The Orphanisation project

Logo for the Orphanisation project, blue and white capital 'O' letter on a white background with a shadow outline effect
Image created and owned by the Orphansation project team

Our latest activity Outputs The rapid growth of expensive 'orphan drugs' used to treat rare diseases is being driven by novel business models within the biopharmaceutical industry, posing major challenges for patients' access to healthcare, and it has become the subject of several high-profile controversies and policy debates over how these medicines should be regulated. As a key term, 'orphan drug' is the formal regulatory designation and term used for a class of treatments for various rare diseases whose development has been incentivised to address the needs of a neglected patient group. The number of orphan drugs available is are growing rapidly, and they are highly profitable, stimulating new business models based on developing high-cost products for niche markets. The very high price of some orphan drugs has led various countries to refuse to pay for them, provoking growing political concern that patients are being denied access to life saving therapies. Meanwhile, some patient organisations have responded by sponsoring more sustainable and lower-cost orphan drug developments.

A major international debate is currently ongoing about how we might improve patients' access to orphan drugs, raising important questions about how to value these medicines, and the ethics of resource allocation involved. Our Wellcome Trust funded project, titled 'Orphan drugs: high prices, access to medicines and the transformation of biopharmaceutical innovation' contributes towards this discussion by looking systemically at the co-production of industrial and technological change, the politics and governance of orphan drugs, and new forms of collaborative knowledge production.

The project is innovative in developing a new concept (orphanisation) as a way of understanding contemporary changes in the biopharmaceutical sector. Specifically, the project examines the extent to which orphanisation occurring in the EU, UK, and USA. Also, how is it shaped by different technologies, institutions, and actors, addressing the implications for industry, health policy and patients?

Our team

Project Lead: Paul Martin

Workstream Leads: Jin Ding (WS1) | Matthew Hanchard (WS2) | Eva Hilberg (WS3)

Collaborators: Michael Hopkins | Andrew Bartlett


  1. Chart the growing industrial development of orphan drugs in the UK/EU/US and analyse the emergence of new orphan business strategies
  2. Understand the role of different actors in the evolution of orphan drug policy, map the controversy around high prices, and analyse proposals to improve access and reform orphan incentives
  3. Describe the crisis in pharmaceutical innovation, explore the emergence of new forms of patient engagement in drug development and review initiatives to support drug repurposing
  4. Assess the implications of orphanisation for health and healthcare and develop proposals for more sustainable models of pharmaceutical innovation

Our project is split into three workstreams: 

Workstream 1:  Industry Dynamics and Orphanisation

This workstream investigates the dynamics of industrial innovation and evolution of orphan drug development in the EU, UK and US, analysing emerging business strategies in the field. 

  1. Research will depict the growth of licensed orphan drugs and products in the development pipeline. A dataset will be compiled by collating data from public sources (MHRA/EMA/FDA) and private database (Pharmaprojects). Analysis will provide a comprehensive picture of orphan products in development and on the market, therapeutic areas and trends in sales. 
  2. We will analyse the industrial structure and dynamics in relation to orphan drug development and commercialisation. An industry dataset will be established based on specialist sources (Deloitte, Informa), press releases and company documents. This will be used to map and visualize the industrial collaboration network with other companies, academics and patient organisations. Key players, structural dynamics, and significant differences between the UK and US will be identified.
  3. The research will also analyse the business models of leading orphan drug companies based on document analysis, ethnographic observation and interviews. This will explore the company strategies employed by SMEs and big pharma, and the development of new business models focusing on orphan drug markets.
Workstream  2: The politics of high orphan drug prices

The workstream examines the politics orphan drug pricing, including the main actors involved, the bases of their arguments, and the impact of patients' equitable access to orphan drugs. It does so through three main strands and a subproject on 'sociotechnical imaginaries of orphan drug access in the USA':

