Glaxo is conducting a randomized
While the IOM did not target the Avandia trial in particular, FDA Commissioner Margaret Hamburg asked the independent, nonprofit medical group to weigh in with at least an initial finding on general ethical issues involving the safety of studying the risks of drugs already in use.
The FDA called in 2007 for the TIDE study, which aims to enroll 16,000 patients and end in 2015, although some critics say it could take longer.
Analyses of other data since then have convinced some researchers that Avandias risks are greater than those of Actos and have repeatedly called for the trial to be halted.
Glaxo has defended its drug, saying data overall shows it does not increase the risk of heart attack, stroke or death.
On Tuesday and Wednesday, FDAs panel of outside experts will weigh numerous studies and analyses before recommending whether Avandia should remain on the market, be pulled from the market, or various options in between.
They also will be asked to weigh in on the TIDE trial.
In its report, the IOM said randomized controlled trials should only be done when a responsible policy decision cannot be made based either on the existing evidence or on evidence from new observational studies.
It also said studies of real world use of a drugknown as observational studies and often done by reviewing insurance claims and other databases — can yield strong data.
In separate FDA documents released on Friday, FDA staff scientists were split over whether the TIDE trial should continue just as they are divided over whether another major Glaxo trial, RECORD, showed excessive heart-attack risks with Avandia.
Some staff also pointed to studies done since 2007, including an FDA analysis of 52 trials on the drug, as well as a review of Medicare data that showed a greater risk of heart attack and other complications with Glaxos drug.
Based on these findings, any proposed head-to-head trial of rosiglitazone vs. pioglitazone is unethical and exploitative, agency reviewers David Graham and Kate Gelperin wrote.
Rosiglitazone is the generic name for Avandia, and pioglitazone is the generic name for Actos.
Another FDA scientist, clinical reviewer Karen Mahoney, said that the TIDE trial does not have many of the limitations of the earlier RECORD study and could be illuminating.
This trial, if it continues to completion, has the potential to address the question of the cardiovascular safety of rosiglitazone more definitively, she wrote in a separate memo.
Reporting by Susan Heavey Editing by Tim Dobbyn source
We make new neurons every day in our brain
What our compound does in allow more of them to survive.
The compound is called P7C3 for now, and the researchers have already started tweaking it to make it more effective. They said it seems safe and appears to work even when taken as a pill.
The compound is similar to Medivation Inc and Pfizer Incs experimental Alzheimers drug, Dimebon, and may provide ways to improve its effects, Pieper and colleagues reported in the journal Cell.
It is also similar to some compounds owned by Serono, the researchers said.
Dimebon, originally a Russian-made antihistamine also known as latrepirdine, failed in a clinical trial for Alzheimers disease in March.
For the sake of patients suffering from Alzheimers disease, it is hoped that the apparently marginal clinical utility of Dimebon might be enhanced by improvements in both its potency and ceiling of proneurogenic, neuroprotective efficacy, the researchers wrote.
If so, our work offers concrete assays for the development of improved versions of these neuroprotective drugs.
Alzheimers gradually destroys the brain and affects 26 million people globally. Drugs, such as Pfizers Aricept, improve symptoms only minimally.
OLD RATS, NEW TRICKS
The researchers went through 1,000 representative compounds from 300,000 chemicals, pooled them and administered them to mice. They then dissected the brains to see whether any of the mice had made new cells in the hippocampus, a region of the brain associated with learning and memory.
They eventually narrowed the field to P7C3.
When they gave it to old rats for two months, the elderly rodents did far better than other old rats in learning their way around a water maze.
When dissected, the treated rats turned out to have three times the usual number of newborn neurons in a brain region called the dentate gyrus.
They made a derivative of P7C3 called A20 that worked even better.
When the researchers tested Dimebon and the Serono compounds, they found these drugs also stimulated the growth of new brain cells. Being able to target their effects could lead to better drugs to treat Alzheimers and perhaps other diseases that destroy brain cells like strokes and amyotrophic lateral sclerosis, also know as ALS or Lou Gehrigs disease.
