MICA: The Newcastle Proximity Laboratory

Lead Research Organisation: Newcastle University
Department Name: Northern Institute for Cancer Research

Abstract

The introduction of new scientific methods has shown that many diseases are much more heterogeneous than originally believed and that differences between cases can have a marked influence on the way that patients respond favourably to treatment. This has led to the concept of "stratified" medicine in which treatment is adjusted to meet the needs of individual patients. This approach ensures that treatment is only given to patients who are likely to respond and has both clinical and economic benefits, as unnecessary toxicity will be avoided and expensive new therapies are conserved.

The introduction of stratified medicine requires the development of diagnostic techniques which can be used in clinical practice. In order for a new test to be adopted it has to be validated using "real-life" samples and adapted so that it can be used reliably in routine clinical laboratories. For many tests this requires input from experts in Cellular Pathology. However, in recent years, due largely to service pressures, many clinical and non-clinical specialists in this discipline have been unable to dedicate time to maintaining their knowledge in Molecular Pathology or to undertake research themselves.

Our bid responds to the three areas for need identified by the MRC in order to ensure that the development of new diagnostic tests keeps pace with the demands of stratified medicine; restoration of the proximity between clinical and research activity; development of a clear path between discovery science and clinical application and addressing the training needs of laboratory staff.

PROXIMITY
We will establish a "Proximity Laboratory" in a busy NHS service department, which is adjacent to the University Medical Faculty, involving both University and clinical staff. Three satellite laboratories will be established in the Medical School and the Transplant Institute (Freeman Hospital), to provide a well-equipped training and research environment close to the discovery laboratories.

PATH
Initial projects undertaken in the Proximity Laboratory will build on current expertise in treatment stratification in the fields of liver, inflammatory bowel and mitochondrial disease and childhood cancer. An advisory panel will be established to assist research teams in the development of new diagnostic approaches and 2-4 projects per year will be selected for support to generate pilot data to underpin applications for validation by funding programmes such as those operated by the NIHR or MRC. Funding by the Proximity Laboratory will generally be for 1-2 years and monitored to prevent stagnation. Links with the Newcastle Diagnostic Evaluation Co-operative (DEC) will assist with the adoption of promising new diagnostic approaches by commercial partners, thereby helping to ensure the maximum impact on clinical practice.

In addition to the support given to biomedical projects the Proximity Laboratory will also promote research activity in the fields of biomedical engineering and computing science. Biomedical engineering projects will focus on the need to improve methods for handling small samples in response to a trend towards the use of minimally invasive biopsy techniques and will involve collaboration with groups based in our established nanotechnology laboratory (NanoLAB) and Diagnostic and Therapeutic Technologies Group. Collaborations will also be established with computer scientists in the Interdisciplinary Computing and Complex BioSystems (ICOS) research group in Newcastle University in order to develop new ways to present complex datasets in a way accessible for clinical application.

PEOPLE
Training in Molecular Pathology will be offered through a range of distance learning opportunities, up to the level of a Master's degree. In addition undergraduates will be encouraged to enter the speciality by offering bursaries for intercalated degrees. This approach will both increase capacity and help to augment the skills of existing staff

Technical Summary

Building on strengths in discovery science we will provide world-class training to a new generation of molecular pathologists, producing a step-change in the delivery of precision medicine. We will prioritise the development of in vitro diagnostics in chronic and rare diseases, ensuring pull-through to industry and clinical practice using well established links with the Newcastle NIHR DEC and our recent Proximity to Discovery Award. Our technical focus will be solving challenges posed by multiparameter analysis of microbiopsies, working with engineers in the Newcastle nanoLAB and Diagnostics & Therapeutic Technologies group. We will develop methods for the data analysis, interpretation and integration of results into clinically useful formats through collaboration with our Interdisciplinary Computing & Complex BioSystems research group and provide high quality samples for research partners using our established Biobank. Our main base will be in an NHS Pathology Department, ensuring close interaction with clinical pathologists. Building on experience gained with developing our Wellcome Trust Translational Medicine & Therapeutics Programme we will extend our e-learning Masters in Translational Medicine & Therapeutics to include a strand on Molecular Pathology, linked to the development of intercalated degrees for medical students to promote capacity building. We shall sit within infrastructure at Newcastle that includes the NIHR BRC in Ageing & Age-Related Chronic Disease, the NIHR BRU in Lewy Body Dementia, the MRC Centre for Brain Ageing & Vitality, the Wellcome Trust Centre for Mitochondrial Research, the MRC Centre for Neuromuscular Disease, an NIHR Bioresource in Rare Diseases and an NIHR Blood and Transplant Research Unit in Organ Donation & Transplantation. Programme Grant awards support research into stratified medicine and the biology of liver, musculoskeletal, neuromuscular diseases and cancer, ensuring a supply of novel approaches for further development.

