The CancerCoverUp.com Newsletter, The Devil's In The Detail (Men) Part II

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Subject:The CancerCoverUp.com Monthly Newsletter | NOVEMBER 2004 |

Volume 3, Issue 11

 

 

Sun, 31 Oct 2004 08:48:07 -0800

 

THE DEVIL'S IN THE DETAIL (MEN)

Part II

By Kathleen Deoul

 

BY KATHLEEN B. DEOUL

 

The role prescription drugs play in fueling America's out-of-control

healthcare costs is widely acknowledged. But while the rising costs of

drugs is recognized as a factor, there is more to the story than the

nominal cost of the drugs themselves. To no small degree the premature

delivery of drugs to the market and the conscious failure of Big

Pharma and its sales personnel to acknowledge potentially serious side

effects that, once manifest, impose enormous additional costs on the

American public are an even more pressing problem. The recent recall

of the popular arthritis drug Vioxx is a prime example.

THE VIOXX RECALL

 

When Vioxx was introduced in 1999, it was Merck & Co.'s entry into a

multibillion race. Billed as part of the " new generation " of

" nonsteroidal anti-inflammatory (NSAID) pain relievers, Vioxx was a

so-called " COX-2 " inhibitor. Drugs in this class are designed to

suppress one of a family of enzymes called cyclo-oxygenases (referred

to as COX-1 and COX-2). This " new generation " of NSAIDs was supposed

to eliminate the potential gastric bleeding problems associated with

early versions such as Advil, Motrin and Aleve. The earlier versions

posed a risk of gastric bleeding because of their suppression of the

" COX-1 enzyme as well as the COX-2. The new ones only suppressed the

COX-2.

 

Vioxx was actually the second entry into this market. Merck & Co.'s

competitor had introduced its own COX-2 drug Celebrex in January of

1999, and by the time Merck got its version to market, 600,000

Celebrex prescriptions had already been written! Merck realized it had

little time to lose and made provisions to add 700 additional sales

representatives to its staff of 4,000. The battle was joined.

 

One consequence of this battle of the Big Pharma Behemoths was to

catapult NSAIDs to a prominent position in the pharmaceutical market.

In 2001, 24.5 Celebrex prescriptions were filled in the United States

making it the 10th largest selling drug and 23.7 million were written

for Vioxx making it the 13th largest seller! Overall NSAIDs accounted

for 20% of the arthritis pain market.

 

It's small wonder then, that the seemingly abrupt recall of Vioxx sent

shock waves through the pharmaceutical industry. As one of the

flagship products for pharmaceutical giant Merck & Co, Vioxx was used

by 2 million people worldwide and 1.3 million in the United States. In

2003, Vioxx brought in $2.5 billion in sales (compared to Celebrex's

$3.1billion). Its withdrawal caused Merck stock to drop $12.

 

Merck tried to put the best face on the recall, characterizing it as

the action of a responsible corporate citizen in its announcement of

the move.

 

" We are taking this action because we believe it best serves the

interests of patients, " said Raymond V. Gilmartin, chairman, president

and chief executive officer of Merck. " Although we believe it would

have been possible to continue to market VIOXX with labeling that

would incorporate these new data, given the availability of

alternative therapies, and the questions raised by the data, we

concluded that a voluntary withdrawal is the responsible course to take. "

 

As reassuring as Merck's self-serving statement was, the truth is that

the company had little choice.

HIDING THE TRUTH

 

The big selling point for all of the NSAIDs was the assertion that

they were safer than other types of pain medication. The emphasis, of

course, was on potential gastric bleeding problems, but the clear

message from the hordes of detail men and women pushing the pills was

that they were GENERALLY safer than other options to treat pain.

 

The only trouble was that there was ample evidence to demonstrate such

claims were untrue YEARS before the recall.

 

In an editorial appearing in the October 21, 2004 New England Journal

of Medicine, Dr. Eric Topol noted that in 2001, the FDA Arthritis

Advisory Panel had a meeting at which it discussed the fact that the

data on Vioxx was showing a " clear-cut excess number of myocardial

infarctions (heart attacks) " .

 

Despite this evidence, Merck continued to market Vioxx without any

warnings of potential cardiac problems for THREE YEARS! During that

period, 80 million people were exposed to the drug!

 

In the editorial Dr. Topol expressed his concern that the FDA could so

cavalierly ignore a major public health issue writing:

 

" We are dealing with an enormous public health issue. Even a fraction

of a percent excess in the rate of serious cardiovascular events would

translate into thousands of affected people. "

 

Dr. Garrett Fitzgerald of the University of Pennsylvania writing in

the same edition of the New England Journal of Medicine warns that the

problem may not be limited to Vioxx. He noted that all three of the

approved COX-2 inhibitors suppress the formation of an enzyme called

prostaglandin 1-2 and that this suppression could be expected to

" elevate blood pressure, accelerate atherogenisis and predispose

patients receiving coxibs to an exaggerated thrombotic response to the

rupture of artherosclerotic plaque. "

 

In plain English what he is saying is that the way in which COX-2

inhibitors work increases the likelihood of patients developing high

blood pressure and blood clots.