This striking demonstration of a treatment that stems age-related cognitive decline in living animals points the way to potential development of the first cures that will address the core illness process in Alzheimers disease, said Dr. Thomas Insel, director of the National Institute on Mental Health, which helped pay for the study. source
It also opens potential new ways finding and developing
We now recognize that these synapse proteins are the molecular basis of many brain diseases, he told reporters before presenting his findings at the Forum for European Neuroscience in Amsterdam on Monday. We know of no other molecular structure which is responsible for more brain diseasesso we think its a major discovery.
Grants team used a technique called proteomics to analyze all the proteins in human brain cells. Humans have around a million billion brains cells and these are connected by synapses, which play a pivotal role because they create circuits that allow the brain to learn and remember things.
The scientists found around 1,500 proteins in human synapses, each of which is encoded by a gene. They then managed to link genetic defects in some of these with key diseases such as autism, bipolar disorder, depression and schizophrenia.
By understanding the composition of the synapse, we can also ask which proteins are important to diseases, and therefore get a sense of the disease burden that the synapse is involved with, Grant said.
Rather than thinking that a gene causes a particular disease, what were seeing now is that the gene mutation disrupts the protein complexes that cause the disease. We found that defects in the genes that encode these human synapse proteins are really a major cause of diseases.
In a follow-up study using mice, Grants team found that by using various drugs to change the proteins in the synapse, the link to disease was also altered.
Grant said his team now planned to investigate whether the links between defects in synapse proteins and disease that they found in mice are also borne out in humans.
If they are, then it has the potential to radically refocus scientists approach to the study of brain diseases, he said.
Editing by David Stamp source
New medications likely hit hardest under tough pricing
The report comes as governments across Europe are seeking to slash drugs prices as they reign in spending to try to tackle runaway budget deficits.
Germanys government approved a draft bill on Tuesday which aims to eventually save some 2 billion euros 2.4 billion each year on the cost of patented drugs by breaking up drugmakers pricing power, and Greece has also moved to slash drug prices by more than a fifth on average.
Our study shows the consequences that pricing and reimbursement regulation can have on pharmaceutical innovation. It also shows that, incorrectly applied, regulation can reduce the value of pharmaceutical projects and curtail the resources available to carry them out, Hans Friederiszick of ESMT CA said in a statement with the report.
Rational investors will naturally look for the most profitable investment choices, which is why regulation has a direct impact on the number and characteristics of the medications developed.
This means the more innovative drugs were like to get the most attention he said, while important areas like the development of new antibiotics may get left behind.
Pharmaceutical companies are already cutting back on research and development RampD as they try to position themselves for a huge cliff of patents on big-selling drugs that are set to expire over the next five years.
The EMST report said that while European governments predominantly see pharmaceutical pricing models as a way of controlling public health costs, they may not realize or acknowledge the implications for product value, and therefore for the development of new drugs.
It said that internal reference pricing IRPa system used within Europe whereby prices in one country are taken as a reference point for others in negotiations — could result in an almost 12 percent drop in prices.
Beyond that, another pricing system called external price benchmarking EPBa model widely used across OECD countries — can lead to an almost 6 percent price drop.
Having some regions of the world under IRP and others under EPB magnifies the problem, since internal prices are then exported to external markets, leading to a 19.8 percent drop in portfolio value, the report said.
Reference pricing is common throughout the Europe Union and even beyond, with countries including Japan and Canada also taking account of European prices when deciding reimbursement. source
The finding opens way for revival controversial
The finding opens the way for a revival of the controversial and unpredictable procedure, which was halted in the mid-1990s after many patients suffered bouts of serious sudden and uncontrolled movements.
Researchers from Britain and Sweden have found that the sudden movements, called dyskinesias, which are a common side effect of treatment for Parkinsons disease, are a result of excess serotonin cells in the transplanted tissue that trick the brain into releasing unregulated levels of dopamine.
Dopamine is a brain chemical that helps control movement, while serotonin is brain chemical which acts as a messenger.
Marios Politis of Imperial College London, who led the study, said its findings should allow scientists to modify the tissue used in future brain transplant trials for Parkinsons patients using foetal cells and from other sources, such as bioengineered cells or stem cells.
