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Research priorities for rare neurological diseases: a representative view of patient representatives and healthcare professionals from the European Reference Network for Rare Neurological Diseases
Orphanet Journal of Rare Diseases volume 16, Article number: 135 (2021)
Patient involvement in research increases the impact of research and the likelihood of adoption in clinical practice. A first step is to know which research themes are important for patients. We distributed a survey on research priorities to ERN-RND members, both patient representatives and healthcare professionals, asking them to prioritize five research themes for rare neurological diseases on a scale ranging from 1 (most important) to 5 (least important). A follow-up e-mail interview was conducted with patient representatives and professionals to assess potential reasons for differences in opinions between these two groups.
In total, 156 responses were analysed: 61 from professionals and 95 from patient representatives. They covered all ERN-RND disease groups and came from 20 different EU countries. Almost half of the respondents considered ‘Developing therapies and preventive strategies’ the most important research theme. In particular, patient representatives prioritized this theme more often than professionals, while professionals prioritized ‘Disease mechanisms and models’. Patient representatives indicated that therapies and prevention were of the utmost importance to them, because their lives are often heavily impacted by the disease and their main goal is to relief the burden of disease. Professionals indicated that investigating disease mechanisms will lead to more knowledge and is indispensable for finding new treatments.
Patients and professionals have different opinions on which research theme should have priority. A qualitative follow-up shows that they respect each others’ view points. Different stakeholders involved in research should be aware of their differences in research theme priority. Explaining these differences to each other leads to more understanding, and could improve patient engagement in research.
In Europe, a disease is classified as ‘rare’ if it has a prevalence of no more than five affected persons per ten thousand . However, the more than seven thousand known rare diseases have a considerable collective impact, with more than thirty million people estimated to be affected in the European Union alone . Because of the low prevalence of each distinct rare disease entity, the overall large total number of patients, and the heterogeneity of rare diseases, research on rare diseases requires concerted action at the European level, according to EURORDIS . Moreover, this research needs to be multidisciplinary, patient-centred, and sustainable on the long-term .
European Reference Networks (ERNs) have been established to meet these research requirements. ERNs were launched in 2017 as a result of the adoption of Directive 2011/24/EU . Currently, there are 24 such virtual networks, involving over three hundred hospitals in 25 EU countries. In addition to promoting research, their goal is to share the highly specialized knowledge needed to care for people affected by rare diseases, so that all patients in need can be reached. According to IRDiRC, ERNs provide a unique opportunity to improve standards of care and to increase access to diagnosis and treatment for patients .
The ERN for Rare Neurological Diseases (ERN-RND) focuses on the following disease groups:
Cerebellar Ataxias & Hereditary Spastic Paraplegias; Huntington’s disease and other Choreas; Frontotemporal dementia; Dystonia, (non-epileptic) Paroxysmal Disorders and Neurodegeneration with Brain Iron Accumulation; Atypical Parkinsonian Syndromes; and Leukodystrophies.
Research priorities for rare diseases
Research priorities for rare diseases are defined by the challenges that patients face, mainly to obtain an accurate and timely diagnosis and to have appropriate treatments available . Although the diagnosis of rare disease was revolutionized during the last decade by the introduction of next‐generation genomics and the concomitant discovery of many new disease-causing mutations in novel genes, many patients experience delays in receiving a correct diagnosis or do not obtain a diagnosis at all . As for therapies, despite some progress , no effective treatment is available for approximately 95% of rare diseases . Moreover, the yearly number of newly approved treatments for previously untreatable rare diseases remains low . Progress in rare disease diagnosis and treatment depends on a multitude of factors. Better insight into pathological mechanisms is essential to identify therapeutic targets, which may be shared by multiple diseases involving the same molecular pathway , as well as to allow the development of diagnostic tests and biomarkers.
