There is nothing like a stack of internal documents to tell a story. And so, the US Senate Finance Committee has released a wad showing Medtronic employees were secretly involved in drafting and editing favorable journal articles about its spinal fusion product while the device maker paid millions to influential doctors whose names were on the studies.
Over a 15-year period, Medtronic paid $210 million to 13 doctors and two corporations linked to doctors, including more than $34 million to University of Wisconsin orthopedic surgeon Thomas Zdeblick, who co-authored a series of papers about the product, according to the documents, which were first reported by The Milwaukee Journal-Sentinel and Medpage Today.
Meanwhile, Medtronic (MDT) execs inserted language into studies that promoted InFuse as a better technique than an alternative by emphasizing the pain associated with the alternative, according to the Senate investigation. And there is an e-mail exchange showing a Medtronic employee recommended against publishing a complete list of adverse events that were possibly associated with InFuse in a 2005 Journal of Bone and Joint Surgery article.
"These publications are prestigious and influential, and their standing rests on rigorous science and objectivity," says US Senator Chuck Grassley in a statement. "It’s in the interest of these journals to take action, and the public will benefit from more transparency and accountability on their part.” Grassley spearheaded investigations into conflicts of interest among physicians and academics with ties to drug and device makers.
The investigation extends long-running scrutiny of the controversial device maker and Infuse, which was approved by the FDA in 2002 and contains a genetically engineered version of a naturally occurring protein. Since then, Infuse has been implanted in more than 500,000 patients by more than 2,300 surgeons and racked up hundreds of millions of dollars in annual sales.
Last year, meanwhile, a medical journal devoted an entire issue to dissecting the controversy over Infuse. The Spine Journal reviewed 13 studies previously published elsewhere and discovered that side effects were downplayed or omitted. These included cancer, sterility, infections and dissolving bones. There was also leg and back pain (back story).
And these occurred between 10 to 50 times the original estimates calculated in the studies. Moreover, all 13 studies were funded by Medtronic. However, none of these side effects were reported in the papers, even though the studies were peer reviewed (see here). The journal is the official publication of the North American Spine Society.
"While the report confirms what was reported in the June 2011 issue of The Spine Journal, the committee’s access to Medtronic’s internal documents presents a more detailed and disturbing picture of what can go wrong when ethics and patient safety are compromised for profit," the organization says in a statement.
For its part, disputed the report. "Medtronic does not agree with many of the findings in the staff report. In particular, Medtronic vigorously disagrees with any suggestion that the company improperly influenced or authored any of the peer-reviewed published manuscripts discussed in the report, or that Medtronic intended to under-report adverse events. In fact, Medtronic reported to the FDA the potential adverse events addressed in the staff report, and these risks were reflected on the product’s FDA-approved label.
In addition, the staff report’s characterization of payments received by physicians is also misleading and unfair. The vast majority of such payments were royalty payments made to compensate physicians for their intellectual property rights and contributions, not consulting payments. In general, royalty and consulting payments are a commonplace and appropriate practice in the medical device industry," the device maker says in a statement.
After the Spine Journal released its issue, Medtronic hired Yale University to oversee an independent review of the safety and effectiveness of Infuse. "This sounds eerily familiar to many of the transgressions we've read about from the pharmaceutical industry," Harlan Krumholz, a Yale professor of medicine who is overseeing the review, tells the paper.
"It paints a picture of a company very heavily involved in the science; marketing contaminating the science; and the medical profession and researchers being complicit," he adds. "It's no wonder the public has lost confidence in the drug and device industries."
The Senate report is quite lengthy - there are more than 2,300 pages - and make take some time to load, but here you can find the link right here.
As for the interesting e-mail, the 2004 note was written by Julie Bearcroft, who was director of technology management in the Medtronic biologics marketing department, and she was involved in editing a 2005 article in the Journal of Bone and Joint Surgery. She recommended against publishing a full list of adverse events.
The complications had been seen in a clinical trial and formatted in a detailed table, according to an internal Medtronic email. But on her suggestion, the table was not included in the published paper. "I personally think it is appropriate to simply report the adverse events were equivalent in the two groups without the detail," Bearcroft wrote in a note on a draft of the article.
After the editing change was made, the lead author of the paper, a surgeon named Ken Burkus sent a draft to his co-authors with the note, "this manuscript documents the superiority in clinical and radiographic outcomes with (Infuse)..." He received $6.4 million from Medtronic from 1998 through 2010, according to the Senate documents. [The first reference to the e-mail can be found on page 9 of the report].
27 Comments
Yes, I know there is the standard sound-off about how the FDA us underfunded ... all true. Their authority and resources are weak. But it doesn't answer the question.
