Patient pathways for rare diseases in Europe: ataxia as an example

The ataxias are a heterogeneous group of chronic progressive neurological disorders, characterized by lack of coordination, difficulty in walking, associated with difficulties in speech, ability to swallow, eye movements, and other symptoms [1]. Gait and balance problems often progress to the point at which patient’s become wheelchair-bound, and the level of disability progresses at the cost of functional independence [2]. Epidemiological studies have estimated an overall ataxia occurrence rate of 26/100,000 in children, and for hereditary cerebellar ataxia an occurrence rate of 2.7–3.3/100,000 [3]. Friedreich’s ataxia, the most common inherited ataxia, has an estimated prevalence of 3.4 cases per 100,000 individuals [4]. Diagnosis is generally a long process because of the rarity and complexity of the different ataxias. Although there are no disease modifying treatments for the majority of progressive ataxias, there are many aspects of the conditions that are treatable, therefore highlighting the importance of guidelines to improve diagnosis and management of the ataxias and associated symptoms [5‐7]. The guidelines are aimed at healthcare professionals (HCP) in primary and secondary care (such as general practitioners (GP), general neurologists, clinical geneticists, physiotherapists, speech and language therapists (SLT), occupational therapists (OT)) who provide care for individuals with progressive ataxia and their families [6, 8]. Early intervention in both the diagnosis and management of patients with the ataxia is critical in working towards maintaining functional ability and therefore independence. Specialist ataxia centres (SAC) can provide the necessary clinical expertise and coordination of care and therefore address the specific needs of ataxia patients [9].

This ataxia study aims to examine health gains resulting from specialist healthcare interventions in comparison with non-specialised ones and converge data evidence to policy recommendations on how to improve the care pathway [10]. The management of orphan diseases is increasingly debated within the disease specific networks (European reference networks) as recommended by the EU policy on rare diseases. This is facilitated by the implementation of reference centres or centres of expertise at country level, which are part of the network. The focus of this study is on patient needs, early intervention, and coordination of care and exploring care pathways as a tool to better understand the care provision in different countries. The results have identified treatment gaps and therefore these data can translate into clinical practice guideline recommendations within health care processes, to improve outcomes for patients with rare diseases [11, 12]. The aim was to have a landscape of the rare diseases in different health systems in Europe that will lead to a white paper to improve policy for patients with rare diseases.

Our multinational survey aimed to expand the evidence base on the value of SACs in being able to deliver early coordinated interventions in both diagnosis and management of ataxia patients [13, 14]. This project explores the patient pathways of individuals with different progressive ataxias in a SAC compared with the care in non-specialist settings. To do so, we ran surveys in the UK, Germany, and Italy to collect information about patient’s pathways including diagnosis, treatment, and care of the ataxias. Here we presented a summary of converging data, from the patient survey, collected and analysed for the three selected countries. The aim of this project is to change policy, improving the care pathway for people living with ataxia across Europe.

This study allowed us to collect valuable data on rare neurological disorders in three countries directly from patients about their journeys towards reaching a diagnosis and receiving treatment and care for their ataxia. We have identified some patients’ needs and treatments gaps and now have a better understanding of the value of SACs in the patient care pathways at the European level. Important outcomes of this project are policy recommendations based on converging data collected.

The recruitment of participants was different between countries, namely in Germany and Italy recruitment of participants was not only via patient associations but was also done by clinicians at the SAC, and this was not the case in the UK where recruitment was only via the patient association. This is likely to have had an impact on the cohorts recruited and contributed to the sample population having a higher proportion of people attending SAC in Germany (68%) and Italy (75%) versus UK (36%). Another consequence of this recruitment might be the lower of proportion of patients receiving a specific diagnosis in the UK versus Germany and Italy. In terms of diagnosis, from the data collected we can’t make any conclusions about the role of SACs in reaching a specific diagnosis.

This study has given us a better understanding of the role of SACs in terms of management of the ataxias and care delivered to patients. Participants reported positive feedback on SAC services in terms of the level of understanding of the management of ataxia and the knowledge about treatments in the three countries and this was more positive than responses given to primary or secondary care services generally. Also, participants reported positive feedback for SACs in coordinating referrals to other HCPs in UK and Italy, and better communication with social care professionals in Italy only (Additional file 7: Table S7). The liaison between SAC and social workers is important to help people to get financial support and any other support towards their needs in living with ataxia. This will be particularly helpful when people need care at home, any adaptation their home, when they can no longer attend a SAC (Additional file 6: Table S6).