The role of patients in setting research priorities
In its position paper , EURORDIS states the centrality of patients in research, who are its ultimate beneficiaries, supporting a patient-centred approach to research projects, the active participation of patients, and the sharing of results with patients . Others also pointed out that research efforts that are relevant to patients should be prioritized . Therefore, projects need to address relevant clinical questions and focus on patient-centred health outcomes . Moreover, involving patients increases the impact of research, as well as the likelihood that its outcomes will be adopted in clinical practice [9, 11]. In its position paper on patient involvement in neuroscience research, the European Federation of Neurological Associations (now European Academy of Neurology) sets as a priority that action should be taken ‘to ensure that the research community understands what is important to people with health conditions’ .
Aim of this survey
We collected the opinion of patient representatives and healthcare professionals within ERN-RND on the prioritization of research priorities for rare neurological diseases. For this purpose, we used the main research themes that the EU Joint Programming for Neurodegenerative Disease Research (JPND) has identified in its strategic research agenda . These research themes include: The origins of disease; Disease definitions and diagnosis; Developing therapies, preventive strategies and interventions; Disease mechanisms and models; Healthcare and social care.
One hundred fifty-six responses to the survey regarding research priorities were collected and analysed. The number of times a certain theme was prioritized as ‘most important’ was counted. Out of the 156 respondents, 74 prioritized ‘Developing therapies and preventive strategies’ as most important (47%, Table 1). The theme ‘Disease mechanisms and models’ was considered the least important, as only 12 respondents prioritized it (8%, Table 1).
We investigated differences in subgroups of respondents, namely patient representatives versus healthcare professionals, and advanced- versus early-stage professionals.
Patient representatives versus healthcare professionals
We compared the prioritizations of 95 patient representatives with those of 61 healthcare professionals. Sixty-one percent of the patient representatives prioritized ‘Developing therapies and preventive strategies’, while only 26% of the professionals made the same choice (Table 2 and Fig. 1), making this theme the second-most important for professionals. Thirty percent of the professionals ranked ‘The origins of disease’ as most important, while only 16% of patient representatives prioritized this theme (Table 2 and Fig. 1), which was ranked as second-most important by patient representatives.
In order to further investigate the differences between patient representatives and professionals, we focused on the two themes showing the largest difference in prioritization: ‘Developing therapies and preventive strategies’, prioritized by more than twice as many patient representatives compared to professionals, and ‘Disease mechanisms and models’, rated as most important by 4.7 times more professionals than patient representatives. We asked patient representatives who rated ‘Developing therapies and preventive strategies’ as most important and professionals who rated ‘Disease mechanisms and models’ as most important for their reasons for making this choice (Table 3).
Patient representatives answered that having control over their disease was essential to reduce the impact of the disease on their life (Table 3). Their view on the theme ‘Disease mechanisms and models’ were in general favourable as well, they agreed that such research is necessary and sympathized with the view of professionals that it is an important research theme, but pointed out the more direct impact of research into ‘Developing therapies and preventive strategies’ (Table 3).
Professionals thought it critical to do research on ‘Disease mechanisms and models’, because they see it as a crucial step on the way to ‘Developing therapies and preventive strategies’ as the ultimate goal (Table 4). When asked what they thought was the motivation for patient representatives to directly prioritise ‘Developing therapies and preventive strategies’, they responded that it is important for patients to be able to live their life as normal as their stage of the disease permits.
The two groups were asked what needs to be done so that professionals and patients understand each other’s needs in prioritising research themes. Both emphasized the importance of dialog. The professionals thought it important for patients to understand why research into disease mechanisms is crucial for the development of new therapies. Patients thought it important for professionals to understand the impact of the disease on their daily life.
Advanced- versus early-stage professionals
The prioritizations of professionals who had reached a career level corresponding to “attending physician” or “laboratory director” were compared to those of professionals who had not yet reached such career level. Forty-one ‘advanced’-stage professionals and 16 ‘early’-stage professionals responded. Four professionals who were experts other than clinicians or researchers were excluded. Both advanced-stage and early-stage professionals prioritized ‘The origins of disease’ as most important, but the groups differed in their prioritisation of the themes ‘Developing therapies and preventive strategies’, chosen by 29% of the advanced-stage professionals compared to 13% of the early-stage professionals (Table 5 and Fig. 2), and ‘Disease mechanisms and models’, prioritized by 25% of early-stage professionals compared to 7% of advanced-stage professionals.
