As previously reported, the FDA and federal law enforcement authorities are becoming increasingly concerned with the sale of counterfeit drugs over the Internet and at pharmacies in Mexican border towns.

Although the operators of several Internet (and mail-order) operations have been arrested recently
 and charged with illegal drug sales through online pharmacies, the authorities have been frustrated by the fact that new websites are up and running almost immediately.

The Mexican problem is also becoming quite serious since counterfeit versions of drugs like Lipitor, Viagra, and Evista, which can be quite dangerous, are readily available in border towns like Juarez, Los Algodones, Nogales, and Tijuana. The FDA has been working with Mexican authorities to address this problem throughout Mexico and, as a result, 19 pharmacies have been suspended and over 105 tons of medicines have been confiscated.
Counterfeiting is known to be taking place in China and Russia.

Now, five heart patients in Hamilton, Ontario, Canada may have died after taking fake medication dispensed from the same pharmacy. The drug in question, Norvasc, is used to treat unstable angina and high blood pressure.
An investigation prompted by a local woman who was suspicious of an oddly colored pill in her supply of Norvasc. The pill turned out to be made of talcum powder.

The CPSC and Polaris Industries of Medina, Minnesota, announced the voluntary product safety recall of an additional 45,000 Polaris All Terrain Vehicles made in the United States. Customers should stop using the product immediately.
 
This expansion of the 15,000 Polaris ATV recall announced on May 3, 2005 includes several additional models, affecting about 45,000 additional units.
The models involved in this expanded recall are: Polaris Model Year 2004.5 Sportsman 500, Model Year 2005 Sportsman 400, Sportsman 500, Sportsman 600, Sportsman 700, Sportsman 6×6, Scrambler 500, Trail Boss and Magnum 330 ATVs.

Some 2004.5 and 2005 Model Year Sportsman, Scrambler 500 ATVs, Trail Boss and Magnum 330 ATVs were assembled with possibly defective Electronic Control Modules (ECM) which may fail and overheat. If this were to occur, excessive heat could cause a fire, possibly resulting in serious injury or death.

Polaris has received 68 reports of the ECM overheating. No injuries have been reported.

Only select model year Polaris ATVs are part of this recall. The Sportsman ATV model and serial number identification decal is located on the front side of the front radiator covering. The Scrambler 500 ATV model and serial number identification decal is located on top of the front cab cover.

The Vehicle Identification Number (VIN), or serial number is also permanently stamped into the left frame rail behind the left front wheel of all Polaris ATVs. Affected units can be verified by comparing the last six digits of the VIN to the serial number range in bold typed below. NOTE: Not all 2004.5 and 2005 model year vehicles are affected. Please review the affected unit table below.
 
Models Affected    Model Number(s)    Serial Number Range

2004.5 SPORTSMAN 500    A04CH50(AO)(AR)(AS)    4XACH50A*4A 347719 – 348073
        4XACH50A*4B 407412 – 407876

2005 SPORTSMAN 400    A05MH42(AB)(AG)(AH)    4XAMH42A*5A 343374 – 343413, 353730 – 355129, 360331 – 360780, 373808 – 374327,379785 – 380385, 600801 – 602060, 609261 – 610515
        4XAMH42A*5B 411353 – 415199, 418895 – 427514, 430095 – 430634, 675596 – 676621, 679861 – 680700

2005 SPORTSMAN 500    A05MH50(AB)(AC)(AG)(AH)(AL)    4XAMH50A*5A 343334 – 343373, 350342 – 351590, 355130 – 355835, 358431 – 360330,362765 – 365588, 373208 – 373807, 378452 – 380569, 600301 – 600800, 605111 – 606260, 609111 – 609665, 612059 – 612811
        4XAMH50A*5B 404297 – 404796, 407877 – 408556, 411833 – 412332, 415200 – 431444, 675381 – 681370

2005 SPORTSMAN 600    A05MH59(AK)(AN)    4XAMH59A*5A 343286 – 343333, 349790 – 350341, 365589 – 366670, 372908 – 377872

2005 SPORTSMAN 700     A05MH68(AK)(AN)(AP)    4XAMH68A*5A 342736 – 343285, 349130 – 356390, 360781 – 377252, 604711 – 605110

