Evelyn Pringle August 5, 2007
On July 20, 2007, the Centers for Medicare & Medicaid Services issued new reimbursement rules that limit the use and dosage for a class of anemia drugs known as erythropoiesis stimulating agents (ESA's), in large part prompted by findings that the medications were being over-prescribed for profit under the current billing rules.
However, right about now, reimbursement rates are probably the least of the worries for the companies that market the drugs, Johnson & Johnson and Amgen. On May 10, 2007, Amgen received a subpoena from the New York attorney general seeking documents related to "promotional activities, sales and marketing activities, medical education, clinical studies, pricing and contracting, license and distribution agreements and corporate communications," according to the firm's May 22, 2007, SEC filing.
Also, a J&J spokeswomen said her company has also received a subpoena that covers the sales, marketing, medical education, and clinical trials of the ESA's, according to the May 25, 2007, Cancer Letter.
The drugs are sold under the brand names Procrit, Epogen, and Aranesp, and Amgen manufactures all three, but Procrit is marketed by J&J.
On April 17, 2007, Newsday reported that the large for-profit dialysis chains like DaVita and Fresenius are negotiating volume discounts that allow them to buy ESA's at a lower price than the reimbursement rate from Medicare, "making the drug a profit center."
A June 2007 report on an investigation by the US Department of Health and Human Services Office of Inspector General found dialysis facilities could acquire the anemia drugs for as much as 10% below Medicare reimbursement levels. Acquisition costs varied substantially, the report notes, with chain-owned freestanding clinics often paying less than non-chain freestanding and hospital-based facilities, but all totaled, 99% of freestanding dialysis facilities could purchase ESA's for less than the Medicare reimbursement rate.
On May 9, 2007, the New York Times reported that J&J and Amgen were paying "hundreds of millions of dollars to doctors every year in return for giving their patients anemia medicines."
Federal law bars drug makers from paying doctors who prescribe drugs in pill form to be purchased at a pharmacy, but companies are allowed to offer rebates to doctors who buy drugs that are administered in their office.
Documents obtained by the Times show that, at just one practice in the Pacific Northwest, six cancer doctors received $2.7 million from Amgen for prescribing $9 million worth of its drugs last year.
Michael Sullivan, who worked as a business manager for the six doctors in the Pacific Northwest for 9 years, told the Times that the rebates inevitably encourage use of the drugs and that as result of the rebates from Amgen, the six doctors made about $1.8 million in net profit on the drugs they prescribed.
On May 10, 2007, the Wall Street Journal reported a review of documents provided by Dean McClellan, a former sales representative who filed a whistleblower lawsuit against J&J alleging that the company "offered excessive financial incentives for doctors" to prescribe Procrit and encouraged doctors to prescribe the drug at higher doses than were approved.
One document, cited by Journal, estimated that a doctor who purchased nearly $1 million worth of Procrit over 15 months would receive $237,885. Another program offered a discount for J&J's product line for hospitals that used Procrit at least 75% of the time. J&J also developed a "Right of First Refusal" contract that required doctors to allow J&J to make a better offer if Amgen lowered the price of Aranesp, making it cheaper than Procrit.
Half of Amgen's total revenue for 2006 was earned by Epogen and Aranesp, bringing in combined sales of $6.6 billion. Procrit was J&J's second best selling drug last year at $3.2 billion, according to Forbes on March 21, 2007.
In the US, the majority of the profits are tax dollars, because Medicare pays for over 90% of services provided to patients with end stage renal disease (ESRD), and the anemia drugs cost approximately $2 billion a year, according to a report by the US House Ways and Means Committee which oversees spending by the Medicare and Medicaid programs.
The drugs are approved only for the limited use with patients who are anemic and undergoing dialysis due to chronic kidney disease, cancer patients who are receiving chemotherapy and patients who are scheduled to have major surgery to reduce the need for blood transfusions.
According to the FDA-approved labeling, before receiving ESA's, patients should have a hemoglobin (red blood cell count) level of 10-12 grams per deciliter of blood, and the drugs are to be used only if the level drops below 10 grams.
Despite the FDA label, a 2006 report by the US Renal Data System, a large federally-funded registry of patients on dialysis, found that more than 40% of dialysis patients have a hemoglobin level greater than 12, and over 20% have hemoglobin levels above 13.
In the past year, investigations have shown that the drugs are being administered to patients who are not receiving dialysis or chemotherapy and in higher doses than approved. In fact, one study found that about 50% of dialysis patients had hemoglobin levels above what the FDA considers safe, and about 20% develop dangerously high levels that can lead to heart attacks and strokes, according to the November 17, 2006, medical journal Lancet.
A November 2006 Dialysis and Transplantation study found that the population with a red blood cell count above the guidelines also had higher costs of $3,100 per patient per year more for just the anemia drug.
Dr Laura Pizzi, a Research Associate Professor of Health Policy at Jefferson Medical College in Philadelphia who led the study, testified at a December 2, 2006 hearing before the House Ways and Means Committee and discussed how the study converted the difference in utilization to dollars amounts between actual usage versus recommended practice based on 2005 Medicare reimbursement rates and estimated that Medicare could have reduced the cost for the drugs by 36% if dialysis facilities adhered to the guidelines.
"If CMS spends $2 billion per year," she said, "it is reasonable to say that several hundred million dollars could have been saved on the drug if providers followed the guidelines."
On December 6, 2006, Dr Ajay Singh, clinical chief of the Renal Division and director of dialysis services at the Brigham and Women's Hospital, testified at a hearing before the US House Ways and Means Committee and told lawmakers that patients in the higher hemoglobin group had a 34% higher risk of death and cardiovascular complications compared to patients in the lower level group.
He testified to a study that found there were 52 deaths in the higher group versus 36 in the lower hemoglobin group, or a 48% higher risk and a 41% higher risk of hospitalizations for heart failure and more cardiovascular adverse events.
Dr Singh also said the study found no benefits for patients who received the drugs and, therefore, "the conclusion was there was both increased risk and no substantive incremental quality of life benefit in raising the hemoglobin among patients with chronic kidney disease not on dialysis."
An editorial in the April 18, 2007, Journal of the American Medical Association, by Dr Daniel Coyne, a professor at Washington University School of Medicine, estimated that it costs the Medicare program $1,700 more for each patients on the higher dose. "Physicians need to challenge industries," he wrote, "that appear to be using patients as profit centers based on bad science."
In February 2007, the FDA notified health care professionals of the results from a large clinical trial evaluating the use of Aranesp to treat cancer patients not receiving chemotherapy in which patients received either Aranesp according to the approved dosing regimen or a placebo.
Patients treated with Aranesp, the FDA reported, had a higher death rate and no reduction in the need for transfusions compared to those treated with placebo. The FDA warned that the finding showed that treating anemic cancer patients not on chemotherapy with an ESA may offer no benefit and may cause serious harm.
In a March 9, 2007, safety alert, the FDA reported that an analyses of four new studies in patients with cancer found a higher rate of serious and life-threatening side effects and/or death with the use of ESA's. The studies were evaluating an unapproved dosing regimen, a patient population for which ESA's are not approved, or a new unapproved ESA.
According to the FDA, as of March 2007, there were five clinical trials that demonstrated decreased survival time in cancer patients receiving ESA's compared with those receiving blood transfusions.
In addition, the agency reported a higher rate of blood clots, strokes, heart failure, heart attacks and death in patients with chronic kidney failure when ESA's were given to raise hemoglobin levels higher than 12.
The FDA advisory also noted that a higher risk of blood clots was reported in patients who were scheduled for major surgery and received ESA's.
The FDA also warned of an increased rate of tumor growth in patients with advanced head and neck cancer receiving radiation therapy and metastatic breast cancer patients receiving chemotherapy, when ESA's were given to maintain levels of more than 12.
There was also a higher rate of death reported, the agency said, but no fewer blood transfusions when ESA's were given to patients who were not receiving chemotherapy.
In March 2007, the FDA revised the product labeling for the drugs to include updated warnings, a new boxed warning and modifications to the dosing instructions. The boxed warning advises doctors to use the lowest ESA dose to gradually increase the hemoglobin level to a concentration sufficient to avoid the need for blood transfusions.
The label revisions, the FDA said, were based on recently completed trials that described an increased risk of death, blood clots, strokes and heart attacks in patients with chronic kidney failure when ESA's were given at doses that resulted in higher than recommended hemoglobin levels.
The revisions also addressed the trial findings for cancer patients, both when ESA's were given at doses intended to result in higher than recommended hemoglobin levels, and when ESA's were given to cancer patients whose anemia was not chemotherapy-related.
The revised label also summarizes the information from the trial that showed an increased risk for deep venous thrombosis in patients following orthopedic surgery when ESA's were administered without the blood clot prevention measures listed on the product label.
On May 8, 2007, the FDA released a report by agency scientists that said there was no evidence to support that ESA's improved the quality of life in patients or extended their survival, while several studies show the drugs can shorten lives when used at high doses.
On June 26, 2007, Robert Vito, Regional Inspector General for Evaluation and Inspections in Philadelphia at the US Department of Health and Human Services' Office of Inspector General, testified at a hearing before the House Ways and Means Committee and described cases where dialysis centers have been found to be submitting false claims for payment to Medicare involving the anemia drugs.
This year, he said, Dialysis Clinic, Inc., which provides services to Medicare beneficiaries with ESRD with clinics located in more than 30 States, agreed to pay $1.8 million to resolve liability under the False Claim Act, with the majority of the settlement associated with the administration and billing of ESA's when it was medically unnecessary.
Showing posts with label prices. Show all posts
Showing posts with label prices. Show all posts
Sunday, August 8, 2010
Saturday, August 7, 2010
Off-Label Depakote Sales Stronger Than Ever
Evelyn Pringle February 11, 2007
The epilepsy drug, Depakote, earned Abbott Laboratories $384 million in the 4th quarter of 2006, and overall sales rose 18.5% to $1.2 billion last year.
The rising sales are a result of Depakote (valproate) being increasingly prescribed for conditions other than epilepsy like mood disorders, manic depression and migraines. Doctors are also prescribing Depakote as a mood stabilizer in off-label combinations with other drugs for uses that have never been FDA approved or tested for safety and efficacy.
Although in the US, drug companies are prohibited by law from promoting the sale of a drug for an off-label use, once a medication is FDA approved for once indication, doctors are free to prescribe it for other conditions if they believe it will be beneficial to a patient.
However, in recent years the rate of off-label prescribing has become epidemic and many drug companies have paid huge fines after being caught promoting drugs for unapproved uses and many more are currently under investigation for illegal marketing schemes.
In 2001, a study by the Agency for Healthcare Research and Quality (AHRQ) found that about 21% of prescriptions written in the US are for conditions not indicated on the label and cardiac medications and anticonvulsants were the most commonly prescribed for unapproved uses. Most off-label use, the study pointed out, occurs without scientific support.
Depakote is one of the drugs prescribed most often off-label, and experts say its not unusual to find patients on Depakote along with 3 or 4 other medications all at once.
On October 13, 2006, the FDA revised the labeling for Depakote to warn of adverse events associated with use of the drug during pregnancy and said that Depakote should only be considered for women of childbearing years if it was essential for the treatment of their condition and the risks and benefits were fully discussed with the patient.
According to the North American Antiepileptic Drug Pregnancy Registry, Depakote use during the first trimester of pregnancy is linked to a 4-fold increased risk of congenital malformations when compared with other antiepileptic drugs (AEDs). The rate malformations with infants exposed to Depakote was 10.7%, or 16 cases in 149 births.
The Registry is set up to determine the safety of anticonvulsants to help gauge the frequency of malformations, such as heart defects, spina bifida and cleft lip. Only major malformations are included in the Registry, defined as a structural abnormality of the infant with surgical, medical, or cosmetic importance.
The CDC reports that the risk of spina bifida among infants born to mothers receiving Depakote during the first trimester is estimated to be 1% to 2%, compared to 0.14% to 0.2% in the general population according to the American College of Obstetricians and Gynecologists.
Although Depakote is most strongly associated with neural tube defects, the FDA notes that other anomalies have also been reported, such as craniofacial defects, cardiovascular malformations, and anomalies involving various body systems with some fatal.
Drugs that cause malformations are known as teratogens. A teratogen can disturb the development of the fetus, halt the pregnancy, or permit the pregnancy to proceed but produce a congenital malformation or birth defect.
Due to the rate of off-label prescribing, pregnant women may be receiving Depakote for other indications and the FDA warns that the increased risk associated with Depakote in pregnant women treated for epilepsy likely reflects an increased risk in treatment for other conditions as well, such as migraines or bipolar disorder.
Depakote has now been moved into "Category C" for pregnant women, which means animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women, or no animal studies have been conducted and there are no adequate and well-controlled studies in pregnant women.
In the case of Depakote, numerous animal studies have established drug-induced teratogenicity. Increased malformations, as well as growth retardation and death, have been found in rats, mice, rabbits, and monkeys following prenatal exposure to the drug, according to the FDA's information listed on Depakote.
Malformations of the skeletal system are the most common structural abnormalities observed in animals, but neural tube closure defects have been seen in mice exposed to plasma Depakote concentrations exceeding 2.3 times the upper limit of the human therapeutic range during periods of embryonic development.
An oral dose equal to about 50% of the maximum human daily dose administered to pregnant rats produced skeletal, cardiac, and urogenital malformations and growth retardation in the offspring. Behavioral deficits have also been reported in the offspring of rats given Depakote throughout most of the pregnancy.
An oral dose of approximately 2 times the maximum human daily dose produced skeletal and visceral malformations in rabbits exposed during organogenesis.
Skeletal malformations, growth retardation, and death have been observed in rhesus monkeys following administration of an oral dose equal to the maximum human daily dose during organogenesis.
The initial report from on-going human study titled, "Neurodevelopmental Effects of Antiepileptic Drugs," in the August 8, 2006, journal, Neurology, found that major congenital abnormalities were more common in infants exposed to Depakote than those exposed to one of 3 other AEDs.
A team of researchers led by Dr Kimford Meador, of the University of Florida, are conducting a study on pregnant women with treated for epilepsy from October 1999 to February 2004, receiving either Depakote, Dilantin, Lamictal, or Tegretol.
The initial report, focuses on the rate of serious adverse events including fetal death or major congenital malformations defined as structural abnormalities with surgical, medical, or cosmetic importance identified during pregnancy, at birth, between birth and 1 year, or at 73 weeks.
The researchers identified 6 fetal deaths and 22 malformations that included malformed hearts and genitals, cleft palate, and artery deformities, with 20.3% found in women taking Depakote.
Based on these initial findings, the researchers advised that Depakote should not be used as the first choice for women of childbearing potential, and if used, its dose should be limited when possible.
In an interview with Shawna Cutting, posted on Epilepsy.com, Dr Meador explained how he became interested in doing the study. "Over the years," he said, "I began to think that these effects might be dramatic in children while their brains are developing, because they could add up over many years."
"That made me think that the effect might be even greater in a fetus because brain development there is so rapid," he said.
"The process of physical growth and the attainment of intelligence and problem-solving ability that begins in infancy; any interruption of this process by a disease or disorder is called developmental delay," Dr Meador explained.
He said studies of animals clearly showed that some antiepileptic drugs could affect behavior of the offspring.
His on-going study will track children until they are 2 or 3, but says children need to be followed until they are at least 6. "This age is so important," Dr Meador said during the interview, "because this is when measures such as IQ begin to match up with adult measures."
"If you measure a child's IQ at 3 years of age," he explained, "it may not predict the child's development."
"But a measurement at 6 years of age," he said, "statistically will predict what will happen when this kid is an adult."
He also noted that this is an important point because children begin school at that age and whatever is going on will effect their learning and said, a "disturbing report" on a study from England suggested that Depakote was producing worse effects.
The epilepsy drug, Depakote, earned Abbott Laboratories $384 million in the 4th quarter of 2006, and overall sales rose 18.5% to $1.2 billion last year.
The rising sales are a result of Depakote (valproate) being increasingly prescribed for conditions other than epilepsy like mood disorders, manic depression and migraines. Doctors are also prescribing Depakote as a mood stabilizer in off-label combinations with other drugs for uses that have never been FDA approved or tested for safety and efficacy.
Although in the US, drug companies are prohibited by law from promoting the sale of a drug for an off-label use, once a medication is FDA approved for once indication, doctors are free to prescribe it for other conditions if they believe it will be beneficial to a patient.
However, in recent years the rate of off-label prescribing has become epidemic and many drug companies have paid huge fines after being caught promoting drugs for unapproved uses and many more are currently under investigation for illegal marketing schemes.
In 2001, a study by the Agency for Healthcare Research and Quality (AHRQ) found that about 21% of prescriptions written in the US are for conditions not indicated on the label and cardiac medications and anticonvulsants were the most commonly prescribed for unapproved uses. Most off-label use, the study pointed out, occurs without scientific support.
Depakote is one of the drugs prescribed most often off-label, and experts say its not unusual to find patients on Depakote along with 3 or 4 other medications all at once.
On October 13, 2006, the FDA revised the labeling for Depakote to warn of adverse events associated with use of the drug during pregnancy and said that Depakote should only be considered for women of childbearing years if it was essential for the treatment of their condition and the risks and benefits were fully discussed with the patient.
According to the North American Antiepileptic Drug Pregnancy Registry, Depakote use during the first trimester of pregnancy is linked to a 4-fold increased risk of congenital malformations when compared with other antiepileptic drugs (AEDs). The rate malformations with infants exposed to Depakote was 10.7%, or 16 cases in 149 births.
The Registry is set up to determine the safety of anticonvulsants to help gauge the frequency of malformations, such as heart defects, spina bifida and cleft lip. Only major malformations are included in the Registry, defined as a structural abnormality of the infant with surgical, medical, or cosmetic importance.
The CDC reports that the risk of spina bifida among infants born to mothers receiving Depakote during the first trimester is estimated to be 1% to 2%, compared to 0.14% to 0.2% in the general population according to the American College of Obstetricians and Gynecologists.
Although Depakote is most strongly associated with neural tube defects, the FDA notes that other anomalies have also been reported, such as craniofacial defects, cardiovascular malformations, and anomalies involving various body systems with some fatal.
Drugs that cause malformations are known as teratogens. A teratogen can disturb the development of the fetus, halt the pregnancy, or permit the pregnancy to proceed but produce a congenital malformation or birth defect.
Due to the rate of off-label prescribing, pregnant women may be receiving Depakote for other indications and the FDA warns that the increased risk associated with Depakote in pregnant women treated for epilepsy likely reflects an increased risk in treatment for other conditions as well, such as migraines or bipolar disorder.
Depakote has now been moved into "Category C" for pregnant women, which means animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women, or no animal studies have been conducted and there are no adequate and well-controlled studies in pregnant women.
In the case of Depakote, numerous animal studies have established drug-induced teratogenicity. Increased malformations, as well as growth retardation and death, have been found in rats, mice, rabbits, and monkeys following prenatal exposure to the drug, according to the FDA's information listed on Depakote.
Malformations of the skeletal system are the most common structural abnormalities observed in animals, but neural tube closure defects have been seen in mice exposed to plasma Depakote concentrations exceeding 2.3 times the upper limit of the human therapeutic range during periods of embryonic development.
An oral dose equal to about 50% of the maximum human daily dose administered to pregnant rats produced skeletal, cardiac, and urogenital malformations and growth retardation in the offspring. Behavioral deficits have also been reported in the offspring of rats given Depakote throughout most of the pregnancy.
An oral dose of approximately 2 times the maximum human daily dose produced skeletal and visceral malformations in rabbits exposed during organogenesis.
Skeletal malformations, growth retardation, and death have been observed in rhesus monkeys following administration of an oral dose equal to the maximum human daily dose during organogenesis.
The initial report from on-going human study titled, "Neurodevelopmental Effects of Antiepileptic Drugs," in the August 8, 2006, journal, Neurology, found that major congenital abnormalities were more common in infants exposed to Depakote than those exposed to one of 3 other AEDs.
A team of researchers led by Dr Kimford Meador, of the University of Florida, are conducting a study on pregnant women with treated for epilepsy from October 1999 to February 2004, receiving either Depakote, Dilantin, Lamictal, or Tegretol.
The initial report, focuses on the rate of serious adverse events including fetal death or major congenital malformations defined as structural abnormalities with surgical, medical, or cosmetic importance identified during pregnancy, at birth, between birth and 1 year, or at 73 weeks.
The researchers identified 6 fetal deaths and 22 malformations that included malformed hearts and genitals, cleft palate, and artery deformities, with 20.3% found in women taking Depakote.
Based on these initial findings, the researchers advised that Depakote should not be used as the first choice for women of childbearing potential, and if used, its dose should be limited when possible.
In an interview with Shawna Cutting, posted on Epilepsy.com, Dr Meador explained how he became interested in doing the study. "Over the years," he said, "I began to think that these effects might be dramatic in children while their brains are developing, because they could add up over many years."
"That made me think that the effect might be even greater in a fetus because brain development there is so rapid," he said.
