{"id":47704,"date":"2020-06-05T18:22:19","date_gmt":"2020-06-05T17:22:19","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=47704"},"modified":"2020-06-12T16:42:03","modified_gmt":"2020-06-12T15:42:03","slug":"jeffrey-aronson-when-i-use-a-word-retraction","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2020\/06\/05\/jeffrey-aronson-when-i-use-a-word-retraction\/","title":{"rendered":"Jeffrey Aronson: When I Use a Word . . . Retraction"},"content":{"rendered":"<p><span style=\"font-weight: 400\">The <\/span><a href=\"https:\/\/retractionwatch.com\/\"><span style=\"font-weight: 400\">retraction<\/span><\/a><span style=\"font-weight: 400\"> yesterday of two publications, one in <\/span><em><a href=\"https:\/\/www.thelancet.com\/lancet\/article\/s0140673620313246\"><span style=\"font-weight: 400\">The Lancet<\/span><\/a><\/em><span style=\"font-weight: 400\"> and one in the <\/span><em><a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMc2021225\"><span style=\"font-weight: 400\">New England Journal of Medicine<\/span><\/a><\/em><span style=\"font-weight: 400\">, reflects a current major problem with research into the management of covid-19\u2014that we have abandoned the tenets of evidence based medicine.<\/span><\/p>\n<p><span style=\"font-weight: 400\">In my recent <\/span><a href=\"https:\/\/blogs.bmj.com\/bmj\/2020\/05\/22\/jeffrey-aronson-when-i-use-a-word-hypotheses-weak-and-strong\"><span style=\"font-weight: 400\">litany<\/span><\/a><span style=\"font-weight: 400\"> on the subject I mentioned the following problems:<\/span><\/p>\n<ul>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">attempts to prove <\/span><a href=\"https:\/\/blogs.bmj.com\/bmj\/2020\/05\/22\/jeffrey-aronson-when-i-use-a-word-hypotheses-weak-and-strong\"><span style=\"font-weight: 400\">weak hypotheses<\/span><\/a><span style=\"font-weight: 400\"> \u2026<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">\u2026 in poorly designed clinical trials;<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">failure to test strong hypotheses;<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">premature reporting of results in press releases and in non-peer reviewed publications;<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">premature termination of trials before clear outcomes have occurred;<\/span><\/li>\n<li style=\"font-weight: 400\"><a href=\"https:\/\/www.cebm.net\/covid-19\/hydroxychloroquine-for-covid-19-what-do-the-clinical-trials-tell-us\"><span style=\"font-weight: 400\">changing<\/span><\/a><span style=\"font-weight: 400\"> prespecified endpoints without explanation and reporting other endpoints instead;<\/span><\/li>\n<li style=\"font-weight: 400\"><span style=\"font-weight: 400\">rapid, and perhaps premature, <\/span><a href=\"https:\/\/www.cebm.net\/covid-19\/emergency-use-authorization-of-remdesivir-by-the-us-food-and-drug-administration\"><span style=\"font-weight: 400\">authorization<\/span><\/a><span style=\"font-weight: 400\"> of new medicines.<\/span><\/li>\n<\/ul>\n<p><span style=\"font-weight: 400\">To all of these I might have added the rush to publish in peer reviewed journals and publication accompanied by striking press releases. Here\u2019s an example from my own experience. A few weeks ago a learned journal asked me to review a paper. Two days later, on a Saturday afternoon, the editor sent me an email: \u201cWe recently invited you to review the above-referenced manuscript. In the meantime, we have received a sufficient number of reviews to complete the review process, and unfortunately, we must proceed without your valued input in order to ensure a fast manuscript review process.\u201d The authors had explained why the medicine they were discussing might be effective, despite the fact that they had also asserted, from mechanistic reasoning, that it should not. I had thought to suggest that they might change their emphasis, and instead discuss why t<\/span><span style=\"font-weight: 400\">h<\/span><span style=\"font-weight: 400\">e drug should be used at all, given that they believed that it was unlikely to be effective. I turned my attention to other matters.