Health Innovation Challenge Fund

Early stage cancer within a lumen, such as the colon, and precancerous polyps, can be removed endoscopically, thus avoiding the need to make a large incision on the body and potentially the creation of an artificial opening from the colon through the abdominal wall (colostomy). However, with the current instrumentation design, even tumours close to the external orifices of the bowel are difficult to remove with absolute certainty of completion. A project team led by Professor Guang Zhong Yang and Professor Ara Darzi at Imperial college are developing a robotic surgical device to facilitate tumour removal without the need for invasive surgery.  Micro-IGES provides a novel microscopic surgical platform with a greater degree of precision and accuracy through integrated sensing, probe-based microscopic imaging and robotically assisted intra-operative guidance. The platform will be evaluated in both in-vivo animal models and human clinical studies.

In addition, the stump does not effectively transmit load and control movement.  This causes tissue problems, which means that patients must frequently visit clinic and sometimes the artificial limb is not used due to discomfort.  These long-term problems are a burden on the NHS and reduce amputees' quality of life.  The ITAP system being developed by Paul Unwin and colleagues at Stanmore Implants Worldwide Ltd uses an implant attached to the bone that projects through the skin, to which the artificial limb is easily attached.  This arrangement transmits load through the skeleton, which is how loads are naturally transferred.  The success of the ITAP implant is reliant on the integration of the skin around the implant to create a seal to prevent infection.  The objective of this programme is an implant that provides patients with an effective solution for the attachment of artificial limbs.

Research led by Professor Mark Emberton and Dr Dean Barratt at University College London (UCL) seeks to rectify this situation. Their project proposes to combine state-of-the-art diagnostic imaging with advanced image guidance technology so that doctors are provided with information on cancer location, shape, and size during surgical procedures. The aim is to transform prostate cancer care by enabling doctors to target clinically important cancers so that these are diagnosed more accurately. The project focuses on developing a novel device called “SmartTarget” which will ensure that information on the location of cancer from medical imaging is at the centre of the diagnosis and treatment of prostate cancer. The SmartTarget device will exploit magnetic resonance imaging (MRI), which can detect clinically important cancers more accurately, and translate information on cancer location, size and shape automatically into the surgical setting. The device aims to achieve this by presenting the doctor with a “picture” that combines information from MRI with information from ultrasound images that are widely used to guide the biopsy needle and treatment delivery. This will allow the doctor to identify and target the cancer on a computer screen in a similar way to a fighter pilot presented with a target on a head-up display.

Anticipated benefits of this technology include fewer biopsies and more accurate cancer diagnosis.  The ability to implement a more selective treatment strategy will result in less harm and cost significantly less than current strategies which treat the whole prostate gland. The specific objectives of the project are to develop and test the prototype SmartTarget device on patients, to develop detailed plans to commercialise the device, and to introduce the technology within the NHS (and potentially other healthcare systems) within a 5 year period.

A research group headed by Professor John Duncan at University College London and Dr Sebastien Ourselin of UCL Centre for Medical Image Computing has implemented methods to identify critical areas of brain function, connections and blood vessels and display these in 3D. They plan to develop this system to enable the neurosurgeon to plan the best operative approach for inserting recording electrodes and for planning surgical resections.  This information will be made available in the MRI scan guidance system in the operating room so that operations are more precise.
They will produce a new system that will result in epilepsy surgery being planned more effectively, resulting in a higher cure rate and fewer complications.

A research group headed by Professor Brian Davidson and Professor David Hawkes at University College London proposes to use the CT scan taken prior to surgery to identify the precise location of the cancer to the surrounding vessels and bile ducts and hence build a computer model of the liver for each individual patient. They will use this to monitor the position of the cancer and the major structures to the liver during the course of the key-hole surgery. This will be combined with a new method of detecting what kind of tissue is directly in front of the cutting instrument. This system is likely to result in a significant increase in the proportion of patients who undergo liver resection using key-hole surgery. The system will be validated on pigs and then evaluated on at least 25 patients. The system developed will also be applicable to operations on the pancreas, kidney and gallbladder.