(non -military application)    A05MH68(CA)    4XAMH68C*5A 353612 – 353618
        4XAMH68C*5P 461037, 461039

2005 Sportsman 6X6    A05CL50(AA)    4XACL50A*54 549671 – 558303, 796545 – 799527

2005 SCRAMBLER 500    A05BG50(AA)    4XABG50A*52 523011 – 523889, 527617 – 528865, 529468
        4XABG50A*54 554662 – 558475, 796577 – 799530

2005 Trail Boss 330    A05CA32(AA)    4XACA32A*5B 410751 – 413970
        4XACA32A*52 532233 – 541659, 751061 – 757439
        4XACA32A*54 550569 – 558765
    A05CA32(AB)    4XACA32A*54 551800 – 553997

2005 Magnum 330 2X4    A05CB32(AA)    4XACB32A*52 527107 – 529313, 537673 – 542424, 752671 – 753030
        4XACB32A*5B 405797 – 405846, 408757 – 409346, 413971 – 414270, 675331 – 679450

2005 Magnum 330 4X4    A05CD32(AA)(AB)(AC)    4XACD32A*52 521885 – 522981, 528132 – 529815, 532671 – 541374
        4XACD32A*5B 405847 – 405896, 409347 – 410750, 414271 – 414534, 431445 – 431756, 675001 – 679051

The ATVs were sold at Polaris dealers nationwide from August 2004 through February 2005 for between $3,799 and $7,699.

Affected customers should contact Polaris for a free repair. Contact your Polaris ATV dealer to schedule an appointment for ECM replacement. Polaris has notified registered affected consumers directly about this recall.

For additional information contact Polaris at (800) 765-2747 between 8 a.m. and 12 midnight ET everyday, or log on to the company’s Web site at www.polarisindustries.com.

On May 24, Guidant disclosed it had waited three years before disclosing it had been aware of an electrical problem that had caused some 28 of 28,900 Ventak Prizm 2 DR defibrillators to malfunction. One death that of a 21-year-old college student, was associated with this model.   

As the story developed, the number of potentially defective defibrillators still in use reached almost 50,000; the 28,900 with the electrical problem and another 21,000 which could malfunction due to a computer memory error (the Vertak Prizm AVT, Vitality AVT, Renewal 3 AVT, and Renewal 4 AVT ICD). There had been 2 reports of failures associated with these other models. Neither report involved injury or death.

Then, a third problem came to light with respect to another potential short-circuit risk associated with the Contak Renewal (Model H135) and the Comtak Renewal 2 (Model H155). Out of those 16,000 devices, 15 reports of failures had been received including one involving a death on May 30. As a result, Guidant issued recalls for all of these devices on June 18.

Many experts openly questioned a monitoring system which essentially leaves the question of disclosure, with respect to potential flaws in such critical medical devices, entirely to the manufacturer. As a result, the Heart Rhythm Society will prepare a set of guidelines with respect to physician alerts and other actions that should be taken by defibrillator makers when they identify a pattern of malfunctions in the devices even if those failures are rare. The Society represents a branch of cardiology known as electrophysiology and is made up of cardiologists who specialize in implanting defibrillators.

Now, less than a week after the major recall, Guidant announced five more of its defibrillator models had a potential electrical defect (faulty switch) that could cause a malfunction. Those models are the Contak Renewal 3 and 4, Renewal 3 and 4 AVT, and Renewal RF.

Guidant has advised doctors to stop implanting these devices until further notice. Currently, however, some 46,000 of them are already in use. Guidant acknowledged the FDA may classify this advisory as a recall. Although no deaths have been reported, as many as five devices have malfunctioned.

The FDA Advisory encourages patients with these defibrillators to discuss the matter with their doctor. Any adverse events or problems should be reported to the FDA at www.FDA.gov/medwatch/ or 1-800-FDA-1088. Additional information about this potential issue is available for physicians and patients at 1-866-GUIDANT (1-866-484-3268) (24/7) and http://www.guidant.com/physician_communications/RENEWAL3_RENEWAL4.pdf.   

