Innovation at Target Health

Target Health has reached a recent count of 50 full time employees.  THI is now considered a medium size corporation.

Target Health’s patented suite of software tools, leading to the paperless office, is building and intensifying. Clients can now check into Target e*CTMS® to see the status of their projects.  Clients now browse Target Document® to view, manage and electronically sign documents.  Target’s clients can login to Target e*CRF® to 1) check on patient enrollment metrics, 2) manage SAEs and 3) perform coding.

The Target Health data management group is using an automated tool to create and define.xml files for eCTD submissions and will soon have a CDISC™ mapper to facilitate the creation of CDISC™ compliant datasets.  One month from now, the Target Health change control process will be online. THI has been able to do “More With Less“ and will continue to innovate. Target Document®, Target e*CTMS®  and Target Encoder® are commercially available and cost effective.

For more information about Target Health contact Warren Pearlson (212-681-2100 ext 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health website at:

www.targethealth.com

Flu Doesn’t Die Out, It Just Hides Out

 

Every autumn, as predictably as falling leaves, flu season descends upon us. Every spring, just as predictably, the season comes to a close. This cyclical pattern, common in temperate regions, is well known, but the driving forces behind it have been in question. Do existing strains die off each 1) ___, only to be replaced each fall by new founding strains from other parts of the world, or does a “hidden chain of sickness“ persist over the summer, seeding the next season’s epidemic? A genetic analysis by University of Michigan postdoctoral fellow Trevor Bedford and colleagues at U-M, Howard Hughes Medical Institute and Florida State University reveals that in the USA, not all strains of influenza die off at the end of winter; some move southward to South America, and some migrate even farther. This research was published online May 27 in the open-access journal PLoS Pathogens. The prevailing view that has developed over the past three years or so is the out-of-tropics hypothesis, in which the strains that bring about each temperate flu season originate from 2) ___ and Southeast Asia, where influenza A is less seasonal. The hypothesis was tested by analyzing 3) ___ sequences from influenza A (H3N2) viruses collected from patients around the world between 1998 and 2009 and constructing a tree showing relationships among the viruses. The resulting mathematical model accounted for evolutionary processes and rates of 4) ___. Although China and Southeast Asia play the largest role in the influenza A migration network, temperate regions – particularly the USA – also make important contributions. Rather than dying off at the end of our flu season, many strains simply move on to more favorable environments. The results have implications for public health efforts aimed at combating the disease. For example, the new knowledge that influenza frequently migrates out of the USA argues for caution in using antivirals, which can promote development of drug-5) ___ strains. If, as previously thought, those strains died out at the end of the season, they would not be a problem, but their newly-discovered ability to survive and circulate means resistant strains can spread from the USA throughout the world. On the flip side, the finding also means that vaccination programs outside of China and Southeast 6) ___ can be effective in curbing influenza’s spread. In addition, growing knowledge about patterns of flu migration eventually may make it possible to tailor 7) ___ to particular locations. For instance, South America gets almost all of its 8) ___ from North America. This would suggest that rather than giving South America the same vaccine that the rest of the world gets, one could construct a vaccine preferentially from the strains that were circulating in North America the previous season. As we gather more data from other regions, this could be done for the entire world. The research also can inform disease surveillance. By doing this kind of research, we get a clearer idea of where in the world flu is actually coming from. We know that it’s mostly Southeast Asia, but now we see that it can come out of temperate regions as well, so our surveillance needs to become more 9) ___. The research was funded by Howard Hughes Medical Institute, the National Institutes of Health and the National Science Foundation.

 

ANSWERS: 1) spring; 2) China; 3) genetic; 4) migration; 5) resistant; 6) Asia; 7) vaccines; 8) flu; 9) global

Living Longer

The average person in this country today is far better off than in any other civilization throughout history. The average length of a human life at different points in history tells a surprising story. By studying human remains, archaeologists can make a pretty good estimate of how long people lived on average, and the results are amazing. The average lifespan throughout most of history was about 30 years, and didn’t change much at all until recently. Whether we are looking at people who lived in small nomadic groups of hunter-gatherers or early farmers or citizens of ancient Greece or Rome, the number is about the same. Right up until the past two centuries, no matter where you looked in the world, people lived for an average of about 30 years. Of course every culture has had elders who lived far longer, but the average lifespan was very short because so many people died young. Without the gifts of modern science, more than half of all babies born did not live into adulthood. Children died regularly and predictably from diseases that we can now easily cure or prevent, as well as from starvation and malnutrition. The word vitamin is less than 100 years old. Another reason that human life spans were so short was because so many women died from childbirth. Without modern medicine, giving birth was dangerous. Of course some women successfully had very large families, but many more perished from complications that are now easily cured. Consider this: England’s Queen Anne lived between 1665 and 1714, and was pregnant at least 18 times, but she was only able to successfully give birth to a live infant five times. Four of these children died before age 2, and her remaining son died at age 11. Queen Anne was one of the most powerful women in history, with access to the best doctors that money could buy. But without modern science, not one of her children lived to grow up. In terms of medical care, the average person in this country today is far better off than a king or a queen just 300 years ago. Today is amazing when you consider all of the diseases and deaths that are prevented by vaccines, clean water and modern nutrition. Today, the average lifespan in this country is about 76-80 years, more than double what it was throughout most of history. Source: Excerpts: Kelly Cline, Ph.D., associate professor of astronomy and mathematics at Carroll College, Helena, Montana

