On Target

ON TARGET
COMPLIMENTARY NEWS LETTER OF TARGET HEALTH® INC.

23 March 2008

I. WHAT'S NEW?
Target Health Expands
Metropolitan Opera Tickets For La Boheme
II. QUIZ - (Fill In The Blanks)
When Price is the Placebo
III. HISTORY OF MEDICINE - HONORING WOMEN'S HISTORY MONTH
James Miranda Barry, MD (1795-1865)
IV. HEMATOLOGY
Treatment of Hypereosinophilic Syndrome With Mepolizumab
V. EPIDEMIOLOGY
Computerized System Reduces Pediatric Medication Errors
VI. RHEUMATOLOGY
Treatment of RA with the IL-6 Receptor Inhibitor, Tocilizumab
VII. REGULATORY AFFAIRS
FDA Approves New Medical Adhesive
VIII. TARGET HEALTH

I. WHAT'S NEW?

Target Health Expands

Target Health has occupied a second floor at 261 Madison Avenue. Data Management, EDC operations (Target e*CRF®), and software development quickly filled up a big chunk of the space but we still have room to grow. In spite of the economic problems in the US, because we are able to save our clients significant amounts of money when they use both our services and software, we are attracting new opportunities from all over the world, .

For more information about Target Document of any of our software tools for clinical research, please contact Dr. Jules T. Mitchel or Joyce Hays. For new business opportunities, contact Dr. Jules T. Mitchel . Please visit our Website and Blog.

Metropolitan Opera Tickets For La Boheme

Target Health is a Corporate Patron of the Metropolitan Opera in Manhattan. We have one more great offer for this opera season: 2 prime orchesta seats in row H center for La Boheme on Friday evening April 18, at 7:30 if you will be in NY. We will make the tickets available to one of our readers of ON TARGET. Please respond immediately to joycehays@targethealth.com if you are interested.

The two tickets offered previously for Tristan and Isolde went to a colleague who is a top glaucoma expert.

II. QUIZ (Fill In The Blanks)

When Price is the Placebo

According to a recent study at the Stanford Graduate School of Business, how well a medication works may be affected by how much it costs, with cheaper products being less successful at stopping 1) ___. Price can have strong behavioral effects. It has long been known that consumers' beliefs and expectations influence their 2) ___ of products and services. In a separate recent study that measured reactions of brain pleasure centers, wine drinkers experienced more pleasure when sipping a vintage they believed was more expensive, while both wines were actually the same. In the study of painkillers, electrical shocks were applied to the wrists of study participants before and after they took a 3) ___ they believed was a pain killer. When the results were compared, 85% of the patients who believed they were taking the expensive pill reported a reduction in pain from the shocks compared to 61% for those in the low-priced sample group. We have these general beliefs about the world--for example, that cheaper products are of lower 4) ___, and they translate into specific expectations. Then, once these 5) ___ are activated, they translate into self-fulfilling prophecies that actually impact our behavior. The experiment may help explain why some high-cost 6) ___ therapies are popular when inexpensive alternatives are available, such as prescription painkillers versus over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs). Not only pricing, but 7) ___ can also impact the effectiveness of a product. Promoting the efficacy of a medication can have significant improvements to a consumer's health. Advertising, if done well, can give rise to a 8) ___ placebo effect. The researchers commented on the strength of the results: "We thought pricing might shape behavior at the margins, but it turned out to be a pretty strong effect across the board. Moreover, it was clear from the studies that people had no idea that price was actually influencing their performance. The results signaled to us that this was largely a non-conscious effect.” This story reports on research from the Stanford Graduate School of Business.

ANSWERS: 1) pain; 2) judgment; 3) placebo; 4) quality; 5) expectations; 6) medical; 7) advertising; 8) positive

III. HISTORY OF MEDICINE - HONORING WOMEN'S HISTORY MONTH

James Miranda Barry, MD (1795-1865)