When participants gave their feedback about overall management of their symptoms and the level of care received being adapted to their needs, there was more positive feedback from people visiting SAC compared to people who have never been to SAC in the UK. This was not the case for Germany and Italy where the feedback was similar whether people went to a SAC or not (Table 5). However, when asked a direct question comparing the overall management of attending an SAC versus a standard of care clinic in Germany there was more positive feedback on the SAC. This was not the case in Italy. This could be due to the different roles SACs play in terms of management of the symptoms versus clinical research activities, with SACs in Italy and Germany focusing more on diagnosis and clinical trials and less on the management (communications from the healthcare professionals who were involved in the survey in these two different countries).

Up to date literature on the ataxia patient care pathway in Europe is scarce. The first step of the care pathway is reaching a specific diagnosis, which can be a challenge considering the rarity of some types of ataxias [15]. An easy access to new techniques for diagnosis including the whole genome sequencing [16] and functional assay is going to provide a higher rate of diagnosis reached and in a timely manner. We published a study on the resource use and burden of Friedreich’s ataxia in the UK and Germany [17], where it is clearly explained how the most common type of ataxia impacts the health and social care of people living with such condition, the caregivers and society. A similar study was done in Spain on cerebellar ataxia showing the costs and impact on patients’ quality of life [18]. There is growing evidence that making a coordinated multidisciplinary care a standard for patients with ataxia would improve the treatment, care, and long-term management of the condition, with the hope to decrease the burden of the disease [19, 20]. Specialist ataxia centres can play such role in delivering knowledge and expertise on ataxia, specific treatments, an adapted care, and coordinating further care needed locally, together with offering opportunities to take part in research studies. One role that Specialist Centres could have is to increase the education of healthcare professionals in primary care to tackle the lack of experience and expertise in the management of the ataxias [6, 8, 21]. One example of such an initiative to educate primary care professionals is a summary of the ataxia guidelines for the management of the ataxias for primary care produced in 2016 by Ataxia UK [22] and published on ‘Guidelines’, the online resource for primary care guidelines in the UK [23]. Another example is the series of educational webinars run by the European Reference Network for Rare Neurological Diseases (ERN-RND) where experts on ataxias have shared their knowledge and expertise on specific aspects of these disorders [24]. In addition, there’s a need to improve appropriate continuous neurorehabilitation and the effort of ERN-RND to promote telerehabilitation protocols for ataxias (Lavorgna L. et al. and Federico A., In preparation). On the other hand, ensuring a liaison between ataxia specialist services and professionals in social care would help to further support patients in their daily quality of life. Despite the efforts of many ataxia specialists in producing ataxia guidelines, such as the Ataxia Guidelines published by members of the UK SACs and others in collaboration with Ataxia UK that were also then endorsed by the ERN-RND, and the educational effort that specialists among the ERN and others are doing, each country also needs to embed the education of rare diseases in its own programme at medical and nursing school level and HCPs continual education training. Then there will be more knowledge and awareness among HCPs about ataxia.

Here we propose some recommendations based on data from our patient survey, on how to improve the care pathway (Table 6).

The ataxias are complex rare neurological disorders with no approved therapies, no disease modifying treatments for most of the patients. The survey has highlighted a pressing need to improve access to specialist ataxia centres as patients feel overall the management is better in that setting compared to primary or secondary settings. From our experience, the collaboration between SACs and ataxia charities has been crucial in their success and a tighter collaboration will facilitate the access to these centres for more patients. Finally, resources should be deployed to support the existing SACs, responding to the increase demand of patients referred to them, implementing telemedicine and to create new SACs where possible.

Three countries with existing adult Specialist Ataxia Centres (SAC) were identified for the purpose of this study: UK (two centres), Germany (nine centres), and Italy (eleven centres) (Additional file 9: Appendix 3). A survey was designed to gather patients’ data on experiences of diagnosis and management of their ataxias, whether they were a patient at a SAC or not.

The participation in the survey was open to all patients (or carers of patients, as proxy respondents) with ataxia, who were 16 years old or over. In each country patients' groups or organisations helped with the recruitment of participants. The survey in the UK was mainly disseminated online through the patient group’s channels (mailing list, website, magazine and on social media). Whereas in Germany and Italy it was disseminated via both patients’ groups channels and clinicians working at the SACs.

Ethical approval was obtained for this study in the UK (REC; reference 19/EE/0030). For the two other countries, as the survey was anonymised no ethical approval was needed.