How PROMOT’s Work Packages Are Coming Together
Rare disease research involves more than collecting clinical information or conducting laboratory analyses. It requires researchers with different areas of expertise to work toward a shared goal—connecting clinical knowledge, meaningful assessments, biological findings, patient perspectives, ethical considerations, and secure approaches to data analysis.
The PROMOT initiative was designed with this collaboration in mind. Its six work packages focus on distinct but closely connected areas of research. As the project progresses, these areas are increasingly coming together to support the development of a rare disease-oriented Master Observational Trial (MOT).
Building a shared understanding of clinical features
Work Package 1 is identifying and organizing the clinical features, or phenotypes, associated with the rare neuromuscular diseases included in PROMOT.
Evidence from literature reviews, clinical forms, existing terminologies, and expert input contributed to the development of the first version of the PROMOT Ontology. Published on BioPortal in August 2026, the ontology provides a structured way to represent clinical concepts and supports the development of a common data model for the project.
This work provides an important foundation for the other work packages. A shared terminology can help researchers describe clinical features consistently, connect information from different sources, and prepare data for future analyses.
Connecting clinical features with meaningful assessments
Work Package 2 is developing the prospective component of the MOT, including the selection and evaluation of outcome measures.
One area of work involves the Virtual Peg Insertion Test (VPIT) which uses digital technology to evaluate upper-limb movement. A feasibility study is underway in Barcelona involving children with congenital myasthenic syndromes and congenital myopathies. The study is examining how VPIT-derived metrics relate to conventional assessments and available clinical information.
Work Packages 1 and 2 will work together to connect relevant clinical phenotypes with assessment procedures, scales, and VPIT metrics.
This alignment will help ensure that the information collected through clinical and digital assessments can be interpreted consistently and incorporated into future versions of the PROMOT Ontology.
Linking clinical information with biological findings
Work Package 3 is investigating potential biological targets in oculopharyngeal muscular dystrophy (OPMD) through proteomic analysis.
More than 9,000 proteins have been measured in samples from participants with OPMD and controls. Preliminary analyses have identified proteins and biological pathways that warrant further investigation, including those related to muscle structure, inflammation, and extracellular matrix remodelling.
The next stage will involve validating selected candidate proteins and integrating the proteomic findings with clinical information such as muscle function, dysphagia, disease severity, and progression.
This connection between biological and clinical data is essential for understanding whether a laboratory finding may also be meaningful in the context of a person’s condition.
Embedding ethics and patient rights throughout the project
Work Package 4 examines the ethical, legal, and social questions associated with conducting an international observational study and using emerging technologies in health research.
Current areas of work include artificial intelligence, biomedical advances, the European Health Data Space, consent, and the return of significant or incidental research findings. These activities help PROMOT consider not only what may be technically possible, but also how research can be conducted responsibly and with appropriate attention to privacy, transparency, and participant rights.
This work will inform decisions across the project, including the development of study materials, approaches to data use, and communication with participants.
Preparing the natural history study
Work Package 5 is bringing several of these components together through the development of the PROMOT natural history study.
The team is refining the study protocol, visit schedule, assessment sequence, consent materials, and participant information. The proposed pilot visit will last approximately 90 minutes, beginning with adults before later expanding to children.
The study will draw on the clinical features identified through Work Package 1 and the assessment work conducted through Work Package 2.
Participant input will also be important for evaluating whether the study materials and procedures are clear, acceptable, and manageable.
Supporting secure analysis and meaningful communication
Work Package 6 focuses on learning and knowledge mobilization. This includes exploring federated learning—an approach that may allow researchers to analyze data held at different institutions without transferring all participant-level information to one central location.
In an initial proof of concept, the PROMOT team compared federated and centralized approaches using an OPMD dataset distributed across simulated sites.
Preliminary results were promising, and further testing will examine how differences in site size and patient populations may influence model performance.
Work Package 6 is also developing a platform to communicate research information and results to patients. Approximately 90 Canadian patients contributed to a survey about their preferences, and their responses will help shape the platform’s content and functions.
Moving forward as one initiative
Each PROMOT work package contributes specialized expertise, but their greatest value comes from their connections.
Clinical phenotypes can inform the selection and interpretation of assessments. Clinical and functional data can help researchers understand biological findings. Ethical and legal work can guide how data are collected, analyzed, and communicated. Natural history research can bring these elements together, while federated learning and patient-focused communication can support responsible data use and meaningful knowledge sharing.
As these activities become increasingly aligned, PROMOT is moving closer to an integrated research approach designed around the complexities of rare neuromuscular diseases and the needs of the people affected by them.
