Target Health at DIA (Washington, DC) and BioMed (Israel)

June will be a busy month for Target Health. We will again have a booth at DIA (June 14-16) and will be sharing our paperless eClinical trial suite of software products as well as our full service CRO capabilities. We anticipate 2 FDA approvals this year as well as an eCTD submission. We will feature Target e*CRF® fully integrated with Target Encoder®, Target e*Pharmacovigilance™ and batch edit checks; Target Document® and Target e*CTMS™. For Pharma companies, we will share our eSource software which will revolutionize the monitoring of clinical trial data. Please contact Warren Pearlson (212-681-2100 ext 104) if you will be attending and would like to see any demos.

During the same week of DIA, Dr. Jules T. Mitchel will be attending BioMed (June 14-16) in Israel. BioMed highlights the biotech industry in Israel and gives us a chance to meet our colleagues in Israel. Let us know if you will be attending so we can plan a get-together. 

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 feel free to also 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: www.targethealth.com

One-a-Day Heart Polypill to Be Tested in New International Trial

In a major new international trial, researchers will be exploring whether a new, very low cost, one-a-day combined “polypill“ could reduce the risk of heart attacks, strokes and other cardiovascular problems. Cardiovascular disease is the world’s biggest 1) ___ and the leading cause of loss of healthy life years. The new “Red Heart Pill“ contains low-dose 2) ___, a statin and two blood pressure-lowering medicines in a single polypill. It is expected to be substantially cheaper than existing medications to combat cardiovascular problems. Researchers are now recruiting 2,000 volunteers who are at high risk of heart attack or stroke, or who have already had such a cardiovascular event, for a two-year trial of the Red Heart Pill. The trial, called UMPIRE (Use of a Multidrug Pill In Reducing cardiovascular Events), launches in London in the UK and at other centers in Ireland, the Netherlands and (pending regulatory approval) in India. Related trials began earlier in the year in New Zealand and Australia and plans for further trials are also underway in Brazil, Canada, China and South Africa. Collectively these parallel trials will include around 7,000 participants in ten countries and can thereby evaluate the potential of the polypill treatment strategy to prevent 3) ___ events. The researchers behind the trial will be investigating whether patients are more likely to stick with a preventive treatment regime using a single, one-a-day polypill, rather than multiple tablets. The researchers will also be exploring whether the Red Heart Pill is effective at reducing blood pressure and lowering 4) ___. If the treatment strategy is effective, the researchers plan to establish how the polypill could be made available to people on low incomes in countries like India, where 80% of health care is paid out of pocket and the majority of 5) ___ do not currently have access to cardiovascular drugs. It is expected that the Red Heart Pill could be made available in low-income countries at a substantially lower cost than separate medications, providing a cost-effective approach that could potentially save millions of lives across the world. In countries like the UK, where heart 6) ___ are more readily available, the researchers want to explore whether the Red Heart Pill could provide a more convenient alternative to existing medications. In the UK, the medications contained in the polypill are currently prescribed individually. Such 7) ___ treatments are recommended by doctors, because they can more than halve the risk of cardiovascular events, but evidence shows that at present many people who start on these medicines do not continue to take them in the long term. Polypills are being used successfully to treat other diseases like 8) ___ and HIV, but we don’t yet know whether they could be effective in those with cardiovascular problems. The UMPIRE trial aims to test whether the polypill does help people take their cardiovascular medicines in the long term and whether there are any unintended problems with this approach.

ANSWERS: 1) killer; 2) aspirins; 3) cardiovascular; 4) cholesterol; 5) people; 6) medications; 7) preventive; 8) tuberculosis

