NIH grant creates opportunities and supports new trial practices
NIH grant creates opportunities and supports new trial practices
Investigators say program was crucial to research
The clinical trials industry has reaped a variety of benefits from the federally-funded Rare Diseases Clinical Research Network (RDCRN), including the creation of dynamic partnerships between investigators and patients/advocates, according to Charles Strange, MD, a professor of pulmonary and critical care medicine at the Medical University of South Carolina in Charleston. "The network has been a very positive experience."
Research resulting from the consortium of rare disease investigators will contribute to general medical practice as well, experts say.
The National Institutes of Health (NIH) gave $71 million in funding over a five-year period to a central data and technology coordinating center and 10 research consortia to investigate rare diseases. Among the consortia are vasculitis, neurologic channelopathies, lung disease, thrombotic disease, genetic diseases of mucociliary clearance, bone marrow failure disease, urea cycle disorders, and Angelman, Rett, & Prader-Willi syndrome.
"One thing that has happened at NIH historically is rare diseases sometimes are not funded at the same level as more common diseases," Strange says. "But what comes out of rare disease research is you learn many basic mechanisms by which more common diseases can be manipulated."
For example, Strange's work is with the lung disease consortium, which is studying lymphangioleiomyomatosis, pulmonary alveolar proteinosis, familial pulmonary fibrosis, and Alpha-1 Antitrypsin Deficiency, a hereditary condition that can result in serious lung disease.
"If you can understand the pathway genesis of Alpha-1, it can be expanded to more common diseases, such as emphysema and chronic obstructive pulmonary disease (COPD)," Strange says. "It will likely have the same public health impact as studying more common diseases."
Many of the researchers who have been awarded grants through the RDCRN have had a longstanding interest in the disorders they're studying, says Steve Skinner, MD, a senior clinical geneticist and associate director of the Greenwood Genetic Center in Greenwood, SC. Skinner also is the director of clinical services and studies Rett syndrome and Angelman's syndrome.
"The concept behind the network is that these are rare diseases that any one investigator or institution won't have a large volume of patients to enroll in a study," Skinner says. "So the network allows them to pull together and collaborate to have the largest number of patients."
Collaboration in the network also improves cooperation and sharing of ideas, Skinner adds.
"In the two studies I'm involved in, you get a chance to meet face-to-face and have frequent telephone conversations with other investigators," Skinner says. "It opens doors for sharing resources and sharing laboratory techniques and capabilities, and that makes it easier and natural to share things across institutional boundaries."
For some of the rare diseases, the network and NIH funding was the only way the research would take place.
"We could not have done this project without the RDCRN network — it's been critical," says Richard J. Barohn, MD, chair and professor of the department of neurology at the University of Kansas Medical Center in Kansas City, KS.
Barohn is conducting research within the neurologic channelopathies consortium, specifically studying Andersen-Tawil Syndrome (ATS) and nondystrophic myotonias (NDM).
"These are a rare group of genetic disorders, usually with autosomal dominance, and they pass from one generation to another," Barohn explains.
Patients' symptoms of NDM include muscle cramps, stiffness, and an inability to relax when the muscles contract, he says.
"A lot of people have cramps, but we don't all have sodium chloride genetic defects," he says.
Patients who are suspected of having melatonin disorders, a sodium channel defect, or a chloride channel defect are the ones who are included in the longitudinal pheno/genotype study, Barohn says.
"We're trying to analyze these patients, obtain a detailed family history, and perform detailed and rigorous series of neurophysiological tests at each of the sites," he says.
"We're trying to understand what is going on in the muscles of these patients, and we're looking at the various muscle pathology, based on stimulating muscles with electric shocks and collecting that data," Barohn explains. "Based on what we find, the tests will tell us the story about these patients."
The research has been enhanced through the network and collaboration with peers.
"You learn a lot by talking with other investigators in completely different fields," Barohn says. "We go to meetings with all of the investigators, and it's interesting to see what other groups are doing with their rare disease — we sort of feed off of each other."
For these reasons and for the many other benefits that have come out of the RDCRN, investigators who received the first round of grants say they hope NIH will renew the grant when it comes up next year.
"We feel that in Rett syndrome we've been very productive and competitive and should be refunded," says Alan K. Percy, MD, professor in pediatrics, neurology, neurobiology, and genetics, and associate director of the Civitan International Research Center at the University of Alabama at Birmingham. Percy, who also is the medical director of the Sparks Clinics in Birmingham, studies Rett syndrome, and in 1983 was one of the first physicians in the United States to recognize Rett syndrome.
Rett syndrome researchers would like to collect at least 10 years of data in the natural history study, and patients weren't enrolled until about a year ago, Percy says.
"We were among the first to enroll patients, and we are far and away ahead in terms of overall numbers, but we would say it's critical that we continue this study for at least another nine years," Percy adds.
"The impression we've gotten is that NIH is committed to continuing this project," Skinner says. "I would imagine they would look at the different activities that have happened so far and make sure the money has been well-spent, maybe shifting and changing some sites."
The funding for rare disease research has long been needed, says Thomas P. Loughran, Jr, MD, director of Penn State Cancer Institute, and professor of medicine at the Penn State College of Medicine in Hershey, PA.
Loughran is involved with the bone marrow failure disease consortium and has phase 1 and 2 clinical trials underway.
"I've been contacting the Office of Rare Diseases on and off throughout my career to see if there were any funding opportunities," Loughran says.
While the first couple years of the five-year grants were spent building the ground work for the network, everyone has been pleased with the progress made, Loughran notes.
"Any time there's an actual funding source, it helps quite a bit with resources being kind of constrained these days," Loughran says.
The RDCRN grant has helped investigators do a better job starting clinical trials and building databases and registries, Loughran says.
"For LGL leukemia, I had already established a registry for that disease and rolled it into a bigger program," Loughran explains. "We were working in the lab before this grant was started, and we developed new drugs that might kill LGL cells in the lab, so that work preceded the founding of the funding stream."
Once the network was established and funding was made available, researchers could move more easily to clinical trials.
"The advantage of the consortium, from an accrual point of view, is that these diseases are rare, and so it's helpful to have a network that could guarantee certain numbers of these patients in the study," Loughran says.
Another advantage of the network is access to the data coordinating center, which is located in Tampa, FL, at Moffitt Cancer Center, Percy says.
"We collect massive amounts of data that would not be possible for us to manage with the limited resources we have," Percy says. "We can dump all the data into this data management system, and they're responsible for maintaining it."
Each site is responsible for its own data quality and analysis, but they have the advantage of using technology developed at the data coordinating center, he adds.
Sites also participate in meetings with other investigators and research staff in their particular consortia.
"The network has created a small community of like-minded individuals, and we've been very fortunate to have very good colleagues across the country and the world to expand our appreciation of this rare disorder," Percy says.
The RDCRN steering committee's representatives from each disease in the consortium meet twice a year and have conference calls on a more frequent basis, Percy says.
"This allows us to get some perspective against a broad group of disorders," he says. "And the data managers and clinic managers also have formed their own group."
The clinical trials industry has reaped a variety of benefits from the federally-funded Rare Diseases Clinical Research Network (RDCRN), including the creation of dynamic partnerships between investigators and patients/advocates, according to Charles Strange, MD, a professor of pulmonary and critical care medicine at the Medical University of South Carolina in Charleston.Subscribe Now for Access
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