Rare Disease Research Partnership (RAinDRoP): a collaborative approach to identify research priorities for rare diseases in Ireland

Ethical considerations

This study received an exemption from full ethical review by the Office of Research Ethics at UCD. The Ethics Exemption Reference Number (REERN): LS-E-19-32-Somanadhan.

Phase I: Public consultation survey (PCS) on Research in Rare Diseases in Ireland

The process of research priority setting for rare diseases can be complex due to heterogeneity, and each rare disease impacts a small population. However, collectively many individuals are affected by these conditions. Therefore, identifying research prioritisation on each rare illness can be challenging in a single priority setting to identify, address and integrate the different perspectives from estimated 7000 rare diseases. Hence, the expert group collaboratively designed the initial framework of the survey from a life-course perspective rather than a disease-specific focus. The focus was on “What questions would you like to see answered by Rare Disease research?”. The expert group identified and co-designed list of priority areas for the survey through a review of existing literature and policies relevant to rare disease. Six key topics were chosen, and these are listed in Table 1.

The survey was officially launched on the National Rare Diseases Day on the 28^th of February 2019. A paper-based and online version using SurveyMonkey® was made available for four weeks (February to March 2019). Social media (Twitter, LinkedIn, Facebook) was utilised to share participant information leaflets (Extended data: File 1²²) and the online survey (Extended data: File 2²²). Content analysis²³ was used to identify the main themes that emerged from the survey respondents.

The survey asked respondents to think of questions they would like to see answered by rare disease research in relation to the six topics identified by the expert group. There was also an open field to capture any other questions respondents felt were important. The expert group met to examine the research issues and statements identified in the survey. Each expert group individually scored statements specific to each theme (Diagnosis, Day to Day Life, Treatment, Self-Management, Integrated and Palliative care, and other). MSExcel was used to gain frequencies and percentages, and any statements that had received a total score of above 50% were included in 10–12 researchable questions or statements per the theme. This was to reduce the number of questions/statements to a manageable level. From this ranking, a total of 29 themes or statements identified from the surveys were brought forward for discussion at the phase II workshop.

As the data was collected anonymously, the UCD Human Research Ethics Committee approved an ethics exemption for the conduct of the phased priority setting exercise. Participants did not receive any incentives for completing the survey. Participants indicated written consent to participate at the beginning of the survey.

Phase II: Research Prioritisation Workshop (RPW)

The phase II RPW took place at UCD. Prior to the event, a short animation²⁴ was produced to promote the event and shared on social media to raise awareness. Targeted invitations to attend the workshop were circulated by the Rare Disease Taskforce, Rare Disease Ireland, National Clinical Programme for Rare Diseases, and IPPOSI. There was a focus on creating a cross-section of individuals from service providers, service users, and the public perspective. Participants included those living with rare diseases, family, carers, clinicians, genetics/scientist, policymakers, research funding bodies, interdisciplinary healthcare and social care professionals, and researchers with a particular interest in rare diseases. Eligibility criteria were as follows: English speaking; 18 years and older; and able to provide informed consent to participate. There was a clear focus in this workshop to achieve gender balance, leading to a 50:50 split of men and women. It was also ensured that minority ethnic groups were included during the invitation.

The workshop sessions were chosen with a life course perspective in mind. The focus of these sessions predominantly centred around three themes distilled by the expert group from phase I (see below). On the morning of the workshop, each theme was introduced by expert speakers, so that participants had an opportunity to learn more about the three themes, ask questions and share knowledge and experiences (Extended data: File 3 contains the RPW agenda²²). The three thematic sessions based on the results of phase I are as follows:

Theme 1: Route to Diagnosis: This session focused on research questions about obtaining a timely diagnosis, methods of diagnosis, as a basis for bespoke treatment options. Aside from basic genetic research challenges, the session also focused on how to communicate diagnosis and treatment options to patients and their families.

Theme 2: Living with and Caring for Rare Diseases (Experience/Quality of Life/Psycho-social needs): This session examined the patient experience of living with a rare disease journey rather than a disease-specific experience.