Often the only treatment is a cornea transplant in which a surgeon removes the damaged cornea and replaces it with a donor cornea or part of a donor cornea. Often this has a good outcome, but the number of donor corneas available for surgery is limited, and risks such as infection or rejection remain.Professor Andrew Quantock’s team at Cardiff University together with collaborators at Kyoto Prefectural University of Medicine and Doshisha University in Japan plan to develop a new surgery for corneal cloudiness which is caused by diseased or damaged cells that line the inside of the cornea. Under local anaesthetic, they will very gently touch the front of the cornea for a few seconds with a new surgical device which very quickly freezes cells. In doing so the diseased endothelial cells at the back of the cornea are destroyed. The researchers will then apply eye drops which will encourage healthy endothelial cells to grow and repopulate the inside of the cornea. In this way the cornea can become healthy and clear again.

Mortality rates are high and long-term disability common in survivors. Studies already show how early resuscitation of the circulation in these patients can considerably improve outcomes. Although it is possible to gauge how much blood the heart is pumping to the tissues (cardiac output) better bedside monitors are needed to assess if the cardiac output is actually adequate for perfusing the organs.Patients who are unwell or undergoing major surgery routinely have a bladder catheter placed to drain urine. Dr Andy Obeid of Oxford Optronix Ltd, together with Professor Mervyn Singer at University College London, plan to use this catheter to co-insert a small, flexible fibre-optic based sensor to continuously monitor oxygen levels within the bladder wall. This device will indicate whether or not the local blood supply transporting oxygen to the bladder is indeed adequate and whether oxygen measurements from the bladder reflect the situation in other parts of the body. Their aim is to assess whether this new technology provides an easy and readily applicable solution to monitoring tissue health during acute injury. This will pave the way for a further clinical investigation in which the circulation is optimised using the device to see if a reduction in post-trauma complications can be achieved.

A research team in Oxford led by Dr J. Duncan Young plans to develop a comfortable wearable physiological monitoring device linked to computers with 'knowledge' of patterns of vital signs in post-ICU patients to automatically measure vital signs and detect warning signs of serious problems, in patients discharged from the ICU. Using the hospital wi-fi network they will monitor the patients' vital signs continuously with a computer system, which will be programmed with information on each individual patient's risk of deterioration obtained during their ICU stay. If the computer detects a change in the patients' vital signs, it will alert medical staff. This approach will allow hospitals to monitor far more patients for a far longer time than would be possible using nurses alone, whilst minimising false alarms by tailoring the alarm limits to each individual patient.  Even modestly reducing these post-ICU deaths to one in twelve discharged patients would save 1,400 lives annually, equivalent to more than half the road deaths in Great Britain. Compliance with government guidance, reduced costs, improved safety and a reduction in insurance premiums will all be used to persuade healthcare teams to adopt the system.

The vital measurement for controlling medication is pulmonary artery pressure (PAP) which currently can only be measured by catheterisation, involving a hospital procedure and some risk. Professor Chris McLeod and colleagues at Imperial College London have developed a tiny pressure sensor with which they propose to measure PAP. Once  the device is placed securely within the artery, measurements can be made at any time by interrogating the sensor by radio from a pocket-sized reader. The reader will be permanently and wirelessly linked to the hospital. Professor Tarassenko's research group at Oxford University will apply its extensive technical and clinical experience of real-time monitoring of patients in hospital and of the use of mobile-phone based telehealth to improve the management of chronic disease. Close control of the medication will be possible, leading to improved patient condition, slower progression of the disease and reduced re-hospitalisation. Measurement quality is guaranteed and measurements during normal activity will be better than current catheter-based measurements in a clinic or hospital bed. The patient will know that they have 24/7 care.

Central to TBI’s devastation is a delayed ‘secondary’ injury that occurs in 30% of TBI patients each year, while they are receiving Intensive Care. Currently, secondary injury is unpredictable, hence unpreventable.
This project, led by Dr Martyn Boutelle of Imperial College London, will deliver a new solution: a real-time Brain Injury Index. This will be produced with a new clinical instrument that will collect electrical and chemical signals from the injured brain, process them and for the first time derive clinically useful risk factors in real-time that will assist doctors with diagnosis and treatment.

The healthcare implications are important: The Brain Injury Index will show clinicians when secondary damage is starting and what is causing it. This will allow them to start the best treatment for that patient at the right time. The Brain Injury Index instrument will save lives, and reduce incidences of severe disability with its huge personal cost to patients and their families.
 

