{"id":334,"date":"2013-09-06T11:10:54","date_gmt":"2013-09-06T09:10:54","guid":{"rendered":"http:\/\/www.ideal.rwth-aachen.de\/?page_id=334"},"modified":"2013-10-05T18:53:44","modified_gmt":"2013-10-05T16:53:44","slug":"wp7-genetic-factors","status":"publish","type":"page","link":"https:\/\/www.ideal.rwth-aachen.de\/?page_id=334","title":{"rendered":"WP7 \u2013 Simulation"},"content":{"rendered":"<\/div><\/div><\/div><!-- close content main div --><\/div><\/div><div id='av_section_1' class='avia-section main_color avia-section-default avia-shadow avia-bg-style-scroll   container_wrap fullsize' style = 'background-image: '  ><div class='container' ><div class='template-page content  av-content-full alpha units'><div class='post-entry post-entry-type-page post-entry-334'><div class='entry-content-wrapper clearfix'>\n<div class=\"flex_column av_three_fourth  flex_column_div first  \" ><div style='padding-bottom:10px; ' class='av-special-heading av-special-heading-h4    '><h4 class='av-special-heading-tag '  itemprop=\"headline\"  >WP7 \u2013 Simulation of clinical trials in small population groups<\/h4><div class='special-heading-border'><div class='special-heading-inner-border' ><\/div><\/div><\/div>\n<section class=\"av_textblock_section \"  itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/CreativeWork\" ><div class='avia_textblock  '   itemprop=\"text\" ><p>We will investigate the impact of model misspecifications in non-linear mixed effects models when it is used for design and analysis of trials and develop methods to mitigate it. In the design stage, clinical trial simulation can be combined with resampling procedures to arrive at more realistic trial outcomes. As a separate strategy, highly mechanistic (physiology-based pharmacokinetic and systems pharmacology) models will be combined with extended models for stochastic components (e.g. stochastic differential equations) for simulation, while more traditional pharmacometric models will be used for evaluation of expected study characteristics. For non-linear mixed effects based analyses of trials in small populations, the performance of randomisation tests and model-averaging procedures will be evaluated and methods for implementation developed.<\/p>\n<p>The model uncertainty is for natural reasons largest when based on estimation in a small sample size (e.g. small population groups) and at the same time a small sample size represent an extra challenge in accurately characterising the uncertainty. Estimation of covariance-variance matrix or bootstrap resampled datasets is common methods for characterising model uncertainty with non-linear mixed effects models. Both of these methods suffer drawbacks especially in application of complex non-linear mixed effects models to studies in small population groups. We intend to demonstrate some practical limitations of these methods and develop extensions to these methodologies to improve characterisation of model uncertainty.<\/p>\n<\/div><\/section><\/div><div class=\"flex_column av_one_fourth  flex_column_div   \" ><p><div style='padding-bottom:10px; ' class='av-special-heading av-special-heading-h4 meta-heading   '><h4 class='av-special-heading-tag '  itemprop=\"headline\"  >Lead participant <\/h4><div class='special-heading-border'><div class='special-heading-inner-border' ><\/div><\/div><\/div><br \/>\n<div class='avia-image-container avia_animated_image avia_animate_when_almost_visible right-to-left av-styling-    avia-align-center '  itemprop=\"ImageObject\" itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/ImageObject\"  ><div class='avia-image-container-inner'><div class='avia-image-overlay-wrap'><a href='?page_id=410' class='avia_image'  ><img class='avia_image ' src='http:\/\/www.ideal.rwth-aachen.de\/wp-content\/uploads\/2013\/08\/uulogo_grey.png' alt='' title=''  itemprop=\"thumbnailUrl\"  \/><\/a><\/div><\/div><\/div><\/p><\/div><div class=\"flex_column av_one_full  flex_column_div first  \" ><\/div>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":0,"parent":58,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-334","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/www.ideal.rwth-aachen.de\/index.php?rest_route=\/wp\/v2\/pages\/334","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ideal.rwth-aachen.de\/index.php?rest_route=\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.ideal.rwth-aachen.de\/index.php?rest_route=\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.ideal.rwth-aachen.de\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ideal.rwth-aachen.de\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=334"}],"version-history":[{"count":5,"href":"https:\/\/www.ideal.rwth-aachen.de\/index.php?rest_route=\/wp\/v2\/pages\/334\/revisions"}],"predecessor-version":[{"id":644,"href":"https:\/\/www.ideal.rwth-aachen.de\/index.php?rest_route=\/wp\/v2\/pages\/334\/revisions\/644"}],"up":[{"embeddable":true,"href":"https:\/\/www.ideal.rwth-aachen.de\/index.php?rest_route=\/wp\/v2\/pages\/58"}],"wp:attachment":[{"href":"https:\/\/www.ideal.rwth-aachen.de\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=334"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}