<\/span><\/p>\n<p><span style=\"font-weight: 400\">The word retraction comes from the Latin verb trahere (past participle tractus), to drag, pull, or draw or carry along in several senses, and by extension to convey an idea mentally. The addition of the usual suffixes gives us a swathe of English words. The <\/span><i><span style=\"font-weight: 400\">abstract<\/span><\/i><span style=\"font-weight: 400\"> of a paper may <\/span><i><span style=\"font-weight: 400\">attract<\/span><\/i><span style=\"font-weight: 400\"> you to read it, or at least an <\/span><i><span style=\"font-weight: 400\">extract<\/span><\/i><span style=\"font-weight: 400\">, rather than the more <\/span><i><span style=\"font-weight: 400\">protracted<\/span><\/i><span style=\"font-weight: 400\"> version; it may prompt a <\/span><i><span style=\"font-weight: 400\">train<\/span><\/i><span style=\"font-weight: 400\"> of thought that will <\/span><i><span style=\"font-weight: 400\">distract<\/span><\/i><span style=\"font-weight: 400\"> you for a while, but when it is <\/span><i><span style=\"font-weight: 400\">retracted<\/span><\/i><span style=\"font-weight: 400\">, you may realize that it is not the <\/span><i><span style=\"font-weight: 400\">treat<\/span><\/i><span style=\"font-weight: 400\"> you thought it was, and the event may <\/span><i><span style=\"font-weight: 400\">detract<\/span><\/i><span style=\"font-weight: 400\"> from your propensity to believe anything published thereafter in the journal that published it.\u00a0\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">In a <\/span><a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/32215814\"><span style=\"font-weight: 400\">review<\/span><\/a><span style=\"font-weight: 400\"> of retracted publications, the highest proportions came from Egypt (304 retractions per million publications), Iran (295), South Korea (219), China (216), India (193), Singapore (161), Thailand (157), Japan (132), Turkey (124), the Netherlands (119), and Germany (108). The authors described twelve reasons for retraction in 2088 cases: plagiarism (19.2%); data fabrication or falsification (17.7%); suspected fraud (17.5%); scientific errors (14.4%); duplicate publication (6.3%); authors&#8217; disputes (3.2%); violation of ethics (2.7%); publishers&#8217; errors (2.6%); problems with copyright (1.1%); manipulation of peer review (0.4%); problems with funding (0.1%); combinations (6.2%); unknown (8.5%).<\/span><\/p>\n<p><span style=\"font-weight: 400\">The story of the recent retractions is salutary. <\/span><i><span style=\"font-weight: 400\">The Lancet<\/span><\/i><span style=\"font-weight: 400\"> issued a press release announcing the forthcoming publication, on 22 May, of a retrospective analysis of data from over 96 000 patients in 671 hospitals worldwide. Mortality was reportedly increased in those who had received a 4-aminoquinolone (chloroquine or hydroxychloroquine), and more so in those who had also received a macrolide antibiotic (azithromycin or clarithromycin). The results were believable, since both types of drug can prolong the electrocardiographic QT interval, with a risk of the polymorphous ventricular tachycardia called <\/span><a href=\"https:\/\/blogs.bmj.com\/bmj\/2020\/05\/29\/jeffrey-aronson-when-i-use-a-word-hydroxychloroquine-and-torsades-de-pointes\"><span style=\"font-weight: 400\">torsades de pointes<\/span><\/a><span style=\"font-weight: 400\"> (Figure 1), and the combinations are better avoided. However, it was not long before <\/span><a href=\"https:\/\/statmodeling.stat.columbia.edu\/2020\/05\/25\/hydroxychloroquine-update\/\"><span style=\"font-weight: 400\">doubts<\/span><\/a><span style=\"font-weight: 400\"> began to be raised about the provenance and accuracy of the data, and the authors have since announced that since they cannot vouch for the data they have retracted the paper.