The contamination of food with certain metals needs to be urgently addressed in light of growing evidence linking trace elements to negative human behaviour, according to a lead researcher in the field.
Metals and other elements can be present in food either naturally, as a result of human activities (such as farming, industry or car exhausts), from contamination during manufacture/processing and storage, or by direct addition.
It has long been known that excessive amounts of any metal could be potentially dangerous, but there is now also strong evidence that some trace elements can contribute to aggressive or anti-social behaviour, said Neil Ward, professor of chemistry at the UK’s University of Surrey.
“Many of the mechanisms are as yet unknown and more case studies are required, but it is clear that elimination produces positive improvements,” said Professor Ward at a Food and Behaviour conference held in Brighton, UK, last week.
Some metals and other elements (such as copper, manganese and zinc) can act as nutrients and are essential for health, while others (such as arsenic, cadmium, lead and mercury) have no known beneficial health effects.
Nutrient depletion
Those elements that have no nutritional benefits could not only be toxic to the system, but they could impede absorption of essential nutrients in the body, which is particularly problematic in children, explained Ward.
For example, lead has been linked to anti-social behaviour, partly because it contributes to nutrient depletion.
“Lead acts as an anti-nutrient, hindering the utilisation of magnesium, zinc and vitamin B1. High lead levels have been linked to a reduction in IQ, negative classroom behaviour ratings by teachers, juvenile delinquency and increased violent behaviour,” he said, citing studies by Needleman et al., which appeared in the New England journal of Medicine, JAMA and Neurotoxic Teratology in 1990, 1996 and 2002 respectively.
Ward, who has studied the relation of trace elements to human disorders for over 25 years, said aluminium has also been linked to anti-social behaviour as it competes for the binding sites of biochemical receptors of other metal ions, such as iron and zinc. For the same reason, suboptimal dietary intake of zinc or iron could explain the uptake of aluminium, he said. References included studies by Moon and Marlow, Wenk and Stemmer, and Birchell and Chappell, which appeared in Biol Trace Elem Res (1986), Brain Res (1983) and the Lancet (1988) respectively.
Missing zinc
Ward also highlighted findings from one of his own studies, conducted in 1995, which examined the heavy metal status of incarcerated young offenders compared to control individuals.
The double-blind case control study used scalp hair and blood serum tests to determine the levels of zinc, lead, cadmium and aluminium in the two groups. Levels of lead, cadmium and aluminium were found to be significantly higher in the young offenders group, whereas zinc levels were lower.
Zinc deficiency is also thought to occur as a result of ingestion of certain food colours, and has been linked to hyperactive behaviour or ADHD in children, said Ward.
“The mode of action is not known, but azo dyes have been linked to behavioural changes in children. These colours could be acting as chelating agents, which bind available blood zinc and create a deficiency. The elimination of azo dye beverages and sweets can have a dramatic effect on some HA or ADHD children,” he said.
Food and Behaviour
Professor Ward was addressing an audience of medical professionals, teachers, healthcare and social workers, and food industry executives at a conference organised by the charity Food and Behaviour Research (FAB).
FAB aims to provide research-based information on how nutrition and diet can affect behaviour, learning and mood. For more information, click here .
28 March 2009
Is Drywall the Next Chinese Import Scandal?
Soon after Danie Beck and her husband bought their two-story town house west of Miami in the summer of 2006, she thought an animal had died somewhere behind the walls. The strong sulfurous odor lingered, she says, and she began having dizzy spells that would keep her in bed for days. She began suffering from insomnia and sore, swollen joints. The house, too, appeared to be ailing: lights began blinking on and off, and Beck noticed discoloration of her wood furniture. The air conditioner, an indispensable appliance in South Florida, kept conking out. "It was an absolute nightmare," the 67-year-old dance teacher says. "I felt as if something in this house was hammering me into the ground every day."
It wasn't until her repairman got fed up with fixing inexplicably corroded air-conditioner coils that Beck finally discovered what she and her home builder suspect is the source of the poltergeist: the Chinese drywall inside the house. Beck is among hundreds of homeowners in Florida alleging that toxic levels of chemical pollutants like sulfur are issuing from contaminated drywall made in some Chinese factories. At least four class actions have been filed in Florida; others have been filed in California, Louisiana and Alabama. (See pictures of China's electronic-waste village.)
The U.S. Consumer Product Safety Commission is investigating the complaints. If the drywall proves to be the culprit, plaintiffs' attorneys say tens of thousands of potentially affected homes could see a further drop in prices already hammered by the credit crisis. "A lot of these people are just getting hit over the head a second time," says David Durkee, a Miami attorney who has filed one of the suits. "This could have a further impact on the mortgage crisis by giving overwhelmed homeowners another incentive to just walk away from their houses."