A research group headed by Prof Tarassenko at University of Oxford proposes to develop an easy-to-use system for patients to monitor their condition, based on mobile communications technology (hence the name of mHealth). The project will make use of the latest generation of smartphones and tablets to enable COPD sufferers to complete patient diaries, respond early to worsening symptoms, and receive support from a respiratory nurse who has access to all of their data. This will lead to improved self-management and a higher quality of life for these patients, with a reduction in the number of severe exacerbations which they experience and which require an unplanned and costly hospital admission.  A key goal of their approach is to bring the costs of telehealth technology by at least an order of magnitude to enable it to be adopted on a much larger scale than at present.

Because VAP is often fatal, antibiotics are administered whenever it is suspected. However VAP is hard to distinguish from several non-infective lung conditions and most patients with suspected VAP do not have pneumonia. Therefore many patients receive unnecessary antibiotics for several days, promoting emergence of  'superbugs'. Laboratory infection results for VAP typically return in 3 days. A simple test rapidly and confidently excluding VAP would improve patient care, reduce unnecessary antibiotics and decrease costs.

Professor John Simpson and his team at University of Newcastle has recently showed that low levels of specific proteins in fluid from the lungs of patients with suspected VAP effectively excluded VAP within 4 hours. The test used is an extension of existing technology produced by the team's commercial partner Becton Dickinson (BD) Biosciences. This test will be rigorously analysed in a clinical trial and if rapid, safe, cost-effective reductions in unnecessary antibiotics are confirmed the test will be rapidly introduced into hospitals through the commercialisation expertise of the University of Newcastle technology transfer team and BD Biosciences. Every intensive care unit worldwide deals with suspected VAP, and this new test would have significant global healthcare impact.

The brain can relearn control of the weak arm, but this needs frequent therapy over many months. There are not enough therapists to provide this on a one-to-one basis and fewer than 20% of patients regain independence after a stroke.
Professor Janet Eyre and her team at University of Newcastle have developed a library of video-games to be played at home, which provide highly motivating therapy for relearning arm and hand movements. The aim of the project is to analyse information about patients' performance of arm and hand movements during the video games in order to provide feedback to the patient and their therapist via the internet. This will enable effective rehabilitation of arm and hand movements to be delivered at home at times and places to suit patients, whilst still maintaining expert supervision from a therapist.

The need for hospital visits will be greatly reduced, patients will have the opportunity to undertake more frequent therapy sessions, therapists will be able to supervise more patients and patients should regain greater independence.

Both ALI and VAP increase hospital mortality, illness costs and result in poor functional long-term patient outcomes.

Prof Chris Haslett's team at Edinburgh University aims to develop a technology to improve the diagnosis of these lung diseases. The team will synthesise and test in vitro and in vivo three novel smart probes. These novel imaging agents in conjunction with revolutionary techniques will be designed to detect the presence of neutrophilic infiltration, the presence of bacteria at sites of lung injury, the gram-status of the bacteria, and the presence of MRSA.

This technology has the potential to determine at the earliest possible stage which patients in ICU are developing secondary infection, identifying the organism responsible and allow rapid and accurate detection/exclusion of hospital-acquired infections. It could also provide a rapid, 'real-time' in situ approach to establishing mechanism-based efficacy of new drugs

Tranexamic acid is not a new drug. It has been used to control bleeding during major surgical operations for many years. The realisation that this drug could be used to treat a much wider range of bleeding conditions holds the promise of important benefits for patients at low cost. The research team,  lead by Professor Ian Roberts at the London School of Hygiene and Tropical Medicine, responsible for the accident victim research are now conducting a trial to see if this drug improves outcome in post-partum bleeding.

Although several treatments are available, the current genetic tests used to guide therapy are not sufficiently precise. This means that some patients suffering from leukaemia may not respond to treatment or may suffer adverse side-effects. In order to be most effective, treatment must be tailored to the individual. This is also important when considering emerging therapies that are extremely expensive and must be used judiciously.Dr Sam Knight and colleagues at University of Oxford have developed specialized approaches that use microarray technology to test, in detail, the genetic make-up of blood cells from patients with B-cell chronic lymphocytic leukaemia. During their three year HIC Fund study, these approaches will be validated and adapted specifically for use in a clinical setting.The more precise detection of relevant genetic alterations will enable doctors to provide the most suitable treatment for patients, minimizing side-effects of treatment, reducing mortality and NHS care costs. The approach will be suitable for use in hospital laboratories worldwide.

