eSource Patent Issued to Target Health Inc.

 

 

Target Health is pleased to announce that the United States Patent Office has issued US Patent 8,041,581 for “ System and Method for Collecting, Processing, and Storing Discrete Data Records Based Upon a Single Data Input.” This patent is part of Target Health’s commitment to the paperless clinical trial and the transformation of clinical trials to 21st century technology. This patent allows for direct data entry (DDE) of clinical trial data and is consistent with the draft eSource guidances issued by FDA and EMA. EDC companies will now be able to provide a method for direct data entry and help the sponsoring pharmaceutical companies improve data quality, enhance safety monitoring and reduce clinical trial costs.

 

This method of direct data entry is currently being used in 2 studies under 2 US IND’s and an NDA is planned for 2012 using fully paperless systems. For more information and to discuss how we can collaborate, please contact Dr. Jules T. Mitchel at Target Health.

 

The abstract of the patent is as follows: “According to the present invention, there is provided a system and method for the collection, capture, processing, storage, and tracking of data for both electronic clinical trial and electronic source health records for purposes, based upon a single data collection instance. Upon the collection of data at a clinical trial site, the data are transmitted to a central server where it is captured as an electronic source document(s) in human readable format. The system then transmits the captured electronic source document to a trusted third-party’s electronic document repository. Then, the system uses the same captured data to populate the clinical trial’s electronic data capture database. The system incorporates security and encryption features to ensure that privacy information requirements are not violated. In the preferred embodiment, the electronic data capture provider for a clinical trial has no control over the server of the trusted third-party vendor, complying with regulatory requirements. Additionally, the collected data can be pushed into a clinical site’s electronic health record system or any equivalent system which houses electronic data. Throughout the operation of the system, an audit trail is maintained which records information relating to all data recording, modifying, and accessing events.” The patent application was filed on July 17, 2009.

 

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

Starving Prostate Cancer: Scientists Discover How to Cut Off Cancer’s Food Supply

 

 

Researchers at the Centenary Institute in Sydney have discovered a potential future treatment for prostate cancer – through starving the tumor 1) ___ of an essential nutrient they need to grow rapidly. Their work, with human cells reveals targets for drugs that could slow the progress of early and late stage prostate cancer. The research has been funded by the Prostate Cancer Foundation of Australia (PCFA) and Movember.

 

Each year about 3,300 Australian men die of prostate cancer. It’s Australia’s second worst cancer killer for 2) ___, matching the impact of breast cancer on women. Current therapies for prostate cancer include surgical removal of the prostate, radiation, freezing the tumor or cutting off the supply of the hormone testosterone – but there are often side-effects including 3) ___ and impotence. Growing cells need an essential nutrient, the amino acid called leucine, which is pumped into the cell by specialized proteins. And this could be prostate cancer’s weak link.

 

Dr Jeff Holst and his team at the Centenary Institute found, in a study to be published this month in Cancer Research, that prostate cancer cells have more pumps than normal. This allows the cancer cells to take in more leucine and outgrow normal cells. “This information allows us to target the pumps – and we’ve tried two routes. We found that we could disrupt the uptake of leucine firstly by reducing the expression amount of the protein pumps, and secondly by introducing a drug that competes with leucine. Both approaches slowed 4) ___ growth, in essence ‘starving’ the cancer cells,” Dr Holst says.

 

First author Dr Qian Wang says by targeting different sets of pumps, we were able to slow tumor growth in both the early and 5) ___ stages of prostate cancer. “In some of the experiments, we were able to slow tumor growth by as much as 50%. Our hope is that we could develop a treatment that slows the growth of the cancer so that it would not require 6) ___ removal.” Dr Holst says one of the other spin-offs of the discovery is a better understanding of the links between prostate cancer and eating foods high in leucine. “Diets high in red meat and dairy are correlated with prostate cancer but still no one really understands why. We have already begun examining whether these pumps can explain the links between diet and 7) ___ cancer.”

 

“This fundamental research tells us more about how prostate and other cancers grow, and will open the way for new treatments in the long term,” says Movember chairman Paul Villanti. Movember is now one of the largest non-government global funders of prostate cancer 8) ___. PCFA CEO Dr Anthony Lowe says research that has the potential to reduce the impact of prostate cancer on those who are diagnosed is a huge priority for the PCFA’s grants program.

