BBI Contributing Editor

DUSSELDORF, Germany The European medical device market is experiencing widespread changes in the types of products and technologies that are in demand due to the influence of recent restructuring of the healthcare system. At the annual MEDICA exhibition, held here in mid-November under the sponsorship of Messe Dusseldorf, a wide range of new products were introduced that promise to enable management of the growing number of patients with chronic diseases in non-acute care settings, including the home.

Remote telemonitoring, including home monitoring, is one of the most rapidly growing segments of the medical device market worldwide and is attracting the interest of numerous companies, both in Europe as well as in the U.S. Remote monitoring is one segment of the larger market for telemedicine products and services, which also is undergoing strong growth in Europe. New technologies for monitoring of patients in the hospital also were introduced at the sprawling MEDICA exposition, including a number of non-invasive monitoring devices that can improve the ability of physicians to closely tailor therapy to individual patient needs while also improving safety and enhancing the efficiency of hospital operations.

Increasingly, medical device technologies are enhancing the ability of healthcare providers to manage patients throughout a continuum of care that extends from the intensive care unit and the surgical suite to sub-acute care settings and into the home, and allows optimal transitioning of patients through the various levels of care based on their clinical status.

Home monitoring, telemedicine help control costs

Home telemonitoring technology emerged in the U.S. market in the early 1990s as a means to provide a more intensive level of care for patients with chronic diseases. The initial focus was on the management of congestive heart failure, to help reduce the number of episodes of hospitalization. Leading suppliers of home telemonitoring equipment in the U.S. include HomMed (Madison, Wisconsin), Health Hero Network (Mountain View, California), American Telecare (Eden Prairie, Minnesota), Philips Medical (Eindhoven, the Netherlands), Viterion Health Care (Tarrytown, New York) and Alere Medical (Reno, Nevada). The technology now is attracting growing interest in Europe, and a new group of companies has emerged to address the opportunity in the region along with some of the companies from the U.S. market. In addition, some of the European telemonitoring companies are now entering the U.S. market as it continues to expand.

Telcomed Advanced Industries (Dublin, Ireland) has developed a modular system for monitoring of patients in the home that employs wireless Blue Tooth technology to connect devices for tracking blood pressure, temperature, oxygen saturation, breathing rate, body weight and electrocardiograms. Two-way video also is available. Any combination of devices can be wirelessly connected to a central gateway in the home, which then transmits the data to a telemonitoring call center using ordinary telephone lines. Telcomed also provides call center software in 10 languages that automatically triages the monitored patients to allow nurses in the call center to focus on those patients who require the most urgent attention. One nurse can monitor about 500 patients on average with the Telcomed system, with the ratio depending on the diseases being managed.

Disease categories or applications for which the Telcomed system has been applied include heart failure, prenatal support, post-surgical management, diabetes, asthma, dementia and hypertension. Another important feature of the system is its ease of use, even for users who are not computer-literate. About 80% of current users are seniors with little experience in the use of computer systems.

Another European supplier, RTX Healthcare A/S (Norresundby, Denmark), has developed a system that offers a highly simplified setup procedure for the user. A wireless interface is built into each of the company's monitoring devices, such as blood pressure meters or weight scales, that is automatically activated when the user receives the device, typically by mail, and installs the batteries. A wireless hub also is delivered to the patient that only requires connection to a regular phone line, and the monitoring network is then brought online remotely from a call center. Data is automatically transmitted whenever the user performs a measurement. RTX is negotiating with potential partners, including home healthcare companies and hospitals in both Europe and the U.S. who are interested in adopting its OEM Wireless Telehealth Solution.

Philips Medical has introduced the Zertiva remote monitoring system for use in managing patients with heart failure. The Zertiva system allows monitoring of weight, blood pressure and ECG via a Philips call center for a rate of EUR 35 per month. A network of 30 call centers has been established in Europe to perform monitoring of patients who are using the Philips equipment.

Other suppliers of telemonitoring equipment in Europe are listed in Table 1 below. The market for home telemonitoring products and services is expected to exhibit rapid growth along with the remainder of the telemedicine market in Europe over the next five years. The target patient population for remote monitoring is about 3% of the total population in European countries such as Germany, or 2.5 million people in that country.

