Monday, March 30, 2009

Vioxx/COX2 studies faked by leading anaesthetist, stunning medical world

Awhile back, I heard something about Vioxx during an interview on Richard Cloutier's morning show that caught my ear.

Why? Well, one reason is that it had been prescribed for me when I lived in Los Angeles when I had arm trouble; when a friend found out he told me there were a lot of potential side effects. The drug worked, but I discontinued use.

The other reason it got my attention was because of what was said in the interview.

To explain further, here is the correspondance between myself and Cloutier's guest that day, Professor Arthur Schaffer.

-----Original Message-----
From: Marty Gold []
Sent: Monday, February 02, 2009 9:58 AM
Subject: Vioxx deaths

Hello Professor Schafer,

I heard you on CJOB this morning. I am writing in regard to your citation of Vioxx as an example of influence-peddling within the medical system and that there were thousands of deaths before the drug was pulled from the market.

Can you direct me to your source about number of deaths?

Thank you,

Marty Gold

On Mon, Feb 2, 2009 at 5:45 PM, Arthur Schafer wrote:

Dear Marty,

I have attached a book chapter I published this autumn, which focuses on Vioxx (and its fellow COX 2 Inhibitor, Celebrex) and which gives a source for the estimate of deaths and injuries relating to Vioxx. My source was John Abramson's book "Overdosed America", published by Harper Collins. But the figure I used is frequently cited in the literature (both scholarly and popular).

Do you mind my asking why you want to know my source? Is it because you doubt the reliability of my claim?


From: Marty Gold []
Sent: Wednesday, February 04, 2009 8:01 AM
To: Arthur Schafer
Subject: Re: Vioxx deaths

Thanks Arthur,

I have learned that, upon hearing of a statistic about a significant public issue for the first time, it is wise for me to research the source and details, as my audience will be sure to raise questions when it is broadcast on my show.


RE: Vioxx deaths
Wednesday, February 4, 2009 8:24 AM
From: "Arthur Schafer"
To: "'Marty Gold'"

Good luck with your show. Is it broadcast on CJOB?


I looked up the information he cited and did some additional research, and found the source of the death rate claims. Here is a synopsis of the most pertinent aspect:

Mr. Chairman and members of the Committee,


Good morning. My name is David Graham, and I am pleased to come before you today to speak about Vioxx, heart attacks and the FDA.

By way of introduction, I graduated from the Johns Hopkins University School of Medicine, and trained in Internal Medicine at Yale and in adult Neurology at the University of Pennsylvania. After this, I completed a three-year fellowship in pharmacoepidemiology and a Masters in Public Health at Johns Hopkins, with a concentration in epidemiology and biostatistics. Over my 20 year career in the field, all of it at FDA, I have served in a variety of capacities. I am currently the Associate Director for Science and Medicine in FDA’s Office of Drug Safety.


In March of 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 found 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 excess cases of heart attack or sudden cardiac death were caused by Vioxx. I emphasize to the Committee that this is an extremely conservative estimate.

FDA always claims that randomized clinical trials provide the best data. If you apply the risk-levels seen in the 2 Merck tria ls, VIGOR and APPROVe, you obtain a more realistic and likely range of estimates for the number of excess cases in the US. This estimate ranges from 88,000 to 139,000 Americans. Of these, 30-40% probably died. For the survivors, their lives were changed forever.

So the 28,000 is actually heart attacks and/or deaths, not just deaths.

And the study says it is more likely says 30-40 percent of people died, which is where the 26,400 figure comes from. Estimates, revised estimates of what he thinks is "likely."

The bottom line---never believe a number repeated in the media, unless you know where it comes from.

Schafer focused on influence peddling, and my curiosity focused on the supposed number of deaths. I saw his comments as ideological in nature, and investigated to determine the accuracy of his facts.

However, the entire subject of the safety of Vioxx just became far more troubling -- and I now agree that the question of influence-peddling raised by Schafer on CJOB should be revisited. He may not have had all the facts, but he was accurate in his concern.

In a breaking story that has been almost totally unreported in the mainstream media, the basis of any claims Vioxx was safe in the first place has been completely undermined.

And shockingly, it took over a decade for authorities to find out.

" Medical journals have been asked to retract 21 studies that touted the benefits of Vioxx, Celebrex and other drugs. According to The Wall Street Journal, Baystate Medical Center, Springfield, Mass. is asking the journals to make the retractions because its former chief of acute pain, Dr. Scott S. Reuben, had faked data used in the studies.