During the heady but reckless days of the recent U.S. housing-construction boom, builders were desperate for materials, and drywall was especially in demand. Before 2005, drywall imports to the U.S. from China were negligible; since 2006, more than 550 million lb. of it has been shipped here, mostly to Florida. The imports amount to a fraction of the 15 million tons of drywall produced domestically each year, but it was used to build more than 60,000 homes in at least a dozen states — including some post-Katrina reconstruction in Louisiana.
More than half the homes built with Chinese drywall are in Florida. Some of the suits there target construction companies; others include German drywall manufacturer Knauf and its Chinese subsidiaries — which are in turn being sued by at least one Florida home builder, Lennar Corp. Miami-based Lennar, which is also suing the U.S. suppliers from which it bought the Chinese drywall, has confronted the problem and initiated a program to do inspections and remove the offending wallboard in many homes, including Beck's. (The process usually involves moving a family out of the house for at least six months to replace its interior.) Another lawsuit defendant, Engle Homes, based in Hollywood, Fla., has also admitted that the drywall problem exists in at least a small number of its homes. In a statement about houses near Fort Myers, Fla., that are part of Durkee's suit, the company says, "Our initial findings tell us that that this seems to be an isolated incident that has affected a small number of Engle Homes in the Fort Myers, Fla., area and we are currently developing a plan to assist our affected homeowners."
Drywall is made from gypsum, a soft mineral, that is pressed between thick paperboard. Plaintiffs' attorneys say the allegedly toxic drywall material probably originated in at least one gypsum mine in China and possibly others. (A few years ago, Knauf and other drywall producers received complaints about a mine in Tianjin, China; Knauf says it stopped using the mine toward the end of 2006.) But Knauf denies that its product is toxic and argues it is not the only supplier of Chinese-made drywall to the U.S. Contacted by TIME, the company referred to a statement by its subsidiary, Knauf Plasterboard Tianjin Ltd.: "Any low levels of sulfur compounds present in the air in homes are not a health risk ... The substances identified in testing are in no greater amounts than [in] the air found outside homes or in soil, marshes or the oceans."
The Florida Department of Health has not yet concluded its own tests of the drywall in question. But Beck and other homeowners insist the common symptoms suffered by the Chinese-drywalled houses and their occupants can't be mere coincidence. The problem came to light last year as those homeowners began commiserating on the Internet about rotten-egg smells in their houses and rashes of nosebleeds and other ailments. At the same time, exasperated air-conditioner repairmen began complaining to builders about copper-coil corrosion in newly built houses. The air-conditioning companies concluded it was caused by high levels of airborne sulfur and moldy toxins. Wires in outlets, appliances and lamps were going bad too, as was wood. That in turn raised red flags for consumer-protection groups, already alarmed in recent years by the flood of defective Chinese-made products like toothpaste and toys.
Depending on how many homes ultimately prove to be contaminated, the repair costs — Beck says Lennar promised to tear her house down "to the studs" — could run into the tens of millions for builders. And that does not include the unspecified damages sought in the lawsuits. One problem plaintiffs face, however, is that many of the builders being sued have gone bankrupt in the recent housing bust. And even if homes are repaired, they may still carry the taint of having been drywall victims. Beck paid $344,000 for her town house; it is now worth $245,000 — less than the amount owed on her mortgage. And she worries that she may not be able to sell it at some point in the future even after Lennar fixes the drywall problem. "I'll admit there are moments when I'm tempted to ask Lennar to just buy the house back," says Beck, whose husband died last year of cancer. (His illness was not related to the drywall.)
Beck's fortunes have taken a pummeling in recent years. She and her husband bought the town house after an arson fire destroyed the Miami home they had lived in for 39 years. And she has become accustomed to seeing its value jeopardized by the threat of hurricanes and by Wall Street malfeasance. But she wasn't expecting any trouble from China.
It wasn't until her repairman got fed up with fixing inexplicably corroded air-conditioner coils that Beck finally discovered what she and her home builder suspect is the source of the poltergeist: the Chinese drywall inside the house. Beck is among hundreds of homeowners in Florida alleging that toxic levels of chemical pollutants like sulfur are issuing from contaminated drywall made in some Chinese factories. At least four class actions have been filed in Florida; others have been filed in California, Louisiana and Alabama. (See pictures of China's electronic-waste village.)
The U.S. Consumer Product Safety Commission is investigating the complaints. If the drywall proves to be the culprit, plaintiffs' attorneys say tens of thousands of potentially affected homes could see a further drop in prices already hammered by the credit crisis. "A lot of these people are just getting hit over the head a second time," says David Durkee, a Miami attorney who has filed one of the suits. "This could have a further impact on the mortgage crisis by giving overwhelmed homeowners another incentive to just walk away from their houses."