 

And where was the FDA while all this was coming to light?

 

Trying to hide the light under a basket!

SUPPRESSING DISSENT

 

At a congressional hearing October 8th, before the Senate Finance

Committee, testimony was heard about the attempt by senior FDA

officials to silence Dr. David J. Graham, associate director for

science of the FDA Drug Center's Office of Drug Safety regarding Vioxx

dangers. Following the hearing Finance Committee Chairman Senator

Charles Grassley said " Dr. Graham described an environment where he

was ostracized [and] subjected to veiled threats and intimidation. "

 

Dr. Graham had been the lead researcher on a study that examined the

records of almost 1.4 million patients participating in the Kaiser

Permanente HMO. Included in this group were over 40,000 who had been

treated with Celebrex and almost 27,000 who had been given Vioxx. The

study found that patients on high doses of Vioxx had their risk of

heart attack and sudden cardiac death tripled. The group concluded

that high does of Vioxx should not be administered.

 

When FDA officials discovered Graham was scheduled to present his

findings at a conference in France, they balked.

 

Ann E. Trontell, deputy director of the FDA's office of Drug Safety

wrote in an August 12 email " I think the recommendation about high

does rofecoxib (Vioxx) is unnecessary and particularly problematic

since FDA funded this study and David's travel to France to present it. "

 

Trontell went on to suggest that Dr. Graham write a journal article

instead of presenting his findings at the conference so that

dissenting scientists at the FDA could include their views.

 

In the end, Graham was able to go to France, but his conclusions

concerning Vioxx were watered down.

 

Remember, the evidence of a possible problem had first surfaced at the

FDA THREE YEARS EARLIER! Graham's work was actually CONFIRMING the

earlier results.

 

Nor is this the only recent example of the FDA attempting to suppress

bad news for its Big Pharma constituency. A few weeks earlier, another

congressional committee heard testimony concerning the attempt to

suppress an analysis by Andrew Mosholder an FDA epidemiologist that

indicated an increased risk of suicidal thoughts and behaviors among

children using antidepressants. In his analysis, Mosholder recommended

that Prozac should be the drug of choice for young people because it

was the one his analysis indicated had the lowest risk. Like Graham,

he was pressured to soften his conclusions.

 

But the real story behind the withdrawal of Vioxx entails much more

than a single product. Rather, it is the archetypical example of a

medical system where physicians have increasingly taken the attitude

that there is a " pill for every ill " and have subordinated their

medical judgment to the blandishments of slick pharmaceutical reps

that put profits ahead of patients.

A PILL FOR EVERY ILL

 

The statistics are stunning.

 

According to a study by the CDC's National Center for Health

Statistics, doctors wrote at least one prescription for their patients

following an office visit 64% of the time! In 2000, that came to over

2.8 billion prescriptions written - more than one for every man, woman

and child in the United States!

 

By 2002, that figure rose to 3.34 billion prescriptions - an increase

of 20% in just two years!

 

Given this figure it's not surprising that HALF of all Americans are

taking at least one prescription drug.

 

That might even be all right if the drugs were purely beneficial. The

problem, however as the Vioxx recall so clearly demonstrates, is that

all too often this mania to medicate may be doing more harm than good!

DANGER IN YOUR MEDICINE CHEST

 

According to an article in the journal Pharmacogenomics, some 106,000

people die as a result of prescription drugs EVERY YEAR! Indeed, among

hospitalized patients the rate of serious or fatal adverse drug events

is 6.7% -- that amounts to one in fifteen patients - and that's just

the most serious incidents. But it's not just the human toll drug

deaths take.

 

According to the same article, adverse events associated with

prescription drugs add $136 billion to healthcare costs each year.

 

As astounding as it sounds, the CDC estimates that some 2.2 million

hospital patients have adverse drug events each year!

 

And hospitals are just part of the problem!

 

A study published in the April 17, 2003 edition of the New England

Journal of Medicine examined 661 patients in the Boston area. The

researchers found that 162 or 25% suffered an adverse drug reaction!

Of these 13% were serious and 11% were preventable. The adverse

reactions included drops in blood pressure and heart rate and bleeding

from the stomach or intestines.

 

Most important, the researchers indicated that the severity and

duration of many of the adverse drug events would have been

substantially reduced if different actions had been taken by the

prescribing physicians.

 

According to study researcher Dr. Tejal K. Gandhi, " Patients often had

symptoms for months without any changes in their medications and only

a small percentage of the patients reported that symptoms led to a

visit to a physician. "

 

Among the reported adverse reactions, 16% required medical attention

including visits to an emergency room. The researchers also noted that

the likelihood of an adverse event increased by 10% for each

additional drug prescribed. For senior citizens who often have

multiple prescriptions, the problem is particularly acute.

 

Of course, if the drug company representative withholds information on

the likelihood a particular adverse event could occur, neither the

physician or the patient is likely to be alert to the potential that

there could be a problem!

