There was a sense of momentum when scientists, clinicians, engineers, biotechnology companies and others met at the National Institutes of Health Bethesda Campus in July to discuss the status of the artificial pancreas.
The two-day meeting, sponsored by the FDA, NIH and Juvenile Diabetes Research Foundation (JDRF), was meant to focus not just on the latest research around the development of a closed-loop insulin delivery system, but also on the business aspects of bringing such technology to market.
“We want to see this go from research to real development,” said Aaron Kowalski, PhD, research director of the JDRF's artificial pancreas project. While his group's primary goal is to have a system that benefits the everyday lives of people with type 1 diabetes, Dr. Kowalski believes that artificial technology may first come into use for hospital patients.
“In the near term, the hospital may provide a fast track to a commercial version of a system because from a regulatory standpoint there would be tight supervision,” said Dr. Kowalski. The meeting included sessions on medical and engineering challenges, clinical trials and marketing issues.
Dr. Kowalski said testing is under way of prototype closed-loop insulin delivery systems composed of various combinations of three key components: a continuous glucose monitoring sensor, an insulin pump and a computer-based algorithm.
“Now we need companies to buckle down and accelerate development of these tools and we need clinicians to apply their knowledge to help make this work for patients,” he said.
Jeffrey Joseph, DO, an anesthesiologist who directs the Artificial Pancreas Center at Jefferson Medical College in Philadelphia and a presenter at the meeting, also came away enthused. “People are now seeing this as an important way to improve patient care and potentially a lucrative market,” he said. A number of companies, including Abbott Laboratories, Medtronic and Johnson & Johnson, are involved in developing technology that could help lead to a marketable closed-loop system in the next several years, he said.
The technology, he said, could “reduce hospital morbidity, mortality and lengths of stay” by providing meticulous management of patients' blood glucose levels, ideally without added demands on the staff. Presumably, an automated closed-loop system could also reduce the risk of errors in insulin dosing.
At the meeting, Dr. Joseph talked about the challenges currently facing hospital staff in monitoring and controlling glucose levels in patients, whether they have previously been diagnosed with diabetes, have newly diagnosed cases, or have transient abnormal blood glucose levels because of illness, surgery or treatment. According to the Centers for Disease Control and Prevention (CDC), the number of hospital discharges with diabetes listed as a diagnosis (either first or otherwise) increased from 2.2 million in 1980 to 5.1 million in 2003.
Although hospitals devote considerable time and resources to monitoring blood glucose levels (it can take a nurse upwards of five minutes to take a single reading), glucose management is not being handled as well as it could be, said Dr. Joseph in an interview. The sliding-scale approach to insulin dosing “has been shown not to work well,” he said, and hospitals tend to take a reactive approach rather than implementing a systematic plan using a patient's individual profile.
“We need new tools, new protocols, new guidelines,” said Dr. Joseph. “Two hours of a nurse's day can be dedicated just to blood glucose monitoring, but nurses don't have two hours a day per patient to do that.”
Kevin Larsen, FACP, chief medical informatics officer for Hennepin County Medical Center in Minneapolis, said reducing errors around the prescribing and administration of insulin therapy is as important a goal as attaining good blood glucose control.
“How do we standardize care so we decrease errors and make things more predictable and understandable?” asked Dr. Larsen, who has worked on implementing such a system at his hospital.
Growing emphasis on reducing hospital lengths of stays and costs has also added to the push to find the ideal approach to glucose control. Strong evidence supports using tight glucose control in ICU patients and cardiac surgery patients to reduce morbidity and mortality, Dr. Joseph said, although there is debate over how best to define “tight.”
An often-cited study of surgical ICU patients published in 2001 in the New England Journal of Medicine found that keeping blood sugar levels below 110 mg/dL cut in-hospital mortality by about one-third and also significantly reduced the chances of bloodstream infections and acute renal failure. But a study of medical ICU patients (New England Journal of Medicine, 2006) found that tight glucose control decreased morbidity but not inhospital mortality, and other findings suggest that intensive glucose management could actually end up causing more harm than good in some hospitalized patients. A New England Journal of Medicine study published in January 2008, for instance, found that intensive insulin therapy increased the risk of hypoglycemic- related problems for patients with severe sepsis compared with conventional therapy. The study was halted for safety concerns.
“We need a good multicenter study to see if tight glucose control makes a difference outside the ICU,” said Stephen Clement, MD, associate professor at Georgetown University Hospital in Washington, D.C. “We live on very, very tight resources, so we need to be very demanding of science and have evidence for what we're doing.”
Facing the challenges
Howard Zisser, ACP Member, director of clinical research and diabetes technology for the Sansum Diabetes Research Institute in Santa Barbara, Calif., said insulin use presents many challenges.
“A tough problem with insulin is that it's like driving a car with just an accelerator. There are no brakes.” Also, Dr. Zisser noted, “the pancreas is a pretty smart organ by itself, and when it's not working properly it's hard to replicate what it does.”
The notion of developing an artificial pancreas for temporary or long-term use has been discussed for decades. Dr. Joseph presented a bit of history at the NIH meeting, showing his audience a photo of the Biostator, a closed-loop system from the late 1970s that didn't make inroads in patient care because it was cumbersome and required a full-time technician. A marketable modern artificial pancreas is not far from becoming a reality, said Dr. Joseph, because the three components needed to make up a closed-loop system already exist in various forms.
Having a first-rate sensing system is key to a closed-loop system, according to Dr. Clement, because “it's a problem of garbage in, garbage out. If a sensor reading is not reliable, then it could do more harm than help.” Research is focusing on alternatives to using interstitial fluid as a means of monitoring glucose levels, including using sensors that can continuously measure intravascular glucose.
Some early data have been published on the use of a closed-loop system in small groups of pediatric and adult patients. A team from Yale University reported in May in Diabetes Care that they were able to achieve near-normal glucose levels in adolescents with type 1 diabetes during the overnight hours using a closed-loop system devised of Medtronic components.
The JDRF is funding studies at seven sites of adults with type 1 diabetes who are brought to the hospital to test the closed-loop insulin delivery approach using various combinations of already existing technologies, Dr. Kowalski noted.
“The studies are going very, very nicely,” he said. “The question is what do we need to do to drive this to a commercial product?”