Target Health launched Target e*CRF in 1999, and last week, the FDA approved the 8th drug  which Target e*CRF was used for key aspects of the development process. In addition to the 8 drug approvals, there have been 2 PMA device and 10 PMA diagnostic approvals. And the best is yet to come.

 

This past year, Target Health launched 1) Target e*Studio™, which is the technology transfer version of Target e*CRF, and 2) Target e*CTR™, which allows for the seamless integration, in clinical trials, of direct data entry, eSource and the EDC database. Target Health expects to submit the first NDA ever, in Q1 2013, which used eSource in lieu of paper patient records.

 

Other software products include Target Document® (eTMF), Target Encoder® (MedDRA/WhoDrug coding); Target e*Pharmacovigilance™ (3500A and CIOMS forms), Target e*CTMS™, Target Monitoring Reports™, etc.

 

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. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com

Eli Hurvitz, Founder of Teva, Dies at 79

 

 

Eli Hurvitz, who began his career washing lab equipment at a drug company and went on to build Teva Pharmaceutical Industries into the largest generic drug maker in the world, has died. While no cause was given, in an interview with the newspaper Yediot Aharonot earlier this year Mr. Hurvitz said he had cancer. “I am not the type to surrender,” he told the paper. “That is how it was in business, and that is how it is with the illness.”

 

Mr. Hurvitz started out in the 1950s at Assia, a small pharmaceutical company partly owned by his father-in-law, in Petah Tikva, east of Tel Aviv. He became managing director in 1976 and merged Assia with two other small firms, Zori and Teva, to form the company now known as Teva, which means “nature” in Hebrew. Mr. Hurvitz was the president and chief executive of Teva for the next 25 years. Through aggressive mergers and acquisitions, a reputation for quality and low prices, Teva grew into a giant that supplied one of every six prescriptions dispensed in the United States. It has a presence in 60 countries and 45,000 employees. In 2010, it reached $16 billion in sales.

 

Eliyahu Hurvitz was born in Jerusalem in 1932 and moved to Tel Aviv with his family as a child. When the state of Israel was founded and the Arab-Israeli war broke out in 1948, Mr. Hurvitz was drafted and spent time on a kibbutz as part of a unit that established agricultural settlements. He then went on to study economics at a branch of the Hebrew University of Jerusalem in Tel Aviv. In 1953, he married Dalia Solomon and began working at Assia.

 

Mr. Hurvitz was awarded the Israel Prize in 2002 for lifetime achievement and his contributions to the state and society. In addition to his business, he had been chairman of Bank Leumi, president of the Manufacturers Association of Israel and chairman of the Israel Democracy Institute, an independent research institute in Jerusalem.

Chewing Gum Cuts Ear Infection Risk in Kids

 

 

 

Ear infections are extremely common, especially in runny-nosed kids. The latest research indicates that when young children get 1) ___, they end up with an ear infection 61% of the time. Chewing gum containing xylitol may actually prevent ear infections in kids. Xylitol is a sugar alcohol derived from the sugar xylose. Xylitol comes from birch bark. An alternative sweetener, Xylitol helps prevent cavities and sweetens foods made for diabetics. It contains 40% fewer calories than sugar and still provides a sweet flavor.

 

Xylitol originates from the fibers in fruits and vegetables, including mushrooms, raspberries, strawberries, yellow plums, lettuce and cauliflower. In fruits and vegetables, xylitol constitutes less than 1%, according to a study led by researcher R. Sreenivas Rao. The act of chewing and 2) ___ assists with the disposal of earwax and clearing the middle ear, while the presence of xylitol prevents the growth of bacteria in the eustachian tubes (auditory or pharyngotympanic tubes) which connect the 3) ___ and ear.

 

When bacteria enter the body, they adhere to the tissues using a variety of sugar complexes. The open nature of xylitol and its ability to form many different sugar-like structures appears to interfere with the ability of many bacteria to adhere. In a double-blind, randomized, controlled trial, saline solutions of xylitol significantly reduced the number of nasal coagulase-negative Staphylococcus bacteria. The study attributed the benefits to the increased effectiveness of endogenous (naturally present in the body) antimicrobial factors. In a small clinical trial nasally administered xylitol reduced ear complaints in children previously having chronic complaints, on the order of almost one a month, by more than 92%. Beneficial effects on asthma with nasal administration, have also been reported.