On Friday, the FDA issued a public notification that Vail Products, Inc., Toledo, Ohio, has initiated a nationwide recall of approximately 5,000 "enclosed" bed systems. The enclosed bed systems have been found to cause patient entrapments, resulting in severe neurological damage or death due to asphyxiation.

Under the terms of the recall, the company has sent new instruction manuals and warning labels to every customer informing them of FDA’s advice to stop using the bed system, move patients to alternative beds systems if possible and consult with their physician.

If, no other bed systems are available, users are advised to follow the safety precautions contained in the new instruction manuals and warning labels to help minimize risk of injury (also available on FDA’s website, see below.)
The FDA notification states: “Vail enclosed bed systems are canopy-like padded beds covered with nylon netting that is zipped into place to enclose the patient. They are used for at-risk patients with cognitive impairment, unpredictable behavior, spasms, seizures, and other disorders. The beds are an alternative to physical or drug restraint to reduce falls or other injury to patients.

The bed systems pose a hazard in that patients can become entrapped between the side-rail and the mattress or between the canopy and mattress. Due to the presence of the canopy, if their head is entrapped, the patient may experience asphyxiation, which can result in permanent neurological injury or death. FDA is aware of approximately 30 entrapments, of which at least 8 resulted in death.”
 
"FDA is making every effort to make sure that patients and healthcare providers are aware of this problem and are given the information needed to help minimize risk," said Dr. Daniel Schultz, Director of FDA’s Center for Devices and Radiological Health.
 
The FDA first issued a Public Health Notification on March 25, 2005 about the potential risk posed by these bed systems. Yesterday it further updated its Public Health Notification (available at http://www.fda.gov/cdrh/safety/032505-vail.html) to reflect the latest information on this problem.

On June 23 and 24, 2005, Vail Products mailed corrected instruction manuals and labeling, including warning labels to all users of its Vail 500, Vail 1000, and Vail 2000 enclosed bed systems.

Vail Products announced on June 16, 2005, that it is permanently ceasing the manufacture, sale, and distribution of all Vail enclosed bed systems. Vail will no longer be available to provide accessories, replacement parts, or retrofit kits.

Users who have not received a copy of the corrected instruction manual may attempt to contact Vail Products at 1-800-235-8245.

The FDA encourages individual users to report any adverse events related to Vail enclosed bed systems to MedWatch, the FDA’s voluntary reporting program at 1-800-FDA-1088; by FAX at 1-800-FDA-0178; by mail to MedWatch, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857-9787; or online at http://www.fda.gov/medwatch/report.htm. Consumers can also report directly to MedWatch.

A study conducted at King’s College London under the leadership of Professor Lynn Fraser, has found that a number of substances may have a seriously negative effect on the human fertilization process.

The presentation to a meeting of the European Society of Human Reproduction and Embryology in Copenhagen showed that a chemical known as genistein causes human sperm to “burn out” before having a chance to penetrate the wall of the egg and initiate fertilization.

Genistein is found in soya, tofu, and legumes. Professor Fraser, an expert in reproductive biology, suggests women who are ovulating should avoid or seriously limit their intake of these foods in order not to expose sperm to the compound.

In related research, two other estrogen-like chemicals were identified as having a similar debilitating effect on sperm. They are 8-prenylnaringenin, found in hops and beer, and nonylphenol, which is contained in industrial products such as paints, pesticides, and cleaning agents.

Genistein and the chemicals with similar effects cause the cap on the head of a sperm (acrosome) to rupture prematurely. This releases the enzymes needed to drill through the egg wall much too soon thereby preventing fertilization. Thus, while the sperm is still alive and moving actively, it has lost its ability to fertilize the egg.

Although Professor Fraser and other experts describe the results of the study as surprising and troubling, they also point out that Asian societies with traditionally soy-rich diets show no signs of reduced fertility and effects on sperm in the lab are often quite different than what may happen in real life.

As we reported on June 19, an FDA advisory panel was scheduled to hold a hearing yesterday to decide whether a “humanitarian device exemption” should be granted with respect to a fully implantable artificial heart called the AbioCor.

Following that hearing, the panel refused to endorse the application by a slim 7-6-1 vote. Two votes to approve the device failed by one vote as did a vote to reject the device. Since 2000, only 23 such exemptions have been granted.

