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Month: September 2021

Birmingham leads the way in delivery of a new advanced therapy in uveal melanoma

BHP founder-member University Hospitals Birmingham is the first site in the UK to treat a uveal melanoma patient with the new therapy Tebentafusp outside a clinical trial. Uveal melanoma is a rare cancer situated within the eye. This initiative is being led by Dr Leila Khoja, Immunotherapy lead for the Birmingham Experimental Cancer Medicine Centre (ECMC) and senior clinical lecturer at another of BHP’s founder members, the University of Birmingham.

Developed by Immunocore PLC, Tebentafusp is a bispecific immunotherapy drug, a type of advanced therapy. Immunotherapies harness the body’s immune system to fight cancer, helping it to attack it and to prevent tumours from growing. However, in some tumours the immune response is inadequate to control the tumour and, even in tumours that respond, resistance to treatment can develop. Tebentafusp’s mechanism of action enables it to attach to the tumour and simultaneously to T-cell immune cells. This means that it is able to pull in and activate tumour specific T-cells in hard to treat tumours.

Birmingham participated in the phase II study of Tebentafusp, and the results were published in Clinical Cancer Research. This led to a phase III trial, where it was shown to offer patients better outcomes in terms of survival, when compared with standard drugs offered by their clinical teams.  It is the first drug of this type for a solid tumour that has been proven to offer this benefit to patients. Regulatory approval for Tebentafusp is in process, but the drug is currently available through a compassionate use programme.

Transferring Tebentafusp into standard clinical care for patients with solid tumours is challenging, as specialist pharmacy, nursing and junior doctor skills are required. Hospitals also need to have sufficient capacity to deliver infusions of the drug on an inpatient basis, as the dose is increased over a three week period, before it can be provided on an outpatient basis. The development of this programme will create a model for similar therapies in the future, and Birmingham ECMC is currently facilitating the setup of clinical trials in this field.

These initiatives underline the importance of the Birmingham ECMC and Midlands Wales Advanced Therapy Treatment Centre (MW-ATTC) networks in supporting the delivery of the innovative therapies of the future, training staff and providing the infrastructure required.

Genetic diagnosis leads the way in childhood eye cancer treatment

Experts from BHP member Birmingham Women’s and Children’s NHS Foundation Trust have transformed the treatment of children’s eye cancer with pioneering new research.

Dr Trevor Cole and Dr Amy Gerrish are the first in the country to develop a treatment called Cell-free DNA for the care of retinoblastoma – a rare type of cancer which typically develops in early childhood and affects around 50 children in the UK every year.

The specialist service based in our Children’s Hospital is one of the top centres in the world for treating the condition.

Until recently, diagnosing the genetic cause of retinoblastoma was only possible if the affected eye was removed as part of a treatment. However, thanks to research carried out by our team, we can now diagnose the genetic cause without removing the eye.

This procedure involves using a tiny volume of fluid taken carefully from the inside of the eye (a tenth of a millilitre) to predict whether the child’s other eye will be affected or any of their siblings or future children. Now, genetic diagnosis is even possible during pregnancy.

Dr Cole said: “Those who carry the germline Rb1 mutation that causes retinoblastoma have a 50 per cent risk of passing it to their children. However, non-invasive prenatal diagnosis is now possible in most pregnancies shown to be at risk of inheriting the gene mutation.”

Kirstie McLaughan, from High Wycombe, mum to three-year-old Aria and Kaleb, aged nine, underwent prenatal testing at our hospital when she was pregnant with her daughter.

“My partner, Callum, was diagnosed with retinoblastoma as a child, so we knew there was a risk that our children would develop the condition. In June 2012, my son was diagnosed with retinoblastoma, and we were transferred to Birmingham Children’s Hospital to begin treatment.”

Kaleb was told he was out of risk at the age of three following treatment our specialist retinoblastoma centre. “We couldn’t have asked for better care,” added Kirstie. “They really are an amazing team at the Eye Department. They couldn’t have done any more; they were so welcoming and friendly and were always on the other end of the phone should I have any questions or worries.”

When Kirstie found out a few years later that she was pregnant with their daughter, Aria, she knew there was a 50 per cent chance she would also inherit the gene that causes the condition. However, doctors at Birmingham Women’s Hospital could carry out genetic testing during pregnancy, taking a simple blood test from Kirstie.