"The process of physical growth and the attainment of intelligence and problem-solving ability that begins in infancy; any interruption of this process by a disease or disorder is called developmental delay," Dr Meador explained.
He said studies of animals clearly showed that some antiepileptic drugs could affect behavior of the offspring.
His on-going study will track children until they are 2 or 3, but says children need to be followed until they are at least 6. "This age is so important," Dr Meador said during the interview, "because this is when measures such as IQ begin to match up with adult measures."
"If you measure a child's IQ at 3 years of age," he explained, "it may not predict the child's development."
"But a measurement at 6 years of age," he said, "statistically will predict what will happen when this kid is an adult."
He also noted that this is an important point because children begin school at that age and whatever is going on will effect their learning and said, a "disturbing report" on a study from England suggested that Depakote was producing worse effects.
Drug Eluting Stent Patients Beware
Evelyn Pringle January 24, 2007
Drug eluting stents were promoted as working so much better than the old bare metal stents that 6 million people worldwide have received them in the few years since the arrived on the market.
"It was a modern record for any medical device," the Boston Globe reported on December 4, 2006. Some 2 to 3 million people in the US now carry one of these devices in an artery, according to FDA estimates, with new implants topping 900,000 per year.
Only two brands of DES are sold in the US, the Taxus, by Boston Scientific, and the Cypher, by Johnson & Johnson's Cordis Division.
The trials submitted by the DES makers to obtain FDA approval for use in limited procedures with non-complex patients with single-vessel heart disease, involved a low risk population. However, off-label DES use for procedures not approved by the FDA has become rampant and according to the agency:
"It is estimated that a majority of DES are implanted in lesions outside of their current indications for use, such as in-stent restenosis lesions, bifurcation lesions, coronary artery bypass grafts, acute myocardial infarction, chronic total occlusions, overlapping and multiple stents per vessel and in patients with multivessel disease and chronic renal insufficiency."
Surgeons have been implanting the new devices in every kind of heart patient. And for good reason. The stenting business represents maga bucks to device makers, hospitals and surgeons alike. In the US, the implant procedure itself costs $38,203, according to a report by the Associated Press on December 26, 2006.
But as has been the case with so many pharmaceutical products in recent years, after being massively promoted, and implanted in millions of patients for indications not approved, DES are proving to be no better than the bare metal stents, and in fact research has shown them to worse because they come with more adverse reactions.
In early December 2006, the FDA's Circulatory System Devices Advisory Committee held a public meeting to review data on thrombosis both when DES were used according to their label and when they are implanted off-label for unapproved uses, and to address the appropriate duration for the use of the blood-thinning drug, Plavix, with DES patients.
In the briefing provided to the Committee before the hearing, the FDA informed the panel that recent presentations at scientific meetings had indicated a small but significant increase in the rates of death or myocardial infarction, and non-cardiac mortality, in DES patients when compared to patients who received bare metal stents.
The briefing included a specific discussion of presentations made at the Transcatheter Cardiovascular Therapeutics meeting, in October 2006, where doctors, Martin Leon and Gregg Stone, presented a meta-analyses of patient data from the Cypher and Taxus clinical trails.
Based on these analyses, Dr Stuart Pocock reported that after one year, five Cypher patients, compared to no bare metal patients, had experienced late thrombosis, and with the Taxus, thrombosis occurred in nine patients after one year compared with two bare metal stent patients.
Last year, the Swiss government commissioned a study to determine whether the DES were worth their price of between $2,200 and $2,700, when compared to the $600 to $800 for bare metal stents, and also to test how long Plavix should be prescribed to patients after the implantation of a DES to prevent blood clots from developing.
The study appeared in the December 19, 2006, Journal of the American College of Cardiology, and reported that patients with DES had double the risk of cardiac problems after stopping Plavix compared to patients with bare metal stents.
The Swiss researchers, led by Dr Matthias Pfisterer, found that when patients stop taking Plavix, they had a small but serious risk of blood clots leading to death or heart attack.
The lead author noted that the majority of DES implants in the study were off-label. "About two-thirds of our patients were really treated with off-label use of drug-eluting stents," Dr Pfisterer told WebMD on December 5, 2006.
"The FDA label says these are only for stable patients with limited disease," he notes. "But, in fact," he told WebMD, "most doctors who use drug-eluting stents use them in unstable patients and in more complex disease."
In an editorial accompanying the Pfisterer study, Dr Robert Califf and Dr Robert Harrington, warned that research on DES has not kept up with clinical realities. "As is frequently seen with new cardiac devices," they wrote, "rapid increase in clinical adoption quickly outstripped what is known about the device from limited clinical trials."
Medical professionals say an important point to keep in mind when considering the risks associated with the DES is that these devices have only been on the market in the US for less than four years and that many more unknown risks could surface in years to come.
More problems may have already surfaced according to Dr Joseph Muhlestein, a professor at the University of Utah. He told ABC New's Healthday reporter on December 4, 2006, that his research group has followed patients receiving DES implants very carefully and has found "something we don't understand."
As expected, he said, the DES did reduce artery closure at the site where they were implanted, but the incidence of artery problems at other sites occurred "significantly more often than when we used bare-metal stents," he told Healthday.
So, the overall incidence of artery problems ended up being the same, regardless of which type of stent was implanted, Dr Muhlestein said.
It is possible that the problem occurred because DES were used on more high-risk patients, he noted. But it's also possible, he said, that the DES interfered with the endothelium, the delicate tissue that lines the arteries.
These doubts have caused some doctors to cut back on DES use. "We used to use them in 90 percent of cases," Dr Muhlestein told Healthday. "Now, it's about 40 percent."
Finally, experts are warning that if unexpected health problems do develop in patients already implanted with the DES, removal of the stent is not possible because once it is placed in the body, the tissue in the artery grows over the stent.
Drug eluting stents were promoted as working so much better than the old bare metal stents that 6 million people worldwide have received them in the few years since the arrived on the market.
"It was a modern record for any medical device," the Boston Globe reported on December 4, 2006. Some 2 to 3 million people in the US now carry one of these devices in an artery, according to FDA estimates, with new implants topping 900,000 per year.
Only two brands of DES are sold in the US, the Taxus, by Boston Scientific, and the Cypher, by Johnson & Johnson's Cordis Division.
The trials submitted by the DES makers to obtain FDA approval for use in limited procedures with non-complex patients with single-vessel heart disease, involved a low risk population. However, off-label DES use for procedures not approved by the FDA has become rampant and according to the agency:
"It is estimated that a majority of DES are implanted in lesions outside of their current indications for use, such as in-stent restenosis lesions, bifurcation lesions, coronary artery bypass grafts, acute myocardial infarction, chronic total occlusions, overlapping and multiple stents per vessel and in patients with multivessel disease and chronic renal insufficiency."
Surgeons have been implanting the new devices in every kind of heart patient. And for good reason. The stenting business represents maga bucks to device makers, hospitals and surgeons alike. In the US, the implant procedure itself costs $38,203, according to a report by the Associated Press on December 26, 2006.
But as has been the case with so many pharmaceutical products in recent years, after being massively promoted, and implanted in millions of patients for indications not approved, DES are proving to be no better than the bare metal stents, and in fact research has shown them to worse because they come with more adverse reactions.
In early December 2006, the FDA's Circulatory System Devices Advisory Committee held a public meeting to review data on thrombosis both when DES were used according to their label and when they are implanted off-label for unapproved uses, and to address the appropriate duration for the use of the blood-thinning drug, Plavix, with DES patients.
In the briefing provided to the Committee before the hearing, the FDA informed the panel that recent presentations at scientific meetings had indicated a small but significant increase in the rates of death or myocardial infarction, and non-cardiac mortality, in DES patients when compared to patients who received bare metal stents.
The briefing included a specific discussion of presentations made at the Transcatheter Cardiovascular Therapeutics meeting, in October 2006, where doctors, Martin Leon and Gregg Stone, presented a meta-analyses of patient data from the Cypher and Taxus clinical trails.
Based on these analyses, Dr Stuart Pocock reported that after one year, five Cypher patients, compared to no bare metal patients, had experienced late thrombosis, and with the Taxus, thrombosis occurred in nine patients after one year compared with two bare metal stent patients.
Last year, the Swiss government commissioned a study to determine whether the DES were worth their price of between $2,200 and $2,700, when compared to the $600 to $800 for bare metal stents, and also to test how long Plavix should be prescribed to patients after the implantation of a DES to prevent blood clots from developing.
The study appeared in the December 19, 2006, Journal of the American College of Cardiology, and reported that patients with DES had double the risk of cardiac problems after stopping Plavix compared to patients with bare metal stents.
The Swiss researchers, led by Dr Matthias Pfisterer, found that when patients stop taking Plavix, they had a small but serious risk of blood clots leading to death or heart attack.
The lead author noted that the majority of DES implants in the study were off-label. "About two-thirds of our patients were really treated with off-label use of drug-eluting stents," Dr Pfisterer told WebMD on December 5, 2006.
"The FDA label says these are only for stable patients with limited disease," he notes. "But, in fact," he told WebMD, "most doctors who use drug-eluting stents use them in unstable patients and in more complex disease."
In an editorial accompanying the Pfisterer study, Dr Robert Califf and Dr Robert Harrington, warned that research on DES has not kept up with clinical realities. "As is frequently seen with new cardiac devices," they wrote, "rapid increase in clinical adoption quickly outstripped what is known about the device from limited clinical trials."
Medical professionals say an important point to keep in mind when considering the risks associated with the DES is that these devices have only been on the market in the US for less than four years and that many more unknown risks could surface in years to come.
More problems may have already surfaced according to Dr Joseph Muhlestein, a professor at the University of Utah. He told ABC New's Healthday reporter on December 4, 2006, that his research group has followed patients receiving DES implants very carefully and has found "something we don't understand."
As expected, he said, the DES did reduce artery closure at the site where they were implanted, but the incidence of artery problems at other sites occurred "significantly more often than when we used bare-metal stents," he told Healthday.
So, the overall incidence of artery problems ended up being the same, regardless of which type of stent was implanted, Dr Muhlestein said.
It is possible that the problem occurred because DES were used on more high-risk patients, he noted. But it's also possible, he said, that the DES interfered with the endothelium, the delicate tissue that lines the arteries.
These doubts have caused some doctors to cut back on DES use. "We used to use them in 90 percent of cases," Dr Muhlestein told Healthday. "Now, it's about 40 percent."
Finally, experts are warning that if unexpected health problems do develop in patients already implanted with the DES, removal of the stent is not possible because once it is placed in the body, the tissue in the artery grows over the stent.
Off-Label Prescribing of Pain Lollipops Turns Deadly
Evelyn Pringle January 24, 2007
The painkilling lollipop, Actiq, is approved to treat chronic pain in cancer patients who are already on an opioid drug. But a recent study by Prime Therapeutics found the drug is being prescribed off-label for unapproved uses nearly 90% of the time.
For those suffering with the agonizing pain of late stage cancer, the painkiller on a stick brings fast relief because it is 80 times more potent than morphine, which makes it a prime drug to watch for law enforcement officials because of its potential for illicit use.
Actiq contains fentanyl, a drug classified as a Schedule II substance by the Drug Enforcement Administration, in the same category as cocaine, opium, methamphetamine and methadone. Schedule II drugs have the highest potential for abuse and overdose.
Fentanyl is also available in a skin patch, and overall, prescriptions for the drug have increased from about 0.5 million in 1994 to 6.95 million in 2005, according to IMS Health, a pharmaceutical industry tracking firm.
Actiq is only FDA approved for the management of pain in cancer patients who are already being treated with opioids because life-threatening conditions can occur at any dose in patients without a built-up tolerance for opioids.
According to a November 5, 1998, talk paper prepared for agency personnel at the time of the product's approval, the FDA approved Actiq, as a "new product developed specifically for cancer patients with severe pain that breaks through their regular narcotic therapy."
"Because Actiq may be fatal to children (as well as to adults not already taking opioid narcotics)," the paper said, "FDA approved Actiq under special regulations that restrict distribution as defined in a comprehensive risk management plan."
The FDA noted that the agency was "extremely concerned that this product be packaged and marketed to minimize the opportunity for diversion, abuse, or access by children."
However, the DEA, reports that fentanyl is being diverted by pharmacy theft, fraudulent prescriptions and illicit distribution by patients, physicians and pharmacists, and theft at nursing homes and other long-term care facilities. Actiq is typically sold on the street for $20-25 per lollipop and the drug's street name is "perc-a-pop."
In 2004, there were an estimated 8,000 emergency-room visits for fentanyl overdoses, according the US Substance Abuse and Mental Health Services Administration. Overdose can result in sudden death through respiratory arrest, cardiac arrest, severe respiratory depression, cardiovascular collapse or severe anaphylactic reaction, according to the agency. As of November 16, 2006, there were 653 deaths confirmed in the US since 2005.
On June 20, 2006, the US Department of Health and Human Service sent a letter to emergency department physicians and personnel to make them aware that the CDC was receiving increasing reports of fentanyl overdoses among illicit drug users in multiple states.
However, the fact that fentanyl cannot be detected with standard opiate screens has caused major problems. Currently, the ER protocol recommended is to assume the presence of fentanyl when a patient has symptoms of narcotic overdose but fails to test positive for heroin.
The Utah based drug maker Anesta Corp, a company acquired by Cephalon in 2000, developed Actiq. Since the Cephalon taker-over in 2000, Actiq has become one of the drugs most often prescribed off-label in the US.
Off-label refers to the use of drugs to treat conditions other than those approved by the FDA and can include prescribing drugs to unapproved populations such as children or the elderly or in higher doses than specified in the drug's labeling. Drug companies are not allowed to promote a drug for off-label uses, but doctors are permitted to prescribe a drug for any use they believe would be helpful.
The study released this month by Prime Therapeutics, a pharmacy benefit manager, analyzed 95 patient claims from a Midwestern commercial health plan from April through June 2005, and found that only 21 patients had a diagnosis of cancer or AIDS.
In addition, Prime found that only 11 of those 21 patients were taking a long-acting opioid painkiller. Overall, 84 of the 95 Actiq prescriptions, or nearly 90%, were off-label.
The Prime study also found that more than 15% of the prescriptions were for more than the recommended dose of 120 lollipops per month.
Government investigators have been looking into Cephalon's off-label promotion of Actiq in Connecticut and the Philadelphia area for two years, and the company is also being investigated by the FDA's Office of Criminal Investigations.
In November 2006, Connecticut Attorney General, Richard Blumenthal, concluded an investigation, which according to the Wall Street Journal, uncovered evidence that suggests Cephalon set high sales quotas for its sales representatives that could not be reached without promoting Actiq off-label.
Of course, just like every other company busted for off-label marketing in recent years, Cephalon claims it does not market Actiq off-label. But internal company documents reveal that sales reps were regularly sent to primary care doctors and specialists, who treat no cancer patients, armed with free coupons for doctors to pass out to patients.
For instance, Dr Stephen Leighton, a general practitioner who says he only has 3 cancer patients at any given time, told the Journal that a Cephalon saleswoman comes by once a month and gives him about 60 to 70 coupons for patients to trade in for six Actiq sticks.
He says the coupons spurred him to try the drug on patients with migraines and back pain and that he prescribes Actiq 15 to 20 times a month to patients who do not have cancer.
As a further indication of off-label promotion by Cephalon's Actiq sales force, the Journal cites a survey by the research firm ImpactRx, that found visits to non-cancer doctors increased 6-fold from 2002 to 2005.
According to company documents, Cephalon instructed sales reps to ask non-cancer doctors, "Do you have the potential to treat cancer pain?"
And even if the answer was no, they were instructed to give the doctors free coupons to pass out. One document quoted by the Journal, says the coupon program "is a remarkably effective promotional tool" that increased sales by 75 prescriptions a week at little cost.
Cephalon uses many tactics to influence doctor's prescribing habits. Mr Blumenthal's investigation found instances where Cephalon flew doctors to company funded seminars where paid speakers promoted the off-label use of Actiq. For instance, the Journal described a September 2003, New York seminar, where one of the topics was "Opioid use in headache."
At another October 2003, meeting, the Journal reports, a topic was "Use of Actiq in opioid-naive patients," even though the product label says it should be prescribed only to patients already taking opiate narcotics and can tolerate the drug.
In fact, the Actiq package insert states: "Do Not Take OTFC if you: are not already taking other opioid pain medicines for your constant (around-the-clock) cancer pain."
It also states: "Never use OTFC for short-term pain from injuries or surgery or pain that will go away in a few days, such as pain from doctor or dentist visits, or any short-lasting pain."
In 2002, Cephalon began zeroing in on neurologists and a document titled "Actiq in Migraine," instructed sales reps to pitch Actiq as "an ER on a stick."
The off-label use of Actiq by opioid naive patients has resulted in devastating consequences for some people. On January 22, 2006, the Free Press reported that the wife of a minister, former schoolteacher, and the mother of three sons, was arrested and charged with involuntary manslaughter because she gave Actiq, her cancer pain medication, to a friend who had a migraine and the friend died of a drug overdose.
On November 3, 2006, the Journal reported a case where a pregnant woman was prescribed Actiq for migraines by a neurologist. By the time of delivery, the woman, who the Journal noted had previously struggled with addictions to milder narcotics, was consuming five lollipops a day.
Upon birth, the infant was cranky and could not sleep and doctors told the woman that her son had become addicted to Actiq and was going through withdrawal.
When approving Actiq in 1998, the FDA set up a risk-management program with guidelines that said sales reps should "promote only to the target audiences," defined as oncologists, pain specialists, their nurses and office staff.
An provision of the program requires Cephalon to report whether "groups of physicians (such as a particular specialty)" who represent "potential off-label usage greater than 15 percent" are prescribing Actiq. If such a group exists, the FDA says, Cephalon should warn the doctors against the off-label use of the drug.
According to the market research firm, Verispan, for the first half of 2006, two groups of doctors exceeded the 15% quota, anesthesiologists at 29.5%, and physical medicine and rehabilitation specialists at 16%. Oncologists or cancer doctors accounted for only 1% of the prescriptions at retail pharmacies in the US, the Journal reports quoting Verispan.
In 2003, a company auditor, David Brennan, determined that Cephalon was not complying with the 15% rule, but says he was fired when he reported his findings to his superiors, according to a June 2004, wrongful termination lawsuit filed in Camden, NJ.
For Cephalon to act naive about the level of off-label prescribing of Actiq while the cash register is ringing up the sales is laughable. According to the November 3, 2006, report in the Journal, sales of Actiq went from $15 million in 2000, to more than $400 million today.
The painkilling lollipop, Actiq, is approved to treat chronic pain in cancer patients who are already on an opioid drug. But a recent study by Prime Therapeutics found the drug is being prescribed off-label for unapproved uses nearly 90% of the time.
For those suffering with the agonizing pain of late stage cancer, the painkiller on a stick brings fast relief because it is 80 times more potent than morphine, which makes it a prime drug to watch for law enforcement officials because of its potential for illicit use.
Actiq contains fentanyl, a drug classified as a Schedule II substance by the Drug Enforcement Administration, in the same category as cocaine, opium, methamphetamine and methadone. Schedule II drugs have the highest potential for abuse and overdose.
Fentanyl is also available in a skin patch, and overall, prescriptions for the drug have increased from about 0.5 million in 1994 to 6.95 million in 2005, according to IMS Health, a pharmaceutical industry tracking firm.
Actiq is only FDA approved for the management of pain in cancer patients who are already being treated with opioids because life-threatening conditions can occur at any dose in patients without a built-up tolerance for opioids.
According to a November 5, 1998, talk paper prepared for agency personnel at the time of the product's approval, the FDA approved Actiq, as a "new product developed specifically for cancer patients with severe pain that breaks through their regular narcotic therapy."
"Because Actiq may be fatal to children (as well as to adults not already taking opioid narcotics)," the paper said, "FDA approved Actiq under special regulations that restrict distribution as defined in a comprehensive risk management plan."
The FDA noted that the agency was "extremely concerned that this product be packaged and marketed to minimize the opportunity for diversion, abuse, or access by children."
However, the DEA, reports that fentanyl is being diverted by pharmacy theft, fraudulent prescriptions and illicit distribution by patients, physicians and pharmacists, and theft at nursing homes and other long-term care facilities. Actiq is typically sold on the street for $20-25 per lollipop and the drug's street name is "perc-a-pop."
In 2004, there were an estimated 8,000 emergency-room visits for fentanyl overdoses, according the US Substance Abuse and Mental Health Services Administration. Overdose can result in sudden death through respiratory arrest, cardiac arrest, severe respiratory depression, cardiovascular collapse or severe anaphylactic reaction, according to the agency. As of November 16, 2006, there were 653 deaths confirmed in the US since 2005.
On June 20, 2006, the US Department of Health and Human Service sent a letter to emergency department physicians and personnel to make them aware that the CDC was receiving increasing reports of fentanyl overdoses among illicit drug users in multiple states.
