On Target

ON TARGET
COMPLIMENTARY NEWS LETTER OF TARGET HEALTH® INC.

16 March 2008

I. WHAT'S NEW?
Target Health Goes Paperless
Metropolitan Opera Tickets For Tristan and Isolde
II. QUIZ - (Fill In The Blanks)
Loss of Smell Linked to Alzheimer's Disease
III. HISTORY OF MEDICINE - HONORING WOMEN'S HISTORY MONTH
Doctoring: Conduct Unbecoming Women, The Forgotten Minority
IV. CARDIOLOGY
Smoking Increases Risk of Cardiovascular Disease - Korean Study
V. ONCOLOGY
Molecular Diagnostic Test for Prostate Cancer
VI. PSYCHOSOMATIC MEDICINE
Depression and Hostility Affect Inflammatory Markers
VII. REGULATORY AFFAIRS
Janet Woodcock Appointed as Permanent Director of CDER - Congratulations
VIII. TARGET HEALTH

I. WHAT'S NEW?

Target Health Goes Paperless

By using Target Document®, our proprietary document management and document sharing system, Target Health has formally transitioned to paperless storage of all regulatory and clinical documents. Since all of our regulatory submissions over the past several years have been fully scanned, we will be freeing up some cabinet space. Our clients will also be using Target Document for storing and viewing all Trial Master File (TMF) documents. Our clients will have full control over and real time access to all of the documents.

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 Tristan and Isolde

Target Health has 2 great tickets at the Met for March 28 for Tristan and Isolde. We will make them available to one of our readers of ON TARGET. Please respond immediately to joycehays@targethealth.com if you are interested and will be in NY..

II. QUIZ (Fill In The Blanks)

Loss of Smell Linked to Alzheimer's Disease

A study published in Archives of General Psychiatry, suggest that those with difficulty identifying familiar smells are more likely to develop the degenerative 1) ___ disorder, Alzheimer’s Disease (AD). Researchers at Rush University Medical Center in Chicago asked nearly 600 adults between the ages of 54 and 100 to sniff and identify a dozen common scents, including black pepper, pineapple, paint thinner, soap, onion, lemon, cinnamon, gasoline, smoke, rose, banana, and chocolate. Over the following five years, the subjects also completed a number of 2) ___ tests designed to track changes in memory and thinking skills. Subjects who made at least four errors on the sniff tests were 50% more likely to develop problems with thinking and memory than subjects who made no more than one error. Trouble identifying familiar odors was linked to a greater likelihood of advancing from a state of mild cognitive impairment to AD. Identifying odors is a complex process that involves first perceiving a particular smell and then comparing it against the brain's 3) ___ bank of smells. AD gradually robs individuals of their memories; even those for various odors. However, inability to recognize certain odors often has a far less ominous cause. Disorders of smell are relatively common in the general population, especially among older adults. As many as half of folks aged 65 and older are thought to suffer some loss of their sense of smell. The most common causes are upper 4) ___ tract infections, head trauma, and nasal and sinus disorders, including allergies and chronic sinusitis. Certain medications, illnesses, and nutritional deficiencies can also contribute to smell disturbances. Cigarette smoking may dull the senses to some degree, but rarely causes a complete loss of smell. Using currently available diagnostic tests, physicians can diagnose individuals with moderate to severe AD with about 90% accuracy. However, making the diagnosis in the early stages of the illness is far more difficult. Early 5) ___ of the disease is becoming increasingly important, as new and more effective treatments are introduced. The good news is that preventative measures, like taking a supplement of B-Vitamin folate, can help ward off Alzheimer's disease. The results of a University of California, Irvine study suggest that older Americans whose total daily folate intake is at or above the recommended dietary allowance could dramatically cut their chances of developing AD. At the start of this study, researchers collected dietary information from more than 500 healthy volunteers aged 60 and older who showed no signs of AD. The subjects recorded the foods they ate during a typical week and reported whether they took supplements containing 6) ___. Study participants who reported folate intakes that were equal to or greater than the recommended daily allowance of 400 micrograms had a 55% reduction in the risk of AD. Although folate is present in many foods, most of the subjects who achieved the recommended daily intake levels did so by taking folate supplements. Other 7) ___ measures are physical activities which enhance blood flow to the brain, thus improving its function; mental activities like working puzzles and learning new skills, which boost cognitive functions. While a number of AD drugs are under investigation, few effective treatments currently are available. At this point, preventive measures appear to be the best defense, and the sooner in life they're started, the better.