In addition to Vioxx and Celebrex, some of the 21 studies involved the fibromyalgia drug Lyrica and the antidepressant Effexor XR. Reuben’s study claimed to show that these drug worked well as painkillers, the Journal said. All of the studies were published between 1996 and 2008.

According to The Wall Street Journal, these studies had a great deal of influence on the practice of medicine. Because of Reuben’s “research”, it had become routine for doctors to combine the use of painkillers like Celebrex and Lyrica for patients undergoing common procedures such as knee and hip replacements, the Journal said.

Reuben even had the ear of the Food & Drug Administration (FDA), and had written the agency asking it not to restrict the use of many of the painkillers he studied. He often cited his fake data to make his case, the Journal said."

An investigation by Anesthesia & Analgesia found that 21 articles based on patient data had been partially or completely faked.

This next article dated March 10, 2009, provided by a doctor who listens to TGCTS, details just how corrupted the research and verifiction process was:

- "Reuben, 50, has been stripped of his research and educational duties and has been on medical leave since May. He received his medical degree from the State University of New York at Buffalo School of Medicine & Biomedical Sciences in 1985 and did his residency at the Mount Sinai Medical Center in New York City. In 1991, he joined Baystate, which serves as the western campus for Tufts University School of Medicine, and has worked as a staff anesthesiologist and the director of acute pain management ... (and) revolutionized the way physicians provide pain relief to patients undergoing orthopedic surgery for everything from torn ligaments to worn-out hips."

- "He claimed that using COX2 inhibitors, such as Vioxx, Celebrex, and Pfizer's Bextra (valdecoxib) in combination with the Pfizer anticonvulsant Neurontin (gabapentin), and later Lyrica (pregabalin), prior to and during surgery could be effective in decreasing postoperative pain and reduce the use of addictive painkillers, such as morphine, during recovery."

- "A 2007 editorial in Anesthesia & Analgesia stated that Reuben had been at the "forefront of redesigning pain management protocols" through his "carefully planned" and "meticulously documented" studies."

- "Baystate Medical Center in Springfield, Mass., began investigating Reuben's findings last May after its chief academic officer, Hal Jenson, discovered during a routine audit that Reuben had not received approval from the hospital's review board to conduct two of his studies"

- "... in 2004, Vioxx and Bextra were pulled from the market because of their link to an increased risk of heart attacks and strokes, leaving Pfizer's Celebrex as the only COX2 inhibitor available." (One of the most widely used drugs ever withdrawn, Merck had sales $2.5 billion from Vioxx in the previous year.)

- "Celebrex sales plunged 40 percent after a (2004) study ... suggesting that it, too, posed a heart attack risk. Despite this, Reuben continued to present "findings" in research funded by Pfizer that trumpeted Celebrex's alleged benefits and downplayed its potential negative side effects."

- Dr. Evan Ekman, an orthopedic surgeon at Southern Orthopaedic Sports Medicine in Columbia, S.C. "began to suspect foul play. In addition to collaborating with Reuben on the now-retracted Celebrex study, Ekman agreed to review a Reuben manuscript on surgery on the anterior cruciate ligament (ACL) in the knee. But when he asked the anesthesiologist for the name of the orthopedic surgeon on the study, Reuben ceased communication with him.

Then, last year, Ekman was invited by Pfizer to give a talk. While there, he was handed a version of the very manuscript Reuben had asked him to review, which had subsequently been published in Anesthesia & Analgesia.

To his surprise, and horror, he was listed as a co-author: Reuben had forged his signature on the submission form, Ekman says."

- " Although Pfizer funded Reuben's research between 2002 and 2007, Baystate has no records of those payments and says that the research funds could have been paid directly to Reuben... Baystate spokesperson Jane Albert says "I don't know how many dollars went to Dr. Reuben or his group."

The reason why this could go undetected for 12 years?
The audit rate is only about 5% of the 200 or so studies published each year.

And there is plenty of blame to pass around: the article states in the final paragraph, "Anesthesia & Analgesia editors Shafer and White admit that it should have been a "red flag" that Reuben's studies were consistently favorable to the drugs he studied."

So although the anti-Vioxx scepticism of critics such as Prof. Schafer may have been ideological in nature (the ideology of anti-Pharma), so too was the support for Vioxx being thrust on a trusting public -- the ideology of naked greed.

In this case, an excess of caution may in fact, have been the appropriate response after all.

And this should serve as a warning to all of us, that the drugs that our family doctors and specialists trust, are only as good as the research and studies that back them up- which might not be any good to start with.

Postscript: Tonight, Merck is claiming that a Saskatchewan class-action suit about Vioxx has had its certification dismissed.