Politis and colleagues, whose results were published in the journal Science Translational Medicine on Wednesday, studied two Parkinsons patients who had received transplants of brain cells from aborted foetuses 13 and 16 years ago.
Although these patients experienced remarkable improvement in their Parkinsons symptoms and their transplants were still functional, they were suffering from troublesome dyskinesias.
Using positron emission tomography PET scans and radiotracers that can visualise the function of brain chemicals in living humans, the researchers found that the transplants had replaced some of the dopamine-producing brain cells that decay during Parkinsons disease.
But they also found abnormally high levels of serotonin-producing neurons within the transplanted tissue.
The serotonin cells were very very highly excessive compared to what normal people have, Politis said in a telephone interview. This provoked a false action by taking the dopamine and releasing it in an unregulated manner, and this created these involuntary movements.
Parkinsons is a neurodegenerative disease that affects one to two percent of people over the age of 65. Sufferers have tremors, sluggish movement, muscle stiffness, and difficulty with balance. Although drugs can improve symptoms for a while, there are none that can slow or halt the disease.
These study results come just ahead of a scheduled new round of experimental work due to be carried out by European and American experts, who plan to begin new brain tissue transplant trials in Parkinsons patients from 2012.
Politis said the study also suggested that drugs known as serotonin receptor agonistssuch as the anxiety drug buspirone which is available as a generic and sold by Bristol-Myers Squibb under the brand Buspar — could be used to reduce dyskinesias in Parkinsons patients who are still suffering the side-effects from previous transplants.
But he said since buspirone was a short-acting drug, it would be good to see drug firms developing longer acting and slow-release versions which may be of more benefit.
Editing by Jon Hemming source
But findings dont necessarily mean nationwide prostate
Researchers from the University of Gothenburg conducted a trial involving 20,000 men who were divided equally into a group that was offered prostate screening and a group that was not.
The screening method used was so-called prostate-specific antigen PSA testing, which is widely used in the United States and other developed countries to detect early signs of tumors.
Over 14 years of follow-up, prostate cancer death rates were cut almost by half in the screening group compared with the non-screening group, as men were diagnosed and treated in time to stop the cancer from killing them.
Jonas Hugosson, who led the study, said the results showed that PSA screening of all men this age group can result in a relevant reduction in cancer mortality.
Screening for canceror for clues such as pre-cancerous cells — is strongly encouraged in wealthy nations as a way of improving public health. But there are growing doubts about whether the screenings benefits always outweigh the negatives, with the main concerns centering on the risk of overdiagnosis.
A large U.S. study published last year found that routine prostate screening has resulted in more than 1 million American men being diagnosed with tumors who might otherwise have suffered no ill effects from them. In that study, researchers said that around 20 men had to be diagnosed and treated for every one who benefited.
In the Swedish study, which was published in The Lancet medical journal Thursday, the researchers said the risk of overdiagnosis was less, but still 12 men needed to be diagnosed to save one life.
Prostate cancer is the second most common cancer in men after lung cancer, killing around 254,000 men a year around the world. U.S. doctors have routinely recommended PSA screening in men over 50 based on the assumption that early diagnosis and treatment is better than standing by and doing nothing.
But fears about overdiagnosis, which can lead to treatments such as surgery, radiation or hormone therapy that can cause serious side-effects such as impotence and incontinence, have so far dissuaded many European countries from nationwide screening.
A similar debate over breast cancer screening is also raging among doctors in Europe and United States, with critics of national mammography screening programs saying they needlessly harm thousands of womens lives by picking up tumors that would otherwise not have caused a problem.
In a commentary on the Swedish study, David Neal from Britains Cambridge University, said it showed that in certain circumstances, PSA testing and early diagnosis reduces death from prostate cancer.
But he added It does not imply that PSA screening programs should now be introduced internationally.
Editing by Noah Barkin source
The consortium of researchers from across europe
The signals we have identified provide important clues to the biological basis of type 2 diabetes. The challenge will be to turn these genetic findings into better ways of treating and preventing the condition, said Mark McCarthy of the center for human genetics at Oxford University, who led the study.
Type 2 diabetes is caused by the bodys inability to adequately use insulin, a hormone produced by the pancreas, to control glucose sugar produced from food. Sugar levels rise and can damage the eyes, kidneys, nerves, heart and major arteries.
