Efficiencies resulting from rare disease network

Patients 'phone in' answers to questions

Researchers studying rare diseases have disadvantages in obtaining data that some have learned how to turn into assets.

For example, patients with rare diseases are difficult to study geographically because the numbers needed for a study's enrollment are too challenging for any one site to accrue, even in large cities.

So when several sites are working together to accrue a desired number of patients, there needs to be ways to bridge the geographical challenges.

Clinical trial sites involved in the National Institutes of Health's Rare Diseases Clinical Research Network (RDCRN) have found and developed innovative ways of meeting this challenge.

For example, the neurologic channelopathies consortium has been using a novel way to collect data on patients' symptoms.

"We're doing it over time, using an interactive voice response (IVR) call-in system," 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 the principal investigator of the nondystrophic myotonias (NDM) group.

"Patients who enter into the study are instructed on how to call in on the IVR system every week for several months," Barohn says. "There's a telephone prompt device, and they're asked on a scale of zero to nine how much weakness they had this week."

Other questions include how much stiffness, pain, and fatigue they've experienced, he adds.

"That's never been done before in this series of disorders," Barohn says. "We show that with the IVR responses, the patient calls each week are very consistent."

Barohn and co-investigators will present information about this at the American Academy of Neurology meeting, held April 28 to May 5, 2007, in Boston.

The group will demonstrate how useful the phone data is, he adds.

"It sounds low-tech, but despite the fancy neurologic stuff we do, this method appears to be the most reliable way of following patients' symptoms over time," Barohn notes.

Another goal of the neurologic channelopathies group is to develop therapeutic trials in hopes of developing new therapies for muscle pain and stiffness, Barohn says.

"And we're working on those now," he says. "We've submitted to the FDA to study a drug that may reduce muscle stiffness and pain."

The IVR method of collecting data will continue to be used throughout the three-year trial, assuming funding comes through, Barohn says.

"We'd have two years of background IVR data before we go into actual treatment," Barohn explains. "In the treatment trial, we'll use new IVR data from patients put on the drug or a placebo, and every week they will call in for four weeks, and then they'll be flipped, and those on the active drug will go on the placebo."

This way, researchers hope to learn whether the drug works.

The RDCRN funding paid for the groundwork research that was necessary before investigators could reach the point of designing a therapeutic trial, Barohn notes.

"We're hoping RDCRN gets refunded, and our site is refunded," he says. "It's conceivable that if there is another round of funding to our site, we might be able to do the trial without additional funds — but you can never bank on it, so we're actively pursuing grant funding from additional sources."

The bone marrow failure disease consortium's clinical research also has advanced as a result of the network.

Investigators have conducted clinical trials involving a potential treatment for large granular lymphocyte (LGL) leukemia, which is a very rare form of leukemia, 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.

"We've identified a certain biological molecular pathway that the study drug Zarnestra turns off," Loughran explains. "In the lab, all LGL cells are readily killed by medicine."

The network enabled investigators to more quickly enroll patients in the first phase of the study, which tested seven patients with the rare disease to see what the toxicity and side effects were in using the study drug, he says.

"Soon after the protocol was activated, for example, we had four patients at the Moffitt Cancer Center in Tampa, FL, and we had three from here go on the protocol right away," Loughran says. "So we enrolled our first seven patients very quickly for a rare disease."

Zarnestra, the drug's trade name, showed some definite biological activity in terms of killing the LGL cells in patients, Loughran says.

"The bone marrows improved, but there wasn't a definite response in terms of improving the actual blood counts," he adds. "So we're trying to figure out whether we go to a second phase of it which calls for increasing the dose of medicine or whether we change it and continue with the current dose."