However, the fact that fentanyl cannot be detected with standard opiate screens has caused major problems. Currently, the ER protocol recommended is to assume the presence of fentanyl when a patient has symptoms of narcotic overdose but fails to test positive for heroin.
The Utah based drug maker Anesta Corp, a company acquired by Cephalon in 2000, developed Actiq. Since the Cephalon taker-over in 2000, Actiq has become one of the drugs most often prescribed off-label in the US.
Off-label refers to the use of drugs to treat conditions other than those approved by the FDA and can include prescribing drugs to unapproved populations such as children or the elderly or in higher doses than specified in the drug's labeling. Drug companies are not allowed to promote a drug for off-label uses, but doctors are permitted to prescribe a drug for any use they believe would be helpful.
The study released this month by Prime Therapeutics, a pharmacy benefit manager, analyzed 95 patient claims from a Midwestern commercial health plan from April through June 2005, and found that only 21 patients had a diagnosis of cancer or AIDS.
In addition, Prime found that only 11 of those 21 patients were taking a long-acting opioid painkiller. Overall, 84 of the 95 Actiq prescriptions, or nearly 90%, were off-label.
The Prime study also found that more than 15% of the prescriptions were for more than the recommended dose of 120 lollipops per month.
Government investigators have been looking into Cephalon's off-label promotion of Actiq in Connecticut and the Philadelphia area for two years, and the company is also being investigated by the FDA's Office of Criminal Investigations.
In November 2006, Connecticut Attorney General, Richard Blumenthal, concluded an investigation, which according to the Wall Street Journal, uncovered evidence that suggests Cephalon set high sales quotas for its sales representatives that could not be reached without promoting Actiq off-label.
Of course, just like every other company busted for off-label marketing in recent years, Cephalon claims it does not market Actiq off-label. But internal company documents reveal that sales reps were regularly sent to primary care doctors and specialists, who treat no cancer patients, armed with free coupons for doctors to pass out to patients.
For instance, Dr Stephen Leighton, a general practitioner who says he only has 3 cancer patients at any given time, told the Journal that a Cephalon saleswoman comes by once a month and gives him about 60 to 70 coupons for patients to trade in for six Actiq sticks.
He says the coupons spurred him to try the drug on patients with migraines and back pain and that he prescribes Actiq 15 to 20 times a month to patients who do not have cancer.
As a further indication of off-label promotion by Cephalon's Actiq sales force, the Journal cites a survey by the research firm ImpactRx, that found visits to non-cancer doctors increased 6-fold from 2002 to 2005.
According to company documents, Cephalon instructed sales reps to ask non-cancer doctors, "Do you have the potential to treat cancer pain?"
And even if the answer was no, they were instructed to give the doctors free coupons to pass out. One document quoted by the Journal, says the coupon program "is a remarkably effective promotional tool" that increased sales by 75 prescriptions a week at little cost.
Cephalon uses many tactics to influence doctor's prescribing habits. Mr Blumenthal's investigation found instances where Cephalon flew doctors to company funded seminars where paid speakers promoted the off-label use of Actiq. For instance, the Journal described a September 2003, New York seminar, where one of the topics was "Opioid use in headache."
At another October 2003, meeting, the Journal reports, a topic was "Use of Actiq in opioid-naive patients," even though the product label says it should be prescribed only to patients already taking opiate narcotics and can tolerate the drug.
In fact, the Actiq package insert states: "Do Not Take OTFC if you: are not already taking other opioid pain medicines for your constant (around-the-clock) cancer pain."
It also states: "Never use OTFC for short-term pain from injuries or surgery or pain that will go away in a few days, such as pain from doctor or dentist visits, or any short-lasting pain."
In 2002, Cephalon began zeroing in on neurologists and a document titled "Actiq in Migraine," instructed sales reps to pitch Actiq as "an ER on a stick."
The off-label use of Actiq by opioid naive patients has resulted in devastating consequences for some people. On January 22, 2006, the Free Press reported that the wife of a minister, former schoolteacher, and the mother of three sons, was arrested and charged with involuntary manslaughter because she gave Actiq, her cancer pain medication, to a friend who had a migraine and the friend died of a drug overdose.
On November 3, 2006, the Journal reported a case where a pregnant woman was prescribed Actiq for migraines by a neurologist. By the time of delivery, the woman, who the Journal noted had previously struggled with addictions to milder narcotics, was consuming five lollipops a day.
Upon birth, the infant was cranky and could not sleep and doctors told the woman that her son had become addicted to Actiq and was going through withdrawal.
When approving Actiq in 1998, the FDA set up a risk-management program with guidelines that said sales reps should "promote only to the target audiences," defined as oncologists, pain specialists, their nurses and office staff.
An provision of the program requires Cephalon to report whether "groups of physicians (such as a particular specialty)" who represent "potential off-label usage greater than 15 percent" are prescribing Actiq. If such a group exists, the FDA says, Cephalon should warn the doctors against the off-label use of the drug.
According to the market research firm, Verispan, for the first half of 2006, two groups of doctors exceeded the 15% quota, anesthesiologists at 29.5%, and physical medicine and rehabilitation specialists at 16%. Oncologists or cancer doctors accounted for only 1% of the prescriptions at retail pharmacies in the US, the Journal reports quoting Verispan.
In 2003, a company auditor, David Brennan, determined that Cephalon was not complying with the 15% rule, but says he was fired when he reported his findings to his superiors, according to a June 2004, wrongful termination lawsuit filed in Camden, NJ.
For Cephalon to act naive about the level of off-label prescribing of Actiq while the cash register is ringing up the sales is laughable. According to the November 3, 2006, report in the Journal, sales of Actiq went from $15 million in 2000, to more than $400 million today.
Flu Vaccines - Open Season
Evelyn Pringle December 15, 2006
For all the frantic, unvaccinated citizens fearing the "upcoming" peak of flu season—rest assured, coming down with a flu infection is the least of your worries.
Despite the governments statements urging individuals to vaccinate their children, the threat of an infantile influenza fatality is just about as serious as the dreaded hangnail.
Nonetheless, the Centers for Disease Control and Prevention (CDC) recently declared November 27 to December 3 as National Influenza Vaccination Week. The order stems from the governments "concern" that infection rates will soon come to a season high and, as having the flu is such a dire condition within the general population, the well-being of society rests on mass inoculation.
In fact, government agents are so adamant about protecting the nation that new recommendations have been made concerning vaccine administration, which, by the way, only protects against three specific strains of the countless, ever-evolving strains of the virus.
According to a November CDC publication, children less than two years of age are at high risk for infections and therefore, advocate ALL children aged 6 months to 18 years, in addition to pregnant women, be inoculated at least once a year.
Furthermore, if children under 9 years of age are getting injections for the first time, they are advised to receive two shots a month apart. CDC members say vaccinations should be administered in October or November, but since infections can occur as late as April "getting the vaccine in December or later still offers protection in most [I repeat, most] years."
That being said, one has to question why the Health Industry Distributors Association's (HIDA) April publishing states that demands for flu vaccines are highest in September and October "despite the public campaign to stretch flu shot 'season' into January."
Weird...there must be a mistake somewhere; surely these decisions result from valid scientific studies, as well as endless hours of analyses and discussion regarding the best interests of the public.
Comforting maybe, but accurate—not so much.
Despite lack of publicity, programs have been in place for almost 20 years now that acknowledge vaccine injuries; the National Vaccine Injury Compensation Program (VICP) was launched in 1988 as a means of "reimbursing" patients' adversely affected by inoculations, as if any amount of money can make up for a lifetime of suffering or more so, the death of a child. In addition, two years subsequent, the CDC and FDA created the Vaccine Adverse Event Reporting System (VAERS) so affected individuals or their representatives can report negative reactions occurring post-vaccination, which currently contains hundreds of thousands of documented tragedies.
Currently circulating flu vaccines contain the mercury-based preservative thimerosal. As if further explanation is needed, mercury is a horrible neurotoxin with a toxicity level 1000x higher than that of lead. Previously banned from over-the-counter products, animal vaccines, and ironically, in some states every other vaccine given to children, thimerosal remains in full concentration in flu vaccines.
Knowing that mercury levels in drinking water cannot exceed 2 parts per billion (ppb) without being toxic, or more appropriately, since any liquid containing more than 200 ppb of mercury is considered hazardous waste—it's sickening that circulating vials of flu vaccine has 50,000 ppb of mercury, the only exceptions being Sanofi-Pasteur's preservative free vaccines.
With four out of five manufacturers producing thimerosal-containing flu vaccines, over 90% of the 115 million doses distributed in America will contain 25 micrograms (mg) of mercury. This means that once the remaining 10% of mercury-free doses are used up, pregnant women and children will only have access to vials containing toxins measuring 250x the EPA's safety limit.
For a person to safely receive the amount of mercury in one vaccine, he or she would have to weigh over 550 lbs, making the recommendation for pregnant women and children nothing less than an act of brutality.
As told in the Journal of American Physicians and Surgeons (Summer 2006), pregnant women who get inoculated with thimerosal-containing vaccines will be exposed to 3.5x the organic mercury limit set by EPA officials, but since mercury accumulates in fetal tissue, especially those of the central nervous system, concentrations found in the developing fetus can exceed maternal levels by a factor of 4.3.
The results of such an attack are devastating. "...brain damage, mental retardation, incoordination, blindness, seizures, and inability to speak" are just a few of the fetal reactions found by the Agency for Toxic Substances and Disease Registry (ATSDR).
In addition, the team clearly identified mercury, of any form, as posing a threat to the nervous system. Children exposed to mercury experience brain functioning difficulties such as "...irritability, shyness, tremors, changes in vision or hearing, and memory problems", which further explains why American children are riddled with neurodevelopmental disorders ranging from autism and ADHD, to Guillain-Barre syndrome and speech disorders.
Americans will soon see for themselves what the selfish, money-driven vaccine industry has done for society. Not even officials will be able to deny the ever escalating autism epidemic when it stares them square in the eye; human flesh and blood, just as themselves, rather than numbers on a page in their office.
When the country's social security trust depletes due to the cost of special education and assisted living facilities for these disabled children, and there are neither enough patients nor finances remaining to support the vicious "damage-treat" circle created by manufacturers and their loyal elected lapdogs—who will be blamed then? Where will the fingers point when greed isn't paralyzing their conscience?
Time will soon provide the answer; unfortunately.
For those who still cannot seem to grasp the severity of thimerosal-containing vaccines, perhaps this will put things into perspective: if someone spilled a bottle of thimerosal indoors, the entire building would have to be evacuated immediately and remain so until a time when hazard crews thoroughly cleaned and secured the area.
It makes no sense to jeopardize a human life for a theoretical risk, especially not for a condition where, according to the November 30th publishing American's Concern for Skin Infection, Flu, Spreads Across the County, "Proper handwashing is the simplest and most effective way to prevent these infections."
As far as numbers go, the rate of influenza infections leaves something to be desired of the government's national quest for total inoculation. According to the CDC's Weekly Report: Influenza Summary Update (week ending November 18, 2006), World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System (NREVSS) laboratories have tested 15,707 samples of suspected influenza viruses, with only 477 testing positive. Of the positive results, 308 were reported from Florida alone.
Now, call it audacity, but that sounds more reassuring than anything. Not only does it show incidence rates to be low throughout the country, it further establishes grounds for the useless vaccine debate. Highly counterproductive on their part, the preceding data shows just how easily misdiagnoses occurs and therefore, shows how ambiguous the reported 36,000 annual flu infections are.
Though that's not all officials have up their sleeves, on top of being uncalled for and dangerous—the vaccines haven't even been proven effective in providing immunity!
Dating back to 1935, a study conducted on thimerosal's antibacterial and antifungal efficiency concluded the dangerous preservative, so to speak, was "35.3 times more toxic for embryonic chick heart tissue than for Staphylococcus aureus", making it, as said by the FDA, "no better than water" in killing bacteria.
Confirming suspicions was the 1948, Journal of the American Medical Association's publishing where authors concluded thimerosal was ineffective as a "disinfectant, germicide, and antiseptic," in addition to stating thimerosal "may not completely kill cultures of ...streptococci... in mice receiving an intraperitoneal injection of the culture-germicide mixture, after ten minutes' [sic] exposure of the organisms to the drugs... usually die [all but one of the 17 mice injected], and hemolytic streptococci can be isolated from the heart's blood after death of the mice."
Subsequently, an American Academy of Pediatrics (1985) study revealed thimerosal to be "...only weakly bactericidal... not an ideal preservative", which explains the FDA's 1980 proposal to ban thimerosal from topical ointments, skin creams, and other over-the-counter products, along with the 1999 decision to exclude the chemical from future vaccine production due to "safety and efficiency" concerns.
Though, perhaps 2004 brought the most irrefutable of evidence when the British-based Chiron factory was found to have serious contamination problems. The company's flu vaccine, Fluvirin, was pulled from distribution due to an unspecified number of lots containing an extremely dangerous microorganism, serratia, which is precisely the kind of threat thimerosal is supposed to eliminate.
Officials see the American public naively accepting whatever is put in front of them (i.e. Hepatitis B vaccines for 12 hour old babies, recent HPV vaccinations, unnecessary flu shots), and with the demolished state of check-and-balance within government bodies, officials are free to do whatever they choose without the fear of consequence.
As long as each scratches the others back, "scientific evidence" favoring the use of flu vaccines, and anything else they can think of, will continue regardless of necessity or safety. Manufacturers' charge between $9.00 to $12.50 for every 10-pack of flu vaccines, so with over 100 million ready for distribution this year its not surprising that every government agency is practically celebrating vaccination.
Though perhaps the true motivation for mass vaccination lies in the Medicare reimbursement rate for flu vaccine administration, which, from 2002 to 2005, increased more that four times from an average of $3.98 to $18.57; or maybe in the five-year, $274 million contract awarded to GlaxoSmithKline in May 2006 to develop cell-based production models for future flu vaccines, but then again, it could be related to the "measly" $429 million reported in Chiron's 2004 fourth quarter Fluvirin revenue, as opposed to the preceding years $555 million.
Whatever the situation, rather than simply accepting what is being pushed on us, its time to use some common sense and question why history is showing us one side of the story, while the government portrays a very different other.
Influenza infections, for the majority of citizens, are not life threatening, and even if they were—the occurrence rates do not justify injecting what both science and history has proven to be POISON into the desperately fragile bodies of infants and children.
For all the frantic, unvaccinated citizens fearing the "upcoming" peak of flu season—rest assured, coming down with a flu infection is the least of your worries.
Despite the governments statements urging individuals to vaccinate their children, the threat of an infantile influenza fatality is just about as serious as the dreaded hangnail.
Nonetheless, the Centers for Disease Control and Prevention (CDC) recently declared November 27 to December 3 as National Influenza Vaccination Week. The order stems from the governments "concern" that infection rates will soon come to a season high and, as having the flu is such a dire condition within the general population, the well-being of society rests on mass inoculation.
In fact, government agents are so adamant about protecting the nation that new recommendations have been made concerning vaccine administration, which, by the way, only protects against three specific strains of the countless, ever-evolving strains of the virus.
According to a November CDC publication, children less than two years of age are at high risk for infections and therefore, advocate ALL children aged 6 months to 18 years, in addition to pregnant women, be inoculated at least once a year.
Furthermore, if children under 9 years of age are getting injections for the first time, they are advised to receive two shots a month apart. CDC members say vaccinations should be administered in October or November, but since infections can occur as late as April "getting the vaccine in December or later still offers protection in most [I repeat, most] years."
That being said, one has to question why the Health Industry Distributors Association's (HIDA) April publishing states that demands for flu vaccines are highest in September and October "despite the public campaign to stretch flu shot 'season' into January."
Weird...there must be a mistake somewhere; surely these decisions result from valid scientific studies, as well as endless hours of analyses and discussion regarding the best interests of the public.
Comforting maybe, but accurate—not so much.
Despite lack of publicity, programs have been in place for almost 20 years now that acknowledge vaccine injuries; the National Vaccine Injury Compensation Program (VICP) was launched in 1988 as a means of "reimbursing" patients' adversely affected by inoculations, as if any amount of money can make up for a lifetime of suffering or more so, the death of a child. In addition, two years subsequent, the CDC and FDA created the Vaccine Adverse Event Reporting System (VAERS) so affected individuals or their representatives can report negative reactions occurring post-vaccination, which currently contains hundreds of thousands of documented tragedies.
Currently circulating flu vaccines contain the mercury-based preservative thimerosal. As if further explanation is needed, mercury is a horrible neurotoxin with a toxicity level 1000x higher than that of lead. Previously banned from over-the-counter products, animal vaccines, and ironically, in some states every other vaccine given to children, thimerosal remains in full concentration in flu vaccines.
Knowing that mercury levels in drinking water cannot exceed 2 parts per billion (ppb) without being toxic, or more appropriately, since any liquid containing more than 200 ppb of mercury is considered hazardous waste—it's sickening that circulating vials of flu vaccine has 50,000 ppb of mercury, the only exceptions being Sanofi-Pasteur's preservative free vaccines.
With four out of five manufacturers producing thimerosal-containing flu vaccines, over 90% of the 115 million doses distributed in America will contain 25 micrograms (mg) of mercury. This means that once the remaining 10% of mercury-free doses are used up, pregnant women and children will only have access to vials containing toxins measuring 250x the EPA's safety limit.
For a person to safely receive the amount of mercury in one vaccine, he or she would have to weigh over 550 lbs, making the recommendation for pregnant women and children nothing less than an act of brutality.
As told in the Journal of American Physicians and Surgeons (Summer 2006), pregnant women who get inoculated with thimerosal-containing vaccines will be exposed to 3.5x the organic mercury limit set by EPA officials, but since mercury accumulates in fetal tissue, especially those of the central nervous system, concentrations found in the developing fetus can exceed maternal levels by a factor of 4.3.
The results of such an attack are devastating. "...brain damage, mental retardation, incoordination, blindness, seizures, and inability to speak" are just a few of the fetal reactions found by the Agency for Toxic Substances and Disease Registry (ATSDR).
In addition, the team clearly identified mercury, of any form, as posing a threat to the nervous system. Children exposed to mercury experience brain functioning difficulties such as "...irritability, shyness, tremors, changes in vision or hearing, and memory problems", which further explains why American children are riddled with neurodevelopmental disorders ranging from autism and ADHD, to Guillain-Barre syndrome and speech disorders.
Americans will soon see for themselves what the selfish, money-driven vaccine industry has done for society. Not even officials will be able to deny the ever escalating autism epidemic when it stares them square in the eye; human flesh and blood, just as themselves, rather than numbers on a page in their office.
When the country's social security trust depletes due to the cost of special education and assisted living facilities for these disabled children, and there are neither enough patients nor finances remaining to support the vicious "damage-treat" circle created by manufacturers and their loyal elected lapdogs—who will be blamed then? Where will the fingers point when greed isn't paralyzing their conscience?
Time will soon provide the answer; unfortunately.
For those who still cannot seem to grasp the severity of thimerosal-containing vaccines, perhaps this will put things into perspective: if someone spilled a bottle of thimerosal indoors, the entire building would have to be evacuated immediately and remain so until a time when hazard crews thoroughly cleaned and secured the area.
It makes no sense to jeopardize a human life for a theoretical risk, especially not for a condition where, according to the November 30th publishing American's Concern for Skin Infection, Flu, Spreads Across the County, "Proper handwashing is the simplest and most effective way to prevent these infections."
As far as numbers go, the rate of influenza infections leaves something to be desired of the government's national quest for total inoculation. According to the CDC's Weekly Report: Influenza Summary Update (week ending November 18, 2006), World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System (NREVSS) laboratories have tested 15,707 samples of suspected influenza viruses, with only 477 testing positive. Of the positive results, 308 were reported from Florida alone.
Now, call it audacity, but that sounds more reassuring than anything. Not only does it show incidence rates to be low throughout the country, it further establishes grounds for the useless vaccine debate. Highly counterproductive on their part, the preceding data shows just how easily misdiagnoses occurs and therefore, shows how ambiguous the reported 36,000 annual flu infections are.
Though that's not all officials have up their sleeves, on top of being uncalled for and dangerous—the vaccines haven't even been proven effective in providing immunity!
Dating back to 1935, a study conducted on thimerosal's antibacterial and antifungal efficiency concluded the dangerous preservative, so to speak, was "35.3 times more toxic for embryonic chick heart tissue than for Staphylococcus aureus", making it, as said by the FDA, "no better than water" in killing bacteria.
Confirming suspicions was the 1948, Journal of the American Medical Association's publishing where authors concluded thimerosal was ineffective as a "disinfectant, germicide, and antiseptic," in addition to stating thimerosal "may not completely kill cultures of ...streptococci... in mice receiving an intraperitoneal injection of the culture-germicide mixture, after ten minutes' [sic] exposure of the organisms to the drugs... usually die [all but one of the 17 mice injected], and hemolytic streptococci can be isolated from the heart's blood after death of the mice."
