0.919)<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.745<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> (4.416–7.474)<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.477<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> (0.386–0.590)<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \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">Sessile serrated polyp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Heigh 2014<a class="elsevierStyleCrossRef" href="#bib0225">14</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.552 (0.357–0.736) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.909 (0.865–0.943) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.432<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.287–0.591)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.942<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.903–0.965)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.095<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (3.611–10.288)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.493<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.328–0.740)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \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">Advanced colorectal neoplasm<a class="elsevierStyleCrossRef" href="#tblfn0035">d</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Imperiale 2014<a class="elsevierStyleCrossRef" href="#bib0220">13</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.464<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.429–0.498)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.866 (0.859–0.872) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.236 (0.216–0.258) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.947 (0.942–0.952) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.452<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (3.154–3.777)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.620<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.581–0.661)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Lidgard 2013<a class="elsevierStyleCrossRef" href="#bib0230">15</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.754<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.689–0.811)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.900 (0.879–0.919)<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.593<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (6.074–9.493)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.274<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.214–0.347)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top">Cologuard™ Prototype</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Colorectal cancer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0240">17</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.867 (0.693–0.962) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0235">16</a>,<a class="elsevierStyleCrossRef" href="#tblfn0030">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.849 (0.799–0.891) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.890 (0.856–0.918) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.697<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (5.849–10.130)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.169<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.126–0.228)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \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">Advanced adenoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0240">17</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.818 (0.615–0.927) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">ND \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0235">16</a>,<a class="elsevierStyleCrossRef" href="#tblfn0030">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.541 (0.453–0.628) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.891 (0.849–0.924) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.957<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (3.450–7.122)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.515<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.426–0.622)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \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">Advanced colorectal neoplasm<a class="elsevierStyleCrossRef" href="#tblfn0035">d</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0240">17</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.846 (0.719–0.931) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.935 (0.821–0.986) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.974<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (4.318–38.981)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.165<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.087–0.313)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0235">16</a>,<a class="elsevierStyleCrossRef" href="#tblfn0030">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.743<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.696–0.786)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.891<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.849–0.924)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.802<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (4.879–9.482)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.289<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> (0.242–0.344)<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab971651.png" ] ] ] "notaPie" => array:4 [ 0 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "a" "nota" => "Values calculated by the authors of this review based on data from the original studies." ] 1 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "b" "nota" => "Values calculated by the authors of this review based on data from the original study, assuming a specificity of 90%." ] 2 => array:3 [ "identificador" => "tblfn0030" "etiqueta" => "c" "nota" => "Results referring to all patients as a whole." ] 3 => array:3 [ "identificador" => "tblfn0035" "etiqueta" => "d" "nota" => "Including colorectal cancer and advanced adenoma." ] ] ] "descripcion" => array:1 [ "en" => "Efficacy results in terms of diagnostic validity." ] ] 4 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "Abbreviations: FOBTi, immunologic fecal occult blood test." "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="" 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">Cologuard™<a class="elsevierStyleCrossRefs" href="#bib0220">13–15</a> \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">Cologuard™ Prototype<a class="elsevierStyleCrossRefs" href="#bib0235">16,17</a> \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">Quantitative FOBTi<a class="elsevierStyleCrossRef" href="#bib0220">13</a> \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">Septin 9<a class="elsevierStyleCrossRef" href="#bib0240">17</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" title="table-entry " colspan="5" align="left" valign="top">Stage</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.897<a class="elsevierStyleCrossRef" href="#tblfn0040">a</a>–0.952 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.844–0.857 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.655 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.570 \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">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000<a class="elsevierStyleCrossRef" href="#tblfn0040">a</a>–1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.800–0.857 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.762 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.570 \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">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.900<a class="elsevierStyleCrossRef" href="#tblfn0040">a</a>–0.968 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.949–1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.900 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.380 \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">IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.750<a class="elsevierStyleCrossRef" href="#tblfn0040">a</a>–1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.704–0.750 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.750 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.880 \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">I-III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.933–0.974 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.871–0.910 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.733 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.500 \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"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Location</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proximal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.900<a class="elsevierStyleCrossRef" href="#tblfn0040">a</a>–1.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.874–0.920 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.667 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.460 \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">Distal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.940–0.943<a class="elsevierStyleCrossRef" href="#tblfn0040">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.810–0.828 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.800 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.690 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab971650.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0040" "etiqueta" => "a" "nota" => "Data from the study reports submitted to the Food and Drug Administration for approval of Cologuard™.60" ] ] ] "descripcion" => array:1 [ "en" => "Results of sensitivity for detecting colorectal cancer lesions." ] ] 5 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "Abbreviations: NC, not specified; FOBTi, immunologic fecal occult blood test." "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="" 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">Cologuard™<a class="elsevierStyleCrossRefs" href="#bib0220">13–15</a> \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">Cologuard™ prototype<a class="elsevierStyleCrossRefs" href="#bib0235">16,17</a> \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">Quantitative FOBTi<a class="elsevierStyleCrossRef" href="#bib0220">13</a> \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">Septin 9<a class="elsevierStyleCrossRef" href="#bib0240">17</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" title="table-entry " colspan="5" align="left" valign="top">Type</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Advanced adenoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.424–0.570 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.541–0.818 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.238 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.140 \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">High-grade dysplasia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.629–0.833 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.462<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \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">Sessile serrated polyp \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.424–0.600<a class="elsevierStyleCrossRef" href="#tblfn0045">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.05<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \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">Location</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Proximal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.332–0.513 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.552 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.155<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \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">Distal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.545–0.676 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.533 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.348<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \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"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Size</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≤5mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.200<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.200<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \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">6–9mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.321<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \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">10–19mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.392<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a>–0.570 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.540<a class="elsevierStyleCrossRef" href="#tblfn0055">d</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.209<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \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">20–29mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.646<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.765 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.430<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \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">≥30mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.684<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a>–0.833 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.860<a class="elsevierStyleCrossRef" href="#tblfn0060">e</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.421<a class="elsevierStyleCrossRef" href="#tblfn0050">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \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">>40mm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.916 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NC \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab971649.png" ] ] ] "notaPie" => array:4 [ 0 => array:3 [ "identificador" => "tblfn0045" "etiqueta" => "b" "nota" => "This range of values also includes the results from the Heigh et al. study." ] 1 => array:3 [ "identificador" => "tblfn0050" "etiqueta" => "c" "nota" => "Data from the study report submitted to the Food and Drug Administration for approval of Cologuard™." ] 2 => array:3 [ "identificador" => "tblfn0055" "etiqueta" => "d" "nota" => "Data regarding AA measuring ≥10mm." ] 3 => array:3 [ "identificador" => "tblfn0060" "etiqueta" => "e" "nota" => "Data regarding AA measuring >30mm." ] ] ] "descripcion" => array:1 [ "en" => "Results of Sensitivity for detecting advanced precancerous lesions." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:31 [ 0 => array:3 [ "identificador" => "bib0160" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "GLOBOCAN 2012. Colorectal cancer. Estimated incidence, mortality and prevalence worldwide in 2012 [Base de datos en Internet]. Lyon: International Agency for Research on Cancer. World Health Organization; 2014 [accessed 16.09.14]. Available from: <a href="http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx">http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx</a>." ] ] ] 1 => array:3 [ "identificador" => "bib0165" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Sociedad Española de Oncología Médica. Las Cifras del Cáncer en España 2014 [Internet]. Madrid: Sociedad Española de Oncología Médica; 2014 [accessed 16.09.14]. Available from: <a href="http://www.seom.org/en/prensa/el-cancer-en-espanyacom/104582-el-cancer-en-espana-2014">http://www.seom.org/en/prensa/el-cancer-en-espanyacom/104582-el-cancer-en-espana-2014</a>." ] ] ] 2 => array:3 [ "identificador" => "bib0170" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Sistema Nacional de Salud. Informe del grupo de expertos sobre concreción de cartera común de servicios para cribado de cáncer [Internet]. Madrid: Ministerio de Sanidad, Servicios Sociales e igualdad; 2013 [accessed 30.07.14]. Available from: http://www.msssi.gob.es/profesionales/saludPublica/prevPromocion/docs/ResumenEjecutivoCribadoCancer.pdf." ] ] ] 3 => array:3 [ "identificador" => "bib0175" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "National Comprehensive Cancer Network Guidelines (NCCN Guidelines). Colorectal Cancer Screening. Version 1.2014 [Internet]. Washington: NCCN Guidelines; 2014 [accessed 29.07.14]. Clinical Practice Guidelines in Oncology (NCCN Guidelines). Available from: http://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf." ] ] ] 4 => array:3 [ "identificador" => "bib0180" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Segnan, N., Patnick, J., von Karsa (eds). European guidelines for quality assurance in colorectal cancer screening and diagnosis [Internet]. Luxemburgo: Publications Office of the European Union; 2010 [accessed 28.09.14]. Available from: http://www.kolorektum.cz/res/file/guidelines/CRC-screening-guidelines-EC-2011-02-03.pdf." ] ] ] 5 => array:3 [ "identificador" => "bib0185" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Lin, J.S., Webber, E.M., Beil, T.L., Goddard, K.A., Whitlock, E.P. Fecal DNA testing in screening for colorectal cancer in average risk adults [Internet]. Rockville (MD): Agency for Healthcare Research and Quality; 2012 [accessed 11.07.14]. 52 p. Available from: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0041016/pdf/TOC.pdf." ] ] ] 6 => array:3 [ "identificador" => "bib0190" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "ECRI. Cologuard Stool DNA Test for Colorectal Cancer Screening; 2014 [accessed 12.07.14]. Available from: https://www.ecri.org/components/Forecast/Pages/12954.aspx?tab=2." ] ] ] 7 => array:3 [ "identificador" => "bib0195" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Food and Drug Administration (FDA) [Internet]. United States: FDA. FDA approves first non-invasive DNA screening test for colorectal cancer; 2014 [updated 08.08.14; accessed 16.09.14]. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm409021.htm." ] ] ] 8 => array:3 [ "identificador" => "bib0200" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Declaración PRISMA: una propuesta para mejorar la publicación de revisiones sistemáticas y meta-análisis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G. Urrutia" 1 => "X. Bonfill" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin" "fecha" => "2010" "volumen" => "135" "paginaInicial" => "507" "paginaFinal" => "511" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0205" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Withing" 1 => "A. Rutjes" 2 => "J. Reitsma" 3 => "P. Bossuyt" 4 => "J. Kleijnen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2288-3-25" "Revista" => array:5 [ "tituloSerie" => "BMC Med Res Methodol" "fecha" => "2003" "volumen" => "3" "paginaInicial" => "25" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14606960" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0210" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quadas-2: a revised tool for the quality assessment of diagnostic accuracy studies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.F. Whiting" 1 => "A.W.S. Rutjes" 2 => "M.E. Westwood" 3 => "S. Mallett" 4 => "J.J. Deeks" 5 => "J.B. Reitsma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-155-8-201110180-00009" "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2011" "volumen" => "155" "paginaInicial" => "529" "paginaFinal" => "536" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22007046" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0215" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "National Institute for Health and Clinical Excellence (NICE). The guidelines manual. Manchester: NICE; 2012 [accessed 30.07.14]. Available from: http://www.nice.org.uk/article/pmg6/resources/non-guidance-the-guidelines-manual-pdf." ] ] ] 12 => array:3 [ "identificador" => "bib0220" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multitarget stool DNA testing for colorectal-cancer screening" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.F. Imperiale" 1 => "D.F. Ransohoff" 2 => "S.H. Itzkowitz" 3 => "T.R. Levin" 4 => "P. Lavin" 5 => "G.P. Lidgard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1311194" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2014" "volumen" => "370" "paginaInicial" => "1287" "paginaFinal" => "1297" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24645800" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0225" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Detection of colorectal serrated polyps by stool DNA testing: comparison with fecal immunochemical testing for occult blood (FIT) [Internet]" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.I. Heigh" 1 => "T.C. Yab" 2 => "W.R. Taylor" 3 => "F.T.N. Hussain" 4 => "T.C. Smyrk" 5 => "D.W. Mahoney" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0085659" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2014" "volumen" => "9" "paginaInicial" => "e85659" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24465639" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0230" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical performance of an automated stool DNA assay for detection of colorectal neoplasia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G.P. Lidgard" 1 => "M.J. Domanico" 2 => "J.J. Bruinsma" 3 => "J. Light" 4 => "Z.D. Gagrat" 5 => "R.L. Oldham-Haltom" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cgh.2013.04.023" "Revista" => array:6 [ "tituloSerie" => "Clin Gastroenterol Hepatol" "fecha" => "2013" "volumen" => "11" "paginaInicial" => "1313" "paginaFinal" => "1318" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23639600" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0235" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Next-generation stool DNA test accurately detects colorectal cancer and large adenomas" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.A. Ahlquist" 1 => "H. Zou" 2 => "M. Domanico" 3 => "D.W. Mahoney" 4 => "T.C. Yab" 5 => "W.R. Taylor" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2011.10.031" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2012" "volumen" => "142" "paginaInicial" => "248" "paginaFinal" => "256" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22062357" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0240" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The stool DNA test is more accurate than the plasma septin 9 test in detecting colorectal neoplasia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.A. Ahlquist" 1 => "W.R. Taylor" 2 => "D.W. Mahoney" 3 => "H. Zou" 4 => "M. Domanico" 5 => "S.N. Thibodeau" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cgh.2011.10.008" "Revista" => array:6 [ "tituloSerie" => "Clin Gastroenterol Hepatol" "fecha" => "2012" "volumen" => "10" "paginaInicial" => "272" "paginaFinal" => "277" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22019796" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0245" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evidence base of clinical diagnosis. The architecture of diagnostic research" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D. Sackett" 1 => "R. Haynes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "BMJ" "fecha" => "2002" "volumen" => "324" "paginaInicial" => "539" "paginaFinal" => "541" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11872558" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0250" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Zauber, A.G., Lansdorp-Vogelaar, I., Knudsen, A.B., Wilschut, J., van Ballegooijen, M., Kuntz, K.M. Evaluating test strategies for colorectal cancer screening—age to begin, age to stop, and timing of screening intervals: a decision analysis of colorectal cancer screening for the U.S. Preventive Services Task Force from the Cancer Intervention and Surveillance Modeling Network (CISNET) [Internet]. United States: Agency for Healthcare Research and Quality; 2009 [accessed 30.07.14]. 61 p. Available from: http://www.uspreventiveservicestaskforce.org/uspstf08/colocancer/colcanes2.pdf." ] ] ] 19 => array:3 [ "identificador" => "bib0255" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A concordance correlation coefficient to evaluate reproducibility" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "L.I. Lin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Biometrics" "fecha" => "1989" "volumen" => "45" "paginaInicial" => "255" "paginaFinal" => "268" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2720055" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0260" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Agency for Healthcare Research and Quality (AHRQ). The guide to clinical preventive services 2014. Recommendations of the U.S. Preventive services task force. United States: AHRQ; 2014 [accessed 30.07.14]. 123 p. Available from: http://www.ahrq.gov/professionals/clinicians-providers/guidelines-recommendations/guide/cpsguide.pdf." ] ] ] 21 => array:3 [ "identificador" => "bib0265" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Screening for colorectal cancer using the faecal occult blood test, Hemoccult" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Hewitson" 1 => "P. Glasziou" 2 => "L. Irwig" 3 => "B. Towler" 4 => "E. Watson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/14651858.CD009601" "Revista" => array:4 [ "tituloSerie" => "Cochrane database Syst Rev" "fecha" => "2007" "volumen" => "1" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22259004" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0270" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cribado del cáncer colorrectal" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D. Sánchez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Clin Esp" "fecha" => "2014" "volumen" => "214" "paginaInicial" => "275" "paginaFinal" => "276" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0275" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Participation and detection rates by age and sex for colonoscopy versus fecal immunochemical testing in colorectal cancer screening" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Salas" 1 => "M. Vanaclocha" 2 => "J. Ibáñez" 3 => "A. Molina-Barceló" 4 => "V. Hernández" 5 => "J. Cubiella" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10552-014-0398-y" "Revista" => array:6 [ "tituloSerie" => "Cancer Causes Control" "fecha" => "2014" "volumen" => "25" "paginaInicial" => "985" "paginaFinal" => "997" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24859111" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0280" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Colonoscopia versus sangre oculta en heces en el cribado del cáncer colorrectal" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. García" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Clin Esp" "fecha" => "2012" "volumen" => "212" "paginaInicial" => "407" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23115776" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0285" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pólipos colorrectales" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Bacchiddu" 1 => "A. Álvarez-Urturri" 2 => "X. Bessa-Caserras" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "FMC" "fecha" => "2012" "volumen" => "19" "paginaInicial" => "472" "paginaFinal" => "480" ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0290" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rate of detection of advanced neoplasms in proximal colon by simulated sigmoidoscopy vs fecal immunochemical tests" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Castells" 1 => "E. Quintero" 2 => "C. Álvarez" 3 => "L. Bujanda" 4 => "J. Cubiella" 5 => "D. Salas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cgh.2014.03.022" "Revista" => array:6 [ "tituloSerie" => "Clin Gastroenterol Hepatol" "fecha" => "2014" "volumen" => "12" "paginaInicial" => "1708" "paginaFinal" => "1716" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24681078" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0295" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Empirical evidence of design-related bias in studies of diagnostic tests" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.G. Lijmer" 1 => "B.W. Mol" 2 => "S. Heisterkamp" 3 => "G.J. Bonsel" 4 => "M.H. Prins" 5 => "J.H. van der Meulen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "1999" "volumen" => "282" "paginaInicial" => "1061" "paginaFinal" => "1066" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10493205" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0300" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "ECRI Institute AHRQ Healthcare Horizon Scanning System–Potential high impact interventions report. Priority area 02: cancer [Internet]. Plymouth: ECRI Institute; 2014 [accessed 25.10.14]. 144 p. Available from: http://effectivehealthcare.ahrq.gov/ehc/assets/File/Cancer-Horizon-Scan-High-Impact-1406.pdf." ] ] ] 29 => array:3 [ "identificador" => "bib0305" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluating test strategies for colorectal cancer screening: a decision analysis for the U.S. Preventive Services Task Force" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.G. Zauber" 1 => "I. Lansdorp-Vogelaar" 2 => "A.B. Knudsen" 3 => "J. Wilschut" 4 => "M. van Ballegooijen" 5 => "K.M. Kuntz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2008" "volumen" => "149" "paginaInicial" => "659" "paginaFinal" => "669" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18838717" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0310" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Exact Sciences [Internet]. Madison, Wisconsin: Exact Sciences Corporation; 2014. FDA Approves Exact Sciences’ Cologuard®; First and Only Stool DNA Noninvasive Colorectal Cancer Screening Test. [updated 12.08.14; accessed 25.10.14]. Available from: http://investor.exactsciences.com/releasedetail.cfm?ReleaseID=865698." ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack199860" "titulo" => "Acknowledgements" "texto" => "This work has benefited from the contributions of Dr. Manuel Romero Gomez, as well as from the planning and documentation work of Dr. Antonio Romero-Tabares." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/22548874/0000021500000009/v2_201601010034/S2254887415000934/v2_201601010034/en/main.assets" "Apartado" => array:4 [ "identificador" => "46200" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021500000009/v2_201601010034/S2254887415000934/v2_201601010034/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887415000934?idApp=WRCEE"]

