Case study: Personalised treatment of childhood arthritis 

Biomarker test introduced into clinical practice to predict responsiveness to drugs and allow for personalised treatment of childhood arthritis 

Juvenile idiopathic arthritis (JIA) is a condition that affects 1 in 1,000 children in the UK. JIA is defined as inflammation in one or more joints before a child turns 16 and is caused by the immune system attacking the body’s own tissues. There is a spectrum of severity, ranging from arthritis in a single joint to a severe form that affects the entire body and has multiple complications including uveitis, an eye condition that can cause blindness. There are a range of drugs available to treat JIA but children don’t always respond well or have debilitating side effects. 

Since 2005 Sparks and Great Ormond Street Hospital Children's Charity have supported a project called CHARMS (the Childhood Arthritis Response to Medication Study) with the goal of identifying genetic, cellular or molecular ‘biomarkers’ to predict the response of a child to medications, ultimately allowing for a personalised approach to treating JIA. This national project turned international and ultimately recruited more than 800 children into the genetic study. During the project the team developed a simple blood test that allows doctors to predict which children will respond well to one of the drugs currently used to treat JIA. The test was piloted in a research cohort of 190 children and was then successfully introduced into routine clinical practice at Great Ormond Street Hospital in 2016.  

Carrying this important work forward, in 2018 the team behind CHARMS were awarded £5 million of follow-on funding from the Medical Research Council and Arthritis Research UK (now Versus Arthritis) for a new stratified medicine project called CLUSTER, which will follow 5,000 children with JIA and uveitis. The project aims to create new ways of identifying the right treatment for each individual patient as early as possible, ensuring symptoms are effectively managed and that the condition doesn’t progress into lifelong disability. 

Case study: Person-centred care for progressive conditions 

An intervention called SNAP has been developed to help people with progressive incurable conditions identify and communicate their support needs to healthcare professionals 

Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory condition that requires significant care at the end of life with a high cost to the NHS, making it important to improve support for patients. Person-centred care is considered the best way to ensure people’s needs are identified and met, but in practice this has been shown to be challenging.  

In order to overcome barriers to implementing this type of care, the NIHR School for Primary Care Research invested in the development of an intervention called SNAP (Support Needs Approach for Patients). SNAP consists of a copyrighted tool comprising 15 evidence-based questions to help patients identify areas they might need support in, like help managing symptoms or access to financial benefits, and a needs-led conversation with a healthcare professional informed by their completed SNAP tool.  

SNAP is a direct response to one of the six key recommendations of the Living with Breathlessness Study, which was co-funded by a previous Marie Curie research grant and a NIHR Career Development Fellowship. Led by Dr Morag Farquhar at the University of East Anglia, and Carole Gardener and Dr Gail Ewing at the University of Cambridge, Marie Curie funded the second phase of this programme to validate the tool, improve its design and content, develop an accompanying training and support package for the SNAP intervention, and bring SNAP into clinical practice.  

SNAP has now been used in a range of clinical settings including primary, community and secondary care, and there have been requests to translate the tool into multiple languages. The Taskforce for Lung Health, led by the British Lung Foundation, specifically suggested SNAP as an intervention to identify and address unmet support needs of patients in their five year plan for lung health. It has been similarly recommended in the RCGP and Marie Curie Daffodil Standards. Going forward, SNAP has the potential to be applied to other progressive incurable conditions such as heart failure, neurological conditions and cancer. 

Case study: A device for dignity 

The “Head Up collar” is a neck support system that improves quality of life for people with motor neurone disease 

Motor neurone disease (MND), also called ALS, is a life-shortening illness where the death of nerve cells that control movement leads to muscle weakening and wasting. There is no cure for MND but some symptoms can be managed in order to lessen the impact on day to day life. One consequence of the disease can be loss of neck muscle strength, making it difficult or impossible for some people with MND to hold their heads up straight. People living with MND reported that existing products were uncomfortable, unattractive and restrictive. They identified better head and neck support as a priority to improve their quality of life. 