Subsequently, an American Academy of Pediatrics (1985) study revealed thimerosal to be "...only weakly bactericidal... not an ideal preservative", which explains the FDA's 1980 proposal to ban thimerosal from topical ointments, skin creams, and other over-the-counter products, along with the 1999 decision to exclude the chemical from future vaccine production due to "safety and efficiency" concerns.
Though, perhaps 2004 brought the most irrefutable of evidence when the British-based Chiron factory was found to have serious contamination problems. The company's flu vaccine, Fluvirin, was pulled from distribution due to an unspecified number of lots containing an extremely dangerous microorganism, serratia, which is precisely the kind of threat thimerosal is supposed to eliminate.
Officials see the American public naively accepting whatever is put in front of them (i.e. Hepatitis B vaccines for 12 hour old babies, recent HPV vaccinations, unnecessary flu shots), and with the demolished state of check-and-balance within government bodies, officials are free to do whatever they choose without the fear of consequence.
As long as each scratches the others back, "scientific evidence" favoring the use of flu vaccines, and anything else they can think of, will continue regardless of necessity or safety. Manufacturers' charge between $9.00 to $12.50 for every 10-pack of flu vaccines, so with over 100 million ready for distribution this year its not surprising that every government agency is practically celebrating vaccination.
Though perhaps the true motivation for mass vaccination lies in the Medicare reimbursement rate for flu vaccine administration, which, from 2002 to 2005, increased more that four times from an average of $3.98 to $18.57; or maybe in the five-year, $274 million contract awarded to GlaxoSmithKline in May 2006 to develop cell-based production models for future flu vaccines, but then again, it could be related to the "measly" $429 million reported in Chiron's 2004 fourth quarter Fluvirin revenue, as opposed to the preceding years $555 million.
Whatever the situation, rather than simply accepting what is being pushed on us, its time to use some common sense and question why history is showing us one side of the story, while the government portrays a very different other.
Influenza infections, for the majority of citizens, are not life threatening, and even if they were—the occurrence rates do not justify injecting what both science and history has proven to be POISON into the desperately fragile bodies of infants and children.
Mental Illness Epidemic Hits US
Evelyn Pringle December 6, 2006
In the run-up to the December 13, 2006, meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, to review the suicidality data from adult SSRI studies, a host of newly identified disorders have been popping up in the media, all treatable with SSRIs.
The committee is expected to vote on whether the association between the selective serotonin reuptake inhibitor antidepressants and suicide in adults should be included in a Black Box warning label on all SSRIs, including Paxil, Prozac, Zoloft, Lexapro, and Celexa.
In light of all these new SSRI treatable disorders in the news, advocates who have been campaigning for the Black Box warning are wondering whether the SSRI makers have received some kind of inside information from the FDA, or the advisory committee members, that is not known to the public.
In fact, its quite possible that the public will have no access to any information that will be discussed at the hearing until the last minute, because the FDA announcement says: "The background material will become available no later than the day before the meeting and will be posted on FDA's Web site."
Critics say it seems odd that drug makers would be pouring money into studies to increase the use of SSRIs by finding new "disorders" to add to the DSM, at the very same time that stronger warnings to doctors and consumers on the use of the drugs are being considered.
The ever-expanding Diagnostic and Statistical Manual for Mental Disorders, was released in 1952, and had about 106 different mental disorders. It has since gone through 5 revisions and now has about 375.
The next version of what is referred to as the "Psychiatric Billing Bible," is not due out until 2011, but there are definite sightings of new "disorders" already on the horizon.
For instance, to the "untrained eye," a person afflicted with one of the newly identified ailments would probably be viewed as a typical and harmless everyday slob; but GlaxoSmithKline is apparently getting ready market Paxil as a cure for what a new study estimates to be 2 million everyday slobs in the US.
On November 10, 2006, HealthDay News discussed the study, published in the Journal of Psychiatric Research, that said Paxil is effective in treating people with a condition called "compulsive hoarding syndrome."
The researchers claim it has 3 main features: (1) severe anxiety prevents patients from throwing out seemingly worthless items; (2) patients are prone to acquiring things, sometimes leading to buying sprees; and (3) there is excessive clutter in the patient's home and work spaces.
Indecisiveness, procrastination and disorganization are also listed as other symptoms. Although the syndrome is found in patients with other diseases, such as dementia, Alzheimer's, schizophrenia and anorexia, the researches note, it is most often seen in patients with obsessive-compulsive disorder (OCD).
According to Healthday, the research team is not yet certain whether compulsive hoarding is a subtype of OCD, or a separate disorder. The study included 79 patients with OCD, and 32 were found to have "compulsive hoarding syndrome."
The good news is that the researchers say that both the hoarding and non-hoarding patients showed significant improvement in their symptoms when treated with Paxil.
Moving on to the next earth-shaking discovery, a study from Stanford University, in the October 2006, American Journal of Psychiatry, measured the prevalence of the dreaded, "compulsive buying disorder," and found that more than 1 in 20 adults in the US suffers from this ailment.
On October 3, 2006, the New York Times reported that compulsive buying is not a recognized psychiatric diagnosis, "but it is now being considered for inclusion in the next edition of the Diagnostic and Statistical Manual of Mental Disorders."
Lorrin Koran, a professor at Stanford, and senior author of the study, told the San Francisco Chronicle on October 13, 2006, that the results were a surprise. "It was thought previously that this was a disorder that primarily affects women," he said. "It turns out that it afflicts almost as many men."
The study found that about 6% of women and 5.5% of men show symptoms of "compulsive buying disorder," which is characterized by "an irresistible, intrusive and often senseless impulse to buy."
A finding that doubles the number of "compulsive buying" patients had to be good news for Forest Laboratories, the company that not only paid for the study, but believes its top money making SSRI drugs, Lexapro and Celexa, can be used to treat the disorder.
"My hope," Dr Koran told the Times, "is that people who think they have this disorder will seek help because available studies suggest that psychotherapy or medications help many compulsive buyers to stop."
Critics say from an economic stand point, the amount of money that could be saved by seeking treatment would depend on the shopaholic. If weekly therapy sessions cost $200 and the prescription for Lexapro runs $250 a month, a patient might end up in the hole.
Then there is the little-known disorder called "night-eating syndrome," discussed in an article titled, "Midnight munchies can signal big problems," in the October 26, 2006 Courier-Journal.
"Those who skip breakfast, eat more than half the day's calories after dinner and sometimes wake up and snack likely have this condition," the Courier reported.
"It's characterized by hormonal imbalances," the article says, "that lead to disturbed patterns of sleep and eating."
But help can be found in the old reliable SSRIs here as well. "Research at the University of Pennsylvania has found the antidepressant Zoloft helped," the Courier reports, "along with therapy to change eating and exercise patterns."
Considering the recent estimates that more than a third of all Americans are considered obese, with a good PR firm, Zoloft sales could go through the roof if the "night-eating syndrome," gets enough publicity because according to the Courier, "some research has found that up to 28 percent of obese people have it."
Zoloft is on a roll. In the October 2006, Journal of Clinical Psychiatry, researchers reported that low doses of Zoloft taken for 2 weeks before the menstrual period may be an effective treatment for moderate-to-severe premenstrual syndrome, or PMS.
Pfizer already managed to get Zoloft approved for the treatment of premenstrual dysphoric disorder (PMDD), referred to as a severe form of premenstrual syndrome.
Apparently, this study is meant to snag customers among the gals whose suffering is less severe. By the way, Pfizer paid for the study that found its drug helpful for PMS.
As for recruitment efforts aimed at the other gender, according to Health Day News on September 9, 2006, "SSRIs, which are used to treat depression and other psychiatric disorders, are now also used "off-label" as a treatment for premature ejaculation."
However, the article reports that experts say continued use of SSRIs can have negative side effects, such as psychiatric problems, skin reactions, weight gain, and loss of libido.
But not to be discouraged, researchers have gone ahead and developed a new SSRI, dapoxetine, just for premature ejaculation. "This is the first drug specifically developed for premature ejaculation," lead researcher Dr Jon Pryor, a professor and chairman of urologic surgery at the University of Minnesota, told Health Day News.
In a study, after 12 weeks, men taking a 30-milligram dose of the drug increased their time to ejaculation to 2.78 minutes, and men receiving a 60-milligram dose went for 3.32 minutes. For men taking a placebo, the time to ejaculation averaged 1.75 minutes.
Dr Pryor thinks this study will get people talking about the problem. "I hope this paper brings premature ejaculation out of the closet," he told Health Day News.
Moving on to the next SSRI miracle, in what is sure to be an extremely successful widening of the customer base for Paxil and Effexor, doctors at the University of Rochester Medical Center, now claim that nearly half of all Parkinson's patients suffer from depression, but they assume that depression is something they just have to live with.
Not so, say the doctors who announced a nationwide study to test the effectiveness of Paxil and Effexor with Parkinson's patients, in a September 19, 2006 Press Release.
The doctors say the study is funded by the "National Institute of Neurological Disorders and Stroke," which can mean one of two things. One, that tax payers are funding the research to find new uses for these drugs, or two, the drug makes are funneling money by way of contributions to the Institute, which the government Web site says it accepts.
The benefit that results from the funneling scheme is that when the doctors find the drugs effective, which they no doubt will, instead of saying the research was paid for by the drug's makers, it lists the government as the funding source.
Either way, no tax dollars should be spent on this type of study. If there is funding available for research on Parkinson's disease, it should be spent on finding a cure.
If GlaxoSmithKline and Wyeth want to go on a wild-goose chase looking for new uses for Paxil and Effexor, let them do it on their own dime and time. And after that, they need to apply for approval of any new use with the FDA, instead of using a trumped up study as justification for prescribing the drugs off-label.
In a completely different field of medicine, on October 30, 2006, Reuters reported that researchers at Jerusalem's Hebrew University discovered what surely must be described as another scientific wonder. Their study found that depression can lead to brittle bones and the Israeli scientists suggest that SSRIs can be used to treat osteoporosis.
They reached this conclusion after they found that mice that were given drugs to induce human-like depression suffered a loss of bone mass, but after receiving SSRIs, their bone density increased, along with their level of activity and social interaction.
According to Reuters, an earlier study at the Forsyth Institute in Boston also found that Prozac increased bone mass - in mice.
When mulling over all the new "disorders" being considered for the DSM, it should be recognized that according to a study in the April 2006, Psychotherapy and Psychosomatics journal, 80% of the members on the expert panels, involved in approving most of the off-the-wall disorders for the DSM in recent years, had undisclosed financial ties to the drug companies whose drugs would be used to treat the disorders approved.
In fact, the review found that 100% of the experts involved in writing diagnostic criteria for depression and schizophrenia had undisclosed financial relationships with the drug companies who market drugs to treat those conditions.
In the run-up to the December 13, 2006, meeting of the FDA's Psychopharmacologic Drugs Advisory Committee, to review the suicidality data from adult SSRI studies, a host of newly identified disorders have been popping up in the media, all treatable with SSRIs.
The committee is expected to vote on whether the association between the selective serotonin reuptake inhibitor antidepressants and suicide in adults should be included in a Black Box warning label on all SSRIs, including Paxil, Prozac, Zoloft, Lexapro, and Celexa.
In light of all these new SSRI treatable disorders in the news, advocates who have been campaigning for the Black Box warning are wondering whether the SSRI makers have received some kind of inside information from the FDA, or the advisory committee members, that is not known to the public.
In fact, its quite possible that the public will have no access to any information that will be discussed at the hearing until the last minute, because the FDA announcement says: "The background material will become available no later than the day before the meeting and will be posted on FDA's Web site."
Critics say it seems odd that drug makers would be pouring money into studies to increase the use of SSRIs by finding new "disorders" to add to the DSM, at the very same time that stronger warnings to doctors and consumers on the use of the drugs are being considered.
The ever-expanding Diagnostic and Statistical Manual for Mental Disorders, was released in 1952, and had about 106 different mental disorders. It has since gone through 5 revisions and now has about 375.
The next version of what is referred to as the "Psychiatric Billing Bible," is not due out until 2011, but there are definite sightings of new "disorders" already on the horizon.
For instance, to the "untrained eye," a person afflicted with one of the newly identified ailments would probably be viewed as a typical and harmless everyday slob; but GlaxoSmithKline is apparently getting ready market Paxil as a cure for what a new study estimates to be 2 million everyday slobs in the US.
On November 10, 2006, HealthDay News discussed the study, published in the Journal of Psychiatric Research, that said Paxil is effective in treating people with a condition called "compulsive hoarding syndrome."
The researchers claim it has 3 main features: (1) severe anxiety prevents patients from throwing out seemingly worthless items; (2) patients are prone to acquiring things, sometimes leading to buying sprees; and (3) there is excessive clutter in the patient's home and work spaces.
Indecisiveness, procrastination and disorganization are also listed as other symptoms. Although the syndrome is found in patients with other diseases, such as dementia, Alzheimer's, schizophrenia and anorexia, the researches note, it is most often seen in patients with obsessive-compulsive disorder (OCD).
According to Healthday, the research team is not yet certain whether compulsive hoarding is a subtype of OCD, or a separate disorder. The study included 79 patients with OCD, and 32 were found to have "compulsive hoarding syndrome."
The good news is that the researchers say that both the hoarding and non-hoarding patients showed significant improvement in their symptoms when treated with Paxil.
Moving on to the next earth-shaking discovery, a study from Stanford University, in the October 2006, American Journal of Psychiatry, measured the prevalence of the dreaded, "compulsive buying disorder," and found that more than 1 in 20 adults in the US suffers from this ailment.
On October 3, 2006, the New York Times reported that compulsive buying is not a recognized psychiatric diagnosis, "but it is now being considered for inclusion in the next edition of the Diagnostic and Statistical Manual of Mental Disorders."
Lorrin Koran, a professor at Stanford, and senior author of the study, told the San Francisco Chronicle on October 13, 2006, that the results were a surprise. "It was thought previously that this was a disorder that primarily affects women," he said. "It turns out that it afflicts almost as many men."
The study found that about 6% of women and 5.5% of men show symptoms of "compulsive buying disorder," which is characterized by "an irresistible, intrusive and often senseless impulse to buy."
A finding that doubles the number of "compulsive buying" patients had to be good news for Forest Laboratories, the company that not only paid for the study, but believes its top money making SSRI drugs, Lexapro and Celexa, can be used to treat the disorder.
"My hope," Dr Koran told the Times, "is that people who think they have this disorder will seek help because available studies suggest that psychotherapy or medications help many compulsive buyers to stop."
Critics say from an economic stand point, the amount of money that could be saved by seeking treatment would depend on the shopaholic. If weekly therapy sessions cost $200 and the prescription for Lexapro runs $250 a month, a patient might end up in the hole.
Then there is the little-known disorder called "night-eating syndrome," discussed in an article titled, "Midnight munchies can signal big problems," in the October 26, 2006 Courier-Journal.
"Those who skip breakfast, eat more than half the day's calories after dinner and sometimes wake up and snack likely have this condition," the Courier reported.
"It's characterized by hormonal imbalances," the article says, "that lead to disturbed patterns of sleep and eating."
But help can be found in the old reliable SSRIs here as well. "Research at the University of Pennsylvania has found the antidepressant Zoloft helped," the Courier reports, "along with therapy to change eating and exercise patterns."
Considering the recent estimates that more than a third of all Americans are considered obese, with a good PR firm, Zoloft sales could go through the roof if the "night-eating syndrome," gets enough publicity because according to the Courier, "some research has found that up to 28 percent of obese people have it."
Zoloft is on a roll. In the October 2006, Journal of Clinical Psychiatry, researchers reported that low doses of Zoloft taken for 2 weeks before the menstrual period may be an effective treatment for moderate-to-severe premenstrual syndrome, or PMS.
Pfizer already managed to get Zoloft approved for the treatment of premenstrual dysphoric disorder (PMDD), referred to as a severe form of premenstrual syndrome.
Apparently, this study is meant to snag customers among the gals whose suffering is less severe. By the way, Pfizer paid for the study that found its drug helpful for PMS.
As for recruitment efforts aimed at the other gender, according to Health Day News on September 9, 2006, "SSRIs, which are used to treat depression and other psychiatric disorders, are now also used "off-label" as a treatment for premature ejaculation."
However, the article reports that experts say continued use of SSRIs can have negative side effects, such as psychiatric problems, skin reactions, weight gain, and loss of libido.
But not to be discouraged, researchers have gone ahead and developed a new SSRI, dapoxetine, just for premature ejaculation. "This is the first drug specifically developed for premature ejaculation," lead researcher Dr Jon Pryor, a professor and chairman of urologic surgery at the University of Minnesota, told Health Day News.
In a study, after 12 weeks, men taking a 30-milligram dose of the drug increased their time to ejaculation to 2.78 minutes, and men receiving a 60-milligram dose went for 3.32 minutes. For men taking a placebo, the time to ejaculation averaged 1.75 minutes.
Dr Pryor thinks this study will get people talking about the problem. "I hope this paper brings premature ejaculation out of the closet," he told Health Day News.
Moving on to the next SSRI miracle, in what is sure to be an extremely successful widening of the customer base for Paxil and Effexor, doctors at the University of Rochester Medical Center, now claim that nearly half of all Parkinson's patients suffer from depression, but they assume that depression is something they just have to live with.
Not so, say the doctors who announced a nationwide study to test the effectiveness of Paxil and Effexor with Parkinson's patients, in a September 19, 2006 Press Release.
The doctors say the study is funded by the "National Institute of Neurological Disorders and Stroke," which can mean one of two things. One, that tax payers are funding the research to find new uses for these drugs, or two, the drug makes are funneling money by way of contributions to the Institute, which the government Web site says it accepts.
The benefit that results from the funneling scheme is that when the doctors find the drugs effective, which they no doubt will, instead of saying the research was paid for by the drug's makers, it lists the government as the funding source.
Either way, no tax dollars should be spent on this type of study. If there is funding available for research on Parkinson's disease, it should be spent on finding a cure.
If GlaxoSmithKline and Wyeth want to go on a wild-goose chase looking for new uses for Paxil and Effexor, let them do it on their own dime and time. And after that, they need to apply for approval of any new use with the FDA, instead of using a trumped up study as justification for prescribing the drugs off-label.
In a completely different field of medicine, on October 30, 2006, Reuters reported that researchers at Jerusalem's Hebrew University discovered what surely must be described as another scientific wonder. Their study found that depression can lead to brittle bones and the Israeli scientists suggest that SSRIs can be used to treat osteoporosis.
They reached this conclusion after they found that mice that were given drugs to induce human-like depression suffered a loss of bone mass, but after receiving SSRIs, their bone density increased, along with their level of activity and social interaction.
According to Reuters, an earlier study at the Forsyth Institute in Boston also found that Prozac increased bone mass - in mice.
When mulling over all the new "disorders" being considered for the DSM, it should be recognized that according to a study in the April 2006, Psychotherapy and Psychosomatics journal, 80% of the members on the expert panels, involved in approving most of the off-the-wall disorders for the DSM in recent years, had undisclosed financial ties to the drug companies whose drugs would be used to treat the disorders approved.
In fact, the review found that 100% of the experts involved in writing diagnostic criteria for depression and schizophrenia had undisclosed financial relationships with the drug companies who market drugs to treat those conditions.
Big Pharma's Battle Over Direct to Consumer Advertising
Evelyn Pringle November 21, 2006
Big Pharma has Americans running to the doctor demanding the latest advertised drug to treat the latest promoted disorder based on the latest commercial they see on TV.
According to a report by CBS News on October 22, 2006, the United States makes up just 5 percent of the world's population, "but it accounts for a whopping 42 percent of the world's spending on prescription drugs — more than $250 billion just last year."
And yet, when compared to nearly two dozen other industrialized countries, the US has the highest infant mortality rate and the lowest life expectancy for people who have reached the age of 60, according to a September 20, 2006 report by The Commonwealth Fund's Commission on a High Performance Health System.
In August 1997, the FDA relaxed the restrictions on television and radio DTC advertising, permitting drug companies to mention both the name of the drug, and the disease or symptoms that the medication treats in the same ad.
Industry critics say the end result of the easing of restrictions has been massive advertising campaigns that regularly promote drugs for off-label unapproved uses, understate risks and overstate benefits, and make efficacy and safety claims that are not backed up by clinical studies.
The most common strategy used these days to mass-market a drug is "disease mongering" to increase the number of potential customers diagnosed with a new disorder. Big Pharma even hires PR firms to come up with the most sellable names for the disorders.
"At Brand Institute, Inc., a Miami marketing firm," CBS reports, "naming, or re-naming, syndromes for drug companies is 20 percent of the business."
The key, the company's president, Jim Dettore, told CBS, is a name that describes the symptom in a nice way, making it OK to seek help, preferably with the client's drug. "These acronyms allow them to communicate more effectively with less pressure," Mr Dettore said.
Disease mongering through DTC advertising can dramatically increase the sales of just about any product. For instance, Lamisil is used to treat toenail fungus. The main adverse effect of the fungus is that it turns the toenail yellow and it can hurt, but no one has died of toenail fungus.