Statistics

Review

A systematic review of the clinical validity of the Cologuard™ genetic test for screening colorectal cancer

Validez clínica de la prueba genética Cologuard™ para el cribado de cáncer colorrectal: revisión sistemática

M.Á. Onieva-Garcíaa,

Corresponding author

mariaa.onieva@gmail.com

Corresponding author.

, A. Llanos-Méndezb, E. Baños-Álvarezb, R. Isabel-Gómezb

a UGC Interniveles de Salud Pública de Granada, Spain

b Agencia de Evaluación de Tecnologías Sanitarias de Andalucía, Consejería de Salud de la Junta de Andalucía, Sevilla, Spain

Read

Times
was read the article

Total PDF

Total HTML

Share statistics

 array:23 [
  "pii" => "S2254887415000934"
  "issn" => "22548874"
  "doi" => "10.1016/j.rceng.2015.08.006"
  "estado" => "S300"
  "fechaPublicacion" => "2015-12-01"
  "aid" => "1188"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; y Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
  "copyrightAnyo" => "2015"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "ssu"
  "cita" => "Rev Clin Esp. 2015;215:527-36"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:2 [
    "total" => 37
    "formatos" => array:2 [
      "HTML" => 36
      "PDF" => 1
    ]
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0014256515002180"
      "issn" => "00142565"
      "doi" => "10.1016/j.rce.2015.08.002"
      "estado" => "S300"
      "fechaPublicacion" => "2015-12-01"
      "aid" => "1188"
      "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; y Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "ssu"
      "cita" => "Rev Clin Esp. 2015;215:527-36"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 563
        "formatos" => array:2 [
          "HTML" => 114
          "PDF" => 449
        ]
      ]
      "es" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">REVISI&#211;N</span>"
        "titulo" => "Validez cl&#237;nica de la prueba gen&#233;tica Cologuard<span class="elsevierStyleSup"><span class="elsevierStyleBold">TM</span></span> para el cribado de c&#225;ncer colorrectal&#58; revisi&#243;n sistem&#225;tica"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "527"
            "paginaFinal" => "536"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "A systematic review of the clinical validity of the Cologuard&#8482; genetic test for screening colorectal cancer"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0005"
            "etiqueta" => "Figura 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 1779
                "Ancho" => 1650
                "Tamanyo" => 197583
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Diagrama de flujo de la selecci&#243;n de art&#237;culos&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "M&#46;&#193;&#46; Onieva-Garc&#237;a, A&#46; Llanos-M&#233;ndez, E&#46; Ba&#241;os-&#193;lvarez, R&#46; Isabel-G&#243;mez"
            "autores" => array:4 [
              0 => array:2 [
                "nombre" => "M&#46;&#193;&#46;"
                "apellidos" => "Onieva-Garc&#237;a"
              ]
              1 => array:2 [
                "nombre" => "A&#46;"
                "apellidos" => "Llanos-M&#233;ndez"
              ]
              2 => array:2 [
                "nombre" => "E&#46;"
                "apellidos" => "Ba&#241;os-&#193;lvarez"
              ]
              3 => array:2 [
                "nombre" => "R&#46;"
                "apellidos" => "Isabel-G&#243;mez"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2254887415000934"
          "doi" => "10.1016/j.rceng.2015.08.006"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887415000934?idApp=WRCEE"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256515002180?idApp=WRCEE"
      "url" => "/00142565/0000021500000009/v2_201601010043/S0014256515002180/v2_201601010043/es/main.assets"
    ]
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2254887415000922"
    "issn" => "22548874"
    "doi" => "10.1016/j.rceng.2015.08.005"
    "estado" => "S300"
    "fechaPublicacion" => "2015-12-01"
    "aid" => "1189"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; y Sociedad Espa&#241;ola de Medicina Interna &#40;SEMI&#41;"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "ssu"
    "cita" => "Rev Clin Esp. 2015;215:515-26"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:2 [
      "total" => 57
      "formatos" => array:2 [
        "HTML" => 54
        "PDF" => 3
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
      "titulo" => "Clinical practice guidelines for postmenopausal&#44; glucocorticoid-induced and male osteoporosis&#46; Spanish Society for Research on Bone and Mineral Metabolism &#40;3rd updated version 2014&#41;"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "515"
          "paginaFinal" => "526"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Gu&#237;as de pr&#225;ctica cl&#237;nica en la osteoporosis posmenop&#225;usica&#44; glucocorticoidea y del var&#243;n&#46; Sociedad Espa&#241;ola de Investigaci&#243;n &#211;sea y del Metabolismo Mineral &#40;3&#46;&#170; versi&#243;n actualizada 2014&#41;"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 2325
              "Ancho" => 3295
              "Tamanyo" => 420884
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Drug selection algorithm&#46; Abbreviations&#58; DS&#44; digestive system&#59; ALN&#44; alendronate&#59; Dmab&#44; denosumab&#59; BMD&#44; bone mineral density&#59; FN&#44; femoral neck&#59; RF&#44; renal failure&#59; PTH 1-34&#44; teriparatide&#59; SR&#44; strontium ranelate&#59; RIS&#44; risedronate&#59; SERMs&#44; selective estrogen receptor modulators&#59; ZOLE&#44; zoledronate&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "J&#46; Gonz&#225;lez-Mac&#237;as, J&#46; del Pino-Montes, J&#46;M&#46; Olmos, X&#46; Nogu&#233;s"
          "autores" => array:5 [
            0 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "Gonz&#225;lez-Mac&#237;as"
            ]
            1 => array:2 [
              "nombre" => "J&#46;"
              "apellidos" => "del Pino-Montes"
            ]
            2 => array:2 [
              "nombre" => "J&#46;M&#46;"
              "apellidos" => "Olmos"
            ]
            3 => array:2 [
              "nombre" => "X&#46;"
              "apellidos" => "Nogu&#233;s"
            ]
            4 => array:1 [
              "colaborador" => "on behalf of the Comisi&#243;n de Redacci&#243;n de las Gu&#237;as de Osteoporosis de la SEIOMM"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0014256515002192"
        "doi" => "10.1016/j.rce.2015.08.003"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256515002192?idApp=WRCEE"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887415000922?idApp=WRCEE"
    "url" => "/22548874/0000021500000009/v2_201601010034/S2254887415000922/v2_201601010034/en/main.assets"
  ]
  "en" => array:21 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review</span>"
    "titulo" => "A systematic review of the clinical validity of the Cologuard&#8482; genetic test for screening colorectal cancer"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "527"
        "paginaFinal" => "536"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "M&#46;&#193;&#46; Onieva-Garc&#237;a, A&#46; Llanos-M&#233;ndez, E&#46; Ba&#241;os-&#193;lvarez, R&#46; Isabel-G&#243;mez"
        "autores" => array:4 [
          0 => array:4 [
            "nombre" => "M&#46;&#193;&#46;"
            "apellidos" => "Onieva-Garc&#237;a"
            "email" => array:1 [
              0 => "mariaa&#46;onieva&#64;gmail&#46;com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "A&#46;"
            "apellidos" => "Llanos-M&#233;ndez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "E&#46;"
            "apellidos" => "Ba&#241;os-&#193;lvarez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "R&#46;"
            "apellidos" => "Isabel-G&#243;mez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "UGC Interniveles de Salud P&#250;blica de Granada&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Agencia de Evaluaci&#243;n de Tecnolog&#237;as Sanitarias de Andaluc&#237;a&#44; Consejer&#237;a de Salud de la Junta de Andaluc&#237;a&#44; Sevilla&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Validez cl&#237;nica de la prueba gen&#233;tica Cologuard&#8482; para el cribado de c&#225;ncer colorrectal&#58; revisi&#243;n sistem&#225;tica"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1657
            "Ancho" => 1650
            "Tamanyo" => 200381
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Risk of bias&#46; Applicability of each study&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Colorectal cancer &#40;CRC&#41; is the most common malignancy in Europe and Spain and constitutes the second leading cause of overall mortality from cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a> It is estimated that the mortality rate from CRC has decreased by 13&#37; in the last two decades in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">2</span></a> However&#44; this decrease is still well below that achieved in other European countries and the United States&#44; and screening detection rates remain suboptimal&#44; mainly due to the low participation of the population&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Current screening methods targeted toward the population aged 50 years or more at moderate risk include annual high-sensitivity fecal occult blood tests &#40;FOBT&#41; &#40;guaiac-based or immunological &#91;FOBTi&#93;&#41;&#59; sigmoidoscopy every 5 years and FOBT every 3 years&#59; or colonoscopy every 10 years&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">4&#44;5</span></a> The method of choice in Spain is FOBTi every 2 years&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">3</span></a> Although there is consensus for recommending any of these alternatives&#44; there is still controversy regarding the cost-effectiveness of deoxyribonucleic acid &#40;DNA&#41; tests in feces due to the lack of data for determining the screening interval&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Stool DNA tests are designed to detect molecular abnormalities in the epithelial cells of precancerous adenomatous polyps &#40;advanced adenoma &#91;AA&#93; or sessile serrated polyp &#91;SSP&#93;&#41; or sloughed CRC cells into the large intestine lumen&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">7</span></a> To date&#44; only two DNA tests have been marketed &#40;PreGen Plus&#8482; and ColoSure&#8482;&#41;&#44; none of which have been approved by the Food and Drug Administration&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">6</span></a> The multitarget stool DNA test marketed as Cologuard&#8482; has recently been approved by the Food and Drug Administration as a screening test for population at moderate risk of CRC and has been included as a healthcare provision in the Medicare and Medicaid services of the United States&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">8</span></a> The main differences from its predecessors &#40;PreGen Plus&#8482; and ColoSure&#8482;&#41; lies in the detected genetic markers&#44; the incorporation of fecal occult blood &#40;FOB&#41; detection and the use of QuARTS technology&#8482; for real-time DNA amplification&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">6</span></a> This emerging technology could be an alternative noninvasive screening&#44; which&#44; with optimal performance and increased adherence rate&#44; might reduce the incidence and mortality of CRC&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this systematic review was to combine the available evidence to analyze the validity&#44; diagnostic accuracy and clinical utility of the multitarget stool DNA test &#40;Cologuard&#8482;&#41; in CRC screening&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A systematic literature review was performed by following the PRISMA recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">9</span></a> The results were summarized in narrative form&#46; A statistical analysis was not possible due to the heterogeneity of the studies&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Information sources</span><p id="par0030" class="elsevierStylePara elsevierViewall">The MedLine&#44; EMBASE&#44; Web of Science and PubMed databases were consulted until July 2014&#46; In addition&#44; we also consulted the Centre for Reviews and Dissemination&#44; the International Information Network on New and Emerging Health Technologies &#40;EuroScan&#41;&#44; the Cochrane Library&#44; the website of agencies not included in the International Network of Agencies for Health Technology Assessment&#44; the Ministry of Health&#44; Social Services and Equality&#44; the platforms of Agencies and Health Technology Assessment Units&#44; the World Health Organization&#44; the Centers for Disease Control and Prevention&#44; the Emergency Care Research Institute &#40;ECRI&#41; and the National Institute for Health and Clinical Excellence&#46; Secondary references were also reviewed&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">For this purpose&#44; both natural and controlled language was employed&#44; using the terms&#58; &#8220;colorectal neoplasms&#44;&#8221; &#8220;DNA mutational analysis&#44;&#8221; &#8220;stool DNA test&#44;&#8221; &#8220;Cologuard&#44;&#8221; &#8220;mass screening&#44;&#8221; &#8220;screening&#44;&#8221; &#8220;early detection of cancer&#44;&#8221; &#8220;sensitivity&#44;&#8221; &#8220;specificity&#44;&#8221; &#8220;likelihood functions&#44;&#8221; &#8220;reproducibility of results&#8221; and &#8220;area under the curve&#44;&#8221; among others&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Selection of studies</span><p id="par0040" class="elsevierStylePara elsevierViewall">Two reviewers independently selected studies that examined the validity and diagnostic accuracy of the multitarget stool DNA test&#44; comparing it with any method for the diagnosis or screening of CRC in asymptomatic populations&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Assessment reports and summaries of emerging technologies were also included&#44; because they contain useful information for corroborating the methodological rigor of our search&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Narrative reviews&#44; letters to the editor&#44; editorials&#44; meeting abstracts and preclinical studies were excluded&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Data extraction</span><p id="par0055" class="elsevierStylePara elsevierViewall">The variables included the characteristics of the study &#40;author&#44; year of publication&#44; country&#44; study period&#44; objectives&#44; phase of the study and funding&#41;&#59; the population &#40;sample size&#44; sociodemographic and clinical features&#44; inclusion and exclusion criteria&#41;&#59; and the intervention &#40;screening test and reference&#41;&#46; In addition&#44; the results relating to diagnostic validity and accuracy &#40;sensitivity&#44; specificity&#44; predictive values&#44; likelihood ratios&#44; ROC curve and intraobserver and interobserver variability&#41; were extracted&#46; When possible&#44; 2<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>2 contingency tables were generated to calculate these parameters from each study&#39;s data&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Assessment of risk of bias and evidence level</span><p id="par0060" class="elsevierStylePara elsevierViewall">In addition&#44; two reviewers independently assessed the quality and risk of bias according to the Quality Assessment of Diagnostic Accuracy Studies-1 and Quality Assessment of Diagnostic Accuracy Studies-2 tool&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">10&#44;11</span></a> Discrepancies were resolved by consensus&#46; The level of evidence was defined according to The National Institute for