#apaperaday: The Dutch Dystrophinopathy Database: A National Registry with Standardized Patient and Clinician Reported Real-World Data
In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: The Dutch Dystrophinopathy Database: A National Registry with Standardized Patient and Clinician Reported Real-World Data
Today’s pick is the Duchenne Center Netherlands and collaborators paper on the Dutch dystrophinopathy database by van de Velde et al in @journal_nd. The database collects high quality data in a prospective manner. DOI: 10.3233/JND-240061.
Dystrophinopathies can lead to Duchenne and Becker, and female dystrophinopathy. Duchenne has the most severe trajectory but with good care, patients now live longer. Furthermore, trials to assess efficacy of potential treatments are now happening.
A challenge is that treatments aim to slow down disease progression, and that progression is relatively slow and varies between patients. This makes trial design difficult and makes reimbursement difficult as well (how to robustly show patients benefit?).
Collecting quality real-world evidence beyond clinical trials is important for this. Clinical trials have placebo groups that provide high-quality data, but these are generally short-term. Natural history studies have difficulty recruiting patients.
Authors present a way to collect prospective data on milestones and function longitudinally for Dutch patients that are registered. The first database was started in 2008, but the focus here is on the latest iteration, which has online functions and a governance structure.
It collects both patient self-reports and clinician reports. Consent can be given online at different levels: 1. Only basic information (name and diagnosis), 2. Basic disease milestone information, 3. Clinical visit data included, and 4 and 5 for data-sharing purposes.
Patients can opt to share data with non-commercial (level 4) and commercial (level 5) partners. Note that this is detailed individual data sharing, not aggregated anonymized data sharing.
The database is GDPR-compliant, and there is a governance structure with representation from academic centers and patient organizations involved. Furthermore, the Duchenne Centrum has an advisory board, which also advises on the database.
Currently, there are 742 patients registered in the database (as of 2023): 524 Duchenne (169 who have passed away), 174 Becker (39 who have passed away), and 44 female carriers. Duchenne and Becker patients died on average at age 25.8 and 49.5 years.
Note that this is not the same as life expectancy, as there are also older patients in the database who are still alive. Median age: Duchenne patients 21 years, Becker patients 38 years, and female carriers 47 years. A genetic diagnosis was available for 89% of patients.
The distribution of mutation types is similar to what is reported globally. Notably, all Becker patients with deletions had in-frame deletions. For 94% of individuals, yearly milestone questionnaires are filled out; 90% and 61% allow sharing non-commercially and commercially.
73% of Duchenne patients and 3% of Becker patients use steroids, mostly on an intermittent regime (traditional in the Netherlands). Notably, 4 Duchenne patients are on daily vamorolone (not yet commercially available in the Netherlands, so these patients participated in the trial).
76% of Duchenne and 10% of Becker patients are non-ambulant. So far, aggregated data has been shared to inform 9 commercial trials, 5 investigator-initiated studies, inform payers about conditional reimbursement of ataluren, and data has been shared for TREAT-NMD inquiries.
Patients are kept up to date with regular newsletters. Authors discuss that based on the incidence of Duchenne, an expected 500 patients are alive in the Netherlands, meaning 70% are in the database. However, the estimation may not be correct.
On one hand, the incidence may go down due to counseling, while on the other hand, patients now live longer. Only a very small number of female carriers is registered in the database. Authors discuss this is mainly because there has been no active recruitment (yet).
Functional data captured by trained physiotherapists is added from annual visits. This means the data is currently only available for patients visiting the 3 academic centers that are part of Duchenne Centrum and not the other academic centers.
It is possible that adults with Duchenne are missed, as care can be coordinated by respiratory centers. Authors discuss that so far, no commercial request for individual data has been made, and they stress the importance of ontology (using defined terms for interoperability).
The database does not capture patient-reported outcomes, but Duchenne Parent Project has built the Duchenne Data Platform to capture this, and this platform can perform patient preference studies. Data exchange between this platform and the Dutch dystrophinopathy database is foreseen.
Finally, authors outline that sustaining the database is challenging and requires funding for a database manager and for running, maintaining, and updating the database. As the database captures longitudinally, the longer it will capture, the more valuable the data become.
