In Europe, between 27 and 36 million people are living with a rare disease. Around 80% of those diseases have a genetic origin, and 70% of them start in childhood.
However, diagnosing rare diseases can be incredibly difficult. It takes an average of 4.7 years for people to receive a diagnosis, and this journey – known as the diagnostic odyssey in the community – is fraught with tough experiences, including hospitalisations, taking the incorrect treatment, undergoing a battery of tests and more.
Screen4CARE have developed two tools that will help patients to avoid a diagnostic odyssey and get a true diagnosis earlier and faster.
It starts with newborns
In all EU countries, newborns are tested for certain diseases using a heel-prick test. These tests are not genetic tests – they are based on the presence of certain metabolites. Screen4CARE developed a genetic tool called the TREAT panel, which looks very similar to what is used today for metabolic screening. The heel-prick test requires a few drops of blood for the metabolic screening panel – similarly, two to four drops of blood are needed from the baby’s heel for the TREAT panel to analyse.
From those drops of blood, DNA is extracted and input into the TREAT panel, where it is analysed for 245 genes that cause rare diseases. The idea is that the methodology should be as close as possible to routine treatment, so that there is no need for extensive training of maternity staff and the TREAT panel can be easily added into the hospital’s routine.
Under the Screen4CARE project, this sequencing activity is centralised at the Bambino Gesù Hospital in Rome, while the output analysis occurs in two centres, CNAG (Centro Nacional de Análisis Genómico) in Barcelona and Genoox in Amsterdam. Babies are recruited to take place in the analysis at several Screen4CARE birth centres found in Italy, France, Germany, the Czech Republic, Greece and Poland, and the data curation is carried out there.
Screen4CARE’s project coordinator, Alessandra Ferlini of the University of Ferrara, in Italy, stresses that in an ideal world, where all 27 EU member states would be running genetic screening programmes for rare diseases in infants, sequencing tasks would be centralised in a few “master” hubs, to ensure that potentially millions of samples could be analysed in a fast and timely fashion.
“Running newborn samples through next generation sequencing genetic tools requires centralised platforms and centres. It cannot be carried out by fifty different centres per country. That is not appropriate, neither in terms of feasibility nor in terms of affordability nor cost benefit,” she says. “In addition, establishing a few genomic centres in the EU would represent tremendous added value for genomic medicine and research.”
Screen4CARE is currently carrying out a pilot study involving 18 000 children across six countries: Italy, France, Germany, the Czech Republic, Poland and Greece. The study aims to prove the effectiveness, robustness, and applicability of rolling out genetic newborn screening within health systems. In addition, it will demonstrate that early and fast diagnosis of infants with rare diseases will reduce the diagnostic odyssey often experienced by people with rare diseases and will ensure that access to the correct treatment happens sooner.
Readying the TREAT panel for EU-wide roll-out
At present, a child born in the EU will be tested for different diseases depending on which country they are born in. Ferlini is advocating for a common approach, in line with what the EU Strategy on the Rights of the Child promises: that each child has the right to the highest attainable standard of healthcare, irrespective of where they live.
“It cannot be that in France they are screening for six diseases, in Germany 21 and in Italy 48. That’s not fair. That’s against the principle of equality and equity,” she says. “We can redesign the TREAT panel “on demand” into a version that tackles a certain number of core rare diseases that all the EU countries can agree on, keeping the costs affordable and centralising the sequencing and genetic analysis.”
Of course, before any tool can be rolled out for widespread use across Europe, it has to be assessed by regulators. Screen4CARE is initiating interactions to better understand the regulatory pathways and the steps that need to be taken, for instance for further developing the TREAT panel tool as an in vitro diagnostic.
An app that records symptoms, is inclusive and respects privacy
Originally, Screen4CARE planned to develop a symptom checker app to help shorten the diagnostic odyssey, but when they reviewed what was already on the market they pivoted.
