The FDA was Embarrassed Part I: The Story of Vioxx

Remember the "super aspirin", Vioxx? You might recall Bruce Jenner or Dorothy Hamill plugging its ability to treat everything from arthritis pain to muscle cramps. No?

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If not, you may still remember the hullabaloo surrounding Merck's abrupt withdrawal of Vioxx in 2004, just five years after it received FDA approval. The accompanying media circus, multi-billion dollar settlement, and FDA refusal to approve any Cox-2 inhibitor drugs since (despite their widespread use in Europe and elsewhere) has dramatically affected the lives of millions of patients. In an attempt to "play" the FDA and the market, Merck reduced healthcare options for every American.

Cox-2 drugs provide all the pain relief of drugs like Aspirin, without the same severe gastrointestinal side effects. Before the fall of Vioxx, approximately 25 million Americans had benefited from the wonder drug. It was a special godsend for those who suffered from GI problems, since approximately 15,000 people a year die of GI-related side effects.

Hope that's not in bad taste. Source

                               

So what happened between 1999 (when Vioxx was approved) and 2004? A few things. Merck, the producer of Vioxx, released a study designed to confirm the apparent. Known as the VIGOR Study, its objective was to compare the GI effects of pain-relievers Vioxx and  Naproxen. True to expectations, the study proved (page 83) that participants taking Naproxen experienced over twice as many adverse GI effects as those taking Vioxx.

In other words, Vioxx was shown to be the safer drug. Nevertheless, Vioxx was removed from the market, while Naproxen is still available. Why?

Conventional wisdom states that Vioxx was removed because, despite the FDA assurance of its safety and effectiveness, it directly causes heart attacks, and that the VIGOR study proves this. You will find that claim in any number of news articles from sources such as the New York Times, Huffington Post, CBS, and others. Just google "Vioxx heart" and no doubt you will be beset by articles touting the dangers of Vioxx. The one place you will not find it is in the New England Journal of Medicine, which published the original VIGOR study in 2000, and released a defense of the study in 2006, in which they fully stood by their original conclusions.

It has never been proven that Vioxx causes heart attacks in a statistically significant way. Yet Merck, in a moment of political posturing, suggested that it did. On September 30, 2004, Merck's Chief Executive Raymond Gilmartin released a statement, claiming that Merck would be withdrawing Vioxx based on inconclusive results from an unfinished study. At that time, Merck released no conclusive evidence, and even the FDA did not have the data necessary to conclude that Vioxx was harmful.

My theory on Merck's poorly conceived strategy is this: Merck was planning to release the "new-and-improved" version of Vioxx, known as Arcoxia. It was being reviewed by the FDA at the time of the Merck press release on Vioxx. If Merck was viewed as being particularly noble in withdrawing a drug out of the deepest concern for its patients, this "sacrifice" would make them look good, provide free publicity for Arcoxia, and allow them to avoid having to contend with generic forms of Vioxx cutting into their sales. This is nothing new: a similar maneuver was used when Seldane was replaced by Allegra in 1997.

Sadly for Merck, they embarrassed the FDA. One of their "safe and effective" drugs was hailed as being unsafe. It consequently did not defend Vioxx, and it certainly did not grant approval to Arcoxia. Merck had to shell out billions of dollars in litigation fees, and received no return on their investment in Arcoxia in the American market. In addition, it withdrew another Cox-2 inhibitor drug, Bextra, leaving Americans patients looking for Cox-2 inhibiting medication with only one option (Celebrex).

In the case of Vioxx, the FDA did not protect patients, nor the drug companies whose medicines it approved from costly litigation. Thanks to Merck and the FDA, individuals suffering from pain and GI problems now have fewer choices than ever. The lives of millions of Americans were thus manipulated by a powerful regulator with little to no concern for its stated mission. The FDA's vindictive refusal to approve Arcoxia may have shown Merck up, but the American people are left holding the bag in these power plays.

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Darvon's Withdrawal

The case against Darvon, which was FDA-approved in 1957 and abruptly withdrawn in 2010, is confusing. Dr. Sidney Wolfe, author of Worst Pills, Best Pills and a health lobbyist connected to Ralph Nader, has wanted Darvon banned from the market for decades, claiming links to suicide, heart arrhythmia, and other serious problems. His petitions to have the drug banned were rejected in 1978 and 2006, and it wasn't until November 2010, months after Wolfe's appointment to the FDA's Drug Safety and Risk Management Committee, that the drug was finally pulled from the market.

