<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0120-1751</journal-id>
<journal-title><![CDATA[Revista Colombiana de Estadística]]></journal-title>
<abbrev-journal-title><![CDATA[Rev.Colomb.Estad.]]></abbrev-journal-title>
<issn>0120-1751</issn>
<publisher>
<publisher-name><![CDATA[Departamento de Estadística - Universidad Nacional de Colombia.]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0120-17512012000200004</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[¿ Cuándo inicia la enfermedad de Alzheimer? Kaplan-Meier versus Turnbull: una aplicación a datos con censura arbitraria]]></article-title>
<article-title xml:lang="en"><![CDATA[¿ When does Alzheimer's Disease Begin? Kaplan-Meier versus Turnbull: An Application to Arbitrary Censoring Data]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[LOPERA-GÓMEZ]]></surname>
<given-names><![CDATA[CARLOS MARIO]]></given-names>
</name>
<xref ref-type="aff" rid="A01"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[JARAMILLO-ELORZA]]></surname>
<given-names><![CDATA[MARIO CÉSAR]]></given-names>
</name>
<xref ref-type="aff" rid="A02"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[ACOSTA-BAENA]]></surname>
<given-names><![CDATA[NATALIA]]></given-names>
</name>
<xref ref-type="aff" rid="A03"/>
</contrib>
</contrib-group>
<aff id="A01">
<institution><![CDATA[,Universidad Nacional de Colombia Facultad de Ciencias Escuela de Estadística]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="A02">
<institution><![CDATA[,Universidad Nacional de Colombia Facultad de Ciencias Escuela de Estadística]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="A03">
<institution><![CDATA[,Universidad de Antioquia Facultad de Medicina Grupo de Neurociencias de Antioquia y Grupo Académico de Epidemiología Clínica-GRAEPIC]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<pub-date pub-type="pub">
<day>20</day>
<month>06</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub">
<day>20</day>
<month>06</month>
<year>2012</year>
</pub-date>
<volume>35</volume>
<numero>spe2</numero>
<fpage>239</fpage>
<lpage>254</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0120-17512012000200004&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0120-17512012000200004&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0120-17512012000200004&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[La mayoría de los análisis de supervivencia se basan en tiempos de falla exactos y observaciones censuradas a la derecha, utilizándose métodos ampliamente difundidos como el método de Kaplan-Meier (KM). Para estimar la edad de inicio de la Enfermedad de Alzheimer (EA) familiar cuando las censuras son arbitrarias (censura a derecha, a izquierda o en intervalo), ¿cuál es el cambio en los resultados clínicos, si se utiliza el método de KM mediante imputación comparado con el método de Turnbull sugerido para este tipo de datos? El método de Turnbull se comparó con el método de KM mediante un estudio de simulación y una aplicación con datos reales. Se realizó KM con imputación a través del punto medio del intervalo (PM) y en el extremo derecho (ED). Se analizaron diferentes tamaños de muestra y diferentes tiempos entre visitas. En todos los escenarios de simulación, las funciones que fueron estimadas, usando imputación de datos, difieren significativamente de la verdadera función de supervivencia S(t). La edad de inicio de la EA determinada a través de un método de imputación tiene implicaciones clínicas relevantes que afectarían la toma de decisiones a la hora de iniciar una terapia preventiva. El método de Turnbull presenta un menor sesgo cuando se necesita realizar un análisis de supervivencia con censuras arbitrarias.