GENETICS

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Gene Pattern May Identify Kidney Transplant Recipients Who Don’t Need Life-Long Anti-Rejection Drugs

In 2008, more than 80,000 people in the United States were living with a kidney transplant. Following a kidney transplant, recipients must be placed on immunosuppressive therapy or their immune systems will reject the transplanted organ. However, these drugs suppress the entire immune system, reducing an individual’s ability to fight infections, and sometimes leading to diseases related to a weakened immune system, such as cancer. The drugs also have other severe side effects such as diabetes, hypertension and heart disease, as well as swelling, weight gain, and excessive hair growth and acne that many people find intolerable. In rare cases, a physician may stop a transplant recipient’s immunosuppressive drugs because of a serious medical problem such as cancer or life-threatening infection. In other cases, transplant recipients decide to reduce or stop immunosuppressive therapy against their physicians’ advice, even though by doing so, they risk losing their transplanted organ. However, in a very small percentage of such cases, rejection does not occur after the drugs are stopped. According to an article published online in the Journal of Clinical Investigation (24 May 2010), a distinct pattern of gene expression has been identified in the largest reported group of kidney transplant recipients who have not rejected the transplant kidneys even though they stopped taking anti-rejection drugs. This finding may help identify other transplant recipients who could safely reduce or end use of immunosuppressive therapy. The findings come from the Immune Tolerance Network (ITN), an international research consortium supported by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases, of the National Institutes of Health, and the Juvenile Diabetes Research Foundation International. The study included 25 kidney transplant recipients who had ceased taking their immunosuppressive drugs of their own accord and yet had retained normal kidney function for more than one year. The study compared this group with two other groups: recipients who were still taking their immunosuppressive medication and had healthy kidneys, and healthy, non-transplant controls. Gene expression was analyzed of the cells in whole blood and it was observed that the transplant recipients who were not taking medication had a distinct pattern of genes expressed by B cells, a type of white blood cell. White blood cells include T and B cells. Recent studies of immune tolerance have focused on the role of a subset of T cells, called regulatory T cells (Tregs). Work in animal models indicates that B cells also may help promote immune tolerance. The gene expression pattern differed from those seen in participants who were still on immunosuppressive therapy and in non-transplant healthy control subjects. Further study identified a pattern of expression of three B cell genes that was far more common in patients who had stopped taking their medications yet maintained good graft function. Identifying potential biomarkers of immune tolerance is the first step in identifying transplant recipients whose immunosuppression therapy could be reduced. According to the authors, if it is possible to develop a reliable tolerance signature – a pattern of gene expression that indicates that someone will not reject a transplant – then it may be possible to find patients who would make good candidates for supervised drug withdrawal.

Impact of Bariatric Surgery on Hypertensive Disorders in Pregnancy: Retrospective Analysis of Insurance Claims Data

According to an article published in the British Medical Journal (2010;340:c1662), a retrospective cohort study was performed to determine whether women who had a delivery after bariatric surgery have lower rates of hypertensive disorders in pregnancy compared with women who had a delivery before bariatric surgery. For the study, claims data for 2002-2006 were evaluated from seven insurance plans in the United States. Study participants included 585 women aged 16-45 who had undergone bariatric surgery, had at least one pregnancy and delivery, and had continuous insurance coverage during pregnancy plus two weeks after delivery. The main outcome measure was hypertensive disorders in pregnancy defined with ICD-9 codes. The independent variable was the timing of delivery in relation to bariatric surgery, classified as deliveries before and after surgery. Logistic regression was used to calculate odds ratios and confidence intervals for each type of hypertensive disorder in pregnancy. Results showed that among the 585 women who had undergone bariatric surgery and had a delivery, 269 delivered before surgery (control group) and 316 delivered after surgery (intervention group). Gastric bypass was the surgery in 82% (477) of all women. Women who delivered before surgery were younger at the time of delivery (mean age 31.3 v 32.5) but had higher rates of pre-existing diabetes and gestational diabetes mellitus. Compared with women who delivered before surgery, women who delivered after surgery had substantially lower rates of pre-eclampsia and eclampsia (odds ratio 0.20), chronic hypertension complicating pregnancy (0.39), and gestational hypertension (0.16), even after adjustment for age at delivery, multiple pregnancy (that is, twins or more), surgical procedure, pre-existing diabetes, and insurance plan. According to the authors, in this retrospective analysis of US women, bariatric surgery was associated with lower rates of hypertensive disorders in subsequent pregnancy.

