It is being realized belatedly that budgetary cuts in laboratory in vitro diagnostic testing may be counter-productive. The European Diagnostic Manufacturers Association (EDMA; Brussels, Belgium), which recorded a 4.6% European market growth in 2000 to $5.6 billion — including $712 million in instrumentation — pointed out that the extent of savings that in vitro testing can bring about can only be fully appreciated if costs are viewed from an overall health care standpoint, as opposed to an isolated laboratory budget point of view.

EDMA, in a recent review, identified diabetes monitoring, the detection of Helicobacter pylori, chemotherapy monitoring and therapeutic drug monitoring as being clearly identifiable sectors in which medium- and long-term cost savings can arise.

Using the Diabetes Control and Complications Trial Research Group (DCCT) study in the U.S. and Canada, the Arthur D. Little consulting firm applied direct costs in Germany and calculated net savings of $3,693 per year for Germany's 350,000 Type 1 diabetics if intensive monitoring (testing four times a day) and therapy (adjusting insulin injection levels three times a day) were used. This represents a potential saving of $1.3 billion a year, in addition to which significant decreases in end-stage renal disease and severe neuropathic disabilities like diabetic ulcers, amputations and loss of sight could be expected.

H. pylori, which infects more than 50% of the world's population, is present in 95% of duodenal ulcers and more than 70% of gastric ulcers. In addition, the World Health Organization (WHO; Geneva, Switzerland) estimates that the eradication of H. pylori infection will lead to a reduction of 60% to 80% of stomach carcinomas. Diagnostic identification and therapy can eradicate infection in 10 days if outpatient treatment, and in Britain the National Health Service has estimated that this could result in savings of $600 million to $850 million over six years for chronic patients alone.

Cancer patients on aggressive chemotherapy have a high risk of infection and often need isolation and expensive barrier nursing. Preventive care is likely to include oral antimicrobial antifungal agents and hematopoetic growth factors to stimulate neutrophil production. Infection is still a high risk, however, so that accurate neutrophil monitoring using high-resolution laser flow cytometry is vital to maximize the therapeutic benefit of chemotherapy while reducing the infection risk and the need for barrier nursing.

Therapeutic drug monitoring (TDM) is an important factor in many therapy regimens to ensure that the patient is receiving the correct drug at the optimum dosage level. One important application is the monitoring of immunosuppressant therapy following a transplant procedure. Levels of immunosuppressant have to be high enough to prevent rejection, but not so high that the patient is at risk from opportunistic infections. TDM of antibiotic therapy is also becoming more important in the fight against bacterial resistance. Recent studies have shown that antibiotic susceptibility testing can save more than $4,000 per patient, as well as reducing infection-related death rates and hospital length of stay.

Update on xenotransplantation

The European Commission's Committee on Medicinal Products and Medical Devices has published a report, "The State of the Art Concerning Xenotransplantation," which is likely to influence European Union (EU) thinking on the subject for years to come. The way in which these experts have addressed the issue has direct implications on regulatory procedures and is clearly affected by ethical and public opinion concerns. In particular, it expresses concern that if the issue is not tackled at the European level, confusion may result from divergent decisions at national level.

The use of non-viable animal materials already is regulated by the European Medical Devices Directive (MDD) adopted in 1993, which covers such items as porcine heart valves, bovine bone, calf pericardium, collagen and gelatin, all of which are subject to extensive inactivation procedures. But human contact with viable animal cells and the re-introduction of cultured autologous or allogeneic cells or fluids into a patient presents a different risk level, especially concerning cross-infection.

A major concern of the committee has clearly been that xenotransplantation carries a significant risk of infection, not only for the recipient but also for the population at large. "If xenotransplantation is seen to be a successful therapy, it is likely to develop rapidly and be used internationally — so that any xenogeneic disease may also spread widely and rapidly," says the report. Its allusions to BSE/CJD and to HIV/AIDS clearly shows that its caution is inspired by current health concerns when it concedes that "public consequences could be catastrophic."

