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The mathematical modelling of disease progression is an essential part of several projects of the Innovative Medicine Initiative (IMI), namely AETIONOMY, EPAD, RADAR-AD; and it is subject of an entire work package in the European H2020 project VirtualBrainCloud.

The joint interest in mathematical modelling of disease progression prompted us to come together for a first workshop on disease progression modelling. At the invitation of Martin Hofmann-Apitius of the Fraunhofer Institute for Algorithms and Scientific Computing (SCAI), leading scientists in the field met for two days in Bonn (Germany) on 4 and 5 April to exchange ideas and to report on their strategies for modelling disease progression in neurodegenerative diseases and psychiatric conditions. It was a great experience and a very productive workshop.

We are pleased that the website about disease progression models is now online. It contains videos and presentations of the first disease progression modelling workshop that took place in Bonn. Have a look here: http://www.diseaseprogressionmodels.eu/

Please note that the next workshop will take place in Paris (France) in spring 2020. More information will follow in due time. Stay tuned!

What is your current role in EPAD?

I am an active member of the Recruitment Core Team, which includes looking at how to increase recruitment by reaching out to sites where necessary and troubleshooting problems as they occur. I am also the country coordinator for Scotland’s TDCs and I am an expert blinded rater for the CDR in all of the Scottish sites. I work for EPAD as a member of the Recruitment Core Team one day per week.

What did you do prior to joining EPAD?

I still work as the Network Manager for NHS Scotland in the Neuroprogressive and Dementia network 4 days per week. My professional background is Mental Health Nursing and have over 20 years experience in ‘hands on’ nursing people with dementia in both in a hospital and community setting before working as a manager with the network.

Tell us a bit about the institution/company/organisation you work for.

I work for the NHS and feel passionately proud of the NHS and the concept of access to free healthcare from cradle to grave. The Neuroprogressive and Dementia Network is funded by the Scottish Government’s Chief Scientist’s Office but delivered through the NHS. We encourage access and opportunities for all, to high quality clinical research throughout Scotland for people with these diseases.

What are your expectations from the EPAD project?

Our main barrier to delivering studies is recruitment. I hope that EPAD can deliver the necessary cohort of trial ready participants to allow medicinal preparations to be tested quickly and safely and therefore we find something that can change the lives of people who have dementia or are at risk of developing it. 

What is your current role in EPAD?

I am a co-lead of Work Package 2 – The Statistical Engine Room.  The Statistical Work Package has two main focuses in the EPAD project – the design of the proof-of-concept platform trial and the disease modeling work from the Longitudinal Cohort Study (LCS).  I have been focused on working with the EPAD team to create a platform trial design for the phase 2 proof-of-concept trial (PoC). This will allow multiple therapies to be investigated simultaneously in the same protocol creating a great deal of synergy – for example sharing controls across arms.

What did you do prior to joining EPAD?

I am a PhD Statistician and President at Berry Consultants, a statistical consulting company specializing in designing adaptive and innovative trial designs, typically from a Bayesian perspective.  We work for a wide range of sponsors – large and small pharma, device companies, federally funded trials, and NGO based efforts.  We work on designing flexible adaptive trials.  This process involves creating the modeling and adaptive features of a design.  Typically, this involves detailed clinical trial simulations in order to optimize the design – making sure that the adaptive features, modeling and threshold are all optimized for the goals of the trial.  The design of adaptive trials is a very detailed process of iterative trial design aspects tied to detailed clinical trial simulations.  Traditional, fixed, trials can be understood with pencil-and-paper calculations, but more complex trial designs are simulated to understand their behavior – much like the simulation design of airplanes, automobiles, and bridges – well almost everything nowadays.  Trials constructed through simulations have been given the moniker of “complex” innovative trials.  This has been the space of trial designs we have been working on. 

