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UCL Translational Research Office Blog



Early Career Innovators: Personalised Therapy for Prostate Cancer from Diagnosis, Devices & Diagnostics TIN

By Alina Shrourou, on 4 February 2021

In the first Devices & Diagnostics TIN interview as part of the Early Career Innovators series, acknowledging the amazing translational work being done by early career researchers within the UCL Therapeutic Innovation Networks (TINs), Dr Hayley Pye highlights her Devices & Diagnostics TIN (co-lead by the UCL Institute of Healthcare Engineering’s Translational & Industry Delivery Group) Pilot Data Fund awarded project, “Personalising pathology for prostate cancer, a unique opportunity at UCL/UCLH”.

What is the title of your project and what does it involve?

I was recently awarded money from UCL TRO’s Therapeutic Innovations Network, specifically the Devices & Diagnostics TIN, to carry out some proof on concept work predicting molecular pathways from diagnostic histology images. The project is called: “Personalising pathology for prostate cancer, a unique opportunity at UCL/UCLH.”

Prostate cancer is the 2nd most common cause of cancer death in males in the UK with over 11,000 men dying each year. Around 350 people are diagnosed with prostate cancer every day. In the UK there are no molecular profiling tests recommended for risk profiling or treatment selection. Despite high quality research in this area, molecular tests to diagnose only the more aggressive cancers that require treatment are largely unadopted. Our device will provide a completely novel way to implement personalised diagnosis and pave the way for the implementation of these tests.


Every cancer diagnosis requires the analysis of a histopathology image, this image (right) is produced from staining a human tissue sample with two dyes (hematoxylin and eosin).

I want to apply machine learning techniques to these whole-slide-images (WSI) and predict for clinically actionable genetic mutations or pathway activation in prostate cancer. This would promote personalised therapy from the point of diagnosis.

Our network provides a unique environment to test this in clinical hands and in real life clinical data sets that are relevant to the target population.

What is the motivation behind your project/therapeutic?

Traditional ‘one size fits all’ treatments for prostate cancer can cause a lot of off target urinary, sexual and bowel symptoms, and overtreatment is common. Our device ultimately will be pathway to implement augmented filters that would overlay an individual’s standard of care diagnostic whole-slide-images (WSI) and inform the patient if they could be spared treatment and/or if a modern targeted treatment could work. This device would help introduce molecular profiling at diagnosis (not yet standard of care) and therapy choice based on the individual cancer’s molecular characteristics.

The diversity in molecular characteristics present in prostate cancer means simple molecular signatures often either struggle to predict treatment sensitivity accurately, or are not present in sufficient numbers of patients. In depth genetic and transcriptomic sequencing can provide comprehensive information about individual tumours but it is expensive, requires the destruction of tissue samples, and the time to result can be long. The translation of in depth genetic and transcriptomic sequencing tests into clinical implementation is challenging due to issues of scale, as well as financial and infrastructural limitations in many centres. The ubiquity of the ‘standard of care’ histopathology slides alongside our device would allow for quick and cheap pre-screening of patients and without any additional tissue.

Why did you want to apply to the Devices & Diagnostics TIN Pilot Data Fund?

Since I am a postdoctoral research associate, the opportunities to raise money and lead your own research project are rare and competitive. However they are also essential if you want to continue a career in academic research. These opportunities are especially challenging as it all has to be done on top of an already busy and challenging day job as a research associate. The TIN Pilot Data Fund is perfectly sized and suited for an opportunity to carry out some independent research within my current role at UCL. In addition, the amount of support and guidance is phenomenal, ideal for someone like myself trying to make that first step into independence.

Learn more about TIN opportunities for researchers

How did you find the process for the TIN Pilot Data Fund? What did you learn?

I felt very supported and encouraged throughout the process. I am still learning and hoping to take advance of all that ACCELERATE can provide, they are very approachable and all the content so far has been appropriate and all very reasonable and relevant. I have attended the following courses: ‘Mentoring for Medical Innovation’, ‘Grant Writing for Translational Research’ and a ‘Pitching Skills Workshop’ as well as applying for a ‘Dragon’s Den’ style grant from the Devices & Diagnostics Therapeutic Innovations Network.