 

Leucine, which isn’t produced by the 9) ___ body, is found in protein-rich animal foods such as beef, chicken, fish, dairy, and eggs. Listed below, is the amount of leucine (in descending order) in some protein rich foods:

 

  • Egg, white, raw, fresh Leucine: 4233mg
  • Soy protein isolate, potassium type, crude protein basis Leucine: 4226mg
  • Seaweed, spirulina, raw Leucine: 3915mg
  • Chicken, broilers or fryers, breast, meat only, cooked, rotisserie, original seasoning Leucine: 3698mg
  • Fish, tuna, light, canned in water, drained solids Leucine: 3574mg
  • Turkey, fryer-roasters, breast, meat only, cooked, roasted Leucine: 3549mg
  • Cheese, cottage, lowfat, 1% milkfat Leucine: 3540mg
  • Beef, center-cut, cooked Leucine: 2943

 

ANSWERS: 1) cells; 2) men; 3) incontinence; 4) cancer; 5) late; 6) surgical; 7) prostate; 8) research; 9) human

Eric Richard Kandel MD (1929 to Present)

 

 

Eric Richard Kandel (born November 7, 1929) is an American neuropsychiatrist who was a recipient of the 2000 Nobel Prize in Physiology or Medicine for his research on the physiological basis of memory storage in neurons. Kandel is professor of biochemistry and biophysics at the Columbia University College of Physicians and Surgeons and a Senior Investigator in the Howard Hughes Medical Institute. He was also the founding director of the Center for Neurobiology and Behavior, which is now the Department of Neuroscience at Columbia. Kandel authored In Search of Memory: The Emergence of a New Science of Mind (WW Norton), which chronicles his life and research.

 

Kandel was born in 1929 in Vienna, Austria, in a middle-class Jewish family. When Eric was 9, he and his brother Ludwig, 14, boarded the “Gerolstein” at Antwerp in Belgium and joined their uncle in Brooklyn on May 11, 1939. After arriving in the United States, Kandel was tutored by his grandfather in Judaic studies, and was accepted at the Yeshiva of Flatbush, graduating in 1944. He attended Brooklyn’s Erasmus Hall High School, a Public high school.

 

Kandel’s initial intellectual interests lay in the area of history. (History and Literature was his undergraduate major at Harvard University.) He wrote an honors dissertation on “The Attitude Toward National Socialism of Three German Writers: Carl Zuckmayer, Hans Carossa, and Ernst Junger.” While at Harvard, a place dominated by the work of B. F. Skinner, Kandel became interested in learning and memory. It should be noted, however, that while Skinner championed a strict separation of psychology, as its own level of discourse, from biological considerations such as neurology, Kandel’s work is essentially centered on an explication of the relationships between psychology and neurology.

 

The world of neuroscience was first opened up to Kandel through his interactions with a college girlfriend, Anna Kris, whose parents were Freudian psychoanalysts. Freud, a pioneer in revealing the importance of unconscious neural processes, was at the root of Kandel’s interest in the biology of motivation and unconscious and conscious memory. In 1952 Kandel started at the New York University Medical School. Kandel was first exposed to research in Harry Grundfest’s laboratory at Columbia University. Grundfest was known for using the oscilloscope to demonstrate that action potential conduction velocity depends on axon diameter. The researchers Kandel interacted with were contemplating the technically challenging idea of intracellular recordings of the electrical activity of the relatively small neurons of the vertebrate brain.

 

After starting his neurobiological work in the difficult thicket of the electrophysiology of the cerebral cortex, Kandel was impressed by the progress that had been made by Stephen Kuffler using a much more experimentally accessible system: neurons isolated from marine invertebrates. After becoming aware of Kuffler’s work in 1955, Kandel graduated from medical school and learned from Stanley Crain how to make microelectrodes that could be used for intracellular recordings of relatively large crayfish giant axons.

 

When Kandel joined the Laboratory of Neurophysiology at the NIH in 1957, William Beecher Scoville and Brenda Milner had recently described the patient HM, who had lost explicit memory storage following removal of the hippocampus. Kandel took on the task of performing electrophysiological recordings of hippocampal pyramidal neurons. Working with Alden Spencer, electrophysiological evidence was found for action potentials in the dendritic trees of hippocampal neurons. They also noticed the spontaneous pace-maker-like activity of these neurons and a robust recurrent inhibition in the hippocampus. With respect to memory, there was nothing in the general electrophysiological properties of hippocampal neurons that suggested why the hippocampus was special for explicit memory storage.

