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.

Two prospective studies published in the June issue of Cancer Causes and Control suggest current use of chewing tobacco or snuff increases mortality from heart disease and stroke.

The researchers analyzed baseline information from two Cancer Prevention Studies (CPS-I in 1959 and CPS-II in 1982) involving 192,216 men and follow-up data (1971 for CPS-I and 2000 for CPS-II) which included 31,459 deaths.

After making the appropriate adjustments for key variables, the investigators concluded that, compared with men who did not use tobacco, men currently using chewing tobacco or snuff had higher death rates from all causes in both studies.

In CPS-I, they found the use of chewing tobacco or snuff (collectively referred to as “spit tobacco”) was statistically significantly associated with death from coronary heart disease (CHD), stroke, and respiratory tract, digestive tract, and genitourinary diseases, but not with death from cancer.

In CPS-II, use of chewing tobacco or snuff was significantly associated with death from CHD, stroke, all cancers combined, lung cancer, and cirrhosis.

The researchers pointed out that the studies did not establish a true causal connection between spit tobacco and an increased risk of death from heart disease or stroke. The results may only reflect the existence of other factors such as the lower socioeconomic status of the men who use such products.

The CPSC, in cooperation with FF Acquisition Wheeled Goods Corp. of West Point, Mississippi announced a voluntary recall of approximately 10,000 Yerf-Dog Go-Karts manufactured in the United States. Consumers should stop using recalled products immediately.

The suspension assembly can crack causing the rider to lose control of the go-kart. The manufacturer has received five reports of the suspension assembly cracking and causing the rider to lose control, including reports of bruises and head and back injuries.

This recall involves one- and two-seater model Yerf-Dog Spiderbox series go-karts. The go-karts have full suspension and 150cc engines. Date codes and model numbers are located on a plate attached to the engine casing. Date codes and model numbers included in this recall are:

Model    Date Codes
3206    July 20, 2004 through March 4, 2005
4209    July 20, 2004 through February 18, 2005
42092    July 20, 2004 through November 22, 2004
42093    August 9, 2004 through November 19, 2004
42101    July 28, 2004 through October 12, 2004

The go-karts were sold at Yerf-Dog dealers nationwide from July 2004 through May 2005 for between $1,500 and $1,800.

Consumers should stop using the recalled go-karts immediately and contact FF Acquisition Wheeled Goods for repair information. Registered owners will be notified directly about the recall.

For additional information, contact FF Acquisition Wheeled Goods Corp. at (800) 683-0072 between 8 a.m. and 5 p.m. CT Monday through Friday, or visit the firm’s Web site at www.yerf-dog.com

The CPSC, in cooperation with Belkin Corporation of Comptom, California, announced the product safety recall of approximately 10,300 Li-Polymer battery packs sold with Bluetooth™ Global Positioning System (GPS) Navigation System manufactured in China. Customers should stop using the product immediately unless otherwise instructed.

The battery can overheat, expand, and possibly rupture, creating an explosion or fire hazard. Belkin reports 15 incidents of batteries overheating and expanding. No injuries or property damage have been reported.
The recall involves Li-Polymer battery packs sold with Belkin Bluetooth™ GPS Navigation System models F8T051 and F8T051-DL. The GPS model number can be found on a label on the bottom of the unit. “Part No.: 300-203712001” and Model No.: AE-8210” are written on the side of the battery.

The Belkin Web site, other Web retailers and computer and electronics stores sold the GPS device with recalled batteries nationwide from November 2003 through February 2005 for about $400.

Consumers are advised to stop using the GPS product immediately and contact Belkin for information on receiving a free replacement battery.

For more information, call Belkin toll-free at (800) 223-5546 ext. 2064 between 8:00 a.m. and 5:00 p.m. PT, Monday through Friday, or visit their Web site at www.belkin.com

Heroin and other opiate drugs are highly addictive substances thus making them extremely difficult to stop using. Smokers consistently find it very hard to stop smoking. Coincidence? Not according to a new animal study at the University of Pennsylvania, and published in the journal Neuron, which found nicotine produces a brain response similar to that of heroin and the other opiates.

It appears that nicotine causes an increase in the level of naturally occurring opioids, which are very similar to opiate drugs. Thus, the researchers found that nicotine produced a rise in the level of a protein thought to be involved in the brain’s response to several narcotic drugs. In addition, nicotine also affects the brain pathway activated by heroin and other opiates.      

Interestingly, when the nicotine-addicted mice were placed in the same cage where they had previously received nicotine, the same signals were set off in their brains.

When a drug that reverses the effects of narcotic drugs (naloxone) was administered, it blocked the effect of nicotine as well as the similar effect produced in the nicotine-associated cage.

