{"id":42623,"date":"2018-07-17T09:25:57","date_gmt":"2018-07-17T08:25:57","guid":{"rendered":"https:\/\/blogs.bmj.com\/bmj\/?p=42623"},"modified":"2019-02-23T19:20:48","modified_gmt":"2019-02-23T18:20:48","slug":"nick-wilson-and-matt-morgan-is-the-bench-to-bedside-broken","status":"publish","type":"post","link":"https:\/\/blogs.bmj.com\/bmj\/2018\/07\/17\/nick-wilson-and-matt-morgan-is-the-bench-to-bedside-broken\/","title":{"rendered":"Nick Wilson and Matt Morgan: Is the \u201cbench to bedside\u201d broken?"},"content":{"rendered":"<p><span style=\"font-weight: 400\">Over <\/span><span style=\"font-weight: 400\">recent decades, the UK has been a key innovator in medicine. The UK ranked 2nd overall between 1996-2017 in the number of medical publications (<\/span><span style=\"font-weight: 400\">1,059,287). [1]\u00a0<a href=\"https:\/\/blogs.bmj.com\/bmj\/2018\/03\/27\/matt-morgan-and-jade-cole-research-matters\/\">The benefits of research are obvious,\u00a0<\/a>for example, the development of new treatments, diagnostic tools, and changes in patient management. But research also helps patients directly, with hospitals and departments involved in research producing better patient outcomes. [2] With these benefits to be enjoyed and in a changing and strained healthcare system, we need to think hard about how research is carried out.<\/span><\/p>\n<p><span style=\"font-weight: 400\">The term \u201ctranslational science\u201d was first coined in the 1980s, but is not really a new concept. Simply, it is the practice of taking scientific discoveries and research and applying them in clinical practice to generate new therapeutics and treatments. [3] A dramatic example of this process is the development of monoclonal antibody therapies, where a molecular target (e.g. TNF\u03b1 for Infliximab) must first be identified and implicated in a disease process. Only then can an antibody be produced followed by rigorous drug trials before reaching the clinic door.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Carrying out research and drug development has become more costly and complex with many barriers. In 2016, it was estimated that large pharmaceutical companies spent approximately US$2.56 billion to bring a drug to market. [4] This monumental figure also took into account the low clinical success rate, with 88% of drugs having their development abandoned. This low success rate, combined with the high cost of development, would seem to make the complete development of a new drug an almost impossible feat for non-commercialised ventures. Applicants slaving over research grant forms for a \u201cbench to bedside\u201d project are surely stretching the truth to what the funders may want to hear.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Taking research from a lab all the way to the clinic is not only costly, but also a lengthy process. To identify a target implicated in a disease, understand its biology fully, develop a treatment, and then to enter lengthy drug trials will mostly take decades and countless numbers different professionals. All of these factors are barriers to cohesive translational research projects. The attractiveness of a complete translational research project to a grant awarding body is also questionable. The time taken for these projects, as well as their unpredictability, would make a single grant unfeasible. As would applying for a grant for a conceptual treatment based on limited evidence from early lab work.<\/span><\/p>\n<p><span style=\"font-weight: 400\">Another criticism of the model of translational research is the sheer unpredictability of medicine. Many medical discoveries have been completely by chance as opposed to being due to an understanding of the science underpinning the practice. Sildenafil (Viagra), a drug previously developed for hypertension, when launched by Pfizer in 1988 became the leading drug for erectile dysfunction and doubled Pfizer\u2019s share price overnight. [5] The fortuitous discovery of its potency in erectile dysfunction was only noticed however, during phase I trials to assess its benefit in angina as the original \u201cbench to bedside\u201d application form would have read. <\/span><span style=\"font-weight: 400\">They just didn\u2019t know at the time it would literally be from bench to bedside.<\/span><span style=\"font-weight: 400\">\u00a0<\/span><\/p>\n<p><span style=\"font-weight: 400\">The switching and assessment of already clinically approved and safe drugs for the treatment of different conditions is now termed \u201cdrug repositioning\u201d and companies like NovaLead Pharma and Numedicus are entirely set-up around this concept. [6] Drug repositioning shortcuts translational research, using drug screening technology to assess different functions of drugs. An example is the use of itraconazole (an anti-fungal medication) for its action as an inhibitor of blood vessel growth. Itraconazole had shown promise in cancer models and recently showed positive results in Phase II trials in lung and prostate cancer. [7]<\/span><\/p>\n<p><span style=\"font-weight: 400\">There will still however, always be a requirement for new therapeutics for still unmet clinical needs. These needs include many degenerative neurological conditions (e.g. Alzheimer\u2019s and Parkinson\u2019s disease), chronic untreatable diseases (e.g. pulmonary hypertension and pulmonary fibrosis) and rare diseases. These needs will have to be met by translational research in some form or another. And while the process of translational research may have become more fragmented, allowing researchers into the clinic and engaging with scientific research could be a small step towards redeveloping a culture which can again support the practice of translational research and again reap the benefits. Grant calls should embrace this uncertainty and allow longer-term, more explorative research or else remove the promise in short-term funding to deliver patient benefit in that area in an unrealistic timescale.