Theme 3: Integrated and Palliative Care: Providing integrated care pathways. The session aimed to identify integrated care challenges about rare diseases and areas for research.

The afternoon of the workshop focused on creative conversations in smaller interdisciplinary and heterogeneous groups. In-depth discussions following the prioritisation exercise were referred to as ‘RAinDRoP cafés’. Two ‘café hosts’ per session guided the groups through the process. Each group had approximately 40 minutes to discuss a theme (either Route to Diagnosis; Living with Rare Disease; or Integrated and Palliative Care). Café agenda was as follows:

Figure 2. Example of a prioritisation board used in phase II.

Three prioritisation poster boards per session were available to determine similarities and differences of ratings between the three groups:

Board 1: People living with a rare disease (PwRDs) (including family members, carers, patient advocates, advocacy groups).

Board 2: Health Care Practitioners (HCPs), including all clinical policymakers.

Board 3: Academic, including researchers, academic policymakers, research managers

Participants were then given colour-coded stickers to assign a level of importance, and feasibility to each subtheme. To further clarify their decision-making and encourage active participation, each participant was given play money and asked to invest it as they saw fit – to put their money where their mouth is! However, we only considered their score for importance when generating the top priorities due to indifference approach across three workshops.

There was a total of 28 research themes or statements identified from the at the phase II prioritisation workshop. We identified top 10 research priorities that can inform the direction of rare disease research over the next seven years. However, we noticed from the percentage scale from the respondents from the three workshop (n=42) top priorities list were scored almost identical. The expert group agreed to create a list of 15 priorities instead of 10 and that should also be sent out in a public validation survey.

Phase III: Prioritisation Ranking Survey (PRS)

The top 15 research priorities defined during phase II were opened to the broader public for ranking by priority. There was no formal target sample size set for this survey. The ranking survey was also constructed with SurveyMonkey ® (Extended data: File 4²²). The PRS link was distributed by email and the survey was also available in paper format if participants preferred. The RAinDRoP expert group members and partners were asked to promote the survey to stakeholders via email, relevant meetings, social media, web sites, and any other opportunities that arose. A social media promotion plan was developed, similar to phase I, and there were no incentives offered for return of the survey. Respondents were asked to rank the top 15 research priority areas in order of importance. All respondents’ votes were considered equally valuable, and no weighting system was applied. Based on respondent rankings, we identified which of the top 15 rare disease research priorities were the most important. The survey was live for four weeks between May 2019 to June 2019.

Phase I: PCS

In total, there were 240 respondents to the survey. However, a total of 144 survey participants skipped their answers to describe their category. In total, 96 survey participants provided information on their background: 32% (n=31) self-identified as a person living with a rare disease(s); 32% (n=31) self-identified as health and social care professionals (e.g. doctors, nurses, consultants, researchers, managers); 19% (n=18) self-identified as a friend or family member of a person living with a rare disease; 11% (n=10) self-identified as carers of a person living with a rare disease; and 6% (n=5) indicated 'other' (including academic researchers). A total of 1015 statements were submitted through the survey, which reflected issues and shared challenges in rare diseases (Underlying data: File 1²²; Figure 3). Most research questions proposed by participants were related to ‘diagnosis’, e.g. “What is the best way to tell someone about the diagnosis?”; followed by ‘day-to-day life’ with rare disease, e.g. “How do rare diseases affect family life?”, and ‘treatment’, e.g. “How often do GPs or consultants put patients with a rare disease forward for clinical trials?". Initial grouping of questions into themes by the expert group are available in Underlying data: File 2²².

Figure 3. Survey responses (n=1015) identifying shared challenges in rare diseases by topic.

