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WHO & Pharma under fire over swine flu

Posted by medconsumers on April 2, 2010

Before the faux swine flu pandemic fades from memory, consider this: One country—Poland—made the decision not to knuckle under to the pharmaceutical industry and buy H1N1 swine flu vaccines for its citizens. Dr. Ewa Kopacz, who is Poland’s minister of health, decided against a national vaccination campaign for several good reasons. She was not convinced that the vaccines were completely safe. Furthermore, the H1N1 flu appeared to be relatively mild in the countries of the southern hemisphere where the flu season was coming to an end. But it was the “conditions of purchase” that confirmed her decision. She was told by the vaccine companies that only the government could purchase their products—-vaccines would not be sold to clinics or anyone in Poland.

The price of each vaccine would be two to three times the cost of the yearly seasonal vaccine, though Dr. Kopacz knew the H1N1 vaccine is based on exactly the same technology. What’s more, it was not known at the time whether people would need one or two vaccines for full protection. And most outrageous: the Polish government was expected to sign a contract, stating that anyone injured by a vaccine would be the government’s responsibility. (Note: the U.S. government had long ago accepted this one-sided agreement.) Poland had fewer swine flu deaths this season and the virus was less virulent than in other countries. Though only half the vaccines in the U.S. were used, the estimated number of U.S. flu deaths this season was the lowest in years.

For standing up to the vaccine companies’ threats of dire consequences of her decision, Dr. Kopacz was the star of a hearing conducted on Monday by the Council of Europe in Paris, and attended by members of parliament. The gathering aimed its initial ire at the World Health Organization (WHO) for its changing definitions of pandemic and its alarmist warnings that were described as a “monumental mistake.” The result: a huge waste of money, unnecessary fear and anxiety; and a distortion of health services. Several speakers listed other pandemics like SARS, Creutzfeldt-Jakob disease (“mad cow”) and the avian (bird) flu that never lived up to the threat level announced by WHO. “Not a single person died from the avian flu in my country,” said the professor who was the former head of the French Red Cross. It is like the boy who cried ‘wolf,’ warned Paul Flynn, MP from the U.K, “If a truly dangerous virus does emerge some day, few people will take notice of it. The trust in the WHO has been undermined and it must be rebuilt.”

The WHO was the proverbial empty chair at this meeting because it declined the invitation and, the MPs said, had cloaked itself in secrecy at a prior meeting which was the first attempt to get answers to questions like: who decides that something is a ‘phase-6 pandemic’? And based on what evidence? (Another meeting, this time with WHO representatives, is planned for April 15 in Geneva.) Dr. Tom Jefferson of the Cochrane Collaboration spoke of how little reliable scientific evidence there is—not only to support vaccine use but also for understanding influenza itself. “The randomized trials that have been conducted are too small and too short [in duration],” he said, referring to vaccine trials that are usually funded by companies that make the vaccines. “The harms are not even looked for. We can’t answer the question of whether vaccines are safe.” Dr. Jefferson called for a large taxpayer-funded multi-country vaccine trial to fill the serious information gaps about vaccine effectiveness and possible harms.

As the hearing went on, the pharmaceutical industry became the major target. Several speakers called for more scrutiny of the pharmaceutical industry’s influence on health policy. They know that billions of pounds and Euros were spent on vaccines and unproven antiviral drugs like Tamiflu, and now they want to know who profited from WHO decisions. There must be more scrutiny of WHO’s key opinion leaders, especially those who fanned the flames of pandemic fears while taking pharmacuetical industry consulting fees. (Though unmentioned at this hearing, one H1N1 key advisor to WHO has been under investigation for personally profiting from the vaccination. Click here for more.)

Dr. Marek Twardowski, Poland’s undersecretary of state, ministry of health, brought the discussion back to the vaccine companies’ preposterous contract that his country was expected to sign. “Your governments did in fact sign contracts that shifted the responsibility for vaccine-related harm to your governments, and these agreements were made in confidence [i.e., secret],” he told the MPs. “As of March of this year, none of the vaccine companies brought their products into your countries under normal marketing conditions. Can you imagine if car companies like Toyota decided that they will only sell their cars to a government and then when a serious defect shows up like the Toyota’s accelerator problem, the taxpayers are expected to pay for it?” This is an “extremely dangerous precedent,” he said. “And I hope that today’s deliberations result in this never happening again.”

It’s hard to imagine such a conversation taking place in the U.S. Congress, which is bought and paid for by the pharmaceutical industry. And it’s unlikely many Americans know that vaccine companies already made sure the government pays for injuries caused by their products. In the wake of 9/11, Congress passed a federal law that allows vaccine companies to be protected from liability in the event of a vaccine-related injury. Authorities need only declare a public health emergency for the protection to go into effect. And if you think that the vaccine companies need protection from lawsuits to continue making vaccines, see this Bush-era press release from Public Citizen: “Flu Vaccine Shortage: Another Example of How Bush Dis-Torts the Truth About Lawsuits”

Click here to see the Webcast of the March 29 Council of Europe hearing.

Maryann Napoli, Center for Medical Consumers©ISSN 2155-1480

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Risks of Biologic Drugs

Posted by medconsumers on December 1, 2008

New Concerns About a Class of Drugs Called Biologics

The fastest growing class of new drugs in the U.S. is the so-called biologics. Although the first in this class of drugs was approved in 1982, most have been marketed for a decade or less and little information was available about their safety. A team of Dutch researchers set about to address this important knowledge gap and their findings were recently published in the Journal of The American Medical Association.