Register for upcoming ACCELERATE events

What do you hope to achieve in the 6 months duration of your project?

Funds from this grant will help to progress a proof of concept computer algorithm through to testing on real-world diagnostic data. Work will involve curating and cleaning the cohort(s) for this type of work, building a strong hypothesis on which to build a model, generating molecular label data for the test cohort, designing suitable approaches for the data pipeline, and finally applying at least one algorithm to real-world diagnostic data. Hopefully I will then be in a strong position to apply for further funding, leveraged by this work, to both access a larger clinically relevant biobank, expand the algorithms to other molecular signatures and embed our tools into a commercial platform already embedded for NHS-wide deployment.

What are your next steps from now?

The most difficult and time-consuming task will be generating reliable and high-quality molecular label data. So this is my main focus at the moment.

About Dr Hayley Pye

Hayley Pye

Dr Hayley Pye is a Postdoctoral Research Associate based in the Division of Surgery at UCL. She is currently working on a clinical trial evaluating new blood and urine biomarkers in combination with MRI imaging for improved prostate cancer diagnosis and prognosis. She also has experience in the early-stage development of antibody-drug conjugates (ADC) that can be activated by light (photodynamic) sound (sonodynamic) or carrying chemotherapeutic drugs for cancer.

She is driven to better understand the way we currently diagnose and choose modern therapeutics for cancer in the clinic and wants to disrupt the stratification by ‘organ of origin’ and the research silos we currently work in.

Medical Devices Regulation (MDR) 2021 – Implications for the Devices Academic Community

By Alina Shrourou, on 9 September 2020

Following last week’s announcement from the MHRA regarding changes to the regulation for devices to be marketed in the UK, we asked Translational Research Manager Dr Simon Eaglestone, who has represented the UCL Translational Research Office in various discussions around the new Medical Devices Regulation (MDR) for 2021, to comment on the implications this has for the devices academic community and the support available at UCL to ensure compliance and accelerate translation of medical devices to the market.

What do the new Medical Device Regulations mean for device projects in academia?
From 1 January 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) will take on the responsibilities for the UK medical devices and in vitro diagnostic medical devices market that are currently undertaken through the EU system (i.e. CE mark). The new product marking will be termed UK Conformity Assessed (UKCA), with the current Medical Devices Regulations 2002 (UK MDR 2002) continuing to have effect in Great Britain after the transition period.

CE marking will continue to be used and recognised until 30 June 2023, with medical device manufacturers in the UK having to prepare to satisfy the new EU Medical Device Regulation 2017/745 (MDR) to be fully implemented 26 May 2021. Even with this most recent announcement of how medical devices are to enter the market in Great Britain it remains clear that to market UK medical devices in the EU, manufacturers will have to satisfy the new MDR and gain CE mark certification. Whilst the MDR is written to provide clarity of regulatory requirements of economic operators and sponsors of clinical investigations, there has been confusion and uncertainty amid the academic community regarding what the MDR actually means for those investigators working in universities and partner healthcare institutes on early stage medical device projects.

What are the most significant changes in the Medical Device Regulations?
The MDR defines new obligations for manufacturing a medical device that include revised risk classification, requirements of safety and performance, clinical evidence and vigilance reporting. Arguably, the most pertinent change to affect the academic community relates to Annex I of the MDR (the General Safety and Performance requirements) and the increased needs for technical documentation and quality management systems (QMS).

Article 10 of the MDR states what manufacturers need to put in place as a minimum QMS. The QMS encompasses a defined series of processes to ensure the appropriate documentation of the entire life cycle of a medical device (including regulatory compliance, risk management, design & manufacturing, product information, usage, safety and impact). As referenced in the MDR, ISO 13485 is the recommended (but not compulsory) international standard for QMS, whereby an organization needs to demonstrate its ability to provide medical devices and related services that consistently meet customer needs and applicable regulatory requirements.

