4 September 2006

ON TARGET - Weekly Journal from Target Health Inc.

(Complimentary Newsletter from Target Health Inc.)

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4 September 2006

I. WHAT'S NEW?
Conference on EDC and Electronic Health Record (EHR)
II. QUIZ (Fill In The Blanks)
Virus, Plus Cold Meat = Healthy Snack
III. HISTORY OF MEDICINE
Medicinal Honey
IV. PUBLIC HEALTH
Bipolar Disease May Be More Costly Than Depression In the Workplace
V. ONCOLOGY
Gene Therapy For Melanoma Using Autologous Lymphocytes
VI. NEUROLOGY
C-Reactive Protein and Stroke
VII. PUBLIC HEALTH
Just Being Overweight Increases Death-Risk
VIII. FDA
Informed Consent - Life-Threatening Situation
IX. Target Health Inc.

I. WHAT'S NEW

Conference on EDC and Electronic Health Record (EHR)

Target Health is pleased to announce that Dr. Mitchel will be presenting a talk on merging EHR and EDC at a conference entitled "Merging Electronic Health Records & Electronic Data Capture - Integrating Patient Information with Drug Development." The meeting will be held at the Sheraton Four Points, Washington DC (September 18-19, 2006). For more information, and/or a discount if you attend, please contact Dr. Jules T. Mitchel.

II. QUIZ (Fill In The Blanks)

Virus, Plus Cold Meat = Healthy Snack

If you enjoy cold deli meats and sausages, how about a dash of live virus on the side? According to the US Food and Drug Administration it could help keep you healthy. In the last week of August 2006, the FDA approved a cocktail of six viruses as a 1) __ additive to be sprayed on ready-to-eat meat before it is packaged to protect against Listeria monocytogenes. This bacterium sometimes grows on cold meat and causes about 2500 cases of severe food 2) ___ and 500 deaths a year in the US alone. The viruses in the additive are 3) ___, that is, they only attack bacterial 4) ___, and are the first to gain FDA approval for use as a food 5) ___. Since they do not harm plant or animal cells they should be safe for 6) ___. In fact, some kinds of 7) __ bacteriophage naturally inhabit the human 8) ___ tract. Intralytix of Baltimore, Maryland, which developed the additive, says that it has licensed the product to an undisclosed multinational company.

ANSWERS: 1) food; 2) poisoning; 3) bacteriophages; 4) cells; 5) additive; 6) humans; 7) viral; 8) digestive

III. HISTORY OF MEDICINE

Medicinal Honey

Honey is collected and used worldwide and is one of the oldest and most revered of foods. The use of honey as medicine is mentioned in the most ancient written records. Physicians in ancient Rome used honey to help their patients fall asleep, while Hippocrates, the famous fifth century B.C.E. Greek physician hailed as the "Father of Medicine," praised honey's healing powers and formulated many honey-based cures for ailments such as skin disorders, ulcers and sores. Meanwhile, the ancient Egyptians used honey to treat cataracts, open wounds, cuts and burns. In World War I, German doctors used honey mixed with cod liver oil to surgically dress soldiers' wounds sustained in battle. During the Afghan-Soviet war, an Arab physician reported that conditions in the clinics and hospitals were so appalling, that honey had to be used to sterilize wounds. For years, singers have used honey to boost their energy and soothe their throats before performances. Edited by Alexander Hays.