Their findings? Almost one in four new biologics approved in the US and/or the EU between 1995 and 2007 had safety problems serious enough to require regulatory action after their approval. The term biologics (also known as biologicals) refers to drugs derived from living material, which can be human, plant, animal or microorganism in origin. Production of biologics is considered to be much more complex than that of traditional drugs. According to the Dutch researchers, “small differences and changes in the production process can therefore have major [safety] implications.” Examples of popular biologics include Enbrel and Remicade for rheumatoid arthritis, Tysabri for multiple sclerosis and Avastin and Herceptin for cancer.

While no biologic has been withdrawn, 19 were found to have had safety problems severe enough for regulators to require black box warnings on the labeling. Adverse events include life-threatening infections, acute hypersensitivity reactions and worsening heart failure—among others. Most of the regulatory actions were taken between 3 ½ and 5 years after approval.

There are some important overall lessons to be learned from this study. First, the data lends supports to the advice that, if better-understood treatments are available, a newly approved drug should be used with extreme caution, if at all, for at least the first five years after marketing. Second, the Dutch researchers suggest that the mode of action and complexity of biologics should demand heightened safety scrutiny by regulatory authorities before approval. In addition, there is some evidence that biologics may have higher rates of safety problems than traditional drugs. This is especially worrisome since about one quarter of newly approved drugs are biologics and their numbers are expected to grow rapidly in the coming years.

One possible reform in the FDA approval process that I believe would address this concern, and which I strongly support, would be to create a new option for FDA to grant “conditional approval” of a new drug when there is any hint of serious safety problems. At present, the FDA can only approve or disapprove a new drug; there is no middle ground. A conditional approval option could constrain the use of a newly approved drug suspected of safety problems by imposing limits on its prescribing and distribution by requiring its makers to accept rigorous safety monitoring.

The pre-approval trials currently required by the FDA suffer from serious limitations. For example, there are often only a few patients in the trial and the trials are often too short to get a full picture of the drugs’ effects. As a result, safety problems often go undetected until the drug is in widespread use. By that time thousands of people may have been exposed to serious harm.

I believe that establishing a conditional approval option would be a win-win for patients. It would result in a better understanding of a new treatment’s safety and prevent harm. And it would provide access to new treatments for patients with life-threatening conditions that are unresponsive to other therapies.

Arthur A. Levin, MPH, Center for Medical Consumers ©

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Osteoporsis Drug: New Adverse Effects

Posted by medconsumers on August 1, 2008

More Bad News About Fosamax

An unusual type of severe fracture has been reported in people taking Fosamax for more than five years. Ironically, this drug is widely prescribed to prevent fractures in people with bone loss. The new finding came from a series of case reports published in the May/June Journal of Orthopaedic Trauma.

The fractures occurred in the femur, which is the large thighbone that connects to the hip. They are particularly alarming because of the unusual pattern described by many of the people whose cases were reported. Their thighbones had ached inexplicably for months or weeks and then broke spontaneously while walking or standing. Nineteen of the 20 people in the case series had been taking Fosamax for an average of nearly seven years.

These are not the first reports of what is called atypical low-energy fractures after long-term Fosamax (generic name: alendronate) therapy. In 2005, the Journal of Clinical Endocrinology & Metabolism published case reports of nine women who sustained spontaneous non-spinal fractures while on Fosamax, six of whom showed either delayed healing or no healing for three months to two years. And last year, the Journal of Bone and Joint Surgery reported that nine Fosamax-treated women in Singapore showed the same early warning signs prior to a spontaneous fracture.

These adverse effects are not unexpected. Ever since Fosamax first came on the market over a decade ago, some osteoporosis researchers have periodically expressed safety concerns about prolonged usage, mostly in letters to medical journals. The drug improves bone density, but it does so by suppressing the bone remodeling process by which microscopic parts of old bone are constantly being dissolved and new bone is added.

Here’s how bone physiologist Susan Ott, MD, describes Fosamax’s effect on this process, “The bisphosphonates get deposited in the bone and will accumulate for years. It is possible that many years of continuous medicine would make bone more brittle or impair the ability to repair damage. Bisphosphonates do reduce fractures and improve measurements of bone strength for the first five years in both animal studies and in women who have osteoporosis. After five years, the fracture rates are as high in the women who keep taking alendronate as in the women who quit (see http://courses.washington.edu/bonephys).”

Although Fosamax advertising has focused women and doctors on the importance of bone density, bone strength is now regarded by osteoporosis researchers as more important to fracture prevention (see HealthFacts, April 2008).

Atypical low-energy fractures did not appear in the clinical trials required of Merck, maker of Fosamax, for FDA approval because these trials lasted only three to five years. Although these fractures are considered to be a rare side effect at this time, some osteoporosis experts are now advising against taking the drug beyond five years.

The published case reports all involved Fosamax, which is one of a drug class called bisphosphonates. Others in the class include: Actonel, Boniva, Aredia and Didronel. That all the case reports are confined to Fosamax may be explained by the fact that Fosamax was the first bisphosphonate to be aggressively marketed for the treatment of osteoporosis, and many more women worldwide have been taking this particular bone drug and for a longer time.