Other segments of the telemonitoring market include video conferencing for specialist consults, imaging data management and other specialized types of telemedicine products as shown in Table 2 (below), which presents data for the German telemedicine market in 2003 presented at the MEDICA meeting by Katherine Shariq of Frost and Sullivan (Palo Alto, California). The total telemedicine market in Germany is expected to grow at over 30% per year through 2007. The imaging data segment will remain the largest throughout the forecast period, as growth continues in adoption of hospital imaging data management products (primarily PACS) and the emerging market for clinic and physicians' office image data management products enters a rapid expansion phase in the latter half of the decade. PACS products for hospital use are expected to dominate the dollar volume market, although not the unit volume market, over the next five years. In Germany, the market will transition from a 60/40 split between hospitals and individual clinics, to a 75/25 split by 2007, according to Shariq.

Specialized applications of imaging technology also may become important, exploiting the power of imaging technology to manage virtually all types of patient data. For example, RIMEC GmbH (Nuernberg, Germany) exhibited a new magnetic optical disk data storage device at the MEDICA meeting, the DuoCard, that may have important applications in electronic patient records. The system employs imaging techniques to capture and store patient charts, records of consults, laboratory results and diagnostic images on a small card that can be carried by the patient. Data is captured and stored on the card using a doctor's office system costing $500 to $1,000. The patient then can use the DuoCard as an adjunct to the personal health card that will be issued to all German citizens in early 2006. The DuoCard can be used to greatly expand the range and amount of data that can be maintained by the patient. The cost to the patient is $30 per year.

A new device for the detection of atrial fibrillation has been developed by Geratherm Medical AG (Geschwenda, Germany). Atrial fibrillation, which afflicts about 2 million in the U.S. and can lead to an increased risk of stroke, is difficult to diagnose and often can only be recognized by long-term ECG monitoring. The AFD monitor from Geratherm is a simple, mobile ECG system that can inform the patient or physician of cardiac rhythm abnormalities, and is intended for use to detect recurrent atrial fibrillation after cardioversion to restore sinus rhythm after an initial event. The AFD Monitor will be sold to physicians who can use it to monitor patients for a 60-minute period. The device automatically detects an episode of atrial fibrillation and can also be activated by the patient if an episode is suspected. Geratherm expects to receive a CE mark for the AFD Monitor this spring and will launch the product in Europe with an expected price of about EUR 1,000.

Innovation in hospital monitoring sector

Advances in hospital patient monitoring also were announced at the MEDICA exhibition. A new non-invasive cardiac output monitor was exhibited by Hanbyul (Jeonju, South Korea). The EUR 20,000 monitor, which has recently been launched in the European market, uses impedance cardiography to determine pulse wave velocity, referencing measurements of aortic flow to carotid flow. The device uses a low-measurement current and can use standard ECG electrodes, resulting in lower cost vs. other bioimpedance systems used for cardiac output monitoring. The company plans to add a highly precise noninvasive blood pressure measurement capability and is seeking partners to help it penetrate the U.S. market and provide funding for additional product development.

Another noninvasive cardiac output monitoring system was exhibited by USCOM Ltd. (Sydney, Australia) that uses continuous wave Doppler technology operating at 2.0/3.3MHz to provide real-time beat-to-beat readings using a single, compact transcutaneous probe (the FlowFinder). The probe is reusable, thereby avoiding the cost of a disposable probe. The system is priced at EUR 25,000, making it competitive with the Hanbyul system.

Pulsion Medical Systems AG (Munich, Germany) is a supplier of minimally invasive cardiac output monitoring systems and announced a new license agreement for its PICCO continuous cardiac output technology at the MEDICA exhibition that calls for integration of the PICCO into the Infinity Patient Monitoring System manufactured by Drager Medical AG & Co. (Lubeck, Germany), a Drager and Siemens company. The PICCO uses thermodilution to measure cardiac output, but is less invasive than a traditional thermodilution measurement since a right heart catheter is not required. The system is priced at EUR 12,900 in Germany plus EUR 150 for disposables. Pulsion also has established a partnership with Philips Medical Systems under which the PICCO has been integrated as a module in the Philips CMS and IntelliVue monitors. Pulsion claims to be the leader in hemodynamic monitoring in the intensive care unit in Europe, with about 3,000 PICCO units sold worldwide, along with 4,000 licensed products.

