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Warfarin is an anti-coagulant drug prescribed to tens of millions of people in the UK and US who are at high risk of developing blood clots. Because individual sensitivity to warfarin varies in the population there is a risk of overdosing the drug and causing serious bleeding and even stroke in many people when starting treatment. In 1999 researchers at Newcastle University were the first to demonstrate a statistically significant link between a person's genotype and the appropriate dose of warfarin. In 2010 the US Food and Drug Administration (FDA) mandated inclusion of a table of dose recommendations based on genotype in the warfarin prescribing information leaflet accompanying the drug. Newcastle research forms the basis of the 2009 international standard algorithm for gene-guided dosing of warfarin. This approach has been adopted by large US medical centres and the FDA states that it will prevent 17,000 strokes a year in the US.
Research led by Professor Keith Hawton in Oxford starting in 2003 showed that the painkiller co- proxamol (`Distalgesic') was the most common drug used for fatal self-poisoning in the UK. The findings led to its complete withdrawal in the UK by 2008, and further research demonstrated that this was followed by a reduction in deaths from suicide and accidental poisoning. The findings were instrumental in the European Medicines Agency decision in 2010 to recommend withdrawal of the toxic component of co-proxamol, dextropropoxyphene, in all EU countries. This has also occurred in the USA, Canada, and several other countries. The withdrawal of co-proxamol is estimated to have led to approximately 600 fewer deaths by 2012 in the UK alone.
Bladder cancer is the fifth most common form of cancer, with over 70% of cases presenting as non-muscle invasive bladder carcinomas (NMIBC). Research in the Institute of Cancer Therapeutics at the University of Bradford led to the evaluation of Apaziquone (EO9) in phase II clinical trials against high risk NMIBC in The Netherlands, and two multi-centre phase III clinical trials involving 106 centres across the USA, Canada and Europe. A total of 1,746 patients with low or high risk NMIBC received EO9 and significant reductions in the rates of recurrence at two years have been reported. Our research has impacted upon the health and welfare of patients with NMIBC.
Patients are more likely to get the most effective healthcare, at affordable cost to the NHS, as a result of research methodology, developed by researchers at the University of Bristol, that allows the efficacy and cost-effectiveness of multiple treatment options to be compared, based on all the available evidence, much more efficiently than in the past. Since 2008, these methods have been used to inform Clinical Guidelines issued by the National Institute for Health and Care Excellence (NICE) and in submissions to NICE's Technology Appraisals. Guidance in NICE's Technology Appraisals is mandatory and therefore impacts directly on clinical practice. The methodology is used in decision making by NICE's equivalents in other countries including Canada, Germany, and South Korea, and by consultancy firms that conduct analyses for pharmaceutical companies.
Infection of patients with cystic fibrosis (CF) with the multidrug-resistant Nontuberculous mycobacteria (NTM), Mycobacterium abscessus, has rapidly increased over the past decade and currently affects 5-10% of CF patients worldwide. Our work has identified two possible mechanisms by which M. abscessus infection rates may be increasing: chronic azithromycin therapy may predispose individuals to infection through inhibition of autophagic-killing of mycobacteria; secondly, there is frequent person-to-person transmission of M. abscessus despite conventional infection control measures. This research has had a direct impact on how CF is treated, and has influenced infection control guidelines throughout the UK.
The World Health Organization (WHO) estimate 3.3 billion people are at risk of malaria, with 219 million cases and over half a million deaths annually. The Liverpool School of Tropical Medicine (LSTM) has applied new methods of research synthesis to malaria, and the results of this work have directly influenced important global decisions on malaria policies, including the adoption of new antimalarial drugs. In this case study, we report on the influence of the LSTM on malaria control over the last 15 years by preparing rigorous, up-to-date, timely systematic reviews on malaria. This work has also contributed to substantive improvements in the methodological rigor and transparency of the WHO malaria policy group in evidence-based policy formulation and guideline development.
Clinical pharmacology studies conducted at Newcastle have led to optimisation of the administration of the chemotherapy drug carboplatin in children with neuroblastoma and other cancers. The research provided the rationale for carboplatin dosing based on patient renal function, with individualised dosing resulting in increased drug efficacy and reduced toxicity. This approach is now in widespread use in national and European treatment protocols, benefitting over 2,500 children. Similar drug monitoring approaches are being implemented for an increasing number of important drugs. Following a recent Newcastle-led national clinical trial, new dosing guidelines for the drug 13-cis retinoic acid have been adopted for high-risk neuroblastoma patients across Europe.
Research at the University of Sheffield contributed to the development by GlaxoSmithKline (GSK) of a drug to treat Irritable Bowel Syndrome (IBS) that has transformed the lives of thousands of patients and generated significant revenue. The drug, alosetron, which blocks 5-HT3 receptors in the gastrointestinal tract, was approved by the Food and Drug Administration (US) (FDA) in 2000 and launched under the trade name Lotronex. It is currently the only drug on the market aimed specifically at the treatment of diarrheal IBS. Although GSK voluntarily withdrew the drug from the market following concerns over possible side effects, Lotronex was relaunched in 2004 following petition from IBS sufferers and user groups. The licence for Lotronex was sold in 2008 to Prometheus Laboratories, Inc. and annual sales of the drug now exceed $34 million. In 2011 Prometheus was bought by Nestle for an estimated $1.1billion. This case study has significant impact on commerce and health and welfare.
Non-steroidal anti-inflammatory drugs (NSAIDs) are valuable analgesics, but cause dyspepsia, ulcers and hospitalisation (UK: 3,500pa, USA: 100,000pa) for complications that can lead to death (UK: 400-1,000pa, USA: 16,500pa). Acid inhibition by proton pump inhibitors (PPIs), the only widely accepted preventative strategy, was proposed and systematically proved by studies from Nottingham. NICE now recommends PPIs for all patients using NSAIDs and PPIs are central to all major international guidelines. PPI co-prescription has increased worldwide (from 27.6% in 2008 to 44.1% in 2012, in the UK); and reduces the risk of hospitalisation for gastrointestinal bleeding by 54% and symptomatic ulcer by 63%, thereby preventing up to 540 deaths per annum in the UK.
Paracetamol self-poisoning is a major cause of liver failure and death. Research by Professor Keith Hawton and colleagues in Oxford in the 1990s revealed the extent and characteristics of the problem, and led to UK legislation to restrict pack size in 1998. Hawton and colleagues then showed that this was followed by a substantial reduction, over 30%, in the number of deaths from paracetamol poisoning. Importantly, a 2013 analysis shows that the benefit has been sustained and is not diminishing, with an estimated 374 fewer deaths in the UK since 2008. Registrations for liver transplants due to paracetamol toxicity have also decreased. As a result of these benefits, three other countries have introduced similar restrictions since 2008.