Planned Impact

Work conducted by the Newcastle node will have commercial value and patient benefit and provide training to develop a skilled workforce in Molecular Pathology.

COMMERCIAL VALUE AND PATIENT BENEFIT

The main purpose of the Proximity Laboratory is to facilitate the development of novel tests for use in stratified medicine. With improved knowledge of the molecular basis of many diseases there has been a sharp rise in the number of therapies directed at specific, molecularly defined, subgroups. This fragmentation of disease classification has led to a rise in the cost of treatment to compensate for a fall in the size of the target patient group. In order to ensure future financial sustainability it is essential that targeted therapies are only given to the group who will benefit. Precision in prescribing also has health benefits as patients are not exposed to unnecessary and potentially toxic therapy.

The development of fully validated assays for use as a companion diagnostic for an expensive new therapy will have a considerable market value, as long as there is an actionable outcome. Deploying new assays requires considerable investment in terms of quality control and product support. Under the current system these can only be efficiently provided by commercialisation. The node will work closely with commercial partners to maximise the chance that new assays will be made available for exploitation whilst ensuring a reasonable return for the associated intellectual property for further investment in research activity. In addition, the activity of the node is also expected to lead to new methods of sample handling. With the introduction of improved methods for treatment stratification there is an urgent need to ensure that successful biopsies are obtained in as many patients as possible. There is also a drive towards reducing sample size in order to reduce collateral damage to normal tissues- for example in neurosurgery. This leads to need to improve techniques for manipulating small samples in such a way as to minimise wastage. The outcome of collaborative research in the node with biomedical engineers is likely to lead to new approaches with commercial value in the medical sector and beyond- for example in animal based research and veterinary practice.

The introduction of a range of 'omics approaches to accurate disease stratification poses a considerable challenge for presenting data with rapid clinical utility. Teams using the Proximity Laboratory will have access to computer scientists based in the University's Interdisciplinary Computing and Complex BioSystems research group and have the opportunity to develop novel ways of presenting data which make them easy to interpret for the non-specialist, and therefore of greatly enhanced value in clinical practice.

The link between the development of new assays for treatment stratification or methods for sample handling in the Proximity Laboratory and commercial development is unlikely to be direct therefore the timescale in most cases is expected to be 3-5 years. The timescale is expected to be much shorter in the case of software development where further validation by, for example, the DEC or via downstream funding is less likely to be necessary.

TRAINING OF A SKILLED WORKFORCE

The existence of a well-trained workforce will be essential for the development of the UK as a base for innovation in molecular pathology. The Proximity Laboratory will provide a focus for a range of training initiatives aimed at promoting molecular pathology as a career choice for undergraduates and for improving the skills of trainees and established members of staff. There will also be opportunities for non-clinically qualified staff based in the NHS and the University to be exposed to new approaches and techniques to add to their portfolio.

Publications


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Grantham HJ (2017) Doxycycline: a first-line treatment for bullous pemphigoid? in Lancet (London, England)
 
Description Diagnosis Matters Event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The North East and North Cumbria (NENC) Academic Health Sciences Network (AHSN) working with Voice North held a 'Diagnosis Matters' PPI outreach event. The event supported engagement between the NENC population and a variety of very significant initiatives bringing innovative practice and technologies into the Healthcare system.

Professor Andy Hall presented The Newcastle Molecular Pathology Node alongside two other significant initiatives -The National Institute of Health Research 'Diagnostic Evidence Collaborative', led by Professor John Simpson and The NHS England Genomics Medicine Centre and 100,000 Genomes, led by Dr Paul Brennan.

The presentations covered the practicalities, myths, technologies, consent, ethics, commercial involvement in technology development and some theory around how ailments and conditions are identified and treatments decided upon.

Common to all of the presentations and discussions was the virtuous circle of clinical practice informing and enabling research, the pull-through of that research into practice and the dissemination of the innovations and best practice as quickly as possible to help as many patients as possible.

Plans are now being formulated to build on the success of this event with potential to take the speakers to a series of other regional events to enable further dissemination of the message.
Year(s) Of Engagement Activity 2015
 
Description Informed Consent (CCB Meeting) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The National Cancer Research Institute's (NCRI) Confederation of Cancer Biobanks and the MRC Newcastle Molecular Pathology Node held a meeting entitled "Informed Consent in a Digital Age".