“I had non-invasive prenatal testing when I was pregnant with Aria. The test meant that if my daughter also had retinoblastoma, we could begin treatment right away,” explained Kirstie. “Luckily, the test came back all clear. It was such huge relief. It meant I didn’t have added worry or stress during my pregnancy.

“The team are amazing. The difference in testing available from when Kaleb was treated to when Aria was born really is extraordinary; their research is outstanding.”

Back in 2020, the team won the Ulverscroft David Owen Prize for this ground-breaking research.

Dr Cole and Dr Gerrish’s Cell-free DNA in retinoblastoma research is leading the way in transforming how we treat children’s eye cancer, providing significant savings for the NHS and less stress for patients and their families.

SPIRIT-PRO extension: guidelines for inclusion of patient-reported outcomes in protocols of clinical trials

Patient Reported Outcomes (PROs) can provide valuable evidence on the impact of disease and treatment on patients’ symptoms, function and quality of life. High-quality PRO data from trials can inform clinical care, regulatory decisions and health policy. However, problems such as poor data collection, analysis, reporting and interpretation often reduce or negate their value. This paper attempts to raise standards by enhancing the international SPIRIT-PRO guidelines that were created to optimise the design of clinical trials and encourage the consistent, high-quality reporting of PROs and ultimately to inform patient-centred care. This case study originally appeared on the HDR UK website – visit to read further health data case studies.


The PRO content of past trial protocols has often been incomplete or unclear leading to research waste. An appraisal of the PRO content of >350 past trial protocols showed that many lacked the specific information needed for high-quality PRO data collection and evidence generation. As a result this may lead to poor quality or non-reporting of PRO trial results, which may hinder the potential for PRO evidence to be used in regulatory decision-making, health policy and clinical care

The SPIRIT-PRO guidance and the subsequent SPIRIT-PRO Extension (a 16-item checklist intended to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection) were created to establish standards to improve the content and quality of trial protocols. However, further work is required to support uptake and implementation.


A team led by Melanie Calvert, NIHR Senior Investigator, Professor of Outcomes Methodology at the University of Birmingham and Director of Centre for Patient Reported Outcomes Research and Professor Madeleine King, University of Sydney, have developed tools to support the use of SPIRIT-PRO by researchers to generate high quality PRO data to inform patient care. This includes a protocol template, detailed descriptions and examples of good practice.

Impact and outcomes

While trial protocols are the foundation for study planning, conduct, reporting and appraisal, they vary greatly in content and quality. By providing specific recommendations about PRO endpoints it is possible to improve the situation – providing valuable information for clinicians and patients about the risks, benefits and tolerability of an intervention.

The work carried out by Prof. Calvert, Prof. King, Dr Olalekan Aiyegbusi with international collaborators (supported by UCB Pharma, Macmillan Cancer Support, the NIHR and HDR UK) has the potential to dramatically improve the quality and value of PRO data gathering and reporting in clinical trials. This in turn has far-reaching implications for care – allowing patients and their care teams to understand how an intervention will affect someone, whether it is appropriate or if an alternative should be considered.

Patient and Public Involvement and Engagement

Patient partners were involved in the design, conduct, reporting and dissemination plans of the research. This included the development of the SPIRIT-PRO Extension, the paper, protocol template, tools to support implementation by patient partners. Patient partners are included as co-authors.

Insights from the HDR UK Impact Committee

The HDR UK Impact Committee serves to raise the profile of both ours and our contributors’ outputs. The Impact Committee are keen to celebrate significant impacts which clearly demonstrate the value of of our mission to unite the UK’s health data to enable discoveries that improve people’s lives.


Prof. Calvert:

Scientists discover new pathway that prevents bowel cancer treatment from working

Leading scientists at BHP founder-member the University of Birmingham have discovered a previously unknown pathway that prevents specific drugs from working in patients with bowel cancer.

The research findings pave the way for increasing the number of bowel cancer patients who can be successfully treated, say the scientists.

Bowel cancer, also called colorectal cancer, affects the large bowel, which is made up of the colon and rectum. It is the fourth most common cancer in the UK, with over 42,000 people diagnosed with bowel cancer every year in the UK. It is also the second biggest cancer killer, with 16,000 people with bowel cancer dying in the UK every year.