Here is a link to what Dr. Wolfe has to say. This video was posted on the day of the FDA vote (Nov. 19, 2010) and is short on evidence against Darvon.

Several doctors I know have complained that they used Darvon effectively for years without incident, and were bewildered as to why it was banned. I found it curious that not only were Wolfe's petitions rejected twice, but the FDA voted to remove the drug by a margin of 14-12, certainly not an overwhelming majority.

I read this memorandum by Dr. Wolfe, which he submitted to the FDA Center for Drug Evaluation and Research one day before the vote on Darvon. It certainly is heavy on implication and warnings, but there is very little conclusive evidence that Darvon users who did not have prior cardiovascular problems and did not overdose suffered from any unusual symptoms while using Darvon.

Thankfully, Darvon is not a groundbreaking cancer drug, and its loss from the market, while annoying, will likely not transform lives. However, it is frustrating to think that one lobbyist's obsession (Dr. Wolfe never actually practiced medicine) could remove people's ability to make educated choices about which medicines they would like to use. Particularly when that removal is based on shabby evidence.

Postscript:  I am happy to be back and looking forward to continuing to take on the FDA! Also, welcome to readers from urbansurvival.com! George Ure always has interesting perspectives and I so appreciate his mentioning the FDA Monitor!

Glee, Christmas Miracles, and the FDA

Let's talk Glee. There are a number of things that are realistic on that show. People can sing. People can dance. BUT people cannot find Rewalks under their Christmas trees in the United States of America.

Sorry, Artie. Source*

Why? The easy answer is that the FDA hasn't approved it yet. That could be because of concerns that the V.A., Medicaid, and other payers may not be able to fund an expensive device like the Rewalk Personal. But the FDA's refusal to approve it clearly flies in the face of its mission statement to "protect and advance" public health. While the FDA has approved Rewalk Rehabilitation, a model only used in medical facilities, it has remained quiet about its plans regarding the Rewalk Personal, which individuals can take home to use where and when they please. 

The issue came up recently during President Obama's visit to Israel. As the President viewed a demonstration of the Rewalk by two disabled veterans (U.S. Sgt. Theresa Hannigan and Israeli soldier Radi Kaiuf), Rewalk's creator, quadriplegic Dr. Amit Goffer, had this to say:

“This device is already improving the quality of life for many people and we look forward to seeing its continued expansion around the world including in the US where we are awaiting FDA clearance for daily personal use.”

In other words, it is a shame that Americans who are disabled cannot join the over 100 individuals in Europe and Israel who are currently benefiting from the device. 

In my first post, I asked what the price of FDA interference and so-called protection is in terms of time, efficiency, and money. Here, it is clear that the effects of FDA inaction go beyond that. There are people sitting at home right now who could be walking, or at least raising money to be able to walk, as this man is trying to do in Leicestershire, England, or as Claire Lomas, a British athlete, succeeded in doing. Dr. Goffer, who was inspired to create Rewalk because of his own struggle with paralysis, said he hopes costs will go down soon as the company shifts to mass production. He also stated that Rewalk does much more than merely improve people's fitness. As one woman stated, the best part is being able to speak to other adults at eye level. Why is the FDA holding people back from improving their health and emotional well-being? 

Claire Lomas breaking old boundaries at the London Marathon thanks to Rewalk. Source*

I can think of only two possibilities. Either Rewalk Personal is sitting on a desk somewhere and FDA employees are too busy measuring caffeine in syrup to bother with it, or they are waiting for the device to gain enough traction and popularity in Israel and Europe to enable the company to shift to mass production so that the costs will be lower by the time it hits the American market. In the meantime, it is one less thing to worry about fitting into Obamacare. 

Obama and the Morning After

Here is a telling excerpt from a HuffPo article today:

"The FDA was preparing in 2011 to allow over-the-counter sale of the morning-after pill with no age limits when Health and Human Services Secretary Kathleen Sebelius overruled her own scientists in an unprecedented move."

In all the hullabaloo about the "morning-after" pill being available to fifteen-year-old girls, it is not widely reported that, back in 2011, the FDA was fully prepared to approve its use for ANY woman of child-bearing age, though it did not specify what that age was. It was prevented from doing so by Health and Human Services Secretary Kathleen Sebelius, and her decision was overruled by New York Judge Edward Korman. Since Korman's ruling, the FDA has agreed to make the morning-after pill available without a prescription to girls who are fifteen and older.

