{"id":41367,"date":"2018-02-09T15:13:04","date_gmt":"2018-02-09T14:13:04","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=41367"},"modified":"2018-02-16T17:49:33","modified_gmt":"2018-02-16T16:49:33","slug":"jeffrey-aronson-when-i-use-a-word-the-wheel-of-evidence","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2018\/02\/09\/jeffrey-aronson-when-i-use-a-word-the-wheel-of-evidence\/","title":{"rendered":"Jeffrey Aronson: When I Use a Word . . . The wheel of evidence"},"content":{"rendered":"<p><a href=\"https:\/\/blogs.bmj.com\/bmj\/files\/2014\/12\/jeffrey_aronson.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"alignleft wp-image-32935\" src=\"https:\/\/blogs.bmj.com\/bmj\/files\/2014\/12\/jeffrey_aronson-223x300.jpg\" alt=\"jeffrey_aronson\" width=\"140\" height=\"169\" \/><\/a><span style=\"font-weight: 400\">Last week I discussed the concept of <\/span><a href=\"https:\/\/blogs.bmj.com\/bmj\/2018\/02\/02\/jeffrey-aronson-when-i-use-a-word-teleoanalysis\"><span style=\"font-weight: 400\">teleoanalysis<\/span><\/a><span style=\"font-weight: 400\">, in which different types of evidence from disparate sources are analysed either simultaneously or sequentially. To be clear, the term implies not the very last analysis that could be done, but a thorough systematic analysis of all the evidence available at the time, from, for example, randomised trials, non-randomised studies, epidemiological studies, n-of-1 studies, case reports, and any other forms of adducible evidence, such as laboratory evidence and <\/span><a href=\"https:\/\/blogs.bmj.com\/bmj\/2016\/04\/15\/jeffrey-aronson-when-i-use-a-word-mechanisms-and-evidence\"><span style=\"font-weight: 400\">mechanistic arguments<\/span><\/a><span style=\"font-weight: 400\">. Teleoanalysis can be a quantitative analysis of quantitative data or, if the data do not lend themselves to formal analysis, a narrative account. Furthermore, the results of qualitative studies can be used as an adjunct to a quantitative teleoanalysis or as part of a narrative teleoanalysis, aiding interpretation. If other evidence becomes available, it can be included in a revised teleoanalysis.<\/span><\/p>\n<p><span style=\"font-weight: 400\">This concept reminds us that it is fallacious to think of evidence as being arrayed in hierarchies, based on the idea that some forms of evidence are intrinsically more reliable than others. The first <\/span><a href=\"http:\/\/etheses.lse.ac.uk\/3284\/\"><span style=\"font-weight: 400\">hierarchies<\/span><\/a><span style=\"font-weight: 400\"> put systematic reviews of randomised controlled trials at the top (high quality) and anecdotal reports and expert opinion (wrongly categorised\u2014opinion is not evidence) at the bottom (low quality). However, it has gradually been recognised that different types of evidence have different uses and that in some circumstances the varieties in the middle of the list or at the bottom may have as much value as those at the top. Hierarchies distort this.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Randomised studies, it is generally agreed, provide the most convincing quantitative evidence. Controlled n-of-1 studies, in which the effects of an intervention are studied in an individual and compared with a placebo or other comparator, can give excellent evidence in the individual. However, such designs have limitations. For example, the results of a randomised study may not be applicable to the general population (the problem of <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23481429\"><span style=\"font-weight: 400\">external validity<\/span><\/a><span style=\"font-weight: 400\">) and are not good at detecting rare events; n-of-1 studies are applicable only in some conditions.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Observational studies are often much larger than randomised studies and although confounding is a major problem they can give information that randomised studies cannot give or not as readily, <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17008675\"><span style=\"font-weight: 400\">particularly<\/span><\/a><span style=\"font-weight: 400\"> in poorly resourced settings. Meta-analysis of randomised studies can elucidate <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/26994216\"><span style=\"font-weight: 400\">dose response relations<\/span><\/a><span style=\"font-weight: 400\"> when they have involved a range of doses, but if not observational studies can do the job instead. If a drug-event pair has been shown to be causatively linked in a randomised study, the risk estimate of the association derived from meta-analyses of observational studies is <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21559325\"><span style=\"font-weight: 400\">similar<\/span><\/a><span style=\"font-weight: 400\"> to the risk estimate calculated from a meta-analysis of randomised studies. In studying drug-drug interactions it may be impractical to study enough individuals to reveal an effect, especially if the interaction affects only a subset of individuals. For example, a large observational <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/9496982\"><span style=\"font-weight: 400\">study<\/span><\/a><span style=\"font-weight: 400\"> showed that paracetamol potentiates the anticoagulant action of warfarin, and the more paracetamol you take for longer, the bigger the effect is; this dose and time related adverse drug-drug interaction was first demonstrated in a case control study of patients with an INR of 6 or over and was not seen in small randomised studies. Similarly, in a case-control <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/15025752\"><span style=\"font-weight: 400\">study<\/span><\/a><span style=\"font-weight: 400\"> of the interaction of laxatives with acenocoumarol or phenprocoumon, lactulose increased the risk of an INR over 6 by 3.4 times.