Olympic Medical (Seattle, Washington) exhibited a new neurological monitoring system for use in the hospital post-natal unit. The Olympic CFM6000 Infant Brain Monitor was cleared for marketing by the FDA in May of last year and also has received CE mark certification in Europe. Olympic is now building the market for the product in Europe, targeting applications in the neonatal intensive care unit to assess the neurological status of the brain. The CFM uses three small electrodes that are placed on the infant's scalp and can be used in situations where conventional multi-lead EEG monitoring or cerebral magnetic resonance imaging may not be immediately available. The system enhances the ability of the clinician to identify the presence of seizures or to identify infants at risk for hypoxic-ischemic encephalopathy and other brain abnormalities. CFM monitoring can be initiated within minutes of birth.

Another neurological monitoring system, the Cerebral State Monitor from Danmeter (Odense, Denmark), uses electroencephalographic readings to derive the Cerebral State Index, a parameter that can be used to quantify the direct effect of anesthetics and sedative drugs on the brain. The EUR 2,135 analyzer is very compact, fitting in the palm of the hand, and the CFM data can be wirelessly integrated with data from a multi-parameter vital signs monitor.

Two new imaging systems that promise to improve the treatment of cancer patients in the hospital were exhibited at MEDICA. General Equipment for Medical Imaging SL (GEM Imaging; Valencia, Spain) showed the Sentinella 102 hand-held mini gamma camera, a compact, high-sensitivity nuclear imaging device that can be used for guidance of sentinel node biopsy procedures in the hospital. The Sentinella does not require an external power source, and can be used during a surgical procedure to map tumors following radioisotope labeling. The device uses a position-sensitive photomultiplier detector, and has applications in sentinel node mapping for patients with breast, prostate, penile and bladder cancer, and for melanoma patients. The camera is priced at EUR 42,000 in single quantities, but the price drops as low as EUR 18,900 for quantities of 100.

Another imaging system with applications in breast cancer diagnosis was exhibited by Imaging Diagnostic Systems (IDS; Plantation, Florida). The Computed Tomography Laser Breast Imaging System (CTLM) is used in conjunction with mammography and detects angiogenesis associated with a growing breast tumor via near-infrared tomographic imaging. The technology is particularly useful in diagnosis of tumors in women with dense breasts, where conventional mammography has a low sensitivity of 30% to 50%. Overall, mammography also has a high (80%) false positive rate, leading to a significant number of unneeded biopsies. According to IDS, 80% of breast biopsies are negative. Studies with the CTLM system have demonstrated 100% sensitivity and 64% specificity for the technique when used in conjunction with mammography, and an approximately two-fold reduction in biopsy rate. About 45 systems have been sold worldwide, mainly in Europe, Latin America and China. The CTLM received regulatory approval in Canada in early November, and the company has filed for marketing clearance in the U.S. Another advantage of the technology is the lack of use of harmful radiation.

Continued advances in diabetes management

Another focus of development activity featured at the MEDICA exposition was new technologies for diabetes management. A number of companies, including established players in the diabetes management market and new technology-based ventures, are developing devices for less invasive and noninvasive glucose monitoring. The market for glucose testing products (see Table 3) is one of the most rapidly growing segments of the medical device market in Europe. Integrity Applications Ltd. (Ashkelon, Israel) is developing the GlucoTrack noninvasive glucose monitor for use by Type 1 and Type 2 diabetics, individuals with pre-diabetes and gestation diabetes, and persons with impaired glucose tolerance. The system uses three different measurement modalities simultaneously and applies an algorithm to compare and average the readings to arrive at a consensus result. The modalities include an ultrasound measurement of the speed of sound in blood, an electromagnetic determination of blood conductivity and an electronic measurement of heat capacity, which is related to glucose content according to the company. The sensing element is attached to the user's earlobe and connected to a hand-held measurement unit, which powers the sensor and displays results. Both individual (spot) measurements as well as continuous measurements can be performed. By tracking trends in the three measured parameters, calibration can be maintained over a period of a few months. One GlucoTrack meter can serve up to three users, helping to lower the cost of use. Integrity has not yet determined a cost for the GlucoTrack. About 20 patients have been included in trials so far, and the company estimates that the product is at least one year away from market introduction.