 

Kandel began to realize that memory storage must rely on modifications in the synaptic connections between neurons and that the complex connectivity of the hippocampus did not provide the best system for study of the detailed function of synapses. Kandel was aware that comparative studies of behavior, such as those by Konrad Lorenz, Niko Tinbergen, and Karl von Frisch had revealed conservation of simple forms of learning across all animals. Kandel felt it would be productive to select a simple animal model that would facilitate electrophysiological analysis of the synaptic changes involved in learning and memory storage. This decision was not without risks since many senior biologists and psychologists believed that nothing useful could be learned about human memory by studying invertebrate physiology.

 

In 1962, after completing his residency in psychiatry, Kandel went to Paris to learn about the marine mollusc Aplysia californica. Kandel had realized that simple forms of learning such as habituation, sensitization, classical conditioning, and operant conditioning could readily be studied with ganglia isolated from Aplysia. While recording the behavior of a single cell in a ganglion, one nerve axon pathway to the ganglion could be stimulated weakly electrically as a conditioned [tactile] stimulus, while another pathway was stimulated as an unconditioned [pain] stimulus, following the exact protocol used for classical conditioning with natural stimuli in intact animals. Electrophysiological changes resulting from the combined stimuli could then be traced to specific synapses. In 1965 Kandel published his initial results, including a form of pre-synaptic potentiation that seemed to correspond to a simple form of learning.

 

 

Eric Kandel in 1978

 

Kandel took a position in the Departments of Physiology and Psychiatry at the New York University Medical School, eventually forming the Division of Neurobiology and Behavior. Working with Irving Kupferman and Harold Pinsker it was possible to develop protocols for demonstrating simple forms of learning by intact Aplysia. In particular, the now famous gill-withdrawal reflex, by which the tender Aplysia gill tissue is withdrawn from danger, was shown to be sensitive to both habituation and sensitization. By 1971 Tom Carew joined the research group and helped extend the work from studies restricted to short-term memory to additional experiments that included additional physiological processes required for long-term memory.

 

By 1981, laboratory members including Terry Walters, Tom Abrams, and Robert Hawkins had been able to extend the Aplysia system into the study of classical conditioning, a finding which helped close the apparent gap between the simple forms of learning often associated with invertebrates and more complex types of learning more often recognized in vertebrates. Along with the fundamental behavioral studies, other work in the lab traced the neuronal circuits of sensory neurons, interneurons, and motor neurons involved in the learned behaviors. This allowed analysis of the specific synaptic connections that are modified by learning in the intact animals. The results from Kandel’s laboratory provided solid evidence for the mechanistic basis of learning as “a change in the functional effectiveness of previously existing excitatory connections.”

 

Starting in 1966 James Schwartz collaborated with Kandel on a biochemical analysis of changes in neurons associated with learning and memory storage. By this time it was known that long-term memory, unlike short-term memory, involved the synthesis of new proteins. By 1972 they had evidence that the second messenger molecule cyclic AMP (cAMP) was produced in Aplysia ganglia under conditions that cause short-term memory formation (sensitization). In 1974 the Kandel lab moved to Columbia University as founding director of the Center for Neurobiology and Behavior. It was soon found that the neurotransmitter serotonin acting to produce the second messenger cAMP is involved in the molecular basis of sensitization of the gill-withdrawal reflex. By 1980, collaboration with Paul Greengard resulted in demonstration that cAMP-dependent protein kinase (PKA) acted in this biochemical pathway in response to elevated levels of cAMP.

 

In 1983 Kandel helped form the Howard Hughes Medical Research Institute at Columbia devoted to molecular neural science. The Kandel lab took on the task of identifying proteins that had to be synthesized in order to convert short-term memories into long-lasting memories. The Kandel lab has also performed important experiments using transgenic mice as a system for investigating the molecular basis of memory storage in the vertebrate hippocampus. Kandel’s original idea that learning mechanisms would be conserved between all animals has been confirmed. Neurotransmitters, second messenger systems, protein kinases, ion channels, and transcription factors have been confirmed to function in both vertebrate and invertebrate learning and memory storage.

Rare Autoinflammatory Disease in Children

 

Dr. Mark L. Horn, our CMO will be attending the American Rheumatology Association meeting this week. Let us know if you are attending.

 

An international collaboration of scientists, including those at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), has identified a genetic mutation that causes a rare childhood disease characterized predominantly by inflammation and fat loss. The research suggests that the disorder, named chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), actually represents a spectrum of diseases that have been described in the literature under a variety of names. More importantly, since no effective treatment for this disease currently exists, the findings may have uncovered a possible target for future treatments.

