Recently in Dangerous Drugs Category

Kudos to Evelyn Pringle of the Media Monitors Network for an excellent case study of how drug companies promote profits by paying for research supporting off-label uses for their products.  "Just What Kids Need - Sparlon - Another ADHD Drug" (March 2006).

The report features DuBose Ravenel, MD, a pediatrician with 25 years experience with ADHD children, who testified for the International Center for the Study of Psychiatry and Psychology at the FDA's March 23, 2006 meeting of the Psychopharmacologic Drugs Advisory Committee and blew the whistle on Joseph Biederman's conflict of interest in his research supporting an off-label use for an ADHD drug.

Together Evelyn Pringle and Dr. Ravenel raised ethical questions of Dr. Biederman relationships to a drug companies.  Add that to the recent revelations by the New York Times'  "Researchers Fail to Reveal Drug Pay" June 8, 2008 and you will see why I recommended in my previous article on this topic that Harvard make a public example of their "payola" faculty by firing them.  

Here is what Ms. Pringle wrote in March 2006.

"The pharmaceutical company, Cephalon Inc, is going through the motions of legitimizing the sale of Sparlon for the treatment of ADHD even though its active ingredient, modafinil, has been heavily promoted and sold under the name Provigil, for off-label treatment of ADHD by Cephalon for years.

"Last October, the FDA sent an "approvable" letter to Cephalon for the pediatric use of Sparlon pending a March 23, 2006, meeting of the Psychopharmacologic Drugs Advisory Committee to review the drug's approval.

"Modafinil-based Provigil is currently only approved for narcolepsy, sleep apnea and shift work sleep disorder, according to the FDA. However, it is estimated that half of all Provigil prescriptions are written for off-label use.

"Doctors now prescribe it to treat everything from attention deficit hyperactivity disorder (ADHD) to fatigue associated with multiple sclerosis and depression," according to the November 1, 2004 Business Week Online.

"Cephalon gets nearly half of its $1.2 billion in annual sales from modafinil.

* * *

"With Sparlon's application to FDA approval, Cephalon claimed 3 studies involving more than 600 children aged 6 to 17, found the drug to be more effective than a placebo.

 * * *

"Dr DuBose Ravenel, MD, who will testify on behalf of the International Center for the Study of Psychiatry and Psychology at the advisory committee hearing on March 23, makes the point that although "48% of drug treated subjects at final follow-up were "much" or "very much" improved clinically, 52% were not."

"This is a substantially lower response rate than has been reported for traditional stimulants," the doctor notes.

Dr Dubose Ravenel is a pediatrician with 25 years experience in private practice with a heavy emphasis upon behavioral issues, including diagnosing and managing ADHD.

"In addition, she notes, with regard to potential conflicts of interest, itemized conflicts for each of the Pediatric study's authors are numerous.

"For instance, "Dr. Biederman received research support from 10 companies, serves on speakers' bureaus for 4 companies, and is on advisory boards of 6 companies,"" Dr Dubose Ravenel reveals.

"Other authors have numerous listed conflicts as well she notes.

"In light of recent widely publicized articles showing widespread deceptive practices engaged in by pharmaceutical companies in designing, selective reporting, and interpreting studies," she says, "the large number of pharmaceutical company ties with the authors of the study do not lend confidence to the reader even beyond the aforementioned concerns."

And "thank you" to Dr. Ravenel for reporting on conflicts of interest in drug research investigations.  Good job.

Onward.

Richard Alexander

Drug company money influences and corrupts research.  That is a given.

What is less understood is why drug manufacturers spend billions for research on off-label uses for their products - uses that were never cleared with the FDA when the drug was submitted for approval.

Off-label use allows drug companies to get "through the back door" what they could never, and I mean never, get away with by going directly to the FDA for approval for a new use of a product - what is known today as an off-label use.  

You would hope that researchers wouldn't corrupt the commercial experimentation of a new, or off-label, use of a drug to treat children by covering up their consulting fees from Big Pharma.  But that's what happened.

More important than what happened is why it happened and at the bottom of all this is a terrible mistake the U.S. has made in allowing the exploitation of off-label use.