We did not pursue a qualitative analysis of the opinions of these groups due to a rather low response rate when asked to participate in a follow-up interview.
Here, we present the results of a survey on research priorities of ERN-RND members, both patient representatives and healthcare professionals. Almost half of the respondents considered ‘Developing therapies and preventive strategies’ the most important research theme, more so than ‘The origins of disease’, ‘Disease definitions and diagnosis’, ‘Disease mechanisms and models’, or ‘Healthcare and social care’.
Patient representatives prioritized ‘Developing therapies and preventive strategies’ more often than professionals, while more professionals prioritized ‘Disease mechanisms and models’. An e-mail interview was conducted with patient representatives and professionals to assess potential reasons for this difference. Patient representatives indicated that therapies and prevention were of the utmost importance to them, because their lives are often heavily impacted by the disease and their main goal is to relief the burden of disease. Professionals indicated that investigating disease mechanisms will lead to more knowledge and is indispensable for finding new treatments.
Patient representatives and professionals both agreed that a dialogue between patients and professionals is essential to understand each other’s views and expectations. Patient representatives suggested several options for such interactions. The patients’ voice and opinions are brought in by European patient advocacy groups (ePAGs, managed by EURORDIS), which are active in all ERN-RND disease and working groups and are represented in all decision making bodies.
Within ERN-RND, a discussion on research priorities between patient representatives and professionals can be included in the Disease Groups. More in general, EURORDIS and EFNA (European Academy of Neurology), among others, provide training and information about different processes in medical research to enable patient representatives to understand how research is being performed. A good example of such training courses are Schools organised by the EURORDIS Open Academy (https://openacademy.eurordis.org/).
In addition, there were differences in prioritization between advanced-stage and early-stage professionals. The former more often chose ‘Developing treatments and preventive strategies’ as most important, while the latter deemed ‘Disease mechanisms and models’ to be more important. Due to the limited number of responses, we cannot give the reasons for this difference here. Possibly early-stage professionals, who perform ‘hands-on’ research, are more directly involved in studying disease mechanisms and developing models to learn as much as they can about the disease they are specializing in. On the other hand, advanced-stage professionals may feel more compelled to directly address patient needs.
In this study we did not assess differences in prioritization of research themes between clinical and laboratory-based professionals. Most professionals that replied to the survey indicated that they were clinicians (n = 34), while others identified themselves as both clinician and laboratory-based scientist (n = 22). Only one respondent indicated that they were solely laboratory-based, which made an analysis of differences between these two groups impossible.
Moreover, we did not assess differences in research theme prioritization between different countries. Of the 20 countries from which we received responses to our survey, only two countries (Germany and France) were more than 20 times represented. Moreover, the amount of patient representatives and professionals per country is very skewed. From some countries, we only received replies from patient representatives (Australia, Austria, Ireland, Malta, Norway, Sweden, and Switzerland), while from other countries only professionals replied to our survey (Bulgaria, Czech Republic, Hungary, Lithuania, Slovenia, and Spain).
There are various methods that can be used for priority setting of research themes, amongst others the health equity lens model, and the James Lind Alliance (JLA) priority setting partnership model. In these models, patient representatives are already involved in the formulation of the research themes. In the health equity lens model, a survey is then conducted among a different set of patients to prioritize these research themes , while the JLA process makes use of workshops with patients for the same purpose . The five JPND research priorities used in this analysis were developed in collaboration with various stakeholders, among which were patient representatives .
Patient engagement in research does not end with priority setting. There are multiple other ways in which patients can be involved in research, for example in the planning and conduct of research in particular on outcome measure that reflect real life . In the view of ERN-RND ePAGs, patients are increasingly involved in the preparation and development of protocols for clinical trials, as well as the results from trials being shared with patients. Moreover, there are several patient-initiated projects, of which HEALTHE-RND is an example. In this project a unique disease-specific quality of life instrument is developed, which is not symptom-based, but focuses on enabling the patient.