Phase II: RPW

Sixty-two (n=62) people participated in the event. These included living with rare diseases (n=15), family (n=10), carers (n=10), clinicians (n=10), genetics/scientist (n=5), policymakers (n=5), research funding bodies (n=2), interdisciplinary healthcare and social care professionals (n=15), and researchers with a special interest in rare diseases (n=10). Of the 62 participants, 42 took part in the RAinDRoP café portion of the day. We assigned them to three cafés (see Table 2). Each group contained a cross-section of health care professionals (HCPs), people living with a rare disease (PwRD), including family members, carers, patient advocates and advocacy groups, and others, including academics, researchers, academic policymakers and research managers.

Each participant was given sticker sets and play money (as described in the Methods). Participants were then asked to assign a level of importance and feasibility to each subtheme using the colour coded stickers. To further clarify their decision-making, each participant was asked to invest the play money as they saw fit – to put their money where their mouth is! Data was sorted by % of high priorities, and then % of euro investment. Applied heat mapping to show which themes are more dominant within the high priority group are available as Underlying data: File3²².

The RPW identified the top subthemes from each café within each main theme by importance. The top priority refers to the number (count) of “high priority” stickers. Each Cafe distributed stickers in a variety of three colours (red, yellow and blue). In Cafes 2 & 3 red stickers were used to denote “high” priority and in Café 1 blue stickers were used to denote “high priority”- the colours are nominal, we refer to them as high, medium or low priority stickers.

Café 3 (Integrated and Palliative Care) had two subthemes that were equally ranked in 1^st, 2^nd and 7^th, 8^th position. ‘Data sharing and integration’ and ‘co-designing services’ ranked evenly as high importance (24 high importance stickers each) but euro investment was €945 for data sharing and €365 for co-designing services (Table 3).

The RPW also revealed differences in prioritisation between Health Care Professionals (HCPs), People living with Rare Diseases (PwRDs) and others. The two priorities equally identified by these three groups were ‘co-designing services’ and ‘data sharing and integration’. PwRDs scored high importance score (9), and HCPs scored (7) for the theme ‘support at the time of diagnosis’ compared to others, and they scored (3). PwRDs identified the ‘best way to deliver diagnosis’ as their top research priority. They scored it 10 while respondents of the ‘others’ category assigned a score of 0 and HCPs gave a rating of 3. ‘Patient voice’ as part of research was highly prioritised by the PwRD (9), and it is worth noticing that this was HCPs least prioritised theme with a score = 1. The different views expressed in the scoring illustrate the importance to including all stakeholders in the research prioritisation process. Table 4 highlighted overall scoring from the RPW and Underlying data: File 4²² highlights priority ratings in terms of importance by all café groups in phase II.

Phase III: Prioritisation Ranking Survey (PRS)

Following the Priority Setting workshop, the team decided to extend the ranking of priorities to the wider public using an online survey. All topics from the research prioritisation workshop were included, and respondents were asked to rank these areas in order of importance. From this, a final set of research priorities were identified to inform the future direction of rare disease research. There were 75 total responses to the PRS. However, 27 survey participants did not complete the demographic section. A total of 48 survey participants described their categories: 67% were from the Leinster province; 30% (n=14) self-reported as a friend or family member of someone with a rare disease, whereas 19% (n=9) self-reported as a PwRDs. Underlying data: File 5²² provides priorities ranked in the first position by respondents during the PRS. Of the 15 topics for ranking, ‘support at the time of diagnosis’ ranked the highest with 23% (n=10) of respondents identifying this as a top priority area. ‘Diagnostic testing for rare disease’ and ‘education and training’ also ranked highly at 14% (n=6) each. Research into ‘how best to deliver a rare disease diagnosis’ was not identified as a priority by any of the survey respondents. It may be the case that respondents felt this was already captured by the theme ‘support at the time of diagnosis’. Table 5 highlighted Top 15 Rare Disease research related themes from phase III PRS. Table 6 contains the top 15 rare disease research related priority themes in full.

Limitations

The research priority setting exercise itself has cleared several key limitations. It is important to note that the number of research priorities identified for rare disease is not just focused on a specific disease category. However, the priorities are broadly related to shared challenges of Rare Diseases from a life-course perspective.

