FDA Fails To Pursue Off-Label Violations: Report
41 CommentsBy Ed Silverman // July 28th, 2008 // 1:00 pm
The FDA takes an average of seven months to issue warnings to drugmakers for off-label marketing, and the drugmakers take an average of four months to address violations, according to the Associated Press, citing a report compiled by the Government Accountability Office. Here it is.
The report also found the FDA has no one assigned to specifically monitor off-label violations. The agency’s Division of Drug Marketing, Advertising and Communications, which has 44 employees reviewing DTC ads, monitors off-label marketing.
The division examined about 68,000 ads last year, but lacks the resources to review all info received by the FDA, according to the report. The agency uses a prioritization system to select which ads should be reviewed, but the GAO found no evidence the FDA “systematically prioritizes all the submissions it receives.” In other words, the agency isn’t applying its own criteria to most submissions. (see page 40).
From 2003 to 2007, DDMAC issued 42 notices of potential violations related to off-label use, most of which prompted drugmakers to end misrepresentations in their ads. Another 11 cases involving off-label promotion were pursued by the Justice Department during the same period.
Chuck Grassley, the Republican Senator from Iowa, who requested the report, issued a statement saying the FDA “isn’t keeping track of how drugs are marketed for off-label use, even though marketing for off-label use is illegal and it’s the FDA’s job to enforce that law As a result, drugmakers aren’t being held accountable for promoting unapproved use of medicine and patient safety is diminished.”
UPDATE: An astute reader reminds us that, earlier this year, drugmakers began lobbying Washington to push for looser government restrictions on off-label promotion. Ten drugmakers, including Pfizer, Bayer, AstraZeneca and Johnson & Johnson, formed a coalition to push for looser off-label restrictions with an eye toward submitting comments to the FDA, which has been soliciting comments on its proposed off-label promotion guidelines. Back story.
MidwestRebel
What a pathetic lot…big pharma is always whining about their self-inflicted wounds. In April 2008, they whined (with Daniel Troy leading the pack) per the WSJ blog, that off-label oversight is TOO harsh. After reading today about the obvious LACK of oversight, I say balderdash!! Recent case in point is the blatant off-label promotion of Viagra for women!! The JAMA article was picked up ALL over the news, nevermind that it’s never been approved for women…and the list of authors’ financial disclosures was nearly as long as the study.
pharma PR hack
The study was picked up all over the news because it was pushed by a PR firm. Not because it was a large scale or solid study.
atlex
Hack,
If you’re so sure that it was pushed by a PR firm, please identify the firm and show a link to the manufacturer. Given Grassley’s continued focus on off-label promotion, I doubt seriously that the manufacturer was involved in any way. More likely, the media picked up what is considers a sexy topic for it readers or viewers.
Atlex
pharma PR hack
Atlex,
I don’t know who is working the viagra account now but I know for certain these types of things are pushed because I have done it for clients. Studies are big news and often it isn’t corporate com but the brand managers PR team that handles pushing a study by email. I invite you to send Shara an email to see if she actually read the JAMA study or got an email blurb before embargo from a PR firm which may have been “representing” the authors but paid for by Pfizer.
DOW JONES NEWSWIRES
A study published in the Journal of the American Medical Association found that Pfizer Inc.’s (PFE) erectile dysfunction drug Viagra can reduce adverse sexual effects in women caused by antidepressant use.
Sales of the drug, which haven’t been growing for years, could get a boost if the findings result in a new market being opened for Viagra, which hit the market a decade ago.
The doctors who conducted the study, from the University of New Mexico School of Medicine, estimate antidepressant treatment-associated sexual dysfunction occurs in 30% to 70% of people treated for major depression. The JAMA article said it is “believed no randomized controlled trial has demonstrated an effective treatment for women experiencing sexual dysfunction” from antidepressant drugs.
But researchers found that only 28% of women taking Viagra showed no improvement, as opposed to 73% of women taking a placebo. The study showed no serious adverse effects.
The authors noted women experience major depressive disorder at nearly double the rate of men and also experience greater subsequent sexual dysfunction. They wrote that by treating the treatment-associated problem it can “reduce the current high rates of premature medication discontinuation and improve depression disease management.”
Pfizer, the world’s largest drug maker by sales, has been battling existing and impending generic competition for its top-selling drugs.
Pfizer shares rose 1.7% to $18.40 in recent trading.