 

In a meta-analysis of three Finnish studies, children who chewed 4) ___ — or took other products laden with xylitol, including lozenges or syrup — had about a 25% lower risk of developing acute otitis media compared with control interventions, Amir Azarpazhooh, DMD, of the University of Toronto, and colleagues reported in Cochrane Reviews. “Based on the studies we reviewed, xylitol seems to be a promising alternative to conventional therapies to prevent acute otitis media among healthy 5) ___,” they wrote.

 

Acute otitis media is the most common infection for which kids are treated with 6) ___, which has spurred concerns over antibiotic resistance. So researchers have searched for alternative means of prevention or treatment, not all of which have been successful. Xylitol, or birch sugar, has been one such alternative. It’s a five-carbon polyol sugar alcohol found in a number of fruits, which has been shown to inhibit the growth and acid production of certain bacteria, particularly S. mutans. It is for this feature that some dentists recommend it for preventing 7) ___, the researchers said.

 

Since a key step in the pathogenesis of otitis media is the colonization of the upper airway with 8) ___ that move from the nasopharynx to the middle ear via the eustachian tubes, the researchers hypothesized that it may be effective for preventing middle ear infections. So they conducted a review and meta-analysis of four studies: three randomized controlled trials in 1,826 Finnish children, and another among 1,277 Finnish children in day care who had a respiratory infection. In a meta-analysis of the three trials, the researchers saw a reduced risk of acute otitis media in children who were given 8 to 10 g/day of xylitol in any form — either as gum, a lozenge, or syrup — compared with control interventions (RR 0.75). In the fourth trial, however, xylitol had no effect on reducing the occurrence of acute otitis media in kids with upper respiratory infection.

 

Gum appeared to work best; in healthy children, chewing xylitol was superior to syrup at preventing otitis media (RR 0.59), though it had no advantages if given during respiratory infection. There were no differences between xylitol lozenges and syrups in preventing ear infections in healthy kids or in those who had respiratory infections, and there was no difference between gum and lozenges for preventing 9) ___ infections in healthy kids or in those with a respiratory infection. The authors noted that the study was limited because the data arise from a small number of studies, mainly from the same research group.

 

A number of factors prevent xylitol chewing gum from being used more widely to prevent ear infection. First, school rules against chewing gum may hamper its preventive use in a place where it may be needed most. Also, previous surveys have shown that only about half of clinicians know about the medical uses of xylitol.

Still, Azarpazhooh and colleagues concluded that a daily dose of about 8 g of xylitol — potentially as two pieces of chewing gum five times a day after meals for at least five minutes — can prevent acute otitis media in kids without acute upper respiratory 10) ___.

 

ANSWERS: 1) colds; 2) swallowing; 3) nose; 4) gum; 5) children; 6) antibiotics; 7) cavities; 8) bacteria; 9) ear; 10) infection

Richmond’s Medical Miracle

 

Photo Source: Library of Congress Chimborazo Hospital, Richmond, Va.

 

 

During the opening months of the Civil War, the streets of Richmond, Va., filled with bloodied bodies. The thousands of Confederate wounded were treated in a range of makeshift hospitals hastily established in hotels, factories and private homes. But by autumn, as hopes the conflict would be brief faded, it became clear a war of this magnitude required a modernized medical response. That fall Samuel P. Moore, the Confederate surgeon general, secured both the facilities and the personnel to provide such a response at Chimborazo, a 40-acre plateau just east of the Confederate capital’s stately Church Hill neighborhood. The site got its name from Mount Chimborazo, an inactive volcano in Ecuador, famous at the time after being “discovered” by the German explorer-scientist Alexander von Humboldt.

 

Occupying 150 buildings, it was one of the largest hospitals in the world, typically serving around 4,000 sick and wounded soldiers at a time. Over the next three and a half years it treated 77,000 patients — twice the entire population of Richmond at the outbreak of the war. But Chimborazo was remarkable for more than just its gargantuan size. It would prove to be among the world’s most efficient, modern and sanitary hospitals of the period, an achievement due in no small part to Moore’s appointment of James B. McCaw to run the facility. The son, grandson and great-grandson of physicians, McCaw embodied the emergence of the modern, professional doctor. After attending medical school in New York, he returned to his native Richmond, accepting a professorship at the Medical College of Virginia and editorship of the Virginia Medical and Surgical Journal. His nascent understanding of the hygienic importance of cleanliness, his ties to M.C.V., the only medical school in the Confederacy to remain operational throughout the war, allowing Chimborazo to pioneer the practices of a teaching hospital, and his talent as an administrator proved invaluable in superintending Chimborazo.