The devil is in the details, so here is the story as it has unfolded.

Leading Harvard professors studying off-label uses, the gold mine of the drug industry, have violated National Institute of Health reporting requirements when more than $10,000 has been received from a subject company, according to the New York Times, "Researchers Fail to Reveal Drug Pay" June 8, 2008.  

Johnson & Johnson, Eli Lilly, Merck and the other big time operators, the leading exploiters of junk science, thrive on talking the FDA into approving a drug for one use and then encouraging research so doctors will use it for other purposes. Everybody knows the FDA can't stop toxic food from being unloaded on Americans.  Yet few realize that the drug companies have hired off the FDA's most seasoned researchers, leaving juniors guarding our public health. 

So it is easy to wing a drug application past the FDA's lap dogs and once that occurs, off-label use can exploited by the manufacturers. 

Off-label use is allowed under our law on the theory that the doctor knows best, and once a drug is approved by FDA for one purpose, a physician can prescribe the medication for other uses.  That's where the big money is in pharmaceuticals.  Off-label drug use accounted for more than 20 percent of drug sales in 2006, according to the Annals of Internal Medicine, which provides an excellent overview of who's in charge of safeguarding patient welfare and FDA off-label policies.  

Drug companies cannot directly market off-label use.  That's against the law and major companies such as Eli Lilly, Pfizer and Astrazenica have been prosecuted for doing so and causing serious personal injuries and deaths.  

In many cases the harm caused by off-label continues for years.  That's the case with Wyeth's Pondimin® and Redux®, better known as Fen-Phen, an off-label use for weight loss that is responsible for primary pulmonary hypertension. Fen-Phen continues to devastate lives with tragic and deadly personal injuries a decade after its marketing demise.  I know.  These innocent victims are my clients.

But what the FDA takes away from drug manufacturers on one hand it gives back on the other.  Today there is a loophole in prohibitions against marketing off-label use big enough to drive a train through.  Our FDA watch-kittens have eased the rules which allow drug companies to republish and distribute scientific articles on the topic. 

It's a bad policy that has been blasted by a leading Stanford researcher, Dr. Randall Stafford who said so in an editorial in the New England Journal of Medicine in April 2008. 

The drug companies know the trick is to get someone else to talk about new ways to use their drugs and then pass on copies of the research articles they cannot publish themselves to every doctor in the western world under the companies' First Amendment right to free speech.  That's why Merck wrote drug studies for doctors.  

Drug companies need to have researchers finding new off-label uses.  Since pushing research for off-label use is a key to profitability, that is what drug companies do and to the extent that it promotes scientific discovery that's good, but it has to be above board. 

Turns out that Dr. Joseph Biederman, a world-renowned Harvard child psychiatrist and his Harvard sidekick Dr. Timothy Wilens have been operating below the board.  They either cannot count over $10,000, or they have willfully violated NIH mandates and federal reporting requirements.

The duo collected $1.6 million in unreported consulting fees from drug makers since 2000 to experiment with antipsychotic medicines in children, but nary a disclosure.

They are not the only ones.

Dr. Thomas Spencer, another Harvard professor, pulled down at least $1 million in unreported drug money and reporting also slipped his mind.

So there must be more.

Thank you Senator Charles Grassley for forcing them to disclose.  Good work.

Harvard needs to end this skullduggery by requiring their big league faculty to annually turn in their tax returns with the W-2s and 1099s attached to guarantee full disclosure and compliance with ethical research requirements.  Then post it on a website.  Let them complain.  If they want the Harvard imprimatur, that's the price.

Other major research institutions also need to make sure that disclosure requirements are mandatory, not merely "ethical" expectations.  If the public and regulators are to have any confidence in research, the source of funds and the amounts must be publicly disclosed.

Harvard needs to make a strong public statement by making a public example of these outlaws. Saying "sorry" isn't enough.  

If Harvard doesn't fire them, it will be complicit in the cover-up.  

Throw them off campus.  Ring the bell loud and clear that no matter how renown or stellar, if you don't play by the rules, you can't play at all.  And the NIH should forever ban them from receiving grants.

