Forcing useless deaths ?/!

Vioxx: How an insider exposed the flaws of the FDA and how these flaws can cost 100,000 Americans their lives.

alternative medicine

The True Story of David J. Graham, MD, MPH

Graduated from the John Hopkins University School of Medicine
Trained in Internal Medicine at Yale and in Adult Neurology at the University of Pennsylvania
Three-year fellowship in Pharmacoepidemiology
Masters in Public Health at John Hopkins, with a concentration in Epidemiology and Biostatistics.

Drugs, Lies & Crimes:

In November 18, 2004, he was the Associate Director for Science and Medicine in the FDA’s Office of Drug Safety and had spent more than 20 years working for the FDA. A great researcher with an impeccable career. According two the FDA he had only a couple of flaws, ethics and morals.

In this society what used to be a quality is now viewed as a defect and you will understand why, as you continue reading the article further. Now let us hear what Dr. David Graham has to say in his own words as he tells us his story, as he told it in front of a Congressional committee. This entire deposition can be found on the Internet as well. To say the least, it is sad to see how hundreds of thousands of people are sacrificed in vain in the name of greed and bad politics – without remorse.

Doing His Job Too Well

During my career, I believe I have made a real difference for the cause of patients’ safety. My research and efforts within FDA led to the withdrawal from the US market of:

• Omniflox, an antibiotic that caused hemolytic anemia.
• Rezulin, a diabetes drug that caused acute liver failure.
• Fen-Phen and Redux, weight loss drugs that caused heart valve injury.
• PPA (phenylpropanolamine), an over-the-counter decongestant and weight loss product that caused hemorrhagic stroke in young women.
• Trovan, an antibiotic that caused acute liver failure and death.
• Lotronex, a drug for irritable bowel syndrome that causes ischemic colitis.
• Baycol, a cholesterol-lowering drug that caused severe muscle injury, kidney failure and death.
• Seldane, an antihistamine that caused heart arrhythmias and death.
• Propulsid, a drug for nighttime heartburn that caused heart arrythmias and death.

I have done extensive work concerning the issue of pregnancy exposure to Accutane, a drug that is used to treat acne. It can cause birth defects in some children who are exposed in utero if their mothers take the drug during the first trimester.

During my career, I recommended the withdrawal of 12 drugs from the market. Today, only two of those remain, which are Accutane and Arava, a drug for the treatment of rheumatoid arthritis. My co-worker and I believed that Arava causes an unacceptably high risk of acute liver failure and death.

A Lone Voice Against Vioxx:

Let me begin by describing what we found in our study, what others have found, and what this means for the American people. Prior to the approval of Vioxx, a study was performed by Merck named 090. This study found nearly a 7-fold increase in heart attack risk with low dose Vioxx. The labeling at approval said nothing about heart attack risks.

During the next four years, studies after studies, where there was an increasing link between Vioxx and increased incidents of heart failure. Finally the FDA made a labeling change about heart attack risk with high-dose Vioxx, but did not place this in the “Warnings” section. Also, it did not ban the high-dose formulation and its use. I believe such a ban should have been implemented.

In March 2004, another epidemiologic study reported that both high-dose and low-dose Vioxx increased the risk of heart attacks compared to Vioxx’s leading competitor, Celebrex.

Our study, first reported in late August of this year that Vioxx increased the risk of heart attack and sudden death by 3.7 fold for high dose and 1.5 fold for low dose, compared to Celebrex. A study report describing this work was put on the FDA website on Election Day.

Among many things, this report estimated that nearly 28,000 cases of heart attack or sudden cardiac death were caused by Vioxx. I emphasized to the committee that this is an extremely conservative estimate.

Announced Deaths

The FDA always claimed that randomized clinical trials provide the best data. If you apply the risk levels seen in the two Merck trials, VIGOR and APPROV, you obtain a more realistic and likely range of estimates for the number of cases in the US. This estimate ranges from 88,000 to 139,000 Americans.

Let us get a better picture as to how many lives we are talking about. We are not just talking numbers. Imagine that instead of a serious side effect of a widely used prescription drug, we were talking about jetliners. Please ignore the obvious difference in fatality rates between a heart attack and a plane crash and focus on the larger analogy that I am trying to draw. If there were an average of 150 to 200 people on an aircraft, this would bring to a total of about 88,000 to 138,000 people, which would be equivalent to 500 to 900 aircrafts dropping from the sky.