Health and Clinical Excellence recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">12</span></a></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0065" class="elsevierStylePara elsevierViewall">A total of 299 references were identified&#46; After the selection process&#44; 5 primary studies of diagnostic tests &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; were included&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;17</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Likewise&#44; a summary report published by ECRI that assessed the impact of Cologuard&#8482; was included&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">7</span></a> The authors predicted&#44; regarding the current screening tests&#44; an increase in the adherence rate and early detection of lesions that consequently results in greater health benefits but also increased costs&#46;</p><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Characteristics of the primary studies</span><p id="par0075" class="elsevierStylePara elsevierViewall">All studies examined the validity of DNA biomarkers in feces&#44; along with the FOB in the detection rate of CRC or advanced precancerous lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;17</span></a> The reference test was colonoscopy&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;17</span></a> considering the index lesion the most advanced colorectal epithelial lesion<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;17</span></a> or the larger among two or more similar lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#44;16</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The three studies<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;15</span></a> that used the DNA Cologuard&#8482; biomarker panel assessed aberrant methylations in the promoter region of bone morphogenetic protein 3 &#40;BMP3&#41; and N-Myc downstream-regulated gene 4 &#40;NDRG4&#41;&#44; 7-point mutations in the Kirsten rat sarcoma viral oncogene homolog &#40;KRAS&#41; gene and detected FOB by quantitative FOBTi&#46; The remaining two studies evaluated the Cologuard&#8482; prototype&#44;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">16&#44;17</span></a> which also detects aberrant methylations in the vimentin &#40;VIM&#41; and tissue factor pathway inhibitor 2 &#40;TFPI2&#41; genes&#46; FOB was detected by the porphyrin method&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The cumulative study population for analyzing the performance of the Cologuard&#8482; test was 14&#44;235 participants &#40;13&#44;691 apparently asymptomatic and 544 with symptoms suggestive of CRC&#41;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;15</span></a> and 825 for the prototype &#40;including asymptomatic individuals and those with suggestive symptoms&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">16&#44;17</span></a> The percentage of women ranged from 50&#37; to 55&#37;&#44; and the mean age ranged from 60 to 65 years &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The excluded patients were those with syndromes at high risk for CRC &#40;Lynch syndrome or familial adenomatous polyposis&#41;&#44; inflammatory bowel disease&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#44;14&#44;16</span></a> previous colorectal resection&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#44;14</span></a> recent screening test&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#44;14</span></a> a history of gastrointestinal neoplasia or bleeding in the past 30 days<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a> or who underwent incomplete colonoscopy&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">14</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Risk of bias in the primary studies</span><p id="par0090" class="elsevierStylePara elsevierViewall">The methodological quality of the prospective studies was high<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#44;14</span></a> &#40;or Sackett phase <span class="elsevierStyleSmallCaps">III</span><a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">18</span></a>&#41; with level Ib evidence&#46; The rest of the studies had moderate quality<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">15&#8211;17</span></a> and a case-control design &#40;Sackett phase <span class="elsevierStyleSmallCaps">II</span>&#41; and level <span class="elsevierStyleSmallCaps">III</span> evidence&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The main risk of bias was related to the characteristics of the participants in the case-control studies &#40;selection bias&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">15&#8211;17</span></a> The inclusion of patients with symptoms suggestive of the target disease could overestimate the diagnostic validity parameters &#40;predictive values and sensitivity&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">The risk of bias in the interpretation of the study test results was low&#44; because the positivity of the test was objectively defined with a pre-set cutoff value&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;17</span></a> In contrast&#44; there was a risk of observer bias in three studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">15&#8211;17</span></a> The observers did not record whether the colonoscopy &#40;a subjective test&#41; was performed without knowing the test&#39;s positivity or negativity&#44; which could have influenced the interpretation of the colonoscopy results and biased the results&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">All patients had undergone colonoscopy as the reference test&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;17</span></a> Regarding the patient classification&#44; it was considered that there had been no errors in the diagnosis of precancerous or cancerous lesions found during the colonoscopy because&#44; except for 9 lesions in the Heigh et al&#46; study&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">14</span></a> all lesions were confirmed by pathology &#40;gold standard&#41;&#46; Moreover&#44; although there is some uncertainty about the correct classification of the healthy participants who did not undergo pathology&#44; this was not considered relevant according to the colonoscopy diagnostic performance &#40;95&#37; sensitivity and 90&#37; specificity&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">19</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The time interval between the colonoscopy and the study test was reported in 1 study &#40;90 days at most&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a> In the remaining studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">14&#8211;17</span></a> this interval was not specified&#44; raising doubts about the similarity of the spectrum of patients undergoing each test at two different times&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Only the Imperiale et al&#46; study suffered losses &#40;21&#46;8&#37; of participants&#41;&#46; The authors found significant differences in age and race between the participants who completed the study and were evaluated and those who did not complete it and were not included in the analysis&#46; The magnitude of these differences was not noticeable except for the participants older than 74 years&#46; The proportion of these participants was 9&#37; in the evaluated group compared to 13&#46;6&#37; in the nonevaluated group&#46; This could have underestimated the detection of proximal cancers&#44; which are more common than distal cancers at the age of 70 or older&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results of the primary studies</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Diagnostic accuracy and overall performance of the Cologuard&#8482; test</span><p id="par0120" class="elsevierStylePara elsevierViewall">The sensitivity ranged from 92&#46;3&#37; to 97&#46;8&#37; for CRC and from 42&#46;4&#37; to 57&#37; for AA&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#44;14</span></a> The sensitivity for SSP was 55&#46;2&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">14</span></a> The specificity for advanced colorectal neoplasia &#40;including CRC and AA&#41; achieved a range between 86&#46;6&#37; and 90&#37;&#46; The positive likelihood ratio &#40;LR&#43;&#41; ranged from 5&#46;9 to 9&#46;8 for CRC and from 3&#46;2 to 5&#46;7 for AA&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#44;14</span></a> indicating the number of times more likely the test will be positive for a sick patient than for a healthy one&#46; Therefore&#44; a positive test result provides strong diagnostic evidence for CRC&#44; while it is less useful for detecting AA&#44; although its detection could be considered clinically relevant &#40;values above 10 indicate conclusive diagnostic evidence&#59; between 5 and 10 indicates strong evidence&#59; and between 1 and 2 indicates low evidence&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">20</span></a> Furthermore&#44; the negative likelihood ratio &#40;LR&#8722;&#41; ranged from 0&#46;02 to 0&#46;09 for CRC and from 0&#46;5 to 0&#46;7 for AA&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#44;14</span></a> indicating the number of times more likely the test will be negative for a sick patient than for a healthy one&#46; Thus&#44; a negative test result provides conclusive diagnostic evidence against CRC&#44; in other words&#44; it is an excellent test for ruling out CRC&#46; A negative test result also provides low evidence for ruling out AA &#40;values below 0&#46;1 indicate conclusive diagnostic evidence&#59; lower than 0&#46;2 indicates strong evidence&#59; and between 0&#46;6 and 1 indicates low evidence&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">20</span></a> The overall test performance was higher for CRC &#40;area under the curve&#58; 0&#46;94&#41; than for advanced colorectal neoplasia &#40;0&#46;73&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a> Heigh et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">14</span></a> measured the discriminative ability of each marker and found statistically significant values for BMP3&#44; NDRG4 and KRAS &#40;0&#46;87 &#91;95&#37; CI 0&#46;80&#8211;0&#46;95&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#59; 0&#46;79 &#91;95&#37; CI 0&#46;70&#8211;0&#46;88&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#59; 0&#46;64 &#91;95&#37; CI 0&#46;53&#8211;0&#46;75&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0068&#44; respectively&#41; but not for occult hemoglobin &#40;0&#46;50 &#91;95&#37; CI 0&#46;40&#8211;0&#46;61&#93;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;47&#41;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#44;14</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Diagnostic validity and overall performance of Cologuard&#8482; prototype</span><p id="par0125" class="elsevierStylePara elsevierViewall">The sensitivity ranged from 84&#46;9&#37; to 86&#46;7&#37; for CRC and from 54&#46;1&#37; to 81&#46;8&#37; for AA&#46; The specificity for advanced colorectal neoplasia was 89&#46;1&#37;&#46; This test provided strong diagnostic evidence to detect and rule out CRC &#40;LR&#43;&#44; 7&#46;7&#59; LR&#8722;&#44; 0&#46;2&#41; and was less useful for AA &#40;LR&#43;&#44; 4&#46;9&#59; LR&#8722;&#44; 0&#46;5&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">16&#44;17</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Ahlquist et al&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a> found an area under the curve of 0&#46;90 &#40;95&#37; CI 0&#46;86&#8211;0&#46;93&#41; for the full marker panel &#40;BMP3&#44; NDRG4&#44; KRAS&#44; TFPI2&#44; VIM and hemoglobin&#41; versus 0&#46;88 &#40;95&#37; CI 0&#46;84&#8211;0&#46;91&#41; for the panel without hemoglobin&#46; The relative contribution of TFPI2 and VIM was minimal&#44; increasing the sensitivity from 1 to 3 percentage points&#46; In contrast&#44; BMP3&#44; NDRG4 and KRAS significantly contributed to the test&#39;s discriminative ability &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Accuracy</span><p id="par0135" class="elsevierStylePara elsevierViewall">Ahlquist et al&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a> found a high degree of agreement in the results among the various laboratories &#40;correlation coefficient of 0&#46;978&#8211;0&#46;996&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Comparison with other screening tests</span><p id="par0140" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Comparison of Cologuard&#8482; with quantitative FOBTi &#40;OC-FIT CHEK&#44; Polymedco&#41;&#46; In the study by Heigh et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">14</span></a> the detection rate for SSP<span class="elsevierStyleHsp" style=""></span>&#8805;1<span class="elsevierStyleHsp" style=""></span>cm using the Cologuard&#8482; BMP3 test was 66&#37; and 63&#37; for the predetermined specificities of 91&#37; and 95&#37;&#44; respectively&#44; compared to the 10&#37; and 0&#37; achieved with FOBTi&#46; These differences were statistically significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;003&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#44; respectively&#41;&#46; In the Imperiale et al&#46; study&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a> Cologuard&#8482; was more sensitive for detecting CRC in any stage &#40;stages <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">III</span>&#41; and for both locations &#40;proximal and distal&#41;&#44; with values of approximately 90&#37; or higher&#46; The absolute differences of 24 percentage points for stages I and <span class="elsevierStyleSmallCaps">II</span>&#44; and the proximal location stand out&#46; Although the sensitivity of Cologuard&#8482; achieved lower values &#40;approximately 50&#37;&#41; for AA detection&#44; the sensitivity was also greater&#44; with absolute differences ranging from 16 to 26 percentage points and up to 37 points for SSP detection&#46; However&#44; the specificity of FOBTi &#40;94&#46;9&#8211;96&#46;4&#37;&#41; was higher than that of Cologuard&#8482; &#40;86&#46;6&#8211;89&#46;8&#37;&#41;&#44; with false positive rates of 3&#46;6&#8211;5&#46;1&#37; and 10&#46;2&#8211;13&#46;4&#37;&#44; respectively<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a> &#40;<a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3 and 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Comparison of the Cologuard&#8482; prototype with methylated SEPT9 gene in plasma &#40;Septin 9&#41;&#46; The sensitivity for detecting CRC and large AA with the Cologuard&#8482; prototype was higher than that of Septin 9 &#40;85&#37; vs&#46; 40&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46; The same occurred with the isolated sensitivity for detecting large AA &#40;82&#37; vs&#46; 14&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#44; CRC &#40;87&#37; vs&#46; 60&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;046&#41;&#44; stages <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">III</span> of CRC &#40;95&#37; vs&#46; 50&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;013&#41; and proximal CRC &#40;92&#37; vs&#46; 46&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;034&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">17</span></a> The false positive rate of Septin 9 was higher than that of the prototype &#40;21&#37; vs&#46; 7&#37;&#41; &#40;<a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3 and 4</a>&#41;&#46;</p></li></ul></p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0155" class="elsevierStylePara elsevierViewall">Spain has recently approved the inclusion of CRC screening in the National Health System&#39;s basic portfolio of services&#44; using FOBTi &#40;performed every 2 years&#41; for the population