It’s reasonable to assume that the spontaneous fracture risk is associated with prolonged use of any bisphosphonate until research proves otherwise. Read this March 15, 2010 notice from FDA, stating that the agency has reviewed the relevant data and “found no clear connection between bisphosphonate use and a risk of atyical subtrochanteric femur fractures.” Also, read this 2009 updates on this topic “Osteonecrosis of the jaw—more common than previously thought” and this article written for the American Journal of Nursing “The Marketing of Osteoporosis–How a risk factor became a disease.”

Maryann Napoli, Center for Medical Consumers ©

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Women-in-Towels Evista Ad Critiqued

Posted by medconsumers on July 1, 2008

The women in Eli Lilly’s new ad campaign are attractive, healthy-looking and wearing nothing but towels. “Cut two risks with Evista. The only agent indicated to treat osteoporosis and reduce the risk for invasive breast cancer.”

That two-for-one claim for Evista makes it different from other drugs taken by symptom-free people. Studies showed that the harm related to each disease drops a percentage point or two in those who took Evista, compared to those who did not. The drug is better than a placebo (or it would not get FDA approval), but not much better. This is a recurring theme in Center for Medical Consumers articles because it’s a recurring theme in many drug trials. And often the small risk of a serious adverse reaction to the drug equals that small chance of benefit.

Evista (generic name: raloxifene) has been on the market since 1997 as an osteoporosis drug. It produces a 2%-3% increase in bone density; reduces the rate of vertebral (spinal) fractures; but does not prevent the most serious type of fracture (hip). Vertebral fractures can cause pain and a dowager’s hump in advanced age, but many are symptomless. The studies did not last long enough for Lilly to make claims regarding prevention of a dowager’s hump or loss of height.
Breast Cancer “Risk Reduction”

Last year Lilly received FDA approval to promote Evista as a drug that can “reduce the risk of invasive breast cancer.” This careful wording from the Evista ads is important. Lilly cannot claim its drug prevents breast cancer because the disease can take anywhere from 8 to 17 years to develop. There were, in fact, fewer breast cancers diagnosed in the women taking Evista, compared to those taking placebos. But the trials didn’t last long enough to determine whether the drug prevents breast cancer or simply delays its onset. In Evista trials that lasted up to eight years—breast cancer was diagnosed in 2.5% of the women taking a placebo and 1% of the women taking Evista.

The other claim for Evista is based on the fact that the women in the studies already had osteoporosis (bone loss). One way bone drug companies can inflate the benefit of their product is to count symptomless vertebral fractures that can be detected only on x-ray. (In other words, the women are unaware of them.) At the start of the Evista trial about half the women had painful vertebral fractures and the other half had “fractures diagnosed radiographically.” After four years, things looked better for Lilly when results for all women were combined, but less impressive when women with painful fractures were singled out. In the latter group, only about 1% fewer Evista-treated women had new painful vertebral fractures than the women taking placebos.

Thus far serious adverse reactions to Evista include deep vein thrombosis, pulmonary embolism, retinol vein thrombosis and an increased risk of fatal stroke. (See boxed warning of the FDA-approved label). Separately, each is classified as rare, which, according to FDA standards, describes any drug reaction that occurs in less than 2% of study participants. Collectively, though, these potentially fatal adverse reactions could reach 1-2% which comes close to the percentage of women who benefited from Evista in the FDA-required clinical trials.

And lastly, the visual message conveyed by the women-in-towels ad is misleading. Most of the women look to be in their fifties. At the start of the Evista trials, however, most participants were over age 65 years, a time of life when vertebral fractures are far more likely to occur.

Maryann Napoli, Center for Medical Consumers ©
July 2008

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Chantix: Another FDA Failure?

Posted by medconsumers on June 1, 2008

For an inveterate FDA watcher like me it was an interesting spring. First, the agency’s failure to police the safety of imported medical products became front-page news when it was revealed that batches of the blood-thinner heparin caused fatal allergic reactions because of contaminated ingredients imported from China. Coming on top of the lead-painted children’s toy and poisoned pet food episodes of a year earlier, the incident confirmed that the FDA lacked sufficient resources to carry out the requisite inspections of overseas manufacturers under its jurisdiction.

The predictable result was a firestorm of criticism from Congress and the press. For the first time that anyone could remember an FDA Commissioner violated the Washington protocol that political appointees do not lobby Congress on behalf of their own agency. Andrew von Eschenbach did just that in a letter to a key Senator requesting $275 million as a supplemental appropriation

Predictably, a Bush Administration spokesperson said that the additional funds are not necessary.
Besides introducing legislation to provide additional funding, lawmakers are considering a requirement that imported drugs, medical devices and food products be labeled with the country of origin and a special identification number to help FDA track unsafe products back to their manufacturer. Legislation has also been proposed that would impose fees on manufacturers and importers to fund overseas inspections of their manufacturing facilities. Significantly, some lawmakers want to give the FDA the power to order recalls of unsafe imported food and medical products. At present the FDA can only ask a manufacturer to withdraw its product.

On the domestic front, a report linking the antismoking drug Chantix to a large number of deaths and serious injuries was released recently by the Institute for Safe Medication Practices (ISMP). Earlier, the FDA had issued a Public Health Advisory warning that the drug was associated with serious neuropsychiatric reactions, including suicide.

