Survival and quality of life for patients affected by spinal muscular atrophy (SMA) are thought to have improved over the last decade due to changes in care. In addition, targeted treatments for SMA ...have been developed based on a better understanding of the molecular pathology. In 2016 and 2017, nusinersen was the first drug to be approved for treatment of all types of SMA in the United States and in Europe based on well-controlled clinical trials in a small subgroup of pediatric SMA patients. Systems are required to monitor treated and untreated SMA patients in a real-life environment to optimize treatment and care, and to provide outcome data to regulators, payers, and the SMA community.
Within SMArtCARE, we conduct a prospective, multicenter non-randomized registration and outcome study. SMArtCARE collects longitudinal data on all available SMA patients independent of their actual treatment regime as disease-specific SMA registry. For this purpose, we provide an online platform for SMA patients seen by health-care providers in Germany, Austria and Switzerland. All data are collected during routine patient visits. Items for data collection are aligned with the international consensus for SMA registries. Data analysis is carried out independent of commercial partners.
A prospective monitoring of all SMA patients will lead to a better understanding of the natural history of SMA and the influence of drug treatment. This is crucial to improve the care of SMA patients. Further, we will establish a network for neuromuscular centers to share experience with SMA patients and to promote research projects on SMA.
German Clinical Trials Register ("Deutsches Register klinischer Studien") DRKS00012699. Registered 09 August 2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012699 .
Estimation of incidence in rare diseases is often challenging due to unspecific and incomplete coding and recording systems. Patient- and health care provider-driven data collections are held with ...different organizations behind firewalls to protect the privacy of patients. They tend to be fragmented, incomplete and their aggregation leads to further inaccuracies, as the duplicated records cannot easily be identified. We here report about a novel approach to evaluate the incidences of Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) in Germany.
We performed a retrospective epidemiological study collecting data from patients with dystrophinopathies (DMD and Becker muscular dystrophy) and SMA born between 1995 and 2018. We invited all neuromuscular centers, genetic institutes and the patient registries for DMD and SMA in Germany to participate in the data collection. A novel web-based application for data entry was developed converting patient identifying information into a hash code. Duplicate entries were reliably allocated to the distinct patient.
We collected 5409 data entries in our web-based database representing 1955 distinct patients with dystrophinopathies and 1287 patients with SMA. 55.0% of distinct patients were found in one of the 3 data sources only, while 32.0% were found in 2, and 13.0% in all 3 data sources. The highest number of SMA patients was reported by genetic testing laboratories, while for DMD the highest number was reported by the clinical specialist centers. After the removal of duplicate records, the highest yearly incidence for DMD was calculated as 2.57:10,000 in 2001 and the highest incidence for SMA as 1.36:10,000 in 2014.
With our novel approach (compliant with data protection regulations), we were able to identify unique patient records and estimate the incidence of DMD and SMA in Germany combining and de-duplicating data from patient registries, genetic institutes, and clinical care centers. Although we combined three different data sources, an unknown number of patients might not have been reported by any of these sources. Therefore, our results reflect the minimal incidence of these diseases.
Observational studies have proven to be a valuable resource in medical research, especially when performed on a large scale. Recently, mobile device-based observational studies have been discovered ...by an increasing number of researchers as a promising new source of information. However, the development and deployment of app-based studies is not trivial and requires profound programming skills.
The aim of this project was to develop a modular online research platform that allows researchers to create medical studies for mobile devices without extensive programming skills.
The platform approach for a modular research platform consists of three major components. A Web-based platform forms the researchers' main workplace. This platform communicates via a shared database with a platform independent mobile app. Furthermore, a separate Web-based login platform for physicians and other health care professionals is outlined and completes the concept.
A prototype of the research platform has been developed and is currently in beta testing. Simple questionnaire studies can be created within minutes and published for testing purposes. Screenshots of an example study are provided, and the general working principle is displayed.
In this project, we have created a basis for a novel research platform. The necessity and implications of a modular approach were displayed and an outline for future development given. International researchers are invited and encouraged to participate in this ongoing project.
This study aims to describe the data structure and harmonisation process, explore data quality and define characteristics, treatment, and outcomes of patients across six federated antineutrophil ...cytoplasmic antibody-associated vasculitis (AAV) registries.