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[Most of the survival analysis are based on exact failure times and right censored observations, using methods widely known as the Kaplan-Meier (KM). To estimate the onset age of familial Alzheimers Disease (AD) when the censor times are arbitrary (right, left or interval censor), what is the change in clinical outcomes, using the KM method with data imputation compared with procedure proposed by Turnbull for this kind of data? Turnbulls method was compared with KM method in a simulation study and an application with real data. KM method was based on data imputation through the midpoint of the interval (MP) and the right side of the interval (RS), considering several sample sizes and different times between visits. In all simulation scenarios estimated functions using data imputation differ significantly from the actual simulated survival function S(t). The estimated onset age of AD through data imputation methods has relevant clinical implications that would affect decision-making in initiating preventive therapy. Turnbulls method has fewer bias when was compared with KM with imputation to perform a survival analysis with arbitrary censure data.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[análisis de supervivencia]]></kwd>
<kwd lng="es"><![CDATA[censura de intervalo]]></kwd>
<kwd lng="es"><![CDATA[edad de inicio]]></kwd>
<kwd lng="es"><![CDATA[enfermedad de Alzheimer familiar]]></kwd>
<kwd lng="en"><![CDATA[Age of onset]]></kwd>
<kwd lng="en"><![CDATA[Familial Alzheimer's disease]]></kwd>
<kwd lng="en"><![CDATA[Interval censoring]]></kwd>
<kwd lng="en"><![CDATA[Survival analysis]]></kwd>
</kwd-group>
</article-meta>
</front><body><![CDATA[  <font size="2" face="verdana">      <p> <b> <font size="4">     <center> &iquest;Cu&aacute;ndo inicia la enfermedad de Alzheimer? Kaplan-Meier versus Turnbull: una aplicaci&oacute;n a datos con censura arbitraria </center> </font> </b> </p>      <p> <b> <font size="3">     <center> &iquest;When does Alzheimer's Disease Begin? Kaplan-Meier versus Turnbull: An Application to Arbitrary Censoring Data </center> </font> </b> </p>      <p>     <center> CARLOS MARIO LOPERA-G&Oacute;MEZ<sup>1</sup>,  MARIO C&Eacute;SAR JARAMILLO-ELORZA<sup>2</sup>,  NATALIA ACOSTA-BAENA<sup>3</sup> </center> </p>      <p> <sup>1</sup>Universidad Nacional de Colombia, Facultad de Ciencias, Escuela de Estad&iacute;stica, Medell&iacute;n, Colombia. Profesor asistente. Email: <a href="mailto:cmlopera@unal.edu.co">cmlopera@unal.edu.co</a>     <br>  <sup>2</sup>Universidad Nacional de Colombia, Facultad de Ciencias, Escuela de Estad&iacute;stica, Medell&iacute;n, Colombia. Profesor asociado. Email: <a href="mailto:mjarami@unal.edu.co">mjarami@unal.edu.co</a>     <br>  <sup>3</sup>Universidad de Antioquia, Facultad de Medicina, Grupo de Neurociencias de Antioquia y Grupo Acad&eacute;mico de Epidemiolog&iacute;a Cl&iacute;nica-GRAEPIC, Medell&iacute;n, Colombia. Profesora. Email: <a href="mailto:natalia.acosta@neurociencias.udea.edu.co">natalia.acosta@neurociencias.udea.edu.co</a>     ]]></body>
<body><![CDATA[<br> </p>  <hr size="1">      <p> <b>     <center> Resumen </center> </b> </p>      <p> La mayor&iacute;a de los an&aacute;lisis de supervivencia se basan en tiempos de falla exactos y observaciones censuradas a la derecha, utiliz&aacute;ndose m&eacute;todos ampliamente difundidos como el m&eacute;todo de Kaplan-Meier (KM). Para estimar la edad de inicio de la Enfermedad de Alzheimer (EA) familiar cuando las censuras son arbitrarias (censura a derecha, a izquierda o en intervalo), &iquest;cu&aacute;l es el cambio en los resultados cl&iacute;nicos, si se utiliza el m&eacute;todo de KM mediante imputaci&oacute;n comparado con el m&eacute;todo de Turnbull sugerido para este tipo de datos?     <br>  El m&eacute;todo de Turnbull se compar&oacute; con el m&eacute;todo de KM mediante un estudio de simulaci&oacute;n y una aplicaci&oacute;n con datos reales. Se realiz&oacute; KM con imputaci&oacute;n a trav&eacute;s del punto medio del intervalo (PM) y en el extremo derecho (ED). Se analizaron diferentes tama&ntilde;os de muestra y diferentes tiempos entre visitas.     <br>  En todos los escenarios de simulaci&oacute;n, las funciones que fueron estimadas, usando imputaci&oacute;n de datos, difieren significativamente de la verdadera funci&oacute;n de supervivencia S(t).     <br>  La edad de inicio de la EA determinada a trav&eacute;s de un m&eacute;todo de imputaci&oacute;n tiene implicaciones cl&iacute;nicas relevantes que afectar&iacute;an la toma de decisiones a la hora de iniciar una terapia preventiva. El m&eacute;todo de Turnbull presenta un menor sesgo cuando se necesita realizar un an&aacute;lisis de supervivencia con censuras arbitrarias. </p>      <p> <b> Palabras clave: </b> an&aacute;lisis de supervivencia, censura de intervalo, edad de inicio, enfermedad de Alzheimer familiar. </p>  <hr size="1">      <p> <b>     <center> Abstract </center> </b> </p>      ]]></body>
<body><![CDATA[<p> Most of the survival analysis are based on exact failure times and right censored observations, using methods widely known as the Kaplan-Meier (KM). To estimate the onset age of familial Alzheimers Disease (AD) when the censor times are arbitrary (right, left or interval censor), what is the change in clinical outcomes, using the KM method with data imputation compared with procedure proposed by Turnbull for this kind of data?     <br>  Turnbulls method was compared with KM method in a simulation study and an application with real data. KM method was based on data imputation through the midpoint of the interval (MP) and the right side of the interval (RS), considering several sample sizes and different times between visits.     <br>  In all simulation scenarios estimated functions using data imputation differ significantly from the actual simulated survival function S(t).     <br>  The estimated onset age of AD through data imputation methods has relevant clinical implications that would affect decision-making in initiating preventive therapy. Turnbulls method has fewer bias when was compared with KM with imputation to perform a survival analysis with arbitrary censure data. </p>      <p> <b> Key words: </b> Age of onset, Familial Alzheimer's disease, Interval censoring, Survival analysis. </p>  <hr size="1">      <p> Texto completo disponible en <a href="pdf/rce/v35nspe2/v35nspe2a04.pdf">PDF</a> </p>  <hr size="1">      <p> <b> <font size="3"> Referencias </font> </b> </p>       <!-- ref --><p> 1. 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Rucker, G. &amp; Messerer, D. (1988), 'Remission duration: An example of interval-censored observation', <i>Statistics in Medicine</i> <b>7</b>, 1139-1145. &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;[&#160;<a href="javascript:void(0);" onclick="javascript: window.open('/scielo.php?script=sci_nlinks&ref=000043&pid=S0120-1751201200020000400014&lng=','','width=640,height=500,resizable=yes,scrollbars=1,menubar=yes,');">Links</a>&#160;]<!-- end-ref --><!-- ref --><p> 15. Strobel, G. (2011), Detecting Familial AD Ever Earlier: Subtle Memory Signs 15 Years Before, 'Alzheimer Research Forum'. Consultado en septiembre 6, 2011. *<a href="http://www.alzforum.org/new/detail.asp?id2725"  target="_blank">http://www.alzforum.org/new/detail.asp?id2725</a> &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;[&#160;<a href="javascript:void(0);" onclick="javascript: window.open('/scielo.php?script=sci_nlinks&ref=000044&pid=S0120-1751201200020000400015&lng=','','width=640,height=500,resizable=yes,scrollbars=1,menubar=yes,');">Links</a>&#160;]<!