However, people taking Lamisil have died from the drug, according to "Pill Pushers," in Forbes.com on May 8, 2006, "Federal regulators have linked the drug to 16 cases of liver failure, including 11 deaths."
The Forbes article reports that 10 million Americans have taken Lamisil, at a cost of $850 for a 3-month treatment, even though the drug only cures the problem in 38% of the patients.
The advertising campaign for the drug featured a cartoon character called "Digger the Dermatophyte" being crushed by a giant Lamisil pill.
The ad so overstated the benefits of the drug, Forbes said, that regulators objected and the company was forced to pull the ad. But the campaign was obviously a huge success because in 2004, Lamisil sales increased by 19% to reach $1.2 billion worldwide and held steady in 2005.
Prescription drug advertising has provided a steady stream of revenue for print and broadcast media since the FDA lifted the restrictions. IMS Health, an industry tracking firm, reports that overall in 2004, drug companies spent about $4 billion on DTC advertising.
According to contributing editor, Judy Lieberman, in the July-August 2005, Columbia Journalism Review, the CJR monitored the evening newscasts on ABC, CBS, and NBC for one week in April 2005, and found that network viewers saw an average of 16 ads for prescription drugs and on average 18 commercials for over-the-counter drugs every night.
In 1999, the five networks, including Fox News and CNN, received $569 million in advertising revenue from drug companies, according to TNS Media Intelligence. But by 2004, advertising revenue nearly tripled to $1.5 billion, according to Ms Lieberman.
As far as advertising dollars spent on print media, at the end of 2004, Ms Lieberman found that drug company ads for Time magazine totaled $67 million; $43 million for Newsweek; and the New York Times took in $13 million.
Advertising dollars pay big dividends. A 2003 Harvard Public Health study commissioned by the Kaiser Family Foundation determined that for every $1 spent on direct advertising, drug companies took in an additional $4.20 in sales.
No other drugs in history have received more promotion and media attention than the Cox 2 inhibitors which include Merck's Vioxx, and Celebrex and Bextra, by GD Searle, a company bought later by Pharmacia. Celebrex went on the market in January 1999, and Vioxx was FDA approved on May 20, 1999.
The study, "Promotion of Prescription Drugs to Consumers: A Look at the Numbers," in the February 14, 2002, New England Journal of Medicine, found Vioxx to be the most highly promoted drug in 2000 with Merck spending $161 million.
The only real selling point for the Cox 2 inhibitors was the claim by drug makers that the new medications supposedly did not cause stomach bleeding and ulcers that sometimes resulted after lengthily use of painkillers like aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs (NSAIDs).
That assertion was untrue and in fact, the FDA refused to allow the companies to make that claim in advertising or the drug's guidelines for use, since it was not backed up by any clinical studies. The package insert that did accompany the new pain relievers contained the same warning as the older NSAIDs.
But never known to let a little FDA warning stand in the way of profits, in no time at all the drug makers had the mainstream press and medical literature flooded with ghost-written articles and press releases with the names of "experts" attached, describing the bleeding problems and deaths caused by NSAIDs, followed by the effectiveness and safety of the Cox 2 inhibitors.
For instance, Vioxx was approved on May 20, 1999, two days later on May 22, 1999, the Washington Post ran the headline, "FDA Approves Pain Reliever with Fewer Side Effects," and article reported that NSAIDs cause "107,000 hospitalizations and the death of 16,500 people every year."
Never mind that the same year, a survey by the Centers for Disease Control reported that less than 6,000 people died the year before from any and all types of gastrointestinal bleeding disorders combined.
However, apparently Merck found a different group of people to survey because on the December 26, 2000, Jim Lahrer News Hour, Dr Roger Perlmutter, who was listed as overseeing basic research at Merck, said, "Each year something in excess of 8,500 deaths and more than 50,000 hospitalizations result from the chronic use of non-steroidal anti-inflammatory drugs."
He claimed that NSAIDs produced dangerous and even deadly side effects in about 4% of patients, including bleeding in the stomach or intestine. "The result," Dr Perlmutter said, "is an increase in ulceration and severe gastrointestinal complications."
At the time of their arrival on the market, Wall Street analysts referred to the launch of the Cox 2 inhibitors as the most successful marketing coup in the history of the pharmaceutical industry.
Drug company sales reps swarmed into medical clinics with free samples galore and millions of patients began demanded prescriptions for the new miracle arthritis pain relievers and sales took off the minute the drugs hit the shelves.
Pain relief drugs that cost pennies a day were history and millions of patients were conned into forking over three to 6 bucks for pills that were no more effective, and as it turns out, much less safe than aspirins.
Reportedly, over 100 million people were prescribed Vioxx and massive DTC advertising has been singled out as the main factor that led to an unusually high number of patients being prescribed the drug before the lethal side effects were known.
In an August 30, 2005, interview with Manette Loudon, career FDA scientist, Dr David Graham said the Vioxx disaster would not have been half as bad if not for DTC advertising. "I submit," he said, "that the numbers would have been far lower than what they were."
Due to heavy marketing of new drugs like Vioxx, Dr Graham says, patients and doctors will often use a drug that is no better than others already on the market, even though the FDA does not require that new drugs be equivalent to, or better than, the drugs that are already there. All they have to prove is that a drug works better than a sugar pill, he says.
Merck finally withdrew Vioxx from the market in September 2004, but not before an "estimated 88,000-140,000 excess cases of serious coronary heart disease probably occurred in the USA over the market life of Vioxx," according to Dr Graham.
The US national estimate of the case-fatality rate was 44%, he says, which suggests that many of the excess cases attributable to Vioxx use were fatal.
An expert witness in one of the Vioxx trials, the respected biostatistician, Richard Kronmal, from the University of Washington, testified that as early as April 2001, Merck had data that showed a 4-fold increase risk of death in Vioxx patients from a clinical trial that Merck was conducting to determine whether the drug was effective in treating Alzheimer's and yet the company continued the study until 2003.
"They had evidence that they were potentially killing people and they let that trial go on for another two years," he said.
According to Merck, as of September 30, 2006, there are close to 24,000 Vioxx-related lawsuits filed against the company on behalf of over 41,000 plaintiff's groups, and an additional 275 class actions seeking personal injury damages or reimbursement for the costs of buying a drug that Merck misrepresented as being safe and more effective than it actually was.
The Vioxx debacle has placed Merck, the FDA, and the issue of drug safety on center stage and the spotlight is focused on the faulty process by which new drugs are approved and advertised along with the inadequate post approval safety surveillance program.
Lawmakers on both sides of the isle have accused FDA officials of being too cozy with Merck and the over-promotion of Vioxx has led to several pieces of reform legislation aimed at the FDA's lack of regulatory efforts toward curtailing DTC advertising abuses.
On November 17, 2006, the Senate Committee on Health, Education, Labor, and Pensions, held a hearing and gave Democrats their first chance to exercise their muscle to demonstrate how they will deal with the FDA's stance on DTC once they become the majority in Congress next year.
The hearing titled, "Building a 21st Century FDA: Proposals to Improve Drug Safety and Innovation," focused on Senate Bill 3807, the "Enhancing Drug Safe and Innovation Act of 2006," co-sponsored by committee chairman, Senator Michael Enzi (R-WY), and Senator Ted Kennedy (D-MA), the next chairman of the committee.
A prepared statement from Senator Enzi's office said the Senate Bill will "ensure that drug safety is not an afterthought," and Senator Kennedy said that as chairman, he plans to hold a series of hearings aimed at FDA oversight early in 2007.
Dr Steven Nissen, MD, from the Cleveland Clinic, testified at the hearing and told the panel that the post marketing surveillance system for prescription drugs functions poorly. "Adverse event reporting," he notes, "is voluntary and studies show that only 1 to 10% of serious adverse events are ever reported to the Agency."
And therefore, he informed the committee, "the actual incidence of serious or life-threatened complications cannot be calculated accurately."
Dr Nissen also said that DTC advertising requires legislative action. "The standard for acceptable DTC advertising," he told the panel, "should require demonstration of a compelling public health benefit for this type of communication."
"Drugs with an addiction potential, such as sleeping medication," he said, "should be specifically prohibited from consumer advertising."
As it is now, according to Pill Pushers, by Forbes on May 8, 2006, prescriptions for sleeping pills increased 48% in five years to 43 million prescriptions annually, driven by the DTC advertising of Ambien and Lunesta, and sales in the same period rose to $2.76 billion.
Jim Guest, president and CEO of Consumers Union, publisher of Consumer Reports, testified on behalf of Consumers Union, and asked lawmakers to limit advertising of new drugs for three years, instead of the two year requirement in the Senate bill, because most adverse events do not show up until nearly seven years after a drug has been on the market, he said.
However, a Johnson & Johnson vice president, Adrian Thomas, told the committee that a 2-year moratorium on DTC advertising for newly approved drugs "represents a troubling change."
"Appropriate DTC advertising plays a valuable role in educating patients about diseases and treatments," Mr Thomas told the panel.
"The value of this education to patients," he continued, "as well as important First Amendment issues that arise from banning truthful speech, even for a period of time, must be carefully considered before legislating in this area."
Mr Guest testified that consumer advertising is not an educational tool, but rather a vehicle to mass market drugs before the serious side effects become known. "The direct-to-consumer advertising," he told the panel, "is not a good way for consumers, physicians or medical providers to be informed."
Big Pharma has Americans running to the doctor demanding the latest advertised drug to treat the latest promoted disorder based on the latest commercial they see on TV.
According to a report by CBS News on October 22, 2006, the United States makes up just 5 percent of the world's population, "but it accounts for a whopping 42 percent of the world's spending on prescription drugs — more than $250 billion just last year."
And yet, when compared to nearly two dozen other industrialized countries, the US has the highest infant mortality rate and the lowest life expectancy for people who have reached the age of 60, according to a September 20, 2006 report by The Commonwealth Fund's Commission on a High Performance Health System.
In August 1997, the FDA relaxed the restrictions on television and radio DTC advertising, permitting drug companies to mention both the name of the drug, and the disease or symptoms that the medication treats in the same ad.
Industry critics say the end result of the easing of restrictions has been massive advertising campaigns that regularly promote drugs for off-label unapproved uses, understate risks and overstate benefits, and make efficacy and safety claims that are not backed up by clinical studies.
The most common strategy used these days to mass-market a drug is "disease mongering" to increase the number of potential customers diagnosed with a new disorder. Big Pharma even hires PR firms to come up with the most sellable names for the disorders.
"At Brand Institute, Inc., a Miami marketing firm," CBS reports, "naming, or re-naming, syndromes for drug companies is 20 percent of the business."
The key, the company's president, Jim Dettore, told CBS, is a name that describes the symptom in a nice way, making it OK to seek help, preferably with the client's drug. "These acronyms allow them to communicate more effectively with less pressure," Mr Dettore said.
Disease mongering through DTC advertising can dramatically increase the sales of just about any product. For instance, Lamisil is used to treat toenail fungus. The main adverse effect of the fungus is that it turns the toenail yellow and it can hurt, but no one has died of toenail fungus.
However, people taking Lamisil have died from the drug, according to "Pill Pushers," in Forbes.com on May 8, 2006, "Federal regulators have linked the drug to 16 cases of liver failure, including 11 deaths."
The Forbes article reports that 10 million Americans have taken Lamisil, at a cost of $850 for a 3-month treatment, even though the drug only cures the problem in 38% of the patients.
The advertising campaign for the drug featured a cartoon character called "Digger the Dermatophyte" being crushed by a giant Lamisil pill.
The ad so overstated the benefits of the drug, Forbes said, that regulators objected and the company was forced to pull the ad. But the campaign was obviously a huge success because in 2004, Lamisil sales increased by 19% to reach $1.2 billion worldwide and held steady in 2005.
Prescription drug advertising has provided a steady stream of revenue for print and broadcast media since the FDA lifted the restrictions. IMS Health, an industry tracking firm, reports that overall in 2004, drug companies spent about $4 billion on DTC advertising.
According to contributing editor, Judy Lieberman, in the July-August 2005, Columbia Journalism Review, the CJR monitored the evening newscasts on ABC, CBS, and NBC for one week in April 2005, and found that network viewers saw an average of 16 ads for prescription drugs and on average 18 commercials for over-the-counter drugs every night.
In 1999, the five networks, including Fox News and CNN, received $569 million in advertising revenue from drug companies, according to TNS Media Intelligence. But by 2004, advertising revenue nearly tripled to $1.5 billion, according to Ms Lieberman.
As far as advertising dollars spent on print media, at the end of 2004, Ms Lieberman found that drug company ads for Time magazine totaled $67 million; $43 million for Newsweek; and the New York Times took in $13 million.
Advertising dollars pay big dividends. A 2003 Harvard Public Health study commissioned by the Kaiser Family Foundation determined that for every $1 spent on direct advertising, drug companies took in an additional $4.20 in sales.
No other drugs in history have received more promotion and media attention than the Cox 2 inhibitors which include Merck's Vioxx, and Celebrex and Bextra, by GD Searle, a company bought later by Pharmacia. Celebrex went on the market in January 1999, and Vioxx was FDA approved on May 20, 1999.
The study, "Promotion of Prescription Drugs to Consumers: A Look at the Numbers," in the February 14, 2002, New England Journal of Medicine, found Vioxx to be the most highly promoted drug in 2000 with Merck spending $161 million.
The only real selling point for the Cox 2 inhibitors was the claim by drug makers that the new medications supposedly did not cause stomach bleeding and ulcers that sometimes resulted after lengthily use of painkillers like aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs (NSAIDs).
That assertion was untrue and in fact, the FDA refused to allow the companies to make that claim in advertising or the drug's guidelines for use, since it was not backed up by any clinical studies. The package insert that did accompany the new pain relievers contained the same warning as the older NSAIDs.
But never known to let a little FDA warning stand in the way of profits, in no time at all the drug makers had the mainstream press and medical literature flooded with ghost-written articles and press releases with the names of "experts" attached, describing the bleeding problems and deaths caused by NSAIDs, followed by the effectiveness and safety of the Cox 2 inhibitors.
For instance, Vioxx was approved on May 20, 1999, two days later on May 22, 1999, the Washington Post ran the headline, "FDA Approves Pain Reliever with Fewer Side Effects," and article reported that NSAIDs cause "107,000 hospitalizations and the death of 16,500 people every year."
Never mind that the same year, a survey by the Centers for Disease Control reported that less than 6,000 people died the year before from any and all types of gastrointestinal bleeding disorders combined.
However, apparently Merck found a different group of people to survey because on the December 26, 2000, Jim Lahrer News Hour, Dr Roger Perlmutter, who was listed as overseeing basic research at Merck, said, "Each year something in excess of 8,500 deaths and more than 50,000 hospitalizations result from the chronic use of non-steroidal anti-inflammatory drugs."
He claimed that NSAIDs produced dangerous and even deadly side effects in about 4% of patients, including bleeding in the stomach or intestine. "The result," Dr Perlmutter said, "is an increase in ulceration and severe gastrointestinal complications."
At the time of their arrival on the market, Wall Street analysts referred to the launch of the Cox 2 inhibitors as the most successful marketing coup in the history of the pharmaceutical industry.
Drug company sales reps swarmed into medical clinics with free samples galore and millions of patients began demanded prescriptions for the new miracle arthritis pain relievers and sales took off the minute the drugs hit the shelves.
Pain relief drugs that cost pennies a day were history and millions of patients were conned into forking over three to 6 bucks for pills that were no more effective, and as it turns out, much less safe than aspirins.
Reportedly, over 100 million people were prescribed Vioxx and massive DTC advertising has been singled out as the main factor that led to an unusually high number of patients being prescribed the drug before the lethal side effects were known.
In an August 30, 2005, interview with Manette Loudon, career FDA scientist, Dr David Graham said the Vioxx disaster would not have been half as bad if not for DTC advertising. "I submit," he said, "that the numbers would have been far lower than what they were."
Due to heavy marketing of new drugs like Vioxx, Dr Graham says, patients and doctors will often use a drug that is no better than others already on the market, even though the FDA does not require that new drugs be equivalent to, or better than, the drugs that are already there. All they have to prove is that a drug works better than a sugar pill, he says.
Merck finally withdrew Vioxx from the market in September 2004, but not before an "estimated 88,000-140,000 excess cases of serious coronary heart disease probably occurred in the USA over the market life of Vioxx," according to Dr Graham.
The US national estimate of the case-fatality rate was 44%, he says, which suggests that many of the excess cases attributable to Vioxx use were fatal.
An expert witness in one of the Vioxx trials, the respected biostatistician, Richard Kronmal, from the University of Washington, testified that as early as April 2001, Merck had data that showed a 4-fold increase risk of death in Vioxx patients from a clinical trial that Merck was conducting to determine whether the drug was effective in treating Alzheimer's and yet the company continued the study until 2003.
"They had evidence that they were potentially killing people and they let that trial go on for another two years," he said.
According to Merck, as of September 30, 2006, there are close to 24,000 Vioxx-related lawsuits filed against the company on behalf of over 41,000 plaintiff's groups, and an additional 275 class actions seeking personal injury damages or reimbursement for the costs of buying a drug that Merck misrepresented as being safe and more effective than it actually was.
The Vioxx debacle has placed Merck, the FDA, and the issue of drug safety on center stage and the spotlight is focused on the faulty process by which new drugs are approved and advertised along with the inadequate post approval safety surveillance program.
Lawmakers on both sides of the isle have accused FDA officials of being too cozy with Merck and the over-promotion of Vioxx has led to several pieces of reform legislation aimed at the FDA's lack of regulatory efforts toward curtailing DTC advertising abuses.
On November 17, 2006, the Senate Committee on Health, Education, Labor, and Pensions, held a hearing and gave Democrats their first chance to exercise their muscle to demonstrate how they will deal with the FDA's stance on DTC once they become the majority in Congress next year.
The hearing titled, "Building a 21st Century FDA: Proposals to Improve Drug Safety and Innovation," focused on Senate Bill 3807, the "Enhancing Drug Safe and Innovation Act of 2006," co-sponsored by committee chairman, Senator Michael Enzi (R-WY), and Senator Ted Kennedy (D-MA), the next chairman of the committee.
A prepared statement from Senator Enzi's office said the Senate Bill will "ensure that drug safety is not an afterthought," and Senator Kennedy said that as chairman, he plans to hold a series of hearings aimed at FDA oversight early in 2007.
Dr Steven Nissen, MD, from the Cleveland Clinic, testified at the hearing and told the panel that the post marketing surveillance system for prescription drugs functions poorly. "Adverse event reporting," he notes, "is voluntary and studies show that only 1 to 10% of serious adverse events are ever reported to the Agency."
And therefore, he informed the committee, "the actual incidence of serious or life-threatened complications cannot be calculated accurately."
Dr Nissen also said that DTC advertising requires legislative action. "The standard for acceptable DTC advertising," he told the panel, "should require demonstration of a compelling public health benefit for this type of communication."
"Drugs with an addiction potential, such as sleeping medication," he said, "should be specifically prohibited from consumer advertising."
As it is now, according to Pill Pushers, by Forbes on May 8, 2006, prescriptions for sleeping pills increased 48% in five years to 43 million prescriptions annually, driven by the DTC advertising of Ambien and Lunesta, and sales in the same period rose to $2.76 billion.
Jim Guest, president and CEO of Consumers Union, publisher of Consumer Reports, testified on behalf of Consumers Union, and asked lawmakers to limit advertising of new drugs for three years, instead of the two year requirement in the Senate bill, because most adverse events do not show up until nearly seven years after a drug has been on the market, he said.
However, a Johnson & Johnson vice president, Adrian Thomas, told the committee that a 2-year moratorium on DTC advertising for newly approved drugs "represents a troubling change."
"Appropriate DTC advertising plays a valuable role in educating patients about diseases and treatments," Mr Thomas told the panel.
"The value of this education to patients," he continued, "as well as important First Amendment issues that arise from banning truthful speech, even for a period of time, must be carefully considered before legislating in this area."
Mr Guest testified that consumer advertising is not an educational tool, but rather a vehicle to mass market drugs before the serious side effects become known. "The direct-to-consumer advertising," he told the panel, "is not a good way for consumers, physicians or medical providers to be informed."
Friday, August 6, 2010
ACE Inhibitors and Birth Defects - More Expensive and Less Effective
Evelyn Pringle November 9, 2006
About one in every four American adults has high blood pressure which is a major risk factor for heart and kidney disease, as well as stroke and heart failure, but often occurs with no warning signs.
Blood pressure is the force of blood pushing against blood vessel walls. The heart pumps blood into the arteries which carry the blood throughout the body. High blood pressure makes the heart work harder to pump blood and contributes to hardening of the arteries or atherosclerosis, according to WebMD.
Sometimes chronic hypertension or gestational hypertension leads to preeclampsia, a serious condition characterized by high blood pressure and protein in the urine, which often indicates kidney problems.
One in four pregnant women with chronic high blood pressure develops preeclampsia. In addition to increased blood pressure and protein in the urine, hand and facial swelling, sudden weight gain, persistent headaches, blurred vision, dizziness and abdominal pain, may also occur in women with the condition.