The FDA dedicates enormous amounts of resources to hapless things like providing comments to companies on their draft promotional materials. I used to work with these company teams, countless drafts are sent to the agency for comment by companies all across the industry. It's a waste. The companies do not need this support. They have teams of regulatory reviewers and lawyers who know the rules. Stronger enforcement will guarantee more compliance, far more than hundreds of comment letters.
And the area involved here is an area that the FDA seems afraid to step into -- medical journals. But they need to. Articles that present genuine new data, that are science-based and vetted by a genuine peer-review committee should be regarded as science and left alone by the FDA. But articles that are manipulated by the companies using paid writers should not be treated as science, they should be treated and regulated as promotion because that's what they are.
The FDA has to develop some courage and some strength and step into this area. One very strong enforcement action treating a manipulated or ghost-written article as promotion and we will see publication practices across the industry changing rapidly.
Congress should be focused on passing bills that help to address our fiscal crisis, failing infra-structure, immigration issues and energy dependence. We do not need Congress being compelled to step in to do the FDA's job, no more than we need US Attorneys and the OIG doing it either.
This little girl now rides a bike instead of sitting in a wheelchair with an oxygen mask.
http://www.dailymail.co.uk/health/article-2193501/Wonder-drug-Kalydeco-heal-lungs-Cystic-Fibrosis-sufferers.html
And then there is Glaxo's malaria vaccine, which reduced the risk of severe infection by 50% in children under age 1 1/2.
That being said, we're very sorry not to have lived up to your standards of scientific enquiry. We promise to try harder.
Here's the car I used to rent to drive my KOL'S to dinner:
http://media.photobucket.com/image/pimpmobile/whitlockt/pimpmobile.jpg?o=14
" In addition, the staff report’s characterization of payments received by physicians is also misleading and unfair. The vast majority of such payments were royalty payments made to compensate physicians for their intellectual property rights and contributions, not consulting payments. In general, royalty and consulting payments are a commonplace and appropriate practice in the medical device industry."
As I have reviewed the case, it is true that one or two surgeon's got a big chunk of the relevant bucks for royalties. But there were many more who got enormous pay-outs that had nothing to do with royalties. Medtronic appears to be making the claim based on total dollar amount rather than number of surgeons and amounts to each. Kind of knowing what "is" is.
As for the FDA, also true that FDA had many of the spun studies. Carragee of The Spine Journal had to use a FOIA to get materials from FDA, and even then it was not easy. Some of the harm data was there. Some was impossible to retrieve because, according to Carragee, initial study design was biased to conceal it.
A group at Yale is now reviewing the case. Because of the last factor mentioned, Carragee has little hope the reality will ever really come out.
All you need is a personalized license plate and your hand painted name on each door to match your ego.
What would we do with all your comments? I kind of think if you did not post all your facts on any subject, these pages would be a lot smaller.
Could you be the "Most Interesting Man in the world"?
For me to attempt to defend every action undertaken by every representative of the medical device/pharmaceutical industry over the last 30 years would be just as foolish as this sort of deliberately provocative broadside.
Observer, I'm pleased to know you are alive and healthy without every having taken advantage of pharmaceutical industry innovations such as vaccines, antibiotics, blood pressure drugs, and the like. And that you don't know anyone who has benefited from rituxan, herceptin, androgen deprivation therapy, HIV protease inhibitors, or the like.
But some of us think those things have value. If you don't, you really don't have to read the papers.
You will probably observe that I'm the more laid back, if also mildy cynical, as well.
EAT ME
Heck, don't stop trying...ask for computer time (just like astronomers request telescope time) from the multi-billion $$$$ NSA spying apparatus in Utah to crunch "real time" data for you to prove that allowing even 30% of medical research to go all snakeoil salesman with mob accountants is impacting "miracle discoveries" timeline by "x" amount of time.
Here are a few guesses, perhaps you can point me to which is correct?
1) There have not been dramatic improvements in the treatment of hepatitis C, Cystic Fibrosis, and malaria vaccine research in the last 18 months.
2) There have been, but they don't matter.
3) I should continue to do something that I explicitly stated I am not doing now.
Thanks. Once your point is clarified, I can address it.
Did the cure come from the Mother Ship?
How many decades has Hep C been around? And MALARIA - now there's a new one for humanity...(snark)
Why don't YOU tell us all what's been happening differently in the past 18 months? Save the industry - what's being done right for a change?
You know darn well what my point is...who you kiddin'?
1) Should have happened 10,000 years ago, when the disease first jumped species from birds?
2) That the fact that this did not happen is evidence of a conspiracy or fatal incompetence?