ANSWERS: 1) brain; 2) cognitive; 3) memory; 4) respiratory; 5) diagnosis; 6) folate; 7) preventative

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

Doctoring: Conduct Unbecoming Women, The Forgotten Minority

Before 1850, the field of medicine was almost completely closed to women, who were excluded from virtually every medical college. In 1850, a group of radical reformist male Quaker physicians and associates founded the Female Medical College of Pennsylvania to offer formal medical training to women. By the 1890s, under the guidance of a series of pioneering women deans, aided by loyal male allies, the school grew into a strong and progressive medical college, renamed the Woman's Medical College of Pennsylvania (WMC). This development occurred despite the stubborn and at times near-violent opposition of most of the male medical community of Philadelphia. The WMC survived periods of crisis and instability, making it not only a remarkable experiment in single-gender professional education, but also a rare 19th-century case of female-male collaboration in science and medicine. Other women's medical schools followed the bold experiment in Philadelphia, but, largely for financial reasons, all of these closed by 1921. Through its unique survival, WMC provided rare opportunities for women physicians and scientists to teach and carry out research, while maintaining a secure assurance of medical education free from gender discrimination. Later in the 20th century, external forces and a wavering sense of purpose led leaders of the school to opt for admitting men to the medical classes and changing the name to Medical College of Pennsylvania. Jewish and African American women, gained admission to WMC by the 1870s. Traditionally, learning the art of medicine required only an apprenticeship with a practicing physician. The Industrial Revolution of the 18th century proved to be the watershed between learning through apprenticeships and the 19th century move toward earning credentials through education. This move away from apprenticing to formal education created a major stumbling block for women in their quest to become physicians. For male physicians in the early 1800s, a degree was still optional although often desired. But performing an apprenticeship alone was not enough of an education for the majority of women; a degree from a medical institution was required. In 1847, Harriet K. Hunt, applied to the Harvard Medical School for admission. She had been in medical practice for twelve years. The Harvard trustees responded to her requests by passing a resolution forbidding the admission of women that was not repealed until 1946. As late as 1947, there were 77 approved medical colleges in America with four still closed to women; these coed schools often limited their enrollment of women, to 5% of the class. Even when opportunities for medical education improved, female physicians experienced discrimination as they tried to seek internships and arrange residencies for additional medical training. Women were discouraged from becoming specialists except in the areas that were recognized as feminine, such as pediatrics and gynecology. This is one of the many factors why, even today, women are less represented in medical specialties. Women in medicine confronted these obstacles by vigorously pursuing their education at home and abroad, forming their own medical colleges and organizing their own professional societies. Rather than wait for men to accept them, they created their own place in a rapidly changing world. In 1878 the New England Hospital Medical Society became the first women's medical society in the United States. It began as a response to the Massachusetts Medical Society being closed to women. In 1893 the Women's Medical Journal was founded and in 1915 the American Medical Women's Association began.

IV. CARDIOLOGY

Smoking Increases Risk of Cardiovascular Disease - Korean Study

The association of smoking with cardiovascular diseases in populations with low cholesterol levels is unclear and this lack of clarity may have contributed to the very high prevalence of smoking in East Asian men. The effect of smoking on stroke subtypes is particularly unclear. As a result, a study published in the journal Stroke (2008;39:760-767), was performed to assess the association of smoking and cardiovascular disease in a population with low cholesterol levels. For the study, data were used from a prospective cohort study of 648,346 Korean men aged 30 to 64 years at their baseline assessment in 1992. Results showed the mean total cholesterol at baseline was 4.9 mmol/L (or 189 mg/L) and 59% of the men were current smokers. Over the follow-up period of 10 years, 9,475 men experienced any type of stroke, 4,768 experienced an ischemic stroke, 2,380 an intracerebral hemorrhage, 786 a subarachnoid hemorrhage, 3,329 men experienced a myocardial infarction, and 269 an aortic aneurysm. Smoking at baseline was associated with marked increases in risk of ischemic stroke (hazard ratio comparing current smokers with never smokers 1.58), subarachnoid hemorrhage (1.91), myocardial infarction (2.01), and aortic aneurysm (1.47) with these effects remaining after adjustment for potential confounding factors and with the first 5 years of events excluded from the analyses. The effect of smoking on these outcomes was the same among men with cholesterol levels below the median value for this population as among those with higher levels. There was no association of smoking with intracerebral hemorrhage. Smoking accounted for 20% of all cardiovascular disease outcomes in this population. According to the authors, smoking is a major risk factor for cardiovascular diseases in populations with low cholesterol levels and global interventions are required to halt the emerging tobacco epidemic in low- and middle-income countries.