Reflecting their charitable status, universities do not generally ‘hold’ CE mark certification or place products on the market (i.e. do not act as economic operators). Successful translation of academic device projects is usually achieved by increasing asset value within the context of academic research until such time that a strategic exit is made, either by establishing a ‘spin out’ company or brokering a licensing deal with an established device manufacturer. Either of these external parties would then take on the responsibility of managing an ISO 13485-certified QMS to support their application for CE mark certification and market authority approval for the new medical device.

What should be the impending approach to quality management systems in academia?
Universities and associated healthcare institutes undertake domestic development of non-CE marked devices, or research on modified CE marked devices or those used out of intended function (i.e. ‘CE-broken’). Whilst effectively acting as the manufacturers of these early-stage devices, the implementation and maintenance of an ISO 13485-certified QMS is resource demanding and rarely undertaken by academic centres. However, there clearly is the pressing need for a change in research culture and practice that addresses the need for appropriate technical documentation in the early life cycle of medical devices.

The incoming MDR has prompted health institutions to migrate their existing QMS infrastructure from ISO 9001- to ISO 13485-certification. Health institution exemption (HIE) from MDR may be secured for manufacturing, modifying and using custom made devices ‘on a non-industrial scale’, within the same health institution (i.e. legal entity). However this ‘in house manufacturing’ demands appropriate QMS and documentation to ensure such products meet the relevant General Safety and Performance Requirements. Significantly, health institutions will be compelled to apply for exemption under the new MDR, thereby closing a potentially overused pathway for academic medical device research via partner health institutions.

Making academic medical device translational more successful
To promote medical device development and successful translation to market with enhanced patient benefit, there is growing support in the academic community for initiatives that will improve knowledge of regulatory requirements and present investigators with both pragmatic and the least onerous solutions to satisfy regulatory compliance in early-stage device projects and facilitate commercialisation.

Whilst the academic exit strategy described earlier negates the need for implementing a fully certified QMS, there is a compelling incentive for device researchers within universities to commit time, effort and resources to implementing a proportionate QMS for each medical device project. The ability to attract external investment to support the progression of a university’s domestic device to market is greatly enhanced by the existence of a balanced QMS and documentation developed throughout the entire project lifetime toward ‘CE-readiness’.

The future for UCL
Just as the Clinical Trials Directive of 2001 enhanced the conduct of clinical trials on medicinal products for market within the European Union, the incoming MDR has presented a motivation for enhancement to the culture and way in which UCL researchers undertake and ultimately improve the likelihood of successful translation of university medical device development.

Throughout 2020, UCL’s Translational Research Office (TRO), Institute of Healthcare Engineering (IHE) and Joint Research Office (JRO) have been working closely to develop standardised tools that will support investigators in keeping and updating device project records.

Over the coming months, the Devices & Diagnostics Therapeutic Innovation Network (D&D TIN) shall be hosting community events to enable investigators to access local resources (e.g. QMS & document templates) and implement solutions for centralised management of a university department/Sponsor device project portfolio. Whilst non-compliance with the QMS would not preclude their ongoing research activity, it would likely hamper investigators ability to progress at a later stage (e.g. refusal of Sponsorship for clinical investigation).

Watch this space for the Devices & Diagnostics TIN QMS workshop, scheduled to take place before the end of the year (date TBC). In the meantime, become part of the Devices & Diagnostics community at UCL by joining the Therapeutic Innovation Networks: a platform for UCL, partner Biomedical Research Centres (BRCs) and industry partners to connect, collaborate and share best practices to translate at pace. Any workshops relating to the new MDR will be communicated to the Devices & Diagnostics TIN community through Teams and via email before being announced more publicly.