IV. PSYCHIATRY

Bipolar Disease May Be More Costly Than Depression In the Workplace

Until recently, studies on the workplace costs of mood disorders has focused largely on major depressive episodes. Bipolar disorder has been overlooked, both because of the failure to distinguish between major depressive disorder and bipolar disorder, and by the failure to evaluate the workplace costs of mania/hypomania. As a result, a study published in the American Journal of Psychiatry (2006;163:1561-1568) was performed to evaluate the effects of bipolar disorder in the workplace. The study used the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) to diagnose bipolar disease, and the WHO Health and Work Performance Questionnaire to measure work. The study results were based on one-year data from 3378 employed respondents to the National Co-morbidity Survey Replication, a nationally representative household survey of 9,282 U.S. adults, conducted in 2001-2003. The questionnaire measured the persistence of the disorders by asking respondents how many days during the past year they experienced an episode of mood disorder. Respondents judged the severity based on symptoms during a worst month. Lost work days due to absence or poor functioning on the job, combined with salary data, yielded an estimate of lost productivity due to the disorders. Interestingly, poor functioning while at work accounted for more lost days than absenteeism. Although only about 1% of workers have bipolar disorder in a year in the U.S., compared to 6.4% with major depression, it was projected that bipolar disorder accounts for 96.2 million lost workdays and $14.1 billion in lost salary-equivalent productivity, compared to 225 million workdays and $36.6 billion for major depression. About three-fourths of bipolar respondents had experienced depressive episodes over the past year, with about 63% also having agitated manic or hypomanic episodes. The bipolar-associated depressive episodes were much more persistent -- affecting 134-164 days -- compared to only 98 days for major depression. All measures of lost work performance were consistently higher among workers with bipolar disorder who had major depressive episodes than those who reported only manic or hypomanic episodes. The latter workers' lost performance was on a par with workers who had major depressive disorder. According to the authors, employer interest in workplace costs of mood disorders should be broadened beyond major depressive disorder to include bipolar disorder, and that effectiveness trials are needed to study the return on employer investment of coordinated programs for workplace screening and treatment of bipolar disorder and major depressive disorder.

V. ONCOLOGY

Gene Therapy For Melanoma Using Autologous Lymphocytes

Skin cancer is the most common of all cancers. According to the American Cancer Society, melanoma accounts for about 4% of skin cancer cases, but it is also the most serious and most aggressive type. In the U.S., an estimated 62,190 new cases of melanoma will be diagnosed and approximately 7,910 people will die of the disease in 2006. According to an article published on line in Science Express (31 August 2006), a sustained regression of advanced melanoma has been demonstrated in a study of 17 patients by genetically engineering patients' own white blood cells to recognize and attack their own cancer cells. For the study, a small sample of blood was withdrawn that contained normal lymphocytes from individual patients with melanoma, and these normal cells were infected with a retrovirus in the laboratory. The retrovirus acts like a carrier pigeon to deliver genes that encode specific proteins, called T cell receptors (TCRs), into cells. When the genes are turned on, TCRs are made and these receptor proteins decorate the outer surface of the lymphocytes. The TCRs act as homing devices in that they recognize and bind to certain molecules found on the surface of tumor cells. The TCRs then activate the lymphocytes to destroy the cancer cells. In the present study, newly engineered lymphocytes were infused into 17 patients with advanced metastatic melanoma. There were three groups of patients in this study. The first group consisted of three patients who showed no delay in the progression of their disease. As the study evolved, the treatment method of lymphocytes improved so that the cells could be administered in their most active growth phase. In the remaining two groups, patients received the improved treatments. Results showed that two patients 1) experienced cancer regression, 2) had sustained high levels of genetically altered lymphocytes, and 3) remained disease-free over one year. One month after receiving gene therapy, all patients in the last two groups still had 9% to 56% of their TCR-expressing lymphocytes. There were no toxic side effects attributed to the genetically modified cells in any patient. According to the authors, approaches to increase the function of the engineered TCRs, including the development of TCRs that can bind to tumor cells more tightly, and to further optimize delivery methods using retroviruses are under investigation. The authors added that these very exciting successes in treating advanced melanoma bring hope that this type of gene therapy, altering lymphocytes, could be used in many types of common cancers and could be achievable in the near future.

VI. NEUROLOGY

C-Reactive Protein and Stroke

C-reactive protein (CRP) has evolved as an inflammatory risk marker of cardiovascular disease. Several single-nucleotide polymorphisms at the CRP locus have been found to be associated with CRP levels. As a result, a study published in the journal Stroke (2006 37: 2018-2023), was performed to investigate CRP levels and genetic variants in etiological subtypes of ischemic stroke. The study included 600 consecutive ischemic stroke cases (18 to 69 years) and 600 matched controls from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) from western Sweden. Stroke subtypes were defined by the TOAST classification. Serum CRP levels were determined by a high-sensitivity immunometric assay. Results showed that CRP levels were significantly higher for all ischemic stroke subtypes compared with controls, both in the acute phase and at the 3-month follow-up. After adjustment for traditional risk factors, CRP at follow-up was related to higher odds ratios (ORs) of overall ischemic stroke (OR, 1.25) and large-vessel disease (OR, 1.48). The CRP –286C>T>A, 1059G>C, and 1444C>T single-nucleotide polymorphisms showed significant associations with CRP levels. However, neither CRP genotypes nor haplotypes showed an association to overall ischemic stroke. According to the authors, this is the first large study on CRP in different TOAST subtypes in a young ischemic stroke population. CRP levels differed between etiological subtypes of ischemic stroke both in the acute phase and at the 3-month follow-up. CRP at follow-up was associated with overall ischemic stroke and the large-vessel disease subtype. Genetic variants at the CRP locus were associated with CRP levels, but no association was detected for overall ischemic stroke.