During the heady but reckless days of the recent U.S. housing-construction boom, builders were desperate for materials, and drywall was especially in demand. Before 2005, drywall imports to the U.S. from China were negligible; since 2006, more than 550 million lb. of it has been shipped here, mostly to Florida. The imports amount to a fraction of the 15 million tons of drywall produced domestically each year, but it was used to build more than 60,000 homes in at least a dozen states — including some post-Katrina reconstruction in Louisiana.
More than half the homes built with Chinese drywall are in Florida. Some of the suits there target construction companies; others include German drywall manufacturer Knauf and its Chinese subsidiaries — which are in turn being sued by at least one Florida home builder, Lennar Corp. Miami-based Lennar, which is also suing the U.S. suppliers from which it bought the Chinese drywall, has confronted the problem and initiated a program to do inspections and remove the offending wallboard in many homes, including Beck's. (The process usually involves moving a family out of the house for at least six months to replace its interior.) Another lawsuit defendant, Engle Homes, based in Hollywood, Fla., has also admitted that the drywall problem exists in at least a small number of its homes. In a statement about houses near Fort Myers, Fla., that are part of Durkee's suit, the company says, "Our initial findings tell us that that this seems to be an isolated incident that has affected a small number of Engle Homes in the Fort Myers, Fla., area and we are currently developing a plan to assist our affected homeowners."
Drywall is made from gypsum, a soft mineral, that is pressed between thick paperboard. Plaintiffs' attorneys say the allegedly toxic drywall material probably originated in at least one gypsum mine in China and possibly others. (A few years ago, Knauf and other drywall producers received complaints about a mine in Tianjin, China; Knauf says it stopped using the mine toward the end of 2006.) But Knauf denies that its product is toxic and argues it is not the only supplier of Chinese-made drywall to the U.S. Contacted by TIME, the company referred to a statement by its subsidiary, Knauf Plasterboard Tianjin Ltd.: "Any low levels of sulfur compounds present in the air in homes are not a health risk ... The substances identified in testing are in no greater amounts than [in] the air found outside homes or in soil, marshes or the oceans."
The Florida Department of Health has not yet concluded its own tests of the drywall in question. But Beck and other homeowners insist the common symptoms suffered by the Chinese-drywalled houses and their occupants can't be mere coincidence. The problem came to light last year as those homeowners began commiserating on the Internet about rotten-egg smells in their houses and rashes of nosebleeds and other ailments. At the same time, exasperated air-conditioner repairmen began complaining to builders about copper-coil corrosion in newly built houses. The air-conditioning companies concluded it was caused by high levels of airborne sulfur and moldy toxins. Wires in outlets, appliances and lamps were going bad too, as was wood. That in turn raised red flags for consumer-protection groups, already alarmed in recent years by the flood of defective Chinese-made products like toothpaste and toys.
Depending on how many homes ultimately prove to be contaminated, the repair costs — Beck says Lennar promised to tear her house down "to the studs" — could run into the tens of millions for builders. And that does not include the unspecified damages sought in the lawsuits. One problem plaintiffs face, however, is that many of the builders being sued have gone bankrupt in the recent housing bust. And even if homes are repaired, they may still carry the taint of having been drywall victims. Beck paid $344,000 for her town house; it is now worth $245,000 — less than the amount owed on her mortgage. And she worries that she may not be able to sell it at some point in the future even after Lennar fixes the drywall problem. "I'll admit there are moments when I'm tempted to ask Lennar to just buy the house back," says Beck, whose husband died last year of cancer. (His illness was not related to the drywall.)
Beck's fortunes have taken a pummeling in recent years. She and her husband bought the town house after an arson fire destroyed the Miami home they had lived in for 39 years. And she has become accustomed to seeing its value jeopardized by the threat of hurricanes and by Wall Street malfeasance. But she wasn't expecting any trouble from China.
Indonesian Government Stops Trusting Drug Companies and Reconsiders Vaccinations for Children
Indonesia's controversial health minister says she wants to end vaccinating children against meningitis, mumps and some other diseases because she fears foreign drug companies are using the country as a testing ground.
Health Minister Siti Fadillah Supari — who first drew widespread attention by boycotting the World Health Organization's 50-year-old virus sharing system in 2007 — said Tuesday she wanted "scientific proof" that shots for illnesses like pneumonia, chicken pox, the flu, rubella and typhoid were "beneficial".
"If not, they have to be stopped," she said, declining to say exactly what that would mean. "We don't want our country to be a testing place for drugs, as has been the case in Africa."
Supari said she still would advocate immunizations against measles, polio, tetanus, hepatitis B and tuberculosis.
Her statement comes at a time when Indonesia is struggling to contain outbreaks of preventable childhood illnesses.
