24 February 2008
I. WHAT'S NEW?
Regulatory Affairs at Target Health
II. QUIZ - (Fill In The Blanks)
Cloning is a Reproductive Trick of Nature, When Survival is Everything
III. HISTORY OF MEDICINE - HONORS BLACK HISTORY MONTH
Halle Tanner Dillon Johnson, MD (1864–1901)
IV. CARDIOLOGY
Aprotinin Use and Risk of Death
V. OPHTHALMOLOGY
Bi-Annual Treatment Better Than Annual Treatment For Trachoma
VI. EPIDEMIOLOGY
Factors Determining Longevity to Age 90 in Males
VII.
REGULATORY AFFAIRS
FDA Licenses New Hemophilia Treatment
VIII. TARGET HEALTH
Regulatory Affairs at Target Health
Last year we submitted one NDA and one PMA. One of our clients submitted a BLA. These submissions used Target e*CRF® as the EDC tool for the pivotal trials. Already this year we have submitted one IND and a 2nd IND is going in this week. One of our clients is submitting an NDA this quarter which also used Target e*CRF® as the EDC tool for all of the clinical trials. We now also represent over 25 companies at FDA. Our regulatory group is headed by Dr. Glen Park with a strong team including: Mary Shatzoff, Fredy Varela, Daisy Sun, and Carlos Figueroa.Cloning is a Reproductive Trick of Nature, When Survival is Everything
Many fish, amphibians and reptiles — have lots of reproductive tricks. 1) ___ can store sperm for a long time, tiding them over when conditions may be poor for reproduction. Another trick is the natural ability to clone. DNA analysis of seeming “miracle embryos” show that every bit of their 2) ___ simply came from the female. Virgin birth, known to biologists as 3) ___ (from the Greek, “parthen” meaning virgin or maiden and “genesis,” beginning), has been seen in species over the years. Some lizards, like the Komodo Dragon, occasionally produce offspring by 4) ___. So do several species of fish, including a female hammerhead shark at the Henry Doorly Zoo in Omaha, Nebraska that produced offspring without a male in 2007. The shark example is particularly striking because sharks are very primitive living fish, having shared a common ancestor with us over 400 million years ago. Biological cloning is not a recent invention of scientists; it is an ancient ability, from nature. Sharks, fish and lizards are probably only the tip of the iceberg. We know of this 5) ___ cloning, only in those rare instances when we’ve been lucky enough to see it. Nobody knows how common it is because there has been no systematic search for the phenomenon. The big question that parthenogenesis raises is, if some females can get along without males, why does any species have males? The reason is that naturally cloned hatchlings are simply genetic duplicates of the mother. In a world of clones, there would not be enough variation for populations to adapt. Biological cloning is a great stopgap measure to ensure the survival of a species, but works against it in the long haul. Cloning is one of many mechanisms species use to 6) ___ in a dangerous world. Some reptiles do not determine gender genetically, but rely on different incubation temperatures to determine the development of males and females. Other creatures can actually switch gender during their lifetimes, being born male and developing as females. Still others can switch gender based on behavioral cues in the social group. However, without 7) ___, the world would be static and unchangeable, and species would gradually disappear as they failed to meet challenges like changing climates and environments.IV. CARDIOLOGY
Aprotinin Use and Risk of Death
Aprotinin, also known as bovine pancreatic trypsin inhibitor, BPTI (Trasylol®, Bayer) is a protein, that is used as medication administered by injection to reduce bleeding during complex surgery, such as heart and liver surgery. Its main effect is the slowing down of fibrinolysis the process that leads to the breakdown of blood clots. The aim in its use is to decrease the need for blood transfusions during surgery, as well as end-organ damage due to hypotension (low blood pressure) as a result of marked blood loss. The drug was temporarily withdrawn worldwide in 2007 after studies suggested that its use increased the risk of complications or death. According to an article published in the New England Journal of Medicine (2008;358:771-783), death outcome data were analyzed for hospitalized patients with operating-room charges for the use of aprotinin (33,517 patients) or aminocaproic acid (44,682 patients) on the day of their CABG procedure. Results showed that 1,512 of the 33,517 aprotinin recipients (4.5%) and 1,101 of the 44,682 aminocaproic acid recipients (2.5%) died. After adjustment for 41 characteristics of patients and hospitals, the estimated risk of death was 64% higher in the aprotinin group than in the aminocaproic acid group. In the first 7 days after surgery, the adjusted relative risk of in-hospital death in the aprotinin group was 1.78. Postoperative revascularization and dialysis were also more frequent among recipients of aprotinin than among recipients of aminocaproic acid. According to the authors, patients who received aprotinin alone on the day of CABG surgery had a higher mortality than patients who received aminocaproic acid alone, and that characteristics of neither the patients nor the surgeons explain the difference, which persisted through several approaches to control confounding.V. OPHTHALMOLOGY
Bi-Annual Treatment Better Than Annual Treatment For Trachoma
Trachoma (Ancient Greek: "rough eye") is an infectious eye disease, and the leading cause of the world’s preventable blindness. Trachoma is caused by the bacterium Chlamydia trachomatis and it is spread by direct contact with eye, nose, and throat secretions from affected individuals, or contact with fomites (inanimate objects), such as towels and/or washcloths, that have had similar contact with these secretions. Untreated, repeated trachoma infections result in a painful form of permanent blindness when the eyelids turn inward, causing the eyelashes to scratch the cornea. Children are the most susceptible to infection, but the effects are often not felt until adulthood. Globally, 84 million people suffer from active infection and nearly 8 million people are visually impaired as a result of this disease. Treatment recommendations for trachoma assume that repeated mass antibiotic distributions can control, but not eradicate, or even locally eliminate, the ocular strains