{"id":1133,"date":"2015-07-24T20:33:22","date_gmt":"2015-07-24T19:33:22","guid":{"rendered":"https:\/\/blogs.bmj.com\/adc\/?p=1133"},"modified":"2015-07-15T13:13:23","modified_gmt":"2015-07-15T12:13:23","slug":"stopping-rules","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/adc\/2015\/07\/24\/stopping-rules\/","title":{"rendered":"Stopping Rules"},"content":{"rendered":"<p><img loading=\"lazy\" decoding=\"async\" class=\"alignleft\" style=\"margin-right: 10px\" src=\"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/thumb\/5\/51\/Mandatory_road_sign_stop.svg\/600px-Mandatory_road_sign_stop.svg.png\" alt=\"\" width=\"186\" height=\"186\" \/>If you were cycling or driving, you&#8217;d probably know what the stopping rules were. Traffic not moving, big red sign, large goose with malevolent glare (Lincolnshire speciality).<\/p>\n<p>What if you&#8217;re doing a clinical trial?<\/p>\n<p>There are a variety of things what have been described, some of them are qualitative (SUSAR &#8211; sudden, unexpected, serious adverse reactions) and some statistical. The latter have with them a set of maths that leads to reasons to discontinue, either for proven benefit or futility.<\/p>\n<p><!--more--><\/p>\n<p>The maths is argued over by clever people, but they all conceptually do the same thing. They ask &#8220;what is the likelihood of this difference being a chance finding?&#8221; and balance this with &#8220;and if we keep looking and looking, eventually we will see something&#8221;.<\/p>\n<p>This means that the trial designers need to decide what their <a href=\"https:\/\/blogs.bmj.com\/adc\/2013\/09\/12\/statsminiblog-type-i-and-ii-errors\/\">significance level and power<\/a> are that they are aiming for, their <a href=\"https:\/\/blogs.bmj.com\/adc\/2015\/06\/26\/is-breathlessness-worth-reporting-at-all\/\">minimally clinically important difference<\/a>\u00a0and then <a href=\"https:\/\/blogs.bmj.com\/adc\/2015\/07\/17\/ministatsblog-bonferroni-correction\/\">how many times they are going to look<\/a>. (The simplest idea is that if you look twice, you have to halve the p-value you&#8217;re going to accept as significant, cause you&#8217;ve used up one lot of assessing.) This then produces a size estimation for the study and\u00a0boundaries for &#8220;better &#8211; stop!&#8221; and &#8220;futile &#8211; stop!&#8221; at each reassessment.<\/p>\n<p>The usual maths\u00a0of doing this is with the &#8216;Flemming-O&#8217;Brien alpha spending function&#8217;, but a more efficient variant is the Triangular Test, which recalibrates as it ammasses data.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter\" src=\"http:\/\/lh6.ggpht.com\/_1wtadqGaaPs\/THaQHGSn6GI\/AAAAAAAAWGg\/LwPoRDFbQCk\/tmp3A8370_thumb_thumb.png?imgmax=800\" alt=\"\" width=\"382\" height=\"263\" \/><\/p>\n<p>&#8211; Archi<\/p>\n<p>(PS &#8211; This post was requested by &#8211; You can ask too!)<\/p>\n<blockquote class=\"twitter-tweet\">\n<p dir=\"ltr\" lang=\"en\"><a href=\"https:\/\/twitter.com\/drbobphillips\">@drbobphillips<\/a> can you do a blog piece on &#8216;triangular test?&#8217; Google not helping. Authors closed study because of results of this? ?<\/p>\n<p>\u2014 XOXO \u0628\u0646\u062a \u0627\u0644\u0642\u064a\u0644 (@hhassan90210) <a href=\"https:\/\/twitter.com\/hhassan90210\/status\/620652723449524224\">July 13, 2015<\/a><\/p><\/blockquote>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>(If you want a longer &amp; more intellectual read &#8211; <a href=\"http:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1884206\/\">try here<\/a>.)<\/p>\n<p>&nbsp;<!--TrendMD v2.4.8--><\/p>\n","protected":false},"excerpt":{"rendered":"<p>If you were cycling or driving, you&#8217;d probably know what the stopping rules were. Traffic not moving, big red sign, large goose with malevolent glare (Lincolnshire speciality). What if you&#8217;re doing a clinical trial? There are a variety of things what have been described, some of them are qualitative (SUSAR &#8211; sudden, unexpected, serious adverse [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/adc\/2015\/07\/24\/stopping-rules\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[79,2676],"tags":[],"class_list":["post-1133","post","type-post","status-publish","format-standard","hentry","category-archimedes","category-stats"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Stopping Rules - ADC Online Blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/blogs.bmj.com\/adc\/2015\/07\/24\/stopping-rules\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Stopping Rules - ADC Online Blog\" \/>\n<meta property=\"og:description\" content=\"If you were cycling or driving, you&#8217;d probably know what the stopping rules were. Traffic not moving, big red sign, large goose with malevolent glare (Lincolnshire speciality). What if you&#8217;re doing a clinical trial? 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