Devices & Diagnostics TIN logoWhat is the Devices & Diagnostics Therapeutic Innovation Network (TIN)?
The Devices & Diagnostics TIN is one of 6 UCL Therapeutic Innovation Networks hosted by the UCL Translational Research Office, positioned around a specific modality rather than subject area, to encourage the formation of strategic multidisciplinary alliances to close the academic/clinical/patient/industry interface.

Additionally, the TINs aim to widen participation and remove barriers to translation by providing education and funding opportunities to basic and translational researchers from Early Career Researchers to PIs.

Using Immersive Virtual Reality to Increase levels of Self-Compassion in Patients with Depression

By Alina Shrourou, on 25 September 2019

Dr John King and Professor Chris Brewin have recently gained an NIHR i4i Mental Health Challenge Award (an award to develop an innovative technological solution to which will improve the care pathway and outcomes of patients experiencing mental ill-health) for their translational research project, “Treating depression with self-compassion in virtual reality”. In this interview, they discuss the motivation behind their work and provide an overview of the project which they will be starting this autumn.

Please highlight the prevalence and burden of depression.

The community prevalence in the UK is about 3.3%, which translates to approximately 1.7 million adults currently experiencing depression.

It is estimated that the economic burden of depression in the UK is around 12 billion pounds a year through the costs of treatments, losses from patients being unable to work and extended effects on other people who may be involved (carers for example).

However when you consider burden, it is important to think of it not only in terms of cost, but also from a personal perspective. Depression is a debilitating condition that involves a sense of hopelessness and causes huge changes to quality of life. Those changes also extend to anyone close to an individual experiencing depression.

What are the current challenges associated with overcoming depression or other mental health conditions such as anxiety?

Current methods of addressing mental health problems are generally very good, but have a high economic cost. For example, we can be reasonably confident at treating people with depression successfully if we give them the best available talking therapies. CBT delivered to a high standard will help up to 50% of sufferers to recover.

However the problem is that delivering gold standard CBT to every person with a mental health condition is very expensive, so the health service is driven to find alternative ways of delivering efficient treatments. It’s important to find the right treatment for the right people and to have a diverse enough range of treatments for patients so that we can find something that’s a good fit. That in itself creates other challenges because you then have to identify people who are suitable for a briefer form of treatment, for example.

Another difficulty with depression is that it’s a disorder that comes and goes – people may have periods where they are relatively well but if they are under pressure, their depression may come back. It might be that a patient experiences a relapse but are they are unable to reach a therapist because their treatment has finished.

We’re hoping that we will be able to provide something eventually that’s available in patients’ own homes. This could be a huge advantage in just getting them through those ups and downs when they may be feeling very unsupported and alone.

What is the main contributor to depression and how are you targeting this in the treatment that you are investigating?

I don’t think you can say that there’s a single main contributor. Everyone’s life experience is different and everyone has different predispositions – some may be genetic, for example, some socioeconomic.

However, we have identified one contributor that is very common in people experiencing depression, and that’s self-criticism – something which can appear quite early in life and seems often to be a critical factor in terms of the onset and maintenance of depression.

What we have learnt through being part of a much wider network of people working in these fields, is that one way of addressing self-criticism is with self-compassion. It’s not that these things are opposite to each other, but self-compassion can act as a counter-narrative to the negative stories that people tell about themselves when they are prone to self-criticism.

Please provide a brief overview of your project.

Currently, treatments for depression are largely talking therapies or medications. We want to use virtual reality and computer science to provide something new because there’s a real shortage of novel approaches, and we want to meet the unmet medical need of providing an alternative solution that may be more suited to some individuals.

Our approach draws on two sets of scientific findings. One is compassion-focussed work, involving learning to be more kind and self-soothing. There’s a large body of work emerging showing that compassion-focussed therapy can be valuable in helping people with depression and anxiety, and can also create resilience – protective aspects that can help people to withstand the challenges of difficult life events.

The other field is virtual reality and computer science. This derived originally from conversations Chris was having with Mel Slater, a professor of computer science and one of the world’s leading experts in virtual reality, who until very recently was based at UCL. They were discussing some work that Mel had been doing on avatar re-embodiment.