Chronic funding problems and chaotic decentralization efforts since the 1998 ouster of longtime dictator Suharto have forced many local clinics in the poorest parts of the nation to scale back operations, reducing the time and money spent on education and routine immunizations.
The number of cases of measles, tuberculosis and other diseases has skyrocketed. Polio briefly re-emerged after a decade-long absence in 2005.
The U.N. children's agency said it would wait until the country officially changes its immunization policy before commenting.
"We are continuing to support the government as technical partners in their implementation of the evidence-based programs," said Anne Vincent at UNICEF.
Indonesia's health minister is no stranger to controversy — or conspiracy theories.
When she stopped sharing bird flu viruses with the international community two years ago she argued, among other things, that the U.S. government could use the samples to create a biological weapon. In November, she issued a decree banning foreign drug makers from selling products in Indonesia unless they build local production facilities.
Health Minister Siti Fadillah Supari — who first drew widespread attention by boycotting the World Health Organization's 50-year-old virus sharing system in 2007 — said Tuesday she wanted "scientific proof" that shots for illnesses like pneumonia, chicken pox, the flu, rubella and typhoid were "beneficial".
"If not, they have to be stopped," she said, declining to say exactly what that would mean. "We don't want our country to be a testing place for drugs, as has been the case in Africa."
Supari said she still would advocate immunizations against measles, polio, tetanus, hepatitis B and tuberculosis.
Her statement comes at a time when Indonesia is struggling to contain outbreaks of preventable childhood illnesses.
Chronic funding problems and chaotic decentralization efforts since the 1998 ouster of longtime dictator Suharto have forced many local clinics in the poorest parts of the nation to scale back operations, reducing the time and money spent on education and routine immunizations.
The number of cases of measles, tuberculosis and other diseases has skyrocketed. Polio briefly re-emerged after a decade-long absence in 2005.
The U.N. children's agency said it would wait until the country officially changes its immunization policy before commenting.
"We are continuing to support the government as technical partners in their implementation of the evidence-based programs," said Anne Vincent at UNICEF.
Indonesia's health minister is no stranger to controversy — or conspiracy theories.
When she stopped sharing bird flu viruses with the international community two years ago she argued, among other things, that the U.S. government could use the samples to create a biological weapon. In November, she issued a decree banning foreign drug makers from selling products in Indonesia unless they build local production facilities.
U.S. Psychiatrists Will End Drug Company Seminars
CHICAGO (Reuters) - The American Psychiatric Association said on Wednesday it will end medical education seminars and meals sponsored by drug companies at its annual meetings to reduce chances for financial conflicts of interest.
The group, which represents 38,000 doctors, is among the first to say no to the drug-company sponsored seminars at its meetings, which many critics say blur the line between education and advertising.
Psychiatrists have been at the front of a controversy over conflicts of interest following accusations last year by Republican U.S. Senator Charles Grassley that prominent Harvard University psychiatrist Dr. Joseph Biederman and others failed to fully disclose payments from drug companies.
Psychiatric drugs represent billions of dollars in global sales. Last July, Grassley asked the APA to provide information about its financial ties with the drug industry.
Dr. Nada Stotland, president of the APA, said the group began working on the issue a year ago, long before it became the subject of a probe.
"We're not blaming the pharmaceutical companies for anything and we're not severing all relations with them," Stotland said in a telephone interview.
She said drug companies paid the group in order to sponsor glitzy education symposiums put on by prominent doctors during its annual meetings, typically over breakfast or dinner.
And while Stotland said the group took care to avoid biased reporting at these presentations, she said the notion of mixing something that is basically a gift with education "wasn't the healthiest mixture."
The move includes the elimination of industry-supplied meals that were provided during the symposiums.
"There is a perception that accepting meals provided by pharmaceutical companies may have a subtle influence on doctors' prescribing habits," Dr. James Scully, APA's medical director and chief executive officer, said in a statement.
"While industry-funded meals used to be normal operating procedure at medical meetings, a sea change is currently underway in how we manage industry relationships," he said.
"What was acceptable five years ago isn't necessarily acceptable today."
Earlier this year, many drug makers said they would stop giving out small gifts such as pens and flash drives as part of new voluntary guidelines from the Pharmaceutical Research and Manufacturers of America, an industry group in Washington.
The group's 2002 code already bans more costly gifts like trips to resorts, and calls for companies that pay for medical education at conferences to leave the content to outside experts.
The group, which represents 38,000 doctors, is among the first to say no to the drug-company sponsored seminars at its meetings, which many critics say blur the line between education and advertising.
Psychiatrists have been at the front of a controversy over conflicts of interest following accusations last year by Republican U.S. Senator Charles Grassley that prominent Harvard University psychiatrist Dr. Joseph Biederman and others failed to fully disclose payments from drug companies.