In 1999, the Council of Europe called for a ban on xenotransplantation of whole organs, cells and tissues, and on associated clinical trials. Up to now, the 15-member European Union has not yet put this proposal into legal effect. Extracorporeal perfusion and xenotransplantation of cells already are being conducted within the EU, and the start of clinical trials on humans is on the horizon. Some companies have, however, decided to play it safe and moved research to the U.S. Novartis Pharma (Basel, Switzerland) and BioTransplant (Charlestown, Maryland) have formed a joint venture, Immerge BioTherapeutics (Boston, Massachusetts), with Novartis owning 67% of the shares. The companies propose to combine complementary expertise to address the host rejection response, with Novartis contributing expertise in immunosuppression and BioTransplant its tolerance- induction program and inbred miniature pigs. Another firm, Cryobiogenics (Woodbridge, New Jersey), is developing products for tissue and organ replacement based on technology originating in the former Soviet Union. The company set up laboratories in New Jersey last year duplicating those in Eastern Europe, and plans to import the European pigs to prepare for clinical testing.

Opinions expressed in the report are far from negative: it embraces the positive potential of refining xenotransplantation technology just as firmly as it lists the risks. It even suggests it could be a money-saver in the end. "There may also be a socio-economic impact if xenotransplantation is accepted. In the short term, it could seriously affect, or be limited by, health care budgets. In the long term, however, there may be significant savings in not having to pay for chronic treatments and allowing people to resume a normal life, including work," the report proposes.

The report tends to emphasize more the potential risks of viral and other infections from animals and between humans. The cumulative effect of so much caution may be that regulatory controls stifle development in Europe. The Committee of Experts acknowledges that excessive caution is the wrong response: "There is no such thing as zero risk." But these wise words seem to get overlooked in the general air of anxiety conveyed in the report.

Antimicrobial resistance

Over the years, antimicrobials have saved the lives and eased the suffering of millions of people. By helping to bring many serious infectious diseases under control, these drugs have also contributed to the major gains in life expectancy recorded in the latter part of the last century.

These gains are now jeopardized by another more recent development: the emergence and spread of microbes which are resistant to cheap and effective first choice, or "first-line" drugs. The Alexander Project of 1998 looked at levels of penicillin-resistant pneumococci in Europe, and revealed resistance levels of up to 41% in some areas. At any one time in the United Kingdom, approximately one in 10 hospitalized patients being treated for acute conditions, has hospital-acquired infections (HAI). Patients who present with one or more HAIs during their stay incur costs that are, on average, 2.9 times greater than uninfected patients and remain in hospital on average 2.9 times longer — equal to an additional 14 days' stay.

Monitoring and surveillance of the spread of antimicrobial resistance requires the use of information technology (IT) to analyze and interpret the potentially huge amount of data generated. Current methods, often based on card systems, are difficult to use in trend monitoring and for establishing patterns of infection. WWA Sysmed (Egham, England) has developed the PathMan Infection Control package, designed to integrate with any IT system and allowing the user to exploit data generated within a microbiology laboratory to identify infection pattern trends. It generates automatic warnings to notifiable organizations and is fully web-enabled.

WHO also distributes a computer software program, WHONET, to help improve the systematic monitoring of drug resistance in hospitals and communities, enabling microbiologists and infection control experts to share their data in a common format between national networks.

Epilepsy therapy advances

Michel Le Van Quyen and Jacques Martinerie of the laboratory of cognitive neurosciences at the Hopital Pite -Salpetri re (Paris) have recently published evidence of a "pre-crisis" phase that precedes the first symptoms of an epilepsy episode by about seven minutes.

In some forms of epilepsy, the patient can avoid the crisis by relaxation and breathing techniques. In these cases, an alert seven minutes in advance would help in reducing the severity and frequency of attacks. According to Van Quyen, the plan is to implant electrodes in the temporal lobe of the brain, with signals continuously analyzed by microcomputer implanted in the patient's chest so that the patient can be alerted of the imminence of a crisis.

Levetiracetam is a new anti-epileptic that first came into use in Europe at the end of 1999. It was found to significantly reduce the incidence of epilectic fits even in patients who had failed to respond to existing commonly used anti-epileptics. However, since levetiracetam is chemically unrelated to existing antiepileptic drugs (AEDs), therapeutic drug monitoring techniques used to quantify serum/plasma levels of other AEDs cannot be used for this new drug. In addition, it is not possible to determine levetiracetam immunologically.

Chromsystems (Martinsried, Germany) has developed a new HPLC-based technique using only 100 microliters of serum or plasma to determine levetiracetam levels rapidly using any simple isocratic HPLC system with UV detection.