Defibrillators

Ventricular fibrillation – uncontrolled fluttering of the heart that can lead to death within minutes – was a phenomenon well known as early as 1850. In fact, it was known that an electric current could start these abnormal contractions in a healthy heart. In 1899, two Swiss researchers experimenting with dogs discovered that the fibrillation could also be stopped and normal beats restored in the same way, by shocking the heart. The New York Times reported the finding on July 3, 1899, but it did not resurface until a short unsigned article was published on July 28, 1948, which described a lung operation in a Trenton, NJ hospital that had gone seriously wrong. The patient’s heart had stopped just as the surgeon made a chest incision. There were apparently some quick-thinking, well-informed people in the operating room. While the surgeon massaged the man’s heart manually, the article said, “a makeshift defibrillator’ was rigged to administer instantaneous electric shock treatment.“ The article described a process that was shocking in more ways than one. When the man’s heart went into ventricular fibrillation – an event that means death in less than five minutes – operating room workers hooked two copper electrodes to an examining lamp that happened to be in the room, touched the other ends to the man’s heart, and shocked it into normal rhythm. The operation was postponed, and four hours later, the article reported, the patient died in his hospital room. The “Philadelphia specialist“ who dared to attach the wires “requested that his name be withheld from publication,“ no doubt with good reason. But whoever he was, he was probably up to date on the latest in defibrillation. He may have known of a report, published in The Journal of the American Medical Association seven months earlier, of the first case of ventricular fibrillation in a human successfully treated with electric shock when an apparently dead 14-year-old boy brought back to life. He did not read of it in The Times, which took no note of it. The Times did not mention defibrillators again until Jan. 23, 1957, under the headline “Shock Treatment for Heart Urged.“ The unsigned article reported that “Equipment for defibrillation in the operating room has been developed and is now employed at Johns Hopkins and several other hospitals“ and that the researchers were “working on the development of defibrillating equipment that might be used in the field.“ Portable defibrillators are now routinely carried today in police cars and ambulances, and untrained people have successfully used those placed in shopping malls, sports arenas, schools, airplanes and other public places. Source: The New York Times, by Nicholas Bakalar

GENETICS

Filed Under News | Leave a Comment

First Genomic Collection of Human Microbes

The human microbiome consists of all the microorganisms that reside in or on the human body. Outnumbering cells in the human body by 10 to 1, some of the microorganisms cause illnesses, but many are necessary for good health. Currently, researchers can grow only some of the bacteria, fungi and viruses in a laboratory setting.  However, new genomic techniques can identify minute amounts of microbial DNA in an individual and determine its identity by comparing the genetic signature to known sequences in the project’s data base. The Human Microbiome Project (HMP) published an analysis of 178 genomes from microbes that live in or on the human body (Science May 21 2010: 994-999). The project has discovered novel genes and proteins that serve functions in human health and disease, adding a new level of understanding to what is known about the complexity and diversity of these organisms. Launched in 2008 as part of the NIH Common Fund’s Roadmap for Medical Research, the HMP is a $157 million, five-year effort that will implement a series of increasingly complicated studies that reveal the interactive role of the microbiome in human health. The 178 microbial genomes in this report launch the HMP reference collection that eventually will total approximately 900 microbial genomes of bacteria, viruses and fungi. These data will then be used by HMP researchers to characterize the microbial communities found in samples taken from healthy human volunteers and, later, those with specific illnesses. Samples are currently being collected for HMP from five areas of the body: the digestive tract, the mouth, the skin, the nose and the vagina. The study also conducted a preliminary survey to gain insights into the function of some of the newly identified genes and proteins unique to individual microbial strains. For instance, previously unknown proteins produced by bacteria that live in the stomach that may cause gastric ulceration were identified. In addition, a small number of newly identified novel proteins associated with how sugars and amino acids are metabolized were found. The study also evaluated the microbial diversity present in the HMP reference collection. For example, 29,693 previously undiscovered, unique proteins in the reference collection were found, representing more proteins than there are estimated genes in the human genome. One of the primary goals of the HMP reference collection is to expand researchers’ ability to interpret data from metagenomic studies. Metagenomics is the study of a collection of genetic material (genomes) from a mixed community of organisms. Comparing metagenomic sequence data with genomes in the reference collection can help researchers determine whether they are novel or already existing sequences.

Receptor Variant Influences Dopamine Response to Alcohol

Receptors for brain molecules known as opioid peptides help initiate the neurochemical reactions that underlie the positive effects produced by alcohol. Activation of the mu-subtype of opioid receptor following alcohol consumption triggers the release of dopamine from the forebrain. Dopamine is involved in transmitting the euphoria and other positive subjective effects produced by alcohol. According to an article published online in Molecular Psychiatry (18 May 2010), a genetic variant of a receptor in the brain’s reward circuitry plays an important role in determining whether the neurotransmitter dopamine is released in the brain following alcohol intake. Previous studies have indicated that people who carry the mu-opioid receptor variant designated as 118G, report increased euphoria following alcohol consumption. A similar mu-opioid receptor variant in monkeys heightens the stimulating effects of alcohol and increases their alcohol consumption. The current study explored whether the 118G mu-opioid receptor variant influences dopamine release from a forebrain region called the ventral striatum in response to alcohol. Using human positron emission tomography (PET), an imaging technique that allowed the researchers to analyze dopamine activity in the brain, dopamine release was compared in two groups of people that had been given a dose of alcohol. The groups consisted of those who carried a copy of the gene for the 118G mu-opioid receptor variant, and those who carried only genes for the more common 118A variant. Results showed that only people with the 118G variant had a dopamine response to alcohol and no such response happened in subjects with the 118A receptor variant. In a separate experiment, genes for the human 118G or 118A mu-opioid receptor variants were inserted into mice and then directly measured the animals’ dopamine response to a dose of alcohol. Mice with the 118G variant showed a fourfold higher peak dopamine response to the alcohol challenge compared to mice with the 118A variant. According to the authors, the data strongly support a causal role of the 118G variant of the mu-opioid receptor to confer a more vigorous dopamine response to alcohol in the ventral striatum. The authors added that the findings add further support to the notion that individuals who possess this receptor variant may experience enhanced pleasurable effects from alcohol that could increase their risk for developing alcohol abuse and dependence. It may also explain why these individuals, once addicted, benefit more from treatment with blockers of endogenous opioids.