-By Shara Tibken, Dow Jones Newswires; 201-938-2168; shara.tibken@dowjones.com
(END) Dow Jones Newswires
07-22-08 1409ET
Copyright (c) 2008 Dow Jones & Company, Inc.
pharma PR hack
And Atlex, this isn’t some study Pfizer just got lucky on the media pickup on.. as the LA Times finally picked up on..
“Doctors said the study, which was funded with a grant from Pfizer, could foster broader experimentation with Viagra for women, although they added that the drug was unlikely to become the blockbuster phenomenon it is among men. Its effectiveness in women is limited compared with men, and Pfizer has said it does not plan to develop the drug for female disorders.”
When my clients have funded a study, extra honoraria was paid to the doctor to be available for media interviews, the doctor has furnished the abstract, study to craft pitches and the doctor has told of the publication date upon his finding out.
I’m not sure what you do within pharma but this is the one area I don’t have any doubts about my knowledge base.
truthman30
The FDA is a smokescreen ..
pharma PR hack
That isn’t to say any of that is any different than what is done in any other industry with a product launch, media tour or customer testimonial tour.
Promoting a product and getting/growing awareness is not a bad thing.
I work with really great people who honestly believe they are making a difference in the lives of their customers in healthcare as well as in other consumer goods. Granted the difference in healthcare is more poignant.
The fine line between shareholder value and public health of pharmaceutical/device/biotech products is one every person in the industry directly or tertiary grapples with every day.
Justice in MI
While the issue was not off-label promotion, but rather knowingly inaccurate efficacy claims, we have good documentation that some companies count on FDA delays in reviewing promo material. I documented one such example in a recent thread.
Deliberate misrepresentation of efficacy is obviously less heinous than misrepresentation of risk. But the two often go togther. That is, in the instance cited, the company also knew that their drug has risks not present in others in its class. So false efficacy claims can lead to rx’ing and related serious consequences, needless to say.
As we consider FDA preemption, I hope such examples will remain salient. All of these activities go on essentially outside of FDA review. That is because, by the time FDA gets to them, the damage has already been done.
If there defending such practice ethically, I would certainly be interested in hearing it.
atlex
Hack,
As usual, you make accusations with absolutely no foundation. When you can back up your claim, let us know.
Atlex
Justice in MI
Hi Atlex,
In case you missed it, here is some of the documentation that originally appeared on Pharmalot related to my post above. This is from someone who was present at the discussions described:
“Senior Management discussed the risks associated with using material that likely violated FDA regulations and concluded that it would be acceptable to use because by the time the FDA reviewed the questionable material, another [drug name] sales aid would be out, and therefore the impact of any FDA warning letter would be negligible.”
As it turned out, the impact of the FDA response, by the time it actually came, was less than “neglible.” And, as the saga continued, people died or were seriously injured who probably would not have otherwise.
I have great respect for you, Jack2, and others from industry who post here, and who seem to me to be people of principle as much as anyone I know. So I hope you will agree that behavior of this sort is a problem that should concern all of us.
atlex
JiM,
I don’t at all disagree with your issue. We’ve had the conversation before…our only disagreement was over the frequency of such activity today vs a few years ago as opposed to whether it occurs or not.
In this instance, I am specifically focused on Hack, who positions himself as an industry insider and regularly makes all kinds of very specific wild accusations without any foundation.
Atlex
Justice in MI
Atlex, Thanks for the word. I am not even sure we disagree about frequency. The truth is that I have no idea. I trust and hope it is as you suggest, and, in fact, some folks with whom I am in touch suggest your assessment of the current situation is just as you say.
pharma PR hack
Atlex,
Maybe you are right. Pfizer just paid for the study and had no hand in promoting it. It just naturally got all that media. Which is pretty amazing considering in 2004, Pfizer gave up on trying to prove it had a sexual effect on women. Which was going to be huge for them.
http://www.nytimes.com/2004/02/28/business/28viagra.html?ex=1393390800&en=eccf3ce764e04dd3&ei=5007&partner=USERLAND
The article said the following:
“The market for such treatments could be huge. A study published in 1999 in The Journal of the American Medical Association found that 43 percent of women experienced some form of sexual dysfunction, compared with 31 percent of men.”
As for me throwing out wild accusations.
