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Impact of research into selection bias and ethical issues on published medical guidelines and legal judgements

Summary of the impact

Professor Hutton's research considers the biasing effect of selection of data due to consent procedures or selective reporting, and its consequences for the validity of conclusions and reliability of results. This research has had impacts on patients directly; on health and legal professionals by informing and influencing national and international guidelines for the treatment of epilepsy used by healthcare professionals and practitioners; and has provided expert evidence to legal professionals for the conclusion of civil litigations and a General Medical Council professional misconduct trial. Hutton's research also informs ethical debate associated with the validity and robustness of study results. This work has determined guidelines for ethical conduct of research, and requirements for publications, which are significant for all biomedical researchers.

Submitting Institution

University of Warwick

Unit of Assessment

Mathematical Sciences

Summary Impact Type

Health

Research Subject Area(s)

Mathematical Sciences: Statistics

Statin Therapy: Patient Selection, Clinical Guidelines and revision of safety labelling

Summary of the impact

Over the past ten years, the prescription of cholesterol-lowering statins has soared and they are now the most prescribed drugs in the UK and the US. However, this has raised concerns about inappropriate prescribing. University of Glasgow research has been pivotal in addressing this issue and has triggered revision of major international guidelines to stratify patients in the general population for statin therapy and guide statin use in the rheumatoid arthritis patient population. The identification of a statin-associated risk for diabetes prompted the European Medicines Agency and the US Food & Drug Administration to revise safety labelling for all classes of statins. This risk is now communicated to the 27 million patients in the UK and US who are prescribed statins.

Submitting Institution

University of Glasgow

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services

Global adoption of statins for cardiovascular disease prevention

Summary of the impact

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.

Submitting Institution

University of Glasgow

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Public Health and Health Services

Development of novel adaptive designs to improve efficiency in clinical trials

Summary of the impact

Clinical trials are costly to the pharmaceutical industry and public funding bodies, require major commitment from volunteer patients and take significant time to lead to patient benefit. Adaptive designs are one approach which seeks to improve the efficiency of such studies. Statistical research at Reading has led to novel methodology for the design and analysis of clinical drug trials within the framework of adaptive designs which has the potential to reduce the time taken for effective drugs to reach the market and thus benefit specific patient groups. To date the research has had impact in three major ways: i) it has been adopted by pharmaceutical companies as a means of improving the efficiency of their clinical trials, ii) the research has been cited in the regulatory guidance on adaptive clinical trial design, and iii) it has increased awareness by clinicians and other medical professionals of the potential benefit of the adaptive design methodology to their patient groups. Hence, the research has influenced industry, regulatory and health professionals with potential significant economic benefit and improved outcome for patients.

Submitting Institution

University of Reading

Unit of Assessment

Mathematical Sciences

Summary Impact Type

Political

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Oncology and Carcinogenesis, Pharmacology and Pharmaceutical Sciences

Improving the Methodology, Ethics, and Implementation of Evidence-Based Medicine

Summary of the impact

Dr Jeremy Howick's research into philosophical issues concerning the nature of the evidence invoked in evidence-based medicine has led both to a revision of the standards for reporting trials, and to a redesign of the Oxford Centre for Evidence-Based Medicine `Levels of Evidence': one of the most widely used systems for ranking medical evidence, and thereby for deciding whether treatments are effective, in the world. His research into philosophical issues concerning the ethics of using placebos in clinical trials and in clinical practice has influenced practitioners as well as patients by helping to determine how treatments are developed and applied. Through his research in both of these areas he has enhanced public understanding of the use of placebos.

Submitting Institution

University of Oxford

Unit of Assessment

Philosophy

Summary Impact Type

Societal

Research Subject Area(s)

Medical and Health Sciences: Clinical Sciences, Pharmacology and Pharmaceutical Sciences, Public Health and Health Services

Practice-changing clinical trials expand the treatment options for heart disease

Summary of the impact

Randomised placebo-controlled trials (RCTs) are the most robust way to demonstrate the effectiveness of medical therapies. The University of Glasgow's Robertson Centre for Biostatistics (RCB) is internationally renowned for its biostatistical input and leading roles on landmark RCTs of cardiovascular therapies. The findings of the BEAUTIFUL and SHIFT studies underpinned European and UK regulatory approval for a novel use of the heart-rate-lowering drug ivabradine, potentially preventing thousands of hospital admissions for heart failure every year. The IONA trial supported UK approval of generic versions of another heart drug (nicorandil), thereby enhancing cost-effectiveness for the NHS. The BEAUTIFUL, SHIFT, DOT-HF and CAPRICORN trials provided the evidence base for US, European and UK guideline recommendations, steering best practice for treatment of patients with heart disease worldwide.