VII. PUBLIC HEALTH

Just Being Overweight Increases Death-Risk

Obesity, defined by a body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) of 30.0 or more, is associated with an increased risk of death. However, the relation between overweight (a BMI of 25.0 to 29.9) and the risk of death has been questioned. As a result, a study published in the New England Journal of medicine (2006;355:763-778) was performed to prospectively examine BMI in relation to the risk of death from any cause in 527,265 U.S. men and women. Study participants were derived from the National Institutes of Health–AARP cohort who were 50 to 71 years old at enrollment in 1995–1996. BMI was calculated from self-reported weight and height. Relative risks and 95% confidence intervals were adjusted for age, race or ethnic group, level of education, smoking status, physical activity, and alcohol intake. Alternative analyses were conducted to address potential biases related to preexisting chronic disease and smoking status. Results showed that during a maximum follow-up of 10 years through 2005, 61,317 participants (42,173 men and 19,144 women) died. Initial analyses showed an increased risk of death for the highest and lowest categories of BMI among both men and women, in all racial or ethnic groups, and at all ages. When the analysis was restricted to healthy people who had never smoked, the risk of death was associated with both overweight and obesity among men and women. In analyses of BMI during midlife (age of 50 years) among those who had never smoked, the associations became stronger, with the risk of death increasing by 20 to 40% among overweight persons. This risk increased by 2-3x among obese persons, and the risk of death among underweight persons was attenuated. According to the authors, excess body weight during midlife, including overweight, is associated with an increased risk of death.

VIII. FDA

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.

Informed Consent - Life-Threatening Situation

On rare occasions and under carefully regulated circumstances, a person in a life-threatening situation, because of his or her medical condition, can be enrolled in an emergency research study without being able to give his or her informed consent. Since 1996, FDA has received a sizable number of requests to conduct a clinical investigation under § 50.24. The FDA is now taking a close look at the implementation of its 1996 regulation, 21 CFR 50.24, which allows clinical emergency research when informed consent cannot be obtained. Such emergency research has been allowed under very restricted circumstances since 1996 when FDA regulations went into effect providing for a narrow exception to the informed consent research requirements. The current initiative is part of FDA's ongoing effort to ensure the highest level of scientific and ethical rigor in clinical research and is one of many projects under its Human Subject Protection and Bioresearch Monitoring Program (HSP/BIMO Program). The HSP/BIMO Initiative is part of a series of new policy and regulatory developments aimed at strengthening the Agency's oversight and protection of patients in clinical trials and the integrity of resulting data. HSP/BIMO encompasses devices, foods, human drugs, biological drug products and veterinary medicine.

FDA's review of emergency research with an exception from informed consent has two key components:

A public hearing on emergency research that will be held October 11, 2006, at the University of Maryland Shady Grove Center, 9630 Gudelsky Drive, Rockville, MD.
A draft guidance (Guidance for Institutional Review Boards (IRBs), Clinical Investigators, and Sponsors; Exception from Informed Consent Requirements for Emergency Research) is being made available to assist IRBs, clinical investigators, and sponsors in the development and conduct of emergency research.

For more on the specific criteria that must be met before a planned clinical emergency research program can be initiated, see the draft Guidance for IRBs, Clinical Investigators, and Sponsors; Exception from Informed consent Requirements for Emergency Research:
For more information about our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

IX. TARGET HEALTH

TARGET HEALTH INC. (www.targethealth.com) is a full service e*CRO 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 (PADT) 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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Dr. Jules T. Mitchel, President
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