Rare Disease Impact Case Richard Woolley | OSIRIS Workshop, Valencia 10-11 October 2018 www.ingenio.upv.es

background Rare diseases stretch the socio-political fabric of liberal democratic societies as they, by definition, often require the dedication of disproportionately large amounts of resources to the welfare of small groups of citizens. Historically, many RD patients waited years, even decades, for a diagnosis, which largely depended on the interaction of doctors who happened to have encountered a patient with a particular condition, and the activities of families and patient organisations In recent decades, rapid increase in awareness and innovation in multiple forms of organising in support of RDs Now an increasingly strongly institutionalised political, medical, and societal domain in which scientific research is a key dynamic

problem area Rare disease: a condition defined (in the EU) as affecting 5 in every 10,000 persons. Ultra-rare disease: a condition affecting 2 in every 10,000. Around 8,500 rare diseases that have been identified and classified, but new conditions are added to this list at the rate of around 25 per month. Around 80% of known rare diseases are genetic conditions. Around 50% of identified diseases have been associated with a specific genetic mutation. The organisation of scientific research (and innovation) is interwoven in problematics of rare disease diagnosis, treatment, and care.

impact pathways in original case description Basic sequencing and bioinformatics research and the identification of new mutations – this knowledge reshapes diagnosis and clinical practice 2) Clinical research and the transition from RD as the private hobby of isolated GPS and paediatricians into institutionalised networks of professional expertise that seek to make the ‘rare expertise’ available to isolated patients and create contexts of treatment and care that link to emerging therapies 3) University hospital centres of excellence which conduct clinical research, participate in national and EU framework program research, create spinoffs that conduct clinical trials for pharmaceutical companies – links strongly to policy in terms of choices to subsidise medicines and other costly treatments (QALY assessments) 4) Continuing medical treatment and social care are linked very closely in RD and many models are being tried to integrate them. Patient organisations are key actors in this area (and all others), with the ‘social’ component of research also being important in the advice given to policy makers about the organisation of treatment and care, including vital service delivery at the community level (physio, nutrition, psych, legal, etc.)

key problem area process domains basic human genome research multilevel multimodal organising NGS technology clinical research & clinical trials integration diagnosis treatment care

key field configuring events (FCEs) ECRD conference IRDiRC conferences & workshops International research conferences EURORDIS Summer School National Plan conference(s) ??????????

empirical work strategy with key research actors & stakeholders EURORDIS Leading international genomics lab national-regional-local patient orgs European Reference Network ERN Centre of Expertise A Centre of Expertise B Centre of Expertise C

research approach Hybrid strategy (both/and) Focus on process approach to impact generation Establish relational structure of the field, identify key events and dynamics that configure and re-configure the field and can be associated with emergent impacts (RD and metabolic sub-field levels) AND concurrently develop a variance approach – three Centres of Expertise in three different national, cultural, policy contexts Comparative analysis of how common (epistemological, technical, social) processes and transformative dynamics are interpreted and addressed in context How is the generation of impact is shaped by these dual (multiple) dynamics? For which actors & in what forms? (Mietinnen et al. 2015) (metabolic sub-field and organisation levels)

research strategy 2019 Step 1: further appreciation of the structuration of the RD field – key FCEs and associated actors (continuing into 2020) Step 2: map and understand the network of actors in RD sub-field, how they are integrated, what activities they implement Step 3: map and understand the mix of knowledge drivers – genomic, clinical, technological, social – that shape transformation (impact) in the RD sub-field How: Attend several RD FCEs; continue informal contacts at EU/national levels Bibliometric analysis of the sub-field knowledge base Agree participation and conduct First set of interviews with Directors, clinicians, researchers in three Centres of Expertise within a ERN; contact key linked stakeholders & partners Identification of FCEs at RD sub-field level

Richard Woolley Ingenio (CSIC-UPV) ricwoo@ingenio.upv.es www.ingenio.upv.es