Don't throw out the baby with the bath water.  Once appropriate punishment has been served, give these researchers a chance to polish their tarnished reputations. Allow them to conduct research under the supervision of a responsible administrator who knows that "veritas," means truth, accuracy, honesty, and uprightness and that it's more than just a motto.

Onward. 

Richard Alexander 

Would you like to turn over control of your health and viability - possibly your very longevity - to an understaffed, underfunded government bureaucracy?  

Doesn't appeal to you, does it?   

The FDA (U.S. Food & Drug Administration), which if you think about it for a little while, has extraordinary power over your personal well-being - may gain even more dominance over your destiny.  The battle for world domination of your body will occur this fall in the august chambers of the U.S. Supreme Court.

The foundation of the legal fight is the Vermont Supreme Court decision in Levine v. Wyeth. 

Diana Levine, a professional musician, was treated, in April 2000, for a severe migraine headache and nausea.  Staff at the Vermont Health Center injected her with Phenergan, a nausea medication. They used her arm to administer the injection and the outcome was very disastrous: she lost her right arm below the elbow, and left the hospital an amputee.

Levine sued Wyeth, which sells Phenergan, on the basis that the warning label on Phenergan - although it complied with FDA requirements - was inadequate.  Levine won a jury trial and was awarded about $6.8 million.

Wyeth appealed the decision because it wants to hide behind the FDA. The case went to the Vermont Supreme Court which ruled against Wyeth, saying, in essence, the drug manufacturer had a duty under state law to strengthen the warning label on the drug, regardless of the FDA's confusing, and sometime conflicting, regulations on when, or if, warning labels should be revised.

The Politics of Pre-Emption

At the heart of the upcoming U.S. Supreme Court battle is the concept of pre-emption: that federal law pre-empts the right of victims such as Diana Levine to sue for the damages inflicted upon them in state courts. 

The [supposed] logic is this: if the FDA has approved the drug, or medical device, and the label, then drug manufacturers need only to comply with the FDA's requirements to be granted sweeping immunity against personal injury law suits filed in state court for damages based for failure to warn.  Or as the New York Times stated the drug companies are looking for  "a legal shield" against being held accountable.

Why is it that major corporations, and many of their Republican supporters, are always talking about accountability and responsibility, until it comes to them?

The whole thing is scary.

Here is an agency - the FDA - which is understaffed and not keeping up with technology - faced with the possibility of assuming even more control over our very being.   USA Today published a story - citing an independent panel review of the FDA - which revealed that the agency has about the same size staff as 15 years ago.  According to the article, Instead of being proactive, the agency (FDA) is often in "fire-fighting" mode.

If the U.S. Supreme Court rules in favor of Wyeth, upholding the pre-emption rule, it takes away one of the major legal remedies the average U.S. citizen has when events such as Diana Levine's nightmare occurs.  

And yes, politics, notably the Bush administration, is solidly evident. The Bush Administration has moved stealthily to prevent state common law claims. 

In January 2006, the FDA adopted new regulations, the ultimate purpose was to torpedo efforts to allow personal injury claims to be heard by state court juries. 

The FDA said "it is the expert federal public agency charged by Congress with insuring that drugs are safe and effective and that their labeling adequately informs users of the risks and benefits of the product and is truthful and not misleading."   Translation: "if we say it won't kill you, it won't kill you."

And since when is the FDA in the job of insuring anything?  These are the same folks who can even inspect imported food to make sure it is safe.

Take all the extremely technical legal argument out of this and there is still the factor of human error, of an understaffed agency monitoring an exponentially growing number of pharmaceutical products, and the potential for this agency to slam the door in a citizen's face should a medical catastrophe occur.

In May, the Congressional Committee on Oversight and Government Reform held hearings on the pre-emption issue. Chairman, Rep. Henry Waxman, said in his statement, that if the pharmaceutical managers, the FDA and the Bush Administration have their way in court, "...one of the most powerful incentives for safety, the threat of liability, would vanish."

Whose body is it anyway?  Yours, or the FDA's?

Onward.