Recently platform trials have been gaining in popularity.  The I-Spy2 trial was one of the first platform trails (with more than 14 different experimental agents moving through the phase 2 trial) and its popularity and growing need for more efficient methods have led to this growth and demand for platform trials.  Platform trials are being constructed in multiple cancers, ALS, Duchenne muscular dystrophy, various infectious diseases, PTSD, as well as familial Alzheimer’s.  These trials typically fall in this bucket of complex trial designs.   

Tell us a bit about the institution/company/organisation you work for.

Berry Consultants has offices in the UK and the United States, and we focus on statistical innovation – typically tied to the design and analysis of innovative trial designs.  Berry Consultants is approaching its 20^th year – after being founded in 2000 by Don Berry and myself.  We have since grown to more than 30 employees – experts in statistics, clinical trials, and clinical trial simulation.  In addition to the design of trials, Berry Consultants has created and continues to develop a software package for clinical trial simulations, for the evaluation and optimization of trial designs (Fixed and Adaptive Clinical Trial Simulator, FACTS). 

What are your expectations from the EPAD project?

I have incredibly high hopes for EPAD.  I believe the PoC trial that comes out of the EPAD project will continue perpetually as long as there is a need in the slowing and prevention of Alzheimer’s disease.  The project is unique in the construction of the LCS feeding to the PoC trial.  I believe the PoC trial will prove to be an incredibly efficient ‘machine’ for phase 2 Alzheimer’s drugs – which will decrease costs, improve timelines, and ultimately improve the industries ability to investigate experimental drugs.  Not only will this have substantial impact on Alzheimer’s disease but the project itself will likely become a model project that can be emulated in many other diseases. 

The fourth Scottish Dementia Research Consortium (SDRC) conference was held in Glasgow on 15 April 2019. The annual SDRC conference showcased the world-leading dementia research taking place across Scotland and focused on early career researchers with this year’s theme being the fundamental sciences. It was an excellent conference with a variety of talks and posters where delegates shared their research, projects and experiences in an atmosphere of collaboration.

One of the highlights was ‘Cohort Corner’, showcasing the excellent cohorts led from Scotland. Several Epadistas from the University of Edinburgh’s Centre for Dementia Prevention attended and presented a poster as part of cohort corner titled “EPAD: an overview of data collection, data release and data access in the Longitudinal Cohort Study (LCS)” during the great exhibition and lively networking time. In the accompanying poster, it was reported that the EPAD-LCS has recruited over 1,500 participants from seven European countries aged 50 or above that do not have a diagnosis of dementia. The poster emphasised the data access process and the online informatics platform where EPAD-LCS data will be hosted. Researchers will be allocated a workspace to access and analyse the available data. It was also shown that the cohort data will be accessible to the entire research community (v500.0 in November 2019). Many attendees commented on the fantastic initiative for EPAD to have open data access and were excited for the data access process to open in 2019.

For more information, please contact: info@alzheimer.noemi.lu. You can view the full conference programme by clicking here.

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Professor Craig Ritchie, of the University of Edinburgh, is jointly leading the EPAD project, a Europe-wide collaboration aiming to improve the understanding of the early stages of Alzheimer’s disease. EPAD combines knowledge and expertise from 39 European partner organisations across multiple sectors.

Craig Ritchie and one of the EPAD study participants Eileen Penman have recently been featured in national UK news to provide comments on the potential impact of Brexit on EU/UK research collaboration and projects such as EPAD in particular. Both Craig and Eileen highlighted the importance of EU wide collaboration and their concerns on the future standing of Scotland in research outside of the EU.

 “While funding for the present project is secure, what happens as we move forward with our research findings?” “Normally, we would be very excited about following on with the results of our research and using that as a platform to the development of treatment.” “But we can’t be excited because of the uncertainty of future EU funding and continued collaboration.”, said Craig.

