After DIA 2009…………ON TARGET Readership Now Over 3,000


Target Health Inc. just completed 4 days at DIA in beautiful San Diego. The booth was very active with visitors from China, Japan, Australia, Europe, Eastern Europe, Chile, Argentina, Canada, US, etc. Our visitors included regulators from Italy and FDA and serious discussions took place on how Target Health’s expertise in regulatory affairs, clinical operations and clinical trial software can allow for a greater transparency of clinical trial data. Irene Ghilezan, Yong Joong Kim, Mark Horn, Joyce Hays and Jules Mitchel represented Target Health to tell our story. The ON TARGET Mailing list is now over 3,000 current readers.

For more information about Target Health and any of our software tools for paperless clinical trials, please contact Dr. Jules T. Mitchel (212-681-2100 ext 0) or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website, and if you like the weekly newsletter, ON TARGET, you’ll love the Blog.

Evo-Devo: Combined Study of Evolution and Development


Since its beginnings as a single 1) ___, life has evolved into a spectacular array of shapes and sizes. How could such diversity of form arise out of evolution’s myriad random genetic mutations? The advent of molecular 2) ___ reinvigorated the study of developmental biology in the 1980s. The evo-devo quickly got scientists’ attention when early breakthroughs revealed that the same master genes were laying out fundamental body plans and parts across the animal kingdom. Genes are stretches of 3) ___ that can be switched on so that they will produce molecules known as proteins. Proteins can then do a number of jobs in the cell or outside it, working to make parts of organisms, switching other genes on and so on. When genes are switched on to produce 4) ___, they can do so at a low level in a limited area or they can crank out lots of protein in many cells. The development of an organism – how one end gets designated as the head or the tail, how feet are enticed to grow at the end of a leg rather than at the wrist – is controlled by a hierarchy of genes, with master genes at the top controlling a next tier of genes, controlling a next and so on. But the real interest for evolutionary biologists is that these hierarchies not only favor the evolution of certain forms but also disallow the growth of others, determining what can and cannot arise not only in the course of the growth of an embryo, but also over the history of life itself. There aren’t new genes arising every time a new species arises. Basically you take existing 5) ___ and processes and modify them, and that’s why humans and chimps can be 99% similar at the genome level and still be different in many ways. Evo-devo has also begun to shine a light on a phenomenon with which evolutionary biologists have long been familiar, the way in which different species will come up with similar solutions when confronted with the same challenges. One of evo-devo’s greatest strengths is its cross-disciplinary nature, bridging not only evolutionary and developmental studies but gaps as broad as those between fossil-hunting paleontologists and molecular biologists. Last year, evolutionary biologist (Univ. Chicago) Dr. Neil Shubin reported the discovery of a fossil fish on Ellesmere Island in northern Canada, that he named, Tiktaalik; special because it has a flat head with eyes on top and has gills and lungs. It’s an animal that’s exploring the interface between water and 6) ___. Tiktaalik was a stunning discovery because this water-loving fish bore wrists, an attribute thought to have been an innovation confined strictly to animals that had already made the transition to land. The genetic tools or toolkit genes for making limbs to walk on land appear to have been present long before 7) ___ made that critical leap. Then, Dr Shubin began a study of the living but ancient fish known as the paddlefish, finding that, these fish were turning on control genes known as Hox genes, in a manner characteristic of the four-limbed, land beasts known as 8) ___, which include cows, people, birds, rodents, etc. The potential for making fingers, hands and feet, crucial innovations used, in emerging from the water to a life of walking and crawling on land, appears to have been present in fish, long before they began flip-flopping their way out of the muck. The genetic tools to build fingers and toes were in place for a long time. Lacking were the 9) ___ conditions where these structures would be useful. Fingers arose when the right environments arose. Major events in 10) ___ like the transition from life in the water to life on land are not necessarily set off by the arising of the genetic mutations that will build the required body parts, or even the appearance of the body parts themselves. Instead, it is theorized that the right ecological situation, the right habitat in which such bold, new forms will prove to be particularly advantageous, may be what is required to set these major transitions in motion.