The disease, often linked to poor diet and lack of exercise, is reaching epidemic levels as rates of obesity rise. An estimated 180 million people worldwide now have diabetes.
The identification of 12 new genes brings the total number of genetic regions known to be linked with type 2 diabetes to 38. The international team, whose work was published in the journal Nature on Sunday, said the genes they found tend to be involved in the working of pancreatic cells that produce insulin and in the control of insulins action in the body.
The researchers said each of the gene variants carried only a very small effect on diabetes risk, and even combined, their capacity to predict future risk of diabetes was modest.
But McCarthy said one particularly important theme of their findings was that several of the genes seem to be important in controlling the number of pancreatic beta-cells a person has.
Beta-cells are the cells in the pancreas that produce insulin, and McCarthy said this result would help settle a long-standing puzzle about the role of beta-cell numbers in type 2 diabetes. It also points to the importance of developing therapies that are able to preserve or restore depleted numbers of beta-cells, he said.
The team used gene sequencing technology to compare the DNA of over 8,000 people with type 2 diabetes with almost 40,000 people without the condition at almost 2.5 million places across the genome. They then checked the genetic variations they found in another group of more than 34,000 people with diabetes and around 60,000 more without it.
Jim Wilson of the University of Edinburgh, who also worked on the study, said another interesting finding was that the diabetes susceptibility genes also contain variants that increase the risk of other unrelated diseases, including skin and prostate cancer, heart disease and high cholesterol.
This implies that different regulation of these genes can lead to many different diseases, he said.
Editing by Ralph Boulton source
The findings could bring cost of immunization
A needle-free jet injector made by Bioject Medical Technologies was used to deliver the vaccine beneath the skin at ages 2, 4 and 6 months. Blood tests showed more than 95 percent of the infants mounted an effective immune response against polio.
Babies who got a lower dose had fewer antibodies against polio but the researchers said that should not be a problem.
Its still way over what would still be considered protective levels, Dr. Roland Sutter of the World Health Organization said in a telephone interview.
The injectable vaccine costs about 3 per dose. The oral polio vaccine is much cheaper, at about 15 cents, but it contains a weakened virus that can mutate and sometimes cause polio in patients or when it gets into sewage.
So public health experts now favor the injectable vaccine.
With this study, we know we can use this means to lower the price, Sutter said. If we can do one-fifth the dose, we can at least get it down to one dollar, so we are getting into the neighborhood of a price that may be affordable for developing countries in the future.
Polio continues to be common in Afghanistan, India, Pakistan and Nigeria, sometimes because of war, sometimes because of overcrowding, Dr. John Modlin of Dartmouth Medical School in New Hampshire wrote in a commentary.
The big problem in Nigeria, Africas most populous nation, was a one-year ban on the vaccine in some northern states, beginning in 2003, after some state governors and religious leaders in the predominately Muslim north claimed Western powers had contaminated the vaccines to spread sterility and AIDS among Muslims.
The study of 373 children was done in Oman, in part because there was little risk that natural polio would influence the results, Sutter said.
While just 4.3 percent of parents said they preferred needle vaccination for their child, 93 percent said they liked the needle-free method better, usually because the baby did not cry.
Polio, which spreads in areas with poor sanitation, attacks the nervous system and can cause irreversible paralysis within hours of infection. Children under 4 are the most vulnerable to the disease that until the 1950s crippled thousands of people every year in rich nations.
The World Health Organization has suggested a budget of 2.6 billion for its polio eradication efforts in 2010-2012, but says it faces a shortfall of about half of funds for that period.
Editing by Maggie Fox and Mohammad Zargham source
They found way interpret real time brain images show
The scans were more accurate than the volunteers were, Emily Falk and colleagues at the University of California Los Angeles reported in the Journal of Neuroscience.
We are trying to figure out whether there is hidden wisdom that the brain contains, Falk said in a telephone interview.
Many people decide to do things, but then dont do them, Matthew Lieberman, a professor of psychology who led the study, added in a statement.
But with functional magnetic resonance imaging or fMRI, Falk and colleagues were able to go beyond good intentions to predict actual behavior.
