Working towards standardisation and collaboration across rare disease research

by Matthew Hanchard

View from back of the room in a large lecture hall, red walls, people seated with backs to the camera
A talk at IRDiRC 2022

The ‘International Congress of Research and Rare and Orphan Diseases’ (15-Mar-2023 to 18-Mar-2023) - or ‘(RE)ACT Congress’ for short, was co-organised by three separates bodies:

  • Blackswan foundation - a Swiss not-for-Profit company that supports therapeutic research and public awareness of rare disease and orphan drugs; 
  • European Joint Programme on Rare Diseases (EJP-RD) - a European Commission and member-state funded collaboration including 24 reference networks which supports various research projects on rare disease.
  • International Rare Disease Research Consortium (IRDiRC) - a joint venture between the European Commission and US National Institutes of Health (NIH) that also supports various approaches to rare disease research.       

As a venue, the Spanish red decor of Hotel Meliá provided a warmth and playfulness to discussions, complimented by its location; nestled between Berlin’s quietly rolling River Spree and the bustling urbanity of Friedrichstraße. The attendees, an international mix of business and industry representatives, clinicians, economists, regulators, researchers of all kinds brought together into this space generated an openness to participate in meaningful dialogue. It was reassuring too, to see a few familiar faces from the SPIN Conference in Utrecht a week before, and a few others that we would later go on to see at the World EPA Congress in Amsterdam a week later. At the event, the poster hall sessions and lobby stands were equally diverse, ranging from qualitative social science to computing, with clinical detail, evocative testimony, and health economics jostling for attendees’ attention. Our own Jin Ding presented and received several compliments on her poster comparing orphan drug approvals in the EU, UK, and US. Outside, stalls hired by a not-for-profit company offered mice procurement services (humanised and wild), while other vendors offered data and/or research services. Further down the hall, a single large conference room provided talks that were equally broad-ranging. 

The opening midday session had eight talks covering therapeutic development, innovative clinical trials, and precision medicine, each setting a tone and theme to follow. The disparate range of talks marked what we suspect was a crafty means for organisers to avoid overly curating the agenda - a manoeuvre in-line with their overarching sentiment of nurturing open dialogue. The session started with Martina Cornel’s (Amsterdam University Medical Centre) talk on the evolution of next generation sequencing of exomes and genomes, and what it might mean for infant screening programmes to identify rare diseases earlier in a patients’ life (much like the UK Newborn Genomes Project). Cornel warned that in order to do so, we need to become far better at demonstrating the value of testing for early diagnosis. Following on, Julia Forman presented work from DECIPHER, a platform for sharing anonymised phenotypic data from rare disease patients with over 43,500 records. Forman highlighted the role of DECIPHER as a federated partner in GA4GH and the Matchmaker exchange, and thus on the importance of managed data-sharing and collaboration. 

Next, came Clara van Karnenbeek’s (Amsterdam University Medical Centre) talk on the promise and limitations of exome sequencing (ES), drawing on inborn metabolic disorders as a case study. van Karnenbeek’s argued that as ES advances, we should promote P4 approaches to medicine (ie.. predictive, preventive, personalised, and participatory), using ES to work towards greater personalisation. The talk left space for a smooth transition to Tudor Groza’s (European Bioinformatics Institute) on precision medicine and the need for more complex multivariate analyses. Looking to recent advances in artificial intelligence (machine learning and natural language processing in particular) and at the value of data science in general, Groza suggested the development of a standardised ontology (computing not social). In short, a shared language used globally by clinicians, patients and policymakers when discussing rare disease, championing the Monarch Initiative as a tentative step in that direction. In concert, Kym Boycott (University of Ottawa) next covered the diagnostic odyssey faced by many rare disease patients, and the possibility of utilising machine learning and electronic health records for better and faster diagnoses. However, Boycott was quick to add that doing so would require international collaboration and data-sharing given the small patient population for many rare diseases; a key barrier at present. 

As a shift in tone, the next speakers, Anneliene Jonker (University of Twente) and Marc Dooms (University Hospitals Leuven) turned to discuss medical devices for rare diseases. These ranged from diagnostic and surgical instruments to medical aids that patients use within their daily lives. Setting out results from the IRDiRC MedTech working group, Jonker and Dooms highlighted medical devices as a vastly underdeveloped field in the rare disease space where there is ample opportunity for patient engagement. Taken together, the opening session spanned advances on genomics, AI, data management, and data science to set up themes around the promise of future technologies, the need for finding new ways to demonstrate value, an increased move towards personalised medicine, with calls for international collaboration and greater patient engagement.