 1) cell; 2) biology; 3) DNA; 4) proteins; 5) genes; 6) land; 7) fish; 8) tetrapods; 9) environmental; 10) evolution

Eye Glasses


The earliest historical reference to magnification dates back to ancient Egyptian hieroglyphs in the 8th century BCE, which depict “simple glass meniscal lenses”. The earliest written record of magnification dates back to the 1st century CE, when Seneca the Younger, a tutor of Emperor Nero, wrote: “Letters, however small and indistinct, are seen enlarged and more clearly through a globe or glass filled with water”. Emperor Nero is also said to have watched the gladiatorial games using an emerald as a corrective lens. Corrective lenses were said to be used by Abbas Ibn Firnas in the 9th century, who had devised a way to produce very clear glass. These glasses could be shaped and polished into round rocks used for viewing and were known as reading stones. The earliest evidence of “a magnifying device, a convex lens forming a magnified image,” dates back the Book of Optics published by Alhazen in 1021. Its translation into Latin in the 12th century was instrumental to the invention of eyeglasses in 13th century Italy. Sunglasses, in the form of flat panes of smoky quartz, protected the eyes from glare and were used in China in the 12th century or possibly earlier. However, they did not offer any corrective powers. Around 1284 in Italy, Salvino D’Armate is credited with inventing the first wearable eye glasses. The earliest pictorial evidence for the use of eyeglasses, however, is Tomaso da Modena’s 1352 portrait of the cardinal Hugh de Provence reading in a scriptorium. Many theories exist for who should be credited for the invention of traditional eyeglasses. In 1676, Francesco Redi, a professor of medicine at the University of Pisa, wrote that he possessed a 1289 manuscript whose author complains that he would be unable to read or write were it not for the recent invention of glasses. Other stories, possibly legendary, credit Roger Bacon with the invention. Bacon is known to have made one of the first recorded references to the magnifying properties of lenses in 1262, though this was predated by Alhazen’s Book of Optics in 1021. Bacon’s treatise De iride (“On the Rainbow”), which was written while he was a student of Robert Grosseteste, no later than 1235, mentions using optics to “read the smallest letters at incredible distances”. While the exact date and inventor may be forever disputed, it is almost certain that spectacles were invented between 1280 and 1300 in Italy. These early spectacles had convex lenses that could correct both hyperopia (farsightedness), and the presbyopia that commonly develops as a symptom of aging. However, it was not until 1604 that Johannes Kepler published in his treatise on optics and astronomy, the first correct explanation as to why convex and concave lenses could correct presbyopia and myopia. The American scientist Benjamin Franklin, who suffered from both myopia and presbyopia, invented bifocals in 1784 to avoid having to regularly switch between two pairs of glasses. The first lenses for correcting astigmatism were constructed by the British astronomer George Airy in 1825. Early eyepieces were designed to be either held in place by hand or by exerting pressure on the nose (pince-nez). Girolamo Savonarola suggested that eyepieces could be held in place by a ribbon passed over the wearer’s head, this in turn secured by the weight of a hat. The modern style of glasses, held by temples passing over the ears, was developed in 1727 by the British optician Edward Scarlett. These designs were not immediately successful, however, and various styles with attached handles such as “scissors-glasses” and lorgnettes remained fashionable throughout the 18th and into the early 19th century

Body Mass Index and Risk, Age of Onset, and Survival in Patients with Pancreatic Cancer

Obesity has been implicated as a risk factor for pancreatic cancer. As a result, a study published in the Journal of the American Medical Association (2009;301:2553-2562) was performed to evaluate whether there was an association of excess body weight across an age cohort with the risk, age of onset, and overall survival of patients with pancreatic cancer. The investigation was a case-control study of 841 patients with pancreatic adenocarcinoma and 754 healthy individuals frequency matched by age, race, and gender. height and body weight histories were collected by personal interview starting at ages 14 to 19 years and over 10-year intervals progressing to the year prior to recruitment in the study. The main outcome measures were the associations between patients’ body mass index (BMI) and risk of pancreatic cancer, age at onset, and overall survival. Results showed that individuals who were overweight (a BMI of 25-29.9) from the ages of 14 to 39 years or obese (a BMI > 30) from the ages of 20 to 49 years, had a 1.7 and 2.6 increased risk of pancreatic cancer, respectively. This risk was independent of diabetes status and an association was stronger in men. The population-attributable risk percentage of pancreatic cancer based on the mean BMI from the ages of 14 to 59 years was 10.3% for never smokers and 21.3% for ever smokers. Individuals who were overweight or obese from the ages of 20 to 49 years had an earlier onset of pancreatic cancer by 2 to 6 years (median age of onset was 64 years for patients with normal weight, 61 years for overweight patients, and 59 years for obese patients [P < .001]). Compared with those with normal body weight and after adjusting for all clinical factors, individuals who were overweight or obese from the ages of 30 to 79 years, or in the year prior to recruitment, had reduced overall survival of pancreatic cancer regardless of disease stage and tumor resection status. According to the authors, overweight or obesity during early adulthood was associated with a greater risk of pancreatic cancer and a younger age of disease onset and that obesity at an older age was associated with a lower overall survival in patients with pancreatic cancer.

