Applied research project highlights

Hypertension (high blood pressure (BP)) is a major risk factor for stroke and heart disease, with almost 7 million people in England currently receiving antihypertensive treatment. However, research suggests that perhaps twice as many people have undetected hypertension and, for many of those being treated, it is poorly controlled. BP can be easily and accurately measured using electronic BP monitors and evidence suggests that patients can successfully self-monitor using this equipment.

An Oxford University-led NIHR Programme Grant, which began in early 2012, aims to provide new information regarding the use of self-monitoring of BP in both the detection and treatment of hypertension. The research is led by Professor Richard McManus and builds on three self-monitoring trials (TASMINH, TASMINH 2, TASMIN-SR), and a model-based analysis which determined the most appropriate method for diagnosing hypertension, that subsequently informed NICE hypertension guidelines. All four studies involved members of HEU as collaborators.

Continuing this successful collaboration, the health economics aspects of the current programme are led by Sue Jowett and Pelham Barton, with Mark Monahan employed on this study for the next two years. Decision modelling is being used to explore four main research questions:

• Is the use of a risk-based algorithm to determine who receives home BP monitoring/ambulatory BP monitoring cost-effective? This work builds on the analysis undertaken for the NICE guidelines.
• Could the use of blood pressure self-screening kiosks in the community be a cost effective method of screening for hypertension?
• What is the most cost-effective method of hypertension screening and subsequent cardiovascular risk assessment?

It is hoped that the results of this research will influence guidelines produced by NICE and be followed by GPs nationally. Ultimately, the purpose is to result in better management of hypertension and reduce the risk of cardiovascular disease.

Postpartum haemorrhage (PPH) is a leading cause of maternal death worldwide. The World Health Organisation (WHO) currently recommend uterotonic agents for the prevention of PPH, however past research has only ever compared a maximum of 2 uterotonic agents at any one time.

Researchers based at University of Birmingham and Birmingham Women’s hospital have gained funding from the NIHR to compile a network meta-analysis to rank the effectiveness and cost-effectiveness of all uterotonic agents used for the prevention of PPH. The research is led by Professor Arri Coomarasamy, with the Health Economics side being led by Professor Tracy Roberts. Karen Pickering is also working on the project, which is due for completion in October 2016.

The WHO is expected to review their guidelines around PPH in the near future, and we anticipate our research will have an impact in their decisions.

Haemorrhage (excessive blood loss) is the leading cause of direct maternal death in sequential Confidential Enquiry into Maternal and Child Health (CEMACE) reports. Haemorrhage is more common in women who have Caesarean sections (CS) whether planned or emergency and hence CS results in the administration of large amounts of donor blood. Approximately 70,000 units of blood are given annually in the maternity setting at a current cost of £140 per unit. Approximately 140,000 CS are performed annually in the UK, so any reduction in the amount of blood required could significantly reduce the cost of blood transfusions to the NHS.

Intra-operative cell salvage (IOCS) collects the patient’s own blood lost during an operation, processes it and returns it to their circulation. Its use has been proven to reduce the amount of donor blood given in other operations, however its use in CS has not yet been adequately examined. NICE currently only recommends IOCS for emergency CS, but has called for robust evidence from clinical trials to support its wider, routine use.

The SALVO trial, funded by the NIHR, is an individually randomised, controlled, multi-centre trial comparing the use of IOCS during CS in women with high risk of haemorrhage to the current practice (no IOCS), with the objective of determining whether the routine use of IOCS reduces the need for donor blood transfusion. The aim of the economic evaluation, conducted by Carol McLoughlin supported by Professor Tracy Roberts, is to determine the relative cost-effectiveness of IOCS compared with current practice. It is hoped that the results of this trial and the economic evaluation will influence guidelines produced by NICE.

Annually, 210 million women become pregnant world-wide.  From these pregnancies, 33 million have been estimated to end in miscarriage, with most of them taking place in low income countries.  In these countries, miscarriage surgery is one of the most common operations performed and the associated infection rate has been reported to be up to 30%.  Infections can lead to serious illness, infertility or death from severe haemorrhage and have profound social and economic impacts.

