Diabetes is one of those diseases that has generated not just one but a series of "Holy Grails," including a totally non-invasive glucose monitor and — the most holy of all — a cure. But short of producing the non-invasive monitor, and with the possibility of a cure in the very distant future, the next most ideal of the "grails" in this sector is an artificial pancreas. Such a device would combine a continuous sensor system with an insulin pump, the sensors detecting when insulin is needed and then signaling the pump to deliver it in a closed-loop system, all in a totally implantable device package.
The possibilities for developing such a device and research progress in the area were discussed in various presentations and most specifically during the Artificial Pancreas Symposium at the second annual meeting of the Diabetes Technology Society (San Francisco, California) last month in Atlanta, Georgia. Because such a device is still so far in the future as a commercialized reality, the discussions focused primarily on the developmental progress of the primary components of such a system. The message of those presentations, more often than not, was that the progress in these areas is littered with large uncertainties and larger frustrations.
As one instance, the market potential of continuous glucose monitoring was downplayed by Meinhard Schmidt of Roche Diagnostics (Mannheim, Germany), who said his company sees the continuous monitoring approach as unlikely to be the most prominent in a future consumer market. He compared the spectrum from spot monitoring to continuous monitoring to the range from single photograph to a moving picture and, by further analogy, to early images of the galloping horse to determine if its legs were ever completely off the ground. Each type provides different kinds of information and has its respective drawbacks in terms of accuracy and complexity, he said. While continuous glucose monitoring would be a part of Roche's product mix, it would not be the most important and that the company would, he said, focus on keeping "its feet on the ground."
John Pickup, MD, PhD, a physician at Guys Hospital (London), offered perhaps the most pessimistic view of progress in the field of diabetes and the artificial pancreas particularly, noting that some technologies in the sector had been launched about 40 years ago, with total maturity yet to be achieved for many of them. One illustration that he offered was a comparison of a continuous monitor from Medtronic MiniMed (Northridge, California) with the GlucoWatch from Cygnus (Redwood City, California), his graphic renderings showing wide variability between the devices and some areas of missed readings for both.
Pickup was followed by William Tamborlane, PhD, head of the Diabetes Research in Children Network at Yale University (New Haven, Connecticut), who described ongoing research with the MiniMed and Cygnus devices to determine the usefulness of continuous monitoring in young adults and children. That research should be completed next year, he said, and is likely to provide further insight into broader applications of continuous glucose monitoring.
Focusing on the insulin pump feature of a device such as this, Marina Scavini, MD, PhD, a professor at the University of New Mexico (Albuquerque, New Mexico), listed a wide range of barriers to future development. These include problems with stable insulin preparations, the need for high levels of professional training among clinicians implanting the devices and a lack of competition among manufacturers in device development, primarily because of high R&D costs for such an effort. She cited a variety of potential co-morbidities with implantable pump devices, including "pump pocket complications" and high rates of explants and the resultant psychological complications.
Besides the rather distant prospects for an artificial pancreas, other presenters at the meeting provided insights into other advanced systems for improving diabetes management. Benjamin Feldman, PhD, of TheraSense (Alameda, California), reported on continuing development of a subcutaneous electrochemical sensing systems that produced blood glucose values at 15-minute intervals over a three-day implant period. Added to the device were membrane layers improving both signal take-up and biocompatibility.
Research on various computer and telemedical systems was cited as offering other possibilities for improved diabetes management.
Ronald Merrel, MD, of the department of surgery at Virginia Commonwealth University (Richmond, Virginia) presented research on home management of the data, via sensors, to transmit digital data on glucose, retinal status alerts for hypoglycemia and mental status, diet and weight changes to a management center. But Merrel also issued the rather large caveats that such systems "should be compatible with office practice and the lifestyle of patients and must not be prohibitively expensive."
Riccardo Bellazzi, PhD, of the University of Pavia (Pavia, Italy), gave an overview of telemedical projects in Europe, including eight homecare telemedicine applications focused on diabetes. One of them, the M2Dm project (for Multi-Access Services for Managing Diabetes Mellitus patients) has been launched to design and test a platform enabling the collection of data in a central database server to be accessed through the Internet, through the phone or through dedicated software for data downloading from glucometers. He said that four medical centers are following 80 patients in three European countries and will evaluate the effectiveness of the program in terms of clinical, organizational, economical, quality of life and usability outcomes.