 

The collaboration began when NIAMS rheumatologist Dr. Raphaela Goldbach-Mansky, started seeking the cause of inflammatory skin lesions, fat loss and fevers in two of her young patients. At a scientific meeting, she learned about recent publications by two other research groups — one led by dermatologists Dr. Antonio Torrelo from the Boy Jesus Hospital, Madrid, and Dr. Amy Paller from Northwestern University, Chicago, and the other led by Dr. Abraham Zlotogorski from the Hadassah-Hebrew University Medical Center, Jerusalem – describing similar conditions.

 

Based on the clinical presentation and, particularly, the unusual skin lesions seen in the children, it was hypothesized that the children must have the same disease. Subsequent analyses involving biopsies, blood tests and genetic testing confirmed the hypothesis. All but one child had at least one mutation in a gene called PSMB8, which had been recently identified in three adult patients with a disease called joint contractures, muscle atrophy and panniculitis-associated lipodystrophy (JMP). PSMB8 is one of more than 20 components involved in making a cellular structure called a proteasome, which recycles proteins from cells that are stressed or dying.

 

The one patient without the mutation had a blood profile that was identical to the ones who did, and showed the same accumulation of waste products in the cells seen in children with the genetic mutation. Blood tests also showed high levels of an inflammatory chemical called interferon gamma-induced protein 10 (IP-10) that is stimulated by interferons. The chemical is produced in response to some infections, and the group suspects that it also may be produced in the cellular stress response.

 

The discovery, which is reported online in Arthritis & Rheumatism (27 Oct 2011), unifies several different diseases into one spectrum of proteasome-associated autoinflammatory syndromes. The authors hope that these findings will enable the identification of more children who fit into this spectrum of difficult-to-treat disorders so that they can develop a better understanding of the disorders and their treatment.

 

Despite the best treatments currently available — which, in most cases, consist of high doses of steroids — children with these disorders continue to lose fat and suffer metabolic changes that lead to a range of problems, including loss of muscle mass, dilated heart muscles and cardiac arrhythmias. Treatments for other inflammatory diseases have little, if any, effect on the prognoses of these diseases. The group’s findings, however, suggest new therapeutic targets.

ONCOLOGY

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No Effect of Radiograph Screening on Lung Cancer Mortality

 

The effect on mortality of screening for lung cancer with modern chest radiographs is unknown. As a result, a study published online in the Journal of the American Medical Association (2011;306:1865-1873) was performed to evaluate the effect on mortality of screening for lung cancer using radiographs.

 

The investigation was part of the randomized Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial that involved 154,901 participants aged 55 through 74 years, 77,445 of whom were assigned to annual screenings and 77,456 to usual care.

 

Study participants in the intervention group were offered annual posteroanterior  view chest radiograph for 4 years. Diagnostic follow-up of positive screening results was determined by participants and their health care practitioners. Participants in the usual care group were offered no interventions and received their usual medical care. All diagnosed cancers, deaths, and causes of death were ascertained through the earlier of 13 years of follow-up or until December 31, 2009. The main outcome measures was mortality from lung cancer. Secondary outcomes included lung cancer incidence, complications associated with diagnostic procedures, and all-cause mortality.

 

Results showed that screening adherence was 86.6% at baseline and 79% to 84% at years 1 through 3. Cumulative lung cancer incidence rates through 13 years of follow-up were 20.1 per 10,000 person-years in the intervention group and 19.2 per 10,000 person-years in the usual care group. A total of 1,213 lung cancer deaths were observed in the intervention group compared with 1,230 in usual care group through 13 years (mortality RR, 0.99). Stage and histology were similar between the 2 groups.

 

According to the authors, annual screening with chest radiograph did not reduce lung cancer mortality compared with usual care.

Broad Spectrum of Cancer Risk for Organ Transplant Recipients

 

In 2010, a total of 28,664 organ transplants were performed in the U.S., including 16,899 kidney, 6,291 liver, 2,333 heart, and 1,770 lung transplants.

 

It has been well documented that transplant recipients are at a higher risk for developing cancer than the general population. But past studies of cancer risk in transplant recipients focused mainly on those who received kidney transplants, and other studies were too small to accurately estimate risk for all but the most common cancer types. As a result, a study published in the Journal of the American Medical Association (2011;306:1891-1901), has now shown that organ transplant recipients in the U.S. have a high risk of developing 32 different types of cancer. The study evaluated medical data from more than 175,700 transplant recipients, accounting for about 40% of all organ transplant recipients in the country.