In limited trial implantations, the device had extended the average life expectancy in fourteen men with severe heart failure from less than 30 days to an average of 5.3 months.

In the AbioCor, Abiomed Inc. of Danvers, Massachusetts, has succeeded in creating a design that allows this artificial heart to operate without the need for an internal wire to be connected to an external air pumping console. That older technology significantly limited a patient’s activity and posed a risk of infection.

One 70-year-old recipient, Tom Christerson, lived for 17 months after having the AbioCor implanted in September 2001. Although he had been given less than a month to live, he was able to resume and enjoy many normal activities for almost a year and a half.

The “humanitarian device exemption” would have allowed the device, which had not yet gone through final large scale trials, to be marketed if it could be used beneficially by 4,000 or fewer people per year.

The AbioCor is a 2-pound titanium and plastic device that is implanted in the space left when most of the patient’s cardiac muscle is surgically removed. It is powered by internal and external batteries.

The main use for the AbioCor was seen as a permanent replacement for patients with severe heart failure. Temporary use by patients waiting for extended periods of time for heart transplant surgery was also a possibility.

The AbioCor was seen as a device that would prolong a patient’s life for about 20-months. The next generation AbioCor II was anticipated to extend that figure to about five years.

Abiomed saw the device as the only alternative for desperately ill  end-stage heart failure patients for whom heart transplantation is not an option due to a shortage of donor hearts or because of medical conditions which disqualify the recipient.

Although other similar devices are in development, advances have been slow due to technological limitations, adverse blood interactions, and the risk of bleeding, strokes, and blood clotting. AbioCor recipients suffered these side effects as well as two cases where the device itself failed. Mr. Cristerson was one of the volunteers whose AbioCor failed. He declined a second implantation.

According to the Associated Press, in debating the special exemption, the FDA’s chief reviewer (Julie Swain) questioned whether the device was really “prolonging life” as opposed to “prolonging death.” Another panelist (Dr. John C. Somberg), however, saw the device as providing a benefit to “some patients facing near death.

The panel also considered the fact that six of the recipients were never able to leave the hospital and one lived for 53 days without regaining consciousness. In addition, about 75% of the recipients suffered multiple debilitating strokes following implantation surgery.

In the end, the vote was a technical one as to whether the device met the agency’s definition of a humanitarian device, namely, one whose probable benefits outweigh its potential risks. The panel determined it did not meet that threshold. The $250,000 price tag was also a negative factor.     

This was probably because the maker failed to offer enough objective proof of improved quality of life with the device. Although some family members of volunteers told the committee that the device allowed them to spend more quality time with their loved ones, several of the recipients remained debilitated and even noncommunicative after surgery.   

Nonetheless, some panelists supported the application under the theory that, to a terminally ill patient, some hope of survival is better than no hope at all. Thus, even the high risk of stroke and other serious complications was worth the prospect of extending the life of someone with no other chance of survival.

Although the CEO of Abiomed (Dr. Michael Minogue) expressed the company’s disappointment at the vote, he has not given up hope of approval. Abiomed intends to enter discussions with the FDA to see if enough data can be provided to support an application to approve the device.

The government (federal, state, or local) has always had the power to take private property through the process known as “eminent domain.” While governmental condemnation of privately owned real estate and the buildings, businesses, and homes built on it has never been a favorite of the average landowner, at least the concept behind it made sense.

Eminent domain (at least until yesterday) has always meant that the government may condemn privately owned real estate by showing that the property was going to be put to a “public use.” The affected owners would be given a fair market value for their property and then move out.

Public use of the condemned land had always been understood to mean things like highways, bridges, tunnels, dams, railway lines, train yards, public works projects, wider local roads, and the like.

It was never thought to include waterfront luxury condominium projects, shopping malls, corporate headquarters, sports stadiums, and exclusively private for-profit projects with no governmental connection except for a general promise to either boost economic growth, permit more profitable use of the land, or provide employment to private-sector workers.

Eminent domain could never have been envisioned to mean taking away a three-generation family-owned hardware store, a “mom and pop” furniture store, a 75-year old restaurant, and a row of private homes to build an IKEA mega store and parking lot or condemning an entire neighborhood in order to allow a pharmaceutical company to build a corporate headquarters; or could it?