aged 50&#8211;69 years&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">3</span></a> Although FOBTi has proven to be cost-effective&#44;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">21&#8211;23</span></a> the low participation rate &#40;approximately 35&#37;&#41; has led to suboptimal results&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">3&#44;24&#44;25</span></a> The acceptance rate is even lower when colonoscopy is the screening test of choice &#40;approximately 25&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">24&#44;25</span></a> New genetic tests&#44; such as Cologuard&#8482;&#44; represent an alternative screening that could improve the program&#39;s performance as a whole&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">5</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Considering that sensitivity is the most important attribute of a diagnostic test designed for mass screening&#44; one could conclude that Cologuard&#8482; is a valid test for detecting CRC at any stage&#44; including early stages and both proximal and distal locations&#44; with sensitivities of over 90&#37;&#46; An LR&#8722; lower than 0&#46;1 also makes it an excellent test for ruling out CRC&#46; However&#44; its utility in detecting AA is lower&#44; with sensitivities of approximately 40&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;15</span></a> although always higher than those obtained by FOBTi&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a> The results for the prototype were similar but with slightly lower LR&#8722; and sensitivity values&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">16&#44;17</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">There are two remarkable findings that could play a major role in clinical practice&#46; One of these findings is the increased sensitivity of Cologuard&#8482; for serrated polyps compared with FOBTi&#44; given that the polyp-cancer sequence appears fastest in the serrated pathway&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">26</span></a> The other important aspect is that proximal cancer detection with Cologuard&#8482; was substantially higher than with FOBTi&#46; This finding is particularly relevant because of the lower diagnostic performance when detecting proximal malignancies &#40;when compared with distal malignancies&#41; reported for FOBT and lower endoscopy&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">27</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The articles included in this review could be considered a compendium of consecutive studies of increasing complexity that gradually control the various biases that can affect the validation process&#44; seeking more pragmatic goals that are applicable to clinical practice&#46; Thus&#44; we can see that the Ahlquist et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">16&#44;17</span></a> and Lidgard et al&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">15</span></a> &#40;case-control design&#41; studies have methodological deficits &#40;mainly related to the spectrum of patients&#41; to a greater degree than the Heigh et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">14</span></a> and Imperiale et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a> &#40;prospective design&#41; studies&#46; As previously mentioned&#44; the inclusion of patients with similar symptoms to those of the target disease in the Alhquist et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">16&#44;17</span></a> and Lidgard et al&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">15</span></a> studies would theoretically increase the prevalence of the disease&#44; overestimating the diagnostic validity parameters related to the post-test probability &#40;predictive values&#41;&#46; Thus&#44; an increase in the number of patients would indirectly increase the test sensitivity&#46; For this reason and given that the case-control design is the most critical aspect in the introduction of risk of bias&#44;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">28</span></a> we have assigned more importance to the prospective studies in the conclusions of this systematic review&#46; These studies were able to minimize the risk of bias in each assessed aspect&#58; adequate spectrum of patients&#44; blind interpretation of results&#44; appropriate reference test and adequate reporting of losses&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The external validity was limited by the heterogeneity in the test&#39;s maturity&#44; as a number of studies used the marketed test &#40;Cologuard&#8482;&#41;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;15</span></a> while others used the prototype&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">16&#44;17</span></a> Another aspect of the external validity was the study setting&#44; which was focused primarily on North America&#46; However&#44; the extrapolation of results to a hypothetical Spanish population does not imply&#44; in theory&#44; a lower diagnostic validity for the test &#40;in terms of post-test probability&#41;&#44; given that the prevalence of CRC in Spain is higher than in North America&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">1</span></a> It is also noteworthy that the funding for most of the studies came from the company that developed and distributed the test&#44; which could represent a conflict of interest&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">It has already been stated that Cologuard&#8482; is a valid test&#44; a prerequisite for any screening or diagnostic test&#44; but it is not sufficient&#46; Its success in a screening program&#44; measured in terms of health benefits&#44; will depend on many other factors that have yet to be analyzed&#46; Thus&#44; the possibility of including Cologuard&#8482; in the National Health System&#39;s portfolio of services depends on ethical&#44; social and organizational aspects&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">First&#44; we should assess the acceptance of the screening test by the population&#46; The authors of the summary report from the ECRI<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">7</span></a> measured greater adherence compared with the current screening tests&#46; However&#44; there are limiting factors&#46; For example&#44; 36<span class="elsevierStyleHsp" style=""></span>g of feces are required for the proper processing of Cologuard&#8482;&#44; which could hinder both population recruitment and laboratory handling&#46; Moreover&#44; Cologuard&#8482; and FOBT share the same sample collection procedure&#59; therefore&#44; from the patient&#39;s point of view&#44; both tests would be similar&#46; In our opinion&#44; these issues could lessen the hypothetical increase in adherence with the use of Cologuard&#8482;&#46; We should be aware that the higher adherence mentioned by the ECRI authors was based on expert forecasts and opinions&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Second&#44; the rate at which Cologuard&#8482; should be performed to ensure lesion detection is not yet known&#46; The company that marketed the test has proposed a 3-year interval between two consecutive screenings&#44;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">29</span></a> but the studies included in this review do not provide sufficient data on this issue&#46; It is essential to determine this interval to measure the effects of Cologuard&#8482; in reducing CRC incidence and mortality and to compare it with other screening methods&#44; given that the literature shows that periodicity determines&#44; along with other factors&#44; the achievement &#40;or not&#41; of optimum results&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">30</span></a> It would therefore be advisable to have studies that compare the frequency of the test to that of current tests and compare the overall performance of the screening program for various strategies&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Third&#44; the specificity of the test should be considered&#46; Although the sensitivity is necessary for the screening tests&#44; it is not sufficient&#46; The lower specificity found for Cologuard&#8482; compared with FOBT increases the probability of finding false positives&#44; thereby resulting in the need for confirmation by colonoscopy&#46; Therefore&#44; although Cologuard&#8482; is a valid test in terms of efficiency&#44; it might be inefficient for most patients who end up needing a colonoscopy&#44; with the resulting consumption of resources &#40;cost increase&#41; and side effects such as overdiagnosis&#44; anxiety and risk of complications from invasive tests such as colonoscopy&#46; The estimated cost for Cologuard&#8482; is also 30 times higher than that of FOBT&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">31</span></a> which significantly increases the cost of the screening program&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">In conclusion&#44; this systematic review shows that the multitarget stool DNA test Cologuard&#8482; is an effective &#40;and valid&#41; screening test for ruling out cancerous lesions and&#44; to a lesser extent&#44; precancerous lesions&#46; However&#44; there are no data for determining whether the Cologuard&#8482; screening program could obtain greater health benefits compared with current programs&#59; that is&#44; whether it would be more effective in terms of reducing CRC incidence and mortality&#46; To determine to what extent this test could provide improvements&#44; future studies should delve deeper into issues such as the impact on population participation &#40;adherence&#41;&#44; the time interval between two consecutive screenings to ensure early lesion detection and test efficiency through cost-effectiveness studies&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Funding</span><p id="par0205" class="elsevierStylePara elsevierViewall">This document was developed under the collaboration agreement signed by the Institute of Health Carlos <span class="elsevierStyleSmallCaps">III</span>&#44; an autonomous body of the Ministry of Economy and Competitiveness and the Department of Equality&#44; Health and Social Policy of the Andalusian Government as part of the development of activities of the Spanish Network of Agencies for Health Technology Assessment and Services of the NHS&#44; funded by the Ministry of Health&#44; Social Services and Equality&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflict of interests</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:12 [
        0 => array:3 [
          "identificador" => "xres594218"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Objectives"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Material and methods"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Conclusions"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec609140"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres594217"
          "titulo" => "Resumen"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Objetivos"
            ]
            1 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "Material y m&#233;todos"
            ]
            2 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Resultados"
            ]
            3 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "Conclusiones"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec609141"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Background"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Methods"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Information sources"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Selection of studies"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Data extraction"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Assessment of risk of bias and evidence level"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0035"
          "titulo" => "Results"
          "secciones" => array:5 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Characteristics of the primary studies"
            ]
            1 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Risk of bias in the primary studies"
            ]
            2 => array:3 [
              "identificador" => "sec0050"
              "titulo" => "Results of the primary studies"
              "secciones" => array:2 [
                0 => array:2 [
                  "identificador" => "sec0055"
                  "titulo" => "Diagnostic accuracy and overall performance of the Cologuard&#8482; test"
                ]
                1 => array:2 [
                  "identificador" => "sec0060"
                  "titulo" => "Diagnostic validity and overall performance of Cologuard&#8482; prototype"
                ]
              ]
            ]
            3 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Accuracy"
            ]
            4 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Comparison with other screening tests"
            ]
          ]
        ]
        7 => array:2 [
          "identificador" => "sec0075"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Funding"
        ]
        9 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conflict of interests"
        ]
        10 => array:2 [
          "identificador" => "xack199860"
          "titulo" => "Acknowledgements"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2015-04-09"
    "fechaAceptado" => "2015-08-19"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec609140"
          "palabras" => array:5 [
            0 => "Systematic review"
            1 => "Colorectal cancer"
            2 => "Screening"
            3 => "Analysis of DNA mutations"
            4 => "Feces"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec609141"
          "palabras" => array:5 [
            0 => "Revisi&#243;n sistem&#225;tica"
            1 => "C&#225;ncer colorrectal"
            2 => "Cribado"
            3 => "An&#225;lisis de mutaciones de ADN"