 

The study, which linked data from the U.S. registry of transplant recipients (from 1987 through 2008) with 13 state or regional cancer registries of all solid organ types, allowed the authors to provide more accurate estimates of risk for both common and rarer cancers in a representative sample of the U.S. transplant population. Results showed a twofold overall increased risk of cancer among all transplant recipients, which is similar to results from past studies but also an elevated risk for 32 different types of cancer, some known to be related to infectious agents (e.g., anal cancer, Kaposi sarcoma) and others unrelated to infections (e.g., melanoma, thyroid cancer).

 

The study also found that the most common cancers among transplant recipients were non-Hodgkin lymphoma (14.1% of all cancers in transplant recipients), lung cancer (12.6%), liver cancer (8.7%), and kidney cancer (7.1%). The authors carried out additional analyses of these four cancers and, based on known risk and their new study, report:

 

— Non-Hodgkin lymphoma is elevated more than sevenfold in transplant recipients, with non-Hodgkin lymphoma incidence highest among those who received transplants as children or older adults. This cancer is known to be related to immune suppression and infection with Epstein-Barr virus. Non-Hodgkin lymphoma incidence was highest in lung recipients, intermediate in liver and heart recipients, and lowest in kidney recipients.

 

— Lung cancer risk was highest in lung recipients, with smoking-related disease often the reason for the transplant. Studies of cancer show that among lung recipients, most of whom received a single lung transplant, lung cancer typically arises in the recipient’s remaining diseased lung rather than the transplanted one. Increased risk for lung cancer may also be related to inflammation or chronic lung infections.

 

— The risk of liver cancer was elevated only among liver recipients. Studies of cancer show, in this group, the occurrence of liver cancer can be partly attributed to recurrent hepatitis B or C infection in the transplanted liver, or to diabetes mellitus, which is also common among transplant recipients.

 

— Risk of kidney cancer is increased for all recipients. There are multiple reasons for an elevated risk of kidney cancer in transplant recipients. Recipients who get kidney transplants have damaged kidneys, frequently including multiple kidney cysts, which can become cancerous. However, an elevated risk was also observed among recipients of other organs. Therefore, the researchers suggest the risk for kidney cancer could be partly due to exposure to immune-suppressive medications, which may have direct carcinogenic effects.

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

 

FDA Approvals in 2011:
35 Innovative New Drugs Approved by FDA

 

Over the past 12 months, the FDA has approved 35 new medicines. This is among the highest number of approvals in the past decade, surpassed only by 2009 (37). Many of the drugs are important advances for patients, including: two new treatments for hepatitis C; a drug for late-stage prostate cancer; the first new drug for Hodgkin’s lymphoma in 30 years; and the first new drug for lupus in 50 years.

 

In a report released today, FY 2011 Innovative Drug Approvals, the FDA provided details of how it used expedited approval authorities, flexibility in clinical trial requirements and resources collected under the Prescription Drug User Fee Act (PDUFA) to boost the number of innovative drug approvals to 35 for the fiscal year (FY) ending Sept. 30, 2011.

 

The report shows faster approval times in the United States when compared to the FDA’s counterparts around the globe. Twenty-four of the 35 approvals occurred in the United States before any other country in the world and also before the European Union, continuing a trend of the United States leading the world in first approval of new medicines.

 

Among the new drugs approved in FY 2011, a number are notable for their advances in patient care and for the efficiency with which they were approved:

 

— Two of the drugs – one for melanoma and one for lung cancer – are breakthroughs in personalized medicine. Each was approved with a diagnostic test that helps identify patients for whom the drug is most likely to bring benefits;

 

— Seven of the new medicines provide major advances in cancer treatment;

 

— Almost half of the drugs were judged to be significant therapeutic advances over existing therapies for heart attack, stroke and kidney transplant rejection;

 

— Ten are for rare or “orphan” diseases, which frequently lack any therapy because of the small number of patients with the condition, such as a treatment for hereditary angioedema;

 

— Almost half (16) were approved under “priority review,” in which the FDA has a six month goal to complete its review for safety and effectiveness;

 

— Two-thirds of the new approvals were completed in a single review cycle, meaning sufficient evidence was provided by the manufacturer so that the FDA could move the application through the review process without requesting major new information;

 

— Three were approved using “accelerated approval,” a program under which the FDA approves safe and effective medically important new drugs quickly, and relies on subsequent post-market studies to confirm clinical benefit. For example, Corifact, the first treatment approved for a rare blood clotting disorder, was approved under this program; and

 

— Thirty-four of 35 were approved on or before the review time targets agreed to with industry under PDUFA, including three cancer drugs that FDA approved in less than six months.