“When we started this project, we did a horizon scan of the existing symptom checkers that are available and we discovered to our horror that most of them were not using medically validated information,” said Lizbeth Goodman of University College Dublin, who is in charge of the work package that is developing the app. “This could lead to misdiagnoses and raises ethical concerns.”
Based on the results of their initial analysis the project made a strategic decision not to create a symptom checker app, but instead to develop an app that was missing from the market – an app that could reliably track a person’s symptoms while ensuring data privacy. At the same time, the app could also provide a source of medically-validated, up-to-date and trustworthy information on rare diseases.
“We are not giving a diagnosis through this app. Only human beings, expert medical doctors should be giving diagnoses,” says Goodman. “This is a tool that will hopefully lead to faster diagnosis and will help doctors to better understand the patient’s journey.”
The app has four parts:
- Touch RD where the user selects an avatar that is most similar to him or herself – e.g. a child, a baby, an adult – and then can input the symptoms that they are experiencing through multiple modes: touching the screen, or speaking into the microphone, or adding text.
- Talk RD translates the information regarding symptoms provided by the patients from the lay language of the user to a clinical description with appropriate symptom codes, to help patients talk to their doctors effectively, and to help clinicians make faster progress in diagnosis.
- Teach RD which allows the user to enter a virtual room and learn about their disease through various games and activities linked to medically-validated information from reliable sources.
- The Symptom Suitcase where the user can input all of their symptoms in diary format, secure in the knowledge that the data is safe and will not be shared with third parties. The app will then recommend the user to see their doctor if there are two or more unusual combinations of symptoms present which could indicate a problem. The Symptom Suitcase will be an aide to clinicians and doctors by providing a list of symptoms including information on when and how frequently they were experienced.
Privacy-by-design and accessible to all
The app developers made a conscious decision not to use an AI-based model, because data privacy could not be guaranteed and because AI is known to hallucinate, which could result in patients receiving incorrect information. Instead, they decided to pursue a ‘privacy-by-design’ model.
This has a number of advantages. In some countries where healthcare is privatised, if insurance companies have access to private health information, a person may be denied coverage. A person using the Screen4CARE app can be secure in the knowledge that their data will not be leaked to a third party and cannot be accessed by an insurance company without their knowledge. The user retains full ownership over their data.
“We must be cognisant of privacy and allow people to have control over their own data,” says Huw Williams of SMARTlab, the team leading the app development.
A key feature of the app is its accessibility. With the patient in mind, and knowing that rare disease patients can have a wide range of symptoms affecting how they interact with the world, the Screen4CARE app was developed using an Inclusive Design methodology. This involves creating products that can be used by the widest group of people possible, starting by imagining how people with varying accessibility requirements could access and use the app. Using avatars and allowing people to touch the screen opens the app up to people who may not be able to speak or type well enough to explain their condition. In this way, the designers ensure that the app is useable by everyone.
Scroll through the app below:
Patients at the core of the design process
From the beginning, the project engaged with patients to inform the app’s development. Focus groups were set up and demo versions of the app were tested. The developers then took the feedback and used it to improve the next version of the app. The project is currently in a phase of validation with the patient groups, meaning that interviews are being setting up with individual patients with rare diseases and tests are being carried out to see if the app should be tweaked further.
“At the end of the validation process, we’ll be at Technology Readiness Level 5 (TRL5), and we’ll know for sure that the app that the patients have asked for is what we’ve delivered,” says Goodman.
By the end of the Screen4CARE project, a minimum viable version of the app will be developed. Some further validation will be needed before it can be released on to the market, but Goodman anticipates that it could potentially be available to patients by mid-late 2027, resources permitting.
Both tools will shorten the diagnostic odyssey that patients currently have to wade through. By detecting rare diseases at the very start of life, and by using a digital app that can serve as a diary, alarm system, source of information and diagnostic aide, the goal is to speed up diagnosis and make sure that patients receive the correct treatment, sooner.
Screen4CARE is supported by the Innovative Medicines Initiative, a partnership between the European Union and the European pharmaceutical industry.