Three companies have introduced continuous glucose monitoring systems, although none can be categorized as completely noninvasive. Medtronic MiniMed (Northridge, California) is marketing the CGMS System Gold worldwide, which uses a subcutaneous biosensor to monitor glucose every five minutes for up to three days at a time. Cygnus (Redwood City, California) has introduced the GlucoWatch Biographer, primarily in the U.S. market, which employs reverse iontophoresis to measure glucose in interstitial fluid at intervals of about 14 minutes for up to 13 hours before replacement of the sensor patch and recalibration is required. However, the GlucoWatch is no longer actively marketed as a result of a decision by Cygnus' marketing partner, Sankyo Pharma (Tokyo), to discontinue distribution of the product. In Europe, A. Menarini Diagnostics (Florence, Italy) has introduced a new continuous glucose monitor, the GlucoDay. There are now about 200 users of the GlucoDay in Europe. The EUR 4,000 monitor measures glucose levels in subcutaneous interstitial fluid using a microdialysis fiber amperometric sensor, provides a reading every three minutes for a period of up to 48 hours, has a response time delay (vs. blood glucose level) of under two minutes, and includes an alarm (buzzer or vibration) that sounds if hypo- or hyperglycemia is detected. The prescribing physician has the option to configure the unit to display real-time readings for the patient or to store the values for subsequent review.

Another continuous glucose monitor, the GlucOnLine from Roche Diagnostics (Basel, Switzerland), is under development that will provide readings at three-minute intervals over a three-day period. The GlucOnLine uses viscometric sensing technology to measure glucose-dependent viscosity changes in a liquid that contains dextran and Concanavalin A. Development of the GlucOnLine was initiated by Disetronic Medical, a Swiss company that was acquired by Roche last year. Launch of the GlucOnLine in the European market is planned for 2005.

Senzime (Uppsala, Sweden) also is developing a continuous monitoring system that measures glucose, lacate and urea, and that could have important applications in point-of-care testing in intensive care settings. Recent clinical studies using in vitro whole blood glucose monitoring have demonstrated a significant improvement in outcomes, including reduced in-hospital mortality, for intensive care patients whose glucose levels are tightly controlled. The Senzime system can be attached to an IV line and consumes about 2 ml to 3 ml of blood per hour. The company is seeking funding for development of a multi-analyte version of the device and hopes to launch the product in about a year.

TheraSense (Alameda, California) also is developing a continuous glucose monitor, the FreeStyle Navigator, using a subcutaneous sensor, and recently filed a premarket approval (PMA) application for the product in the U.S. The FreeStyle Navigator is a continuous glucose monitor that utilizes the company's proprietary Wired Enzyme technology and is designed to measure glucose levels in the patient's interstitial fluid every 60 seconds and transmit the results to a wireless pager-sized receiver. Abbott Laboratories (Abbott Park, Illinois) reported in mid-January its intention to acquire TheraSense in a $1.2 billion deal expected to close during 2Q04.

Pendragon Medical (Zurich, Switzerland) may be the first company to introduce a truly noninvasive continuous glucose monitoring system in the European market. The company is developing the Pendra monitor, which uses impedance spectroscopy to monitor changes in blood glucose. A CE mark has already been obtained for the Pendra, and a PMA application has been filed with the FDA. The company is estimating product launch in five European markets this month: Germany, the Netherlands, Greece, Austria and Switzerland. End-user price for the Pendra will be EUR 2,500, and a disposable component will not be required.

The cost of the system will be equivalent to about three years worth of supplies used for conventional glucose testing. The useful life for the meter is estimated at four years. A daily fingerstick reading will be required to maintain accurate calibration, so that the cost of use for a diabetic who now performs four fingerstick tests per day will be about the same with the Pendra. The meter will provide readings as often as once per minute, and also provides high and low alarms on a continuous basis, so it could prove useful in warning of hypoglycemic and hyperglycemic events that now go undetected.

A second development-stage continuous monitor, the GluCall, employing reverse iontophoresis sensing similar to that used in the Cygnus GlucoWatch, is under development by KM Holdings Ltd. (Seoul, South Korea). The KM device differs from the GlucoWatch, however, in that it employs a much lower extraction current, which results in less skin irritation, according to the company. The single-use disposable sensor performs a measurement every 20 minutes and stores more than 8,000 readings in memory.