The next session took expanded these themes in various ways, focussing on ’diagnostics, whole genome sequencing, artificial intelligence, and new technologies’. It started with Tim Buckinx (CEO of epihunter) describing his journey from commercial computing expert to rare disease medical device designer maker. Drawing on a personal example, Buckinx explained that his son was saddened by being told off at school for acting strangely - with little care given to the root cause - silent epileptic seizures. Buckinx’s son wished for a light-bulb to show up above his head before seizures took place, alerting the teacher in advance. In response, Buckinx gave up his day job and began making a headset using electroencephalogram (EEG) sensors, demonstrating the finished product in his talk. As informed futurism, Buckinx noted that Sony Entertainment have invested heavily in EEG sensors for the development for their next platform - the Sony PS6 - adding that it offered potential for an upcoming generation of highly sophisticated technologies and thus a proliferation of EEG devices. Also on how technologies could be developed when combined with real-time AI. 

Lucia Pannese (Imaginary s.r.l.) quickly followed Buckinx with a talk similarly focussed on devices, albeit less materially, covering gamification and enabling devices instead. Here, Pannese presented two technologies: myCyFapp, a Tamagotchi style online game aimed at children with cystic fibrosis (CF) to educate and promote CF relevant better nutrition; and REHABIILITY Neuro, designed to help patients with stroke, multiple sclerosis, Parkinson’s disease, spinal cord injuries develop a personalised physiotherapy plan. What Pannese highlighted was the issue around reimbursement. For instance, how might a patients’ ability to return to work be measured tangibly? Likewise, once a product is listed as a medical device, must it be accessed off-label to manage reimbursement, or could a new model be found; a key question for regulators. 

As the event progressed, it moved through sessions on clinical trials, precision medicine, regulatory science, clinical research, cell and gene therapies, and finally systems thinking on access. Yet throughout, it maintained a focus on the themes set out in the opening session. In a discussion about regulatory science, for example, Dan O’Connor’s (Deputy Director of the Innovation Accelerator and Regulatory Science at the UK Medicines and Healthcare products Regulatory agency) gave a talk on the evolving landscape of regulatory science in the face of growing rare disease prevalence, on the new challenges that regulators face, and on the potential of real-world evidence for post-market surveillance. Others, such as    Julianne Vaillancourt (Captain in the US Public Health Service Commissioned Corps and Policy Advisor to the Office of the Director at the US Food and Drug Administration’s Center for Biologics Evaluation and Research [FDA/CBER]) spoke in more positive terms of the promise of novel biologics. Here, Vaillancourt noted that in recent years there had been an “unprecedented growth in the number investigational new drug applications”.However, echoing O’Connor, she hasted to add that it meant that at CBER “we are overstretched”. Albeit with new programmes afoot to optimises regulatory process following the success of recent mass vaccine roll-outs via Operation Warp-speed. 

Other talks were far more technical, for instance, Isabell Batsu (Sanofi’s Global Project Head for Clinical Development in Rare Disease) discussed her commercial decision to partner with a patient organisation (National Tay-Sachs and Allied Disease Association) during phase I clinical trials - to better understand the natural history of the disease - aiding the development of treatment venglustat. Rather than covering drug development, the next speaker, PJ Brooks (Deputy Director in the Office of Rare Diseases Research for the National Centre for Advancing Translational Sciences {NCTAS]) moved on to discuss etiology; specifically the work of IRDiRC’s task force on ShAred Molecular Etiologies (SaME) in applying the basket trial approach used within oncology to cover multiple rare diseases.. Meanwhile, in their discussion of gene and cell therapies, speakers like Arjan Lankaster (Professor in Pediatrics and Pediatric Stem Cell Transplantation at Leiden University Hospital) discussed allogeneic stem cell transplantation (HSCT) and autologous haematopoietic stem cell-based gene therapies for immunodeficiency diseases, and their limitations. Expanding on this further, Lankaster presented work from RECOMB, an EU HORIZON funded trial for a lentiviral-based gene therapy for RAG1 deficient and thus severely auto-immune deficient infants. Similarly,Carl Morris’ (Chief Scientific Officer at Solid Bioscience Inc.), talk covered the potential of adeno-associated viruses as gene delivery mechanisms owing to their low immunogenicity, and its capacity for treating Duchenne muscular dystrophy.     

As a closing session, debate centred on directing systems thinking towards access, in which speakers such as Mary Wang (Programme Director for Rare Disease International) argue for a need to standardise terminology and to collaborate internationally in developing a descriptive framework for rare disease. Samuel Agyei Wiafe (Rare Disease Ghana Initiative) followed on, with a more internal call to collaborate, with diagnoses and treatments as core concerns. Esehere, Yarlalu Thomas presented Lyfe languages as a project steeped in translating medical knowledge and terminology into Indigenous Australian languages, and in working towards a mobile app for non-English speaking First Nations people to help navigate the healthcare system.   

Across sessions, a need for collaboration and data-sharing became apparent, as did the pressures on regulators, scientists, and patients alike. Uncertainty remained in the air over how medical devices might be reimbursed, and on how artificial intelligence and data science might best be utilised to aid research disease diagnosis and treatment. What we took away was an overview that alliances are often formed, at times ephemerally, between various actors (i.e. pharmaceutical companies and patient organisations), but that much work is needed on standardisation - of data sets, languages, ontologies, and processes. Rather than providing resolution, the conference felt more of a call to action, one steeped in hope for technological advancement.

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