Lessons Learned From Translational Research in Neuromuscular Diseases: Impact on Study Design, Outcome Measures and Managing Expectation

  • 4,940

    Total downloads

  • 19k

    Total views and downloads

Submit your idea

Select the journal/section where you want your idea to be submitted:

Submit your manuscript

About this Research Topic

Submission closed

Background

The last 15 years have seen an impressive development of new therapeutic approaches for neuromuscular diseases, in particular in Duchenne muscular dystrophy (DMD) and Spinal muscular atrophy (SMA), with a rapid increase in the number of interventional clinical trials and the first few drugs approved and integrated as part of the care for some patients. Conversely, the field has also seen several phase III clinical trials fail due to inability to show a significant improvement on the chosen outcome measures, regardless of promising pre-clinical efficacy data. In addition, some drugs taken to regulators for evaluation for approvals were refused due to lack of evidences in demonstrating a clinical significant impact on patient underlying condition and quality of life. These failures highlight the need for strong preclinical data, rigour in clinical trial designs, ensiling the chosen endpoints are of a sufficient quality and possess clinical meaning to the individuals involved. The regulatory approval process has also demonstrated variable assessment criteria from different regulators and payers, leading to unequal access to new treatments.

Therapeutic approaches targeting the underlying cause of the disease seem to be more attractive and promising, however open new study design and ethical issues when more than one approach might be available either in clinical trial or in the form of license drugs with no comparative/superiority data available. Moreover trials targeting the primary genetic defect could jeopardise recruitment in trials aiming to impact the downstream pathogenic effects. Will these trials still play a role in neuromuscular diseases? The translational research experience in neuromuscular diseases has highlighted the importance of strong natural history data to support study design, identification of robust outcome measures and anticipated modifiers which are expected to impact the course of the disease. These include pharmacological treatment, physical interventions including physiotherapy and orthotics, and genetic modifiers.

The need to carefully select trial populations to observe a significant drug effect within a reasonable trial timeframe has led to targeting a specific disease stage and population. This can create recruitment issues and impacts the feasibility of clinical trials which do not specifically target the underlying cause of the disease, especially for interventions aiming to address co-morbidities or complications associated with the disease. Strict inclusion criteria have also highlighted regulatory and ethical concerns about extrapolation of study results and accessibility of new treatment to a wider patient population.
With a growing number of clinical trials using new advanced therapies including gene therapy, expectations will need to be carefully managed. Questions emerge regarding subject selection, psychological impacts on patients refused access to these trials or confirmed ineligible to receive disease modifier drugs, and the demand of expensive treatments on national health systems and payers. Families feel that there is still inequality in accessing clinical trials and there are concerns around inequity in accessing treatment if and when they become available.
Lessons learned on all these aspects including considerations for study designs and outcome measure selection, impact of genotype and other external intervention on disease progression and drug effect monitoring, surrogates endpoint and data extrapolation, and ethical and health economy issues should be shared to inform future studies as well as drug development in other neuromuscular and non-neuromuscular rare diseases.

Keywords: muscular dystrophies, neuromuscular disease, study design, outcome measures, clinical trials

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Topic editors

Frequently asked questions

  • Frontiers' Research Topics are collaborative hubs built around an emerging theme.Defined, managed, and led by renowned researchers, they bring communities together around a shared area of interest to stimulate collaboration and innovation.

    Unlike section journals, which serve established specialty communities, Research Topics are pioneer hubs, responding to the evolving scientific landscape and catering to new communities.

  • The goal of Frontiers' publishing program is to empower research communities to actively steer the course of scientific publishing. Our program was implemented as a three-part unit with fixed field journals, flexible specialty sections, and dynamically emerging Research Topics, connecting communities of different sizes and maturity.

    Research Topics originate from the scientific community. Many of our Research Topics are suggested by existing editorial board members who have identified critical challenges or areas of interest in their field.

  • As an editor, Research Topics will help you build your journal, as well as your community, around emerging, cutting-edge research. As research trailblazers, Research Topics attract high-quality submissions from leading experts all over the world.