Psychiatric drugs represent billions of dollars in global sales. Last July, Grassley asked the APA to provide information about its financial ties with the drug industry.
Dr. Nada Stotland, president of the APA, said the group began working on the issue a year ago, long before it became the subject of a probe.
"We're not blaming the pharmaceutical companies for anything and we're not severing all relations with them," Stotland said in a telephone interview.
She said drug companies paid the group in order to sponsor glitzy education symposiums put on by prominent doctors during its annual meetings, typically over breakfast or dinner.
And while Stotland said the group took care to avoid biased reporting at these presentations, she said the notion of mixing something that is basically a gift with education "wasn't the healthiest mixture."
The move includes the elimination of industry-supplied meals that were provided during the symposiums.
"There is a perception that accepting meals provided by pharmaceutical companies may have a subtle influence on doctors' prescribing habits," Dr. James Scully, APA's medical director and chief executive officer, said in a statement.
"While industry-funded meals used to be normal operating procedure at medical meetings, a sea change is currently underway in how we manage industry relationships," he said.
"What was acceptable five years ago isn't necessarily acceptable today."
Earlier this year, many drug makers said they would stop giving out small gifts such as pens and flash drives as part of new voluntary guidelines from the Pharmaceutical Research and Manufacturers of America, an industry group in Washington.
The group's 2002 code already bans more costly gifts like trips to resorts, and calls for companies that pay for medical education at conferences to leave the content to outside experts.
24 March 2009
A Silenced Drug Study Creates An Uproar
By Shankar Vedantam
Washington Post Staff Writer
Wednesday, March 18, 2009; Page A01
The study would come to be called "cursed," but it started out just as Study 15.
It was a long-term trial of the antipsychotic drug Seroquel. The common wisdom in psychiatric circles was that newer drugs were far better than older drugs, but Study 15's results suggested otherwise.
As a result, newly unearthed documents show, Study 15 suffered the same fate as many industry-sponsored trials that yield data drugmakers don't like: It got buried. It took eight years before a taxpayer-funded study rediscovered what Study 15 had found -- and raised serious concerns about an entire new class of expensive drugs.
Study 15 was silenced in 1997, the same year Seroquel was approved by the Food and Drug Administration to treat schizophrenia. The drug went on to be prescribed to hundreds of thousands of patients around the world and has earned billions for London-based AstraZeneca International -- including nearly $12 billion in the past three years.
The results of Study 15 were never published or shared with doctors, even as less rigorous studies that came up with positive results for Seroquel were published and used in marketing campaigns aimed at physicians and in television ads aimed at consumers. The results of Study 15 were provided only to the Food and Drug Administration -- and the agency has strenuously maintained that it does not have the authority to place such studies in the public domain.
AstraZeneca spokesman Tony Jewell defended the Seroquel research and said the company had disclosed the drug's risks. Since 1997, the drug's labeling has noted that weight gain and diabetes were seen in study patients, although the company says the data are not definitive. The label states that the metabolic disorders may be related to patients' underlying diseases.
The FDA, Jewell added, had access to Study 15 when it declared Seroquel safe and effective. The trial, which compared patients taking Seroquel and an older drug called Haldol, "did not identify any safety concerns," AstraZeneca said in an e-mail. Jewell added, "A large proportion of patients dropped out in both groups, which the company felt made the results difficult to interpret."
The saga of Study 15 has become a case study in how drug companies can control the publicly available research about their products, along with other practices that recently have prompted hand-wringing at universities and scientific journals, remonstrations by medical groups about conflicts of interest, and threats of exposure by trial lawyers and congressional watchdogs.
Even if most doctors are ethical, corporate grants, gifts and underwriting have compromised psychiatry, said an editorial this month in the American Journal of Psychiatry, the flagship journal of the American Psychiatric Association.
"The public and private resources available for the care of our patients depend upon the public perception of the integrity of our profession as a whole," wrote Robert Freedman, the editor in chief, and others. "The subsidy that each of us has been receiving is part of what has fueled the excesses that are currently under investigation."
Details of Study 15 have emerged through lawsuits now playing out in courtrooms nationwide alleging that Seroquel caused weight gain, hyperglycemia and diabetes in thousands of patients. The Houston-based law firm Blizzard, McCarthy & Nabers, one of several that have filed about 9,210 lawsuits over Seroquel, publicized the documents, which show that the patients taking Seroquel in Study 15 gained an average of 11 pounds in a year -- alarming company scientists and marketing executives. A Washington Post analysis found that about four out of five patients quit taking the drug in less than a year, raising pointed doubts about its effectiveness.
An FDA report in 1997, moreover, said Study 15 did offer useful safety data. Mentioning few details, the FDA said the study showed that patients taking higher doses of the drug gained more weight.