AIMS is a multinational, randomised, double-blind placebo-controlled trial investigating the effectiveness of prophylactic antibiotics (doxycycline and metronidazole) in reducing the risk of pelvic infection in women undergoing miscarriage surgery. 

The AIMS Trial is led by Professor Arri Coomarasamy and is funded by the Joint Global Health Trials Scheme, a collaborative funding scheme between the Medical Research Council, the Wellcome trust and the Department for International Development. Professor Tracy Roberts and Dr Ilias Goranitis will assess the relative cost-effectiveness of antibiotic prophylaxis in the surgical management of miscarriage.

The findings of the AIMS Trial are expected to have a major impact on maternal health, both at a national and international level.

As a result of smoking, diabetes, high blood pressure and high cholesterol, some people develop atherosclerosis (i.e. hardening of the arteries) in their legs. Atherosclerosis reduces the blood supply, causing pain when walking. As the disease progresses, the supply to the leg can become so poor that people get severe pain. At this stage, even minor injuries to the foot can fail to heal, allowing infection to enter the tissues, resulting in the development of ulceration, even gangrene.

Unless the blood supply to the leg and foot is improved, many affected people will lose the limb and/or die within 12 months as a result of “severe limb ischaemia” (SLI). One in every 1000-2000 people in the UK will be diagnosed with SLI each year and this rate is rising as a result of the ageing population, the large increase in the numbers of people with diabetes, and continuing high rates of smoking. As well causing great suffering, SLI places a substantial economic burden on health and social care services.

To ensure that patients with SLI receive appropriate, effective and cost-effective care, the National Institute for Health Research (NIHR) funds two ongoing studies, the BASIL-2 and BASIL-3 randomised clinical trials. Professor Tracy Roberts and Dr Lazaros Andronis are leading the economic analyses of BASIL-2 and BASIL-3, respectively.

BASIL-2 Trial: Bypass vs Angioplasty for patients with Severe Limb Ischaemia below the knee.

BASIL-2 is concerned with people with disease of the arteries below the knee (also termed infra-geniculate, IG, arteries) which is now the commonest site of severe disease. The trial aims to determine the most effective and cost-effective treatment for preventing amputation and death, getting the ulcers and gangrene to heal, and relieving pain.

Two treatments are commonly used in this patients group: vein bypass (VB), where a vein is used to bypass the blockage, and endovascular treatment (BET), which involves opening up the diseased arteries with balloons and, sometimes, small metal tubes called stents.

BASIL-3 Trial: Balloon vs Stenting for patients with Severe Limb Ischaemia above the knee.

SLI patients with less severe, more limited disease above the knee (i.e. in the femoro-popliteal arteries) are treated by endovascular means, rather than bypass surgery, in the first instance because, in general, it is less risky and expensive; and seems to work as well as bypass in the short term.

For many years, the ‘standard of care’ endovascular treatment for such patients has been ‘plain balloon angioplasty’ (PBA) with the use of ‘bail-out’ (bare metal) stenting (BMS) when PBA alone has been unsuccessful. More recently, drug coated balloons (DCB) and drug eluting stents (DES) have entered the market and are widely used around the world. These DCB and DES release various drugs which act on the vessel wall and are believed to reduce the risks of the artery narrowing down. However, the evidence base underpinning the use of DCB and DES is weak and they are much more expensive than PBA+/-BMS.

Both trials aim to assess the cost-effectiveness of the compared options. To this end, Professor Tracy Roberts and Dr Lazaros Andronis will be undertaking economic evaluations to determine the cost per year of amputation-free survival, cost per year of overall survival, and cost per quality-adjusted life year (QALY) associated with Bypass vs Angioplasty (BASIL-2) and Balloons vs Stenting (BASIL-3). The evaluations will comprise ‘within-study’ analyses, which will be based on data obtained within the trials’ follow-up period, and ‘model-based’ evaluations, which will capture lifetime costs and effects likely to accrue beyond the studies’ follow-up.