Through creation of the vasculitis-specific Findable, Accessible, Interoperable, Reusable, VASCulitis ontology, we harmonised the registries and enabled semantic interoperability. We assessed data quality across the domains of uniqueness, consistency, completeness and correctness. Aggregated data were retrieved using the semantic query language SPARQL Protocol and Resource Description Framework Query Language (SPARQL) and outcome rates were assessed through random effects meta-analysis.
A total of 5282 cases of AAV were identified. Uniqueness and data-type consistency were 100% across all assessed variables. Completeness and correctness varied from 49%-100% to 60%-100%, respectively. There were 2754 (52.1%) cases classified as granulomatosis with polyangiitis (GPA), 1580 (29.9%) as microscopic polyangiitis and 937 (17.7%) as eosinophilic GPA. The pattern of organ involvement included: lung in 3281 (65.1%), ear-nose-throat in 2860 (56.7%) and kidney in 2534 (50.2%). Intravenous cyclophosphamide was used as remission induction therapy in 982 (50.7%), rituximab in 505 (17.7%) and pulsed intravenous glucocorticoid use was highly variable (11%-91%). Overall mortality and incidence rates of end-stage kidney disease were 28.8 (95% CI 19.7 to 42.2) and 24.8 (95% CI 19.7 to 31.1) per 1000 patient-years, respectively.
In the largest reported AAV cohort-study, we federated patient registries using semantic web technologies and highlighted concerns about data quality. The comparison of patient characteristics, treatment and outcomes was hampered by heterogeneous recruitment settings.
Mobile health apps have great potential to support the self-management of chronic conditions such as allergic diseases, which constitute significant challenges in health care. However, the health app ...market is confusing for users, as it is vast, dynamic, and lacks scientific evidence regarding the effectiveness of the apps on offer. To our knowledge, no health app for pollen-related allergic rhinitis has been evaluated.
The aim of our study was to evaluate the Husteblume mobile phone health app, developed in Germany to facilitate the self-management of pollen-related allergic rhinitis.
We evaluated usability and changes in quality of life, health literacy, and self-efficacy for managing one's chronic disease. We conducted 2 online surveys of registered users of the app, 1 before and 1 after the 2017 pollen season, allowing for the analysis of both cross-sectional and longitudinal data in a field setting.
The sample comprised 661 app users at the first measurement point and 143 users at follow-up. The subgroup of study participants at follow-up rated the usability of the app as good or very good. There were no significant changes in patient-reported outcomes such as quality of life, health literacy, and self-efficacy between the 2 measurement points (P>.05). However, those reached at follow-up perceived subjective improvements due to the app: 55.9% (80/143) reported being subjectively better informed about their allergy, 27.3% (39/143) noted improved quality of life, 33.6% (48/143) reported subjectively better coping with their allergy, and 28.0% (40/143) felt better prepared for the consultation with their physician. Finally, 90.9% (130/143) users did not identify any adverse effects of the app.
Despite some methodological caveats, the results of the evaluation of the Husteblume app are encouraging for the subgroup using the app in the long term. However, further studies evaluating the effectiveness of the app are needed.
German Clinical Trials Register DRKS00011897; https://tinyurl.com/yxxrg9av.
The EURO-NMD Registry collects data from all neuromuscular patients seen at EURO-NMD's expert centres. In-kind contributions from three patient organisations have ensured that the registry is ...patient-centred, meaningful, and impactful. The consenting process covers other uses, such as research, cohort finding and trial readiness.
The registry has three-layered datasets, with European Commission-mandated data elements (EU-CDEs), a set of cross-neuromuscular data elements (NMD-CDEs) and a dataset of disease-specific data elements that function modularly (DS-DEs). The registry captures clinical, neuromuscular imaging, neuromuscular histopathology, biological and genetic data and patient-reported outcomes in a computer-interpretable format using selected ontologies and classifications. The EURO-NMD registry is connected to the EURO-NMD Registry Hub through an interoperability layer. The Hub provides an entry point to other neuromuscular registries that follow the FAIR data stewardship principles and enable GDPR-compliant information exchange. Four national or disease-specific patient registries are interoperable with the EURO-NMD Registry, allowing for federated analysis across these different resources.
Collectively, the Registry Hub brings together data that are currently siloed and fragmented to improve healthcare and advance research for neuromuscular diseases.