3) Or that the potential prevention of 655,000 malaria deaths per year (mostly children) would only be a scientific achievement if it had happened sooner?
Please clarify so I can address your issue.
You know what, John?
I think if you loom above a 2 year old and keep telling them that anything they are observing about life and trying to make the REAL connections that 10,000 years of previous human experience can confirm as cause and effect to each other
is something you respond with "I do not know what you are talking about"
and then you are the only person that child has access to in the way of ejewkayshun
you're probably creating an epidemic of environmentally-induced "autism". So you might want to consider the FACT they if you REALLY don't know what someone else is talking about, you need to step back and look under a microscope as step one.
You asked, "1) Should have happened 10,000 years ago, when the disease first jumped species from birds?"
How do you know that exactly that kind of information wasn't destroyed until shamans and other vested interests figured out how to "know what they were talking about"? After all, how much has "human nature" changed in 10,000 years? Not at all when it comes to the tension between science and religion and $$$$.
2) That the fact that this did not happen is evidence of a conspiracy or fatal incompetence?
The risk that a combo of fatal incompetence and political corruption erased knowledge and, worse, forbade more advancement has already been well documented as a fact of life in many historic epochs. For instance, what happened to the "culture" that produced the Antikythera Mechanism at least 1000 years earlier than what was previously thought to be possible? That's just one example....barbarians at the gate break in and wreck it all except for the "gold" that they steal to leverage into more raids in the future - like I said, nothing has changed about human nature. We're still burning books. They did not care about how many people died from malaria and other diseases of wrecked municipal hygiene any more than lots of people care today...GSK did it for the money - isn't that one of the GOOD things about "capitalism" - greed as a motivator for "science" - especially body rent collecting?
3) Or that the potential prevention of 655,000 malaria deaths per year (mostly children) would only be a scientific achievement if it had happened sooner?
Get back to me with the numbers on the "actuals" and then we'll figure out how much of an "advancement" has been made - especially in comparison to the BILLIONS and BILLIONS of dollars spent in the past 18 months on technology that can process so much DATA on human activity that we are all "safer" now
Heck, think of the dent on health care costs if all it really took to deliver GSK's amazing scientific advance was not throwing the non-autistic, non-drugged 15 year old kid into the coal mine before he had a chance to figure out how to build upon Pasteur's work...
Gotta go prepare for a storm to hit NJ et al - so I'm done speculating and offering up theories for why you never know what the point is for today - always did find it boring but believe it's still a duty to contribute to the un-winding of the damage done by "we don't need no stinkin' rules" C-Suite geniuses....
It's a start.
It's a good thing you don't realize who you are talking to, where I came from, where I've been, the ripples I've created in the stream of history, and even more important, where I am going. That spy database is worthless, in the final analysis. What can you possibly know about the soul and mind of a person based on what they bought at WalMart to ride out another 2 weeks without water and electricity? But all you really wanted to know when you built that billion $$$$ spy center in Utah is how much quickly you can get your hands on people's stuff to fund perpetual war. Like everyone doesn't die eventually....what LOGIC is there is spending ALL resources on killing?
Sure, the constant boot of dafeet of "No" has multiplied many times in the past decade for the best and brightest who got here AFTER all the gold diggers of the 19th century, but no one ever argued that the "idea" I have can't be done, they said "No" because, and I quote accurately and directly, "...It's too hard to do...".
Wonder if the same happened to Pasteur? Madame Curie-Sklodowska? Naw, they did okay in France :-))
At some point, even people in the USA won't be rich enough to afford all their in-bred defects as part of the inheritance and with no one doing "science" in the slave mines, there you go - just like 10,000 years ago! See how easy it is to get back to the good old glory days teaching SPECULATION and theory?
Now go blow out some vials before you fill them with the medical miracles...like, duh.
An interesting wrinkle is whether patients who believe they were harmed as a result of the product, and the alleged spinning of studies to surgeons, will have any recourse.
In the SCOTUS decision in the Riegel case, brought by Medtronic (no irony actually), PMA devices are protected from liability based on FDA preemption. However, many of the injuries (but by no means all) attributed to Infuse and accompanying technology were in off-label applications, which were also promoted through alleged spin in the relevant journals.
Assuming that is true, is the company liable? Should it be? Liable in off-label if can be associated with spun journal articles but not on approved use, if also based on spun journal signed by by mega-paid KOLs?
http://www.pharmalot.com/2012/08/what-preemption-medtronic-lawsuit-can-proceed/
How did you find out? That has been a very well kept secret. Now, you spilled the frijoles.
Also most frequently non-attributed quote:
Chris Christie: DON'T BE STUPID!