This led to a series of proof-of-concept studies funded by an MRC Translational Medicine award. Publications from this award supported the current development funded by NIHR of a comprehensive clinical intervention using up-to-date technology.

How does the virtual reality (VR) system you are developing generate an illusion of body ownership?

In virtual reality you can give someone a body, an avatar, and you can make it so the movements of the avatar are completely synchronised with the movements of the user. When you look down at yourself in VR, you see a body and notice that when your arms move, its arms move in exactly the same way. If you were to stand in front of a mirror in VR and do various movement exercises, you quickly understand that the avatar is yours.

What Mel and others had observed over the years, is that when you are embodied in a virtual avatar, you start to take on some of the qualities of that avatar. There have been numerous studies looking at what happens when you take on the avatar of a child, to use a simple example. When you do that, your estimations of size tend to become much larger, because things are larger to you from the perspective of a child.

Working with Professor Paul Gilbert, who pioneered compassion in the UK, we came up with a scenario where people who find it very difficult to be kind and compassionate towards themselves, people high in self-criticism, are placed in a virtual environment, given an avatar and are confronted with a very distressed child. We chose a child because we thought that might make it easier for people to be supportive.

We give them a script to go through which spans several stages of support for the child. As they go through the script, the child’s mood improves so they are no longer distressed. We record this whole interaction and then, this where re-embodiment comes in, we re-embody the participant as the child. There is a mirror opposite them in the scenario so that they realise they are now the child.

VR ChildVirtual reality

The left  image shows what the participant will see while they are comforting the child, versus the right image where they become the child. These images are from pilot studies and the new technology being created for John and Chris’ work will appear far more life-like.

We then play back their earlier intervention so they get the experience of their own words, voice, movements, being compassionate towards “themselves”. This is a very literal experience of self-compassion which many of the people we worked with have found quite an unusual and novel learning experience. It’s that bit of learning that we are trying to get across.

When they are re-embodied as the child, this change of perspective means that they are seeing through the child’s eyes this other avatar which is clearly them because it’s expressing their words and actions. We hope that this will create a new experience of self-compassion.

How does the virtual reality system you are developing generate an illusion of body ownership?

When you embody someone in an avatar, they respond to things happening to that avatar as though it’s happening to themselves. The brain is operating on two levels here: people are aware that this is something outside themselves, yet they respond quite automatically. If you threaten the avatar in VR for example, the person feels threatened themselves quite instinctively – it’s an automatic response. We are trying to use that involuntary reaction created by embodiment, so that the person will come to have these natural experiences of being reassured.

Would it have the same effect if you used the technique with a video recording rather than VR?

The difference between a video recording and VR experience is that there is an irresistible salience to VR that you can’t avoid being influenced by.

To contextualise that – I recently tried out one of the headsets that we’re going to be using in our work. I tried the technology on a rollercoaster experience, which is a common VR demo due to the fast movements and visual flow. In this situation, the imagery was so realistic that I had to remove the headset because I thought I might fall off my chair! It’s that level of instant, forced imagery you can’t ignore, which makes it different to watching a recording.

In our pilot study we looked at the effect of the person just watching themselves being compassionate to the child from the outside, which is much more like conventional interventions such as video or role play techniques – and it did not have the same effect as seeing it though the child’s eyes.

We think it’s that perspective take on actually being in the child and seeing it through your own eyes that makes a much bigger impact – that’s what we’re trying to leverage through VR, as it is something you can’t do in any other way.

Please provide an overview of the sub-contractor for this project. How are they helping to accelerate translation?

The strength of outsourcing the development to an industrial sub-contractor is that they are bang up to date with the fastest and most advanced technology. Previously when we were lab based and trying to develop our technology, the progress was reasonably slow and the headset was clunky, weighing several kilograms – not quite the effortless product we want to come out with.

Now that we are outsourcing this development, we’re expecting that process to be very different this time because they are familiar with the latest technology and software libraries and have a lot more background knowledge on how to solve various problems. The agile sense of being able to work quickly and thus being able to take advantage of new technologies is really attractive to us.