Patients representatives and professionals have different opinions on which research theme should have priority. A qualitative follow-up shows that they respect each others’ view points. Different stakeholders involved in research should be aware of their differences in research theme priority. Explaining these differences to each other leads to more understanding, and could improve patient engagement in research.
All information regarding the ERN-RND can be found on http://www.ern-rnd.eu.
The survey on research priorities was designed by the ERN-RND working group on research and registries, in particular Thomas Klockgether, G. Bernhard Landwehrmeyer, Massimo Pandolfo, and Holm Graessner. Initially, the survey was sent to all ERN-RND participants including patient representatives in January 2018 (Additional file 1). The question posed by the survey was to prioritize five research themes for rare neurological diseases on a scale with five levels, ranging from 1 (most important) to 5 (least important). In addition, the respondents were asked to indicate in which country they were based, what their main disease group focus was, and, if applicable, their profession and career position. The survey was conducted in English. Seventy-two individuals responded, including eight patient representatives and 64 healthcare professionals from a total of 16 countries, covering all ERN-RND disease groups (Additional file 2). Three answers from professionals were excluded from the analysis, because the respondents sent multiple replies to the survey, in which the prioritization of research themes was inconsequent.
In January 2020, additional patient representatives were approached and asked to fill out the survey, in order to improve the balance between responses from patient representatives and professionals. An additional item was included inquiring whether participants agreed to receive follow-up e-mails with regards to this survey. This additional survey was conducted in seven languages: English, German, French, Italian, Dutch, Polish, and Czech. Three hundred and two responses were received, but only 87 were included in the analysis after excluding answers from professionals (n = 5), and answers that used the same rank for multiple research themes (n = 201). The 87 analysed responses originated from 14 different countries. They covered five of the six disease groups of ERN-RND; Leukodystrophies were not included (Additional file 2). This brought the total number of responses analysed to 156, 61 from professionals and 95 from patient representatives. In total, responses from 20 different countries were included in the analysis (Additional file 2).
Twenty-two patient representatives and nine professionals were asked to comment on why they had prioritized a certain theme as most important. These subgroups were chosen based on differences in prioritization of the research themes, and asked for their reasons to prioritize a certain research team. Respondents were able to opt out of their participation at any time without having to provide a reason, and all responses were anonymised. We received answers from six patient representatives and four professionals.
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We would like to thank Alicia Brunelle, Eleonora Passeri, Marek Parowicz and Lubomír Mazouch for translating the survey to respectively French, Italian, Polish, and Czech.
This work is generated within the European Reference Network for Rare Neurological Diseases—Project ID No 739510.
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Thomas Klockgether receives/has received research support from the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF), the Bundesministerium für Gesundheit (BMG), the Robert Bosch Foundation, the European Union (EU), and the National Institutes of Health (NIH). He has received consulting fees from Biohaven, Roche and UBC. He has received a speaker honorarium from Novartis and Bayer. Massimo Pandolfo has received consulting fees from ApoPharma, BioMarin, Minoryx, and Voyager Therapeutics and royalties from Athena Diagnostics. He serves as Deputy Editor of Neurology: Genetics. Holm Graessner receives/has received research support from the Deutsche Forschungsgemeinschaft (DFG), the Bundesministerium für Bildung und Forschung (BMBF), the Bundesministerium für Gesundheit (BMG) and the European Union (EU). He has received consulting fees from Roche. He has received a speaker honorarium from Takeda.
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Cite this article
Post, A.E.M., Klockgether, T., Landwehrmeyer, G.B. et al. Research priorities for rare neurological diseases: a representative view of patient representatives and healthcare professionals from the European Reference Network for Rare Neurological Diseases. Orphanet J Rare Dis 16, 135 (2021). https://doi.org/10.1186/s13023-020-01641-z
- Rare diseases
- Patient involvement
- Research themes