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Sometimes even an anecdotal report can elucidate a beneficial or harmful effect without the need for a randomised study. A whimsical <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/14684649\"><span style=\"font-weight: 400\">example<\/span><\/a><span style=\"font-weight: 400\"> of this is the anecdotal evidence, in the absence of randomised studies, that parachutes \u201c[prevent] death and major trauma related to gravitational challenge\u201d. Other examples show that anecdotes can provide convincing evidence of both <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17303884\"><span style=\"font-weight: 400\">benefits<\/span><\/a><span style=\"font-weight: 400\"> and <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17170419\"><span style=\"font-weight: 400\">harms<\/span><\/a><span style=\"font-weight: 400\"> without the need for randomised or observational studies.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Similar comments could be made about other types of evidence, mechanism based, laboratory based, and qualitative evidence, each of which has a place in the evidence spectrum.<\/span><\/p>\n<p><span style=\"font-weight: 400\">The word \u201cteleoanalysis\u201d comes from the Greek adjective \u03c4\u03ad\u03bb\u03b5\u03bf\u03c2, itself derived from an IndoEuropean root K<\/span><span style=\"font-weight: 400\">W<\/span><span style=\"font-weight: 400\">EL, which implied different forms of turning, as I <\/span><a href=\"https:\/\/blogs.bmj.com\/bmj\/2018\/02\/02\/jeffrey-aronson-when-i-use-a-word-teleoanalysis\"><span style=\"font-weight: 400\">discussed<\/span><\/a><span style=\"font-weight: 400\"> last week. This suggests depicting different forms of evidence and their interrelations as a wheel, with no predominant class. Recognising that all forms of evidence can be of value in different ways emphasises the fallacy of hierarchies and suggests a different way of thinking about how evidence should be analysed. This is illustrated and described in the figure below.<\/span><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright size-full wp-image-41368\" src=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/02\/aronson_wheel.png\" alt=\"\" width=\"770\" height=\"672\" srcset=\"https:\/\/blogs.bmj.com\/bmj\/files\/2018\/02\/aronson_wheel.png 770w, https:\/\/blogs.bmj.com\/bmj\/files\/2018\/02\/aronson_wheel-300x262.png 300w, https:\/\/blogs.bmj.com\/bmj\/files\/2018\/02\/aronson_wheel-768x670.png 768w\" sizes=\"auto, (max-width: 770px) 100vw, 770px\" \/><\/p>\n<p><span style=\"font-weight: 400\">Teleoanalysis and the wheel of evidence.<\/span><\/p>\n<p><span style=\"font-weight: 400\">The green ring shows the different classes of evidence and the blue ring shows some of the types of studies that they comprise:<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">controlled studies, such as randomised trials with placebos or active comparators and controlled n-of-1 studies;<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">observational studies, both controlled and uncontrolled;<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">individualities, such as anecdotal reports and case series;<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">mechanism based evidence, which may come from in vitro, ex vivo, or in vivo studies in cells, tissues, organs, organisms, or populations, human or animal;<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">laboratory based evidence, which can be physiological or pathological, including blood tests, imaging, and instrumentation, in humans or animals;<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">qualitative studies of many kinds, including narrative analysis, semiotic analysis, Delphi studies, and conversation or discourse analysis;<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">qualitative studies with quantitative components, including statistical linguistic analysis and grounded theory.<\/span><\/li>\n<\/ul>\n<p><span style=\"font-weight: 400\">The outer orange ring indicates that any of these types of evidence can be subject to systematic evidence synthesis, for example by meta-analysis, and the inner yellow ring suggest that teleoanalysis can encompass any or all of the different types of evidence illustrated, either simultaneously or sequentially.<\/span><\/p>\n<p><em><strong>Jeffrey Aronson<\/strong>\u00a0is a clinical pharmacologist, working in the Centre for Evidence Based Medicine in Oxford&#8217;s Nuffield Department of Primary Care Health Sciences. He is also president emeritus of the British Pharmacological Society.<\/em><\/p>\n<p><strong>Competing interests:<\/strong>\u00a0None declared.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Last week I discussed the concept of teleoanalysis, in which different types of evidence from disparate sources are analysed either simultaneously or sequentially. To be clear, the term implies not [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/bmj\/2018\/02\/09\/jeffrey-aronson-when-i-use-a-word-the-wheel-of-evidence\/\">More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":38359,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[5762],"tags":[],"class_list":["post-41367","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-jeff-aronsons-words"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.6 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Jeffrey Aronson: When I Use a Word . . . 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