“I’m not a political person, but for the sake of future generations and the millions who could be saved from having to suffer dementia in the future, the thought of Brexit having any detrimental effect on vital medical research, and our access to it, is dreadful.” “For us to face difficulties because of Brexit would be awfully hard to accept.” “When I heard we were to leave the EU, it was a devastating moment and I don’t think people carefully considered what would happen to all these vitally important research programmes.”, said Eileen

We are glad to see that the story was reported on the front cover of The Sunday Post in Scotland in an article titled “Scotland’s universities warn Brexit threatens world-leading dementia work that could transform lives around the globe”. In addition, this report was picked up by broadcast media on STV on its main news bulletins.

https://twitter.com/i/status/1115317346602713088

On 2 April, the Innovative Medicines Initiative (IMI) organised a Projects Communication Event, which brought together more than 70 representatives from many IMI projects responsible for communications. Several members of the EPAD project travelled to Brussels to take part in this exciting event and shared their experiences within our WP6 on Dissemination.

The aim of the workshop was to provide information and networking opportunities to help delegates improve the way they communicate about their projects to diverse audiences throughout the project life-cycle.

The first session addressed topics on IMI communication resources available to IMI projects and digital communication. Con Franklin, Managing Director Health of Ketchum London provided a keynote speech on the communication strategy including some trends, developments and ideas.

The second session included case studies and best practices from three IMI projects: HARMONY, European Lead Factory (ELF) and EPAD. It was a great opportunity to discuss best tactics and ways of communicating. The EPAD team was delighted and honoured to have been invited at this event to present EPAD as an example of good practice of communications. Our WP6 leads Sean Knox (Biogen) and Jean Georges (Alzheimer Europe) shared some practices and experiences on communication and gave an overview of the different tools we are using to promote the EPAD project.

One of the highlights of the day was a brainstorming workshop organised at the end of the day where attendees had the opportunity to exchange on shared challenges and potential hurdles in communication. The workshops were centred on three key questions related to communication-specific situations that a consortium may face:

• How to motivate individual partners in a large consortium to engage in communication activities? How do you assure message consistency?
• Dealing with criticism: how to approach crisis management when negative opinions of your projects reach the public domain and social media?
• How to build a communication strategy to prevent strong public opposition to the objectives of your project?

You can find details of the event and the presentations on the IMI website here.

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Fundació ACE – Barcelona Alzheimer Treatment & Research Center, an entity devoted to the diagnosis, treatment, research and awareness on Alzheimer’s disease, has been incorporated into EPAD (European Prevention of Alzheimer’s Dementia Consortium), a European consortium aiming to work for the prevention of Alzheimer’s dementia through an interdisciplinary research program.

Facing the evidence that Alzheimer’s disease causes brain alterations prior to the onset of symptoms, this project focuses on the early phases of the disease to develop actions that help to prevent and treat this type of dementia. In recent years, research has increasingly focused on this presymptomatic phase in order to offer new preventive treatments and to intervene more effectively.

EPAD is the largest public-private consortium in the field of Alzheimer’s research thanks to the participation of multiple collaborating organisations and more than 1,500 registered participants to date. Fundació ACE becomes a new member of the group and one of the three representatives of Spain, together with the Pasqual Maragall Foundation research center, the Barcelonaβeta Brain Research Center, and the Alzheimer’s CITA Foundation.

Dr. Mercè Boada, medical director of Fundació ACE, attended, last February in Berlin a follow-up meeting of the project along with other experts from the organisation such as Dr. Agustín Ruiz, research director, Dr. Carla Abdelnour, attached to the Clinical Trials Unit, and Mar Buendia, clinical trials coordinator.

Dr. Boada expressed satisfaction with the recent incorporation of the Foundation to the project. “In recent years, at Fundació ACE we focused on the early detection of Alzheimer’s and we devoted many efforts in this direction. It is not an easy task; It is a challenge in which we keep on putting efforts day by day. This is why, we are convinced that it will be very positive to be part of a project that pools the knowledge of so many entities and experts and unites efforts in the prevention and treatment of dementia” she comments.

The challenges of EPAD

In order to carry out its work, EPAD faces several challenges, such as the difficulty of identifying people who may end up developing Alzheimer’s, the lack of understanding of the earliest stages of the illness or the lack of flexibility in the clinical trials development.

