On Target

ON TARGET
COMPLIMENTARY NEWS LETTER OF TARGET HEALTH® INC.

3 May 2008

I. WHAT'S NEW?
28 Days From Last Patient Last Visit (LPLV) to Final Study Report
II. QUIZ - (Fill In The Blanks)
Japanese Mushroom Leads To Breakthrough In Protein Research
III. HISTORY OF MEDICINE
Alzheimer's Disease
IV. CARDIOLOGY
   Home Use External Defibrillator Not Better Than Calling 911
V. GERONTOLOGY
   Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer
VI. HEMATOLOGY
Hemoglobin-Based Blood Substitutes Increase the Risks For Death and MI
VII. REGULATORY AFFAIRS
  FDA Approves Coronary Artery Plaque Imaging Device
VIII. TARGET HEALTH

I. WHAT'S NEW?

28 Business Days From Last Patient Last Visit (LPLV) to Final Study Report

Target Health is pleased to announce that it has delivered a final study report within 28 business days of LPLV. The study involved 40 sites with over 1,600 subjects across the US which Target Health monitored. Because we also did the biostatistical analyses and medical writing, and Target e*CRF® was used for EDC and data management, there was full integration between us and the sponsor. To be quite candid, with a paper trial we would have added at least 6-8 weeks to the program. Last minute queries were resolved rapidly through Target e*CRF®. Management reports provided a running tally of outstanding queries, locked patients and patients signed off by the investigators.

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

II. QUIZ (Fill In The Blanks)

Japanese Mushroom Leads To Breakthrough In Protein Research

Using an enzyme of the Japanese mushroom Grifola frondosa (Maitake or dancing mushroom), 1) ___ can be identified without knowing the organism's genetic composition. This advance simplifies the study of proteins lying at the root of such diseases as cancer and 2) ___. Utrecht University Prof. Albert Heck's research group announced this breakthrough on the website of the journal Nature Methods. Proteins play a critical role in disease and growth processes of humans, animals and plants. Identification was previously only possible when the genetic composition of the organism in question was known. Thanks to Heck's discovery, this is now a thing of the past. Heck used an 3) ___ from the Japanese mushroom Grifola frondosa to identify proteins. This makes it possible to study the proteins of an organism of which the genetic composition is – as yet – unknown (e.g. exotic animal species). In addition, research into proteins responsible for such diseases as 4) ___ and diabetes, which usually undergo modification as a result, is much more effective. In order to study the role proteins play in biological processes, the proteins themselves are 5) ___ into peptides, which are analyzed using a mass spectrometer. The measurements produce a unique ‘fingerprint’ for each peptide. In the past, a protein could only be identified using the fingerprint after comparing the fingerprint to a database of known 6) ___ compositions. The enzyme of the Japanese mushroom that Heck used cleaved the proteins in such a way that the peptides produced simplified fingerprints. As a result, the proteins could be identified even though the organism's 7) ___ has not been mapped out. This greatly simplifies protein identification.

ANSWERS: 1) proteins; 2) diabetes; 3) enzyme; 4) cancer; 5) cleaved; 6) genetic; 7) genome

III. HISTORY OF MEDICINE

Alzheimer's Disease

Although the concept of dementia goes as far back as the ancient Greek and Roman philosophers and physicians, it was in 1901 when Alöis Alzheimer, a German psychiatrist, identified the first case of what became known as Alzheimer's disease in a fifty-year-old woman he called Auguste D. Alöis Alzheimer followed her until she died in 1906, when he first reported the case publicly. In the following five years, eleven similar cases were reported in the medical literature, some of them already using the term Alzheimer's disease. The official consideration of the disease as a distinctive entity is attributed to Emil Kraepelin, who included Alzheimer's disease or presenile dementia as a subtype of senile dementia in the eighth edition of his Textbook of Psychiatry, published in 1910. For most of the 20th century, the diagnosis of Alzheimer's disease was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia. The terminology changed after 1977 when a conference concluded that the clinical and pathological manifestations of presenile and senile dementia were almost identical, although the authors also added that this did not rule out the possibility of different etiologies. This eventually led to the use of Alzheimer's disease independently of onset age of the disease. The term senile dementia of the Alzheimer type (SDAT) was used for a time to describe the condition in those over 65, with classical Alzheimer's disease being used for those younger. Eventually, the term Alzheimer's disease was formally adopted in medical nomenclature to describe individuals of all ages with a characteristic common symptom pattern, disease course, and neuropathology.