Infants Capable of Learning While Asleep

According to an article published online in the Proceedings of the National Academy of Sciences (17 May 2010), newborn infants are capable of a simple form of learning while they’re asleep. The finding may one day lead to a test that can identify infants at risk for developmental disorders that do not become apparent until later in childhood. The study was confined to newborns, so the authors do not know whether older children or adults are capable of learning during sleep. The study used an electroencephalogram, a machine that records the brain’s electrical activity and converts it into patterns, to record the brain activity of each sleeping infant. A video camera recorded each infant’s facial expressions. The researchers played a tone, while a machine blew a faint puff of air at each sleeping infant’s eyelids. In response to the air puff, the infants reflexively squeezed their closed lids tighter. The researchers repeated this nine times, each time pairing the air puff with the tone. For the tenth time in the sequence, however, the researchers played the tone without the air puff. This sequence was repeated over and over again. After roughly 20 minutes, most of the infants (24 out of 26) would scrunch their faces in response to the tone that was not accompanied by the air puff. Moreover, the electroencephalogram detected changes in brain wave activity that occurred simultaneously with the tone, which the authors interpret as further evidence that the infants had learned to associate the tone with the air puff. Infants in the control group, who were exposed to random, unpaired tones and air puffs, did not squeeze their eyelids in response to isolated tones. According to the authors, the current experiment is the first to demonstrate that newborn infants are capable of learning about relationships between stimuli while asleep. The authors commented that it is not known whether learning to make such associations during sleep is unique to infants or could also occur in adults and that it’s possible that the ability might diminish with age. The authors also noted that this type of learning is controlled by the cerebellum, a part of the brain that is implicated in many developmental disorders. This non-invasive measure of cerebellar function in sleeping newborn infants might later provide a means to screen for developmental conditions very early in life.

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

 

Notes from ISPOR

 

ISPOR, the International Society for Pharmacoeconomics and Outcomes Research, just celebrated its 15 Anniversary in Atlanta. Growth has been dramatic and is unsurprising given the Society’s focus on issues which have become critical for health systems across the globe. Personalized Medicine, Genomics, Bayesian Adaptive Clinical Trials, Practical Clinical Trials and Comparative Effectiveness Research were all on the menu. An underlying (perhaps the underlying) driver in all of this is the critical need by payers around the world for data driven and therefore legitimate mechanisms to “bend the cost curve“ in an era of rapid growth in effective, (and expensive) innovations. This will, of course, not be easy since many interests are at play, and these varied interests were much in evidence at the meeting. Payers, (both private and public), industry, regulators, patient advocacy groups, and academics from around the world were all represented among both attendees and presenters. Efforts to define and demonstrate value in an array of clinical settings using multiple modeling techniques were very much in evidence. Among the more interesting sessions was a quite frank discussion about why ISPOR members’ research output has not had a greater impact on health care decision making despite its apparent convergence with the cost concerned “tenor of the times“. Multiple issues were raised, but key among them for Target Clients was an evident lack of trust in industry sponsored pharmacoeconomic research. Future comments in On-Target will explore specifics of these varied issues and research approaches. For now, since challenges present opportunities, clients might consider what actions could increase the likelihood that the pharmaceutical and device industries will be respected contributors in these important areas of research; otherwise, industry may leave the definition of “value“ and potentially reimbursement for products, to others. By Mark L. Horn MD, MPH

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.

Target Health Inc.
261 Madison Avenue
24th Floor
New York, NY 10016

W:   www.targethealth.com
B:   http://Blog.targethealth.com

Joyce Hays, CEO
Jules T. Mitchel President