By the time Dr. James Miranda Barry reached Canada in 1858, he/she was already legendary in medical and military circles. Historical records convey it was believed by many that this renowned doctor passed as a man to gain a medical education and practice medicine. Dr. Barry had a reputation for being a genius of a surgeon – he/she had performed the first successful Cesarean section by a British doctor, and only the sixth known successful Cesarean by a European. He/she understood the importance of sanitation long before European medicine realized how infection worked. In an age when bloodletting by leeches and freezing the patient were common cures, Barry was an apostle of scientific medicine. In an era that thought that bathing, fresh air, and fresh food were harmful, he/she prescribed these things. The mortality rate dropped instantly in any hospital Dr. Barry was in charge of. Dr. Barry was also considered a man of high ideals – he/she fought tirelessly for the right to medical treatment for women, for blacks, and for the poor. Dr. Barry was a vegetarian long before a vegetarian diet was popular. Some attributed his shortness and his/her strange appearance to his/her diet. James Miranda Barry seemed to appear out of nowhere in 1809, when he/she applied to the prestigious medical school at the University of Edinburgh in Scotland. Dr. Barry appeared in the company of an Irish woman named Mary Anne Bulkley, whom he/she usually introduced as his/her aunt, but once told a friend was his/her mother. Bulkley was sister to a famous painter named James Barry, and James Miranda Barry seemed to have inherited his name. Barry’s passage was eased to university by a number of very powerful protectors. One of these was Francisco Miranda – grandfather of South America’s democratic revolutions and first president of Venezuela. Another was the progressive lord David Steuart Erskine, Lord Buchan, who was a firm believer in modern ideas like gender equality. Shortly after Barry arrived, these protectors seemed to have watched over him/her. Barry earned a reputation as a prodigy – his/her age was uncertain, but he/she passed his exams and thesis either in his/her late teens or early twenties. Dr. Barry studied in London under the greatest surgeons of the age. When Dr. Barry died in 1865, there was no will, but Dr. Barry left very careful instructions about the disposal of his/her body. Dr. Barry requested that no examination of it be made, and to be buried in whatever clothes he/she’d died in. Apparently, the servant who’d prepared his body for burial – a woman named Sophia Bishop – didn’t heed these instructions. Bishop had prepared the body for burial, and she claimed that Dr. Barry was a “perfect woman,” and further claimed there were stretch marks that proved that “she” had given birth. Three weeks after Barry had died, the scandal broke. The declaration that one of the military’s highest-ranking doctors was actually a woman became a popular gossip press piece throughout the British Empire. Pretty soon, there was no shortage of people who’d met Barry saying “they knew it all along.” One story about Barry was that Barry was an early feminist, taking the only possible route to a medical career. Barry was very androgynous, and often amorously connected with men (such as Lord Somerset), and this was considered enough evidence to corroborate the story. Furthermore, recent research has shown that he/she was almost certainly Mary Anne Bulkley’s child. Mrs. Bulkley had one son (named John) and two daughters. Her older daughter, Margaret Bulkley, evaporated from history without a trace four years before Mrs. Bulkley accompanies James Barry to Edinburgh. More convincingly, there are samples of Margaret Bulkley’s and James Barry’s handwriting, and they match. As well, Margaret vanishes at the age of fifteen, and Barry appears four years later in his/her late teens. Dr. Barry is considered to be the first woman in the Western hemisphere to obtain a formal medical degree.

IV. HEMATOLOGY

Treatment of Hypereosinophilic Syndrome With Mepolizumab

The hypereosinophilic syndrome is a group of diseases characterized by persistent blood eosinophilia, defined as more than 1,500 cells per microliter with end-organ involvement and no recognized secondary cause. Although most patients have a response to corticosteroids, side effects are common and can lead to considerable morbidity. According to an article published in the New England Journal of Medicine (2008; 358:1215-1228), an international, randomized, double-blind, placebo-controlled trial was performed to evaluate the safety and efficacy of an anti–interleukin-5 monoclonal antibody, mepolizumab (GlaxoSmithKline), in patients with the hypereosinophilic syndrome. In order to be included in the study, patients had to have been negative for the FIP1L1–PDGFRA fusion gene and had to require prednisone monotherapy, 20 to 60 mg per day, to maintain a stable clinical status and a blood eosinophil count of less than 1,000 per microliter. In terms of treatment, patients received either intravenous mepolizumab or placebo while the prednisone dose was tapered. The primary end point was the reduction of the prednisone dose to 10 mg or less per day for 8 or more consecutive weeks. Results showed that he primary end point was reached in 84% of patients in the mepolizumab group, as compared with 43% of patients in the placebo group (hazard ratio, 2.90; P<0.001) with no increase in clinical activity of the hypereosinophilic syndrome. A blood eosinophil count of less than 600 per microliter for 8 or more consecutive weeks was achieved in 95% of patients receiving mepolizumab, as compared with 45% of patients receiving placebo (hazard ratio, 3.53; P<0.001). Serious adverse events occurred in seven patients receiving mepolizumab (14 events, including one death; mean duration of exposure, 6.7±1.9 months) and in five patients receiving placebo (7 events; mean duration of exposure, 4.3±2.6 months). According to the authors, the study shows that treatment with mepolizumab, an agent designed to target eosinophils, can result in corticosteroid-sparing for patients negative for FIP1L1–PDGFRA who have the hypereosinophilic syndrome.