            4 => "Heces"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The aim of this study was to assess the available evidence on the validity&#44; diagnostic accuracy and clinical utility of the multitarget DNA test in feces &#40;Cologuard&#8482;&#41; for screening for colorectal cancer &#40;CRC&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A systematic review was performed by consulting MedLine&#44; EMBASE and Web of Science to July 2014&#46; Studies on diagnostic tests were selected that evaluated the test in asymptomatic adults who underwent CRC screening&#46; The quality and risk of bias were assessed using the Quality Assessment of Diagnostic Accuracy Studies tool&#46; The level of evidence was defined according to the National Institute for Health and Clinical Excellence&#46; A qualitative synthesis was conducted&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 299 literature references were identified&#44; including 1 synthesis report and 5 diagnostic test studies&#46; Three of the five studies had a case-control design in Sackett phase <span class="elsevierStyleSmallCaps">II</span> and were of moderate quality&#44; and two had a prospective design in Sacket phase <span class="elsevierStyleSmallCaps">III</span> and were of high quality&#46; The sensitivity for detecting CRC was greater than 90&#37;&#44; but only 40&#37; for detecting advanced adenomas&#46; The test provided conclusive diagnostic evidence to rule out CRC &#40;negative likelihood ratio&#44; LR&#8722;&#58; 0&#46;02&#8211;0&#46;09&#41;&#44; although it was not useful for ruling out advanced adenoma &#40;LR&#8722;&#58; 0&#46;5&#8211;0&#46;7&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The Cologuard&#8482; test is a valid screening test for ruling out cancerous lesions but is suboptimal for ruling out precancerous lesions&#46; There is no evidence in terms of mortality&#44; survival or cost-effectiveness&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El objetivo fue evaluar la evidencia disponible sobre la validez&#44; precisi&#243;n diagn&#243;stica y utilidad cl&#237;nica del test multidiana de ADN en heces &#40;Cologuard&#8482;&#41; en el cribado de c&#225;ncer colorrectal &#40;CCR&#41;&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; una revisi&#243;n sistem&#225;tica consultando MedLine&#44; EMBASE y Web of Science hasta julio de 2014&#46; Se seleccionaron estudios de pruebas diagn&#243;sticas que evaluaran el test en adultos asintom&#225;ticos sometidos a cribado de CCR&#46; La calidad y el riesgo de sesgo se evaluaron mediante la herramienta <span class="elsevierStyleItalic">Quality Assessment of Diagnostic Accuracy Studies</span>&#46; El nivel de evidencia se defini&#243; seg&#250;n <span class="elsevierStyleItalic">The National Institute for Healthand Clinical Excellence</span>&#46; Se realiz&#243; una s&#237;ntesis cualitativa&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se identificaron 299 referencias bibliogr&#225;ficas&#44; incluy&#233;ndose un informe de s&#237;ntesis y cinco estudios de pruebas diagn&#243;sticas&#44; tres de ellos con dise&#241;o caso-control en fase <span class="elsevierStyleSmallCaps">II</span> de Sackett y de moderada calidad&#44; y dos con dise&#241;o prospectivo en fase <span class="elsevierStyleSmallCaps">III</span> de Sacket y de alta calidad&#46; La sensibilidad para detectar CCR fue superior al 90&#37;&#44; pero solo del 40&#37; para la detecci&#243;n de adenoma avanzado&#46; El test proporcion&#243; evidencia diagn&#243;stica concluyente para descartar CCR &#40;cociente de probabilidad negativo&#44; CPN&#58; 0&#44;02-0&#44;09&#41;&#44; aunque no fue &#250;til para descartar adenoma avanzado &#40;CPN&#58; 0&#44;5-0&#44;7&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El test Cologuard&#8482; es una prueba de cribado v&#225;lida para descartar lesiones cancerosas&#44; resultando sub&#243;ptima para descartar lesiones precancerosas&#46; No hay evidencia sobre resultados en t&#233;rminos de mortalidad o supervivencia&#44; ni sobre coste-efectividad&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivos"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Material y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0065">Please cite this article as&#58; Onieva-Garc&#237;a M&#193;&#44; Llanos-M&#233;ndez A&#44; Ba&#241;os-&#193;lvarez E&#44; Isabel-G&#243;mez R&#46; Validez cl&#237;nica de la prueba gen&#233;tica Cologuard&#8482; para el cribado de c&#225;ncer colorrectal&#58; revisi&#243;n sistem&#225;tica&#46; Rev Clin Esp&#46; 2015&#59;215&#58;527&#8211;536&#46;</p>"
      ]
    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1779
            "Ancho" => 1650
            "Tamanyo" => 187791
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flow diagram for the selection of articles&#46;</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" => 1657
            "Ancho" => 1650
            "Tamanyo" => 200381
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Risk of bias&#46; Applicability of each study&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; <span class="elsevierStyleItalic">N</span>&#44; population size&#59; NA&#44; not applicable&#59; NC&#44; not specified&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Test&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Author and year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Type of patient&#44; <span class="elsevierStyleItalic">n</span>&nbsp;\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">Women&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Mean age&#44; years &#40;range&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></th><th class="td" title="table-head  " align="left" valign="top" scope="col">Race&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\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">CRC stage&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Overall&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Without lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">With lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Overall&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Without lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">With lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleSmallCaps">IV</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cologuard&#8482;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Imperiale 2014<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#44;776&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asymptomatic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5364 &#40;54&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64 &#40;NC&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">White&#44; 8392 &#40;84&#41;African-American&#44; 1068 &#40;11&#41;Other&#44; 523 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Heigh 2014<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">456&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asymptomatic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">138<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;53&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;52&#8211;77&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lidgard 2013<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Asymptomatic&#44; 459Symptomatic&#44; 544&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">549<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;55&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">462<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;58&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">87<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;42&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;38&#8211;87&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65 &#40;50&#8211;84&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65 &#40;38&#8211;87&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">76 &#40;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;8&#41;&nbsp;\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">Cologuard&#8482; prototype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">147&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;51&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> &#40;57&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24 &#40;46&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;51&#8211;75&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> &#40;51&#8211;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">69 &#40;61&#8211;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22 &#40;73&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">678&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">AsymptomaticSymptomatic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">339<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">164<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;56&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">173<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> &#40;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60 &#40;39&#8211;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">57 &#40;41&#8211;87&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63 &#40;39&#8211;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Blanca&#44; 549 &#40;81&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">225 &#40;89&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27 &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab971648.png"
              ]
            ]
          ]
          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Data referring to the assessed population&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Data calculated by the authors of the review based on data from the studies&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Controls paired by age and sex for feces sample &#40;does not include the controls paired by age and sex for plasma sample&#41;&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the study population&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; LR&#8722;&#44; negative likelihood ratio&#59; LR&#43;&#44; positive likelihood ratio&#59; 95&#37; CI&#44; 95&#37; confidence interval&#59; NC&#44; not calculated&#59; ND&#44; no data&#59; NPV&#44; negative predictive value&#59; PPV&#44; positive predictive value&#46;</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">Type of lesion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Author and year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Phase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sensitivity &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Specificity &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PPV &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NPV &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LR&#43; &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LR&#8722; &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="9" align="left" valign="top"><span class="elsevierStyleItalic">Cologuard</span>&#8482;</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>Colorectal cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Imperiale 2014<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;923 &#40;0&#46;832&#8211;0&#46;967&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;844 &#40;0&#46;836&#8211;0&#46;851&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;037 &#40;0&#46;029&#8211;0&#46;048&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;999 &#40;0&#46;998&#8211;0&#46;999&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;902<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;5&#46;428&#8211;6&#46;418&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;091<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;039&#8211;0&#46;212&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lidgard 2013<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;978 &#40;0&#46;924&#8211;0&#46;997&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;900 &#40;0&#46;879&#8211;0&#46;919&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;785<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> &#40;8&#46;033&#8211;11&#46;918&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;024<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> &#40;0&#46;006&#8211;0&#46;094&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\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>Advanced adenoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Imperiale 2014<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;424 &#40;0&#46;389&#8211;0&#46;460&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;866<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;859&#8211;0&#46;872&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;207<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;187&#8211;0&#46;228&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;8657<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;859&#8211;0&#46;872&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;158<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;2&#46;863&#8211;3&#46;483&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;665<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;626&#8211;0&#46;708&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lidgard 2013<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;570 &#40;0&#46;474&#8211;0&#46;663&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;900 &#40;0&#46;879&#8211;0&#46;919&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;745<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> &#40;4&#46;416&#8211;7&#46;474&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;477<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a> &#40;0&#46;386&#8211;0&#46;590&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\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>Sessile serrated polyp&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Heigh 2014<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">14</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;552 &#40;0&#46;357&#8211;0&#46;736&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;909 &#40;0&#46;865&#8211;0&#46;943&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;432<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;287&#8211;0&#46;591&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;942<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;903&#8211;0&#46;965&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;095<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;3&#46;611&#8211;10&#46;288&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;493<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;328&#8211;0&#46;740&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\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>Advanced colorectal neoplasm<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Imperiale 2014<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;464<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;429&#8211;0&#46;498&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;866 &#40;0&#46;859&#8211;0&#46;872&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;236 &#40;0&#46;216&#8211;0&#46;258&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;947 &#40;0&#46;942&#8211;0&#46;952&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;452<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;3&#46;154&#8211;3&#46;777&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;620<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;581&#8211;0&#46;661&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lidgard 2013<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;754<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;689&#8211;0&#46;811&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;900 &#40;0&#46;879&#8211;0&#46;919&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;593<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;6&#46;074&#8211;9&#46;493&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;274<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;214&#8211;0&#46;347&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="9" 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="9" align="left" valign="top"><span class="elsevierStyleItalic">Cologuard</span>&#8482; <span class="elsevierStyleItalic">Prototype</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>Colorectal cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;867 &#40;0&#46;693&#8211;0&#46;962&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;849 &#40;0&#46;799&#8211;0&#46;891&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;890 &#40;0&#46;856&#8211;0&#46;918&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;697<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;5&#46;849&#8211;10&#46;130&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;169<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;126&#8211;0&#46;228&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\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>Advanced adenoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;818 &#40;0&#46;615&#8211;0&#46;927&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;541 &#40;0&#46;453&#8211;0&#46;628&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;891 &#40;0&#46;849&#8211;0&#46;924&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;957<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;3&#46;450&#8211;7&#46;122&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;515<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;426&#8211;0&#46;622&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\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>Advanced colorectal neoplasm<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;846 &#40;0&#46;719&#8211;0&#46;931&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;935 &#40;0&#46;821&#8211;0&#46;986&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#46;974<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;4&#46;318&#8211;38&#46;981&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;165<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;087&#8211;0&#46;313&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ahlquist 2012<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;743<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;696&#8211;0&#46;786&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;891<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;849&#8211;0&#46;924&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;802<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;4&#46;879&#8211;9&#46;482&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;289<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a> &#40;0&#46;242&#8211;0&#46;344&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab971651.png"