The ISMP researchers found that Chantix users had an inordinately large number of severe injuries, major seizures, movement disorders and heart rhythm disturbances often leading to loss of consciousness, as well as transient blindness.

Chantix, which is made by Pfizer, has become the most frequently mentioned drug in serious injury reports to FDA after only 18 months of availability. From October to December 2007, almost 1,000 Chantix injury reports were received by the FDA compared to a median of five injury reports for other problem drugs over the same time span, according to the ISMP.

Because the antismoking drug’s side effects could render a user unconscious or temporarily blind, the ISMP findings set off immediate alarms about Chantix’s risks to airline pilots, train, bus, and subway operators, truck drivers and those who operate any other heavy machinery. To avoid the possibility of a catastrophic airline accident, the FAA promptly banned the drug’s use by flight crews. And, the Federal Motor Carrier Safety Administration issued a warning advising medical examiners “to not qualify anyone currently using this medication for commercial motor vehicle licenses.”

Since drivers of motor vehicles include almost the entire U.S. population over age 16, the FDA should be asking Pfizer to immediately withdraw Chantix from the market. Helping people stop smoking may be an important public health goal but not when the trade-off is an even earlier drug-related death.

Arthur A. Levin, MPH, Center for Medical Consumers ©
June 2008

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Drug-Induced Memory Loss

Posted by medconsumers on June 1, 2008

Memory Loss and the Drugs That Can Cause It

Memory loss, cognitive impairment, dementia, Alzheimer’s disease. As the media frequently remind us, all these problems will soon reach epidemic proportions because more and more Americans are living to an advanced age. Virtually no media attention has been given to the research that is slowly building a case against one large category of prescription drugs linked to a more rapid decline in cognitive function in older people. Known as anticholinergics, these drugs include everything from antihistamines and bronchodilators to blood-thinners and anti-nausea medicines.

The latest study to indict anticholinergic drugs was presented recently at the annual meeting of the American Academy of Neurology. As reported on Medscape, the on-line news service, one woman’s experience with Detrol, a drug for overactive-bladder symptoms, provided the impetus for the new study. It was led by Jack Tsao, MD, associate professor of neurology at the Uniformed Services University of the Health Sciences, Bethesda, MD.

The woman went to her doctor with memory difficulty and hallucinations, Dr. Tsao explained, but tests showed that she did not have Alzheimer’s-type dementia. The focus then went to Detrol, which she had just started taking. Fortunately, her doctor recalled the experience of another patient on the same drug with the same symptoms. That patient’s problems had resolved once the drug was stopped.

The experiences of these two patients prompted Dr. Tsao to contact researchers at Rush University in Chicago, who scrutinized data generated by a large study that has been following nearly 900 older Catholic nuns and clergy ever since it began in 1993. The stated aim of the Rush Religious Orders Study is “to discover what changes in the brain are responsible for memory and movement problems” and “to look closely at the transition from normal functioning of the aging brain to the mild cognitive impairment that can be an early sign of Alzheimer’s disease.” At the time of enrollment, all participants were free of dementia.

Tsao and colleagues found that cognitive decline was more rapid after participants began to use anticholinergic drugs compared to those who did not take these drugs. In a telephone interview, Dr. Tsao emphasized a key discovery about those on anticholinergics. “Even though their cognitive performance was worse, we did not find that they were at an increased risk of being diagnosed with Alzheimer’s disease or dementia.”

Although Dr. Tsao’s study is preliminary, its findings are consistent with those of earlier studies. One, for example, was conducted in France and published in 2006 in the British Medical Journal. Unlike the Religious Orders Study, this one recruited people over age 60 specifically to assess the “potential of anticholinergic drugs as a cause of non-degenerative mild cognitive impairment.”

The 372 participants were given annual cognitive performance assessments as well as blood tests. Over 9% had continuously used anticholinergic drugs during the years before their cognitive skills were tested. “Compared with non-users, they had poorer performance on reaction time, attention, delayed non-verbal memory, narrative recall, visuospatial construction, and language tasks but not on tasks of reasoning, immediate and delayed recall of word lists, and implicit memory,” wrote the French researchers led by Dr. Marie I. Ancelin.

Similar to Dr. Tsao’s conclusion, Ancelin and colleagues found that mild cognitive impairment does not put someone on the path to dementia: “Although the consistent users of anticholinergic drugs were significantly more likely to have a diagnosis of mild cognitive impairment at one-year follow-up (80%) than consistent non-users (35%), we found no difference in overall dementia rates at eight-year follow-up between the drug users and non-users.”

Then there’s the problem of drug interactions. The French researchers noted that it would be inappropriate, even counterproductive, for doctors to prescribe acetylcholinesterase inhibitors to people who are already taking an anticholinergic drug. Sold under brand names of Aricept, Exelon and Razadyne, acetylcholinesterase inhibitors are an aggressively promoted, but minimally effective, class of drugs prescribed for Alzheimer’s and dementia.

Dr. Tsao was asked whether doctors know these two classes of drugs should not be prescribed together. “There have been published reports of people who were taking anticholinergics and then being started on Aricept. So you are pushing and pulling on the same system with different antagonistic drugs. One is inhibiting the anticholinergic system, and the other is trying to enhance it. It’s a common concern among nursing home patients with dementia. They’re already on Aricept and then they are given an anticholinergic, which defeats the purpose.”