While there has been some controversy over the FDA action, people don't seem to realize that the FDA would have been willing to make the pill available without a prescription to virtually any pre-teen in 2011. 

There is an incredible amount of politicking that went into this "scientific" decision, so much, in fact, that it is hard to know where to start pointing fingers. Is Obama at fault? He claimed to be "very comfortable" with the FDA's recent court-ordered action, but it was his secretary who opposed it. Is the judge at fault? He was merely reinforcing the FDA action from 2011. Is it Secretary Sebelius, who interfered with the FDA's scientific work, or was it a bad decision on the part of the FDA which she was right to oppose?

The furor over the FDA's move overlooks the complicated dance that led up to it. Why did Sebelius stop the FDA's action in 2011? Was she afraid it would be too controversial and make her department look bad, even though she may have been relatively secure that her objection would be overturned in court? Why is Obama "comfortable" with a ruling that his own Department of Justice is seeking to appeal? My sense is this a highly political game in which the Obama administration is attempting to sidestep controversy in a confusing and, for many, disturbing development.

A quick timeline:

• 2011: FDA prepares to approve Plan B without a prescription for "all females of child-bearing potential."
• December 2011: Health and Human Services Secretary Sebelius invokes her authority and stops the FDA approval of non-prescription Plan B for "all females of child-bearing potential".
• Reproductive rights organizations seek to overturn Sebelius's decision.
• 2013: New York Judge Edward Korman overturns Sebelius's decision, claiming it was  "politically motivated, scientifically unjustified and contrary to agency precedent."
• 2013: FDA approves non-prescription Plan B drug for females aged 15 and older. President Obama says he is "very comfortable" with the FDA decision.
• 2013: Obama's Justice Department seeks to overturn Judge Korman's ruling, in contrast to Obama's apparent endorsement of it.

Contraception, under-age sex, and abortion can all be tricky political issues, and President Obama might not have wanted those issues playing out during election season. It is possible that he wanted Sebelius to do what she could to delay this issue from coming to the fore until after the presidential election. 

"No One Asked Us"

So said the medical authority behind the FDA Monitor when I asked him about Colchicine, the ancient Greek remedy for gout.

My Big Fat Greek Medication. source*

             
After my post about Quinine, I began to wonder about other reliable drugs that were around long before the FDA, and what became of them. Starting in the 1930's, any new drugs had to be legally approved by the FDA, while older drugs that were considered safe and effective could remain on the market sans FDA approval.

As recently as 2006, however, the FDA began a new, revolutionary program known as the Unapproved Drugs Initiative. As its name suggests, this new initiative involved the FDA evaluating old, unapproved drugs for safety and effectiveness, even after they had been on the market for years.

But the FDA did more than just conduct tests and put its stamp of approval on products. As this article from the New England Journal of Medicine points out, in the case of colchicine, the FDA granted exclusivity to URL Pharma for a drug that was literally thousands of years old and previously widely available. Since then, URL Pharma raised the price per colchicine tablet from $0.09 to $4.85.

The shocking increase in price- a direct result of the sudden monopoly granted to URL Pharma for a popular drug- affected patients, businesses, and of course the government. Medicaid costs for the drug spiked, going from $1 million to $50 million annually. URL Pharma's successful suit to prevent other companies from selling colchicine only made things worse.

While it may have been unfair for URL Pharma to raise the price that high, it had to pay for an expensive drug trial and give tens of millions of dollars to the FDA. It is clear that the FDA's actions had sweeping implications for the health and finances of millions of people throughout the country.

The title of this blog post was inspired by FDAM's medical authority, who said that at a medical conference, he loudly objected to this particular action on the part of the FDA. As a physician who had prescribed colchicine for years, he saw his patients suffer when it became more difficult to obtain. They were forced to turn to other, less safe drugs, because they could no longer afford colchicine. He felt that this was yet another example of doctors being ignored by the FDA, when they are the ones who directly interact with patients and are ultimately held responsible- by the patients, by themselves, and by the FDA.

This is illustrative of the fact that the FDA, and by extension, the government, is responsible for the high cost of drugs- not the medical profession, and not Big Pharma.

   

It's a Quinine World

If you're like me, quinine might put you in mind of this:

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Or, if you're old-school, maybe this:

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But quinine actually has a very long, colorful history.Originally used in Peru to treat a variety of illnesses,  for a long time it was known as a "miracle drug". Quinine was smuggled and fought over in World War II, and Benjamin Franklin even wrote a story about it in Poor Richard's Almanac.