Asbestos death rate projected to keep rising

In spite of increasingly strict exposure standards for asbestos, the number of asbestos-linked cancers will continue to grow because of the length of time required for them to develop. Occupational asbestos exposure in Western Europe, North America, Japan and Australia peaked in the 1970s, but recent estimates show that 30,000 new asbestos-related cancers continue to be diagnosed globally each year. In France, mesothelioma cases increase about 8% a year.

A recent study at the Hopital Erasme (Brussels, Belgium) showed that in a randomly chosen urban population, out of 160 autopsies performed between 1998 and 2000, pleural plaques were found in 14%, and concentrations of more than 1,000 asbestos bodies per gram of dry lung tissue were found in 13% of subjects. In other words, almost one person in seven of a random sample bore signs of asbestos exposure.

A symposium held during the congress of the European Respiratory Society in Berlin, Germany, called for a European task force to centralize data and to define "at risk" groups who might benefit from early screening.

Phase II trials for autologous skin grafts

Over the past two years, Modex Therapeutics (Lausanne, Switzerland) has changed its strategic focus from cell-based technologies to dermatology and has recently announced positive Phase II results for its lead product, EpiDex, an epidermal skin equiivalent derived from the patients own cells.

"We have shown EpiDex to be at least equivalent to split mesh graft, which is currently the gold standard of treatment for chronic wounds," said Ed Baetge, chief scientific officer at Modex. "We also found that wounds treated with EpiDex continue to close, whereas with split mesh they either close or stay open.

"We are now branching out from EpiDex and licensing in molecules for dermatological diseases other than chronic wounds," Baetge said. A second product, Allox, is in Phase I trials for chronic wounds; a stem cell factor modulator is being developed for various skin conditions like age spots; and a reactive oxygen species scavenger is being reviewed as a treatment for skin damage caused by radiation therapy in breast cancer.

Generics sales booming in Germany

"We project an annual growth rate of 14% in the West European generics market over the next four to five years," said Oliver Schl ter, analyst at the DZ Bank (Frankfurt, Germany). In the U.S., he expects a 10% growth annually. In Germany in 2000, 22% of pharma sales were generics, compared to 14% in the U.S. Sales of the top six European generics manufacturers totaled $4.65 billion in 2000, with Novartis Generic (Basel, Switzerland) as market leader ($1.18 billion). Stada (Bad Vilbel, Germany) is probably growing fastest, with sales for the first nine months of 2001, up 15% to $361 million, and profits up 53% to $56 million. Generics currently constitute 56% of Stada sales.

Two firms target Parkinson's

Oxford BioMedica (Oxford, England) has reported positive results from preclinical studies of its Parkinson's disease gene therapy product, ProSavon. Data in the study showed that administration of the lentivector-based ProSavon in a preclinical disease model resulted in production of dopamine in brain cells previously unable to produce the neurotransmitter and also in correction of Parkinson's disease-like symptoms.

Phytopharm (Godmanchester, England) anticipates starting clinical trials later this year on a family of molecules to demonstrate potential activity against Parkinson's. The company also has started a Phase I trial to assess safety, tolerability and the pharmacokinetic profile of its dementia drug P58. The trial also will assess the effects of the oral drug on cognitive performance. P58 is derived from one of a family of plant-based phytochemicals found in a traditional "Asian tonic" for the elderly that Phytopharm claims has been shown to provide benefits against dementia. The company says P58 acts by reversing the loss of nerve-cell receptors in the aging brain, and is in process of patenting a large family of related chemical compounds with similar properties.

Disetronic divests pharma packing units

The Disetronic group (Burgdorf, Switzerland), Europe's leading manufacturer of insulin pumps and custom-made injection systems, is withdrawing from the pharma packaging systems business in order to concentrate on its two core activities, infusion systems and injection systems.

The company has sold its two device packaging companies, Rondo (Allschwil, Switzerland) and Dividella (Grabs, Switzerland), to Korber (Hamburg, Germany) for an undisclosed price. During the 2000/01 business year, the two companies achieved sales of about $25 million, growing by around 12% annually. Thomas Meyer, Disetronic chief executive, said that in view of the superior growth opportunities in the Infusion Systems and Injection Systems divisions, it made sense to concentrate on expanding these two areas.