Then came urban decay, local budget deficits, economically depressed neighborhoods, hardcore unemployment, and various and sundry socio-economic problems associated with everything from the closing down or relocation of dominant employers (like steel mills, automobile assembly plants, and textile mills) to the loss of a professional sports franchise.

The need for jobs, redevelopment of significant areas of vacant commercial and residential property, and the replenishment of local treasuries led politicians as well as enterprising real estate developers and Fortune 500 companies to consider a whole new approach to eminent domain.

Why not simply condemn private property that isn’t producing new jobs, extraordinary tax revenue, or an aesthetically pleasing view, force the occupants out for bargain-basement prices, bulldoze homes and businesses with lifetimes of memories, and then put the land into other private hands which just happen to be filled with the cash or promises of economic revitalization
the city or town desperately needs?

As long as you’re going that far, why not just take peoples’ homes and businesses even if the property they’re on isn’t blighted and the success of the new, but oh so attractive, project is not guaranteed?

This is precisely what is happening around the country in a number of states. As a result, the soon-to-be-displaced middle-class home and business owners mounted legal challenges to what they viewed as overreaching on the part of local government and pandering to the rich and powerful.

Although several cases are pending, one from New London, Connecticut was the first to be selected for review by the Supreme Court.  That case involves seven homeowners who refuse to sell their 15 combined lots to the New London to make way for a riverfront hotel, health club, and offices as part of a local revitalization project.

In a bitterly divided 5-4 decision, the Supreme Court majority decided that the rather innovative use of the eminent domain concept had really been there all along. The three other Justices accounted for in the majority opinion by Justice Stevens were Justices Souter, Ginsburg, and Breyer.

In that opinion, Justice Stevens wrote that: “There is no basis for exempting economic development from our traditionally broad understanding of public purpose.”  This is because; “Promoting economic development is a traditional and long accepted function of government.”

Although Justice Kennedy provided the deciding fifth vote by agreeing in the result reached by Stevens, Souter, Ginsburg, and Breyer, he filed a separate concurring opinion that warned the taking of private property primarily to favor private entities “with only incidental or pretextual public benefits” is not authorized under the Constitution.

The main dissenting opinion was written by Justice O’Connor who saw this as a dark day indeed for the property rights of the average American citizen. The other dissenting Justices were Scalia, Thomas, and Chief Justice Rehnquist.

Justice O’Connor stated that: “Under the banner of economic development, all private property is now vulnerable to being taken and transferred to another private owner, so long as it might be upgraded.” She also wrote that: “The specter of condemnation hangs over all property.” As a result; “Nothing is to prevent the state from replacing any Motel 6 with a Ritz Carlton, any home with a shopping mall, or any farm with a factory.”

While local government officials in the municipalities involved feel vindicated by the decision, the affected residents and business owners are collectively outraged and distraught. Many legal analysts are likewise shocked by the reach of the majority ruling.

Currently, eight states prohibit the use of eminent domain for purely economic development purposes except to eliminate blight. The remainder is divided between states that permit this type of taking and those that have yet to weigh in on the issue. Yesterday’s surprising decision is sure to prompt many states to reconsider their position on the matter.    

The CPSC, in cooperation with American Promotional Events Inc. of Florence, Alabama, have announced a voluntary recall of 9,000 units of Bat Out of Hell and Powder House fireworks manufactured in China. Consumers should stop using recalled products immediately.

Although no incidents or injuries have been reported, these fireworks devices could unexpectedly tip over during use, posing a serious injury hazard to consumers.

The recall involves Bat Out of Hell fireworks with model number CP1129 and Powder House fireworks with model number CP1130. The model number is printed on all four sides of the device above the warning label. These are 1.4g consumer fireworks devices that consist of 16 multiple shots in the shape of a square cube. The name of the product is printed on the packaging, along with the word “TNT.”

The recalled fireworks were sold at fireworks retailers in states permitting the sale of consumer fireworks, from May 2005 through June 2005 for about $20.