The aim of the meeting was to bring together patients, the wider public and professional groups in order to tease apart the key issues involved in obtaining consent to use human samples in research.

A series of presentations covered a broad range of related topics including; a brief background to the concepts underlying so called "fully informed" consent; the 'why' and 'how' consent is taken and the theme of appropriate timing to take consent; the experience of making contact with donor's families to request permission to obtain human tissue and; a powerful presentation from the point of view of a live organ donor.
Others included the position of the regulator - the Human Tissue Authority and the importance of sample-based research; the value of modern technology to support consent and; an overview of a computer-based model of dynamic consent to enable donors to access the level of information that they require to make an "appropriately" informed decision about giving consent.

The event was an opportunity for the Newcastle Molecular Pathology Node to demonstrate its ability to attract a wide audience from across the UK to debate and reaffirm the importance of human tissue collection, storage and analysis to the work of the Node and NCRI. 65 people attended in total.

Useful contacts were made with colleagues from Oxford University and a follow up conference call was held to explore the potential to work together on paediatric Biobanking proposals
Year(s) Of Engagement Activity 2015
 
Description Newcastle Diagnostic Evidence Co-operative 'Adopting MedTech' Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact The Node participated in a 'soft launch' at the Diagnostic Evidence Co-operative's (DEC) 'Adopting MedTech' event at the Centre for Life. The industry-focussed event presented an opportunity to talk about the Node within the unique regional context of the North East, the only region with both a MRC Node and NIHR DEC. Presenting a coherent 'offer' to industry is often cited as an unmet challenge and this event was aimed at addressing this.

The Node had a well-supported stand in the networking area with colleagues from Cellular Pathology and BioEngineering on-hand to meet with delegates to discuss the Node and take contact details; there was a Q&A Panel where the Node was represented by Professor Phil Sloan - the Node Pathology Lead, and the Node was included in the conference programme including a biography of Professor Sloan and a section of the Node and its objectives. The event was well attended with over 100 local and national delegates.

The outcome was the collection of contact details which are being followed up, including a specific request for sample access from a key industrial partner and a telephone interview to discuss collaborative research opportunities.
Year(s) Of Engagement Activity 2016
 
Description Node Project Managers Meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The Manchester Molecular Pathology Node hosted the first meeting of the MRC/EPSRC Molecular Pathology Node Manaagers' at Manchester University. All 6 Nodes were represented. Each presented an overview of their work strands, research themes and partners. The event provided an excellent oppotunity to agree how the network of Nodes will complement each other and work together. The outcome has been the establishment and further development of collaborative opportunities between the Newcastle and Manchester Node on both tissue sample access and training.
Year(s) Of Engagement Activity 2016
 
Description Proximity to Discovery Dermatology/Rheumatology workshop 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Dr Amy Peasland, Newcastle Biobank Central Biobank Manager, presented an overview of the Newcastle Molecular Pathology Node at a workshop of potential industry partners during the Dermatology and Rheumatology MRC Proximity to Discovery (PtD) programme. The event was aimed at showcasing the excellent biomedical resources and facilities available in Newcastle and specifically considered issues such as combining basic research and clinical investigation in order to explore translational science; stratified medicine; training of the next generation of researchers and; collaborative working between industry and academia.

The workshop was held within a programme which encompassed themed lectures and a variety of specialist clinics and open discussions with patients and clinical staff on unmet clinical needs. The Node was positioned within the context of biobanking and sample access opportunities and contact was established with key industrial representatives from GSK, AbbVie, Roche, Lily, Novartis and Nascient. The PtD week was organised by the Faculty of Medical Sciences at Newcastle University during their 'Industry Month' of activities.
Year(s) Of Engagement Activity 2016
 
Description UK Stratified Medicine Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The UK Stratified Medicine Conference was organised by the Stratified Medicine Innovation Platform Programme Coordination Group consisting of the Academy of Medical Sciences, Arthritis Research UK, Cancer Research UK, Department of Health, Innovate UK, Knowledge Transfer Network, MHRA, MRC, NICE, NIHR, NHS England, UK Trade and Investment, Welsh, Scottish and Northern Ireland Governments.

The aim was of the group is to help ensure that, through coordinated action, the UK has the right environment to capture the patient and economic benefits offered by stratified medicine. Participation was an opportunity for the Newcastle Molecular Pathology Node to showcase its involvement in facilitating the development of novel approaches to treatment stratification and training opportunities for staff involved in molecular pathology.

Useful contacts were made with other partners involved in the evolving funding landscape, such as the Precision Medicine Catapult and other Molecular Pathology Nodes.
Year(s) Of Engagement Activity 2015