In approving Seroquel, the agency said 23 percent of patients taking the drug in all studies available up to that point experienced significant weight increases, compared with 6 percent of control-group patients taking sugar pills. In 2006, FDA warned AstraZeneca against minimizing metabolic problems in its sales pitches.
In the years since, taxpayer-funded research has found that newer antipsychotic drugs such as Seroquel, which are 10 times as expensive, offer little advantage over older ones. The older drugs cause involuntary muscle movements known as tardive dyskinesia, and the newer ones have been linked to metabolic problems.
Far from dismissing Study 15, internal documents show that company officials were worried because 45 percent of the Seroquel patients had experienced what AstraZeneca physician Lisa Arvanitis termed "clinically significant" weight gain.
In an e-mail dated Aug. 13, 1997, Arvanitis reported that across all patient groups and treatment regimens, regardless of how numbers were crunched, patients taking Seroquel gained weight: "I'm not sure there is yet any type of competitive opportunity no matter how weak."
In a separate note, company strategist Richard Lawrence praised AstraZeneca's efforts to put a "positive spin" on "this cursed study" and said of Arvanitis: "Lisa has done a great 'smoke and mirrors' job!"
Two years after those exchanges, in 1999, the documents show that the company presented different data at an American Psychiatric Association conference and at a European meeting. The conclusion: Seroquel helped psychotic patients lose weight.
The claim was based on a company-sponsored study by a Chicago psychiatrist, who reviewed the records of 65 patients who switched their medication to Seroquel. It found that patients lost an average of nine pounds over 10 months.
Within the company, meanwhile, officials explicitly discussed misleading physicians. The chief of a team charged with getting articles published, John Tumas, defended "cherry-picking" data.
"That does not mean we should continue to advocate" selective use of data, he wrote on Dec. 6, 1999, referring to a trial, called COSTAR, that also produced unfavorable results. But he added, "Thus far, we have buried Trials 15, 31, 56 and are now considering COSTAR."
Although the company pushed the favorable study to physicians, the documents show that AstraZeneca held the psychiatrist in light regard and had concerns that he had modified study protocols and failed to get informed consent from patients. Company officials wrote that they did not trust the doctor with anything more complicated than chart reviews -- the basis of the 1999 study showing Seroquel helped patients lose weight.
For practicing psychiatrists, Study 15 could have said a lot not just about safety but also effectiveness. Like all antipsychotics, Seroquel does not cure the diseases it has been approved to treat -- schizophrenia and bipolar disorder -- but controls symptoms such as agitation, hallucinations and delusions. When government scientists later decided to test the effectiveness of the class of drugs to which Seroquel belongs, they focused on a simple measure -- how long patients stayed on the drugs. Discontinuation rates, they decided, were the best measure of effectiveness.
Study 15 had three groups of about 90 patients each taking different Seroquel doses, according to an FDA document. Approximately 31 patients were on Haldol. The study showed that Seroquel failed to outperform Haldol in preventing psychotic relapses.
In disputing Study 15's weight-gain data, company officials said they were not reliable because only about 50 patients completed the year-long trial. But even without precise numbers, this suggests a high discontinuation rate among patients taking Seroquel. Even if every single patient taking Haldol dropped out, it appears that at a minimum about 220 patients -- or about 82 percent of patients on Seroquel -- dropped out.
Eight years after Study 15 was buried, an expensive taxpayer-funded study pitted Seroquel and other new drugs against another older antipsychotic drug. The study found that most patients getting the new and supposedly safer drugs stopped taking them because of intolerable side effects. The study also found that the new drugs had few advantages. As with older drugs, the new medications had very high discontinuation rates. The results caused consternation among doctors, who had been kept in the dark about trials such as Study 15.
The federal study also reported the number of Seroquel patients who discontinued the drug within 18 months: 82 percent.
Jeffrey Lieberman, a Columbia University psychiatrist who led the federal study, said doctors missed clues in evaluating antipsychotics such as Seroquel. If a doctor had known about Study 15, he added, "it would raise your eyebrows."
Washington Post Staff Writer
Wednesday, March 18, 2009; Page A01
The study would come to be called "cursed," but it started out just as Study 15.
It was a long-term trial of the antipsychotic drug Seroquel. The common wisdom in psychiatric circles was that newer drugs were far better than older drugs, but Study 15's results suggested otherwise.
As a result, newly unearthed documents show, Study 15 suffered the same fate as many industry-sponsored trials that yield data drugmakers don't like: It got buried. It took eight years before a taxpayer-funded study rediscovered what Study 15 had found -- and raised serious concerns about an entire new class of expensive drugs.
Study 15 was silenced in 1997, the same year Seroquel was approved by the Food and Drug Administration to treat schizophrenia. The drug went on to be prescribed to hundreds of thousands of patients around the world and has earned billions for London-based AstraZeneca International -- including nearly $12 billion in the past three years.