<\/span><\/p>\n<p>Despite this retraction, the reported effects may be real; we can&#8217;t tell. However, two UK trials, COPCOV and PRINCIPLE, were immediately <a href=\"https:\/\/www.cebm.net\/covid-19\/chloroquine-and-hydroxychloroquine\/\">halted<\/a> before the retraction, and now today the RECOVERY investigators have announced that they too will no longer recruit participants into the hydroxychloroquine arm of their trial, following an <a href=\"http:\/\/www.ox.ac.uk\/news\/2020-06-05-no-clinical-benefit-use-hydroxychloroquine-hospitalised-patients-covid-19\/\">analysis<\/a> of the latest data. They randomized 1542 patients to hydroxychloroquine and compared them with 3132 patients randomized to usual care alone. There was no significant difference in the primary endpoint of 28-day mortality (25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence interval 0.98-1.26]; P=0.10) and no evidence of beneficial effects on hospital stay duration or other outcomes. They concluded that &#8220;These data convincingly rule out any meaningful mortality benefit of hydroxychloroquine in patients hospitalised with COVID-19.&#8221; Indeed the data suggest that it is likely that there is increased mortality in those given hydroxychloroquine, the lower 95% confidence limit being only just below 1. The WHO have also halted the hydroxychloroquine arm of their SOLIDARITY trial.\u200b<br \/>\n\u200b<br \/>\nThis must surely be the end of the road for the 4-aminoquinolines, chloroquine and hydroxychloroquine, in the treatment of covid-19.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-47705\" src=\"https:\/\/blogs.bmj.com\/bmj\/files\/2020\/06\/Capture.jpg\" alt=\"\" width=\"674\" height=\"382\" srcset=\"https:\/\/blogs.bmj.com\/bmj\/files\/2020\/06\/Capture.jpg 674w, https:\/\/blogs.bmj.com\/bmj\/files\/2020\/06\/Capture-300x170.jpg 300w, https:\/\/blogs.bmj.com\/bmj\/files\/2020\/06\/Capture-640x363.jpg 640w\" sizes=\"auto, (max-width: 674px) 100vw, 674px\" \/><\/p>\n<p><b>Figure 1.<\/b> <i><span style=\"font-weight: 400\">An example of torsades de pointes (source: <\/span><\/i><a href=\"https:\/\/commons.wikimedia.org\/wiki\/File:Torsades_de_Pointes_TdP.png\"><i><span style=\"font-weight: 400\">Wikimedia Commons<\/span><\/i><\/a><i><span style=\"font-weight: 400\">)<\/span><\/i><\/p>\n<p style=\"text-align: left\"><span style=\"font-weight: 400\"><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><\/span><\/p>\n<p style=\"text-align: left\"><strong>Competing interests:<\/strong> None declared.<\/p>\n<p><a href=\"https:\/\/blogs.bmj.com\/bmj\/2020\/05\/07\/jeffrey-aronson-when-i-use-a-word-chains-of-exponentials\/\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-47711 size-full\" src=\"https:\/\/blogs.bmj.com\/bmj\/files\/2020\/06\/aronson_5june.png\" alt=\"\" width=\"698\" height=\"1742\" srcset=\"https:\/\/blogs.bmj.com\/bmj\/files\/2020\/06\/aronson_5june.png 698w, https:\/\/blogs.bmj.com\/bmj\/files\/2020\/06\/aronson_5june-120x300.png 120w, https:\/\/blogs.bmj.com\/bmj\/files\/2020\/06\/aronson_5june-410x1024.png 410w, https:\/\/blogs.bmj.com\/bmj\/files\/2020\/06\/aronson_5june-615x1536.png 615w, https:\/\/blogs.bmj.com\/bmj\/files\/2020\/06\/aronson_5june-640x1597.png 640w\" sizes=\"auto, (max-width: 698px) 100vw, 698px\" \/><\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>The retraction yesterday of two publications, one in The Lancet and one in the New England Journal of Medicine, reflects a current major problem with research into the management of [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/bmj\/2020\/06\/05\/jeffrey-aronson-when-i-use-a-word-retraction\/\">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-47704","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 v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Jeffrey Aronson: When I Use a Word . . . 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