Consumers are instructed to return the recalled fireworks to the store where purchased for a full refund or contact American Promotional Events for instructions.

For additional information contact American Promotional Events at (800) 243-1189 between 8 a.m. and 5 p.m. CT Monday through Friday, or visit the firm’s Web site at www.TNTFireworks.com

The sudden recall of almost 50,000 implanted defibrillators manufactured by Guidant Corp. on June 17 has many experts questioning a monitoring system which essentially leaves the matter of disclosure, with respect to potential flaws in such critical medical devices, entirely to the manufacturer.

The current system is seen as problematic for a number of reasons. First, the ultimate decision may be based not only on patient safety issues but, also, on extraneous considerations such as potential legal liability and loss of market share to competitors. Second, the FDA does not collect comprehensive data on these devices after they are approved. Finally, hospitals and doctors do not notify the FDA about all device-related problems. Reporting of such incidents is spotty at best.

As a result, the Heart Rhythm Society will prepare a set of  guidelines with respect to physician alerts and other actions that should be taken by defibrillator makers when they identify a pattern of malfunctions in the devices even if those failures are rare. The Society represents a branch of cardiology known as electrophysiology and is made up of cardiologists who specialize in implanting defibrillators.
 
In hindsight, there is no doubt that, while Guidant Corporation maintained its internal heart defibrillator (the Ventak Prizm 2 DR) was safe and extremely reliable, it was fully aware of an electrical problem in some 29,000 of those devices which could cause them to short-circuit when needed.

On May 24, Guidant disclosed for the first time that it had waited three years before disclosing it had been aware of the electrical problem that had caused some 28 of these defibrillators to malfunction.  

As the story developed, the number of potentially defective defibrillators still in use reached almost 50,000; the 28,900 with the electrical problem and another 21,000 which could malfunction due to a computer memory error (the Vertak Prizm AVT, Vitality AVT, Renewal 3 AVT, and Renewal 4 AVT ICD). There had been 2 reports of failures associated with these other models. Neither report involved injury or death.

A third problem came to light with respect to another potential short-circuit risk associated with the Contak Renewal (Model H135) and the Comtak Renewal 2 (Model H155). Out of those 16,000 devices, 15 reports of failures had been received including one involving a death on May 30.

In issuing the recall, Guidant stated the Ventak Prizm 2 DR should be monitored and will be replaced if necessary by Guidant at no charge. For the models with potential memory errors, Guidant is recommending an in office programming change that can reduce the risk until Guidant is able to design a software solution. The remaining devices should be monitored at three-month intervals and undergo a complete trouble-shooting procedure if a yellow warning screen appears on the programmer.

As more and more of Merck’s internal documents come to light, the more questionable the company’s long-standing defense of VIOXX as a safe drug becomes.

Only last month, documents released at a congressional hearing left little doubt that Merck’s sales representatives were given intensive training with respect to deflecting doctors’ questions and concerns about the safety of the drug. Every aspect of the representatives’ interactions with doctors was carefully orchestrated by Merck to minimize both the scope and the duration of risk-related discussions. Those risks were to be downplayed and even trivialized.

Now, the Associated Press reports it has acquired an additional internal document that was “mistakenly provided by Merck” to attorneys representing the plaintiffs in one of many ongoing VIOXX lawsuits. The “communication between Merck researchers and the company’s patent department stated that the way VIOXX works to reduce pain might also increase cardiovascular problems.”

The document reveals a desire to reformulate VIOXX to combine it with an agent that would lessen the cardiovascular risk of the drug. In suggesting this approach, the document clearly discusses a potential mechanism which may be the cause of the problem.

Thus, while Merck has maintained it was always convinced of the drug’s safety, the company’s “desire to reformulate the drug suggests a level of urgency that goes beyond previously disclosed internal e-mails that discussed safety risks.”

A number of legal experts see this document as evidence that Merck’s defense is questionable. Taken in conjunction with all of the other circumstances surrounding VIOXX and the COX-2 class of painkillers (VIOXX, Bextra, and Celebrex), Merck’s approach seems to have been the ultimate triumph of marketing over science.

