2 December 2007
I. WHAT'S NEW?
Clinical Trials at Target Health
II. QUIZ - (Fill In The Blanks)
New Development in Montezuma's Revenge
III. HISTORY OF MEDICINE
Molecular Bases For Disease
IV. WOMEN'S HEALTH
Major Depressive Disorder Affects Bone Mineral Density
V. ONCOLOGY
BMI and Cancer Incidence Studied In Over 1,000,000 Women
VI. RHEUMATOLOGY
Soluble Tumor Necrosis Factor Predicts Mortality in RA
VII.
REGULATORY AFFAIRS
Special Protocol Assessment
VIII. TARGET HEALTH
II. QUIZ
(Fill
In The Blanks)
New Development in Montezuma's Revenge
A new study has shown that a skin patch can prime the 1) ___ system to fend off traveler's diarrhea. 2) ___ that contaminate food and water in developing countries cause roughly 17 million cases of diarrhea each year, many in visitors to those countries. To test a 3) ___ against a strain of Escherichia coli responsible for a large fraction of these bouts, researchers enlisted U.S. volunteers who were planning travel to Mexico or Guatemala. Shortly before each traveler's departure, the scientists mildly abraded a small area of each person's skin and then applied a patch. One-third got the vaccine; the others received an 4) ___ patch. During roughly 2 weeks of travel, 170 participants kept diaries of their health. Five percent of those getting the vaccine patch and 21% of those getting the 5) ___ reported a moderate or severe case of diarrhea on their trips, reports Gregory M. Glenn of Iomai Corp. in Gaithersburg, Md., which makes the vaccine. The patch contains a 6) ___ made by E. coli. In many people, exposure through the skin appears to be enough to induce an immune response without causing disease. According to Glenn, this is an area where there have been few breakthroughs in past years. (meeting of the American Society of Tropical Medicine and Hygiene, week of Dec 1, 2007)IV. WOMEN'S HEALTH
Major Depressive Disorder Affects Bone Mineral Density
An increased prevalence of low bone mineral density (BMD) has been reported in patients with major depressive disorder (MDD), mostly women. As a result, a study published in the Archives of Internal Medicine (2007;167:2329-2336) was performed to obtain additional information, in a controlled prospective study, on the relationship of bone mineral density in premenopausal women with MDD. MDD was defined according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). BMD was measured by dual-energy x-ray absorptiometry at the spine, hip, and forearm. Mean hourly levels of plasma 24-hour cytokines, 24-hour urinary free cortisol, and catecholamine excretion were measured in a subset of women. Results showed that the prevalence of low BMD, defined as a T score of less than -1, was greater in women with MDD vs. controls at the femoral neck (17% vs. 2%; P = .02) and total hip (15% vs. 2%; P = .03), and tended to be greater at the lumbar spine (20% vs. 9%; P = .14). The mean BMD, expressed as grams per square centimeters, was lower in women with MDD at the femoral neck (0.849 vs. 0.866; P = .05) and at the lumbar spine (1.024 vs. 1.043; P = .05) and tended to be lower at the radius (0.696 vs. 0.710; P = .07). Women with MDD had increased mean levels of 24-hour proinflammatory cytokines and decreased levels of anti-inflammatory cytokines. According to the authors, low BMD is more prevalent in premenopausal women with MDD, and that the BMD deficits are of clinical significance and comparable in magnitude to those resulting from established risk factors for osteoporosis, such as smoking and reduced calcium intake. The possible contribution of immune or inflammatory imbalance to low BMD in premenopausal women with MDD remains to be clarified.V. ONCOLOGY
BMI and Cancer Incidence Studied In Over 1,000,000 Women
According to an article published in the British Medical Journal (2007;335:1134-1138), a study was performed to examine the relation between body mass index (BMI; kg/m2) and cancer incidence and mortality. Study participants included 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. The main outcome measures were relative risks of incidence and mortality for all cancers, as well as for 17 specific types of cancer, according to body mass index, adjusted for 1. age, 2. geographical region, 3. socioeconomic status, 4. age at first birth, 4. parity, 5. smoking status, 6. alcohol intake, 7. physical activity, 8. years since menopause, and 9. use of hormone replacement therapy. Results showed that there were 45,037 incident cancers and 17,203 deaths from cancer occurred over the follow-up period. Increasing BMI was associated with an increased incidence of endometrial cancer (2.89), adenocarcinoma of the oesophagus (2.38), kidney cancer (1.53), leukemia (1.50), multiple myeloma (1.31), pancreatic cancer (1.24), non-Hodgkin's lymphoma (1.17), ovarian cancer (1.14), all cancers combined (1.12), breast cancer in postmenopausal women (1.40) and colorectal cancer in premenopausal women (1.61). In general, the relation between BMI and mortality was similar to that for incidence. The authors concluded that increasing BMI is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, BMI represents a major modifiable risk factor and that about half of all cases in postmenopausal women are attributable to overweight or obesity.VI. RHEUMATOLOGY
Soluble Tumor Necrosis Factor Predicts Mortality in RA
According to an article published in Arthritis & Rheumatism (2007;56:3940-3948), a study was performed to investigate whether circulating levels of soluble tumor necrosis factor receptors (sTNFR) are predictive of mortality in rheumatoid arthritis (RA). For the study, 401 white patients with RA followed up for 13 years. Serum levels of sTNFRI and sTNFRII at study entry were quantified using enzyme-linked immunosorbent assays and patients were tracked via the National Health Service Central Register. The relationship between sTNFR levels and mortality was analyzed using a Cox proportional hazards regression model. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated. Results showed that at the end of the 13-year followup period, 132 (32.9%) of 401 patients had died, of whom, 64 (48.5%) died of cardiovascular disease (CVD). Significant associations between all-cause mortality and baseline levels of sTNFRI and sTNFRII were identified in men (HR 1.7 and HR 1.18, respectively) and women (HR 1.33 and HR 1.14, respectively). Analysis including levels of both sTNFRI and sTNFRII indicated that the sTNFRII level was the best overall predictor of mortality. Multivariate analysis also revealed that the sTNFRII level was a predictor of all-cause and CVD mortality independently of age, gender, disease duration, C-reactive protein level, erythrocyte sedimentation rate, rheumatoid factor, nodular disease, modified Health Assessment Questionnaire score, taking CVD drugs, and smoking. According to the authors, the data indicate that serum levels of sTNFR are powerful predictors of mortality in RA and that elevated levels are particularly associated with mortality due to CVD and may be useful for identifying patients at increased risk of premature death.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.Special Protocol Assessment
While some companies choose to enter Phase 3 without subjecting their protocol to a Special Protocol Assessment (SPA), we have never recommended that approach. We have submitted SPAs for several successful programs and as a result, there have been no FDA comments on the study design. FDA buy-ins to the protocol through the SPA process and statistical methodologies via an approved Statistical Analysis Plan (SAP), is critical for a successful clinical program.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
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