 Dr. Julie A. Blendy and the rest of the team see the results as raising the possibility of using opioid-blocking drugs to treat the symptoms of nicotine addition.

Based on many years of professional training, a licensed physician prescribes an FDA approved pain medication to a patient. The patient, who suffers from chronic pain related to a serious medical condition, brings the prescription to a local pharmacy to be filled. The pharmacist refuses to fill the prescription and then refuses to return the prescription to the patient so that it can be filled at another pharmacy. The patient returns home in pain.

If you think this can’t happen, think again. This rather improbable sounding scenario is happening every day in pharmacies across the country with respect to a growing number of important medications like painkillers, Emergency Contraceptive (EC) pills, psychotropic drugs, and birth control pills.

Pharmacists (and the American Pharmacists Association) call it conscience-based refusal; the American Medical Association (AMA) sees it as a wrongful denial of a patient’s access to legally prescribed therapy and medical care.

At its annual meeting on Monday, the AMA voted to use its influence to see that such “conscientious refusals” do not deny patients’ of  needed medical treatment by supporting legislation that would require pharmacists to fill any valid prescription or to refer such patients to another pharmacy that will. The AMA will also press for amendments to existing state laws to allow physicians to dispense medications when there is “no willing pharmacist available within a 30 mile radius.”  

While the American Pharmacists Association recognizes what it sees as a right of individual pharmacists to refuse to fill certain prescriptions, it “supports the establishment of systems to ensure a patient’s access to legally prescribed therapy without compromising the pharmacist’s right of conscientious refusal.” The organization also opposes any confrontation wherein a pharmacist berates, belittles, or lectures a patient.   

Medpage Today reports fourteen states have either passed or are considering legislation protecting pharmacists who refuse to fill prescriptions based on moral, religious, or personal grounds while nine additional states are in the process of enacting laws that would permit pharmacists to refuse prescriptions “for any reason.”

Conscientious refusal first became an issue when some pharmacists refused to fill prescriptions for EC pills viewing them as a form of abortion. The refusals soon spread to birth control pills.

Now, however, many pharmacists have extended their objections to include painkillers and psychotropic drugs. In some situations pharmacists are also refusing to return the prescriptions thereby preventing patients from turning to other pharmacists.

This problem is magnified in areas where the local pharmacist is the only pharmacist or where the nearest alternative pharmacy may be several miles away.

A coalition of medical specialty groups and individual physicians want the AMA to press pharmacists to follow ethical guidelines for the delivery of healthcare. They see this as no different than the ethical duty of doctors to refer patients they are unwilling to treat to another physician.

The crashworthiness of motor vehicles has improved immensely over the past several years. The addition of front, side, and overhead air bags, crumple zones, safety cages, reinforced door panels, and less vulnerable fuel tanks have significantly improved your chances of surviving even a violent collision. These improvements, however, are reaching their limit and may only see smaller advances in the future.

It is for this reason that manufacturers are turning their attention to “crash-avoidance” technology which is designed to enhance driver awareness, reaction, and response in critical situations. This includes computerized systems that avoid collisions, minimize impacts, sense changing road conditions, sound warnings, tighten seatbelts, enhance braking and steering, and improve handling. Even radar sensors are being incorporated into this technology.

Many of the newest systems integrate several features that then act together in dangerous situations thereby producing optimal driver response. This significantly improves the chances of survival for an average or even below average driver.

The potential “dark side” to all of this technology, however, can be found in the sophisticated data-collection or “black box” devices that are now routinely installed in about two-thirds of the new vehicles sold in the United States. Some 30 million vehicles already have these devices known officially as event data recorders.

Currently, these devices are designed to record and store information on such variables as speed, throttle position, braking, airbag deployment, and seat belt use. More elaborate black boxes are used by long-haul trucking companies to monitor the operation of their trucks in great detail.

There are a multitude of uses to which this information can be put. Some of them are very good and some, according to privacy experts, are very bad.

On the positive side, the information gathered may prove helpful in criminal prosecutions, to help convict bad drivers of speeding and drunk driving violations, and to exonerate those wrongly accused of certain offenses. As raw data, without identifying individual drivers, it can aid in improving traffic laws and automobile design and safety.

Many lawmakers and privacy advocates see a real danger that this information will be used in litigation or by insurance companies against drivers who were unaware it was being collected.  
They also fear that once the technology is in place, more and more information can be gathered with very little difficulty. This could include recording information from on-board navigation and cell phone systems. It could also lead to insurance companies structuring rates to penalize drivers who refuse to have one of the devices in their car.

To deal with these concerns, there are proposals requiring disclosure by manufacturers as to which vehicles have the devices and for the installation of cut-off switch that can be activated by the driver.

The CPSC, in cooperation with Midwest Cannon Falls of Cannon Falls, Minnesota, have announced a voluntary recall of 10,000 Serenity Votive Candles manufactured in China. Consumers should stop using the candles immediately.