              ]
            ]
          ]
          "notaPie" => array:4 [
            0 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Values calculated by the authors of this review based on data from the original studies&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Values calculated by the authors of this review based on data from the original study&#44; assuming a specificity of 90&#37;&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0030"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Results referring to all patients as a whole&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0035"
              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Including colorectal cancer and advanced adenoma&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Efficacy results in terms of diagnostic validity&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; FOBTi&#44; immunologic fecal occult blood test&#46;</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="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cologuard&#8482;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cologuard&#8482; Prototype<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">16&#44;17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Quantitative FOBTi<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Septin 9<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Stage</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><span class="elsevierStyleSmallCaps">I</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;897<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&#8211;0&#46;952&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;844&#8211;0&#46;857&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;655&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;570&nbsp;\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><span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;000<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&#8211;1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;800&#8211;0&#46;857&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;762&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;570&nbsp;\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><span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;900<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&#8211;0&#46;968&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;949&#8211;1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;900&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;380&nbsp;\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><span class="elsevierStyleSmallCaps">IV</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;750<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&#8211;1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;704&#8211;0&#46;750&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;750&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;880&nbsp;\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><span class="elsevierStyleSmallCaps">I</span>-<span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;933&#8211;0&#46;974&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;871&#8211;0&#46;910&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;733&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;500&nbsp;\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="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Location</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>Proximal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;900<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&#8211;1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;874&#8211;0&#46;920&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;667&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;460&nbsp;\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>Distal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;940&#8211;0&#46;943<a class="elsevierStyleCrossRef" href="#tblfn0040"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;810&#8211;0&#46;828&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;800&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;690&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab971650.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0040"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Data from the study reports submitted to the Food and Drug Administration for approval of Cologuard&#8482;&#46;<span class="elsevierStyleSup">60</span></p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Results of sensitivity for detecting colorectal cancer lesions&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; NC&#44; not specified&#59; FOBTi&#44; immunologic fecal occult blood test&#46;</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="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cologuard&#8482;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">13&#8211;15</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cologuard&#8482; prototype<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">16&#44;17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Quantitative FOBTi<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">13</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Septin 9<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Type</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>Advanced adenoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;424&#8211;0&#46;570&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;541&#8211;0&#46;818&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;238&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;140&nbsp;\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>High-grade dysplasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;629&#8211;0&#46;833&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;462<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\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>Sessile serrated polyp&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;424&#8211;0&#46;600<a class="elsevierStyleCrossRef" href="#tblfn0045"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;05<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\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">Location</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>Proximal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;332&#8211;0&#46;513&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;552&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;155<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\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>Distal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;545&#8211;0&#46;676&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;533&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;348<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\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="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Size</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>&#8804;5<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;200<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;200<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\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>6&#8211;9<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;321<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\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>10&#8211;19<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;392<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&#8211;0&#46;570&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;540<a class="elsevierStyleCrossRef" href="#tblfn0055"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;209<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\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>20&#8211;29<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;646<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;765&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;430<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\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>&#8805;30<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;684<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&#8211;0&#46;833&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;860<a class="elsevierStyleCrossRef" href="#tblfn0060"><span class="elsevierStyleSup">e</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;421<a class="elsevierStyleCrossRef" href="#tblfn0050"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\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>&#62;40<span class="elsevierStyleHsp" style=""></span>mm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;916&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab971649.png"
              ]
            ]
          ]
          "notaPie" => array:4 [
            0 => array:3 [
              "identificador" => "tblfn0045"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0045">This range of values also includes the results from the Heigh et al&#46; study&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0050"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0050">Data from the study report submitted to the Food and Drug Administration for approval of Cologuard&#8482;&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0055"
              "etiqueta" => "d"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0055">Data regarding AA measuring &#8805;10<span class="elsevierStyleHsp" style=""></span>mm&#46;</p>"
            ]
            3 => array:3 [
              "identificador" => "tblfn0060"
              "etiqueta" => "e"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0060">Data regarding AA measuring &#62;30<span class="elsevierStyleHsp" style=""></span>mm&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Results of Sensitivity for detecting advanced precancerous lesions&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:31 [
            0 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "GLOBOCAN 2012&#46; Colorectal cancer&#46; Estimated incidence&#44; mortality and prevalence worldwide in 2012 &#91;Base de datos en Internet&#93;&#46; Lyon&#58; International Agency for Research on Cancer&#46; World Health Organization&#59; 2014 &#91;accessed 16&#46;09&#46;14&#93;&#46; Available from&#58; <a href="http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx">http&#58;&#47;&#47;globocan&#46;iarc&#46;fr&#47;Pages&#47;fact&#95;sheets&#95;cancer&#46;aspx</a>&#46;"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Sociedad Espa&#241;ola de Oncolog&#237;a M&#233;dica&#46; Las Cifras del C&#225;ncer en Espa&#241;a 2014 &#91;Internet&#93;&#46; Madrid&#58; Sociedad Espa&#241;ola de Oncolog&#237;a M&#233;dica&#59; 2014 &#91;accessed 16&#46;09&#46;14&#93;&#46; Available from&#58; <a href="http://www.seom.org/en/prensa/el-cancer-en-espanyacom/104582-el-cancer-en-espana-2014">http&#58;&#47;&#47;www&#46;seom&#46;org&#47;en&#47;prensa&#47;el-cancer-en-espanyacom&#47;104582-el-cancer-en-espana-2014</a>&#46;"
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Sistema Nacional de Salud&#46; Informe del grupo de expertos sobre concreci&#243;n de cartera com&#250;n de servicios para cribado de c&#225;ncer &#91;Internet&#93;&#46; Madrid&#58; Ministerio de Sanidad&#44; Servicios Sociales e igualdad&#59; 2013 &#91;accessed 30&#46;07&#46;14&#93;&#46; Available from&#58; http&#58;&#47;&#47;www&#46;msssi&#46;gob&#46;es&#47;profesionales&#47;saludPublica&#47;prevPromocion&#47;docs&#47;ResumenEjecutivoCribadoCancer&#46;pdf&#46;"
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "National Comprehensive Cancer Network Guidelines &#40;NCCN Guidelines&#41;&#46; Colorectal Cancer Screening&#46; Version 1&#46;2014 &#91;Internet&#93;&#46; Washington&#58; NCCN Guidelines&#59; 2014 &#91;accessed 29&#46;07&#46;14&#93;&#46; Clinical Practice Guidelines in Oncology &#40;NCCN Guidelines&#41;&#46; Available from&#58; http&#58;&#47;&#47;www&#46;nccn&#46;org&#47;professionals&#47;physician&#95;gls&#47;pdf&#47;colorectal&#95;screening&#46;pdf&#46;"
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Segnan&#44; N&#46;&#44; Patnick&#44; J&#46;&#44; von Karsa &#40;eds&#41;&#46; European guidelines for quality assurance in colorectal cancer screening and diagnosis &#91;Internet&#93;&#46; Luxemburgo&#58; Publications Office of the European Union&#59; 2010 &#91;accessed 28&#46;09&#46;14&#93;&#46; Available from&#58; http&#58;&#47;&#47;www&#46;kolorektum&#46;cz&#47;res&#47;file&#47;guidelines&#47;CRC-screening-guidelines-EC-2011-02-03&#46;pdf&#46;"
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Lin&#44; J&#46;S&#46;&#44; Webber&#44; E&#46;M&#46;&#44; Beil&#44; T&#46;L&#46;&#44; Goddard&#44; K&#46;A&#46;&#44; Whitlock&#44; E&#46;P&#46; Fecal DNA testing in screening for colorectal cancer in average risk adults &#91;Internet&#93;&#46; Rockville &#40;MD&#41;&#58; Agency for Healthcare Research and Quality&#59; 2012 &#91;accessed 11&#46;07&#46;14&#93;&#46; 52 p&#46; Available from&#58; http&#58;&#47;&#47;www&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;pubmedhealth&#47;PMH0041016&#47;pdf&#47;TOC&#46;pdf&#46;"
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "ECRI&#46; Cologuard Stool DNA Test for Colorectal Cancer Screening&#59; 2014 &#91;accessed 12&#46;07&#46;14&#93;&#46; Available from&#58; https&#58;&#47;&#47;www&#46;ecri&#46;org&#47;components&#47;Forecast&#47;Pages&#47;12954&#46;aspx&#63;tab&#61;2&#46;"
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Food and Drug Administration &#40;FDA&#41; &#91;Internet&#93;&#46; United States&#58; FDA&#46; FDA approves first non-invasive DNA screening test for colorectal cancer&#59; 2014 &#91;updated 08&#46;08&#46;14&#59; accessed 16&#46;09&#46;14&#93;&#46; Available from&#58; http&#58;&#47;&#47;www&#46;fda&#46;gov&#47;NewsEvents&#47;Newsroom&#47;PressAnnouncements&#47;ucm409021&#46;htm&#46;"
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Declaraci&#243;n PRISMA&#58; una propuesta para mejorar la publicaci&#243;n de revisiones sistem&#225;ticas y meta-an&#225;lisis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46; Urrutia"
                            1 => "X&#46; Bonfill"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Med Clin"
                        "fecha" => "2010"
                        "volumen" => "135"
                        "paginaInicial" => "507"