David Klonoff, MD, clinical professor of medicine at the Mills-Peninsula Diabetes Research Institute of the University of California, San Francisco, is founder and chair of the Diabetes Technology Society. Klonoff told The BBI Newsletter about 500 persons attended this year's meeting, a 25% increase over the number attending the inaugural event last year.
Pharma future comes in device tech
While pharmaceuticals have traditionally been dispensed in the form of pills and capsules, the new devices and device strategies being developed offer better targeting for drugs rather than systemic application that may cause adverse and uncontrolled side effects. But many challenges still remain, Robert Langer, ScD, told science reporters and writers at a November gathering in Washington sponsored by the American Medical Association (Chicago, Illinois). "Already major advances in non-invasive drug delivery, through the skin and lungs, are in clinical trials. The new smart drug delivery systems, such as intelligent microchips, are being developed," said Langer, the Kenneth Germeshausen professor of chemical and biomedical engineering at the Massachusetts Institute of Technology (Cambridge, Massachusetts).
Langer outlined several examples of drugs introduced in the last five years, with either FDA or CE mark approval, using these innovative delivery techniques, ranging from wafers to new "micro" technologies. Wafers, for example, can be implanted in or near a brain tumor as a controlled-release system for delivering chemotherapy to cancerous cells. "The wafers prevent the unpleasant side effects of chemotherapy associated with oral and intravenous drug delivery," he said. Langer also described a tiny osmotic pump that delivers methylphenidate, a stimulant used to treat attention deficit hyperactivity disorder in children, on a timed release schedule. "The pump is swallowed and delivers the stimulant without having to administer the drug through an injection," he explained.
Still another alternative delivery method is the use of human growth hormone, delivered by injection, Langer said. Given once a month, the injections release human growth hormone continuously rather than intermittently. He also discussed the possible use of drug-eluting stents, currently targeting restenosis but likely to be adapted to a broad range of drugs and disease targets. "These stents will no doubt be used in other applications beyond the current use," he predicted.
Langer also noted that, as with overall trends for reducing the invasiveness of device technologies, similar trends are taking place in drug delivery. "More of the drugs coming to the market in the future are going to be protein or DNA-based derivatives. The only way to deliver these drugs in the past was through injections, but technology is making them available through non-invasive methods," he said.
He also pointed to an invasive use of device technologies that require implantation but with few potential side effects. This will come in the use of microchips with the capability of dispensing drugs or combinations of drugs. These chips will be implanted in patients, with the drugs they carry released through telemetry or through a biosensor contained on the chip, Langer said. The dosages of drugs can be adapted to any combination of medications — in a sense, programmable — because each dose is stored within an individual well on the chip.
AHRQ: Infotech key to bioterror response
Adding clinical practice guidelines and more current data on bioterrorism-related illnesses to existing databases of health information systems is one of several ways to help prepare clinicians for bioterrorism, according to a new report from the Agency for Healthcare Research and Quality (AHRQ; Rockville, Maryland), a division of the U.S. Department of Health and Human Services. Produced by the AHRQ Evidence-Based Practice Center (EPC), a joint collaborative effort between the University of California, San Francisco (UCSF) and Stanford University (Palo Alto, California), the report also finds that efforts to link decision support systems for diagnosing, treating, and preventing bioterrorism illnesses to other hospital information systems could greatly reduce the data entry burden.
The report, "Bioterrorism Preparedness and Response: Use of Information Technologies and Decision Support Systems," is part of AHRQ's $5 million bioterror research effort announced in October 2000. The portfolio of work includes projects examining the clinical training and ability of front-line medical staff to detect and respond to a bioterror event. Other projects assess and improve links between the health system, local and state public health departments and emergency preparedness units.
Some 217 information technologies and decision support systems were abstracted for potential use in the event of a bioterror attack. Most were not designed specifically for bioterrorism but rather were created for detecting and managing naturally occurring illness.