Rare diseases pose many research challenges specific to their scarcity. Advances in potential therapies have made it more important than ever to be able to adequately identify not only patients with ...particular genotypes (via patient registries) but also the medical professionals who provide care for them at particular specialist centres of expertise and who may be competent to participate in trials. Work within the neuromuscular field provides an example of how this may be achieved.
This paper describes the development of the TREAT-NMD Care and Trial Site Registry (CTSR), an initiative of an EU-funded Network of Excellence, and its utility in providing an infrastructure for clinical trial feasibility, recruitment, and other studies.
285 CTSR-registered centres, reporting 35,495 neuromuscular patients, are described alongside an analysis of their provision for DMD. Site characteristics vary by country: the average number of DMD patients seen per site in the United States (96) is more than in Germany (25), and paediatric/adult breakdown is also markedly distinct. Over 70% of sites have previous trial experience, with a majority including a Clinical Trials Unit. Most sites also have MLPA diagnostic capability and access to a range of medical specialists. However, in the three countries reporting most sites (US, the UK and Germany), few had access to all core DMD specialists internally. Over 60% of sites did not report any form of transition arrangement.
Registries of care and trial sites have significant utility for research into rare conditions such as neuromuscular diseases, demonstrated by the significant engagement by industry and other researchers with the CTSR. We suggest that this approach may be applicable to other fields needing to identify centres of expertise with the potential to carry out clinical research and engage in clinical trials. Such registries also lend themselves to the developing context of European Reference Networks (ERNs), which seek to build networks of centres of expertise which fit specific criteria, and which may themselves aid the sustainability of such registries. This is particularly the case given the utility of registries such as the CTSR in enabling networks of best-practice care centres.
Disease progression in patients with spinal muscular atrophy (SMA) has changed dramatically within the past years due to the approval of three different disease-modifying treatments. Nusinersen was ...the first drug to be approved for the treatment of SMA patients. Clinical trials provided data from infants with SMA type 1 and children with SMA type 2, but there is still insufficient evidence and only scarcely reported long-term experience for nusinersen treatment in ambulant patients. Here, we report data from the SMArtCARE registry of ambulant patients under nusinersen treatment with a follow-up period of up to 38 months.
SMArtCARE is a disease-specific registry in Germany, Austria and Switzerland. Data are collected as real-world data during routine patient visits. Our analysis included all patients under treatment with nusinersen able to walk independently before start of treatment with focus on changes in motor function.
Data from 231 ambulant patients were included in the analysis. During the observation period, 31 pediatric walkers (27.2%) and 31 adult walkers (26.5%) experienced a clinically meaningful improvement of≥30 m in the 6-Minute-Walk-Test. In contrast, only five adult walkers (7.7%) showed a decline in walking distance≥30 m, and two pediatric walkers (1.8%) lost the ability to walk unassisted under treatment with nusinersen. HFMSE and RULM scores improved in pediatric and remained stable in adult patients.
Our data demonstrate a positive effect of nusinersen treatment in most ambulant pediatric and adult SMA patients. We not only observed a stabilization of disease progression or lack of deterioration, but clinically meaningful improvements in walking distance.
Publication of comprehensive clinical care guidelines for Duchenne muscular dystrophy (DMD) in 2010 was a milestone for DMD patient management. Our CARE-NMD survey investigates the neuromuscular, ...medical, and psychosocial care of DMD patients in Europe, and compares it to the guidelines.
A cross-sectional survey of 1677 patients contacted via the TREAT-NMD patient registries was conducted using self-report questionnaires in seven European countries.
Survey respondents were 861 children and 201 adults. Data describe a European DMD population with mean age of 13.0 years (range 0.8-46.2) of whom 53% had lost ambulation (at 10.3 years of age, median). Corticosteroid medication raised the median age for ambulatory loss from 10.1 years in patients never medicated to 11.4 years in patients who received steroids (p < 0.0001). The majority of patients reported receiving care in line with guidelines, although we identified significant differences between countries and important shortcomings in prevention and treatment. Summarised, 35% of patients aged≥ nine years received no corticosteroid medication, 24% of all patients received no regular physiotherapy, echocardiograms were not performed regularly in 22% of patients, pulmonary function was not regularly assessed in 71% of non-ambulatory patients. Patients with regular follow-up by neuromuscular specialists were more likely to receive care according to guidelines, were better satisfied, and experienced shorter unplanned hospitalization periods.
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