Ancelin and colleagues had their own warning about prescribing practices. “Not only do doctors commonly fail to associate cognitive dysfunction in elderly people with anticholinergic agents, they also underestimate anticholinergic toxicity, prescribing such drugs at high to excessive doses.”

What you can do:

  • If you must take an anticholinergic drug for a chronic condition, question your doctor about the dose. It may be possible to lower the dose without losing effectiveness.
  • See below for a partial list of anticholinergics.
  • Exercise regularly. In her new book entitled, “Can’t Remember What I Forgot,” (Harmony Books), Sue Halpern found aerobic exercise is the only memory improvement remedy that has good studies to back it up (and she looked at everything from drugs and supplements to fish oil and crossword puzzles). Brisk walking is enough because no additional benefit is shown for extreme or prolonged exercise. Eat lots of blueberries, too.
  • Drink at least three cups of coffee, or six cups of tea, per day. Caffeine protected women over age 65 years from cognitive decline, compared to women who drink one cup or less, according to studies published last year in the journal Neurology.

Maryann Napoli, Center for Medical Consumers ©
June 2008

Is Your Drug an Anticholinergic?

Ask your pharmacist or doctor whether a drug you are taking is an anticholinergic. The usual advice—read the written material that comes with the drug—does not hold in this case. The much-abridged list of anticholinergics below came from a medical journal, but a spot check of the written information that comes with these drugs failed (with one exception) to mention the word anticholinergic.

Lomotil, Lofene, Logen, and many other drugs that contain atropine for diarrhea;

Detrol, Enablex, Trospium, Ditropan for overactive bladder;

Hyosol, Hyospaz for disorders of the gastrointestinal tract;

Prednisone Intensol, Sterapred for certain types of arthritis, severe allergic reactions, etc;

Bronkodyl Elixophyllin, Slo-bid, Theo-24 and other drugs containing theophylline for asthma, chronic bronchitis and other lung diseases;

Codeine for pain and inflammation. Sold under more than two dozen brand names and present in more than 30 combination products;

Xanax, Alprazolam Intensol for anxiety disorders and panic attacks; Valium and Diazepam Intensol for anxiety disorders, muscle spasms, and seizures;

OxyContin, Oxydose, Roxicodone for moderate to severe pain;

Capoten, or captopril, for hypertension and heart failure;

Lasix to reduce the swelling and fluid retention caused by various medical problems, heart or liver disease. It is also used to treat high blood pressure.

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Pharmaceutical Industry to Public: Drop Dead

Posted by medconsumers on May 1, 2008

The Pre-emption Shield Explained

The scenario has become depressingly repetitive: A heavily promoted drug prescribed to millions over the years is found to have potentially fatal adverse reactions; a hundred or so deaths are linked to the drug; the drug maker acts as if it just learned of the harm; a lawsuit precipitates the release of in-house documents showing that company officials knew of the dangers long before its drug went on the market; the injured patients have their day in court.

The last phase of this scenario, the one where people go to court to seek compensation for their injuries, will be eliminated if the pharmaceutical industry gets its way. The industry takes the position that a drug’s safety must be proven to the FDA’s satisfaction before it is allowed on the market; therefore, the drug maker should be held harmless for anything that happens thereafter. “The FDA should not be second guessed by the courts” goes the pharmaceutical industry’s legal argument for what is called pre-emption. Not surprisingly, it has the strong backing of the Bush Administration.

Proof of Safety Inadequate

The presumption that the FDA approval process guarantees safety is absurd. The two clinical trials required by the FDA are usually short-term and always conducted by the drug makers themselves. Rare or uncommon serious adverse reactions to drugs are typically not apparent until hundreds of thousands of people take the drug over the course of many years. Worse of all, drug companies are known to withhold negative trial results from the FDA.

And if that’s not bad enough, a bipartisan Congressional panel recently confirmed what has been known for years: The FDA’s ability to protect the public’s interest is obstructed by the fact that it is seriously underfinanced. This affects everything from the agency’s inability to vet all drug advertising for misleading claims to its drug-safety monitoring system that, according to the nonpartisan Government Accountability Office, captures less then 10% of all serious adverse reactions to drugs after they go on the market.

Most Recent Industry Crimes

Within a recent three-week period alone, the national media spotlighted three cases in which pharmaceutical giants misled the FDA about the safety of their products. Eli Lilly and Alaska agreed to a $15 million settlement on behalf of the state’s Medicaid patients who developed diabetes as a result of Lilly’s antipsychotic drug Zyprexa. The company hid the risks (e.g., deaths, strokes, pancreatitis) and exaggerated the benefits of Zyprexa while encouraging primary care doctors to prescribe it for unapproved uses.

Another case involved the bestselling pain-reliever Vioxx withdrawn in 2004 by its maker Merck because it increased the risk of heart attacks and strokes. And lastly, there’s Johnson & Johnson’s birth control patch, now known to cause blood clots, strokes and deaths. In all three cases, the dangers would have remained unknown—and people would continue to be injured—had it not been for lawsuits.

Among the e-mails, letters and other internal documents released during the Vioxx litigation was damning evidence that Merck knew of the drug’s dangers early-on. The company’s initial research made “the surprising discovery” that “Because selective COX-2 inhibitors [Vioxx, Celebrex, Bextra] do not affect platelet function whereas standard NSAIDs [aspirin, ibuprofen, etc] do, it was hypothesized that selective COX-2 inhibitors might…increase the risk of cardiovascular events.” This warning was repeated twice (at a meeting and in a memo), according to Merck documents—all dated prior to Vioxx’s approval by the FDA in 1999.