Richard Alexander

On May 14, 2008, Bayer HealthCare Pharmaceuticals Inc. announced it was recalling Trasylol and confirmed that it was pulling its U.S. stock from hospitals and doctors.  The announcement was made by the FDA.

Last November, in a thoroughly randomized study conduct in Canada, it was found that the drug increased the risk of personal injury and death compared to competing drugs, which are less expensive.

Rather than demand an immediate cessation of use and a recall in response to the November announcement of the Canadian study, the FDA, known for pandering to the drug industry, opted to request Bayer stop marketing the drug, but allowed it to remain on the market and available for use. 

The FDA ruling favored Bayer, rather than making patient protection its top priority. 

The FDA, the official handmaiden of the drug industry, in its  May 14, 2008 announcement provides Bayer with an unbelievable soft landing. 

The FDA says it  "has not yet received full study data from the study's researchers at the Ottawa Health Research Institute but supports Bayer's decision to completely remove Trasylol from regular use in the U.S. market."

Thanks for protecting patients needing heart bypass surgery by being so pro-active and decisive.  If they worked for me, I would fire them.

This announcement is a classic example of a mealy-mouth bureaucracy dominated by pro-industry supplicants protecting drug companies rather than protecting the public with the truth: Trasylol is far more likely to kill patients compared to longstanding comparable and less expensive medications.

The Canadian study will be published on May 21, 2008. That is the reason why Bayer announced the May 14th recall in advance of the expected firestorm of negative publicity when the study is published.

Bayer, which has long marketed "buffered" aspirin, is "buffering" the anticipated adverse press with whitewash.  

The FDA and Bayer report that from now on Trasylol may only be used on patients "who have no acceptable alternative therapy."  Doctors who elect to use Trasylol "must verify that the benefits of the drug clearly outweigh the risks for their patients" requiring antifibrinolytic drugs in coronary bypass graft surgery to stop the breakdown of blood clots and reduce blood loss due to bleeding.  

The claim that doctors may "elect" to still use Trasylol is nonsense written and promoted by Bayer's lawyers and consultants.  

No surgeon in her or his right mind is using Trasylol when dependable generic anti-bleed drugs are much safer and cheaper.  

Trasylol is simply not worth the risk.  

And the FDA official announcement is nothing but a cover-up.

Never forget that it is the FDA's official position in pending cases before the Supreme Court is that no one injured by a drug should be allowed to sue a drug manufacturer for the harm inflicted upon them.  That position is so ludicrous that it prompted immediate hearings in Congress and the drafting of a Patient's Bill of Rights that will be enacted within a year.  

With that in mind, the FDA's whitewash of Trasylol is understandable. 

Understandable and deplorable.

Learn more about Trasylol on alexanderinjury.com.

Onward.

Richard Alexander

In USA Today, April 23, 2008, the editors opine on the right of citizens to sue the FDA for defective drugs, "Our view on pharmaceutical safety: If a drug has FDA's OK, should you be able to sue?" http://blogs.usatoday.com/oped/2008/04/our-view-on-pha.html.

USA Today acknowledges the important role of attorneys in holding drugs companies accountable but would limit the right of citizens to collect for damages unless they can demonstrate that a company deliberately deceived the FDA or knowingly failed to warn about the risks of its medicines, they shouldn't be able to collect a dime.

Kidney failure, stroke, heart attack and death following open heart or bypass surgery have been caused by Trasylol®, a drug manufactured by the German pharmaceutical conglomerate, Bayer AG.  

It was intended to limit bleeding during surgery procedures. 

But in November 2007 Bayer AG was forced to pull Trasylol® from the market following a request by the FDA. 

MRIs are so routine that medical patients usually feel they have nothing to worry about when their doctors recommend them. 

But an emerging and dangerous disease, that is essentially being ignored by the media, may force people to take a second look. 

Some MRI's inject a contrast into the blood street that contains gadolinium, an exotic magnetic metal.  If the patient has kidney problems, the coating on the gadolinium washes away and the metal invades the bone marrow, causing  nephrogenic systemic fibrosis, a man-made skin disease that causes the hardening of skin and a painful death.