  1. To understand the role of different actors in the evolution of orphan drug policy, this workstream draws on document analyses, ethnographic immersion at conferences, and semi-structured interviews with patient organisations. This strand of the research focusses on the extent to which different actors’ discourses have historically framed the development of orphan drug policy in the EU, UK, and USA, including a meta-narrative review of health policy debates around orphan drug prices. 
  2. To map some of the controversies around high orphan drug prices within the public sphere, this strand includes digital methods analyses of social media discourse and semi-structured interviews with patients/patient organisation representatives. It focusses on identifying specific issue-networks, the key actors involved with constructing and circulating particular narratives/counter-narratives, and their relation to wider notions of health policy.
  3. To examine proposals to improve access to orphan drugs and/or initiatives to reform policy, regulation, and legislation, the stand also draws on document analyses, ethnographic immersion at industry and academic conferences, and semi-structured interviews with policymakers, regulators, and patient organisations. Thus, it provides insights into how different actors currently frame the quandary of high orphan drug prices and proposed solutions to improve access that are being put forward.
Workstream 3: Patient Groups and New Models of Drug Innovation

This workstream sets out to:

  1. Explore the emergence of patient engagement in drug development. The project will undertake detailed case studies of patient organisation involvement in different forms of collaborative orphan drug development including targeted repeat treatment and novel ‘one-off’ gene therapies.
  2. Review initiatives to support drug repurposing. This will focus on patient led activities in this area and the emerging policy framework being developed to support this novel strategy.

Alongside the three workstreams, our team work on several related side projects:  

Patient access of orphan drugs in the UK - from patients’ perspectives

Lead: Jin Ding
Co-investigator(s): Matthew Hanchard | Eva Hilberg | Paul Martin
Funder: University of Sheffield (internal Research England monies)

Since the enactment of orphan drug legislation in the EU in 2000 up to 2020, the number of approved orphan drugs (medicines used to treat rare diseases) in the EU was ~33% of those approved the USA. This gap between the EU and USA has increased rapidly since 2010, in part because unlike the USA, in the EU orphan drugs are assessed on pricing and reimbursement value before the drug is made available to patients. Furthermore, only a third of EU authorised orphan drugs are recommended by NICE (the national medical regulatory body in the UK). Thus, the medical needs of UK rare disease patients are potentially underserved compared to both the USA and EU. Previous studies on orphan drug accessibility have investigated market access and reimbursement, but not from the patients’ perspective. Our project places an emphasis on participation, by involving patients as active and equal participants in the formulation of research questions and as external advisors on policy recommendations. Thus, it provides an alternative to traditional research approaches.

Through an online sample survey, semi-structured interviews, a horizon0scannig workshop, and discussion with relevant actors during ethnographic immersion at relevant conferences (conducted as part of the larger Orphan drugs project), this project: (1) identifies rare disease patients without treatments in the UK; (2) generates empirical findings and social theory on their experiences, needs, and preferences; and (3) provides policy recommendations on how to address the regulatory roadblocks that impair rare disease patients' access to relevant treatment. 

Sociotechnical imaginaries of orphan drug access in the USA

Lead: Matthew Hanchard
Co-investigator(s): Paul Martin
Funder: Funded as part of main 'Orphan drugs: high prices, access to medicines and the transformation of biopharmaceutical innovation' project 

Patients and payers across the USA paid 2.56 times more for the same prescription medicines in 2018 than their counterparts in comparable countries, with list prices increasing far faster than inflation. Critical health economists hold that high drug prices stem from excessive profiteering by pharmaceutical manufacturers, especially for rare disease treatments with orphan drug designation. Industry-sympathetic commentators attribute the heightened prices of orphan drugs with the increased outlay costs for developing innovative new treatments for such small potential markets. As these debates over the economics of orphan drugs pricing continues, their spiralling costs leave patients in the USA unable or unwilling to access relevant medications. In addition, because approximately 60% of rare disease patients in the USA are aged 18 or below, there are a broader set of social concerns too. For example, where patients/parents rely on private work-based health insurance, the choice of job and home become restricted. Meanwhile, a lack of clarity and uniformity across different insurers’ assessment/evaluation frameworks can place great emotional strain on patients and/or parents/primary caregivers, with time and energy costs spent gaining access to relevant treatments often left unmeasured. Yet to date there has been very little social science research on rare disease patients’ practices and/or experiences of navigating access and coverage for relevant treatments, or the broader impact it has on their everyday lives. 

Through ethnographic immersion at conferences and semi-structured interviews with patients and patient organisation representatives, this project address questions about: (1) How rare disease patients, parents, and/or primary caregivers navigate gaining access to treatment, in terms of coverage (i.e. reimbursement, co-payment, insurer, and/or via personal expense)(2) How their experience of doing so has changed over time; (3) and what impact the process of obtaining access to treatment has on patients' everyday lives. 