 

What is particularly disturbing is that the classes of drugs with the

most frequent adverse events: SSRIs (selective serotonin uptake

inhibitors) commonly used to treat depression, heart disease

medications such as beta blockers, ACE inhibitors and calcium channel

blockers and NSAID pain relievers are the most frequently prescribed

pharmaceutical products.

UNEXPECTED RISK

 

But it's not just prescription drugs. In many cases over-the counter

drugs which we give little thought to in terms of safety can pose

enormous dangers. For example, 17,000 deaths each year are linked to

ibuprofen. Even Tylenol, which most people view as safe, is in fact a

very dangerous drug and can cause liver or kidney failure.

 

A study by Dr. William Lee of the University of Texas Southwestern

Medical Center in Dallas tracked 300 acute liver failure cases at 22

hospitals and found 38% were linked to Tylenol whereas only 18% were

linked to other medications. Dr. Lee then looked at 307 cases of

severe liver injury - not outright failure - and found that 35% of

these cases were linked to Tylenol! In Britain Tylenol was used so

frequently in suicides that access to the drug is now restricted!

 

Overall, Tylenol containing products are responsible for 560,000

visits to emergency rooms, 260,000 hospitalizations and 450 deaths!

 

What may shock you is that some 27,000 children die from Tylenol

overdoses each year! That's right 27,000! The reason is that parents

often do not realize that there is a difference between children's

Tylenol and the form used by adults. As a result, it is extremely easy

to give a child too much!

 

The plain and simple truth is that whether it's over-the-counter or

prescription, the dangers of any FDA approved pharmaceutical product

are likely to be far higher than the public suspects - sometimes far

higher than anyone would reasonably be willing to accept. The recent

warnings concerning Remicade, a drug used to treat arthritis and

Crohns Disease certainly are a case in point.

REMICADE: A CURE WORSE THAN THE DISEASE

 

On August 24, 1998, the Food and Drug Administration approved Remicade

for the treatment of Crohns Disease. Two years later the drug was

approved for treatment of Rheumatoid Arthritis. Remicade was the first

of a new family of drugs that inhibited a key inflammatory mediator

called the tumor necrosis factor alpha (TNF-A). Overproduction of this

factor leads to inflammation in conditions such as Crohns Disease,

Rheumatoid Arthritis and other autoimmune diseases. The drug was

hailed as an important alternative to conventional steroids such as

prednisone which had been among the primary treatments for these

conditions.

 

It was not long, however, before the bloom was off the rose. Early on

there were reports that TNF-A inhibitors had a nasty side effect -

they made the body more susceptible to infections, including

tuberculosis. About 15% of the population has tuberculosis in their

systems, but it is controlled by normal immune functions. When they

are given drugs like Remicade, however, their immune functions related

to fighting tuberculosis can be suppressed. Since 1998, 70 cases of

tuberculosis linked to Remicade have been diagnosed.

 

Still, given its benefits, was this the only problem, it might be

dismissed as an acceptable risk. However, tuberculosis is not the only

problem associated with Remicade and its cousins.

 

A much more serious problem is a number of serious blood disorders

that are associated with so-called TNF-A inhibitors. These include

reductions in white blood count, reductions in a specific type of

white blood cell and a general shortage of blood cells and platelets.

Of even greater concern though was a rare neurological condition that

involved inflammation of the blood cells in the nerves and spinal

cord. Some 508 cases of this condition were reported worldwide, but

given the normal underreporting of adverse events the real number

could approach 5,100!

 

But as bad as all of these side effects are - and since they are

potentially fatal they are indeed bad - they pale in comparison to the

latest revelation about Remicade and its cousins.

 

The FDA has now acknowledged that patients taking Remicade and related

drugs have a three fold increase in their risk of developing lymphoma.

According to the FDA, 81% of the lymphomas associated with Remicade

and its cousins are Non-Hodgkin's Lymphoma. What is particularly

disturbing is how rapidly the disease develops. Its onset occurs

within eight weeks of initiating therapy with a TNF-A inhibitor.

Interestingly, in all cases to date, if the TNF-A inhibitor is

stopped, the lymphoma disappears without any other treatment!

 

So, clearly, it is Remicade that is causing the problem, and yet it

remains on the market!

 

When the number of occurrences of each of the different side effects

is totaled, it turns out that Remicade has an 8.4% rate of adverse

events, most of which are either fatal or potentially fatal!

 

What is truly amazing given this fact is that on October 7, 2004 the

FDA approved the use of Remicade in combination with Methotrexate as a

first-line treatment for Rheumatoid Arthritis - in other words the

" preferred " treatment modality!

 

Is it any wonder that adverse event-related medical costs total some

$136 billion a year?

 

But hiding information about adverse events is not the only way in

which Big Pharma and its army of detail men and women, and their

allies at the FDA cause health care costs to increase. They also

contribute to the problem by encouraging the misuse of drugs. Indeed,

this practice may be the cause of one of the most serious global

health problems faced today. Next month Part Three of The Devil's in

the Detail (Men) will show how Big Pharma has manipulated the system

to create a crisis that may threaten us all.

 

Next month: Part Three of " The Devil's in the Detail (Man) "