I have seen it done with a device maker whose treatment had a net effect of patients no longer needing diabetic treatment. It wasn’t what it was improved for but it certainly got some pick-up.
http://www.google.com/search?hl=en&q=weight+loss+surgery+reverses+diabetes+US
Then again I can’t see where FDA off-label guidance pertains to news professionals.
Doc
It really is amazing how much off-label promotion big pharma gets away with, and really no consequences. Oh sure there have been a few big fines, but the companies look on FDA enforcement of off-label as no big deal.
Sam
I guess there is nothing wrong with Pfizer promoting Viagra for just
about anything including their new product Revatio which is promoted
to treat pulmonary arterial hypertension - both products are generically
the same - sildenafil
Lisa Van S
Hey Justice,.. Im a bit curious! Have an agenda? Explanation Maybe?
Lisa Van S
Hey Justice!!!.. Do you have a name? How about credentials? I dont recall anyone asking these questions. Would you like to provide us with some honesty?
Atlex
Sam,
I’m not sure of your point. As far as I know, Revatio is approved for the treatment of PAH. So, of course, it it legal and appropriate to promote Revatio for that purpose. The dosing is different and the name is different…so what.
Atlex
Lisa Van S
Atlex,
Revatio?.. Never heard of it! Is it a Male thing?// Im Curious!!
Lisa Van S
Laurie,
What is revatio?
Nathan
Lisa — It’s absolutely mindboggling that you know how to blog but don’t know how to google. Try this out: http://www.revatio.com.
M Helm, MD
Atlex,
In reference to your contention that Pharma PR Hack is blowing smoke… It is obvious that you’ve never been on a brand team in PhRMA. Everything PR Hack described exactly squares with my experience. Our brand used Burson-Marsteller. This was back in golden age of PhRMA the early to mid 90s - at the time, as now, you can’t buy better PR.
The wonderful thing about using a PR firm is that you can do all kinds of things to build awareness of “new” studies, and there aren’t any obvious corporate fingerprints. Every time we met with our Burson-Marsteller Account Director, I felt like I needed a shower. This is one of the things that drove me out of PhRMA and on to medical school.
It certainly appears to me that there a cadre of folks “back at HQ” working the numbers on the different off-label strategies. It is a risk-reward relationship where (because of ineffective monitoring and generally negligible penalties) the profit reward usually makes the risk worthwhile.
Back in the day, our SVP of Marketing and Sales used to EXPECT that something we did would attract the ire of the FDA just about every quarter. If it didn’t the brand team wasn’t being aggressive enough.
That was more than a dozen years ago, when times in PhRMA were less desparate. Having seen a number of flagrant abuses since, some of which have caused me to make contact with FDA DDMAC if not my State AG, I can only imagine how it goes on the brand teams now.
Nathan
If I understand recall my medicinal chemistry history, Revatio is just Sildenafil marketed for the original indication that was being pursued for Sildenafil. It’s use in ED (aka Viagra) came along pretty much by accident from what I understand. The early R&D certainly was not done with ED in mind.
Anyone recall the history?
Justice in MI
Lisa - I think my “agenda” is pretty clear in everything I post here.
And I’ve mentioned what I do and my “credentials” many times here.
And you know my name because you and I have been in touch directly.
What else do you want to know?
pharma pr hack
Nathan I think you are right. I don’t remember why it wasn’t pushed forward then and is now to be honest.
I have often wondered whether Requip was initially developed for GSK for restless leg syndrome or if that was also a similar situation to Viagra i.e. that was a significant effect.
M Helm, MD
Nathan, I believe your recall of the sequence is correct, the original intent for the PDE5 inhibitors was for Pulmonary Artery Hypertension. I can’t recall well enough to remember if there had been hopes that the mechanism would have been useful in more common conditions (like hypertension or coronary artery disease). PAH is an uncommon, and bad disease.
There used to be no good treatment (other than Oxygen to relax the pulmonary arterial tree). Sildenafil is an oral treatment, so it is more convenient than some alternatives, but I haven’t concerned myself with how well it works.
I’m very confident Pfizer (and the other makers) generate more revenue and profit off of the side effect than the intended effect. That’s likely also true of minoxidil, botulinum toxin, and finesteride. At least in those areas, quality studies were done to validate safety and effectiveness. So, I don’t share Sam’s concern.