In pregnant women, high blood pressure can also decrease the blood flow to the placenta, which affects the supply of oxygen and nutrients to the fetus and increases the risk of preterm delivery.
Persistent high pressure can damage the smaller blood vessels that transport blood to and from the cells and tissues, including the tissues of the heart, lungs, brain, kidneys, liver, and the uterus.
A common class of medications used to treat high blood pressure are ACE inhibitors (angiotensin converting enzyme inhibitors). These drugs arrived on the market about 25 years ago, and they are currently the second most commonly prescribed class of drugs in the US.
The drugs act by inhibiting the production of angiotensin II, a substance that both induces constriction of blood vessels and retention of sodium, which leads to water retention, and an increased blood volume.
According to WebMD, ACE inhibitors dilate blood vessels to improve the amount of blood the heart pumps and lower blood pressure. They also help decrease the amount of work the heart has to do and protect the kidneys from the effects of hypertension and diabetes. Examples of ACE inhibitors include:
* Capoten (captopril)
* Vasotec (enalapril)
* Prinivil, Zestril (lisinopril)
* Lotensin (benazepril)
* Monopril (fosinopril)
* Altace (ramipril)
* Accupril (quinapril)
* Aceon (perindopril)
* Mavik (trandolapril)
* Univasc (moexipril)
Numerous studies have shown that ACE inhibitors can have adverse effects on the developing fetus, and for years, experts have said they should not be prescribed to pregnant women.
The most recent study documenting their harm to the fetus was conducted by researchers from Vanderbilt University, and published in the June 8, 2006, New England Journal of Medicine. The study found that fetal exposure to ACE inhibitors in the first trimester of pregnancy nearly tripled the risk of serious birth defects.
According to the research, one-third of the birth defects identified in newborns born to women who were prescribed ACE inhibitors in the first trimester, involved the heart, one-quarter involved the limbs or face, and one-tenth of the defects involved the brain or spinal cord.
In the study, the researchers examined pharmacy records and data from the Tennessee Medicaid database for the years between 1985 and 2000, which allowed them to review records of ACE inhibitors prescribed for women during the first trimester as well as infant outcomes.
In reaching their results, the researchers compared newborns exposed to ACE inhibitors with a cohort of infants whose mothers received other high blood pressure drugs in the first trimester, and a group of newborns who were not exposed to any hypertension medications.
Some experts expressed alarm at finding such serious adverse events in a study on drugs that have already been on the market for a quarter of a century. In an editorial accompanying the study in JAMA, Dr J M Friedman, MD, PhD, from the University of British Columbia in Vancouver, Canada, said more research on the teratogenic potential of ACE inhibitors in pregnancy is called for.
"This is not the last word on the subject," he wrote, "but it is shocking to realize that it is almost the first."
"Birth defects caused by teratogenic treatments are preventable," Dr Friedman states, "and babies and their mothers are being harmed unnecessarily because we do not know enough about which treatments to use and which to avoid."
"Further study is needed to determine the precise risk and its relationship to individual drugs," he advises, "but the increase appears to be great enough to require discussion with all women of reproductive age who are prescribed ACE inhibitors."
"Detailed fetal ultrasonography and echocardiography at about 18 weeks of gestation," he says, "should be offered to women who have taken such drugs in the first trimester of pregnancy."
"A woman who learns she is pregnant while taking an ACE inhibitor," he warns, "should immediately be switched to another antihypertensive agent to minimize the risk of fetopathy."
But the findings of this study are not actually new. A surveillance study in 2002, of Michigan Medicaid recipients involving 86 newborns exposed to captopril during the first trimester found 4 newborns (4.7%) had major birth defects, including one cardiovascular anomaly, one polydactyly, one limb reduction defect, and one hypospadias.
In addition, ACE inhibitors have long been associated with serious birth defects in infants born to mothers who used the drugs during the second and third trimester of pregnancy. Back on March 13, 1992, the FDA announced that all ACE inhibitors, "will be required to carry a "boxed warning" on the label for women in the advanced stages of pregnancy."
"At the agency's request," the FDA said in a press release, "six pharmaceutical companies are simultaneously sending out a "Dear Doctor" letter emphasizing that women who take the drug in the second and third trimesters of pregnancy are running the risk of causing significant harm to fetuses, including kidney failure and face or skull deformities."
For several years before that announcement, the labeling on ACE inhibitors had warned about the dangers of their use by pregnant women, but nonetheless, additional cases of birth defects continued to be reported. "More than 50 cases of fetal harm have been reported over the past several years," the FDA stated.
"The warnings in the labeling," its press release stated, "are therefore being strengthened by including a boxed warning and other changes."
At the time, pharmacists were also alerted to the label changes and were provided stickers to paste on ACE inhibitor prescription bottles that read, "If you become pregnant consult your doctor promptly about switching to a different drug."
Critics say that in light of all the previous studies, the use of ACE inhibitors with pregnant women should have ended long before the latest Vanderbilt study. Clearly, they say, resistance to the use of other hypertension drugs stems from the heavy promotion of ACE inhibitors to prescribing physicians.
For instance, diuretics and beta-blockers are recommended as the first-line of treatment for uncomplicated hypertension by the Joint National Commission on High Blood Pressure Treatment, yet a survey conducted on 1,700 primary care doctors, published in the December 2003, Journal of General Internal Medicine, showed that doctors believed that diuretics were less effective, and that beta-blockers had more side effects than calcium channel blockers and ACE inhibitors.
In addition, the survey found that doctors who favored prescribing the more expensive medications were more likely to pass out free drug samples provided by pharmaceutical sales representatives. Patients diagnosed with hypertension become life-long customers for Big Pharma and critics say sales reps will use whatever means necessary to lock in a new patient.
"These new, more expensive medications are being more heavily promoted by the drug companies, and one way or another that information influences how people perceive the drug's effectiveness," according to the Journal's study author, Peter Ubel, MD, associate professor of internal medicine at University of Michigan Medical School.
In the hypothetical patient used in the survey, Dr Ubel says, there would be no advantage to taking ACE inhibitors over diuretics or beta-blockers. He also points out that ACE inhibitors tend to have more side effects than diuretics or beta-blockers.
Critics say there is a huge incentive for drug companies to convince doctors to prescribe ACE inhibitors instead of the more effective hypertension drugs that sell for fraction of the cost. According to IMS Health, a pharmaceutical information tracking firm, in 2005, sales of ACE inhibitors brought in more than $3.8 billion.
Chronic heart failure is a debilitating condition in which the heart's ability to pump blood is impaired. Patients with heart failure experience a continuing decline in their health, resulting in an increased frequency of hospitalization and in premature death.
There are often no symptoms in people with hypertension. In fact, according to WebMD, nearly one-third of those who have the condition do not know it. The only way to know for certain whether hypertension is present, is to be tested.
Blood pressure is recorded as two numbers: the first, or the high number, shows the pressure during a heartbeat, and the second lower number shows the pressure between heart beats. The categories of blood pressure include:
* Normal: Less than 120/80
* Prehypertension: 120-139/80-89
* Stage 1 hypertension: 140-159/90-99
* Stage 2 hypertension: 160 and above/100 and above
An estimated 5% of pregnant women have high blood pressure before pregnancy, although many women are not diagnosed with the condition until they begin prenatal care. This is known as "essential hypertension," but it is reportedly no different from the high blood pressure that affects many people who are overweight and inactive.
Another 5 to 8 percent of women develop high blood pressure during pregnancy, known as "gestational hypertension." Although this condition usually goes away after delivery, gestational hypertension may increase the risk of developing chronic high blood pressure in the future.
About one in every four American adults has high blood pressure which is a major risk factor for heart and kidney disease, as well as stroke and heart failure, but often occurs with no warning signs.
Blood pressure is the force of blood pushing against blood vessel walls. The heart pumps blood into the arteries which carry the blood throughout the body. High blood pressure makes the heart work harder to pump blood and contributes to hardening of the arteries or atherosclerosis, according to WebMD.
Sometimes chronic hypertension or gestational hypertension leads to preeclampsia, a serious condition characterized by high blood pressure and protein in the urine, which often indicates kidney problems.
One in four pregnant women with chronic high blood pressure develops preeclampsia. In addition to increased blood pressure and protein in the urine, hand and facial swelling, sudden weight gain, persistent headaches, blurred vision, dizziness and abdominal pain, may also occur in women with the condition.
In pregnant women, high blood pressure can also decrease the blood flow to the placenta, which affects the supply of oxygen and nutrients to the fetus and increases the risk of preterm delivery.
Persistent high pressure can damage the smaller blood vessels that transport blood to and from the cells and tissues, including the tissues of the heart, lungs, brain, kidneys, liver, and the uterus.
A common class of medications used to treat high blood pressure are ACE inhibitors (angiotensin converting enzyme inhibitors). These drugs arrived on the market about 25 years ago, and they are currently the second most commonly prescribed class of drugs in the US.
The drugs act by inhibiting the production of angiotensin II, a substance that both induces constriction of blood vessels and retention of sodium, which leads to water retention, and an increased blood volume.
According to WebMD, ACE inhibitors dilate blood vessels to improve the amount of blood the heart pumps and lower blood pressure. They also help decrease the amount of work the heart has to do and protect the kidneys from the effects of hypertension and diabetes. Examples of ACE inhibitors include:
* Capoten (captopril)
* Vasotec (enalapril)
* Prinivil, Zestril (lisinopril)
* Lotensin (benazepril)
* Monopril (fosinopril)
* Altace (ramipril)
* Accupril (quinapril)
* Aceon (perindopril)
* Mavik (trandolapril)
* Univasc (moexipril)
Numerous studies have shown that ACE inhibitors can have adverse effects on the developing fetus, and for years, experts have said they should not be prescribed to pregnant women.
The most recent study documenting their harm to the fetus was conducted by researchers from Vanderbilt University, and published in the June 8, 2006, New England Journal of Medicine. The study found that fetal exposure to ACE inhibitors in the first trimester of pregnancy nearly tripled the risk of serious birth defects.
According to the research, one-third of the birth defects identified in newborns born to women who were prescribed ACE inhibitors in the first trimester, involved the heart, one-quarter involved the limbs or face, and one-tenth of the defects involved the brain or spinal cord.
In the study, the researchers examined pharmacy records and data from the Tennessee Medicaid database for the years between 1985 and 2000, which allowed them to review records of ACE inhibitors prescribed for women during the first trimester as well as infant outcomes.
In reaching their results, the researchers compared newborns exposed to ACE inhibitors with a cohort of infants whose mothers received other high blood pressure drugs in the first trimester, and a group of newborns who were not exposed to any hypertension medications.
Some experts expressed alarm at finding such serious adverse events in a study on drugs that have already been on the market for a quarter of a century. In an editorial accompanying the study in JAMA, Dr J M Friedman, MD, PhD, from the University of British Columbia in Vancouver, Canada, said more research on the teratogenic potential of ACE inhibitors in pregnancy is called for.
"This is not the last word on the subject," he wrote, "but it is shocking to realize that it is almost the first."
"Birth defects caused by teratogenic treatments are preventable," Dr Friedman states, "and babies and their mothers are being harmed unnecessarily because we do not know enough about which treatments to use and which to avoid."
"Further study is needed to determine the precise risk and its relationship to individual drugs," he advises, "but the increase appears to be great enough to require discussion with all women of reproductive age who are prescribed ACE inhibitors."
"Detailed fetal ultrasonography and echocardiography at about 18 weeks of gestation," he says, "should be offered to women who have taken such drugs in the first trimester of pregnancy."
"A woman who learns she is pregnant while taking an ACE inhibitor," he warns, "should immediately be switched to another antihypertensive agent to minimize the risk of fetopathy."
But the findings of this study are not actually new. A surveillance study in 2002, of Michigan Medicaid recipients involving 86 newborns exposed to captopril during the first trimester found 4 newborns (4.7%) had major birth defects, including one cardiovascular anomaly, one polydactyly, one limb reduction defect, and one hypospadias.
In addition, ACE inhibitors have long been associated with serious birth defects in infants born to mothers who used the drugs during the second and third trimester of pregnancy. Back on March 13, 1992, the FDA announced that all ACE inhibitors, "will be required to carry a "boxed warning" on the label for women in the advanced stages of pregnancy."
"At the agency's request," the FDA said in a press release, "six pharmaceutical companies are simultaneously sending out a "Dear Doctor" letter emphasizing that women who take the drug in the second and third trimesters of pregnancy are running the risk of causing significant harm to fetuses, including kidney failure and face or skull deformities."
For several years before that announcement, the labeling on ACE inhibitors had warned about the dangers of their use by pregnant women, but nonetheless, additional cases of birth defects continued to be reported. "More than 50 cases of fetal harm have been reported over the past several years," the FDA stated.
"The warnings in the labeling," its press release stated, "are therefore being strengthened by including a boxed warning and other changes."
At the time, pharmacists were also alerted to the label changes and were provided stickers to paste on ACE inhibitor prescription bottles that read, "If you become pregnant consult your doctor promptly about switching to a different drug."
Critics say that in light of all the previous studies, the use of ACE inhibitors with pregnant women should have ended long before the latest Vanderbilt study. Clearly, they say, resistance to the use of other hypertension drugs stems from the heavy promotion of ACE inhibitors to prescribing physicians.
For instance, diuretics and beta-blockers are recommended as the first-line of treatment for uncomplicated hypertension by the Joint National Commission on High Blood Pressure Treatment, yet a survey conducted on 1,700 primary care doctors, published in the December 2003, Journal of General Internal Medicine, showed that doctors believed that diuretics were less effective, and that beta-blockers had more side effects than calcium channel blockers and ACE inhibitors.
In addition, the survey found that doctors who favored prescribing the more expensive medications were more likely to pass out free drug samples provided by pharmaceutical sales representatives. Patients diagnosed with hypertension become life-long customers for Big Pharma and critics say sales reps will use whatever means necessary to lock in a new patient.
"These new, more expensive medications are being more heavily promoted by the drug companies, and one way or another that information influences how people perceive the drug's effectiveness," according to the Journal's study author, Peter Ubel, MD, associate professor of internal medicine at University of Michigan Medical School.
In the hypothetical patient used in the survey, Dr Ubel says, there would be no advantage to taking ACE inhibitors over diuretics or beta-blockers. He also points out that ACE inhibitors tend to have more side effects than diuretics or beta-blockers.
Critics say there is a huge incentive for drug companies to convince doctors to prescribe ACE inhibitors instead of the more effective hypertension drugs that sell for fraction of the cost. According to IMS Health, a pharmaceutical information tracking firm, in 2005, sales of ACE inhibitors brought in more than $3.8 billion.
Chronic heart failure is a debilitating condition in which the heart's ability to pump blood is impaired. Patients with heart failure experience a continuing decline in their health, resulting in an increased frequency of hospitalization and in premature death.
There are often no symptoms in people with hypertension. In fact, according to WebMD, nearly one-third of those who have the condition do not know it. The only way to know for certain whether hypertension is present, is to be tested.
Blood pressure is recorded as two numbers: the first, or the high number, shows the pressure during a heartbeat, and the second lower number shows the pressure between heart beats. The categories of blood pressure include:
* Normal: Less than 120/80
* Prehypertension: 120-139/80-89
* Stage 1 hypertension: 140-159/90-99
* Stage 2 hypertension: 160 and above/100 and above
An estimated 5% of pregnant women have high blood pressure before pregnancy, although many women are not diagnosed with the condition until they begin prenatal care. This is known as "essential hypertension," but it is reportedly no different from the high blood pressure that affects many people who are overweight and inactive.
Another 5 to 8 percent of women develop high blood pressure during pregnancy, known as "gestational hypertension." Although this condition usually goes away after delivery, gestational hypertension may increase the risk of developing chronic high blood pressure in the future.
Thursday, August 5, 2010
Boston Scientific and Guidant Off to Texas Slaughterhouse
Evelyn Pringle September 6, 2006
The first, but by no means the last, Guidant trial is scheduled to begin on September 18, 2006, in Neuces County District Court in Corpus Christi, Texas before Judge Jack Hunter.
The two plaintiffs, Louis Motal, 63, and Bernice Hinojosa, 65, are surviving patients implanted with Guidant's Ventak Prizm 2 defibrillators in 2001. The lawsuit claims that Guidant "actively concealed the ... defect, suppressed reports, failed to follow through on FDA notification requirements, and failed to disclose a known defect to patients."
"Instead of revealing the defect," the plaintiffs allege, "defendants continued to represent their product as safe for intended use, and continued to sell the flawed [devices] despite knowing of the dangers."
Both plaintiffs claim they suffered extreme mental anguish from knowing that the defective devices could malfunction at any time.
According to the company's latest tally, there are about 72 class-action lawsuits and about 477 individual lawsuits filed against Guidant in various state and federal courts, Boston Scientific reported in its second quarterly report filed with the SEC. The latter number is up from about 300 cases noted in the firm's first quarterly report filed three months earlier.
As of April 2006, Boston became the proud owner of Guidant after winning a bidding battle with Johnson and Johnson, in what will certainly not go down in history as the deal of the century.
In addition to all the lawsuit already filed, according to Boston latest SEC filing, there are more than 3,300 claims of individuals that may or may not be filed, up from 3,000 claims in the earlier report.
The lawsuits all relate to defective defibrillators and pacemakers. Defibrillators are $30,000 devices that are wired directly to the heart and send electric shocks when abnormal heart rhythms are detected and pacemakers speed up hearts that beat too slowly, and cost between $4,000 and $20,000 for each unit, according to Bloomberg News on June 26, 2006.
According to Boston report, "the majority of claimants allege no physical injury, but are suing for medical monitoring and anxiety."
The numbers have really grown compared to Guidant's regulatory filing with the SEC on February 22, 2006, that predicted as many as 2,500 patients may seek damages. Those claims are distinct, Guidant noted in the filing, from the claims already filed by patients in 211 individual and class action lawsuits in the US and Canada.
And the potentially bleak future of Boston does not hinge entirely on what happens in civil lawsuits. Back on February 23, 2006, the Associated Press reported that the FDA, US Department of Justice, the Securities and Exchange Commission and several state agencies are investigating Guidant over its recalls.
The company is in fact being investigated by three attorneys general on behalf of 34 states, according to the article, Litigation Mounts Over Guidant Heart Devices, in Lawyers Weekly USA, on January 30, 2006.
"In addition," the article states, "New York State and the city of Bethlehem, Pa. are suing Guidant for reimbursement of medical costs involved in replacing the devices."
All lawsuits pending in federal courts have been consolidated under multi-district litigation rules and moved to a US District Court in Minnesota, where Guidant has several manufacturing facilities, with the first federal trial scheduled to begin on March 15, 2007.
On June 13, 2006, the Minnesota Supreme court appointed one judge to preside over all state court cases involving lawsuits linked to last year's Guidant product communications, Boston Scientific notes in its report.
According to Lawyers Weekly USA, the lead counsel for the Texas plaintiffs, Robert Hilliard, of Hilliard & Munoz, said documents obtained during discovery show that Guidant knew about problems with its devices as far back as April 2002, but failed to alert doctors and patients for 3 years.
"They knew they were going to kill people based on this defect," he said.
Ted Meadows, a plaintiffs' attorney with the Beasley Allen lawfirm in Montgomery, Alabama, who specializes in medical device litigation, told Lawyers Weekly, "There were literally tens of thousands of people who've had these devices implanted in them."
"Now they're faced with the concern," he said, "the device might not work properly when they need it most."
And critics say there is certainly plenty of cause for concern. On June 7, 2006, the New York Times reported that least seven patients are known to have died in episodes in which Guidant defibrillators failed to work because of the electrical defect, five involving Contak Renewals.
"But many experts believe that the number is probably higher," the Times wrote, "because an implanted heart device is rarely examined after a patient's death to determine if it was working properly."
According to Mr Meadows, a key to plaintiffs' claims will be showing that Guidant "knew or should have known there was a potential for this problem." In addition, he said, any evidence that indicates Guidant knew about the problem and responded improperly would entitle plaintiffs to seek an award for punitive damages.
Legal experts say this evidence exists and point to a report released in March 2006, by an independent panel appointed to review the recalls that shows Guidant allowed about 4,000 potentially defective defibrillators to be implanted in patients after the company found a flaw in 2002 that caused malfunction.
"The Independent Panel believes," the report says, "that under no circumstances should a potential or manifest risk of a preventable death be superseded by statistical analyses that indicate that performance remains with general guidelines."
The panel also said that Guidant and other devices makers need to increase the level of data collected on device failures because studies have shown that only a relatively small number of failures are reported to the manufacturers and the FDA because doctors and hospitals do not always report problems and devices are not ordinarily inspected after a patient die.
According to Boston Scientific, the devices that may be flawed include certain Insignia and Nexus pacemakers, Contak Renewal TR/TR2 cardiac resynchronization pacemakers, and Ventak Prizm 2, Vitality and Vitality 2 implantable cardioverter defibrillators.