The University of Birmingham-led research involved the study of 184 tumour samples and medical records of bowel cancer patients participating in the COIN trial, as well as research carried out in mice, cell cultures, and a laboratory model for pre-malignant colorectal cancer.

Co-senior author Andrew Beggs, Professor of Cancer Genetics & Surgery at the University of Birmingham, explained: “About 60% of bowel cancers are sensitive to drugs called anti-EGFR inhibitors which work by blocking a key pathway in these cancers.

“However, despite this, in cancers that should be sensitive to them, these drugs only work in patients about 50% of the time.”

Co-senior author Dr Fedor Berditchevski, also of the University of Birmingham, added: “Scientists have previously found that if bowel cancer patients have a mutation in a gene called RAS, the anti-EGFR inhibitors will not work.

“However, our research has now discovered a new pathway involving a tetraspanin protein called TSPAN6 that is frequently inactive in bowel cancer patients and this makes these drugs less effective. Crucially, our research also shows that if this pathway is active in a patient’s cancer then the drug will work, irrespective of whether they have a mutation in RAS or not.”

First author Dr Regina Andrijes, a Postdoctoral Fellow at the University of Birmingham, concludes: “This is the first time a tetraspanin protein has been shown to be directly involved with bowel cancer. Our research findings show that this new pathway could act as a biomarker for treatment with anti-EGFR drugs in bowel cancer, increasing a patient’s chance of survival and the number of patients who could benefit from these drugs who previously would not have.”

The researchers are now set to undertake a clinical trial of using this marker to better identify patients for anti-EGFR treatment.

The study, published in the Proceedings of the National Academy of Sciences (PNAS), was carried out in collaboration with fellow BHP member University Hospitals Birmingham NHS Foundation Trust, working with Semmelweis University in Hungary, and Assiut University in Egypt.

High-profile appointee to lead Birmingham’s Precision Health Technologies Accelerator

The University of Birmingham has announced the appointment of an experienced academic and industrial pharmaceutical professional to the position of Managing Director of its new Precision Health Technologies Accelerator (PHTA).

Professor Luigi ‘Gino’ Martini joins PHTA Ltd – a wholly-owned subsidiary of the University that will operate the new facility – from the Royal Pharmaceutical Society (RPS) where he has held the role of Chief Scientist for more than three years. With extensive experience in oncology, rare and infectious diseases, and drug development, Gino also brings expertise in policy development and external advocacy to his new appointment in Birmingham.

Gino’s career began with Senior Scientist roles at Scherer Drug Delivery Systems and SmithKline Beecham, before joining GSK – initially as Drug Delivery and Strategic Technologies Manager – rising to Senior Directorships across a 10-year stint.

An experienced academic, Gino was formerly Professor of Pharmaceutical Innovation at King’s College London, as well as undertaking visiting professorships and PhD supervision alongside his industry roles. Prior to his appointment at the RPS, he held senior development and advisory positions with Shire Pharmaceuticals and Roche.

PHTA will be dedicated to the rapid development and translation of innovative therapies and technologies from concept to clinical evaluation. By creating new opportunities for businesses and entrepreneurs to grow and commercialise their ideas, it will enable advanced drugs, diagnostics and devices to reach patients more quickly. This signature facility will be the focal point of the forthcoming Birmingham Health Innovation Campus (BHIC) development, providing up to 6,000sqm of innovation, co-creation and incubation space within BHIC’s Phase 1 building.

Commenting on his appointment, Gino explained: “I see the PHTA as a place where innovators in health and life sciences will have global impact. I am a great believer in catalysing innovation through creating hubs where like-minded individuals can converge, connect and – in its simplest terms – ‘try things out’.

“COVID-19 has shown us that hybrid and multidisciplinary models of working really do work and this is my vision for the PHTA – an ecosystem which benefits from co-location of experts and budding entrepreneurs which also crosses boundaries and taps into skillsets and best practice of other UK regions. It’s an incredibly exciting time to be joining the project and forging these connections.”

Professor Tim Jones, University of Birmingham Provost and Vice-Principal, commented: “Through Birmingham Health Partners we have an established track record in collaborating with industry partners at start-up, scale-up, and global levels. The Precision Health Technologies Accelerator is the next stage in the journey towards cementing our position as a leader in the translation of research and innovation in health and life sciences.