To address these difficulties, the Consortium developed three basic strategies:

• The Register: EPAD will create the first single, pan-European register of over half a million people across the risk spectrum for dementia.
• The Cohort: From this register, research participants are invited to join an EPAD cohort of at-risk subjects. At present, more than 1,500 participants from centres throughout Europe with standardized tests are being part of this cohort and are followed for several years.

• The Trial: EPAD will select suitable participants to take part in adaptive trials of drugs designed to prevent Alzheimer’s dementia. In fact, EPAD is a pioneering platform in the implementation of this method. In traditional clinical trials, half of the participants receive the drug under investigation, and half receive a placebo. In adaptive clinical trials, several candidate drugs are simultaneously compared to each other and to a placebo, meaning that a greater proportion of patients benefit from a potentially active treatment.

As a result, a greater proportion of people benefit from a potentially active treatment to reduce the risk of developing dementia in the future. Furthermore, researchers can adapt the trial design in response to emerging results, new candidate drugs can be added, and those that prove ineffective can be dropped. With better data and better decision making, the adaptive tests can increase the likelihood of success and decrease the duration of the development. EPAD started in 2015 and is made up of research centers, universities, pharmaceutical laboratories and associations of patients from all over Europe. The consortium is funded with the subsidy number 115736 of the Innovative Medicines Initiative, which is a joint initiative of the European Commission research and innovation program Horizon 2020 and the European Federation of Pharmaceutical Industries and Associations (EFPIA).

About Fundació ACE, a pioneering model in the world of Alzheimer’s

Fundació ACE – Barcelona Alzheimer Treatment & Research Center, an innovative and reference entity in Spain, was created in 1995 with the aim of addressing the growing demand in the diagnosis and treatment of people with cognitive impairment and dementia, especially Alzheimer’s, offering personalized attention and comprehensive accompaniment to patients and their families. Fundació ACE is considered one of the international benchmarks in research, especially clinical, social, neuropsychological and basic research.

Every year more than 7,000 people go through their Diagnostic Unit. 4,000 of those have dementia (3,000 of them, Alzheimer’s type). Among other research activities, Fundació ACE participates in numerous clinical trials involving worldwide participation in all the phases of the disease. Its team is currently leading two research projects funded by the European Union on Alzheimer’s Genetics (ADAPTED) and on models of patient engagement (MOPEAD).

For further information:

M. Dolors Cuenca
677 14 57 65
mdcuenca@undatia.es

Isabel Rodríguez
93 444 73 18
irodriguez@fundacioace.org

Check out the Spanish press release here.

The European Prevention of Alzheimer’s Dementia initiative (EPAD) recruited its first Research Participant in May 2016 via the University of Edinburgh (UK). The team of Craig Ritchie (principal investigator of the EPAD project in the University of Edinburgh and EPAD Project Co-coordinator) has currently recruited over 100 participants in the EPAD Longitudinal Cohort Study (LCS). We caught up with his team and asked them a few questions about their best practices and recruitment strategies.

Any top tips for running the LCS efficiently at your site?

Here in Edinburgh we were the very first EPAD Trial Delivery Center (TDC) site to open which means we have participants reaching their 5th (Year 3) visit as well as continuing recruitment for new participants. The key to managing this is communication, between the site staff, our colleagues in other teams who support EPAD and our participants. We have weekly meetings between the coordinator, research assistants and study doctors to discuss all participants attending for visits in the upcoming week. These meetings ensure we know who will be seeing the participant, printing reports from bloods and MRIs that we need to confirm safety to complete lumbar punctures, and ensure we have everything we need to complete the visit successfully- including most importantly participant breakfast and lunch! We also have a monthly multi-disciplinary team meeting to catch up on how EPAD is going, focusing on recruitment, retention, data quality, monitoring and participant feedback. We keep in touch with our MRI, laboratory and lumbar puncture practitioners regularly by phone and email. When our participants first join EPAD we find out how they’d like us to communicate with them, phone, email or letter. We then book in upcoming visits far in advance as we know our participants and study partners lead busy lives. This also helps us to know capacity at site each month so we can book in new participants to join the study. We also organise a participant facing newsletter which includes information on latest EPAD news as well as explaining why we do certain procedures such as the MRI and the lumbar puncture. These newsletters now go to all Scottish TDCs to send on to their enrolled participants.