More details about the aims of the trials can be found on the websites below:

University of Birmingham BASIL-2 and University of Birmingham BASIL-3

NIHR HTA portal BASIL-2 and NIHR HTA portal BASIL-3 websites at the NIHR HTA portal  

PD Comm: Randomised Controlled Trial to Compare the Clinical and Cost Effectiveness of Lee Silverman Voice Treatment Versus Standard NHS Speech and Language Therapy Versus Control in Parkinson’s Disease

Parkinson’s disease (PD) is the most common serious movement disorder in the world, affecting approximately 120,000 people in the UK alone. Speech impairments are known to affect a large proportion of the PD population. For those with speech problems, the impact of the impairment is known to be great and is recognised to reduce quality of life.

Whilst NICE guidelines state that Speech and Language Therapy (SLT) should be made available to patients with PD, the evidence regarding effectiveness is limited. NICE therefore recommended that a trial of standard SLT compared with no treatment was needed, however, since this recommendation was made, a specific type of SLT (Lee Silverman Voice Treatment (LSVT)) has become more widely available.

Building on a completed pilot trial, an NIHR HTA-funded study (PD Comm) will compare both LSVT and standard NHS SLT with control therapy. Clinical effectiveness will be assessed in terms of the ability of the therapy to maximise speech intelligibility and communication, and improve the quality of life in people with PD reporting difficulties with speech. It will assess the quality of life of carers, and an economic evaluation will be performed from both a health care and societal perspective.

This trial is led by Professor Cath Sackley at King’s College with involvement from the Birmingham Clinical Trials Unit (BCTU). The health economic analysis is being led by Dr Sue Jowett, who was also involved in the pilot trial. Patient recruitment starts in 2016 and the study is due for completion in early 2020.

Chronic Obstructive Pulmonary disease is a common condition with significant public health impact, accruing over £800 million per annum on the NHS budget. At least half of all patients with the disease remain undiagnosed. Recent evidence suggests that medical management can reduce morbidity, particularly the frequency of exacerbations, and prolong life at any stage of the disease.  It is assumed that the observed benefits will be even greater if undiagnosed patients are found early and appropriate treatment is commenced.

The within-trial analysis of an NIHR funded pragmatic randomised controlled trial (the TargetCOPD trial) shows that compared to routine practice, the NHS would incur £376 for every additional case detected with active case-finding. Active case-finding in this context refers to posting a screening questionnaire to high-risk patients followed by a confirmatory spirometry test in individuals who report symptoms suggestive of COPD.

However, the long-term cost-effectiveness of active case-finding is unknown, therefore, a decision model was built to forecast the long-term costs and benefits of active case finding compared with routine care. Dr Sue Jowett is the lead health economist with Tosin Lambe employed to conduct the analysis.

Venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep vein thrombosis (DVT), is a common condition with an incidence of approximately 1 per 1,000 per annum causing both mortality and serious morbidity. The principal aims of treatment with heparin and warfarin are to prevent extension or recurrence of clot.

However, the recurrence rate following a DVT remains approximately 10% per annum following treatment cessation, irrespective of the duration of warfarin therapy. It is clear therefore that some patients with VTE should continue long-term warfarin however we are currently unable to identify this population. Patients with raised d-dimer levels 1 month after discontinuing oral anticoagulation have been shown to be at high risk of recurrence.

This study will primarily investigate the role of extending treatment with oral anticoagulation for those patients with raised d-dimer levels prior to discontinuing treatment and will study the impact of this management on both recurrence of thrombosis and development of post-thrombotic syndrome, both extremely costly outcomes for the NHS. This strategy would allow those people who require extended anticoagulation treatment to receive it whilst ensuring that those who only require short term treatment are not exposed to unnecessary and potentially dangerous treatment.

The ExACT trial, funded by the NIHR, has three aims:

i) identify those people at highest risk of having recurrent thrombosis;

ii) see if by giving treatment for longer it is possible to prevent the recurrence;

iii) identify those patients at highest risk of developing post-thrombotic syndrome

The health economic analyses, which will be conducted by Hasan Basarir with support from Sue Jowett, will determine the cost-effectiveness of the measurement of d-dimer and subsequent extended treatment with anticoagulation.