The off-label uses which are promoted with inadequate study are what disturb me. That monitoring is inadequate and penalties are laughable should not be acceptable to any of us who read these pages.
M Helm, MD
PR Hack, Requip is truly a drug for Parkinsons Disease. That fact alone should scare anyone who wants to use it for “Restless Leg Syndrome.”
Doc
M Helm MD,
“I can only imagine how it goes on the brand teams now.”
I’m not sure you would believe it Dr. Helm!!! Having recently sat in on numerous marketing strategy meetings - it truly is frightening to see and hear what non-science marketers think is legitimate.
Just A Thought
My friend’s large insurer just refused to cover Lyrica for Fibromyalgia after she’d been taking it for a couple months via samples.
Something come about on that?
atlex
M Helm,
I’ll guarantee I’ve worked on and around brand teams in small and big pharma longer than you. And, while you speak of the “early to mid 90s”, I can speak for 2008. The large settlements and CIAs that most large pharmas have dealt with, have brought about much greater internal scrutiny. As “Doc” mentions above, some marketers do come up with crazy ideas, but systems are in place to ensure that these crazy (potentially illegal) ideas never make it to market. Are the checks and balances foolproof? Probably not completely, but few blatantly illegal activities make it out of marketing departments in big pharma these days.
Atlex
HorusCat
Just A Thought,
I have heard from the Lyrica reps that some insurers require a failure on a generic drug first (even though none of them are indicated for fibro–hypocrisy, anyone?), such as a tricyclic antidepressant, Neurontin, fluoxetine (Prozac), Flexeril (addicting). Depending on the insurer, the doc will have to fill out a prior authorization form indicating adequate trial on one of the non-indicated generics (usually 2-4 weeks). If your friend has failed one of those in the past 6 months, that might be enough. Failing that, the doctor can usually request a doctor-to-doctor consult, getting past the high school graduate who is denying the prior auth. Failing that, the Pfizer reps will probably be glad to keep supplying samples or the doc can have the patient try and fail one of the generics, then re-submit the prior auth.
Ironic, isn’t it, that amid all the uproar over pharma promoting off-label, insurers are requiring the use of medications off-label in order to save money. None of the afore-mentioned generics have good studies showing efficacy in fibro.
HorusCat
Just a Thought,
Some insurers are really picky about how the PA is filled out–for instance, making sure that at least 11 out of 18 tender points are marked as painful, even though there aren’t even 18 listed on the PA form, so the nurse needs to mark “bilateral” where appropriate.
I know all this because I keep in touch with my old partners at Pfe, having a particular interest in fibro, because one of my friends had fibro way back in the 1980’s,when no one was admitting it existed.
Practicing Doc
If the FDA did its job correctly, we wouldn’t have to put up with all of the “snake-oil salesmen” from Big Pharma running into hospitals and offices pushing all this off-label stuff. The greedy, money-driven, Big Pharma executives do this stuff because there’s no real penalties. They make money by the piles, pay a little fine, admit no wrongdoing, and laugh all the way to the bank. IMO, they’re nothing but a bunch of unethical white-collar crooks sucking money from everywhere they can.
Justice in MI
Hi HC - I know nobody wants to rehash the neurontin saga, but - according to the DOJ summary - WL/Pfizer deliberately did not seek approval of neurontin for a number of indications so that the anticipated Lyrica would be there to “fill the void” when patent expired. So, if insurers are insisting on a trial with gabapentin, also irony in that.
I have no idea if fibro was one of the indications then anticipated for Lyrica and “by-passed” for Neurontin.
Just A Thought
I have wondered about Lyrica vs Neurontin and how close they are in chemical make-up. Both being indicated for the same conditions and made by the same company. Maybe that’s why folks have to jump through hoops to get Lyrica? Is it better than the gabapentin generics? I can see the insurer’s questioning it.
I do appreciate you taking the time, HC.
Hypocrisy rules
Practicing doc is absolutely right. He should know. He sees the reps/snake-oil-salesmen coming in and doing their stuff. They come in with fake detail aids, fake studies (written up by paid for docs and printed up to look like real thing)and even home made sales aids to make those offlabel, fales claims. If the doctors believe them fine if not fine again.
The bottom line, enough doctors “buy” these fake claims to Rx the fake-promoted drug for non-indication, so the bigpharmafia makes huge, extra profits to wallow in.