Vioxx made news again recently when the most comprehensive study of Merck’s internal documents released during the Vioxx litigation revealed the manipulation of the company’s clinical trial results. One example: Merck conducted several trials trying to prove that Vioxx slows the progression of cognitive impairment in people with dementia. The company’s early analysis of these trials showed “a significantly increased mortality risk” among the participants assigned to take Vioxx (their death rate was more than twice that of the placebo group). This, however, was not the way Merck reported the results to the FDA. Instead, Merck minimized the death risk by using a less-valid type of data analysis of the same trial results and concluded that Vioxx was “well tolerated.”

When the study of the Merck documents was published last month in the Journal of the American Medical Association, the accompanying editorial made it clear that the manipulation of trial results is not the sole purview of one company. The editors also noted that the evidence necessary to demonstrate Merck’s misdeeds became public—and publishable—only because of litigation. Last fall, Merck agreed to a $4.85 billion settlement to resolve tens of thousands of lawsuits filed by former Vioxx patients or their families.

This is not likely to be the way things will turn out for the young women injured by Johnson & Johnson’s popular Ortho Evra birth control patch. The patch delivered far more estrogen into the bloodstream than standard oral contraceptives, increasing the risk of potentially fatal blood clots. More than 3,000 women and their families have sued Johnson & Johnson claiming that the patch caused heart attacks, strokes and at least 40 deaths. Documents made public by this lawsuit showed that Johnson & Johnson’s own trial revealed these risks in 1999. The company, as The New York Times put it, “obscured the finding in a 435-page report to the FDA.”

The Pre-Emption Dodge

The Ortho Evra plaintiffs are now on hold while a similar lawsuit against yet-another drug company (Wyeth) becomes the test case for the pre-emption shield when it goes to the Supreme Court in November. The Court is expected to rule in favor of industry and make pre-emption the legal standard. A precedent was set in February when the Court ruled that the device industry is immune from damage suits filed by people injured by defective pacemakers, stents, etc.

Pre-emption is just the latest in a series of outrages perpetrated by the pharmaceutical industry against the public. At a time when criminal charges should be brought against company officials who withhold evidence of harm, the industry wants a pass. And it’s likely to get just that given the pro-business, anti-consumer Supreme Court decisions over the last few years.

In the meantime, if you are scheduled for a knee replacement or stent or a new heart valve, be aware that medical devices now come with an invisible warning from industry:

In event of a major defect or other serious harm: You’re on your own.

Maryann Napoli, Center for Medical Consumers © May 2008

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Avoid Drug-Related Injury

Posted by medconsumers on May 1, 2008

One Way to Avoid a Drug-Related Injury

It can take years to learn the full range of serious adverse reactions to prescription drugs. That point was driven home last month when, in one issue of the journal Archives of Internal Medicine, several studies revealed new-found harms. The popular diabetes drugs, Actos and Avandia, increase the chance of having a fracture. Fosamax and other drugs in the class known as bisphosphonates, widely prescribed for osteoporosis since 1995 to prevent fractures, can cause an irregular heartbeat called atrial fibrillation. And postmenopausal hormone drugs, once aggressively urged for all women over 50 to prevent heart attacks and strokes actually cause strokes in some women, regardless of the type of hormone regimen or when it was started.

You get the picture: the drugs taken to prevent one major health problem can often cause another. The editorial that accompanied these new studies offered the excellent suggestion that doctors should quantify the benefits and risks so their patients can fully understand what they are getting into once they are told to go on long-term drug therapy. If, say, a bone drug helps only one in 100 women avoid a hip fracture and the same drug causes a potentially fatal atrial fibrillation in one in 100, then it’s a wash.

Jerry Avorn, MD, and William H. Shrank, MD, Harvard Medical School, offered a more immediate suggestion for avoiding drug-related injuries that targets people over the age of 65 years, the group with a high prevalence of adverse drug reactions. In a recent issue of the British Medical Journal, Avorn and Shrank wrote, “When an elderly person experiences an adverse drug reaction, it may be mistakenly attributed by the patient or doctor to a new disease or (even worse) the aging process itself. Examples include the parkinsonian side effects of many antipsychotic drugs and the fatigue, confusion, or depression-like symptoms that can result from excessive use of heavily marketed psychoactive drugs.”

Avorn and Shrank go on to describe what they called an opportunity for “total cure” by stopping the offending drug or lowering its dose. “In our own practices we have often seen patients on a seemingly inexorable trajectory towards institutional care whose functional capacity was restored by thoughtful reassessment of their drug regimens. This has led to the useful if overstated recommendation that any new symptoms in an older patient should be considered a possible drug side effect until proved otherwise.”

Maryann Napoli, Center for Medical Consumers ©
May 2008

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Osteoporosis: Many Drugs Prescribed, Not So Many Hip Fractures Avoided

Posted by medconsumers on April 1, 2008

Fracture prevention is focused on bone density, but other factors like bone quality and muscle strength are also important, according to a recent commentary by two Toronto physicians for the Journal of the American Medical Association. They advocate a broader view of osteoporosis prevention but first, here is an historical context for this disease that has become a major health concern for women.