Where the project examines how rare disease patients’ negotiate access to relevant treatments, it does so amidst a broad-reaching set of national policy changes in the run up to the US presidential election - with both major political parties holding healthcare pledges as key aspects of their campaign. As such, the project addresses a second set of questions about: (1) how rare disease patients’ negotiating access to relevant treatment relates to broader socio-technical imaginaries and understandings of the US healthcare system. In particular, it examines patients’ attribution of responsibility, i.e. what or whom do patients feel are at base, the cause for any barriers to access encountered. 

Overall, the project develops social theory about rare disease patients' experiences of gaining access to relevant treatments in the USA, the sociotechnical configurations involved (i.e. processes, policies, and encountered), and broader understanding of how both relate to national science and healthcare policy.

The Social LIves of Patient Stories (SLoPS)

Lead: Eva Hilberg
Co-investigator(s): Paul Martin
Funder: Funded as part of main 'Orphan drugs: high prices, access to medicines and the transformation of biopharmaceutical innovation' project 

Patients’ stories are more than anecdotal evidence, and they travel in often unexpected ways. This project traces the telling and the sharing of stories as an engagement of a different quality to statistical information, and seeks to reveal their affective potential in different instances of patient engagement in the field of rare disease. Here, we rely on the notion of ‘stories’ to conceptualise the expert labour that goes into defining, translating, and representing rare disease in a way that links across different sites from research and innovation, to eventual authorisation and the marketing of orphan drugs. The central question of the project focuses on the work that stories do in the space of rare disease, and how they can act as a source of complex interactions in and around patient participation. We argue that the notion of ‘stories’ can connect different elements of a ‘patient journey’ in a new and productive way, especially also by going beyond the immediate act of telling of the stories in different venues. This connection shows that individualised stories can also have a structuring, disciplining effect on interactions, creating for instance a model of a ‘good’ rare disease patient within individualised care practices, written into policy expectations, and influencing the very definition of a particular rare condition. Tracing these stories through decision-making processes concerning orphan drugs allows for reflection on the transcendental performative and affective elements contained in these interactions, and also on the potential limits of these performances in a very closely circumscribed and heavily regulated arena.

Drawing on a Social Lives methodology and analysis of in-depth interviews with expert patients, patient representatives, regulators and other stakeholders involved in the sharing of patient stories, the project: (1) highlights the different places and contexts in which patients' stories become relevant, showing how a 'story' can travel from one to other even without the original source; (2) and shows how sharing of 'stories' and experiences as an act of participation in evidence generation and healthcare governance; (3) whilst re-conceptualising these contributions as an important yet undervalued part of the role of expert patients within the field of rare disease.

A ‘Mixed Economy’ of Innovation? Drug Development for Rare Diseases.

Led by Andy Bartlett
Co-investigator(s): Paul Martin
Funder: Funded as part of main 'Orphan drugs: high prices, access to medicines and the transformation of biopharmaceutical innovation' project 

The rapid growth of expensive “orphan” drugs for the treatment of rare diseases, driven by novel business models in the biopharmaceutical industry, poses a series of major challenges for access to healthcare and has become the subject of a high-profile controversy and policy debate over how they should be regulated and how patient access should be facilitated. The barriers to funding of, research on, and access to orphan drugs varies between countries, with different models of health care and regulatory jurisdictions.

Through a series of qualitative case studies and semi-structured interviews with ‘stakeholders’ involved in drug development, this sub-project describes the emergence of new forms of pharmaceutical inovation not based on the traditional pharmaceutical industry, with a focus on the UK context. In particular, the research examines how patients and patient organisations are becoming involved within drug development pipelines. It also reviews initiatives to support patient-led innovation, where patients and patient groups act as funders, participants, actors involved with research design, and as collaborators in full, i.e. in SPINs (Social Pharmaceutical INnovations).

Funding Information

The research is funded by the Wellcome Trust for five years (2020-2025) under grant reference 219875/Z/19/Z. For the purpose of open access, all outputs will apply a CC BY public copyright licence to any author accepted manuscripts.

Contact details:

Twitter: @orphanisation

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