The candles’ wax can catch fire, causing a high flame. This can cause nearby combustibles to catch fire and result in burns to consumers. Midwest has received one report of the candle wax catching fire. No injuries or property damage have been reported.

The candles consist of a glass votive cup surrounded by a silver holder with a standing angel figure attached. Each holder contains an engraved quotation. The angel stands about 3 inches tall. Each candle has a proverb engraved into the metal holder.

The candles were sold at gift stores nationwide from June 2004 to May 2005 for about $20. Consumers should return these candles to the place of purchase to receive a refund.

For additional information, contact Midwest at (800) 776-2075 between 7:30 a.m. and 5 p.m. CT Monday through Friday, or go the company’s Website at http://www.midwestofcannonfalls.com.

The crashworthiness of motor vehicles has improved immensely over the past several years. The addition of front, side, and overhead air bags, crumple zones, safety cages, reinforced door panels, and less vulnerable fuel tanks have significantly improved your chances of surviving even a violent collision. These improvements, however, are reaching their limit and may only see smaller advances in the future.

It is for this reason that manufacturers are turning their attention to “crash-avoidance” technology which is designed to enhance driver awareness, reaction, and response in critical situations. This includes computerized systems that avoid collisions, minimize impacts, sense changing road conditions, sound warnings, tighten seatbelts, enhance braking and steering, and improve handling. Even radar sensors are being incorporated into this technology.

Many of the newest systems integrate several features that then act together in dangerous situations thereby producing optimal driver response. This significantly improves the chances of survival for an average or even below average driver.

The potential “dark side” to all of this technology, however, can be found in the sophisticated data-collection or “black box” devices that are now routinely installed in about two-thirds of the new vehicles sold in the United States. Some 30 million vehicles already have these devices known officially as event data recorders.

Currently, these devices are designed to record and store information on such variables as speed, throttle position, braking, airbag deployment, and seat belt use. More elaborate black boxes are used by long-haul trucking companies to monitor the operation of their trucks in great detail.

There are a multitude of uses to which this information can be put. Some of them are very good and some, according to privacy experts, are very bad.

On the positive side, the information gathered may prove helpful in criminal prosecutions, to help convict bad drivers of speeding and drunk driving violations, and to exonerate those wrongly accused of certain offenses. As raw data, without identifying individual drivers, it can aid in improving traffic laws and automobile design and safety.

Many lawmakers and privacy advocates see a real danger that this information will be used in litigation or by insurance companies against drivers who were unaware it was being collected.  
They also fear that once the technology is in place, more and more information can be gathered with very little difficulty. This could include recording information from on-board navigation and cell phone systems. It could also lead to insurance companies structuring rates to penalize drivers who refuse to have one of the devices in their car.

To deal with these concerns, there are proposals requiring disclosure by manufacturers as to which vehicles have the devices and for the installation of cut-off switch that can be activated by the driver.

Researchers involved in three separate studies are reporting diagnostic approaches involving brain scans and a blood test may offer a way to identify individuals who are at higher risk of developing Alzheimer’s disease years before the onset of actual symptoms.

This approach, announced Alzheimer’s Association International Conference on Prevention of Dementia, in Washington, D.C., offers a possible two-fold breakthrough by permitting treatment to be commenced at a much earlier stage of the disease and by helping those determined to be at risk to take more complete advantage of preventive therapies which are, or may become, available in the future.

The three studies include one involving “positron emission tomography (PET) scans working in conjunction with a specially designed MRI-linked computer program. The process tracks glucose metabolism in the hippocampus (memory) area of the brain. Decreased metabolic activity is seen as an indicator for cognitive problems and a risk factor for Alzheimer’s.

The second study involved “magnetic resonance spectroscopy (MRS) which is an MRI-type scan used to examine brain biochemical activity as opposed to brain structure. Neurochemical differences between “normal” individuals and those carrying a gene strongly associated with a high predisposition to Alzheimer’s disease indicate the possibility of early detection of cognitive decline.

The final study could be the most promising in terms of availability and expense in that it involves a simple, painless blood test.  The test is used to detect two protein markers which when analyzed together and in ratio with one another provide strong evidence of future development of Alzheimer’s disease.       

Although the high-tech detection methods seem to be further along in terms of development, the blood screen is attractive because it is far less expensive, requires no special equipment or training at the site of the test only laboratory facilities which may analyze blood samples from many locations, makes screening available in remote and less-developed areas, and is more easily assimilated into normal medical office routine.

Early detection of impending Alzheimer’s disease, while encouraging, is somewhat premature as a method of reducing or eradicating the debilitating condition since effective treatments and preventive therapies are largely nonexistent or only in early stages of development at the present time.