Between January 2003 and June 2004, Merck & Co. spent almost $123.9 million dollars in DTC (Direct to Consumer) advertising to persuade the public that VIOXX offered safe and effective treatment for acute and chronic pain associated with osteoarthritis, primary dysmenorrhea (moderate to severe menstrual pain), and other problems.

Attractive actors and celebrities, like Olympic figure skating champion Dorothy Hammil, pitched the drug in carefully orchestrated commercials set to The Rascals’ 1968 hit “Beautiful Morning.”  
    
Unfortunately, all of this was taking place while Merck, the FDA, and many highly respected medical experts were aware that the drug was considerably more dangerous than the public knew or even suspected. Despite the efforts by public interest groups and research organizations to have the drug pulled from the market or labeled with far more serious warnings, Merck refused to acknowledge the significant (heart-related) danger VIOXX posed.

Rather than challenge Merck’s questionable position, the FDA, which had access to all of the incriminating data, continued to approve the drug for wider applications. (In fact, on September 8, 2004, only three weeks before VIOXX was pulled from the market, the FDA approved the use of VIOXX in the treatment of rheumatoid arthritis in children as young as two).

VIOXX was approved for sale by the FDA on May 20, 1999. Almost immediately thereafter evidence began to emerge that the risks associated with the drug were far more serious than Merck had led the FDA to believe.

A safety study done in 2000, and published in the New England Journal of Medicine, showed that VIOXX faced a significantly higher risk of heart attacks and strokes than people taking a traditional pain reliever, naproxen. Although the results of this study should have prompted the FDA to take immediate action in the form of additional warnings, ordering further testing, or suspending the sale of the drug, Merck took the position that the study was inconclusive.  

Merck argued that the study only demonstrated that naproxen probably reduced the risk of heart attack and stroke and not that VIOXX increased that risk.  Merck continued to advertise VIOXX in a way that virtually ignored the results of this study (VIGOR).

In April of 2001, Public Citizen (www.citizen.org/), a well-respected national non-profit public interest organization, advised the public not to use VIOXX because of potential heart-related risks. Despite the results of the study and the warnings from Public Citizen, Merck continued to promote the drug in a way that minimized this risk.

On September 17, 2001 (and, to Merck’s good fortune, lost in the news of the terrorist attacks of 9/11), the FDA issued an 8-page warning letter to Merck concerning its false and misleading promotional campaign. The FDA found:

“You have engaged in a promotional campaign that minimizes the potentially serious cardiovascular findings that were observed in the VIOXX Gastrointestinal Outcomes Research (VIGOR) study, and thus, misrepresents the safety profile for VIOXX. Specifically, your promotional campaign discounts the fact that the VIGOR study patients on VIOXX were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator nonsteroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen).”     
 
This information was published by Public Citizen in November 2001. At that time, Merck was also aware of increased risks of thrombotic (blood clotting) adverse effects such as strokes and blood clots in the legs, hypertension, and altered kidney function.  

However, VIOXX was now a blockbuster moneymaker ($1.5 billion in 2000 and $2.5 billion in 2003) and Merck made a clear business decision to protect this highly profitable asset by whatever means necessary. Many critics now believe that included withholding critical information from the FDA and the public.
      
With 2 million VIOXX users in 80 countries, 84 million total users since 1999, and sales in the billions of dollars annually, Merck’s judgment appears to have succumbed to the power of the bottom line.

When it came to defending every challenge to its claims that VIOXX was a safe drug, Merck simply “stonewalled.”  This attitude simply ignored the mounting evidence that VIOXX was, indeed, the potential killer numerous highly qualified experts had always suspected it of being.  This is all the more obvious when one considers the following facts:
•    Kaiser Permanente, the largest HMO in the United States, found the incidence of sudden cardiac death to be three times greater for VIOXX than Celebrex among its patients.
•    Cigna Health Care regarded VIOXX as a “non-preferred medication” for its policy holders.
•     Aetna, Inc., the third largest health insurer in the United States, announced that VIOXX was the subject of an ongoing study and recommended “alternative drugs” be prescribed in its place.
•    Every study ever conducted with respect to VIOXX between 1999 and 2004 showed an increased risk of heart attack.
•    Several medical research organizations consider the entire COX-2 class of drugs to have an increased cardiac-related risk.
•    A study done at Vanderbilt University, and published in The Lancet on October 5, 2002, noted that patients taking 50mg. of VIOXX for more than 5 days demonstrated a 70% greater likelihood of developing coronary heart disease (CHD).
•    Despite requests from the American Heart Association, the National Stroke Association, and the Arthritis Foundation that Merck conduct additional safety studies, Merck claimed that VIOXX was safe and that it did not plan to conduct any such study.
•    An early 2004 study, which was actually funded by Merck, disclosed that VIOXX posed a risk of heart attack and stroke which was three times greater than that of other COX-2 pain relievers. Shockingly, when this finding was made, Merck had the name of its scientist removed from the list of authors on the study.       