With funding from the MND Association, the NIHR Invention for Innovation (i4i) programme and Sheffield Hallam University, a revolutionary new support collar was designed and created with input from people affected by MND. The entire process, from initial conception to distribution, took about 7 years in total. The product was designed with input from people with MND and was tested in a clinical trial where 100 participants across 10 sites in the UK and Ireland tried out the collars. When the trial concluded, 80% of participants felt the collar helped them and wanted to carry on using it. This patented product is available through the NHS and at least 25 NHS trusts are using the collar.  

This device allows people with MND to do simple everyday things like eat, look someone in the eye, read a book or watch television. Going forward, this collar could benefit people with other conditions that lead to neck muscle problems, including spinal muscular atrophy, multiple sclerosis, stroke and Parkinson’s. 

Case study: The Heart Age Tool 

What age is your heart? A test available on the NHS website helps you assess the health of your heart and prompts you to make healthy lifestyle improvements 

Cardiovascular health is impacted by lifestyle factors like diet, exercise and smoking. Unhealthy lifestyle choices increase the risk of developing serious conditions including coronary heart disease, stroke and type 2 diabetes. For these types of health conditions, preventative intervention is key and increasing public awareness and engagement is the best way to empower individuals to make positive changes. 

The British Heart Foundation, together with the NHS, Public Health England, University College London and Joint British Society, launched an online tool that allows people to assess the health of their heart based on 16 physical and lifestyle questions. The tool tells them what their heart age is and the percentage chance of having a heart attack or stroke over the next decade. They can then see how these could be improved if they lost weight, lowered their cholesterol or reduced their blood pressure. This digital tool is targeted at younger tech-savvy people who are less likely to visit their GP for routine health assessments. 

As of September 2018, the Heart Age Test had been completed more than 1.9 million times and received significant media coverage. Many newspapers shared the alarming fact that 4 out of 5 (78%) people who took the test have a heart age older than they are, and it was described by the BBC as “a wake-up call to make healthy changes”. The British Heart Foundation hopes that this tool will help them to convey the message that it’s never too late to change. 

Case study: Fast track surgery for pancreatic cancer 

Research evidence led the APPG on Pancreatic Research to recommend fast track surgery programmes across the NHS to improve survival rates.  

Pancreatic cancer is the deadliest common cancer. It is often diagnosed late and progresses quickly, meaning that 1 in 4 people die within a month of diagnosis and 3 in 4 people do not survive a year. In 2012, parliamentarians came together with key stakeholders to form the All Party Parliamentary Group (APPG) on Pancreatic Cancer. The APPG has run 3 major enquiries and published several influential reports that aim to improve survival rates and quality of life for people with pancreatic cancer by influencing relevant policies. 

Pancreatic cancer patients often present initially with jaundice and this is usually treated with a stent whilst the patient waits 6-8 weeks for surgical removal of the cancer. This long wait period sometimes means that the condition will progress to the point of no longer being operable. In 2016 Pancreatic Cancer UK funded a team in Birmingham to run a pilot programme to fast track patients into surgery, bypassing the need for a stent. The programme improved patient care, experience and outcomes. People received potentially curative surgery within 16 days instead of 62 days, and 20% more people had the opportunity to have surgery because their cancer hadn’t become inoperable. The fast track process reduced complications, unnecessary treatments and readmissions, ultimately saving the NHS an average of £3,000 per patient. 

The researchers presented their evidence directly to the APPG as part of the most recent enquiry and it forms the basis of one of the 2017 report’s key recommendations – that the Government and NHS England must consider developing national guidance supporting fast track surgery and faster access to treatments. In 2018 NICE published the first ever guidelines for pancreatic cancer, something that the APPG had been pushing for since 2013. The guidelines cite the group’s work and include the recommendation that where appropriate people should receive surgery immediately rather than having a stent first. The compelling evidence from the pilot study in Birmingham and similar work by researchers in Manchester now forms the basis of the “demand faster treatment” campaign recently launched by Pancreatic Research UK that calls for all treatment for all people diagnosed with Pancreatic Cancer within 20 days.   

Case study: Raising awareness about rare forms of dementia 

A research team at UCL supported in part by Alzheimer’s Research UK has engaged with the public and health practitioners in multiple ways to spread awareness and facilitate early diagnosis of a rare form of dementia.  

