Recent years have seen increasing clinical research activities in spinal muscular
atrophy (SMA), involving patients, their families, clinicians, researchers, regulators
and industry [1–3]. This has led to unprecedented advancements in understanding of
genetic determinants of severity and prognosis, the natural history, outcome measures,
and most importantly first marketed therapies [4–8]. However, many patients with SMA
do not benefit yet from effective treatments or show limited clinical response or
impact on their quality of life.
A major barrier to carry out further clinical research is the relatively low incidence
and prevalence of SMA [9, 10], considered a Rare Disorder (RD) covered by Orphan Drug
Regulations in most jurisdictions. Many of the remaining challenges are not specific
to SMA, but common across different RDs, across research domains and are linked to
the unavailability of data of sufficient quality. Clinical trial in RDs considered
as pivotal frequently do not cover the entire disease spectrum such as severity or
age range. These gaps in knowledge lead to marketing approvals granted under the condition
for stringent and comprehensive collection of post marketing, real-life outcome data.
This is not only due to the scarcity of data, but also to the lack of options to reuse
data that does exist. This may include options to take advantage of existing natural
history data; and concerns related to the accuracy of the data collected. Therefore,
international organizations involved in RD research have endorsed mechanisms and standards
enabling data sharing [11–13], including the international charter of principles for
sharing bio-specimens and data and the FAIR principles for data (findable, accessible,
interoperable, reusable). Important issues to address are privacy protection issues,
lack of infrastructure for data sharing, lack of standards and interoperability, reluctance
to share unpublished data, lack of capacity to analyse large amounts of data, and
challenges of linking different datasets in different places. The benefits of sharing
data and samples in RDs are: overcoming the “rare disease problem” in clinical research,
eg cohort size, powering trials and finding confirmatory cases, reducing costs and
duplication of effort, facilitating validation of results and enabling engagement
with experts and the patient community.
A recent workshop with panellists from patient organizations, academia and industry
discussed the challenges and benefits of data sharing in SMA clinical research at
the international conference of SMA Europe in Krakow (full workshop report in the
supplementary material). The discussion brought several activities to light where
international collaboration, close interactions between different stakeholders and
data sharing, have contributed to the recent successes in SMA clinical research, including
the transnational collaboration of patient organizations in SMA Europe, multi-centric
studies into natural history and outcome measures, global trial readiness through
registries and biobanks (TREAT-NMD, 14), and commercially sponsored multinational
trials. Moreover, new opportunities and challenges in SMA research were identified,
that may benefit or have an impact on data sharing, including patient-reported outcome
measures, trials without placebo groups, real-world outcome and safety of marketed
products, and the changing legal environment in European data protection (GDPR, General
Data Protection Regulation).
The following statements were made during the workshop and were broadly agreed to
by the authors:
SMA patients, families and patient organizations want to play a critical role in SMA
research, not only through participation and dissemination, but through governance
and design of studies and outcome measures, as well as access and use of research
Data capture in SMA should wherever possible follow the IRDiRC-recognized “FAIR Guiding
Principles” in order to make the collected data Findable, Accessible, Interoperable
and Reusable and thus maximise their utility for research.
Disease-specific registries are recommended by regulatory agencies, supported by all
stakeholders, and favoured over product-specific registries to avoid fragmentation,
save resources and to allow meaningful analysis across both treated and untreated
Real-life (post-marketing) outcome data capture is warranted due to regulatory and
payer commitments in SMA, and requires a high degree of transnational collaboration
and standardization (eg data items, data capture, IT, monitoring, analysis) to ensure
reporting at the required detail, quality and speed.
Companies sponsoring clinical trials in SMA are encouraged to share their placebo
arm data through an agreed mechanism allowing access to the data by other investigators
both from the academic and the commercial sector, in order to limit or avoid placebo
groups in future clinical trials as recommended by the recent EMA workshop .
Data collections from natural history studies, clinical trials and patient registries
in SMA are precious resources that involve extensive effort and investment from academics,
pharmaceutical companies and most of all the patients themselves. Benefits derived
from these collections must be shared amongst contributing stakeholders and the principles
of equality of access, benefit sharing and return of results should at all times be
The GDPR in Europe coming into effect in May 2018 does not prevent data sharing in
clinical SMA research, but provides legislation that is less divergent amongst different
European member states than current frameworks.
Similar principles and recommendations might be applicable to other areas of SMA research,
such as standards of care, biomarkers and burden of illness, but were not covered
in the workshop. Similarly, data sharing in preclinical research – beyond the publication
in peer-reviewed scientific journals – is very pertinent and reviewed elsewhere.
This statement reflects the personal opinion of the authors, but cannot be seen as
binding to the organisations the authors are affiliated with. It aims to reflect and
summarize a multi-stakeholder discussion that took place at the SMA Europe conference
in Krakow in January 2018.
Click here for additional data file.