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Caulfield co-led and was a principal investigator (PI) on Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Hitman co-led and was a PI on Collaborative AtoRvastatin Diabetes Study (CARDS). These studies dramatically changed national and international guidance for diabetes, hypertension and cholesterol, leading to widespread and far-reaching changes in management of common and potentially fatal risk factors. For example, the proportion of hypertensive patients in England with good BP control (<140/90) rose from 52% in 2006 to 62% in 2011; the mean total cholesterol level of the population has fallen by 0.5 Mmol/L between 1998 and 2011.
The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT; Co-Chairman, Professor Sever) was an investigator designed and led multinational study in which different blood pressure-lowering and lipid-lowering treatment strategies were investigated in an attempt to define optimal programmes for intervention to prevent cardiovascular disease in hypertensive subjects. The outcomes of both the antihypertensive arm and the lipid arm of the trial defined the benefits of more contemporary treatments for hypertensive subjects, including calcium channel blockers, angiotensin converting enzyme inhibitors and statins, which have been incorporated into national and international guidelines (including NICE), and have impacted on current clinical practice in the prevention of cardiovascular disease worldwide.
More than half of UK adults aged over 45 years have high cholesterol levels, the major modifiable risk factor for cardiovascular disease (CVD). Over the past 20 years, University of Glasgow researchers have led numerous landmark clinical trials establishing the benefits of statins for CVD prevention. High-profile international clinical guidelines on lipid lowering cite these studies in the key evidence base for recommendations to guide statin use, demonstrating the considerable influence this work exerts on current clinical practice and public health. This has driven the global uptake of statins and provided the evidence-base for CVD risk assessment and prevention strategies that are now implemented worldwide. The use of statins has transformed patient care, provided a cost-effective prevention strategy for healthcare providers and made major contributions to the falling CVD mortality rates across Europe and the US.
Researchers at the University of Manchester (UoM) have made a significant impact nationally and internationally on improving the outcome for children with acute lymphoblastic leukaemia (ALL) (~450 pa in the UK). The changes in clinical practice based on our research are now national standards of care for children with de novo and relapsed ALL in the UK and Ireland. Other international groups have adopted key findings from the results of our frontline trials. Our relapse protocol for childhood ALL underpins European and North American strategy for the management of relapsed disease.
Impact: Health and welfare; public health studies in Sri Lanka and clinical trials in a cohort of 35,000 pesticide self-poisoning patients have led to the withdrawal of high-dose pralidoxime as a WHO-recommended treatment and bans of three toxic pesticides in Sri Lanka.
Significance: Resultant changes in clinical practice and pesticide regulation have saved 3000 lives in the last four years in Sri Lanka alone; in the rest of Asia many times this as local guidelines and practice have changed.
Beneficiaries: Patients and communities, healthcare providers, policy-makers.
Attribution: Studies designed and led, with international collaborators, by Michael Eddleston, UoE.
Reach: International, particularly Asia, changes in WHO and international guidelines on pesticide use.
The University of Oxford's International Subarachnoid Aneurysm Trial (ISAT) changed clinical practice worldwide by showing that endovascular coiling is a more effective and safer treatment than neurosurgery following subarachnoid haemorrhage, with fewer complications and improved quality of life. Subarachnoid haemorrhages account for 1 in 14 strokes and are caused by bleeding in and around the brain; approximately 85% occur when cerebral aneurysms rupture. ISAT was the first trial to compare neurosurgery, or neuroradiological endovascular coiling in patients with ruptured cerebral aneurysms causing acute subarachnoid haemorrhage.
Three national, multicentre randomised controlled trials and associated studies during a 20-year research programme on abdominal aortic aneurysm (AAA) led by Imperial College researchers have altered international practice. The United Kingdom Small Aneurysm Trial (UKSAT) set the threshold for intervention at 5.5cm to repair AAAs. Population screening programmes and guidelines in Europe (UK, Sweden and Europe as a whole), Australia and the United States are based on these data. The results from EndoVascular abdominal Aortic Repair (EVAR) trials have informed international audits, guidelines (including NICE) and task forces in the same countries.
Prior to the change in WHO recommendations which occurred following this study many patients in Africa and other developing countries were receiving an inferior regimen for the management of tuberculosis, a consequence of which meant that many had to be retreated. Since the implementation of the revised WHO Guidelines in 2010 almost all countries have now switched to the gold standard tuberculosis treatment regimen based on 6 months of isoniazid and rifampicin
Impact: Health and welfare, policy and clinical practice; randomised trial evidence has changed the management and outcome of acute coronary syndromes (ACS) globally.
Significance: Advanced anti-platelet and revascularisation therapies have become standards of care worldwide. There have been large (10-50%) reductions in the death rate from coronary heart disease across Europe. Clopidogrel was the second best-selling drug in the USA in 2011.
Beneficiaries: Patients with ACS, clinical practitioners, NHS and healthcare delivery organisations, policy-makers, pharmaceutical companies.
Attribution: Building on prior studies, Fox (UoE) and colleagues led multicentre randomised controlled trials; international trials were co-chaired by Fox with international investigators.
Reach: Global; guideline changes in Europe and USA; applies to the up to 5% of the population who have ACS.
Research from the University of Nottingham on aminoglycoside antibiotics in cystic fibrosis (CF) has changed clinical practice and improved patient safety internationally. There are over 70,000 people with CF worldwide. Most require frequent and prolonged intravenous courses of aminoglycoside antibiotics (which can cause kidney damage) to treat chronic lung infection with Pseudomonas aeruginosa. This infection may lead to respiratory failure and death. Our research has influenced national and international guidelines, and changed practice, such that once-daily aminoglycosides (less toxic to the kidneys) are now used. We have also stopped the use of gentamicin, in favour of less toxic aminoglycosides.