Although Merck attempted to make the best out of a very bad situation by making it appear as if its voluntary withdrawal of VIOXX was motivated by concern for the public, the evidence does not support that position.  

Most business experts have little doubt that the removal of VIOXX from the market was anything but a purely financial consideration on the part of Merck which stood to lose $700 to $750 million in the fourth quarter of 2004 alone. The lawsuits were piling up and some of the cases were close to trial.

Corporate analysts who commented on Merck’s action saw it as a sound business move under the circumstances.  They did not attribute it to any sudden pangs of conscience on the part of Merck’s CEO or Board of Directors.  

In fact, the evidence showed that Merck was still solely interested in widening the market for COX-2 inhibitors. That evidence included the following:

•    The study (APPROVe trial) which led to Merck’s decision to voluntarily withdraw VIOXX from the market was really aimed at gaining FDA approval for VIOXX as a treatment for preventing the recurrence of colon polyps. (APPROVe stands for Adenomatous Polyp Prevention on VIOXX which clearly shows the study had nothing to do with safety and everything to do with gaining approval from the FDA for even wider use of VIOXX). In Merck’s open letter to “VIOXX Patients,” which appeared in newspapers across the country, Merck claimed that the study was “a clinical trial to better understand the safety profile of VIOXX.” It was actually no such thing. In fact, had the 3-year study not been halted abruptly on September 24 by the Data Safety Monitoring Board for safety reasons, VIOXX would probably still be on the market.
•    Merck had already developed a new COX-2 pain reliever called ARCOXIA which was being marketed in 47 countries and for which Merck expected FDA approval in the near future. While ARCOXIA was not yet the billion dollar drug VIOXX was, it is clear that VIOXX was well on the way to being replaced when it was pulled from the market.
•    Finally, even though VIOXX was finally exposed for what it was; a dangerous drug, Merck stated in its press release that the drug was being withdrawn despite Merck’s belief that “it would have been possible to continue to market VIOXX with labeling that would incorporate these new data…” Thus, Merck would still have kept VIOXX on the market had it not met with the FDA on September 28 and been forced to confront the disastrous results of its own study.

Most experts who are familiar with the history of VIOXX from either a medical or business perspective were not surprised by Merck’s sudden withdrawal of the drug from the market. The only surprise any of these experts seems to have is why it took so long for it to happen.

Dr. Sidney Wolfe of Public Citizen was quoted in the San Francisco Chronicle (10/1/04). He stated: “This family of drugs, the COX-2 inhibitors, once referred to as ‘super aspirins,’ are turning out to be more like super disasters.”

Dr. Eric Topol, Chief of Cardiovascular Medicine and Chief Academic Officer of the Cleveland Clinic, was a co-author of the VIGOR Study discussed above. His comment to the Washington Post (10/1/04) was that Merck’s action was “the right decision about three years too late. This is the sort of thing that Merck should have studied earlier, but they were too busy refuting the warning signs.”

The Wall Street Journal (10/1/04, page B1) noted that “Merck also may face more criticism for having strenuously denied for several years suggestions by outside researchers that use of VIOXX led to heart problems. The company even published its own studies suggesting the drug wasn’t causing harm.”  

The ongoing congressional inquiry, FDA scrutiny, and billions of dollars in personal injury litigation have placed Merck’s corporate philosophy, with respect to VIOXX at least, under a microscope.  In the end, Merck’s decision to aggressively market a drug in the face of scientific evidence of its dangers may prove to be a costly mistake indeed.