Postexposure Protection Of Non-Human Primates Against a Lethal Ebola Virus Challenge With RNA Interference: A Proof of Concept Study

It has been previously showed that small interfering RNAs (siRNAs) targeting the Zaire Ebola virus (ZEBOV) RNA polymerase L protein formulated in stable nucleic acid-lipid particles (SNALPs) completely protected guinea pigs when administered shortly after a lethal ZEBOV challenge. Although rodent models of ZEBOV infection are useful for screening prospective countermeasures, they are frequently not useful for prediction of efficacy in the more stringent non-human primate models. Therefore, a study published in The Lancet (2010;375:1896-1905), was performed to assess the efficacy of modified non-immunostimulatory siRNAs in a uniformly lethal non-human primate model of ZEBOV hemorrhagic fever. For the study, a combination of modified siRNAs targeting the ZEBOV L polymerase (EK-1 mod), viral protein (VP) 24 (VP24-1160 mod), and VP35 (VP35-855 mod) were formulated in SNALPs. A group of macaques (n=3) was given these pooled anti-ZEBOV siRNAs (2 mg/kg per dose, bolus intravenous infusion) after 30 min, and on days 1, 3, and 5 after challenge with ZEBOV. A second group of macaques (n=4) was given the pooled anti-ZEBOV siRNAs after 30 min, and on days 1, 2, 3, 4, 5, and 6 after challenge with ZEBOV. Results showed that 2 (66%) of three rhesus monkeys given four postexposure treatments of the pooled anti-ZEBOV siRNAs were protected from lethal ZEBOV infection, whereas all macaques given seven postexposure treatments were protected. The treatment regimen in the second study was well tolerated with minor changes in liver enzymes that might have been related to viral infection. According to the authors, the complete postexposure protection against ZEBOV in non-human primates provides a model for the treatment of ZEBOV-induced haemorrhagic fever, and that these data show the potential of RNA interference as an effective postexposure treatment strategy for people infected with Ebola virus. The authors added that this strategy might also be useful for treatment of other emerging viral infections.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues. Each week we highlight new information in these challenging areas.

 

FDA Approves New Treatment for Late-Onset Pompe Disease

 

TARGET HEALTH has extensive experience in orphan designation requests and drug development in orphan indications.

Pompe disease, a rare genetic disorder, occurs in an estimated 1 in every 40,000 to 300,000 births. Its primary symptom is heart and skeletal muscle weakness, progressing to respiratory weakness and death from respiratory failure. In Pompe disease, a gene mutation prevents the body from making an enzyme, or making enough of the enzyme called acid alpha-glucosidase (GAA), necessary for proper muscle functioning. GAA is used by the heart and muscle cells to convert a form of sugar called glycogen into energy. Without the enzyme action, glycogen builds up in the cells and, ultimately, weakens the heart and muscles. The FDA has approved Lumizyme (alglucosidase alfa) for patients ages 8 years and older with late-onset (non-infantile) Pompe disease. Lumizyme is believed to work by replacing the deficient GAA, thereby reducing the accumulated glycogen in heart and skeletal muscle cells. Lumizyme is being approved with a risk evaluation and mitigation strategy (REMS). It will only be available through a restricted distribution system called the Lumizyme ACE (Alglucosidase Alfa Control and Education) Program to ensure that it is used by the correct patient group. Lumizyme will carry a Boxed Warning because of the risk of anaphylaxis, severe allergic reactions, and immune-mediated reactions. Currently, the only other treatment for Pompe disease available in the United States is Myozyme, which is also manufactured by Genzyme at its manufacturing facilities in Framingham and Allston Landing, Mass. Myozyme has been in short supply due to limited manufacturing capacity. The manufacturer reserved Myozyme to treat infants and children with Pompe disease because younger patients generally have a much more aggressive form of the disease. Some adult patients in the U.S. received Lumizyme under a temporary access program. The approval of Lumizyme will ensure that treatment is available for all U.S. adult Pompe patients in need of treatment. Lumizyme is manufactured at Genzyme facilities in Ireland and Belgium. Lumizyme’s safety and effectiveness have not been evaluated in patients with infantile-onset Pompe disease or in patients ages 8 years and younger with late-onset disease. These patients should be treated with Myozyme, not Lumizyme. The safety and efficacy of Lumizyme are based on a clinical study in 90 patients, ages 10 years to 70 years, with late-onset Pompe disease. The most commonly reported side effects for Lumizyme were infusion-related reactions and included severe allergic reactions, hives, diarrhea, vomiting, shortness of breath, itchy skin, skin rash, neck pain, partial hearing loss, flushing, pain in extremities, and chest discomfort.

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