Participants across all three phases are not necessarily representative for all stakeholder groups nor for the entire rare disease community in Ireland. Many individuals and families living with rare diseases may not have been able to participate in this exercise. Similarly, from the health and social care field, advocates or academic experts may have been missed. Despite various endeavours to make the workshop itself as accessible and inclusive as possible, it may still have excluded individuals who could not attend on the day.

In the prioritisation process, the focus on research may have been lost for some participants. This became evident in some of the survey responses and at the workshop discussions where distinctions were blurred between advocacy, health and social care support and research. Finally, we made efforts to reflect the differences in perspective from various stakeholders in the final phase as a public ranking to offer the opportunity to respond to this consultation process We cannot rule out a bias towards one or other respondent group as we did not proportionally weigh responses. On a special note, the priority of palliative care at home was integrated as part of phase III community-based services, not as a stand-alone research priority need. The process of research priority setting was complex due to multiple engagement phases, however the use of participatory approach underpinned by PPI principles enabled us to identify, address and integrate the diverse stakeholders values and perspectives³³ throughout the process.

Despite these caveats, the research prioritisation exercise was the first multi-stakeholder participatory approach focused on a broadened scope of rare diseases research in Ireland. There is a need for an ongoing engagement with the RAinDRoP expert group to establish plans for translation of the research priorities into actual research via policies and funding³⁴. Also, to create more patient and public awareness about European wide rare diseases research potential where patients and their families could be part of the research process, for example, ERN, EJP etc.^12,31. Findings from the prioritisation exercise will inform future collaborative research programmes, networking opportunities, joint grants and research engagement events.

Since there is a significant variation in the use of research priority-setting methodology worldwide, there is no gold standard or best practice for evaluating the process of research priority setting³⁵. For this research priority setting exercise we didn’t follow any checklist as part of the project design and engagement process; however, we came across REPRISE checklist and guidelines³³ and tried to refer this guide to facilitate comprehensive and transparent reporting of health research priority-setting exercises.

Implications for policy

Public support of research lends authenticity to research advocacy that it would otherwise be impossible to achieve. The combined public/academic/clinician approach to strategy is more relevant and compelling. Collaborative tools and partnership allowed ethical data sharing for and with patients, and along with co-designing interventions, this will aim at improving patient-reported outcomes³⁶. This activity did not focus on a specific disease but the shared challenges of rare disease. Through the inclusion of interdisciplinary researchers, clinicians and stakeholders, this workshop facilitated and fostered knowledge exchange between those working towards an improved quality of life for people living with a rare disease. Finally, this enabled setting up research priorities based on patients living with rare diseases (rather than their diagnosis specific), which can eventually feed into the emerging policy framework relating to the research session in the Irish Rare Disease National Plan², and rare disease plans and strategies in European member states and the World Health Organization.

Implications for practice

The RAinDRoP research prioritisation activity ensures transforming Irish health and educational systems to increase rare diseases awareness. This type of engagement utilising the PPI approach builds trust between research institutions and society. Involving patients and public in the RAinDRoP project has been demonstrated that their involvement in the research process helped us to identity paucity of evidence currently available to address the experience of living with a rare disease. This form of funding supports engagement to strengthen partnership with HRB and other key stakeholders within the rare disease community, academia, patient, clinicians and public, and also increases responsiveness to societal needs through patient and public engagement.

Ethics approval and consent to participate

All participants received a comprehensive information sheet that outlined the nature and purpose of each survey, along with issues related to consent, confidentiality, voluntary participation and the rights of withdrawal from the survey.

We obtained an exemption from the full ethics review by the University College Dublin Research Ethics Committee (LS-E-19-32-Somanadhan).

Underlying data

Figshare: RAinDRoP Data Set, https://doi.org/10.6084/m9.figshare.11984424.v5²².

This project contains the following underlying data (available in one PDF document):

Extended data

Figshare: RAinDRoP Data Set, https://doi.org/10.6084/m9.figshare.11984424.v5²².

This project contains the following extended data (available in one PDF document):

Data available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).