Patient Data Registry Approach May Enhance Rare Disease Research

Researchers at the Perelman School of Medicine at the University of Pennsylvania have designed a new kind of patient data registry to advance rare disease research.

In a paper published in Cell Reports Medicine, the team describes an innovative patient data registry they developed for Castleman disease, a rare condition involving flu-like symptoms and sometimes life-threatening vital organ dysfunction.

The registry, called ACCELERATE, enables patients with Castleman disease can enroll directly. This patient-powered approach significantly increased enrollment and the availability of data compared to the traditional approach in which physicians at a few designated sites can enroll their patients.

As part of the new registry, researchers request and extract data from the full medical record for each patient who enrolls instead of relying on physicians or patients to enter data. This substantially increases the quantity of data included.

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

“Using this novel, patient-powered study design to centralize high-quality data through ACCELERATE has been transformative for Castleman disease tracking and clinical trial enrollment and may serve as a model for research on thousands of other rare diseases that have no approved therapies.”

In the US, rare diseases are defined as conditions affecting fewer than 200,000 people. Collectively, these diseases afflict nearly five percent of the human population. In most cases, they receive little attention from researchers because of the difficulties involved in enrolling enough patients, as well as collecting associated clinical samples and other relevant data.

Because of these gaps in research, just a small percentage of the conditions classified as rare diseases have specific approved treatments.

Castleman disease is diagnosed in only several thousand people each year in the US. Similar factors that have limited insights into other rare conditions have also hampered research on Castleman disease.

While a monoclonal antibody called siltuximab is approved to treat some forms of Castleman disease, this treatment is not administered to all patients who are likely to benefit and is effective in only a portion of patients.

After the approval of siltuximab in 2016, the European Medicines Agency (EMA) directed the treatment’s manufacturer, Janssen Pharmaceuticals, to establish a patient registry for Castleman disease. The company’s research and development company partnered with Penn Medicine to set up ACCELERATE, which includes a traditional doctor-directed arm but adds an online patient-powered arm.

The doctor-directed arm 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.

In contrast, the patient-powered arm used a website and social media to attract would-be patient participants. The registry team would then contact these patients’ doctors to verify that they met registry criteria, and if so, to obtain clinical data and samples.

With the patient-powered arm, researchers saw the enrollment of more than 250 patients by the end of 2019 compared to fewer than 100 in the doctor-directed arm. Additionally, the registry team was able to gather 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 addition of the patient-powered arm helped the registry reach its five-year enrollment goal in two years.

“Beyond the direct value of this clinical data, we have also used these data and tissue samples in multiple other studies that have led to improved treatment guidelines as well as new insights into the biology of Castleman disease — including potential targets for future treatments,” said Sheila Pierson, MS, the first author of the study and the associate director for clinical research for the CSTL.