It was considered a classic American remedy for leg cramps, fevers, malaria, and muscle tension, until the FDA banned it from the market in 2006. The FDA had previously tried to ban quinine in 1994, citing safety concerns. Now, it only allows doctors to prescribe it for malaria and only by one company, AR Scientific Inc. I wanted to find out why.

This Washington Post article has an interesting take on the subject, but I was very confused by two quotes from the article:

1) "The FDA has issued warnings about the risks of quinine since 1994 and more recently about its minimal effectiveness in treating leg cramps. In 2006, it banned the sale of all drugs containing quinine except the branded drug Qualaquin because of the risk of serious side effects or death. "

2) "If you suffer from nighttime leg cramps, your doctor might prescribe quinine. The Food and Drug Administration has approved it for only one purpose -- to treat malaria -- but doctors can legally prescribe most medications, including quinine, 'off-label' for any treatment they deem appropriate."

So quinine is banned. Yet you can buy it here, and here, and here (albeit only in tonic water or homeopathic drugs). And doctors can prescribe it? And if it is not effective, why do people want it so badly? Why has it been used for centuries? 

I felt that there was something missing in the quinine story. The Washington Post claimed that there is little evidence that quinine works to alleviate leg cramps, but blamed that lack of evidence on poor research. The author did not cite any studies proving that quinine is ineffective. In addition, the writer mentioned that from approximately January 2006 to June 2008, the FDA received 38 reports of "serious adverse events", and that 55 percent of those reports were from people who had taken quinine for leg cramps. Which means that over the course of two and a half years in a nation of hundreds of millions of people, the FDA received 20.9 complaints associated (who knows how distantly) with quinine.

So, no, I am not convinced that quinine is all that dangerous. I referred my questions to the medical authority behind the FDA Monitor, who kindly explained that, while the FDA can say that a drug should only be prescribed for one thing, as long as it is legal for doctors to prescribe it, they may prescribe it for anything they want.

So, despite the FDA's disapproval, doctors continued to prescribe quinine for leg cramps, presumably because their patients felt it was helpful. But when the FDA forbade any other company apart from AR Scientific Inc., to produce quinine, the company was able to make it prohibitively expensive. As a result, people naturally wanted to put it on their prescription plans. Unfortunately for people who want to use it for leg cramps, the FDA's ruling makes it illegal to put quinine on prescription plans for individuals who are not suffering from malaria.

This is a complicated issue, but it is one of the most important I've covered on the FDA Monitor so far. I strongly feel the FDA was playing a game here. It is a game that put scores of companies that used to sell quinine through financial hell, while enriching one drug company. It is an example of the FDA interfering in the doctor-patient relationship as well as the economy. Now, people who had used quinine for years have to jump through hoops to get it, pay too much, or just live with pain. 

not if the FDA can help it. source*

The Rush Limbaugh Factor

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You may hate Rush Limbaugh, and you wouldn't be the only one. But there is no doubt he is relevant in any discussion about the FDA.

For years, one of Limbaugh's main advertisers was Zicam, a homeopathic cold remedy. It was banned in 2009 by the FDA due to claims that it was causing anosmia, or loss of smell, in certain individuals.

Here is Limbaugh's shocked response to the ban from June 18, 2009:

"It's very deceitful, this Zicam stuff, folks, someday I'm going to be able to tell you the truth about this. What the FDA did yesterday regarding Zicam is unprecedented. The FDA has never done before what it did yesterday. This is a company being targeted for, let's face it, obvious reasons."

Again, you may hate Limbaugh. But that does not mean there is no truth to any of his claims. Yesterday, I mentioned that the FDA has not flinched from alarming the public in cases where its reputation was not at stake. I think the Zicam episode is a perfect example.

There are myriad drugs on the market that are homeopathic and, no doubt, very weird. But they are out there and being marketed without FDA approval. Even pepper spray is sold without FDA approval.

All I am saying is, if I want to spritz Zicam up my nose, I should have the right to do so. I am also saying that the FDA putting the kibosh on Zicam was purely political. 

The FDA is one of many government bureaucracies that Limbaugh has taken swipes at, and I think they wanted revenge and found their target in Zicam. 

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I would love to hear your thoughts on this. Do you think the FDA was justified? Do you miss Zicam? More importantly, are you comfortable with the idea of the FDA having the power to summarily pluck homeopathic remedies off of pharmacy shelves?

Or maybe you just think he deserved it. source*