-- end-ref --><!-- ref --><p> 16. Turnbull, B. W. (1974), 'Nonparametric estimation of a survivorship function with doubly censored data', <i>Journal of the American Statistical Association</i> <b>69</b>(345), 169-173. &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;[&#160;<a href="javascript:void(0);" onclick="javascript: window.open('/scielo.php?script=sci_nlinks&ref=000045&pid=S0120-1751201200020000400016&lng=','','width=640,height=500,resizable=yes,scrollbars=1,menubar=yes,');">Links</a>&#160;]<!-- end-ref --><!-- ref --><p> 17. Turnbull, B. W. (1976), 'The empirical distribution function with arbitrarily grouped censored and truncated data', <i>Journal of the Royal Statistical Society, Series B</i> <b>38</b>(3), 290-295. &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;[&#160;<a href="javascript:void(0);" onclick="javascript: window.open('/scielo.php?script=sci_nlinks&ref=000046&pid=S0120-1751201200020000400017&lng=','','width=640,height=500,resizable=yes,scrollbars=1,menubar=yes,');">Links</a>&#160;]<!-- end-ref --><center> <b>&#91;Recibido en septiembre de 2011. Aceptado en febrero de 2012&#93;</b> </center> <hr size="1">      <p> Este art&iacute;culo se puede citar en <i>LaTeX</i> utilizando la siguiente referencia bibliogr&aacute;fica de <i>BibTeX</i>: </p> <code><font size="2">@ARTICLE{RCEv35n2a04,    <br>   AUTHOR = {Lopera-G&oacute;mez, Carlos Mario and Jaramillo-Elorza, Mario C&eacute;sar and Acosta-Baena, Natalia},    <br>   TITLE  = {{&iquest; Cu&aacute;ndo inicia la enfermedad de Alzheimer? Kaplan-Meier versus Turnbull: una aplicaci&oacute;n a datos con censura arbitraria}},    <br>   JOURNAL = {Revista Colombiana de Estad&iacute;stica},    <br>  YEAR  = {2012},    ]]></body>
<body><![CDATA[<br>  volume = {35},    <br>  number = {2},    <br>  pages  = {239-254}    <br> }</font></code>  <hr size="1"> </font>      ]]></body><back>
<ref-list>
<ref id="B1">
<label>1</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Acosta-Baena]]></surname>
<given-names><![CDATA[N.]]></given-names>
</name>
<name>
<surname><![CDATA[Sepúlveda-Falla]]></surname>
<given-names><![CDATA[D.]]></given-names>
</name>
<name>
<surname><![CDATA[Lopera-Gómez]]></surname>
<given-names><![CDATA[C. M.]]></given-names>
</name>
<name>
<surname><![CDATA[Jaramillo-Elorza]]></surname>
<given-names><![CDATA[M. C.]]></given-names>
</name>
<name>
<surname><![CDATA[Moreno]]></surname>
<given-names><![CDATA[S.]]></given-names>
</name>
<name>
<surname><![CDATA[Aguirre-Acevedo]]></surname>
<given-names><![CDATA[D. C.]]></given-names>
</name>
<name>
<surname><![CDATA[Saldarriaga]]></surname>
<given-names><![CDATA[A.]]></given-names>
</name>
<name>
<surname><![CDATA[Lopera]]></surname>
<given-names><![CDATA[F.]]></given-names>
</name>
</person-group>
<article-title xml:lang="en"><![CDATA['Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: A retrospective cohort study']]></article-title>
<source><![CDATA[The Lancet Neurology]]></source>
<year>2011</year>
<volume>10</volume>
<numero>3</numero>
<issue>3</issue>
<page-range>213-220</page-range></nlm-citation>
</ref>
<ref id="B2">
<label>2</label><nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name>
<surname><![CDATA[Dorey]]></surname>
<given-names><![CDATA[F. J.]]></given-names>
</name>
<name>
<surname><![CDATA[Little]]></surname>
<given-names><![CDATA[R.]]></given-names>
</name>
<name>
<surname><![CDATA[Schenker]]></surname>
<given-names><![CDATA[N.]]></given-names>
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