The results of Study 15 were never published or shared with doctors, even as less rigorous studies that came up with positive results for Seroquel were published and used in marketing campaigns aimed at physicians and in television ads aimed at consumers. The results of Study 15 were provided only to the Food and Drug Administration -- and the agency has strenuously maintained that it does not have the authority to place such studies in the public domain.
AstraZeneca spokesman Tony Jewell defended the Seroquel research and said the company had disclosed the drug's risks. Since 1997, the drug's labeling has noted that weight gain and diabetes were seen in study patients, although the company says the data are not definitive. The label states that the metabolic disorders may be related to patients' underlying diseases.
The FDA, Jewell added, had access to Study 15 when it declared Seroquel safe and effective. The trial, which compared patients taking Seroquel and an older drug called Haldol, "did not identify any safety concerns," AstraZeneca said in an e-mail. Jewell added, "A large proportion of patients dropped out in both groups, which the company felt made the results difficult to interpret."
The saga of Study 15 has become a case study in how drug companies can control the publicly available research about their products, along with other practices that recently have prompted hand-wringing at universities and scientific journals, remonstrations by medical groups about conflicts of interest, and threats of exposure by trial lawyers and congressional watchdogs.
Even if most doctors are ethical, corporate grants, gifts and underwriting have compromised psychiatry, said an editorial this month in the American Journal of Psychiatry, the flagship journal of the American Psychiatric Association.
"The public and private resources available for the care of our patients depend upon the public perception of the integrity of our profession as a whole," wrote Robert Freedman, the editor in chief, and others. "The subsidy that each of us has been receiving is part of what has fueled the excesses that are currently under investigation."
Details of Study 15 have emerged through lawsuits now playing out in courtrooms nationwide alleging that Seroquel caused weight gain, hyperglycemia and diabetes in thousands of patients. The Houston-based law firm Blizzard, McCarthy & Nabers, one of several that have filed about 9,210 lawsuits over Seroquel, publicized the documents, which show that the patients taking Seroquel in Study 15 gained an average of 11 pounds in a year -- alarming company scientists and marketing executives. A Washington Post analysis found that about four out of five patients quit taking the drug in less than a year, raising pointed doubts about its effectiveness.
An FDA report in 1997, moreover, said Study 15 did offer useful safety data. Mentioning few details, the FDA said the study showed that patients taking higher doses of the drug gained more weight.
In approving Seroquel, the agency said 23 percent of patients taking the drug in all studies available up to that point experienced significant weight increases, compared with 6 percent of control-group patients taking sugar pills. In 2006, FDA warned AstraZeneca against minimizing metabolic problems in its sales pitches.
In the years since, taxpayer-funded research has found that newer antipsychotic drugs such as Seroquel, which are 10 times as expensive, offer little advantage over older ones. The older drugs cause involuntary muscle movements known as tardive dyskinesia, and the newer ones have been linked to metabolic problems.
Far from dismissing Study 15, internal documents show that company officials were worried because 45 percent of the Seroquel patients had experienced what AstraZeneca physician Lisa Arvanitis termed "clinically significant" weight gain.
In an e-mail dated Aug. 13, 1997, Arvanitis reported that across all patient groups and treatment regimens, regardless of how numbers were crunched, patients taking Seroquel gained weight: "I'm not sure there is yet any type of competitive opportunity no matter how weak."
In a separate note, company strategist Richard Lawrence praised AstraZeneca's efforts to put a "positive spin" on "this cursed study" and said of Arvanitis: "Lisa has done a great 'smoke and mirrors' job!"
Two years after those exchanges, in 1999, the documents show that the company presented different data at an American Psychiatric Association conference and at a European meeting. The conclusion: Seroquel helped psychotic patients lose weight.
The claim was based on a company-sponsored study by a Chicago psychiatrist, who reviewed the records of 65 patients who switched their medication to Seroquel. It found that patients lost an average of nine pounds over 10 months.
Within the company, meanwhile, officials explicitly discussed misleading physicians. The chief of a team charged with getting articles published, John Tumas, defended "cherry-picking" data.
"That does not mean we should continue to advocate" selective use of data, he wrote on Dec. 6, 1999, referring to a trial, called COSTAR, that also produced unfavorable results. But he added, "Thus far, we have buried Trials 15, 31, 56 and are now considering COSTAR."
Although the company pushed the favorable study to physicians, the documents show that AstraZeneca held the psychiatrist in light regard and had concerns that he had modified study protocols and failed to get informed consent from patients. Company officials wrote that they did not trust the doctor with anything more complicated than chart reviews -- the basis of the 1999 study showing Seroquel helped patients lose weight.