 

McCaw organized Chimborazo into five divisions, each with its own surgeon-in-chief. Within each were 90 wards measuring about 80 feet by 28 feet and containing 40 patient beds. The wards were spaced along 40-foot-wide avenues and 10-foot alleys, with 3 doors and 10 windows on the long sides of the buildings to provide ventilation. During the most propinquitous and bloody campaigns, when the number of wounded exceeded the capacity of the wards, 100 Sibley tents were pitched nearby, accommodating up to 10 patients each. Once the tents filled, additional patients were bivouacked in the open air.

 

McCaw Library. An 1863 map of Chimborazo Hospital.

 

The complex also included bathhouses, ice houses, carpentry and blacksmith shops, a soap manufactory, a stable, a chapel, an apothecary shop, a bakery that produced 10,000 loaves daily, a brewery that produced 400 kegs of beer at a time, and five dead houses, one for each of the divisions. Chimborazo maintained a large vegetable garden on a nearby farm, as well as herds of goats and cows. McCaw even secured a canal boat to travel the James River, bringing provisions from as far away as Lexington, Va.

 

In addition to the dozens of physicians, who were organized into a hierarchy of assistant surgeons, surgeons and surgeons-in-charge, the hospital employed enormous nursing and support staffs. Military hospitals had previously been manned largely by convalescing soldiers, but the labor needs at Chimborazo were so great — as was the pressure for any able soldiers to return to the front — that McCaw relied heavily on slaves, free blacks and white women to keep the hospital running.

 

Indeed, African-American labor was paramount to the running of Confederate military hospitals. Though the Civil War is often thought of as the watershed that opened the field of nursing to American women, female nursing was largely a Union, and not a Confederate, phenomenon; 9,000 women served as nurses in Union hospitals, compared to only 1,000 in Confederate hospitals, primarily because the use of hired-out male slaves in the South preempted the recruitment of white women.

 

McCaw repeatedly advertised for slave labor throughout the war, and he pleaded with Moore for impressment of Chimborazo’s enslaved staff, to prevent owners from removing the slaves in his service. Slaves and a smaller number of free blacks cooked, cleaned, and worked in manufacturing – tasks similar to those they’d long been assigned in non-hospital settings. But enslaved men also served in the nursing staff, an arrangement that shocked some of the patients.

 

White women did play a crucial role at Chimborazo, serving as matrons on the wards. Matrons oversaw the preparation and distribution of medicine and meals, as ordered by the physicians. They also provided a range of patient care, from reading Bible passages to writing letters home, and fielding requests for everything from a haircut to a “b’iled sweet pur-r-rta-a-a-tu-ur,” as Phoebe Yates Pember, who served as matron from late 1862 through the fall of Richmond, recalled in her entertaining, if occasionally self-aggrandizing, 1879 memoir, “A Southern Woman’s Story: Life in Confederate Richmond.”

 

Unfortunately, the historical record hasn’t yielded anything analogous to McCaw’s official correspondence or Pember’s memoir to provide the perspective of the enslaved and free black staff regarding their wartime experience at Chimborazo. Nevertheless, in a significant post-bellum coda to the story of Chimborazo, the facility that was constructed with slave labor in October 1861 and employed hired-out slaves throughout the war was converted after the war into a freedmen’s school. Opened in June 1865, it served hundreds of African-American students, many of whom lived on site. Like other freedmen’s schools, Chimborazo attracted a broad swath of the free black population in the years following emancipation; the November 1869 register listed students between ages 4 and 29. Published in the NYTimes, November 23, 2011, by Lois Leveen

Dosing of Clopidogrel (Plavix) Based on CYP2C19 Genotype and the Effect on Platelet Reactivity in Patients with Stable Cardiovascular Disease

 

 

Clopidogrel (Plavix) is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease (CAD), peripheral vascular disease, and cerebrovascular disease. The drug works by irreversibly inhibiting a receptor called P2Y12, an adenosine diphosphate ADP chemoreceptor. Adverse effects include hemorrhage, severe neutropenia, and thrombotic thrombocytopenic purpura (TTP).

 

It has been reported that variants in the CYP2C19 gene influence the pharmacologic and clinical response to the standard 75-mg daily maintenance dose. As a result, a study published in the Journal of the American Medical Association (2011;306:2221-2228) was performed. to test whether higher doses (up to 300 mg daily) improve the response to clopidogrel in the setting of loss-of-function CYP2C19 genotypes.