How are you able to find suitable subjects for the cohort?

We have a diverse recruitment strategy at our site to maximise our ability to identify participants most likely to be suitable to join the proof-of-concept studies coming in 2020. When the site first opened in May 2016 we recruited from our two large parent cohorts, PREVENT Dementia and Generation Scotland. This was a great way to start the recruitment and we successfully recruited over 60 participants from these routes.
We continue to recruit from Generation Scotland but our numbers from this route have now reduced to one or two a month.  We’ve also brought a new parent cohort on board, the DAEM cohort, which we are hoping will bring us in more participants with mild cognitive impairment (MCI).
Our biggest success over the last year has been using the velocity route to identify potential participants and invite them to join EPAD. We work directly with our clinical colleagues in our local memory services who refer people with MCI directly to EPAD. We have also been rolling out the Scottish Brain Health Register (SBHR) which received some set-up funding from the EPAD LCS Recruitment Task Force, a consent to consent research register, which allows people with concerns about their brain, or the public interested in brain health, to be connected to research opportunities in their local area. Follow us on Twitter to find out more @ScotBHR! SBHR allows us to offer EPAD to people who might not have been referred at their clinic visit. We also work with the national registers of Join Dementia Research and SHARE, and are hoping to start working with the Scottish Primary Care Research Network to offer EPAD to people with MCI who are registered with GP surgeries in our local area. We’ve seen these recruitment efforts help us move towards a cohort richer in people with a CDR 0.5 and we are now ambitious in our aims to significantly increase these efforts over 2019.

Any country teleconferences/meetings you are organizing and how frequent?

We are incredibly lucky to be part of a great network of sites in Scotland and frequently talk to our colleagues in the Tayside, Glasgow and Grampian TDCs. We join monthly calls chaired by Emma Law, Network Manager and EPAD National Coordinator, to share best practice and identify challenges across sites that can be tackled with a cross-site strategy. Examples of strategies that we’ve been able to introduce across sites because of this collaboration is the introduction of Join Dementia Research and SHARE as recruitment sources via Velocity.  
We also contribute to the planning of the annual Scottish sites conference in Aberdeen in August. The first of these was held in August 2018 and was a great success. Planning for August 2019 is well underway, with the meeting a perfect place to showcase site activity, network with our EPAD colleagues across Scotland and update our participants about EPADs latest findings.

Any activities in terms of participant engagement?

One of the highlights of running EPAD is definitely being involved with the Scottish participant panel. The panel formed soon after recruitment started in Edinburgh and as of September 2018 started a transition to a represent all of the Scottish TDC. At our next meeting in late March 2019 we will have representatives from all four Scottish sites and we’re excited to see what the next year brings. The panel work alongside us as EPADistas to provide feedback on the participant experience, review documents used in the study, help development of new recruitment and retention ideas and attend conferences and events to showcase EPAD.

Our centre is particularly proud of our participant engagement work and each year we have a growing list of regular events we host or take part in to raise awareness of brain health. Events vary from lecture series, to concerts, to having a stall in local supermarkets. Regardless of the type of event we host we always get a fantastic response from the public. Find out more about what we do by following us on Twitter @CenDemPrevent.

“EPAD is leading the way in brain health research across Europe and we are delighted to lead this from Edinburgh. The EPAD cohort is one of our flagship studies in the Edinburgh Dementia Prevention research group. It’s fantastic to be able to offer EPAD to people I see in clinic who are experiencing early symptoms of Alzheimer’s disease and offer them the opportunity to be part of a pioneering project”, said Craig Ritchie