Red Yeast Rice for Dyslipidemia in Statin-Intolerant Patients

Red yeast rice is an herbal supplement that decreases low-density lipoprotein (LDL) cholesterol level. As a result, a study published in the Annals of Internal Medicine (2009;150:830-839), was performed to evaluate the effectiveness and tolerability of red yeast rice and therapeutic lifestyle change to treat dyslipidemia in patients who cannot tolerate statin therapy. The investigation was a randomized, controlled trial performed in a community-based cardiology practice. Study participants included 62 patients with dyslipidemia and history of discontinuation of statin therapy due to myalgias. For the study, patients were assigned by random allocation software to receive red yeast rice, 1,800 mg (31 patients), or placebo (31 patients) twice daily for 24 weeks. All patients were concomitantly enrolled in a 12-week therapeutic lifestyle change program. The primary outcome was LDL cholesterol level, measured at baseline, week 12, and week 24. Secondary outcomes included total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, liver enzyme, and creatinine phosphokinase (CPK) levels; weight; and Brief Pain Inventory score. In the red yeast rice group, LDL cholesterol decreased by 1.11 mmol/L (43 mg/dL) from baseline at week 12 and by 0.90 mmol/L (35 mg/dL) at week 24. In the placebo group, LDL cholesterol decreased by 0.28 mmol/L (11 mg/dL) at week 12 and by 0.39 mmol/L (15 mg/dL) at week 24. Low-density lipoprotein cholesterol level was significantly lower in the red yeast rice group than in the placebo group at both weeks 12 (P < 0.001) and 24 (P = 0.011). Significant treatment effects were also observed for total cholesterol level at weeks 12 (P < 0.001) and 24 (P = 0.016). Levels of HDL cholesterol, triglyceride, liver enzyme, or CPK; weight loss; and pain severity scores did not significantly differ between groups at either week 12 or week 24. According to the authors, red yeast rice and therapeutic lifestyle change decrease LDL cholesterol level without increasing CPK or pain levels and may be a treatment option for dyslipidemic patients who cannot tolerate statin therapy.

outcome measures were spontaneous preterm birth and small for gestational age infants. Study participants included 80% (n=1992) of women who were non-smokers.

 Smoking Early in Pregnancy is Effective

 According to an article published in the British Medical Journal (2009;338:b1081), a study was performed to compare pregnancy outcomes between women who stopped smoking in early pregnancy and those who either did not smoke in pregnancy or continued to smoke. This prospective cohort study evaluated 2,504 nulliparous women participating in the Screening for Pregnancy Endpoints (SCOPE) study grouped by maternal smoking status at 15 (±1) week’s gestation. The main % (n=261) who had stopped smoking, and 10% (n=251) who were current smokers. Results showed no differences in rates of spontaneous preterm birth (4%, n=88 v 4%, n=10) or small for gestational age infants (10%, n=195 v 10%, n=27) between non-smokers and stopped smokers. Current smokers had higher rates of spontaneous preterm birth (10%, n=25 v 4%, n=10; P=0.006) and small for gestational age infants (17%, n=42 v 10%, n=27; P=0.03) than stopped smokers. According to the authors, in women who stopped smoking before 15 weeks’ gestation, rates of spontaneous preterm birth and small for gestational age infants did not differ from those in non-smokers, indicating that these severe adverse effects of smoking may be reversible if smoking is stopped early in pregnancy.

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 Generic Prescription-Only Version of Plan B Emergency Contraceptive for Women Ages 17 and Under

 The FDA has approved the first generic version of the emergency contraceptive Plan B (levonorgestrel) tablets, 0.75 mg. The generic product will be available by prescription only for women ages 17 and under. Plan B was first approved in 1999 for prescription use only for women of all ages and is manufactured by Duramed Pharmaceuticals Inc., of Cincinnati. In 2006, Plan B was approved for nonprescription use for women ages 18 and older. Plan B remained available as a prescription-only product for women ages 17 and under. Today’s approval allows marketing of a prescription-only generic product for women ages 17 and under. No generic levonorgestrel product for emergency contraception can be approved for nonprescription use in women ages 18 and older until Aug. 24, 2009, when the marketing exclusivity held by Duramed for the nonprescription use expires. The generic levonorgestrel tablets 0.75 mg are made by Watson Laboratories Inc., based in Corona, California. Levonorgestrel can prevent pregnancy but is not effective in terminating an existing pregnancy and does not protect against STDs, including HIV infection.

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

Target Health ( 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 (eCTD), IDE, NDA (eCTD), BLA (eCTD), PMA (eCopy) and 510(k) submissions, execution of Clinical Trials, Project Management, Biostatistics and Data Management, EDC utilizing Target e*CRF®, and Medical Writing. Target Health has developed a full suite of eClinical Trial software including 1) Target e*CRF® (EDC plus randomization and batch edit checks), 2) Target e*CTMSTM, 3) Target Document®, 4) Target Encoder®, 5) Target Newsletter®, 6) Target e*CTRTM (electronic medical record for clinical trials). 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.