Osteoporosis was unknown to the public until the 1980s. The disease used to be diagnosed in the elderly only after a “fragility fracture” had occurred. But a new definition, based on bone mineral density, was established in 1993 at a World Health Organization meeting of osteoporosis researchers. Soon bone scans became a must for all women over age 50.

In 1995, the first non-hormonal drug to prevent osteoporotic fractures—Fosamax—came on the market. Its manufacturer, Merck, sponsored an aggressive ad campaign initially aimed at doctors, featuring a woman who looked no more than 45 and this message: “Don’t wait for a fracture.” Merck’s ads aimed at women simply told them to “ask your doctor whether a bone density test is right for you.” Chances are high that widespread use of bone scans would identify many women as having bone loss. The first step toward a drug prescription.

Many middle-aged women who had never had a fracture were put on Fosamax. It is unlikely that they were told that the drug had been tested only in elderly women who already had a fracture, and the results were unimpressive. After three years, hip fractures occurred in 1% of those on Fosamax, compared with 2% of those on a placebo. (A 50% reduction in hip fracture!” screamed some of the ads.) In time, another “condition” called osteopenia, or pre-osteoporosis, was created by drug makers. By then, other drug companies had introduced their own Fosamax knockoffs like Actonel, Boniva, Reclast, Zometa, etc. All are in the same drug class called bisphosphonates.

Drug prescribing is clearly tied in with bone mineral testing, but the now-popular scanning technique known by the acronym DEXA is not good at predicting which women in their early 50s will have a hip fracture at age 80 years, when it would most likely occur. This was the conclusion of a 1998 report from the British Columbia Office for Health Technology Assessment. The report was ignored in the U.S. where Merck was financing the installation of DEXA machines in doctors’ offices.

In 2005, The Seattle Times published an investigative series of medical articles. The in-depth report on the selling of osteoporosis revealed that two multi-national pharmaceutical giants had financed that 1993 World Health Organization meeting. (Ostensibly, the meeting was about a multi-country study of the prevalence of osteoporosis.) The pharmaceutical funding of this WHO meeting sheds new light on the revised definition of osteoporosis. What had been simply a risk factor (bone loss) became a disease (osteoporosis) at that meeting, where an arbitrary definition of bone loss was also created. Overnight, the number of potential customers for bone drugs had been expanded greatly.

The story of Fosamax and its knockoffs perfectly illustrates how the pharmaceutical industry starts creating a market for a new drug years before it is approved. First industry must sell you fear of a disease, then comes the drug to “prevent” its most serious consequences.

Today, the guidelines for bone density measurement recommend testing not begin before age 60, but now there’s a bigger problem Researchers have known, at least since 2000, that bone strength or bone quality are better predictors of hip fracture than bone density. In 2001, the National Institutes of Health redefined osteoporosis as a combination of bone mineral density and bone quality. But here’s the rub: There is no test for bone quality or bone strength.

In their recent commentary for the Journal of the American Medical Association, the Toronto physicians, Angela M. Cheung, MD, and Allan S. Detsky, MD, said that bone density and bone quality are just two of many factors to be taken into consideration for fracture prevention—in addition to the usual advice about calcium intake, vitamin D, exercise, smoking cessation and reducing alcohol intake. They call for more research into the reasons why elderly people fall, such as oversedation with prescription drugs, orthostatic hypotension (low blood pressure upon standing), impaired gait or balance, poor eyesight and hearing, arthritis, etc. They also want more attention given to tai chi exercises to improve balance and muscle strength. Research for fracture prevention should move beyond the realm of endocrinologists and rheumatologists to include neurologists, physiatrists, physiotherapists, engineers and muscle activation therapists.

Where can someone with osteoporosis find an engineer or a muscle activation therapist? “At an osteoporosis center based at an academic medical center,” answered Dr. Cheung in a telephone interview. “We have much to learn from these folks, and we need to engage in a dialogue with them to help people reduce their fracture risk.” Dr. Cheung, who is at the University Health Network and Mount Sinai Hospital in Toronto, was asked why she still sees a role for bisphosphonates when the trials cited in her commentary had such negative findings. [“...in two well-designed randomized controlled trials in which high-risk elderly people without fracture but low bone mineral density, treatment with bisphosphonates did not decrease the risk of hip fractures.”] “These drugs are not just for hip fractures, but for overall fractures,” she answered, citing the example of her patients who have difficulty eating because the rib cage has collapsed due to spinal fractures. She also praised a 2007 study by Black and colleagues, which showed that hip fracture can be reduced with a more potent bisphosphonate given intravenously to participants, aged 70 to 90 years. [Note: This study showed only a 1% difference between the drug-treated and the placebo groups in terms of hip fracture reduction.]

Unfortunately, the current TV ads for this intravenous once-a-year bisphosphonate drug are conveying the same misleading message shown in the early ads for Fosamax. They feature a thin, fit 60ish woman—far younger than those who participated in the clinical trial.

Maryann Napoli, Center for Medical Consumers ©
April 2008


FDA Alert about Osteoporosis Drugs

The FDA posted an alert on its Web site, “…highlighting the possibility of severe and sometimes incapacitating bone, joint, and/or muscle (musculoskeletal) pain in patients taking bisphosphonates. Although severe musculoskeletal pain is included in the prescribing information for all bisphosphonates, the association between bisphosphonates and severe musculoskeletal pain may be overlooked by healthcare professionals, delaying diagnosis, prolonging pain and/or impairment, and necessitating the use of analgesics.”