<\/span><\/p>\n<p><em><span style=\"font-weight: 400\">Special thanks to Dr <\/span><span style=\"font-weight: 400\">Matthias Eberl, Cardiff University for his input and support.<\/span><\/em><\/p>\n<p><em><span style=\"font-weight: 400\"><strong>Nick Wilson<\/strong>, Medical Student, Cardiff University.<\/span><\/em><\/p>\n<p><span style=\"font-weight: 400\"><em><strong>Matt Morgan<\/strong>, Honorary Senior Research Fellow at Cardiff University, Consultant in Intensive Care Medicine and Head of Research and Development at University Hospital of Wales, and an editor of BMJ OnExamination. He is on twitter<\/em>: <a href=\"https:\/\/twitter.com\/dr_mattmorgan\">@dr_mattmorgan<\/a><\/span><\/p>\n<p><b>References:<\/b><\/p>\n<p><span style=\"font-weight: 400\">[1] Scimago Journal &amp; Country Rank. SJR &#8211; International Science Ranking. Scimagojr.com. 2018. [accessed 3 Jul 2018] Available from: <\/span><a href=\"https:\/\/www.scimagojr.com\/countryrank.php?area=2700\"><span style=\"font-weight: 400\">https:\/\/www.scimagojr.com\/countryrank.php?area=2700<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[2] Ozdemir BA, Karthikesalingam A, Sinha S, Poloniecki JD, Hinchliffe RJ, Thompson MM, Gower JD, Boaz A, Holt PJ. Research activity and the association with mortality. PLoS One. 2015 Feb 26;10(2):e0118253.<\/span><span style=\"font-weight: 400\">Accessed from: <\/span><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4342017\/\"><span style=\"font-weight: 400\">https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4342017\/<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[3]<\/span><span style=\"font-weight: 400\">Emmert-Buck MR. Translational research: From biological discovery to public benefit (or not). Advances in Biology. 2014;2014.Accessed from: <\/span><a href=\"https:\/\/www.hindawi.com\/journals\/ab\/2014\/278789\/\"><span style=\"font-weight: 400\">https:\/\/www.hindawi.com\/journals\/ab\/2014\/278789\/<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[4] DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&amp;D costs. Journal of health economics. 2016 May 1;47:20-33. Accessed from: <\/span><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0167629616000291?via%3Dihub\"><span style=\"font-weight: 400\">https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0167629616000291?via%3Dihub<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[5] Jacque Wilson C. Viagra: The little blue pill that could &#8211; CNN. CNN. 2018. [accessed 20 Jun 2018] Available from: <\/span><a href=\"https:\/\/www.cnn.com\/2013\/03\/27\/health\/viagra-anniversary-timeline\/index.html\"><span style=\"font-weight: 400\">https:\/\/www.cnn.com\/2013\/03\/27\/health\/viagra-anniversary-timeline\/index.html<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[6] Nosengo N. Can you teach old drugs new tricks?. Nature News. 2016 Jun 16;534(7607):314. Accessed from:<\/span><a href=\"https:\/\/www.nature.com\/news\/can-you-teach-old-drugs-new-tricks-1.20091\"><span style=\"font-weight: 400\">https:\/\/www.nature.com\/news\/can-you-teach-old-drugs-new-tricks-1.20091<\/span><\/a><\/p>\n<p><span style=\"font-weight: 400\">[7] Sun W, Sanderson PE, Zheng W. Drug combination therapy increases successful drug repositioning. Drug discovery today. 2016 Jul 1;21(7):1189-95. Accessed from: <\/span><a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1359644616301866\"><span style=\"font-weight: 400\">https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1359644616301866<\/span><\/a><\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Over recent decades, the UK has been a key innovator in medicine. The UK ranked 2nd overall between 1996-2017 in the number of medical publications (1,059,287). [1]\u00a0The benefits of research [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/blogs.bmj.com\/bmj\/2018\/07\/17\/nick-wilson-and-matt-morgan-is-the-bench-to-bedside-broken\/\">More&#8230;<\/a><\/p>\n","protected":false},"author":1,"featured_media":42637,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[18885],"tags":[],"class_list":["post-42623","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-matt-morgan"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Nick Wilson and Matt Morgan: Is the \u201cbench to bedside\u201d broken? - The BMJ<\/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\/bmj\/2018\/07\/17\/nick-wilson-and-matt-morgan-is-the-bench-to-bedside-broken\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Nick Wilson and Matt Morgan: Is the \u201cbench to bedside\u201d broken? - The BMJ\" \/>\n<meta property=\"og:description\" content=\"Over recent decades, the UK has been a key innovator in medicine. 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