Posterior cortical atrophy (PCA) is a rare form of dementia that initially affects vision and often manifests earlier in life than other types of dementia. Over the past six years, Alzheimer’s Research UK has funded a team at the UCL Institute of Neurology to investigate the causes of PCA. In addition to advancing knowledge about the condition, the researchers have actively engaged with the public and practitioners to raise awareness about PCA and dementia in a variety of innovative ways. 

To educate people affected by or interested in dementia about key issues in care and research, one of the researchers launched a free online course called “The many faces of dementia” in 2016. Thousands of people worldwide have benefitted from this course by learning from world-leading experts from UCL and hearing directly from people affected by four less common forms of dementia. 

To enrich public and professional understanding of dementia further, one of the researchers was invited to direct a transdisciplinary centre called “Created Out of Mind” at The Hub in the Wellcome Collection from 2016 to 2018. This unique project brought together artists, scientists, healthcare professionals, people living with or affected by dementia and the public in a space where they could all explore, challenge and shape perceptions and understanding of dementias through science and the creative arts. One of the outputs of this project was an animated film called “Do I see what you see?” that features the voices and experiences of people living with PCA. 

As the first symptom of PCA is visual impairment, the research group has also engaged directly with optometrists to raise awareness and facilitate early diagnosis of the condition. The researchers have been able to influence and educate practitioners through publications in scientific and professional journals and presentations at optometry conferences and training events. A formal collaboration with the College of Optometrists was also initiated in 2015 in order to facilitate and expedite translation of the UCL research team’s findings in the lab into changes in training, policy and practice. 

Case study: Magnetic drug delivery 

Initial investment from Action on Hearing Loss enabled the company Otomagnetics to receive further funding to develop more efficient ways to deliver treatments to the hard-to-reach inner ear. 

One in six people in the UK has hearing loss or is deaf. Despite an increase in the number of people with hearing loss, and the serious impact it has on quality of life and risk of dementia, there are currently no available treatments to protect or restore hearing. 

Not all medicines taken orally or placed into the middle ear will reach the cochlea. Local delivery may also be essential to avoid unwanted side effects. In 2013, Action on Hearing Loss invested £300,000 to enable a US-based company called Otomagnetics to test a new drug delivery system. Their patented device is similar to a syringe, but magnetic forces are used instead of a needle to push drugs linked to biodegradable magnetic particles into the inner ear.  

Several years after this initial investment, Otomagnetics was awarded a $2.3 million grant from the National Institutes of Health to further develop this drug delivery system and bring it closer to use in people. Without the initial funding from Action on Hearing Loss this follow-on funding and further development would not have been possible. Going forward, Otomagnetics hopes to apply their technology to deliver a variety of drug, protein or gene therapies to other hard-to-reach targets like the retina. 

Case study: Partnering for better stroke care 

A collaboration between academia and industry resulted in the development of a blood test for paramedics to determine who is experiencing a stroke and transfer the patient to the nearest specialist unit. 

Stroke is a leading cause of death worldwide and contributes to a large burden on health and social care. The length and extent of recovery relies heavily on the accuracy of initial diagnosis and a fast emergency response, but there are many other conditions which create identical symptoms such as migraine and seizures. Paramedics are often the first to see patients in the crucial period following a stroke, but it can be challenging to identify actual stroke and to choose the best immediate course of action. 

Dr. Christopher Price, a clinical researcher at Newcastle University who the Stroke Association has been supporting through fellowships since 2013, partnered with the UK-based company Sarissa Biomedical in 2016 to show the accuracy of a finger prick blood test in helping paramedics diagnose stroke at the scene or en route to the hospital. This test measures levels of a substance in the blood that rises after oxygen deprivation, which occurs in the brain during stroke, but stays low in other conditions producing the same symptoms. The collaborative team behind the development of this test won a Small Business Research Initiative award from Innovate UK. 

This blood test is now being trialled in a multisite study with three ambulance services and four specialist stroke units. The blood test when used in conjunction with the well-established FAST test (facial drooping, arm weakness, speech difficulties) should improve the ability of paramedics to quickly and correctly distinguish between stroke and other conditions within 5 minutes. This will enable a decision about which is the most appropriate hospital destination and use limited NHS resources more efficiently by avoiding sending people along the stroke treatment pathway who need other types of care. For stroke patients, it may lead to greater confidence in the initial diagnosis and faster administration of treatments which can greatly minimise the disability caused. 