This translates to about two to four airliners every week, week in and week out, for the past 5 years. If you were confronted by this situation, what would be your reaction, what would you want to know and what would you do about it?
The History of the FDA:

In 1938, Congress enacted the Food, Drug and Cosmetic Act, basically creating the FDA, in response to an unfortunate incident in which about 100 children were killed by an elixir of sulfanilamide, a medication that was formulated using anti-freeze. This Act required that animal toxicity testing be performed and safety information be submitted to FDA prior to approval of a drug.

In 1962, Congress enacted the Kefauver-Harris Amendments to the FD&C Act in response to the thalidomide disaster in Europe. Between 1957 and 1961, an estimated 5,000 to 10,000 children were born with thalidomide-related birth defects. These Amendments increased the requirements for toxicity testing and safety information for pre-approval and added the requirement that “substantial evidence” of efficacy be submitted.

TODAY, IN 2004, WE ARE FACED WITH WHAT MAY BE THE SINGLE GREATEST DRUG SAFETY CATASTROPHE IN THE HISTORY OF THIS COUNTRY OR THE HISTORY OF THE WORLD.

We are talking about a catastrophe that I strongly believe could have or should have been largely or completely avoided, but it wasn’t, and over 100,000 Americans have paid immensely for this failure. In my opinion, the FDA has let the American people down, and sadly, betrayed a public trust.
How The FDA Reacted To David J. Graham’s Wish To Go Public With His Research:
“We had planned to present the data at the International Conference on Pharmacoepidemiology, in Bordeaux, France. We concluded that high-dose Vioxx significantly increased the risk of heart attacks and sudden death and that the high doses of the drug should not be prescribed or used by patients.

This conclusion triggered an explosive response from the Office of New Drugs, which approved Vioxx in the first place and was responsible for regulating it post-marketing.

The response from senior management in my office, the Office of Drug Safety, was equally stressful. I was pressured to change my conclusions and recommendations, and basically threatened that if I did not change them, I would not be permitted to present the paper at the conference.

One drug safety manager recommended that I should be barred from presenting the poster at the meeting and also noted that Merck needed to know our study results.

“An email from the Director for the entire Office of New Drugs was revealing. He suggested that since the FDA was “not contemplating” a warning against the use of high-dose Vioxx, my conclusions should be changed.“

Crimes Against Children

In mid August, despite our study results showing an increased risk of heart attack with Vioxx, and despite the results of other studies published in the literature, FDA Announced It Had Approved Vioxx For Use In Children With Rheumatoid Arthritis. Heart warming isn’t it?

September 22

At a meeting attended by the director of the reviewing office who approved Vioxx, the director and deputy director of the reviewing division within that office and senior managers from the Office of Drug Safety, no one thought there was a Vioxx safety issue to be dealt with. At this meeting, the reviewing office director asked why had I even thought to study Vioxx and heart attacks because FDA had made its labeling change and nothing more needed to be done. At this meeting a senior manager from ODS labeled our Vioxx study “a scientific rumor.”

Eight days later, Merck pulled Vioxx from the market, and jetliners stopped dropping from the sky.

Who own the FDA ?

David Graham’s Conclusion:

I would argue that the FDA, as currently configured, is incapable of protecting America against another Vioxx. We are virtually defenseless. It is important that this committee and the American people understand that what has happened with Vioxx is really a symptom of something far more dangerous to the safety of the American people.

A lawyer Tale

Big Pharma Is Learning it The Hard Way

Vioxx generated $2.5 billion in worldwide sales for Merck in 2003, 11 percent of the firm’s total revenues.

Merck spent $100 million on direct-to-consumer Vioxx advertising in 2003, aimed at pushing arthritis sufferers to ask their doctors to prescribe the drug. It expended $500 million more to promote the drug to doctors and pharmacists and in medical journals. As usual, more was spent to sell the drug than to conduct research on its safety and efficacy.

As soon Merck announced the pulling of Vioxx from the market, they lost $27 billion when their stock plummeted on Wall Street. Similarly, when Pfizer announced that they were taking Celebrex off the market, the company’s market value decreased by $25 billion . This might explain why it was so difficult to take a drug off the market when it was previously approved by the FDA. The financial interest and consequences were enormous. Merck could lose another $20 billion settling personal injury suits, which would bring total loss to $47 billion. Perhaps they should have spent more money making medicine that works without killing you, instead of concentrating their efforts on lobbying and advertising.

Conclusion

Thanks to brave whistleblowes like David Graham, the truth about Vioxx finally came out. He also exposed fatal flaws of the FDA, and revealed how these flaws cost many Americans their lives. These deaths could have been avoided. Because of greed and corruption it is too late for them, but let’s make sure they did not die in vain. We must demand reform of the FDA so that dangerous products like Vioxx never make it to the shelf. We must stop placing trust in institutions which fail to earn it.

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