                        "paginaFinal" => "511"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The development of QUADAS&#58; a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Withing"
                            1 => "A&#46; Rutjes"
                            2 => "J&#46; Reitsma"
                            3 => "P&#46; Bossuyt"
                            4 => "J&#46; Kleijnen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2288-3-25"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Med Res Methodol"
                        "fecha" => "2003"
                        "volumen" => "3"
                        "paginaInicial" => "25"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14606960"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Quadas-2&#58; a revised tool for the quality assessment of diagnostic accuracy studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;F&#46; Whiting"
                            1 => "A&#46;W&#46;S&#46; Rutjes"
                            2 => "M&#46;E&#46; Westwood"
                            3 => "S&#46; Mallett"
                            4 => "J&#46;J&#46; Deeks"
                            5 => "J&#46;B&#46; Reitsma"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7326/0003-4819-155-8-201110180-00009"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2011"
                        "volumen" => "155"
                        "paginaInicial" => "529"
                        "paginaFinal" => "536"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22007046"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "National Institute for Health and Clinical Excellence &#40;NICE&#41;&#46; The guidelines manual&#46; Manchester&#58; NICE&#59; 2012 &#91;accessed 30&#46;07&#46;14&#93;&#46; Available from&#58; http&#58;&#47;&#47;www&#46;nice&#46;org&#46;uk&#47;article&#47;pmg6&#47;resources&#47;non-guidance-the-guidelines-manual-pdf&#46;"
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Multitarget stool DNA testing for colorectal-cancer screening"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;F&#46; Imperiale"
                            1 => "D&#46;F&#46; Ransohoff"
                            2 => "S&#46;H&#46; Itzkowitz"
                            3 => "T&#46;R&#46; Levin"
                            4 => "P&#46; Lavin"
                            5 => "G&#46;P&#46; Lidgard"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1311194"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2014"
                        "volumen" => "370"
                        "paginaInicial" => "1287"
                        "paginaFinal" => "1297"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24645800"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Detection of colorectal serrated polyps by stool DNA testing&#58; comparison with fecal immunochemical testing for occult blood &#40;FIT&#41; &#91;Internet&#93;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;I&#46; Heigh"
                            1 => "T&#46;C&#46; Yab"
                            2 => "W&#46;R&#46; Taylor"
                            3 => "F&#46;T&#46;N&#46; Hussain"
                            4 => "T&#46;C&#46; Smyrk"
                            5 => "D&#46;W&#46; Mahoney"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0085659"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLOS ONE"
                        "fecha" => "2014"
                        "volumen" => "9"
                        "paginaInicial" => "e85659"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24465639"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical performance of an automated stool DNA assay for detection of colorectal neoplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46;P&#46; Lidgard"
                            1 => "M&#46;J&#46; Domanico"
                            2 => "J&#46;J&#46; Bruinsma"
                            3 => "J&#46; Light"
                            4 => "Z&#46;D&#46; Gagrat"
                            5 => "R&#46;L&#46; Oldham-Haltom"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cgh.2013.04.023"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Gastroenterol Hepatol"
                        "fecha" => "2013"
                        "volumen" => "11"
                        "paginaInicial" => "1313"
                        "paginaFinal" => "1318"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23639600"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Next-generation stool DNA test accurately detects colorectal cancer and large adenomas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;A&#46; Ahlquist"
                            1 => "H&#46; Zou"
                            2 => "M&#46; Domanico"
                            3 => "D&#46;W&#46; Mahoney"
                            4 => "T&#46;C&#46; Yab"
                            5 => "W&#46;R&#46; Taylor"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2011.10.031"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2012"
                        "volumen" => "142"
                        "paginaInicial" => "248"
                        "paginaFinal" => "256"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22062357"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The stool DNA test is more accurate than the plasma septin 9 test in detecting colorectal neoplasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;A&#46; Ahlquist"
                            1 => "W&#46;R&#46; Taylor"
                            2 => "D&#46;W&#46; Mahoney"
                            3 => "H&#46; Zou"
                            4 => "M&#46; Domanico"
                            5 => "S&#46;N&#46; Thibodeau"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cgh.2011.10.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Gastroenterol Hepatol"
                        "fecha" => "2012"
                        "volumen" => "10"
                        "paginaInicial" => "272"
                        "paginaFinal" => "277"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22019796"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evidence base of clinical diagnosis&#46; The architecture of diagnostic research"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46; Sackett"
                            1 => "R&#46; Haynes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "2002"
                        "volumen" => "324"
                        "paginaInicial" => "539"
                        "paginaFinal" => "541"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11872558"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Zauber&#44; A&#46;G&#46;&#44; Lansdorp-Vogelaar&#44; I&#46;&#44; Knudsen&#44; A&#46;B&#46;&#44; Wilschut&#44; J&#46;&#44; van Ballegooijen&#44; M&#46;&#44; Kuntz&#44; K&#46;M&#46; Evaluating test strategies for colorectal cancer screening&#8212;age to begin&#44; age to stop&#44; and timing of screening intervals&#58; a decision analysis of colorectal cancer screening for the U&#46;S&#46; Preventive Services Task Force from the Cancer Intervention and Surveillance Modeling Network &#40;CISNET&#41; &#91;Internet&#93;&#46; United States&#58; Agency for Healthcare Research and Quality&#59; 2009 &#91;accessed 30&#46;07&#46;14&#93;&#46; 61 p&#46; Available from&#58; http&#58;&#47;&#47;www&#46;uspreventiveservicestaskforce&#46;org&#47;uspstf08&#47;colocancer&#47;colcanes2&#46;pdf&#46;"
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A concordance correlation coefficient to evaluate reproducibility"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "L&#46;I&#46; Lin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Biometrics"
                        "fecha" => "1989"
                        "volumen" => "45"
                        "paginaInicial" => "255"
                        "paginaFinal" => "268"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2720055"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Agency for Healthcare Research and Quality &#40;AHRQ&#41;&#46; The guide to clinical preventive services 2014&#46; Recommendations of the U&#46;S&#46; Preventive services task force&#46; United States&#58; AHRQ&#59; 2014 &#91;accessed 30&#46;07&#46;14&#93;&#46; 123 p&#46; Available from&#58; http&#58;&#47;&#47;www&#46;ahrq&#46;gov&#47;professionals&#47;clinicians-providers&#47;guidelines-recommendations&#47;guide&#47;cpsguide&#46;pdf&#46;"
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Screening for colorectal cancer using the faecal occult blood test&#44; Hemoccult"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Hewitson"
                            1 => "P&#46; Glasziou"
                            2 => "L&#46; Irwig"
                            3 => "B&#46; Towler"
                            4 => "E&#46; Watson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD009601"
                      "Revista" => array:4 [
                        "tituloSerie" => "Cochrane database Syst Rev"
                        "fecha" => "2007"
                        "volumen" => "1"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22259004"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cribado del c&#225;ncer colorrectal"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "D&#46; S&#225;nchez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Clin Esp"
                        "fecha" => "2014"
                        "volumen" => "214"
                        "paginaInicial" => "275"
                        "paginaFinal" => "276"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Participation and detection rates by age and sex for colonoscopy versus fecal immunochemical testing in colorectal cancer screening"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Salas"
                            1 => "M&#46; Vanaclocha"
                            2 => "J&#46; Ib&#225;&#241;ez"
                            3 => "A&#46; Molina-Barcel&#243;"
                            4 => "V&#46; Hern&#225;ndez"
                            5 => "J&#46; Cubiella"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10552-014-0398-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer Causes Control"
                        "fecha" => "2014"
                        "volumen" => "25"
                        "paginaInicial" => "985"
                        "paginaFinal" => "997"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24859111"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Colonoscopia versus sangre oculta en heces en el cribado del c&#225;ncer colorrectal"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46; Garc&#237;a"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Rev Clin Esp"
                        "fecha" => "2012"
                        "volumen" => "212"
                        "paginaInicial" => "407"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23115776"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "P&#243;lipos colorrectales"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Bacchiddu"
                            1 => "A&#46; &#193;lvarez-Urturri"
                            2 => "X&#46; Bessa-Caserras"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "FMC"
                        "fecha" => "2012"
                        "volumen" => "19"
                        "paginaInicial" => "472"
                        "paginaFinal" => "480"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Rate of detection of advanced neoplasms in proximal colon by simulated sigmoidoscopy vs fecal immunochemical tests"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Castells"
                            1 => "E&#46; Quintero"
                            2 => "C&#46; &#193;lvarez"
                            3 => "L&#46; Bujanda"
                            4 => "J&#46; Cubiella"
                            5 => "D&#46; Salas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cgh.2014.03.022"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Gastroenterol Hepatol"
                        "fecha" => "2014"
                        "volumen" => "12"
                        "paginaInicial" => "1708"
                        "paginaFinal" => "1716"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24681078"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Empirical evidence of design-related bias in studies of diagnostic tests"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;G&#46; Lijmer"
                            1 => "B&#46;W&#46; Mol"
                            2 => "S&#46; Heisterkamp"
                            3 => "G&#46;J&#46; Bonsel"
                            4 => "M&#46;H&#46; Prins"
                            5 => "J&#46;H&#46; van der Meulen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "1999"
                        "volumen" => "282"
                        "paginaInicial" => "1061"
                        "paginaFinal" => "1066"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10493205"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "ECRI Institute AHRQ Healthcare Horizon Scanning System&#8211;Potential high impact interventions report&#46; Priority area 02&#58; cancer &#91;Internet&#93;&#46; Plymouth&#58; ECRI Institute&#59; 2014 &#91;accessed 25&#46;10&#46;14&#93;&#46; 144 p&#46; Available from&#58; http&#58;&#47;&#47;effectivehealthcare&#46;ahrq&#46;gov&#47;ehc&#47;assets&#47;File&#47;Cancer-Horizon-Scan-High-Impact-1406&#46;pdf&#46;"
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0305"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluating test strategies for colorectal cancer screening&#58; a decision analysis for the U&#46;S&#46; Preventive Services Task Force"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46;G&#46; Zauber"
                            1 => "I&#46; Lansdorp-Vogelaar"
                            2 => "A&#46;B&#46; Knudsen"
                            3 => "J&#46; Wilschut"
                            4 => "M&#46; van Ballegooijen"
                            5 => "K&#46;M&#46; Kuntz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2008"
                        "volumen" => "149"
                        "paginaInicial" => "659"
                        "paginaFinal" => "669"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18838717"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0310"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Exact Sciences &#91;Internet&#93;&#46; Madison&#44; Wisconsin&#58; Exact Sciences Corporation&#59; 2014&#46; FDA Approves Exact Sciences&#8217; Cologuard&#174;&#59; First and Only Stool DNA Noninvasive Colorectal Cancer Screening Test&#46; &#91;updated 12&#46;08&#46;14&#59; accessed 25&#46;10&#46;14&#93;&#46; Available from&#58; http&#58;&#47;&#47;investor&#46;exactsciences&#46;com&#47;releasedetail&#46;cfm&#63;ReleaseID&#61;865698&#46;"
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack199860"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0215" class="elsevierStylePara elsevierViewall">This work has benefited from the contributions of Dr&#46; Manuel Romero Gomez&#44; as well as from the planning and documentation work of Dr&#46; Antonio Romero-Tabares&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/22548874/0000021500000009/v2_201601010034/S2254887415000934/v2_201601010034/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "46200"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021500000009/v2_201601010034/S2254887415000934/v2_201601010034/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887415000934?idApp=WRCEE"
]

Article information

ISSN: 22548874
Original language: English

DOI:10.1016/j.rceng.2015.08.006

The statistics are updated each day

Year/Month	Html	Pdf	Total

2023 March	5	3	8
2018 February	7	0	7
2018 January	17	0	17
2017 December	12	0	12
2015 November	0	1	1

Indexed in:

Follow us:

Subscribe:

Statistics

Indexed in:

Follow us:

Subscribe:

Statistics

Subscribe to our newsletter