    A thriving Research Topic can potentially evolve into a new specialty section if there is sustained interest and a growing community around it.

  • Each Research Topic must be approved by the specialty chief editor, and it falls under the editorial oversight of our editorial boards, supported by our in-house research integrity team. The same standards and rigorous peer review processes apply to articles published as part of a Research Topic as for any other article we publish.

    In 2023, 80% of the Research Topics we published were edited or co-edited by our editorial board members, who are already familiar with their journal's scope, ethos, and publishing model. All other topics are guest edited by leaders in their field, each vetted and formally approved by the specialty chief editor.

  • Publishing your article within a Research Topic with other related articles increases its discoverability and visibility, which can lead to more views, downloads, and citations. Research Topics grow dynamically as more published articles are added, causing frequent revisiting, and further visibility.

    As Research Topics are multidisciplinary, they are cross-listed in several fields and section journals – increasing your reach even more and giving you the chance to expand your network and collaborate with researchers in different fields, all focusing on expanding knowledge around the same important topic.

    Our larger Research Topics are also converted into ebooks and receive social media promotion from our digital marketing team.

     

  • Frontiers offers multiple article types, but it will depend on the field and section journals in which the Research Topic will be featured. The available article types for a Research Topic will appear in the drop-down menu during the submission process.

    Check available article types here 

  • Yes, we would love to hear your ideas for a topic. Most of our Research Topics are community-led and suggested by researchers in the field. Our in-house editorial team will contact you to talk about your idea and whether you’d like to edit the topic. If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. 

    Suggest your topic here 

  • A team of guest editors (called topic editors) lead their Research Topic. This editorial team oversees the entire process, from the initial topic proposal to calls for participation, the peer review, and final publications.

    The team may also include topic coordinators, who help the topic editors send calls for participation, liaise with topic editors on abstracts, and support contributing authors. In some cases, they can also be assigned as reviewers.

  • As a topic editor (TE), you will take the lead on all editorial decisions for the Research Topic, starting with defining its scope. This allows you to curate research around a topic that interests you, bring together different perspectives from leading researchers across different fields and shape the future of your field. 

     

    You will choose your team of co-editors, curate a list of potential authors, send calls for participation and oversee the peer review process, accepting or recommending rejection for each manuscript submitted.

  • As a topic editor, you're supported at every stage by our in-house team. You will be assigned a single point of contact to help you on both editorial and technical matters. Your topic is managed through our user-friendly online platform, and the peer review process is supported by our industry-first AI review assistant (AIRA).

  • If you’re an early-stage researcher, we will offer you the opportunity to coordinate your topic, with the support of a senior researcher as the topic editor. This provides you with valuable editorial experience, improving your ability to critically evaluate research articles and enhancing your understanding of the quality standards and requirements for scientific publishing, as well as the opportunity to discover new research in your field, and expand your professional network.

  • Yes, certificates can be issued on request. We are happy to provide a certificate for your contribution to editing a successful Research Topic.

  • Research Topics thrive on collaboration and their multi-disciplinary approach around emerging, cutting-edge themes, attract leading researchers from all over the world.

  • As a topic editor, you can set the timeline for your Research Topic, and we will work with you at your pace. Typically, Research Topics are online and open for submissions within a few weeks and remain open for participation for 6 – 12 months. Individual articles within a Research Topic are published as soon as they are ready.

    Find out more about our Research Topics

  • Our fee support program ensures that all articles that pass peer review, including those published in Research Topics, can benefit from open access – regardless of the author's field or funding situation.

    Authors and institutions with insufficient funding can apply for a discount on their publishing fees. A fee support application form is available on our website.

  • In line with our mission to promote healthy lives on a healthy planet, we do not provide printed materials. All our articles and ebooks are available under a CC-BY license, so you can share and print copies.

     

Participating Journals

Impact

  • 19kTopic views
  • 13kArticle views
  • 4,940Article downloads
View impact