Patient-Powered Registry Boosts the Study of a Rare Disease

The development of patient registries and natural history studies for rare diseases are critical to understanding conditions and advancing research needed to discover and develop new therapies. Still, they can be hampered by the small patient populations, the geographic dispersity of where patients live, and the limited number of investigators and sites with access to these patients.

Patient-driven registries that rely on self-enrollment and self-reporting through a central online database can get around some of these obstacles, but the quality and amount of data collected on each patient in this way is often quite limited.

A new study from researchers at the Perelman School of Medicine at the University of Pennsylvania, published in the journal Cell Reports Medicine, suggests a hybrid approach that they used for a Castleman disease registry could provide more rapid enrollment of patients and increase the availability of data if applied to other conditions.

At RARE-X, we understand the importance of stakeholders in the rare disease community working together to build and share data to benefit all. The study showed how an innovative approach could accelerate how data can be gathered and leveraged to create actionable insights into a rare disease.

The European Medicines Agency in 2016, following its approval of Janssen Pharmaceuticals’ siltuximab for Castleman disease, required the company to create a Castleman disease patient registry. The company partnered with the Castleman Disease Collaborative Network and Penn Medicine to create the ACCELERATE registry.

Castleman disease (CD) describes heterogeneous inflammatory disorders that all share a similar lymph node appearance under the microscope. In CD patients, inflammatory cells become hyper-activated and cause flu-like symptoms, lymph node enlargement, and dysfunction of the bone marrow and vital organs including the liver and kidneys. The condition can lead to multiple organ system failures. Because there is significant overlap in symptoms with other conditions, such as lymphoma and autoimmune disorders, patients are often misdiagnosed.

The researchers created a registry with two arms. The first is a doctor-directed arm that was run from nine medical centers in six European countries. Participating physicians enrolled their consenting Castleman disease patients and arranged for patients’ clinical data and tissue samples to be added to a central database/repository. The second arm, a patient-powered arm, relied on a website and social media to attract participants. The registry team then contacted these patients’ doctors to verify that they met registry criteria and obtain clinical data and samples from qualified patients.

The researchers found that this patient-powered approach greatly boosted enrollment and the overall availability of data, compared to the traditional approach in which doctors at a limited number of designated sites enrolled their patients.

The patient-powered arm resulted in the enrollment of more than 250 patients by the end of 2019, compared to fewer than 100 in the doctor-directed arm. The registry team also gathered a median of 683 clinical, laboratory, and imaging data elements per patient in the patient-powered group, compared to a median of just 37 in the doctor-directed arm. The authors said because of the addition of the patient-powered arm, the registry was able to reach its five-year enrollment goal within two years.

“One of the greatest barriers to progress for rare diseases is the lack of high-quality, centralized data,” said study senior author David Fajgenbaum, an assistant professor of Translational Medicine and Human Genetics at the Perelman School of Medicine who directs the Center for Cytokine Storm Treatment & Laboratory and is a patient with Castleman disease.

Fajgenbaum, who is also a member of the RARE-X Patient Advocacy Advisory board, said the use of this “patient-powered” design to centralize high-quality data has been transformative for Castleman disease. He believes it “may serve as a model for research on thousands of other rare diseases that have no approved therapies.”

The approach allowed researchers to enroll a large cohort of patients from a variety of demographics quickly while enabling the collection of extensive longitudinal medical data of high accuracy from primary sources, obtaining biological materials, identifying clinically actionable insights about the natural history and treatment of Castleman disease, and supporting translational research efforts.

Beyond the direct benefits of the approach, the authors said clinical data and tissue samples gathered through the study have been leveraged in other studies that have led to improved treatment guidelines and new insights into Castleman disease including identifying potential targets for future treatments.