V. ONCOLOGY

Molecular Diagnostic Test for Prostate Cancer

A blood test to detect colon cancer at a preventable stage would represent a major advancement. Proteomics involves the identification of proteins and the determination of their role in physiological and pathophysiological functions. Using focused proteomics analysis of nuclear structural proteins, 2 colon cancer–specific markers colon cancer–specific antigen (CCSA)-3 and CCSA-4, have been developed into blood-based markers that are able to distinguish individuals with colorectal cancer from those without. CCSA-2 is another novel colon cancer marker identified using focused proteomics. According to a study published in Clinical Cancer Research (228;14:1349-1354) CCSA-2 was evaluated as a serum-based colon cancer marker. A total of 111 serum samples from individuals who underwent colonoscopy and were subsequently diagnosed as either being normal or having hyperplastic polyps, nonadvanced adenomas, advanced adenomas, and colorectal cancer were evaluated. A diverse control population that consisted of 125 serum samples was also included in this study. Receiver operating characteristic analyses were used to measure the sensitivity and specificity of CCSA-2. CCSA-2 at a cutoff of 10.8 µg/mL has overall specificity of 78.4% and sensitivity of 97.3% in separating individuals with advanced adenomas and colorectal cancer from normal, hyperplastic, and nonadvanced adenoma populations. The receiver operating characteristic curve for CCSA-2 has an area under the curve of 0.90. The authors concluded that CCSA-2 is a potential serum-based marker for colon cancer detection with high sensitivity and specificity.

VI. PSYCHOSOMATIC MEDICINE

Depression and Hostility Affect Inflammatory Markers

Recent evidence suggests that depressive symptoms and hostility may act together, as interacting factors, to have an effect on the circulating levels of inflammatory markers relevant to coronary artery disease. As a result, a study published in Psychosomatic Medicine (2008;70:197-204) was performed to clarify the nature of this interaction by examining the cross-sectional associations of depressive symptoms, hostility, and their interaction with circulating levels of two such inflammatory markers—interleukin-6 (IL-6) and C-reactive protein (CRP). For the study, 316 healthy, older adults completed the Beck Depression Inventory-II and the Cook-Medley Hostility Scale, and also underwent a blood draw for the assessment of serum IL-6 and CRP. Regression analyses were performed to examine depressive symptoms, hostility, and their interaction as predictors of serum IL-6 and CRP. Results showed that after adjustment for demographic factors, cardiovascular risk factors, and health behaviors, there was a statistically significant association of depressive symptoms x hostility interactions for serum IL-6 (p < .01) and CRP (p < .05). Simple slope analyses revealed that hostility was positively related to serum IL-6 only among individuals with higher depressive symptoms. The pattern of results was similar for serum CRP, although none of the simple slopes was significant. According to the authors, the findings suggest that depressive symptoms may moderate the hostility-inflammation relationship, such that hostility may augment inflammatory processes relevant to coronary artery disease only in the presence of depressive symptoms. The authors added that the results also extend previous findings from younger adults to older adults from the general community.

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.

Janet Woodcock Appointed as Permanent Director of CDER - Congratulations

Commissioner of Food and Drugs Dr. Andrew C. von Eschenbach announced the appointment of Janet Woodcock, M.D., as director of the agency's Center for Drug Evaluation and Research (CDER). As a prominent FDA scientist and executive, Dr. Woodcock has received numerous awards, including a Presidential Rank Meritorious Executive Award, the American Medical Association's Nathan Davis Award, the American Association for Cancer Research Public Service Award, the National Organization for Rare Disorders Public Health Leadership Award, the Personalized Medicine Coalition's Award for Leadership in Personalized Medicine, the National Alliance for Hispanic Health's VIDA Award, and six Special Citations from FDA Commissioners. Dr. Woodcock received her Doctor of Medicine from Northwestern Medical School and completed further training and held teaching appointments at the Pennsylvania State University and the University of California in San Francisco. Throughout her career at the FDA, Dr. Woodcock has played an integral role in advancing the health of the American public. Under her strong leadership, the FDA launched the Critical Path Initiative designed to bridge the gap between basic scientific research and the medical product development process. This initiative called for a collaborative cross-sector effort to modernize the drug development process and has resulted in several prominent partnerships looking at a wide variety of scientific issues. Dr. Woodcock will continue to be involved in this initiative, as well as the emerging post-market surveillance collaborations with the private sector. While serving as the agency's Deputy Commissioner and Chief Medical Officer, where she oversaw scientific and regulatory operations, Dr. Woodcock agreed to assume the role of Acting Director of CDER in October 2007. The recently announced Safety First program is one of the initiatives she has led since assuming the Center Director role in an acting capacity. An internist and rheumatologist, Dr. Woodcock has previously held several other leadership positions in the agency, including Director, Office of Therapeutics Research and Review, and Acting Deputy Director, Center for Biologics Evaluation and Research, as well as Director of CDER.

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.

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