FMRI uses a magnetic field to measure blood flow in the brain. It can show which brain regions are more active compared to others, but requires careful interpretation.
Falks team recruited 20 young men and women for their experiment. While in the fMRI scanner they read and listened to messages about the safe use of sunscreen, mixed in with other messages so they would not guess what the experiment was about.
On day one of the experiment, before the scanning session, each participant indicated their sunscreen use over the prior week, their intentions to use sunscreen in the next week and their attitudes toward sunscreen, the researchers wrote.
After they saw the messages, the volunteers answered more questions about their intentions, and then got a goody bag that contained, among other things, sunscreen towelettes.
A week later we did a surprise follow up to find out whether they had used sunscreen, Falk said in a telephone interview.
About half the volunteers had correctly predicted whether they would use sunscreen. The research team analyzed and re-analyzed the MRI scans to see if they could find any brain activity that would do better.
Activity in one area of the brain, a particular part of the medial prefrontal cortex, provided the best information.
From this region of the brain, we can predict for about three-quarters of the people whether they will increase their use of sunscreen beyond what they say they will do, Lieberman said.
It is the one region of the prefrontal cortex that we know is disproportionately larger in humans than in other primates, he added. This region is associated with self-awareness, and seems to be critical for thinking about yourself and thinking about your preferences and values.
Now, Falk said, the team is looking for other regions of the brain that might add to the accuracy of the technique.
While the findings can be important for advertisers seeking to hone a motivational message, they can be equally important for public health experts trying to persuade people to make healthier choices, Falk said.
The team is now preparing a report on experiments to predict whether people would quit smoking after seeing motivational messages.
Editing by Sandra Maler source
The national institute for health and clinical excellence
If these changes were implemented, around 40,000 early deaths could be prevented each year in Britain alone and millions of people could spared the suffering of living with the effects of heart disease and stroke, NICE said.
Mike Kelly, NICEs director for public health, said the financial costs of heart disease added up to around 30 billion pounds 44.5 billion a year in Britain, taking in treatment costs, lost productivity, care and other social costs.
This is a big ticket item. And it is something that is eminently within our power to do something about, he told a briefing. This isnt some mystery virus which we dont understand … this is something where we know precisely what the causes are and we know precisely what we can do about it.
NICE does not produce legislation but it is asked by the government to draw up health policy guidelines.
NICE said policymakers should aim to reduce average adult salt intake in Britain to 3 grams a day by 2025 from around 8.5 grams now and introduce laws on cuts if necessary.
Politicians were also urged to negotiate at European Union and national level to ensure agricultural policy took account of public health issues.
Kelly said this meant encouraging farmers to concentrate on producing high quality food such as fruits and vegetables, low fat dairy products, lean meats and whole grains.
It also urged the government to tighten planning laws to stop fast-food outlets setting up too close to schools, and said legislation should be considered to force the food industry to cut saturated fat levels if they would not do so voluntarily.
A MODEL FOR EUROPE
The European Society of Cardiology praised NICE for setting out a range of evidence-based recommendations for effective action to help reduce levels of heart disease and said its guidelines also had important messages for the rest of Europe.
This is an extremely strong document that clearly underlines how much can be gained … by introducing legislative changes protecting the content of diets, said ESC spokesman Lars Ryden from the Swedens Karolinska Institute.
NICE, which produced its guidelines on preventing heart disease after two years of work, cited scientific research showing that in countries such as Japan, the United States, Denmark and Finlandwhere some laws are in place banning certain fats and forcing lower in salt levels — dramatic health benefits swiftly follow.
The benefits of doing this will be seen remarkably quickly, within 2-3 years, said Simon Capewell, a member of NICEs panel and a professor of epidemiology at Liverpool University.
He said that if salt levels in food were gradually reduced by between 5 and 10 percent a year, most consumers would not notice any difference in taste. This suggests the food industry, which has sometimes argued that consumers complain if it cuts food salt levels too far, has little to back such claims.
Cutting salt intake substantially reduces blood pressure, helping to lower the risk of heart attacks and strokes. High blood pressure is ranked as the worlds number one killer, accounting for 7.5 million deaths a year.
Editing by Noah Barkin source