Medical Device Daily

The National Institutes of Health (NIH; Bethesda, Maryland) last week rolled out plans to launch the first clinical studies of its Rare Diseases Clinical Research Network (RDCRN), which was funded at $71 million for the initiative in 2003.

More than 20 studies are expected to open in the next few months at about 50 sites across the U.S. and in several other countries including the UK, Japan and Brazil.

“The idea is that we're really trying to set up a model of research of rare diseases in which you use multiple research sites throughout the country, and in fact, there are several international studies as well focusing on particular diseases [with] a common protocol for many of the studies,” Stephen Groft, director of the NIH Office of Rare Diseases (ORD), told Medical Device Daily.

The emphasis will be on the genetic basis of these diseases, in essence requiring more “personalized” therapies.

Groft noted that the program is just launching the studies, although the overall funding from the NIH was made available for the program in late 2003.

“During the past year, we've gotten about 23 studies that have been approved by the NIH to start, and we're just in the process of rolling out the studies to people who have these diseases and provide ready access to research sites,” Groft said.

He estimated that there are more than 6,000 rare disorders – specifically defined as a disease or condition affecting fewer than 200,000 persons in the U.S. But the cumulative effect is “a lot,” he said.

The NIH estimates that such diseases impact 25 million Americans.

A central data and technology coordinating center and 10 research consortia will be established to conduct these investigations. Among the diseases to be studied will be:

  • Angelman, Rett, Prader-Willi syndromes;
  • myelodysplastic syndrome and other bone marrow failure conditions;
  • lymphangioleiomyomatosis (LAM), rare genetic disorders of the airways, and other rare lung diseases;
  • episodic ataxia, Andersen-Tawil syndrome, and nondystrophic myotonias;
  • several vasculitides;
  • urea cycle disorders;
  • antiphospholipid syndrome and other rare thrombotic diseases;
  • rare pediatric liver diseases;
  • rare genetic steroid defects.

“By studying the genetic component of these rare diseases, we hope to be able to better predict the course of the illnesses and provide more effective, personalized treatments for those afflicted,” said Elias Zerhouni, MD, director of NIH. “Ultimately, this individualized approach, completely different from how we treat patients today, will allow us to prevent or to promptly treat the complications arising from these genetic disorders.”

The NIH said that few drug companies conduct research into rare diseases since there is little chance to recoup the costs of developing treatments for such small, geographically dispersed populations.

Groft said that when the NIH first began considering the program, it was due to the recognition that the government needed to “do more” to provide incentive to private pharmaceutical companies to conduct such studies, even though the patient populations are small and located across large geographic regions, making studies difficult to conduct.

Although individuals with rare diseases who want to participate in studies will still have to travel, the expectation is that it won't be as far given the number of study sites and therefore will be less burdensome.

The RDCRN has received five-year funding awards and is coordinated primarily by two NIH components – ORD and the National Center for Research Resources (NCRR).

“Increased collaboration among researchers investigating rare diseases will not only lead to discoveries that will help prevent and treat these conditions but may also produce medical advances that will benefit the population in general,” said Groft said in a statement, which he told MDD would likely include the development of specialized diagnostic tests.

The initiative includes interventional trials to test new therapies or drugs, as well as longitudinal or natural history studies that will provide information about the characteristics of rare diseases and their progression over time. Data collection standards have been established for the research projects, and the data produced will be made publicly available with appropriate safeguards for patient confidentiality, NIH said.

“This network was created to share the experience, approaches, and tools for the study of rare diseases and to train the next generation of investigators,” said Barbara Alving, MD, NCRR's acting director. “The adoption of standards and common data elements across diseases is ground-breaking, promotes cross-disease analysis and provides a rich source of information to be mined by researchers around the world.”

Each consortium in the network includes active participation by the relevant patient advocacy groups. In addition, the Coalition of Patient Advocacy Groups (CPAG) was created to represent the more than 30 advocacy organizations involved in the network. CPAG has been doing outreach to the affected populations to gain their input into the development of studies.

“In forming this coalition of rare disease groups, NIH has created a powerful vehicle for us to collaborate and communicate with one another that has already brought dividends,” said Patrick Cochran, CPAG chair and founder of the Periodic Paralysis Association (Loma Linda, California). “Not only have we been able to share information and learn from each other, by working together we have also secured additional support from foundations and corporations.”

The RDCRN is funded by the ORD, NCRR, National Heart, Lung and Blood Institute , National Institute of Child Health and Human Development , National Institute of Neurological Disorders and Stroke , National Institute of Arthritis and Musculoskeletal and Skin Diseases , and National Institute of Diabetes and Digestive and Kidney Diseases – all components of the NIH.