These products were manufactured by the company's Cardiac Rhythm Management Group, formerly Boston Scientific/Guidant's CRM business, and some were implanted in patients as late as between December 2005 and June 2006.
On June 7, 2006, the New York Times reported that in one analysis, Guidant engineers projected that 1 out of every 100 Contak Renewals could short-circuit, a failure rate considered high by experts.
Guidant also suspected by late 2004 that the Renewal models would become increasingly prone to failure as the devices aged, the Times said documents indicate.
The Contak Renewal combines a pacemaker and a defibrillator, often referred to as a cardiac resynchronization therapy device, or CRT-D and costs about $35,000, the Times notes.
On June 6, 2006, Texas Judge Jack Hunter, unsealed documents containing information about recalled defibrillators, saying he did not trust Guidant's claims that they contain trade secrets. The files show that Guidant had drafted, but never sent, a "Dear Doctor" letter detailing significant potential problems with the Contak Renewal and Contak Renewal 2 model defibrillators, according to Bloomberg News on June 7, 2006.
Guidant fought hard to keep the documents confidential and for good reason obviously. The never-sent "Dear Doctor" letter disclosed the short-circuiting problem and stated that the company had "removed all non-implanted Renewal and Renewal 2CRT-Ds from hospital shelves and Guidant inventory."
However, records reveal that by this time Guidant had already sold most of its inventory.
Earlier in 2004, the documents show that company officials drafted a memorandum for their sales representatives explaining why it was asking them to return all the unsold Contak Renewals, but the memorandum was never sent either.
Some documents provide strong evidence that Guidant weighed the risks to patients and the loss of profits and chose to place profits over the lives of patients. For instance, one company document shows that Guidant estimated it would lose about $9 million by purging its inventory of defective Contak Renewal units and parts.
Attorney Hilliard says other documents reveal that Guidant performed a risk analysis that showed there was a possibility the devices could short-circuit, and if they did, "the likelihood of death or serious injury was very likely."
He also told Lawyers Weekly that Guidant also violated federal regulations by redesigning the devices to eliminate the flaw in 2002, without informing the FDA, and that Guidant continued selling the older devices without notifying patients of the risks.
In what experts are calling the strongest evidence to present to a jury, testimony in a 168-page deposition taken in January 2006 in the Texas case, that was made public in February 2006, has Guidant executive, Fred McCoy, acknowledging that the company made changes to one of its defibrillators in 2002, and incorrectly told the FDA that it had no effect on the product's performance.
Mr McCoy testified that Guidant made two modifications to the Ventak Prizm 2 in 2002, to keep it from short-circuiting and that neither was approved by the FDA.
And as it turns out, only one of the changes was disclosed in the company's annual report that year also, and Guidant said that change had no affect on the device's performance.
In addition, in a report filed two years later, the company said that it had received FDA approval to make the changes when it had not.
Mr Hilliard told the Associated Press on February 22, 2006, that Mr McCoy's testimony proves that Guidant sold an unapproved defibrillator in violation of federal law.
In the deposition, Mr McCoy claims that he did not learn about problems with the devices until May 2005.
More damning evidence was revealed on June 23, 2006, when the Pioneer Press reported that, "Guidant's implantable heart devices may fail about 10 times more often than the company had projected last year, according to a U.S. Food and Drug Administration analysis released in a Texas lawsuit."
"A judge in a product-liability lawsuit involving Guidant's defibrillators," the newspaper said, "recently unsealed the FDA document dated June 16, 2005."
Back when Guidant began its recall in the summer of 2005, the firm said no more than 292 of the units were likely to break down. "But the FDA said "most" of the 16,000 recalled Contak Renewal defibrillators may have damaged insulation within five years of use," the Press wrote, "and 40 percent of those damaged devices would fail to produce an adequate electrical shock in a medical emergency."
At that rate, it said, at least 3,200 Renewal units would be likely to fail.
Legal experts predict that the higher projection will hurt Boston Scientific in lawsuits. "This is as damaging a document as we're going to come across," said Attorney Hunter Shkolnik, one of many lawyers representing patients suing Guidant, in an interview with Pioneer Press.
"It flies in the face of all the excuses Guidant has been giving for not telling patients to take these devices out immediately," he added.
It's difficult to imagine how things can get much worse for shareholders. In the second quarter of 2006, the company lost 27% of its value. On June 29, 2006, the Globe & Mail reported that:
"Boston Scientific, which laid out $27.5-billion in cash and shares for Guidant, has bought itself what, so far, looks like a massive and costly series of headaches, in the form of product recalls and lawsuits. These have helped drive its stock price to a four-year low of less than $17 on the New York Stock Exchange, down more than $9 from early January."
However, critics say Boston Scientific also has its laundry list of problems. According to the Globe, before it acquired Guidant, both Boston and its target, received corporate warning letters from the FDA saying that, until they have demonstrably improved their quality control, the agency will not approve new products for sale in the US.
The first, but by no means the last, Guidant trial is scheduled to begin on September 18, 2006, in Neuces County District Court in Corpus Christi, Texas before Judge Jack Hunter.
The two plaintiffs, Louis Motal, 63, and Bernice Hinojosa, 65, are surviving patients implanted with Guidant's Ventak Prizm 2 defibrillators in 2001. The lawsuit claims that Guidant "actively concealed the ... defect, suppressed reports, failed to follow through on FDA notification requirements, and failed to disclose a known defect to patients."
"Instead of revealing the defect," the plaintiffs allege, "defendants continued to represent their product as safe for intended use, and continued to sell the flawed [devices] despite knowing of the dangers."
Both plaintiffs claim they suffered extreme mental anguish from knowing that the defective devices could malfunction at any time.
According to the company's latest tally, there are about 72 class-action lawsuits and about 477 individual lawsuits filed against Guidant in various state and federal courts, Boston Scientific reported in its second quarterly report filed with the SEC. The latter number is up from about 300 cases noted in the firm's first quarterly report filed three months earlier.
As of April 2006, Boston became the proud owner of Guidant after winning a bidding battle with Johnson and Johnson, in what will certainly not go down in history as the deal of the century.
In addition to all the lawsuit already filed, according to Boston latest SEC filing, there are more than 3,300 claims of individuals that may or may not be filed, up from 3,000 claims in the earlier report.
The lawsuits all relate to defective defibrillators and pacemakers. Defibrillators are $30,000 devices that are wired directly to the heart and send electric shocks when abnormal heart rhythms are detected and pacemakers speed up hearts that beat too slowly, and cost between $4,000 and $20,000 for each unit, according to Bloomberg News on June 26, 2006.
According to Boston report, "the majority of claimants allege no physical injury, but are suing for medical monitoring and anxiety."
The numbers have really grown compared to Guidant's regulatory filing with the SEC on February 22, 2006, that predicted as many as 2,500 patients may seek damages. Those claims are distinct, Guidant noted in the filing, from the claims already filed by patients in 211 individual and class action lawsuits in the US and Canada.
And the potentially bleak future of Boston does not hinge entirely on what happens in civil lawsuits. Back on February 23, 2006, the Associated Press reported that the FDA, US Department of Justice, the Securities and Exchange Commission and several state agencies are investigating Guidant over its recalls.
The company is in fact being investigated by three attorneys general on behalf of 34 states, according to the article, Litigation Mounts Over Guidant Heart Devices, in Lawyers Weekly USA, on January 30, 2006.
"In addition," the article states, "New York State and the city of Bethlehem, Pa. are suing Guidant for reimbursement of medical costs involved in replacing the devices."
All lawsuits pending in federal courts have been consolidated under multi-district litigation rules and moved to a US District Court in Minnesota, where Guidant has several manufacturing facilities, with the first federal trial scheduled to begin on March 15, 2007.
On June 13, 2006, the Minnesota Supreme court appointed one judge to preside over all state court cases involving lawsuits linked to last year's Guidant product communications, Boston Scientific notes in its report.
According to Lawyers Weekly USA, the lead counsel for the Texas plaintiffs, Robert Hilliard, of Hilliard & Munoz, said documents obtained during discovery show that Guidant knew about problems with its devices as far back as April 2002, but failed to alert doctors and patients for 3 years.
"They knew they were going to kill people based on this defect," he said.
Ted Meadows, a plaintiffs' attorney with the Beasley Allen lawfirm in Montgomery, Alabama, who specializes in medical device litigation, told Lawyers Weekly, "There were literally tens of thousands of people who've had these devices implanted in them."
"Now they're faced with the concern," he said, "the device might not work properly when they need it most."
And critics say there is certainly plenty of cause for concern. On June 7, 2006, the New York Times reported that least seven patients are known to have died in episodes in which Guidant defibrillators failed to work because of the electrical defect, five involving Contak Renewals.
"But many experts believe that the number is probably higher," the Times wrote, "because an implanted heart device is rarely examined after a patient's death to determine if it was working properly."
According to Mr Meadows, a key to plaintiffs' claims will be showing that Guidant "knew or should have known there was a potential for this problem." In addition, he said, any evidence that indicates Guidant knew about the problem and responded improperly would entitle plaintiffs to seek an award for punitive damages.
Legal experts say this evidence exists and point to a report released in March 2006, by an independent panel appointed to review the recalls that shows Guidant allowed about 4,000 potentially defective defibrillators to be implanted in patients after the company found a flaw in 2002 that caused malfunction.
"The Independent Panel believes," the report says, "that under no circumstances should a potential or manifest risk of a preventable death be superseded by statistical analyses that indicate that performance remains with general guidelines."
The panel also said that Guidant and other devices makers need to increase the level of data collected on device failures because studies have shown that only a relatively small number of failures are reported to the manufacturers and the FDA because doctors and hospitals do not always report problems and devices are not ordinarily inspected after a patient die.
According to Boston Scientific, the devices that may be flawed include certain Insignia and Nexus pacemakers, Contak Renewal TR/TR2 cardiac resynchronization pacemakers, and Ventak Prizm 2, Vitality and Vitality 2 implantable cardioverter defibrillators.
These products were manufactured by the company's Cardiac Rhythm Management Group, formerly Boston Scientific/Guidant's CRM business, and some were implanted in patients as late as between December 2005 and June 2006.
On June 7, 2006, the New York Times reported that in one analysis, Guidant engineers projected that 1 out of every 100 Contak Renewals could short-circuit, a failure rate considered high by experts.
Guidant also suspected by late 2004 that the Renewal models would become increasingly prone to failure as the devices aged, the Times said documents indicate.
The Contak Renewal combines a pacemaker and a defibrillator, often referred to as a cardiac resynchronization therapy device, or CRT-D and costs about $35,000, the Times notes.
On June 6, 2006, Texas Judge Jack Hunter, unsealed documents containing information about recalled defibrillators, saying he did not trust Guidant's claims that they contain trade secrets. The files show that Guidant had drafted, but never sent, a "Dear Doctor" letter detailing significant potential problems with the Contak Renewal and Contak Renewal 2 model defibrillators, according to Bloomberg News on June 7, 2006.
Guidant fought hard to keep the documents confidential and for good reason obviously. The never-sent "Dear Doctor" letter disclosed the short-circuiting problem and stated that the company had "removed all non-implanted Renewal and Renewal 2CRT-Ds from hospital shelves and Guidant inventory."
However, records reveal that by this time Guidant had already sold most of its inventory.
Earlier in 2004, the documents show that company officials drafted a memorandum for their sales representatives explaining why it was asking them to return all the unsold Contak Renewals, but the memorandum was never sent either.
Some documents provide strong evidence that Guidant weighed the risks to patients and the loss of profits and chose to place profits over the lives of patients. For instance, one company document shows that Guidant estimated it would lose about $9 million by purging its inventory of defective Contak Renewal units and parts.
Attorney Hilliard says other documents reveal that Guidant performed a risk analysis that showed there was a possibility the devices could short-circuit, and if they did, "the likelihood of death or serious injury was very likely."
He also told Lawyers Weekly that Guidant also violated federal regulations by redesigning the devices to eliminate the flaw in 2002, without informing the FDA, and that Guidant continued selling the older devices without notifying patients of the risks.
In what experts are calling the strongest evidence to present to a jury, testimony in a 168-page deposition taken in January 2006 in the Texas case, that was made public in February 2006, has Guidant executive, Fred McCoy, acknowledging that the company made changes to one of its defibrillators in 2002, and incorrectly told the FDA that it had no effect on the product's performance.
Mr McCoy testified that Guidant made two modifications to the Ventak Prizm 2 in 2002, to keep it from short-circuiting and that neither was approved by the FDA.
And as it turns out, only one of the changes was disclosed in the company's annual report that year also, and Guidant said that change had no affect on the device's performance.
In addition, in a report filed two years later, the company said that it had received FDA approval to make the changes when it had not.
Mr Hilliard told the Associated Press on February 22, 2006, that Mr McCoy's testimony proves that Guidant sold an unapproved defibrillator in violation of federal law.
In the deposition, Mr McCoy claims that he did not learn about problems with the devices until May 2005.
More damning evidence was revealed on June 23, 2006, when the Pioneer Press reported that, "Guidant's implantable heart devices may fail about 10 times more often than the company had projected last year, according to a U.S. Food and Drug Administration analysis released in a Texas lawsuit."
"A judge in a product-liability lawsuit involving Guidant's defibrillators," the newspaper said, "recently unsealed the FDA document dated June 16, 2005."
Back when Guidant began its recall in the summer of 2005, the firm said no more than 292 of the units were likely to break down. "But the FDA said "most" of the 16,000 recalled Contak Renewal defibrillators may have damaged insulation within five years of use," the Press wrote, "and 40 percent of those damaged devices would fail to produce an adequate electrical shock in a medical emergency."
At that rate, it said, at least 3,200 Renewal units would be likely to fail.
Legal experts predict that the higher projection will hurt Boston Scientific in lawsuits. "This is as damaging a document as we're going to come across," said Attorney Hunter Shkolnik, one of many lawyers representing patients suing Guidant, in an interview with Pioneer Press.
"It flies in the face of all the excuses Guidant has been giving for not telling patients to take these devices out immediately," he added.
It's difficult to imagine how things can get much worse for shareholders. In the second quarter of 2006, the company lost 27% of its value. On June 29, 2006, the Globe & Mail reported that:
"Boston Scientific, which laid out $27.5-billion in cash and shares for Guidant, has bought itself what, so far, looks like a massive and costly series of headaches, in the form of product recalls and lawsuits. These have helped drive its stock price to a four-year low of less than $17 on the New York Stock Exchange, down more than $9 from early January."
However, critics say Boston Scientific also has its laundry list of problems. According to the Globe, before it acquired Guidant, both Boston and its target, received corporate warning letters from the FDA saying that, until they have demonstrably improved their quality control, the agency will not approve new products for sale in the US.
Roche Puts Accutane Profits Over Lives of Consumers
Evelyn Pringle August 31, 2006
In 1985, Accutane's package insert directed at doctors first mentioned reports of depression in patients taking the acne drug, which means that more than 20 years ago, Hoffman-LaRoche at least suspected there might be a risk of depression and suicide by persons taking the drug.
However, Roche's financial records show that the company is not about to let a little thing like the death of its customers get in the way of corporate profits, because the drug is still a best seller and young people with no history of depression who take it are still killing themselves.
On November 14, 2004, BBC News reported that Jon Medland, 22, in the final year of medical school at Manchester University, hanged himself at his student lodgings on January 13, 2004 while on Accutane.
When questioned about the incident, Roche told BBC News that the drug carried a warning of possible mood changes and depression, but said "no causal link had been established between the drug and either depression or suicide."
Less than a year later, in September 2005, BBC News reported that David Roberts, 21, had been on the drug for two months when he hanged himself near his Liverpool home.
And once again, according to BBC News, "Roche insists there is no proven relationship between the drug and depression."
However, David's father, Fred Roberts, said he could think of no other explanation for the tragedy. "David was the most happy-go-lucky, carefree lad you could ever hope to meet. He had plenty of friends, he enjoyed going out, he had a happy family life."
"His acne wasn't severe at all. He had a few spots and, like any young person, he wanted to get rid of them."
"The change in him was so sudden," Mr Roberts said, "there's no other reason for it than the effect of this drug."
On January 15, 2006, 15-year-old Justin Zimmer, of Menasha, Wisconsin, shot himself and his parents blame Accutane.
Justin's parents and a friend told the Appleton Post Crescent on July 18, 2006, that he gave no indication that he was depressed and that he was all excited about getting his driver's license in a couple of weeks.
Roche's comments to the BBC are clearly dishonest considering that in 1986, doctors were notified that Accutane users who became depressed saw their depression lift when they stopped taking the drug but return when they were placed back on the medication. Doctors were also informed that simply stopping Accutane therapy might not be sufficient to treat the depression and that follow up on the depression might be necessary.
In 1998, the FDA notified doctors that Accutane, "may cause depression, psychosis, and rarely, suicidal ideation, suicide attempts and suicide."
The agency issued a MedWatch alert in February 1998, that said due to the adverse event reports received, the FDA felt there was sufficient cause to strengthen the warning on the Accutane label to include the risk of psychosis and suicidal thoughts and actions.
The February 23, 1998, FDA Memorandum, "Isotretinoin and Depression: Spontaneous Report Data," listed 31 cases of suicide, suicide attempt or suicide ideation associated with Accutane. Of those cases, 12 were suicides, 9 were male, 2 were female, and 1 unknown, and the average age was 17. The event occurred on average, 88 days after the patient started taking the drug.
The FDA acknowledged in the memorandum that for "the majority, there was no antecedent history of depression and the patients were not noted or known to be depressed in the time period prior to their suicide."
During a US House Oversight and Investigation Subcommittee hearing on the Safety Issues Relating to Accutane, on December 11, 2002, internal documents from the nation's regulatory agencies were entered into the record that revealed that public health officials had been voicing concerns about patients committing suicide while on Accutane for well over a decade.
For instance, a 1998 memo from the FDA's medical officer in charge of Accutane states: "Given all the pieces of evidence available, it is difficult to avoid the conclusion that Accutane can adversely affect the adult human brain in clinically significant ways and that Accutane use is associated with severe psychiatric disease in some patients."
The memo recommends "active consideration of removal of Accutane from the market."
But instead of removing the drug from the market, on February 25, 1998, the FDA required Roche to add the following bold-face warning to drug's physician package insert:
"WARNINGS - Psychiatric Disorders: Accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts and suicide. Discontinuation of Accutane therapy may be insufficient; further evaluation may be necessary. No mechanism of action has been established for these events."
"ADVERSE REACTIONS - In the postmarketing period, a number of patients treated with Accutane have reported depression, psychosis and rarely, suicidal, ideation, suicide attempts and suicide. Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy."
In perverse twist of logic, in the same year, Roche began actively marketing Accutane as a treatment for depression, under the theory that it could help people who were suffering from depression due to poor self-image as a result of acne.
On March 5, 1998, Roche received a letter from the FDA stating that such promotion was false and misleading, and that Accutane had never been approved for the treatment of depression, and that in fact, just the opposite was true. The letter stated in relevant part:
"Roche ... has not systematically studied the ability of Accutane to modify or prevent such illnesses as depression and has presented no basis for asserting that Accutane is effective in improving the psychosocial and emotional well-being of such patients.
"This claim is particularly troublesome in light of information recently presented in a Dear Doctor letter, that Accutane may cause depression, psychosis, and rarely, suicidal ideation, suicide attempts and suicide."
The FDA also instructed Roche to "prominently disclose information about the psychiatric disorders described in the warnings section of the revised labeling" in Accutane advertisements.
In September 1998, the FDA presented an Advisory Panel with 37 cases of suicide attributed to Accutane since 1983. However, the number was later changed to 44 suicides after Roche corrected its calculations.
The Adverse Event Reporting System (AERS) is a computerized database of post-marketing adverse events, designed to support the FDA's post-marketing surveillance program of all approved drugs.
The reports in AERS are evaluated by agency reviewers in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) to detect safety signals and to monitor drug safety.
The results of a review of AERS by congressional staffers working on behalf of Congressman, Bart Stupak (D-MI), revealed during an October 5, 2000, hearing, reported 54 more suicides by persons on Accutane after the FDA issued its MedWatch in 1998.
In 2004, the Alliance for Human Research Protection, asked Keith Altman, an Adverse Drug Reaction Statistics Analyst, to analyze the FDA's Medwatch database for drug-linked suicides by children under the age of 18. The analysis found that between 1989 and June 2003, there were 216 reports of drug-linked suicides, and 72 were associated with Accutane.
The Alliance points out that MedWatch reflects approximately 1% of actual adverse events, so 72 Accutane suicide reports could represent as many as 7,200 suicides.
Congressman Bart Stupak, lost his son, BJ, to suicide on Mother's Day, May 14, 2000, at the age of 17, from a self-inflicted gunshot wound and BJ was on Accutane at the time of his death.
On December 11, 2002, Rep Stupak told the audience at the Safety Issues Surrounding Accutane Hearing that, "Anyone who knew BJ could not understand why a young man with such an outgoing personality and bright future would end his own life."
"BJ taking his own life," Rep Stupak said, "is contrary to everything he believed in!"