IV. CARDIOLOGY

Home Use External Defibrillator Not Better Than Calling 911

The most common location of out-of-hospital sudden cardiac arrest is the home, a situation in which emergency medical services are challenged to provide timely care. Consequently, home use of an automated external defibrillator (AED) might offer an opportunity to improve survival for patients at risk. In order to evaluate the effectiveness of AEDs, a study published in the New England Journal of Medicine (2008;358:1793-1804) randomly assigned 7001 patients with previous anterior-wall myocardial infarction, who were not candidates for an implantable cardioverter–defibrillator, to receive one of two responses to sudden cardiac arrest occurring at home: either the control response (calling emergency medical services and performing cardiopulmonary resuscitation [CPR]) or the use of an AED, followed by calling emergency medical services and performing CPR. The primary outcome was death from any cause. The median age of the patients was 62 years and 17% were women. The median follow-up was 37.3 months. Overall, 450 patients died: 228 of 3506 patients (6.5%) in the control group and 222 of 3495 patients (6.4%) in the AED group. Mortality did not differ significantly in major prespecified subgroups. Only 160 deaths (35.6%) were considered to be from sudden cardiac arrest from tachyarrhythmia. Of these deaths, 117 occurred at home, with 58 at-home events witnessed. AEDs were used in 32 patients. Of these patients, 14 received an appropriate shock, and 4 survived to hospital discharge. There were no documented inappropriate shocks. According to the authors, for survivors of anterior-wall myocardial infarction who were not candidates for implantation of a cardioverter–defibrillator, access to a home AED did not significantly improve overall survival, as compared with reliance on conventional resuscitation methods.

V. GERONTOLOGY

Treating Hypertension After the Age of 80

While it has been suggested that antihypertensive therapy may reduce the risk of stroke, despite possibly increasing the risk of death in the elderly, it is not clear whether the treatment of patients with hypertension who are 80 years of age or older is beneficial. As a result, a study published in the New England Journal of Medicine (2008;358:1887-1898) randomly assigned 3,845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting–enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke. The active-treatment group (1,933 patients) and the placebo group (1,912 patients) were well matched (mean age, 83.6 years; mean blood pressure while sitting, 173/91 mm Hg); 11.8% had a history of cardiovascular disease. Median follow-up was 1.8 years. At 2 years, the mean blood pressure while sitting was 15/6mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (P=0.06), a 39% reduction in the rate of death from stroke (P=0.05), a 21% reduction in the rate of death from any cause (P=0.02), a 23% reduction in the rate of death from cardiovascular causes (P=0.06), and a 64% reduction in the rate of heart failure (P<0.001). Fewer serious adverse events were reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001). According to the authors, the results provide evidence that antihypertensive treatment with indapamide (sustained release), with or without perindopril, in persons 80 years of age or older is beneficial.

VI. HEMATOLOGY

Hemoglobin-Based Blood Substitutes Increase the Risks For Death and MI

Hemoglobin-based blood substitutes (HBBSs) are infusible oxygen-carrying liquids that have long shelf lives, have no need for refrigeration or cross-matching, and are ideal for treating hemorrhagic shock in remote settings. Some trials of HBBSs during the last decade have reported increased risks without clinical benefit. As a result, a study published online on 28 April 2008 in the Journal of the American Medical Association, was performed to assess the safety of HBBSs in surgical, stroke, and trauma patients. The data sources for the study included: PubMed, EMBASE, and Cochrane Library searches for articles using hemoglobin and blood substitutes from 1980 through March 25, 2008; reviews of FDA advisory committee meeting materials; and Internet searches for company press releases. Study selection included randomized controlled trials which included patients aged 19 years and older who received HBBSs therapeutically. The database searches yielded 70 trials of which 13 met these criteria. In addition, data from 2 other trials were reported in 2 press releases, and additional data were included in 1 relevant FDA review. The primary outcomes of interest were data on death and myocardial infarction (MI). Sixteen trials involving 5 different products and 3,711 patients in varied patient populations were identified. A test for heterogeneity of the results of these trials was not significant for either mortality or MI. Overall, there was a statistically significant increase in the risk of death (164 deaths in the HBBS-treated groups and 123 deaths in the control groups; relative risk [RR], 1.30, and risk of MI (59 MIs in the HBBS-treated groups and 16 MIs in the control groups; RR, 2.71). Subgroup analysis of these trials indicated the increased risk was not restricted to a particular HBBS or clinical indication. According to the authors, based on the available data, use of HBBSs is associated with a significantly increased risk of death and MI. The authors added that it is still not clear as to the reason for these results.

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 Coronary Artery Plaque Imaging Device

Plaque is a deposit made up of cholesterol-rich fat, calcium, and other substances found in the blood. As plaque accumulates on the artery wall, it reduces blood flow to the heart muscle and increases the risk of blood clots which can lead to a heart attack. Nearly one million Americans suffer a heart attack every year and about half die. Many heart attacks occur when a fatty coronary plaque ruptures, forming dangerous blood clots. Pathologic studies of patients who died from heart attack have identified a large lipid (fatty) core among features of coronary artery disease that were associated with plaque rupture and thrombosis (blood clots). The FDA has cleared for marketing a device that a doctor can use to see inside a blood vessel to assess the fat content of the plaque which builds up on the wall of the coronary arteries. The InfraReDx LipiScan NIR Catheter Imaging System uses infrared imaging to detect lipid core-containing plaques of interest and assess a patient's coronary artery lipid core burden index. The device works by placing a catheter equipped with a fiber-optic laser light into the artery. The device shines the near infrared light delivered through the blood to the artery wall, and measures the light reflected back from the artery wall, a technique called spectroscopy. The reflected wavelengths vary depending on how much fat and other substances are in the plaque in the illuminated portion of the wall. LipiScan is manufactured by InfraReDx Inc. of Burlington, MA. The device is cleared for use by physicians who are evaluating patients with symptoms of coronary heart disease during a heart test known as cardiac angiography, to help in detection of plaques that have lipid (fatty) cores.

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.
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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