 

The study, ELEVATE-TIMI 56, was a multicenter, randomized, double-blind trial that enrolled and genotyped 333 patients with cardiovascular disease across 32 sites from October 2010 until September 2011. Study participants received maintenance doses of clopidogrel for 4 treatment periods, each lasting approximately 14 days, based on genotype. In total, 247 noncarriers of a CYP2C19*2 loss-of-function allele were to receive 75 and 150 mg daily of clopidogrel (2 periods each), whereas 86 carriers (80 heterozygotes, 6 homozygotes) were to receive 75, 150, 225, and 300 mg daily. The main outcome measures were platelet function test results (vasodilator-stimulated phosphoprotein [VASP] phosphorylation and VerifyNow P2Y12 assays) and adverse events.

 

Results showed that:

 

1. Treatment with 75 mg daily, CYP2C19*2 heterozygotes had significantly higher on-treatment platelet reactivity than did noncarriers (VASP platelet reactivity index [PRI]: mean, 70.0% vs. 57.5%, and VerifyNow P2Y12 reaction units [PRU]: mean, 225.6 vs. 163.6; P < .001 for both comparisons).

 

2. Among CYP2C19*2 heterozygotes, doses up to 300 mg daily significantly reduced platelet reactivity, with VASP PRI decreasing to 48.9% and PRU to 127.5 (P < .001 for trend across doses for both).

 

3. Whereas 52% of CYP2C19*2 heterozygotes were nonresponders (≥230 PRU) with 75 mg of clopidogrel, only 10% were nonresponders with 225 or 300 mg (P < .001 for both).

 

4. Clopidogrel, 225 mg daily, reduced platelet reactivity in CYP2C19*2 heterozygotes to levels achieved with standard clopidogrel, 75 mg, in noncarriers

 

5. In CYP2C19*2 homozygotes, even with 300 mg daily of clopidogrel, the mean VASP PRI was 68.3% and mean PRU, 287.0.

 

According to the authors, among patients with stable cardiovascular disease, tripling the maintenance dose of clopidogrel to 225 mg daily in CYP2C19*2 heterozygotes achieved levels of platelet reactivity similar to that seen with the standard 75-mg dose in noncarriers; in contrast, for CYP2C19*2 homozygotes, doses as high as 300 mg daily did not result in comparable degrees of platelet inhibition.

Effects on 11-Year Mortality and Morbidity of Lowering LDL Cholesterol with Simvastatin (Zocor, Merck)

 

 

Findings of large randomized trials have shown that lowering LDL cholesterol with statins reduces vascular morbidity and mortality rapidly. However, only limited evidence exists about the long-term efficacy and safety of statin treatment. As a result, an article published in The Lancet, Early Online Publication (23 November 2011), was performed to assess long-term efficacy and safety of lowering LDL cholesterol with statins. The study used data from the extended follow-up of the Heart Protection Study (HPS), to report cause-specific mortality and major morbidity in the in-trial and post-trial periods.

 

For the trial, 20,536 patients at high risk of vascular and non-vascular outcomes were allocated either 40 mg simvastatin daily or placebo, using minimized randomization. Mean in-trial follow-up was 5.3 years (SD 1.2), and post-trial follow-up of surviving patients yielded a mean total duration of 11 years (SD 0.6). The primary outcome of the long-term follow-up was first post-randomization major vascular event. Analysis was by intention to treat.

 

Results showed that allocation to simvastatin yielded an average reduction in LDL cholesterol of 1.0 mmol/L and a proportional decrease in major vascular events of 23% (p<0.0001), with significant divergence each year after the first. During the post-trial period (when statin use and lipid concentrations were similar in both groups), no further significant reductions were noted in either major vascular events. However, during the combined in-trial and post-trial periods, no significant differences were recorded in cancer incidence at all sites (0.98 or any particular site, or in mortality attributed to cancer (1.01) or to non-vascular causes (0.96).

 

According to the authors, more prolonged LDL-lowering statin treatment produces larger absolute reductions in vascular events. Moreover, even after study treatment, benefits persisted for at least 5 years without any evidence of emerging hazards. The authors emphasized that these findings provide further support for the prompt initiation and long-term continuation of statin treatment.