After his suicide, BJ's mother, Laurie, checked out Accutane on the Internet and found many adverse events associated with the drug that they was never told about.
But the most disturbing find she said, was the February 1998 MedWatch stating, "The FDA is advising consumers and health care providers of new safety information regarding the prescription anti-acne drug Accutane (isotretinoin) and isolated reports of depression, psychosis, and rarely suicidal thoughts and actions."
"After we found the MedWatch," Rep Stupak said, "I wondered why the FDA put out this warning, 18 years after the drug was approved?"
"More important," he continued, "why weren't these warnings on BJ's Accutane package which had been revised 4 months after the MedWatch was issued?"
Two other couples testified at the hearing about their sons who had no history of depression, but yet committed suicide while taking Accutane. The spontaneity of the suicides became the center piece of discussion between committee members and witnesses during the hearing.
Susan and Martin Turney from Watertown, New York testified about their 16-year-old son, Matthew, who took his own life on March 14, 2001, and was on Accutane at the time of his death.
In retracing the days leading up to Matt's death, nothing indicated that anything was wrong. The night before the suicide, everything was normal his parents recalled. The family had a nice dinner together, talked about the day's events and joked and laughed with each other like always.
The next morning, Matt got up for school as usual. Before leaving to catch the bus, he looked at his father, smiled and said "Good Bye," and yelled, "Good Bye Mom. I love you," to his mother who was in another room, just like he did every morning.
By all accounts, Matt was fine at school that day. He talked to his guidance counselor about a program she had recommended for the next year. He asked a girl to a dance and she agreed to go. He took a couple of tests and did well.
On the bus ride home, Matt sat with his friends and laughed and fooled around just like any other day. He got off the bus and stopped to pick up the newspaper and mail as usual. He took off his shoes in the entryway, placed the mail and newspaper on the kitchen counter as he always did, and went into his room and hung up his coat.
His parents say it is at this point that Matt's normal routine changed. He did not turn on the TV, or get a snack or check his email as usual. Instead, he apparently went into the master bedroom, unlocked the gun case, took out a gun and shot himself.
His father came home from work and yelled "Hello" to Matt, but got no response so he went looking for him and found Matt on the floor of the bedroom with no heartbeat.
While answering questions from police at the hospital, Matt's parents were asked if Matt was taking any medication and they said Accutane. As soon as they answered, they remembered a TV Dateline program about the parents whose son committed suicide while on Accutane.
After watching the program Matt and his mother had went to the Dermatologist to discuss the story and their concerns about Accutane. The Dermatologist said that there had been a couple of unsubstantiated cases of depression and suicide, but that there was no scientific proof that Accutane could cause it and that Matt "didn't fit the profile anyway."
Matt's parents told the committee how they later found out that Accutane was supposed to be reserved for the most severe cases of nodular, cystic acne and provided the panel with a school picture of their son taken about 2 weeks before he started on Accutane that showed he did not have a severe acne problem.
"After talking to all of Matt's friends, family, teachers, and co-workers," his father told the committee, "we confirmed what we had already known, Matthew was not depressed!"
"His sudden death came as a shock to every person who knew Matt, including us, his parents," he said. Matt's suicide was "spontaneous," his parents said:
"There was no depression. There was no warning. There was nothing for us to look for. There was no reason for his death, other than Accutane."
Michael and Caroline Bencz also testified at the hearing about how their son, James, committed suicide without any sign that he was depressed or troubled. They told the panel that at the time of his death, he had everything to live for stating:
"James was not the person anyone would expect to commit suicide. He had friends and family. He had financial and personal success. He had plans for the future - both near and long term.
"The week James died, he was to leave on a skiing trip to Austria with a few of his firefighter buddies. James had plans for his future, and death was not in that plan."
"He was witty, humorous, talented, a great sportsman, intelligent, and highly competitive," his parent said, "but most of all, above all that, a wonderful human being.
In late 2001, they told the panel, they learned that a doctor prescribed Accutane for James. These parents also provided the committee with a picture of their to show that he never had a severe acne problem. All they could figure out was that maybe the skin diving suit he wore may have irritated his skin on his neck and back.
The last day they heard from James, on February 23, 2002, he called to say he did not feel well, that he had a headache. His last words to his parents were: "I don't feel too good, I'm going to try to get some sleep."
Over the next few days they did not hear from James which was very unusual. It was not like him, his parents said, to disappear for days at a time without letting anyone know where he was.
When he did not turn up, a massive man hunt was conducted, and he was eventually found on March 4, 2002, at the bottom of a lake, with a 44 pound barbell strapped to his body. A lake where James and his sister used to sit as children skipping rocks.
He died, his father told the committee, "under circumstances so bizarre for someone like James - a diver, a firefighter, and an athlete - with so much to live for, and so many future plans."
"We wish every minute of every day that we had never heard of that drug," they told the committee. "It took our son, our life as we know it, and left us with huge craters in our hearts that can never be filled in again."
These reports of inexplicable suicides were alarming to members of the committee. "Is it possible that this medication has an effect, an action that results in spontaneous, impulsive, self destructive behavior that is different from that which occurs from a clinical depression?," Congressman Ted Strickland (D-OH), who has a PhD in psychology, asked.
"I know of no clinical concept of depression that has an instantaneous onset and what we've heard described are people who are emotionally," Rep Strickland said, "psychologically healthy with none of the clinical signs of depression spontaneously doing something to themselves."
"So I'm wondering," he concluded, "if we are dealing here with something other than depression, and that we ought to recognize that."
The FDA Office of Drug Safety keeps a monthly cumulative count of psychiatric adverse event reports in AERS. According to Dr Janet Woodcock, Director of the Center for Drug Evaluation and Research, at the hearing, as of November 30, 2002, AERS contained 3,104 reports with at least one reported psychiatric event.
The FDA is aware of 173 reports of suicide in association with Accutane, she told the panel. She noted that the FDA had requested quarterly summaries of psychiatric events from Roche and said the most recent summary through August 2002 indicated approximately 6,000 additional reports that include psychiatric events
Because the 173 cases of suicides ware based on self reporting, experts say that figure is highly suspect and that being as few as 1% of suicides are reported as adverse events, it could mean that the actual number of suicides may be as high as 17,000.
During his December 11, 2002 statement to the committee, Congressman Stupak pointed the finger of blame directly at the FDA when stating:
"Accutane is a powerful, dangerous drug with devastating consequences for some patients. The birth defects caused by Accutane are horrific. The FDA's response to the birth defects and psychiatric events has been inadequate, irresponsible and unacceptable. Thousands of babies, teenagers, and young adults have died prematurely.
"While the FDA has been aware of the birth defects since at least 1982 and the psychiatric injuries since 1985, their responsibility to protect the public has been inconsistent and without direction."
There is no debate about whether Accutane is a moneymaker. According to the Associated Press on August 21, 2006, patients usually take it for up to a year at a cost of $10 to $15 per day. And in the December 11, 2002 hearing, Congressman Stupak turned the attention of the committee to Roche's conduct of putting profits before people and stated:
"They have done everything possible to prevent the American people from learning of the psychiatric injuries and deaths associated with Accutane. Even, today ... Roche will deny any casual effect of Accutane with the abortions, deaths, and suicides caused by their product."
"We cannot allow the drug manufacturer and the FDA to continue to turn a blind eye to the lives lost, families devastated and dreams dashed by an acne drug," he said.
"The American people, our children," he said, "are not collateral damage in the scheme of corporate profits!"
In 1985, Accutane's package insert directed at doctors first mentioned reports of depression in patients taking the acne drug, which means that more than 20 years ago, Hoffman-LaRoche at least suspected there might be a risk of depression and suicide by persons taking the drug.
However, Roche's financial records show that the company is not about to let a little thing like the death of its customers get in the way of corporate profits, because the drug is still a best seller and young people with no history of depression who take it are still killing themselves.
On November 14, 2004, BBC News reported that Jon Medland, 22, in the final year of medical school at Manchester University, hanged himself at his student lodgings on January 13, 2004 while on Accutane.
When questioned about the incident, Roche told BBC News that the drug carried a warning of possible mood changes and depression, but said "no causal link had been established between the drug and either depression or suicide."
Less than a year later, in September 2005, BBC News reported that David Roberts, 21, had been on the drug for two months when he hanged himself near his Liverpool home.
And once again, according to BBC News, "Roche insists there is no proven relationship between the drug and depression."
However, David's father, Fred Roberts, said he could think of no other explanation for the tragedy. "David was the most happy-go-lucky, carefree lad you could ever hope to meet. He had plenty of friends, he enjoyed going out, he had a happy family life."
"His acne wasn't severe at all. He had a few spots and, like any young person, he wanted to get rid of them."
"The change in him was so sudden," Mr Roberts said, "there's no other reason for it than the effect of this drug."
On January 15, 2006, 15-year-old Justin Zimmer, of Menasha, Wisconsin, shot himself and his parents blame Accutane.
Justin's parents and a friend told the Appleton Post Crescent on July 18, 2006, that he gave no indication that he was depressed and that he was all excited about getting his driver's license in a couple of weeks.
Roche's comments to the BBC are clearly dishonest considering that in 1986, doctors were notified that Accutane users who became depressed saw their depression lift when they stopped taking the drug but return when they were placed back on the medication. Doctors were also informed that simply stopping Accutane therapy might not be sufficient to treat the depression and that follow up on the depression might be necessary.
In 1998, the FDA notified doctors that Accutane, "may cause depression, psychosis, and rarely, suicidal ideation, suicide attempts and suicide."
The agency issued a MedWatch alert in February 1998, that said due to the adverse event reports received, the FDA felt there was sufficient cause to strengthen the warning on the Accutane label to include the risk of psychosis and suicidal thoughts and actions.
The February 23, 1998, FDA Memorandum, "Isotretinoin and Depression: Spontaneous Report Data," listed 31 cases of suicide, suicide attempt or suicide ideation associated with Accutane. Of those cases, 12 were suicides, 9 were male, 2 were female, and 1 unknown, and the average age was 17. The event occurred on average, 88 days after the patient started taking the drug.
The FDA acknowledged in the memorandum that for "the majority, there was no antecedent history of depression and the patients were not noted or known to be depressed in the time period prior to their suicide."
During a US House Oversight and Investigation Subcommittee hearing on the Safety Issues Relating to Accutane, on December 11, 2002, internal documents from the nation's regulatory agencies were entered into the record that revealed that public health officials had been voicing concerns about patients committing suicide while on Accutane for well over a decade.
For instance, a 1998 memo from the FDA's medical officer in charge of Accutane states: "Given all the pieces of evidence available, it is difficult to avoid the conclusion that Accutane can adversely affect the adult human brain in clinically significant ways and that Accutane use is associated with severe psychiatric disease in some patients."
The memo recommends "active consideration of removal of Accutane from the market."
But instead of removing the drug from the market, on February 25, 1998, the FDA required Roche to add the following bold-face warning to drug's physician package insert:
"WARNINGS - Psychiatric Disorders: Accutane may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts and suicide. Discontinuation of Accutane therapy may be insufficient; further evaluation may be necessary. No mechanism of action has been established for these events."
"ADVERSE REACTIONS - In the postmarketing period, a number of patients treated with Accutane have reported depression, psychosis and rarely, suicidal, ideation, suicide attempts and suicide. Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy."
In perverse twist of logic, in the same year, Roche began actively marketing Accutane as a treatment for depression, under the theory that it could help people who were suffering from depression due to poor self-image as a result of acne.
On March 5, 1998, Roche received a letter from the FDA stating that such promotion was false and misleading, and that Accutane had never been approved for the treatment of depression, and that in fact, just the opposite was true. The letter stated in relevant part:
"Roche ... has not systematically studied the ability of Accutane to modify or prevent such illnesses as depression and has presented no basis for asserting that Accutane is effective in improving the psychosocial and emotional well-being of such patients.
"This claim is particularly troublesome in light of information recently presented in a Dear Doctor letter, that Accutane may cause depression, psychosis, and rarely, suicidal ideation, suicide attempts and suicide."
The FDA also instructed Roche to "prominently disclose information about the psychiatric disorders described in the warnings section of the revised labeling" in Accutane advertisements.
In September 1998, the FDA presented an Advisory Panel with 37 cases of suicide attributed to Accutane since 1983. However, the number was later changed to 44 suicides after Roche corrected its calculations.
The Adverse Event Reporting System (AERS) is a computerized database of post-marketing adverse events, designed to support the FDA's post-marketing surveillance program of all approved drugs.
The reports in AERS are evaluated by agency reviewers in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) to detect safety signals and to monitor drug safety.
The results of a review of AERS by congressional staffers working on behalf of Congressman, Bart Stupak (D-MI), revealed during an October 5, 2000, hearing, reported 54 more suicides by persons on Accutane after the FDA issued its MedWatch in 1998.
In 2004, the Alliance for Human Research Protection, asked Keith Altman, an Adverse Drug Reaction Statistics Analyst, to analyze the FDA's Medwatch database for drug-linked suicides by children under the age of 18. The analysis found that between 1989 and June 2003, there were 216 reports of drug-linked suicides, and 72 were associated with Accutane.
The Alliance points out that MedWatch reflects approximately 1% of actual adverse events, so 72 Accutane suicide reports could represent as many as 7,200 suicides.
Congressman Bart Stupak, lost his son, BJ, to suicide on Mother's Day, May 14, 2000, at the age of 17, from a self-inflicted gunshot wound and BJ was on Accutane at the time of his death.
On December 11, 2002, Rep Stupak told the audience at the Safety Issues Surrounding Accutane Hearing that, "Anyone who knew BJ could not understand why a young man with such an outgoing personality and bright future would end his own life."
"BJ taking his own life," Rep Stupak said, "is contrary to everything he believed in!"
After his suicide, BJ's mother, Laurie, checked out Accutane on the Internet and found many adverse events associated with the drug that they was never told about.
But the most disturbing find she said, was the February 1998 MedWatch stating, "The FDA is advising consumers and health care providers of new safety information regarding the prescription anti-acne drug Accutane (isotretinoin) and isolated reports of depression, psychosis, and rarely suicidal thoughts and actions."
"After we found the MedWatch," Rep Stupak said, "I wondered why the FDA put out this warning, 18 years after the drug was approved?"
"More important," he continued, "why weren't these warnings on BJ's Accutane package which had been revised 4 months after the MedWatch was issued?"
Two other couples testified at the hearing about their sons who had no history of depression, but yet committed suicide while taking Accutane. The spontaneity of the suicides became the center piece of discussion between committee members and witnesses during the hearing.
Susan and Martin Turney from Watertown, New York testified about their 16-year-old son, Matthew, who took his own life on March 14, 2001, and was on Accutane at the time of his death.
In retracing the days leading up to Matt's death, nothing indicated that anything was wrong. The night before the suicide, everything was normal his parents recalled. The family had a nice dinner together, talked about the day's events and joked and laughed with each other like always.
The next morning, Matt got up for school as usual. Before leaving to catch the bus, he looked at his father, smiled and said "Good Bye," and yelled, "Good Bye Mom. I love you," to his mother who was in another room, just like he did every morning.
By all accounts, Matt was fine at school that day. He talked to his guidance counselor about a program she had recommended for the next year. He asked a girl to a dance and she agreed to go. He took a couple of tests and did well.
On the bus ride home, Matt sat with his friends and laughed and fooled around just like any other day. He got off the bus and stopped to pick up the newspaper and mail as usual. He took off his shoes in the entryway, placed the mail and newspaper on the kitchen counter as he always did, and went into his room and hung up his coat.
His parents say it is at this point that Matt's normal routine changed. He did not turn on the TV, or get a snack or check his email as usual. Instead, he apparently went into the master bedroom, unlocked the gun case, took out a gun and shot himself.
His father came home from work and yelled "Hello" to Matt, but got no response so he went looking for him and found Matt on the floor of the bedroom with no heartbeat.
While answering questions from police at the hospital, Matt's parents were asked if Matt was taking any medication and they said Accutane. As soon as they answered, they remembered a TV Dateline program about the parents whose son committed suicide while on Accutane.
After watching the program Matt and his mother had went to the Dermatologist to discuss the story and their concerns about Accutane. The Dermatologist said that there had been a couple of unsubstantiated cases of depression and suicide, but that there was no scientific proof that Accutane could cause it and that Matt "didn't fit the profile anyway."
Matt's parents told the committee how they later found out that Accutane was supposed to be reserved for the most severe cases of nodular, cystic acne and provided the panel with a school picture of their son taken about 2 weeks before he started on Accutane that showed he did not have a severe acne problem.
"After talking to all of Matt's friends, family, teachers, and co-workers," his father told the committee, "we confirmed what we had already known, Matthew was not depressed!"
"His sudden death came as a shock to every person who knew Matt, including us, his parents," he said. Matt's suicide was "spontaneous," his parents said:
"There was no depression. There was no warning. There was nothing for us to look for. There was no reason for his death, other than Accutane."
Michael and Caroline Bencz also testified at the hearing about how their son, James, committed suicide without any sign that he was depressed or troubled. They told the panel that at the time of his death, he had everything to live for stating:
"James was not the person anyone would expect to commit suicide. He had friends and family. He had financial and personal success. He had plans for the future - both near and long term.
"The week James died, he was to leave on a skiing trip to Austria with a few of his firefighter buddies. James had plans for his future, and death was not in that plan."
"He was witty, humorous, talented, a great sportsman, intelligent, and highly competitive," his parent said, "but most of all, above all that, a wonderful human being.
In late 2001, they told the panel, they learned that a doctor prescribed Accutane for James. These parents also provided the committee with a picture of their to show that he never had a severe acne problem. All they could figure out was that maybe the skin diving suit he wore may have irritated his skin on his neck and back.
The last day they heard from James, on February 23, 2002, he called to say he did not feel well, that he had a headache. His last words to his parents were: "I don't feel too good, I'm going to try to get some sleep."
Over the next few days they did not hear from James which was very unusual. It was not like him, his parents said, to disappear for days at a time without letting anyone know where he was.
When he did not turn up, a massive man hunt was conducted, and he was eventually found on March 4, 2002, at the bottom of a lake, with a 44 pound barbell strapped to his body. A lake where James and his sister used to sit as children skipping rocks.
He died, his father told the committee, "under circumstances so bizarre for someone like James - a diver, a firefighter, and an athlete - with so much to live for, and so many future plans."
"We wish every minute of every day that we had never heard of that drug," they told the committee. "It took our son, our life as we know it, and left us with huge craters in our hearts that can never be filled in again."
These reports of inexplicable suicides were alarming to members of the committee. "Is it possible that this medication has an effect, an action that results in spontaneous, impulsive, self destructive behavior that is different from that which occurs from a clinical depression?," Congressman Ted Strickland (D-OH), who has a PhD in psychology, asked.
"I know of no clinical concept of depression that has an instantaneous onset and what we've heard described are people who are emotionally," Rep Strickland said, "psychologically healthy with none of the clinical signs of depression spontaneously doing something to themselves."
"So I'm wondering," he concluded, "if we are dealing here with something other than depression, and that we ought to recognize that."
The FDA Office of Drug Safety keeps a monthly cumulative count of psychiatric adverse event reports in AERS. According to Dr Janet Woodcock, Director of the Center for Drug Evaluation and Research, at the hearing, as of November 30, 2002, AERS contained 3,104 reports with at least one reported psychiatric event.
The FDA is aware of 173 reports of suicide in association with Accutane, she told the panel. She noted that the FDA had requested quarterly summaries of psychiatric events from Roche and said the most recent summary through August 2002 indicated approximately 6,000 additional reports that include psychiatric events
Because the 173 cases of suicides ware based on self reporting, experts say that figure is highly suspect and that being as few as 1% of suicides are reported as adverse events, it could mean that the actual number of suicides may be as high as 17,000.
During his December 11, 2002 statement to the committee, Congressman Stupak pointed the finger of blame directly at the FDA when stating:
"Accutane is a powerful, dangerous drug with devastating consequences for some patients. The birth defects caused by Accutane are horrific. The FDA's response to the birth defects and psychiatric events has been inadequate, irresponsible and unacceptable. Thousands of babies, teenagers, and young adults have died prematurely.
"While the FDA has been aware of the birth defects since at least 1982 and the psychiatric injuries since 1985, their responsibility to protect the public has been inconsistent and without direction."
There is no debate about whether Accutane is a moneymaker. According to the Associated Press on August 21, 2006, patients usually take it for up to a year at a cost of $10 to $15 per day. And in the December 11, 2002 hearing, Congressman Stupak turned the attention of the committee to Roche's conduct of putting profits before people and stated:
"They have done everything possible to prevent the American people from learning of the psychiatric injuries and deaths associated with Accutane. Even, today ... Roche will deny any casual effect of Accutane with the abortions, deaths, and suicides caused by their product."
"We cannot allow the drug manufacturer and the FDA to continue to turn a blind eye to the lives lost, families devastated and dreams dashed by an acne drug," he said.
"The American people, our children," he said, "are not collateral damage in the scheme of corporate profits!"
Subscribe to:
Comments (Atom)