“Gino’s leadership will be pivotal in achieving this aim, drawing on his considerable experience in both the pharmaceutical industry and in research-intensive academic environments. We are delighted to welcome him to Birmingham.”

Set to open in late 2023, BHIC is ambitious 10-acre, £210m development delivered through a long-term collaboration between the University of Birmingham, as landowner, and experienced investor-developers Bruntwood SciTech. It will be the only science park in the region dedicated to health and life sciences, offering premium laboratory, office and incubation facilities to companies specialising in medtech, precision medicine and digital healthcare.

As one of only six national Life Sciences Opportunity Zones, BHIC is attracting significant new inward investment to the region. This includes significant investment of up to £14m from the Greater Birmingham and Solihull Local Enterprise Partnership (GBSLEP) which will support the design and fit-out of the state-of-the-art PHTA facilities.

AI to improve treatments for people with multiple long-term conditions

The NIHR has awarded £2.5 million for new artificial intelligence (AI) research led by the University of Birmingham. The study will use AI to produce computer programmes and tools to help doctors improve the choice of drugs for patients with clusters of multiple long-term conditions.

Called the OPTIMAL study (OPTIMising therapies, discovering therapeutic targets and AI assisted clinical management for patients Living with complex multimorbidity), the research aims to understand how different combinations of long-term conditions – and the medicines taken for these diseases – interact over time to worsen or improve a patient’s health.

The study will be led by Dr Thomas Jackson and Professor Krish Nirantharakumar at the University of Birmingham and carried out in collaboration with the University of ManchesterUniversity Hospitals Birmingham NHS Foundation TrustNHS Greater Glasgow & ClydeUniversity of St Andrews,and the Medicines and Healthcare Products Regulatory Agency. Both the University of Birmingham and University Hospitals Birmingham are founding members of BHP.

An estimated 14 million people in England are living with two or more long-term conditions, with two-thirds of adults aged over 65 expected to be living with multiple long-term conditions by 2035.

Dr Thomas Jackson, Associate Professor in Geriatric Medicine at the University of Birmingham, said: “Currently, when people have multiple long-term conditions, we treat each disease separately. This means we prescribe a different drug for each condition, which may not help people with complex multimorbidity, which is a term we use when patients have four or more long-term health problems.

“A drug for one disease can make another disease worse or better, however, presently we do not have information on the effect of one drug on a second disease. This means doctors do not have enough information to know which drug to prescribe to people with complex multimorbidity.”

Krish Nirantharakumar, Professor in Health Data Science and Public Health at the University of Birmingham, added: “Through our research, we can group such people based on their mixes of disease. Then we can study the effects of a drug on each disease mix. This should help doctors prescribe better and reduce the number of drugs patients need. This will lead to changes in healthcare policy which would benefit most people with complex multimorbidity.”

The research is one of a number of studies being funded by the NIHR’s Artificial Intelligence for Multiple Long-Term Conditions (AIM) call, which is aligned to the aims of the NHSX AI Lab, that combine data science and AI methods with health, care and social science expertise to identify new clusters of disease and understand how multiple long-term conditions develop over the life course.

The call will fund up to £23 million of research in two waves, supporting a pipeline of research and capacity building in multiple long-term conditions research. The first wave has invested nearly £12 million into three Research Collaborations, nine Development Awards and a Research Support Facility, including the University of Birmingham-led study.

Improving the lives of people with multiple long-term conditions and their carers through research is an area of strategic focus for the NIHR, with its ambitions set out in its NIHR Strategic Framework for Multiple Long-Term Conditions Research.

Professor Lucy Chappell, NIHR Chief Executive and chair of the AIM funding committee, said: “This large-scale investment in research will improve our understanding of clusters of multiple long-term conditions, including how they develop over a person’s lifetime.

“Over time, findings from this new research will point to solutions that might prevent or slow down the development of further conditions over time. We will also look at how we shape treatment and care to meet the needs of people with multiple long-term conditions and carers.”

To date NIHR has invested £11million into research on multiple long-term conditions through two calls in partnership with the Medical Research Council, offering both pump-priming funds and funding to tackle multimorbidity at scale.