Bisphosphonates are a popular class of drugs prescribed to reduce the risk of fractures from osteoporosis. The alert applies to all drugs in this class, including Fosamax, Boniva, Actonel, Aredia and Didronel. The FDA reports, “The severe musculoskeletal pain may occur within days, months, or years after starting a bisphosphonate. Some patients have reported complete relief of symptoms after discontinuing the bisphosphonate, whereas others have reported slow or incomplete resolution.”

WWW.FDA.gov/medwatch/safety, 1/7/08

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Failed Vytorin Study Raises Questions About Cholesterol

Posted by medconsumers on February 1, 2008

A firestorm of bad publicity erupted over cholesterol drugs last month when an expensive combination drug proved to be no better than an older drug alone. This finding was suppressed for 20 months by Merck and Schering-Plough, the two companies that make Vytorin, which is a one-pill combination of Zetia and Zocor. Their two-year trial failed to prove that Vytorin is better than Zocor alone for slowing plaque accumulation; instead atherosclerosis worsened in those taking Vytorin.

But the study results were not revealed until the two drug companies were pressured into doing so by an article in The New York Times and a Congressional inquiry. Worldwide, about one million prescriptions for Vytorin and Zetia are written each week, and they generated about $5 billion in sales last year. Zocor can be purchased under its generic name simvastatin for less than $6 for a month’s supply; whereas an equivalent amount of Vytorin costs about $100. It was obviously in the two companies’ interest to withhold the negative results for as long as they could get away with it.

When Vytorin came on the market two years ago, it was impossible not to be cynical about its purpose. Merck’s patent for Zocor was running out, and its blockbuster status would soon be diminished with generic competition. The company joined forces with Schering-Plough, maker of Zetia, and sought FDA approval for Vytorin. Their FDA-required trials showed a 17% greater reduction in LDL, the so-called bad cholesterol, than Zocor alone.

Making this 17% reduction in LDL look like an amazing achievement was not much of a stretch. Merck and the makers of other statin drugs like Lipitor and Pravachol had already paved with way. Their respective marketing machines had long ago misled most of us (doctors included) into thinking that cholesterol reductions equal heart attack reductions. One consistently overlooked fact about statins: They are far better at lowering cholesterol than preventing heart attacks or strokes. And those small reductions in heart attacks and strokes shown in clinical trials are largely confined to high-risk middle-aged men and those with heart disease or diabetes. Vytorin, on the other hand, has not been proven to reduce heart attacks or strokes in anyone.

LDL Reduction Irrelevant

Though doctors tend to focus their statin-taking patients on the size of their LDL reductions, heart disease researchers have long ago noted that this is likely irrelevant. Statin trials often show that the size of the cholesterol reductions are not consistent with reductions in heart attacks. Such observations led researchers to suspect that the ability of statins to reduce heart attacks and strokes has less to do with cholesterol reduction and more to do with other biological effects like plaque stability and anti-inflammatory effects. Another important but overlooked observation: “Elevated LDL identify less than one half of individuals who will die from coronary heart disease” (Rosenson et al. Antithrombotic Properties of Statins, JAMA, May 27, 1998).

The fall-out from the Vytorin debacle continues to reverberate. At this writing, Merck and Schering-Plough are running full-page ads daily in the Times and Wall Street Journal, warning people not to be confused by a single study and to continue taking Vytorin. The advice was backed by the American Heart Association, which appeared to be an independent source until The Times reported that the AHA receives nearly $2 million a year from Merck/Schering-Plough Pharmaceuticals.

One of the unintended consequences of two drug companies withholding their negative trial results is that it led some in the media, notably Alex Berenson, an investigative reporter for the Times, to look back at another important failed cholesterol drug trial and question the very foundation of heart disease prevention. In his heretically titled article “Cholesterol as a Danger Has Skeptics,” Berenson cites Pfizer’s trial of its much-anticipated drug torcetrapib that raised HDL, the good cholesterol, and lowered LDL. The trial had to be stopped in 2006 because the drug caused heart attacks and strokes. (Sound familiar? Postmenopausal hormones were widely prescribed because they were so good at improving cholesterol levels but they also increased the risk of heart attack, stroke and blood clots.) “Torcetrapib’s failure shows that lowering cholesterol does not prove a drug will benefit patients,” said a skeptical Walter Reed cardiologist quoted in Berenson’s article.

Many researchers, physicians and scientists around the world have long questioned the import of high cholesterol for anyone other than middle-aged men. In fact there is an International Network of Cholesterol Skeptics (disclosure: we belong), but the skeptics have been marginalized over the years. Now some mainstream media like Business Week and the cardiology Web site, TheHeart.org are willing to give them voice.

Could the house of cards be falling? Would the house of cards be allowed to fall when a worldwide $40 billion-a-year industry is at stake?

For More Information

The International Network of Cholesterol Skeptics www.thincs.org

Business Week magazine (www.businessweek.com) click into past issues, January 17, 2008 Lipitor cover story: “Do Cholesterol Drugs do any Good?”

TheHeart.org from Web MD www.theheart.org, see video blog of Eric J. Topol, MD, who questions the import of LDL reduction in “Temple of the LDL Cholesterol.”

Maryann Napoli, Center for Medical Consumers ©
February 2008

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