The principle of gene therapy is to use the shell of a virus (known as a vector) to carry a segment of DNA into the cells of affected patients where it can have a beneficial effect. In the case of choroideraemia there is deficiency of a gene known as REP1. The project team have put this gene into a viral vector and shown in their laboratory that it can correct the choroideraemia defect. The project has now reached the point where the team are ready to assess the potential benefit of this treatment in patients. Professor MacLaren and colleagues have designed a study involving 12 patients across four NHS sites that would represent the world's first ever clinical trial for this disease. The effects of the gene therapy will be assessed two years after treating each patient.  If these are shown to be successful, subsequent  regionally located follow-on studies will be set up.

Recent encouraging clinical trials have used antisense oligonucleotides (AOs) which, like 'molecular velcros', are able to temporarily repair the mutated DMD gene and restore the lost dystrophin protein to the muscles of DMD patients. However this approach requires repeated administration of the AO drug in order to achieve some repair of the gene in the skeletal muscle; in addition the heart muscle cannot be targeted efficiently with the current AO chemistries. New generation AOs, never tried before in the human, are able to dramatically improve skeletal and cardiac muscle uptake of these molecules in animal models of DMD and significantly improve their therapeutic efficacy. In this study the MDEX Consortium, a world-leading group of preclinical scientists and clinicians based in the UK developing state-of-the-art therapies for neuromuscular disease plans to focus on the development and optimisation of a safe new generation AO drug which we intend to administer to a group of 9 patients affected by DMD after appropriate safety studies.  The project is being lead by Dr Matthew Wood, University of Oxford and Dr Francesco Muntoni, UCL Institute of Child Health.

Less than 5% of people with monogenic diabetes in the UK have been identified, meaning up to 20,000 patients may still be misdiagnosed and receiving inappropriate treatment. The aim of project 'UNITED' is to identify the prevalence of patients with monogenic diabetes resulting from mutations in the HNF1A, HNF4A, or GCK genes, amongst patients with early-onset diabetes, diagnosed at less than 30 years of age.A team led by Professor Andrew Hattersley of the Peninsula Medical School and University of Exeter aims to develop a health economic model of a care pathway leading to the testing of monogenic diabetes. This will help to identify the best way of ensuring that people diagnosed with diabetes under the age of 30 have all the necessary tests to ensure they have the correct treatment for their particular type of diabetes. A small number of people may, as part of this study, be found to have a specific genetic cause of their diabetes and, in these cases, the success and benefits will be measured of changing their treatment, usually from insulin to sulphonylurea tablets.

Research shows that the latest molecular testing methods identify previously undetectable changes in chromosomes allowing new diagnoses to be made. However, clinical use is hampered by the limited availability and inconsistent application of these technologies, and by lack of basic knowledge to link genetic changes directly to symptoms. The consequence is that clinical diagnoses remain impossible except for a small number of children.Dr Nigel Carter of the Wellcome Trust Sanger Institute and colleagues propose to apply state of the art genetic sequencing and molecular testing to 12 000 UK children with abnormal development. The results will provide a unique online catalogue of genetic changes linked to symptoms that will enable clinicians to diagnose developmental disorders. Furthermore, they will design more efficient and cheaper diagnostic assays for relevant genetic testing to be offered to all such patients in the UK and so transform clinical practice for children with abnormal development.

From these rearrangements, the team will develop assays to detect DNA from each patient's cancer that has been released into the bloodstream. Such assays will be highly specific (minimal risk of falsely positive results) and sensitive (capable of detecting one copy of tumour DNA in many millilitres of blood). The programme will measure the amount of disease using blood samples collected before surgery, after surgery, during chemotherapy and at regular time-points post-therapy. Dr Campbell and colleagues will therefore be able to assess the ability of this approach to identify high-risk patients before treatment begins, to monitor response to treatment and to predict cancer relapse before it is clinically apparent.