Reciprocal Seasonal Variation in Vitamin D Status and Tuberculosis Notifications in Cape Town, South Africa

 

 

Vitamin D deficiency is associated with susceptibility to tuberculosis (TB) in HIV-uninfected people in Europe, but it is not known whether such an association exists among HIV-infected people in subtropical Africa. As a result, a study, published in the Proceedings of the National Academy of Sciences (2011;108:19013-19017), was conducted to determine whether vitamin D deficiency was associated with susceptibility to active TB in HIV-uninfected (n = 196) and HIV-infected (n = 174) black Africans in Cape Town, South Africa. The study also investigated whether there was evidence of seasonal variation in vitamin D status and TB notifications in this setting over an 8-year period.

 

Results showed that vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L) was present in 232 (62.7%) of 370 participants and was associated with active TB in both HIV-uninfected (odds ratio = 5.2; P < 0.001) and HIV-infected (odds ratio = 5.6; P < 0.001) people.

 

Vitamin D status also varied according to season: The mean serum 25(OH)D concentration was highest in January through March and lowest in July through September (56.8 vs. 30.7 nmol/L, respectively; P < 0.001). Reciprocal seasonal variation in TB notifications was observed: The mean number of TB notifications per quarter for Cape Town in 2003 to 2010 was lowest in April through June and highest in October through December (4,222 vs. 5,080; P < 0.001).

 

According to the authors, Vitamin D deficiency is highly prevalent among black Africans in Cape Town and is associated with susceptibility to active TB both in the presence and absence of HIV infection. The authors added that reciprocal seasonal variation in serum 25(OH)D concentration and TB notifications suggests that seasonal variations in vitamin D status and TB incidence in this setting may be causally related.

FDA approves Eylea for Wet Age-Related Macular Degeneration (AMD)

 

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

 

Congratulations to our friends and colleagues at Regeneron!

 

Wet (neovascular) age-related macular degeneration AMD gradually destroys a person’s sharp, central vision and is a leading cause of vision loss and blindness in Americans ages 60 and older. AMD affects the macula, the part of the eye that allows people to see fine detail needed to do daily tasks such as reading and driving. There are two forms of AMD, a wet form and a dry form. The wet form of AMD includes the growth of abnormal blood vessels. The blood vessels can leak fluid into the central part of the retina, also known as the macula. When fluid leaks into the macula, the macula thickens and vision loss occurs. An early symptom of wet AMD occurs when straight lines appear to be wavy.

 

The FDA has approved Eylea (aflibercept) to treat patients with AMD. The safety and effectiveness of Eylea was evaluated in two clinical trials involving 2,412 adult patients. People in the study received either Eylea or Lucentis (ranibizumab injection). The primary endpoint in each study was a patient’s clearness of vision (visual acuity) after one year of treatment.

 

Eylea is injected into the eye either every four weeks or every eight weeks by an ophthalmologist. The studies showed that Eylea was as effective as Lucentis in maintaining or improving visual acuity.

 

The most commonly reported side effects in patients receiving Eylea included eye pain, blood at the injection site (conjunctival hemorrhage), the appearance of floating spots in a person’s vision (vitreous floaters), clouding of the eye lens (cataract), and an increase in eye pressure. Eylea should not be used in those who have an active eye infection or active ocular inflammation. Eylea has not been studied in pregnant women, so the treatment should be used only in pregnant women if the potential benefits of the treatment outweigh any potential risks. Age related macular degeneration does not occur in children and Eylea has not been studied in children.

 

Other FDA-approved treatment options for wet AMD include: Visudyne (verteporfin for injection) approved in 2000, Macugen (pegaptanib sodium injection) approved in 2004, and Lucentis (ranibizumab injection) approved in 2006.

 

For more information: NEI: Facts about Age-Related Macular Degeneration

Target Health (www.targethealth.com) a full service e*CRO, is committed to serve the pharmaceutical community through knowledge, experience, technology and connectivity. Target Health strives to optimize the life cycle of drugs, biologics and devices with expertise, leadership, innovation and teamwork. Target Health Inc. has fulltime staff dedicated to all aspects of Regulatory Affairs, Clinical Research, Biostatistics, Data Management, Strategic Planning and Drug and Device Development.

 

Target Health is committed to the paperless clinical trial and has developed a full suite of eClinical Trial software including:

 

1) Target e*CRF® (EDC Made Simple)

2) Target e*CTMS™

3) Target Document®

4) Target Encoder®

5) Target e*Pharmacovigilance™

6) Target e*Monitoring™

7) Target Newsletter®

8) Target e*CTR™ (eSource, 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.

 

 

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