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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.
Abdominal aortic aneurysm (AAA) is a major cause of death in older men, in the UK and elsewhere. A large UK trial led by the University of Cambridge evaluated the long-term benefits of ultrasound screening for AAA in men aged 65-74 years. This provided the basis for the introduction of a UK national AAA screening programme in men aged 65; this was announced in 2008, initiated in 2009, and achieved full coverage of England in 2013. Similar screening has started in Sweden, New Zealand and in parts of Italy, and is being actively discussed in Denmark, Norway and Finland.
Research at UCL firmly established tacrolimus as the optimal calcineurin inhibitor to use in immunosuppressive regimens following liver transplantation. Compared to ciclosporin its use improved graft survival by 6% and patient survival by 7%. Assuming 550 liver transplants per year in the UK since 2008, we can estimate that, with 90% of patients treated with tacrolimus and 10% ciclosporin, tacrolimus-based immunosuppression has resulted in 165 grafts and 192 lives being saved during the period 2008-13.
Before the Hypertension in the Very Elderly Trial (HYVET) it was not clear whether people aged 80 and over with hypertension should receive antihypertensive treatment. The over 80s are one of the fastest growing groups in society and are at high risk of hypertension and its sequelae due to age. HYVET demonstrated benefit of treatment including reduced mortality and cardiovascular comorbidity. Guidelines around the world for the treatment of hypertension have changed as a result. In the UK it is proposed that the Quality Outcomes Framework (QOF) for GPs now includes those over 80 and uses the target blood pressure used in HYVET.
Severe Limb Ischaemia (SLI), in which there is reduced blood flow to the leg(s), is the commonest cause worldwide of gangrene and limb loss. The BASIL trial, led by Professor Andrew Bradbury at the University of Birmingham, was the first (and remains the only) randomised controlled trial to investigate whether surgical bypass or endovascular (`keyhole') treatment is best at relieving symptoms and preventing amputation and/or death in patients with SLI. The outcomes of the study have been of worldwide interest, and the recommendations put forward by the team have been endorsed by a number of high profile clinical organisations. These findings are also nowincorporated within a series of national and international guidelines on SLI.
Trauma is a rapidly increasing global healthcare problem which is predicted by the World Health Organisation (WHO) to overtake infectious disease globally by 2020. The discovery of the acute coagulopathy of trauma (uncontrolled bleeding) and the subsequent establishment of the clot stabiliser tranexamic acid (TXA) as a treatment for this condition has led to a change in national and international trauma management protocols. British armed forces and the US military implemented the use of the drug soon after the results were published. Every injured British or American soldier now receives this treatment. The use of TXA has been included in national and international guidance for trauma care.
Impact: Health and welfare; a UK clinical trial of uterine artery embolisation (UAE), with five-year follow-up, defined the risk- and cost-benefit of UAE versus surgery.
Significance: The trial informed guidelines/recommendations internationally and changed clinical practice. Women worldwide can now make an informed choice about their treatment; economic factors have been quantitated.
Beneficiaries: Uterine fibroid patients, the NHS, healthcare providers.
Attribution: G. Murray, UoE, developed and delivered innovative trial methodology; clinical aspects led by University of Glasgow.
Reach: UK guidelines; worldwide (Australia, USA, Europe) effect on clinical practice that will impact up to 25% of women.
Research undertaken by Professor Atkin has identified a feasible, acceptable and cost-effective method of reducing colorectal cancer incidence and mortality rates, which involves a once-only flexible sigmoidoscopy screening for all men and women at around age 60. The supporting research involved publishing the evidence, developing a fail-safe, efficient, patient-friendly delivery system, developing a surveillance strategy following adenoma-removal, and testing in multicentre randomised trials. After 11 years, incidence and mortality rates were reduced profoundly in the trials, with no observed attenuation of effect. The entire screening strategy was rolled out in a national programme from 2013, with complete population coverage expected by 2016.
Impact: Health and welfare; a clinical trial demonstrated that statin therapy is ineffective in aortic stenosis; this informed international guidelines and changed clinical practice.
Significance: Unnecessary statin therapy is avoided in up to 500,000 people in the UK alone, saving the NHS £169M p.a. Known statin side-effects of myalgia or hepatic dysfunction are avoided in 30,000 patients.
Beneficiaries: Patients with aortic stenosis; the NHS and healthcare delivery organisations, the economy.
Attribution: Newby and Boon, UoE, undertook the first investigator-led randomised controlled trial of statin therapy in aortic stenosis: the SALTIRE trial.
Reach: Aortic stenosis affects 2% of people over 65. The SALTIRE trial results informed European and N American guidelines and have impacted the treatment of millions of people globally.
Between 1996 and 2013 researchers at Swansea University evaluated service initiatives and changing professional roles associated with the management of patients with debilitating gastrointestinal disorders. This work showed the clinical and cost effectiveness of two main innovations: open access to hospital services for patients with inflammatory bowel disease; and increased responsibility for nurses, particularly as endoscopists. Our evidence has had a broad, significant impact on: national policy through incorporation in NHS strategies, professional service standards and commissioning guides; service delivery through the provision of increasing numbers of nurse endoscopists and the wide introduction of nurse-led open access to follow-up; and patient care, as documented in sequential national audits in 2006, 2008 and 2010.