The scary thing is that this is one of quite few of misconducts that bigpharmafia uses to get wht they thing they are entitled to. This misconduct is absolutely planned, deliberate, part of their MO and what is most scary, encouraged and approved by the very top of every bigpharma company.
Considering no bigpharma shot gets in any real trouble, this is a normal behavior.
Remember the classic:”DON’T DO THE CRIME IF YOU CAN’T DO THE TIME”.
The bigpharmafia’s new classic goes like this;”DO THE CRIME, YOU WON’T DO THE TIME”.
The Crime
Why don’t those who do the crime do the time? Second degree murder and manslaughter are crimes. Intentionally hiding lethal side effects, making up and pushing off label use, both of which result in death, should not go unpunished. Paying back the feds some of their costs or giving piddling settlements to families whose hearts are crushed by the loss of a family member due to some pharm drug does not justice make.
Why doesn’t this happen? Every day I think of Syd Taurel in chains.
Justice in MI
This is the relevant paragraph from the Department of Justice write-up of its civil and criminal prosecution of Warner Lambert over off-label Neurontin promotion:
“These tactics were part of a widespread, coordinated national effort to implement an off-label marketing plan. At the same time, Warner-Lambert decided not to seek FDA approval for any of the new uses because it was concerned that approval for any of the non-epilepsy uses would allow generic competitors of Neurontin, which was expected to go off-patent soon, to compete with a “son of Neurontin” drug that Warner-Lambert hoped to have approved by the FDA for both epilepsy and non-epilepsy uses.”
“Son of Neurontin” = Lyrica.
Hypocrisy rules
re paragraph from DOJ: Of course it was widespread, coordinated effort. This only proves what was said before that misconduct by BigPharma is PART of their daily routine and doing busness.
Now they ,BP are always ready to have an explanation. In this case they did not say;
“We did not know it was illegal, judge” but said they were “concerned….”. Of course what happened they simply went ahead with it hoping they would not get caught as many times before. Once caught, their PR and lawyers take over and try to get away with as small punishement as possible.
Another motto they use”It is easier to apologise than ask for permission”. This time it did not work. However that does not mean this Co will stop it. They will find and design other ways much harder to uncover, they’ll hope.
M Helm, MD
For HR, Atlex and HCat -
The way I learned that motto (back in the late 80’s early 90’s PhRMA days): “(Sometimes) It is better to ask forgivness than permission.”
Obviously the “sometimes” was considered optional, but there is a more than semantic difference between the two versions (Better vs. Easier).
Atlex, if you are lucky enough to work for one of the few PhRMA companies that has not engaged in some outrageously unethical if not frankly illegal promotional scheme, then more power to you. However, if you work with the marketing team, then you know that the PR process as Hack described is not only plausible, but also probable.
I could never prove it, but I believed with all my heart that Pfizer’s brand teams must have included at least one lawyer each. The purpose of the lawyer was to rapidly bring suit against any competitor for any possible complaint which might distract the competitor from actually getting out and selling against them. It never seemed to matter if the complaint was valid, just so long as it involved Federal Court.
In my current job, I see a lot of stuff that wouldn’t pass the smell test. How about drug reps calling to obtain prior authorizations for medications with patient information? How about a rep telling a patient and their physician in the doctor’s office how to defraud their own company’s “free trial” program? How about companies targeting physicians who treat only children for detailing on a drug which has no studies or approval for children? How about comparative effectiveness and safety claims when the only published information is placebo comparisons? How about corportate-sponsored “patient protection” state level legislation written explicitly to dimish the ability of public and private payors to implement utilization controls which would actually help to ensure safe and effective use consistent with labeling?
Ethical lapses in pursuit of using meds for “unapproved uses” are not only an industry problem either. HCat would appreciate that there are significant numbers of doctor’s office personnel who will flat out lie to get a PA. This has a name - insurance fraud, and where I am, it is a class D felony.
My preference for PAs involves no forms, but rather, a real time review of medication claims/use history with or without a diagnosis and procedure history. Makes it very hard to lie, and can provide useful information on other medication use and adherence to the clinician. By the way, Hcat, the PA reviewers I work with are all PharmDs - typically more qualified and knowledgeable about the meds than the people making the requests.
SP 2
This is such good news for Big Pharma! No wonder it’s so easy to get away with this stuff. The marketeers and salesgeeks will be on a rampage! Full speed ahead!