Pictured: From left to right: Dr Ben Grey (Study Doctor), Prof Craig Ritchie (PI/CI/EPAD Co-Coordinator), Hannah Jobse (Research Assistant), Dr Catherine Pennington (Sub-investigator), Sarah Gregory (Study Coordinator), Clare Dolan (Research Assistant), Neil Fullerton (Research Assistant), Dr Alison Hunter (Study Doctor), Sarah Sparks (Research Assistant)

EPAD Update

We currently have 21 sites across Europe enrolling. The EPAD LCS Cohort has now over 1,500 Research Participants screened! Congratulations to the TDC in Bristol, who recruited participant number 1,500. There was a total of 83 new research participants enrolled in the EPAD study in February. We are pleased that Pablo Martinez-Lage’s team in San Sebastian (Spain) and José Luis Molinuevo‘s team in Barcelona screened respectively 14 and 9 new research participants.

The 14th​ International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2019) and related neurological disorders took place in Lisbon (Portugal) from 26-31 March. It provided a world class platform for international clinical investigators and scientists to present, discuss and trade expertise on a broad range of themes and topics. The event attracted over 3,800 participants from over 70 countries.

The conference started on 26 March with three pre-conference workshops:

• Common features of neurodegenerative diseases: exploring the brain-eye connection and beyond
• Basic neuropathology of age-associated neurodegenerative disease
• The promise and pitfalls of Real-World-Evidence in Alzheimer’s disease.

The scientific director of the Alzheimer’s Prevention Program of the Barcelonaβeta Brain Research Center (BBRC), Dr José Luis Molinuevo, was invited to give a talk at the preconference meeting and asked to present  the European Prevention of Alzheimer’s Dementia (EPAD) project and the Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) project. He participated in a session about Key Real-World-Evidence initiatives in Alzheimer’s disease chaired by Colin Masters.

In his talk, Dr Molinuevo gave an overview of the EPAD project. He started by introducing the EPAD project, its consortium and objectives. He further explained the Longitudinal Cohort Study (LCS) and highlighted the number of European participating countries. By end March 2019, there were 21 study sites up and running, with more than 1,500 research participants recruited. He also mentioned the data collected within the study and ended with the main achievements of the EPAD project.

Then, Dr Molinuevo presented the AMYPAD project aiming to improve the understanding, diagnosis and management of Alzheimer’s disease through the utilisation of ß-amyloid PET imaging. He mentioned the AMYPAD consortium which is a combination of 9 academic partners, 3 industrial partners, 2 SMEs and 1 patient organisation. He explained the Diagnostic and Patient Management Study (DMPS) and the Prognostic and Natural History Study (PNHS) including their objectives, design and current status. As per 29 March 2019, the DMPS is performed in Geneva, Amsterdam, Toulouse, Cologne, Barcelona and London with 244 patients spread on the active sites. The PNHS has three active sites (Amsterdam, Edinburgh, and Barcelona) with 86 research participants.

On 7 March, EPAD passes the mark of 1.500 research participants for its Longitudinal Cohort Study (LCS)! Congratulations to the Trial Delivery Center in Bristol, who recruited participant number 1500.

The largest ever public-private partnership in Alzheimer’s disease research, EPAD combines knowledge and expertise from 39 organisations across multiple sectors from academia and industry, bringing together a wealth of experience to its activities. By setting up a trial-ready cohort of research participants, creating a pan-European network of trial sites, developing a platform on which new compounds can be tested in a streamlined and efficient way, EPAD aims to accelerate the development of effective therapies.

We have developed three core strategies which deliver benefits for intervention owners and research participants.

1. The Register: EPAD has created the first single, pan-European register of over half a million people across the risk spectrum for dementia.
2. The Cohort: From this register, research participants are invited to join an EPAD cohort of at-risk subjects, the Longitudinal Cohort Study. This group will undergo standardised tests and follow-up over several years.
3. The Trial: EPAD will select participants to take part in streamlined proof-of-concept (PoC) trials of drugs designed to prevent Alzheimer’s dementia

Watch the EPAD video for an overview of our approach.

Currently, EPAD has 21 study sites up and running across Europe and is adding new participants to the cohort every week. The consortium is now preparing the negotiations with the first intervention owner.