of chlamydia that cause trachoma. Elimination may be an important end point because of concern that infection will return to communities that have lost immunity to chlamydia after antibiotics are discontinued. As a result, a study published in the Journal of the American Medical Association (2008;299:778-784, was performed to determine whether biannual treatment can eliminate ocular chlamydial infection from preschool children and to compare results with the World Health Organization’s recommended annual treatment. The study was a cluster-randomized clinical trial of biannual vs. annual mass azithromycin administrations to all residents of 16 rural villages in the Gurage Zone, Ethiopia, from March 2003 to April 2005. At scheduled treatments, all individuals aged 1 year or older were offered a single dose of oral azithromycin either annually or biannually. The main outcome measures were village prevalence of ocular chlamydial infection, and presence of elimination at 24 months in preschool children determined by polymerase chain reaction. Antibiotic treatments were performed after sample collections. Results showed that overall, 14,897 of 16,403 eligible individuals (90.8%) received their scheduled treatment. In the villages in which residents were treated annually, the prevalence of infection in preschool children was reduced from a mean of 42.6% to 6.8% at 24 months. In the villages in which residents were treated biannually, infection was reduced from 31.6% pretreatment to 0.9% at 24 months. Biannual treatment was associated with a lower prevalence at 24 months (P = .03, adjusting for baseline prevalence). According to the authors, local elimination of ocular chlamydial infection appears feasible even in the most severely affected areas, although it may require biannual mass antibiotic distributions at a high coverage level.VI. EPIDEMIOLOGY
Factors Determining Longevity to Age 90 in Males
Prospective data on nongenetic determinants of exceptional longevity are limited, and information on long-lived men and their functional status is particularly sparse. As a result, a study published in the Archives of Internal Medicine (2008;168:284-290) was designed to examine modifiable factors associated with a life span of 90 or more years and late-life function in men. In this prospective cohort study of 2,357 healthy men (mean age, 72 years) within the Physicians' Health Study (1981-2006), biological and lifestyle factors and co-morbid conditions were assessed by self-report with baseline and annual questionnaires. Mortality and incidence of major diseases were confirmed by medical record review. Late-life function was assessed 16 years after baseline by the Medical Outcomes Study 36-Item Short-Form Health Survey. Results showed that a total of 970 men (41%) survived to at least age 90 years. Smoking was associated with increased risk of mortality before age 90 years (hazard ratio [HR]; 2.10), and similar associations were observed with diabetes (HR, 1.86), obesity (HR, 1.44), and hypertension (HR, 1.28). Regular exercise was associated with a nearly 30% lower mortality risk (HR, 0.72). The probability of a 90-year life span at age 70 years was 54% in the absence of smoking, diabetes, obesity, hypertension, or sedentary lifestyle. It ranged from 36% to 22% with 2 adverse factors and was negligible (4%) with 5. Compared with nonsurvivors, men with exceptional longevity had a healthier lifestyle (67% vs 53% had 1 adverse factor), had a lower incidence of chronic diseases, and were 3 to 5 years older at disease onset. They had better late-life physical function (73 ± 23 vs 62 ± 30; P < .001) and mental well-being (mean score, 84 ± 14 vs 81 ± 17; P = .03). More than 68% (vs 45%) rated their late-life health as excellent or very good, and less than 8% (vs 22%) reported fair or poor health (P < .001 for trend). Regular exercise was associated with significantly better - and smoking and overweight with significantly worse - late-life physical function. Smoking also was associated with a significant decrement in mental function. According to the authors, modifiable healthy behaviors during early elderly years, including smoking abstinence, weight management, blood pressure control, and regular exercise, are associated not only with enhanced life span in men but also with good health and function during older age.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 Licenses New Hemophilia Treatment
The FDA has licensed a treatment for hemophilia A, a rare, hereditary blood-clotting disorder that affects only 15,000 individuals in the US, almost exclusively males. The new treatment, called Xyntha Antihemophilic Factor (Recombinant) Plasma/Albumin Free (Wyeth Pharmaceuticals), is a genetically engineered version of factor VIII, a protein essential for the clotting of blood. Factor VIII, known as an anti-hemophilic factor, is missing or decreased in patients with hemophilia A. Xyntha is licensed for the control and prevention of bleeding, which can occur spontaneously or after an accident or injury in patients diagnosed with hemophilia A. Xyntha is also licensed to help prevent surgical bleeding in this patient population. Xyntha is manufactured using recombinant DNA techniques that enable scientists to create new DNA strands with specific traits, such as the capacity to produce a specific protein. To manufacture Xyntha, genes from Chinese Hamster Ovary cells (CHO) are modified to produce factor VIII. These CHO cells are free from known infectious agents, and Xyntha undergoes an additional process of viral inactivation. Also, the culture in which the cells are grown is free of any human or animal material. In clinical trials, Xyntha was shown to be effective at preventing or controlling bleeding, including preventing bleeding in surgery, for hemophilia A patients. Generally, the most frequently reported adverse reaction was headache. For those receiving Xyntha to prevent bleeding in surgery, the most frequently reported adverse reaction was fever. Most adverse reactions reported in either study were considered mild or moderate in severity. In addition, two of 89 individuals who received 50 days of treatment with Xyntha, developed factor VIII inhibitors, which are antibodies that counteract treatment with factor VIII.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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