Case study: Investing in leaders 

Early career support from Epilepsy Research UK helped Dr. Rebecca Bromley establish herself as an expert in her field, enabling her to influence guidance on prescription medicine for women with epilepsy. 

Exposure of a baby to certain prescribed medications in the womb can cause birth defects and negatively impact brain development, leading to poor cognitive and social outcomes for the child. Over the past decade, researcher Dr. Rebecca Bromley and colleagues have investigated the effect of taking antiepileptic drugs during pregnancy on children’s health.  

After receiving her PhD in 2009, early career support from Epilepsy Research UK enabled Dr. Bromley to further extend her earlier research to investigate outcomes in children exposed to various types of antiepileptic medications and this work formed part of her doctorate in clinical psychology. Following completion of her Clinical Psychology training she secured a prestigious National Institute of Health Research postdoctoral fellowship in 2013 and gained further support from Epilepsy Research UK. This was to undertake research with Dr Rachel Charlton at the University of Bath, investigating the optimal methods to assess child development within the context of medication exposure.  

Dr. Bromley quickly became a leader in her field and her work formed part of a growing body of research showing that foetal exposure to the antiepileptic drug sodium valproate can pose a substantial risk to development. Research has now shown that if sodium valproate is taken during pregnancy, up to 4 in 10 babies are at risk of developmental disorders and roughly 1 in 10 are at risk of birth defects. Over the past five years Dr. Bromley has given evidence about these risks to various government and regulatory bodies including the European Medicines Agency (EMA) reviews in 2014 and 2017. 

Following recommendations from the EMA after the evidence presented by Dr. Bromley and other experts in the field, the MHRA issued new guidance on sodium valproate prescriptions in 2018. The guidance states that sodium valproate can no longer be prescribed to women of childbearing age unless they are on a pregnancy prevention plan (PPP). This new regulation will be key to preventing unnecessary risk to babies of women with epilepsy and other conditions for which this drug is prescribed, like bipolar disorder and migraines. Dr Bromley continues working on these issues and last year obtained further Epilepsy Research UK funding to investigate the potential relationship between exposure to seizures in the womb and later child outcomes. She is also now working as part of the EU funded ConcePTION study which aims to improve current systems through which the potential impacts associated with medication use in pregnancy and/or breastfeeding are investigated and disseminated to both patients and healthcare professionals.  

Case study: Warm perfusion of donated kidneys 

Professor Nicholson developed a pioneering technique called warm perfusion that revives, repairs, tests and primes donor kidneys before transplant to maximise the chance of success. 

Eighty percent of the people on the transplant waiting list need a kidney and due to a shortage of viable kidneys, 5 people die each week waiting for this vital organ. Even those who do receive a kidney often experience issues because of the kidney’s performance or acceptance by the body. 

Kidney Research UK invested more than £850,000 of funding to enable Professor Mike Nicholson to develop and test a method called normothermic (‘warm’) perfusion. This method involves flushing the donated kidney with oxygenated blood prior to transplantation, which revives the kidney, repairs damage and primes it with anti-inflammatory agents and other drugs. At the same time this provides the opportunity to test the kidney’s function and make sure there is the best chance of success. So far 138 patients have been recruited across four centres, in a phase II clinical trial. A small study using the technique has also led to the successful transplantation of nine kidneys, previously declined by all UK transplant centres.  

Professor Nicholson’s team have been recognised for their pioneering research with awards and prizes from several national organisations including the British Journal of Surgery, the Royal Society of Medicine, the Royal College of Surgeons of England and the British Transplantation Society. The House of Commons congratulated Professor Nicholson for his positive impact on kidney patients in the UK through an Early Day Motion signed by 33 MPs across parties, specifically noting that this work was made possible by funding from Kidney Research UK.  

This novel technique has the potential to increase the number and quality of donor kidneys and improve outcomes for people with kidney disease. In the future this method could be applied to the transplantation of other vital organs like the liver.