For practicing psychiatrists, Study 15 could have said a lot not just about safety but also effectiveness. Like all antipsychotics, Seroquel does not cure the diseases it has been approved to treat -- schizophrenia and bipolar disorder -- but controls symptoms such as agitation, hallucinations and delusions. When government scientists later decided to test the effectiveness of the class of drugs to which Seroquel belongs, they focused on a simple measure -- how long patients stayed on the drugs. Discontinuation rates, they decided, were the best measure of effectiveness.
Study 15 had three groups of about 90 patients each taking different Seroquel doses, according to an FDA document. Approximately 31 patients were on Haldol. The study showed that Seroquel failed to outperform Haldol in preventing psychotic relapses.
In disputing Study 15's weight-gain data, company officials said they were not reliable because only about 50 patients completed the year-long trial. But even without precise numbers, this suggests a high discontinuation rate among patients taking Seroquel. Even if every single patient taking Haldol dropped out, it appears that at a minimum about 220 patients -- or about 82 percent of patients on Seroquel -- dropped out.
Eight years after Study 15 was buried, an expensive taxpayer-funded study pitted Seroquel and other new drugs against another older antipsychotic drug. The study found that most patients getting the new and supposedly safer drugs stopped taking them because of intolerable side effects. The study also found that the new drugs had few advantages. As with older drugs, the new medications had very high discontinuation rates. The results caused consternation among doctors, who had been kept in the dark about trials such as Study 15.
The federal study also reported the number of Seroquel patients who discontinued the drug within 18 months: 82 percent.
Jeffrey Lieberman, a Columbia University psychiatrist who led the federal study, said doctors missed clues in evaluating antipsychotics such as Seroquel. If a doctor had known about Study 15, he added, "it would raise your eyebrows."
Can Cherries Relieve The Pain Of Osteoarthritis?
ScienceDaily (Mar. 21, 2009) — For the estimated 27 million Americans who suffer from osteoarthritis, pain relief may come with a cherry on top. According to researchers with the Baylor Research Institute, tart cherries, in pill form, may be a promising pain-reliever for this common and debilitating form of arthritis.
More than half of the patients enrolled in a 2007 pilot study at the Baylor Research Institute experienced a significant improvement in pain and function after taking the cherry pills for eight weeks. Osteoarthritis, the most common type of arthritis, is considered degenerative and typically affects the hands, feet, spine, and large weight-bearing joints, such as the hips and knees. Patients with osteoarthritis of the knees were enrolled in this pilot study to assess potential efficacy of the tart cherry pills.
“The current treatment of osteoarthritis is largely focused on controlling pain through use of over-the-counter acetaminophen or prescription pain medications as well as non-steroidal anti-inflammatory drugs,” explains John J. Cush, M.D., rheumatologist and principal investigator of the study. “These conventional medications are widely used, but have not been shown to alter the natural history of the disease. In some cases, overuse may contribute to significant gastrointestinal, cardiovascular, hematologic, renal and liver toxicity.”
Made from Montmorency tart cherries, this preparation is made up of ground whole cherries and given as a soft gelatin capsule (marketed under the brand name CherryFlex®).
“This specific type of tart cherry is one of the best studied natural products and anecdotally has been claimed to have a salutary effect on osteoarthritis and other types of arthritis as well,” adds Dr. Cush.
Baylor Research Institute together with the Arthritis Care & Research Institute is currently enrolling patients in a second study, which will test cherry pills versus placebo in an eight week double blind study.
More than half of the patients enrolled in a 2007 pilot study at the Baylor Research Institute experienced a significant improvement in pain and function after taking the cherry pills for eight weeks. Osteoarthritis, the most common type of arthritis, is considered degenerative and typically affects the hands, feet, spine, and large weight-bearing joints, such as the hips and knees. Patients with osteoarthritis of the knees were enrolled in this pilot study to assess potential efficacy of the tart cherry pills.
“The current treatment of osteoarthritis is largely focused on controlling pain through use of over-the-counter acetaminophen or prescription pain medications as well as non-steroidal anti-inflammatory drugs,” explains John J. Cush, M.D., rheumatologist and principal investigator of the study. “These conventional medications are widely used, but have not been shown to alter the natural history of the disease. In some cases, overuse may contribute to significant gastrointestinal, cardiovascular, hematologic, renal and liver toxicity.”
Made from Montmorency tart cherries, this preparation is made up of ground whole cherries and given as a soft gelatin capsule (marketed under the brand name CherryFlex®).
“This specific type of tart cherry is one of the best studied natural products and anecdotally has been claimed to have a salutary effect on osteoarthritis and other types of arthritis as well,” adds Dr. Cush.
Baylor Research Institute together with the Arthritis Care & Research Institute is currently enrolling patients in a second study, which will test cherry pills versus placebo in an eight week double blind study.
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