V. EPIDEMIOLOGY

Computerized System Reduces Pediatric Medication Errors

Although initial studies have suggested that computerized physician order entry reduces pediatric medication errors, no comprehensive error surveillance studies have evaluated the effect of computerized physician order entry on children. As a result, a study published in Pediatrics (2008;121:e421-e427) was performed to evaluate comprehensively the effect of computerized physician order entry on the rate of inpatient pediatric medication errors. The study used interrupted time-series regression analysis to review all charts, orders, and incident reports for 40 admissions per month to the NICU, PICU, and inpatient pediatric wards for 7 months before and 9 months after implementation of commercial computerized physician order entry in a general hospital. Nurse data extractors, who were unaware of study objectives, used an established error surveillance method to detect possible errors. Two physicians who were unaware of when the possible error occurred rated each possible error. Results showed that in 627 pediatric admissions, 156 medication errors were detected out of 12,672 medication orders written over 3,234 patient-days, including 70 nonintercepted serious medication errors (22/1000 patient-days). Twenty-three errors resulted in patient injury (7/1000 patient-days). In time-series analysis, there was a 7% decrease in level of the rates of nonintercepted serious medication errors. There was no change in the rate of injuries as a result of error after computerized physician order entry implementation. According to the authors, the rate of nonintercepted serious medication errors in this pediatric population was reduced by 7% after the introduction of a commercial computerized physician order entry system. This change was much less than previously reported for adults. However, there was no change in the rate of injuries as a result of error. According to the authors, additional refinements could lead to greater effects on error rates.

VI. RHEUMATOLOGY

Treatment of RA with the IL-6 Receptor Inhibitor, Tocilizumab

Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis (RA) via its broad effects on immune and inflammatory responses. As a result, a study published in The Lancet (2008;371:987-997) was performed to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with RA. The investigation was a double-blind, randomized, placebo-controlled, parallel group phase III study. For the study, 623 patients with moderate to severe active RA were randomly assigned to receive tocilizumab 8 mg/kg (n=205), tocilizumab 4 mg/kg (214), or placebo (204) intravenously every 4 weeks, with methotrexate at stable pre-study doses (10–25 mg/week). Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20% improvement in both swollen and tender joint counts. The primary endpoint was the proportion of patients with 20% improvement in signs and symptoms of RA according to American College of Rheumatology criteria (ACR20 response) at week 24. Analyses were by intention to treat. At 24 weeks, ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo (59% in the 8 mg/kg group, 48% in the 4 mg/kg group, and 26% in the placebo group (p<0•0001). More patients receiving tocilizumab than those receiving placebo had at least one adverse event (69% in the 8 mg/kg group; 71% in the 4 mg/kg group; 63% in the placebo group). The most common serious adverse events were serious infections or infestations, reported by six patients in the 8 mg/kg group, three in the 4 mg/kg group, and two in the placebo group. According to the authors, tocilizumab could be an effective therapeutic approach in patients with moderate to severe active RA.

VII. REGULATORY AFFAIRS

TARGET HEALTH excels in Regulatory Affairs and works closely with many of its clients performing all FDA submissions. TARGET HEALTH receives daily updates of new developments at FDA. Each week, highlights of what is going on at FDA are shared to assure that new information is expeditiously made available.

FDA Approves New Medical Adhesive

Fibrin sealants are tissue adhesives that contain the proteins fibrinogen and thrombin, which are essential in the clotting of blood. The FDA has approved a BLA for a new medical adhesive (a fibrin sealant) called Artiss for use in attaching skin grafts onto burn patients. Artiss (Fibrin Sealant, VH S/D 4) differs from other fibrin sealants in that it contains a lower concentration of thrombin. This lower concentration allows surgeons more time to position skin grafts over burns before the graft begins to adhere to the skin. Artiss also contains aprotinin, a synthetic protein that delays the break down of blood clots. The fibrinogen and thrombin proteins in Artiss are derived from human plasma, collected from FDA-licensed plasma centers. Both proteins undergo purification and virus inactivation treatments to reduce the risk of blood-transmissible infections. During a multicenter clinical trial, Artiss was evaluated for its ability to attach skin grafts on two wound sites for 138 patients. At one test site, the skin graft was fixed with Artiss; at the other test site, the graft was fixed with surgical staples. The results showed that Artiss was, within a statistical error, as good as staples to attain complete wound closure. Frequent adverse events, seen in both treatment groups, included bleeding and fluid collection in the tissues, both of which are common during skin grafting procedures. Artiss is manufactured by Baxter Healthcare Corporation, Deerfield, Ill.

For more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

VIII. TARGET HEALTH

TARGET HEALTH INC. (www.targethealth.com) is a full service eCRO with full-time staff dedicated to all aspects of drug and device development. Areas of expertise include Regulatory Affairs, comprising, but not limited to, IND, IDE, NDA, PMA and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, Web Trials, utilizing Target e*CRF®, our proprietary Internet-based Clinical Trial System, and Medical Writing. TARGET HEALTH's Pharmaceutical Advisory Dream Team assists companies in strategic planning from Discovery to Market Launch. Let us help you on your next project.

TARGET HEALTH INC.
261 Madison Avenue
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Phone: (212) 681-2100; Fax (212) 681-2105

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Dr. Jules T. Mitchel, President
Ms Joyce Hays, CEO