If you have experienced VR before, you may have noticed that there is often a lag between your movements and the response of your avatar, or other features not working properly. When I tested the headsets we will use in our study, not only were they incredibly lightweight, but also absolutely rock solid in terms of wherever I looked, there was no visual delay. It is also a totally standalone product, where all you need to do is have a look around the room to calibrate it, and then it’s ready to go.

We’re going to be using commercially available hardware so our industry partners are involved in the software side only. We want our end users to be able to use standard VR headsets available to consumers everywhere as that makes it much easier to disseminate what we are doing later on. Ideally, clinicians or consumers will be able to download our software via an app, and then use the software with whatever VR hardware they have available.

What challenges did you come across when developing a translational pathway for your work?

It was a big learning process for us. We come from a tradition which is not focussed on commercialisation, rather the tradition in psychology and mental health is that you work hard to develop new ways of treating people, most likely based around talking therapies and changes to currently existing ones, and you publish that. You might give workshops to teach people how to do it or produce materials to help disseminate that work, but there’s not much in the tradition in the talking therapies of commercialising.

Our background didn’t lend itself to understanding some of the things that were being asked of us when we were starting to apply for these streams of funding. Things like: how are you going to manage the intellectual property (IP)? What is your commercialisation plan? These have never been things that we needed to worry about before, so that was a big challenge for us.

How did the UCL TRO help you with your project?

The TRO were essential to us and we certainly would not be in the position we are now with an NIHR i4i award to start our work, if it wasn’t for the TRO.

There’s a culture to understanding translation, and the Translational Research Group within the TRO were people who come from that background and understood what our priorities should be.

Not only did we need to explain the science to potential funders and our hopes for the future, but we also had to explain all the other things relating to translation to them – including commercialisation. The TRO were invaluable because they have a huge amount of experience in doing exactly that. They knew which regulatory bodies we would need to engage with, what the priorities and risks that the funders would be looking for us to manage, and they also had contacts, linking us up with the right people who would be able to advise us in various areas. For example, they introduced us to UCLB, who ended up being central to our conversations with the commercial sub-contractor and making sure that the funder knows what the basis of the IP is going forward.

What are the next steps in your research?

In this particular grant, the award is funding us to develop the technology which we expect to take just under a year. During that process we will introduce the personalised avatars, so that we can give the avatars the faces of the patients using them. That should make the intervention much more potent in terms of people’s identification with the avatars. There are some risks associated with that, so in the first year we will be including a lot of PPI (Public Patient Involvement) input to make sure that what we develop is safe and tolerable to fit expectations of the end users.

After the year, we’ve got two trials to run. The first is a feasibility trial where we will be looking at practicalities, tolerability and safety in a fairly small scale study in a single London IAPT (Improving Access to Psychological Treatments) – a fast track NHS treatment service for people with mild to moderate depression and anxiety.

Following this, we will be doing a larger trial where we recruit people to use the final version of our technology. This time, we will be getting a sense of its effectiveness rather than feasibility. It’s not a pure efficacy trial as we’ll still be recruiting fairly broadly and we will not be targeting specific patients at that point, but would focus on assessing how effective our therapy is compared to other treatments for depression provided by the NHS.

Although that would be the end point of this particular project, during this time we would aim to go back to the funder and look at doing a more closely-defined efficacy study, to help move us towards commercialisation.

About Dr King and Professor BrewinJohn King Chris Brewin


John King (left) is a clinical psychologist at UCL. Although he started his career in neuroscience, his interest has shifted over the last 10 years where more recently, he has been investigating ways we can help difficult and large scale problems including depression and anxiety.

Chris Brewin (right) has been a practising clinical psychologist for the last 30 years and after 19 years at UCL retired, becoming an emeritus professor. His current research interests involve looking at how VR can be used to create experiences in patients that you couldn’t create any other way – in particular, applying some of the insights into treatments for compassion.