Of these, the IAMRARE program is one of the best examples of ways to get involved. Beyond the many other ways these groups help patients and families cope with challenging diseases, participation in research takes rare disorder advocacy to a different level. Objective data can attract the attention of those with the resources to further study the disease, while also giving advocacy groups a seat at the table when researchers or industry become interested.
“Why create a registry? It removes competition between academic centers or industry working on their own. It creates one central source for data-sharing, and the advantage is that advocacy groups have a trusted relationship with the patient community because they are not-for-profit, community-run, and patient-driven,” Ms. Drell explained.
The registry platforms developed for IAMRARE are customizable. With guidance from NORD, the advocacy groups themselves decide what data to collect and what questions they wish to answer, according to Dr. Fink. Once the registries are created, patients and caregivers participate by responding to survey questions on disease onset, progression over time, types and severity of symptoms, and other topics. The data can be de-identified for research purposes. The advocacy groups decide how and when to share the data, including whether to publish findings.
“Some of the groups have been very successful in getting the data published and leveraging their results to drive research forward, but there is variability in the extent of dissemination across the groups,” said Dr. Fink. She noted that many of the registries that NORD has helped set up involve groups whose officers have had little or no prior research experience.
“We have advocacy groups that have had biomedical researchers on staff and other groups that are coming to research completely new,” Dr. Fink said. In trying to get them up to speed on quality data collection, “We try to meet them where they are,” she added, indicating that leading groups to a research-ready status is not just about logistics but can sometimes involve an organizational reorientation.
The examples of peer-reviewed publications that can be directly traced to IAMRARE registries are growing. One example is a registry on Prader-Willi syndrome, which is a complex neurodevelopmental disorder characterized by failure to thrive and by multiple endocrine abnormalities. The registry was developed in NORD’s IAMRARE program by the Foundation for Prader-Willi Research, a nonprofit created in 2003 by parents of children with this disorder.
By 2019, when the first data from the Global Prader-Willi Syndrome Registry were published, they drew from 23,550 surveys completed for 1,696 separate cases of the disorder in 37 countries. The surveys provided some preliminary findings on demographics and on the genetic subtypes most commonly encountered, as well as simply proof that the registry was viable. From its inception in 2015, a significant proportion of the Prader-Willi population in the United States had been enrolled, according to the study authors. With time, the serial accumulation of more data on more cases will be invaluable for documenting disease characteristics. It will be a constantly maturing resource even after fundamental questions on disease impact and prognosis are addressed.
Data accumulation
Only about 10% of rare diseases currently have approved treatments, but there is widespread belief in the rare community that collecting and analyzing the data that can promote understanding of the biology of the disease and identify therapeutic targets could accelerate the development of treatments for diseases that currently have none.
Therefore, data accumulation has become central to the mission of NORD. In addition to IAMRARE, the organization has embarked on several other important initiatives in data accumulation for rare diseases. One is the Rare Disease Cures Accelerator – Data and Analytics Platform (RDCA-DAP), an initiative in which NORD is partnering with the Critical Path Institute. The goal of this program is to gather disparate pools of existing data in a standardized format to increase their power.
“With funding from the Food and Drug Administration, we have helped to support this platform, which is designed specifically to provide a centralized structure for combining and sharing of data,” according to Dr. Fink. In RDCA-DAP, patient-level data is being assembled from a variety of resources, including academic centers, industry, registries, observational studies, and clinical trials. The program was launched in September 2021. In some cases, gaining access to data includes resolving privacy issues or addressing the proprietary concerns of those who currently have the data, but the value of the combined data is a compelling argument for participation.
“What we are trying to do is pull together the data from their current silos into one platform, and then make it generally available,” said Dr. Fink. As with IAMRARE, RDCA-DAP offers enormous potential.
“The primary challenge for those studying rare diseases is the small numbers of patients. Randomized clinical trials for some of these diseases are simply not feasible because there are not enough subjects to power two study arms,” said Dr. Fink in explaining why NORD has turned to novel strategies for data generation. One strategy for maximizing the potential value of data from these small populations of patients is data-sharing. For RDCA-DAP, data access will be open to all stakeholders after scientific review and approval.
“Anyone can get an account and request data from the platform,” said Dr. Fink, who expects this to spur more and novel types of research in rare disorders.
Another example of recent NORD initiatives to advance research and understanding of rare diseases is a study of metachromatic leukodystrophy (MLD) that is now enrolling patients, which also represents a partnership with the FDA. For this study, which is known as the HOME study, NORD hosts a platform where patients and caregivers enter data to capture the natural history of this disease. All MLD patients, even if they are already participating in a clinical trial or another registry, are invited. As with the IAMRARE registries, surveys capture patient or caregiver responses entered from a computer or smart device.
“We have always believed that the fact that so many rare diseases don’t have treatments or are not even being studied by researchers doesn’t reflect a lack of interest among academic or industry researchers. Rather, it reflects a lack of data to support research and to provide a fundamental understanding of the disease,” Dr. Fink said. “If NORD’s expanded research programs can draw the patient community together to provide that crucially needed data, we will have provided an important and essential service to patients, patient organizations, and researchers alike.”
Theodore Bosworth is a freelance journalist and editor specializing in medicine and health.