Another continuous glucose monitor that uses transcutaneous extraction of interstitial fluid and an external sensor and display/data storage device is being developed by Sontra Medical (Franklin, Massachusetts).

Therapeutic technologies focus on cost

New developments in therapeutic technology were also unveiled at MEDICA that promise to improve efficiency in anesthesia and drug delivery. Hudson RCI (Temecula, California) exhibited the AnaConDa, an anesthetic conserving device that was launched in Europe last month. The AnaConDa is a new tool for inhalation sedation and was developed for the ICU setting to allow the use of gas sedation and anesthesia in settings that now rely primarily on IV drugs for sedation. Because recovery time is prolonged to as much as two days with IV sedation, ICU patients may be required to remain on a ventilator for extended periods and may have a prolonged stay in the ICU. By allowing the use of inhalation sedation, the AnaConDa can help in achieving shorter stays, since sedation recovery times are reduced to minutes, and its ability to recycle about 90% of the administered inhalation agent can reduce the cost of anesthetic agents, particularly as compared to expensive drugs used for IV sedation. Enabling the use of inhalation sedation in the ICU also eliminates the hazards of drug interactions that can occur with IV sedation and reduces the risk of adverse effects on organ function. The AnaConDa includes ports for a gas monitor and is typically connected into the breathing circuit of a ventilator system. Hudson said it believes the device can allow expansion of the use of inhalation sedation to areas of the hospital including the ICU that currently are limited to using IV sedation, providing cost and efficiency benefits for the hospital.

Another advance in gas anesthesia and sedation technology was introduced by Phasein AB (Danderyd, Sweden). Phasein has developed the IRMA in-line gas monitor, including the IRMA ICU version that monitors inspired CO₂ and expired O₂, and the IRMA OR that monitors five anesthetic agents in addition to inspired CO₂ and expired O₂. Another version, IRMA OR+, provides agent identification in addition to the other parameters. The entire EUR 1,000 IRMA probe is about the same size as a reusable pulse oximetry sensor, and weighs only 30 grams, vs. 12 to 15 kilograms for a typical tabletop anesthetic gas monitor used in most operating rooms. The IMRA employs infrared sensing technology for gas analysis, measuring absorption at 10 different wavelengths. The device includes intelligent software that allows it to interface to a Windows-based computer, a PDA or a multi-parameter monitor via an RS-232 link to read out the gas values.

A new infusion pump, the AP 34-M, is under development by Q-Core Ltd. (Ramat Gan, Israel). The pump is designed for use both in the hospital as well as in ambulatory care, and allows parameters such as bolus setting, total delivered dose and rate settings to be transmitted via a cell phone link. Parameters can be readjusted by a nurse or the patient using a touch-screen on the pump, providing a convenient approach to monitoring infusion therapy throughout the entire treatment cycle and modifying the drug infusion profile as dictated by patient condition. The AP 34-M can operate in PCA, continuous, intermittent and TPN modes, and can operate for about 25 hours on a single battery charge. Q-Core is now finalizing the design, including the configuration of the infusion set.

Researchers at the Institute for Medical Physics and Laser Medicine, Free University of Berlin (Berlin, Germany) and Laser und Medizin-Technologie Berlin GmbH (LMTB) described a program to develop a new device to assess the quality of red blood cell concentrates in the hospital prior to transfusion. Red blood cell concentrates are very expensive to produce, and in Germany have a mandated shelf life of only 42 days under perfect storage conditions at 4 C. At present, the only approach for assessing quality is visual inspection, and since it is often not possible to guarantee that the blood has not been exposed to higher temperatures, bags often are disposed of prematurely for safety reasons.

LMTB's new prototype blood bag quality sensor, or BBS, is a device for determining the amount of free hemoglobin in the red cell concentrate, which is an indication of red cell lysis. The sensor uses a dual-diode optical sensor to detect free hemoglobin, and also uses a measurement of light scatter to ensure that no red cells are in the optical path when the free hemoglobin measurement is made. The battery-operated device is recharged when the data is read out and, when development is complete, is expected to allow a quality determination to be performed on a bag of red cell concentrate in about 15 minutes. Estimated cost of the device is EUR 2,500. Clinical trials are approaching completion, and LMTB's goal is to license the technology to a company for commercialization.