Submitting Institution

University of Glasgow

Unit of Assessment

Public Health, Health Services and Primary Care

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services

Improving Clinical Trials by Innovative Statistical Design

Summary of the impact

Clinical trials form a crucial step in translating fundamental medical research into improved healthcare. Many hundreds of trials are conducted every year, each involving hundreds, sometimes thousands, of patients. These trials are expensive, with costs as high as 20 or 30 thousand pounds per patient. Research in Bath on group sequential monitoring and the adaptive design of clinical trials has improved the conduct of clinical trials, leading to:

  • faster results: making effective new treatments available sooner; also, stopping negative trials early avoids exposing patients to ineffective treatments and releases resources for new studies;
  • smaller sample sizes: average reductions of 20-30% are possible in sequential trials;
  • the ability to modify trial conditions while retaining statistical validity: this flexibility can accelerate the drug development process by months or even years.

The impact of this research is economic (the business performance of pharmaceutical companies and businesses that support them), societal (by enhancing public health and by changing the policies adopted by regulators) and ethical (ensuring clinical trials remain safe, while bringing life-saving treatments into clinical use as rapidly as possible).

Submitting Institution

University of Bath

Unit of Assessment

Mathematical Sciences

Summary Impact Type

Health

Research Subject Area(s)

Mathematical Sciences: Statistics
Medical and Health Sciences: Public Health and Health Services
Economics: Applied Economics

UOA02-03: Statin Therapy for Preventing Heart Attacks and Strokes

Summary of the impact

Studies coordinated by the University of Oxford's Clinical Trial Service Unit (CTSU) within the Nuffield Department of Population Health (NDPH) have strongly influenced the labelling of statin medication internationally, treatment guidelines, and the resulting changes in prescribing have contributed to reductions in mortality and morbidity from heart attack and ischaemic stroke in many countries. CTSU's randomised trials and meta-analyses of trials have shown that lowering low-density lipoprotein (LDL) cholesterol safely reduces the risk of heart attacks, strokes and revascularisation procedures in a wide range of people, and work conducted in collaboration with the NDPH's Health Economic Research Centre has provided clear evidence of cost-effectiveness of statins.

Submitting Institution

University of Oxford

Unit of Assessment

Public Health, Health Services and Primary Care

Summary Impact Type

Political

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services

Improving the quality of care of people with and at risk of cardiovascular diseases

Summary of the impact

Research led by Professor Harry Hemingway at UCL on the quality and outcomes of care of people with, or at risk of, cardiovascular diseases has informed guidelines and clinical management in a number of areas. The work influenced NICE guidelines on Chest pain of recent onset (CG95) with regard to the use of exercise electrocardiography (ECG) in the diagnosis of stable angina and approaches to sex and ethnicity in diagnosis. Our research also underpinned recommendations on revascularisation in the NICE guidelines on Management of stable angina (CH126). Additionally, the research has led to recommendations about the need to assess psychosocial factors including depression in people with myocardial infarction.

Submitting Institution

University College London

Unit of Assessment

Public Health, Health Services and Primary Care

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services

Improving diagnosis and treatment of canine heart disease

Summary of the impact

RVC research has helped transform differential diagnosis of canine heart disease, in first opinion veterinary practice, by demonstrating the value of peptide biomarkers and collaborating with diagnostics companies to ensure the findings have been translated into commercial assay kits available around the world. Contributions to major clinical trials have complemented this through improvements in canine cardiac disease treatment. This has benefitted dogs and their owners through improved and prolonged canine health; and has additionally delivered new guidance for professional practice, and economic value through increased therapeutic product sales and novel diagnostic services.

Submitting Institution

Royal Veterinary College

Unit of Assessment

Agriculture, Veterinary and Food Science

Summary Impact Type

Technological

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences

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