December 8, 2012

Expendable; Or, And Now The Pharma Pendulum Swings Back The Other Way

Pipeline.jpg
about to reopen?




In a case that could have broad ramifications for the pharmaceutical industry, a federal appeals court on Monday threw out the conviction of a sales representative who sold a drug for uses not approved by the FDA. The judges said that the ban on so-called off-label marketing violated the representative's freedom of speech.

In short: a drug rep is secretly taped, and later convicted, for promoting his drug for off label uses.  To be clear: he wasn't convicted of inventing off label uses, he was convicted for discussing off label uses that had already found their way in peer reviewed journal articles.

Let's agree that peer review is the scientific equivalent of Soviet era cronyism; but however terrible it is, it is a million times better than anything the FDA offers.  It's worth reminding people that the FDA grants approval for a drug indication not because the drug is effective for that purpose, but because it's effective AND the company requested it.  The drug could cure cancer 100% of the time, if the company doesn't ask for it-- if it thinks it's more profitable to pursue an erectile dysfunction indication-- then regardless of how effective it is, it will be off-label.

This case basically confirms that simply discussing off-label uses is not, in itself, illegal.

From the appeals court ruling:

While the government and the FDA have construed the FDCA's misbranding provisions to prohibit off-label promotion by pharmaceutical manufacturers... as we have observed, the FDCA itself does not expressly prohibit or criminalize off-label promotion.

And the closer:

As we now explain, we decline the government's invitation to construe the FDCA's misbranding provisions to criminalize the simple promotion of a drug's off-label use by pharmaceutical manufacturers and their representatives because such a construction-- and a conviction obtained under the government's application of the FDCA -- would run afoul of the First Amendment.

II.

It's probably headed to the Supreme Court. Make no mistake, this is a big deal.  Forget about "truth" and science and public health: the government collects billions of dollars in fines off of this, not to mention getting a role in Pharma's business, how drugs are marketed and sold-- and there's now a 5/9 chance that all that money and influence will disappear.   And if Pharma suddenly gets to do other things with that money AND get a freer hand in marketing, it will almost certainly change the way medicine is practiced.

There are pros and cons, since the cons are obvious and in every blog on the internet I'll offer two of the pros: first, more Pharma research money for off-label uses.  A double edged sword, but anything that frees humanity from the dictatorship of the NIH is a good thing.

Second, Pharma would be permitted (it would find it invaluable) to study their drug's comparative effectiveness.  There's been a disincentive to do this, because even if someone  discovered that Zyprexa was a billion times better than Geodon, or better for a certain kind of schizophrenic, Lilly couldn't say anything,  it's not in the label.  If they discovered a way to lessen the diabetic risk, say mixing it with some other drug or a specific dietary intervention, they couldn't tell anybody.  It's not in the label.

Looking back on it all, it seems to me that what got everyone into trouble was doctors' belief that Pharma was telling them everything; and therefore didn't have to look anything up.  It's unbelievable to me now, as it was then, that doctors thought this, but there you go.    


III.

But you may be interested in the history of this case:



On October 26, 2005, [drug rep] Mr. Caronia went to Dr. Charno's office. He had never met Dr. Charno before, nor had any previous contact with him but for the phone calls from Dr. Charno seeking a promotional speech. During the meeting, Dr. Charno repeatedly asked Mr. Caronia off-label questions and asked to meet Dr. Gleason [a speaker for the company.]


Dr. Gleason eventually came, and, in the presence of Caronia, had a discussion with Dr. Charno about off-label uses for Xyrem (insomnia, restless legs, etc).  Is Caronia responsible?  Should he have stopped Gleason?  The court said yes, and convicted him.

The trick was, Dr. Charno was actually a government informant.  That's odd.  And I have never heard of a doctor who requested a promotional speech.  He cold called a rep he had never met and asked to meet him to discuss a drug he had never prescribed? 

The third witness presented by the United States Government was the confidential informant, Dr. Steven Charno. After pleading guilty to medical insurance fraud stemming from his criminal act of filing fraudulent medical insurance bills in the amount of $821,000.00, Dr. Charno cooperated with the United States Government against Alfred Caronia.

I thought I was reading the script for a bad cop movie.  Did the government use a plea agreement to force Charno to help the government capture drug reps that he had never even met? 


Dr. Charno erroneously testified at first that he only called Alfred Caronia to schedule a meeting in which he could request to meet Dr. Gleason. Suspiciously enough, Dr. Charno never recorded the entraping phone calls in which he asked Alfred Caronia to come to his office. However, it became apparent during cross-examination that Dr. Charno had been instructed by Government agents as to the potential off-label uses of Xyrem prior to calling Alfred Caronia and used it to lure him into his office for a promotional presentation.


In other words (and Caronia contends) there was hardly a conspiracy to misbrand Xyrem when it was Charno who asked the off-label questions and specifically requested to meet with Dr. Gleason-- all at the government's request.

That bit reminded me of something, an old story, 2006, about a Maryland psychiatrist who was famously arrested at a train station for making off-label comments at a speaker "program".  What had jumped out at me at that time was his defense:


[The speaker] insists that he is not guilty of conspiracy. He says that he was charged only after he refused to help the government build a case against the drug's maker, Jazz Pharmaceuticals -- a sequence of events that court documents seem to support.

That speaker was Dr. Gleason:
 


gleason.jpg




And the man driving him to the very train station where he was arrested was Caronia, after a meeting with Dr. Charno.

So.... Charno was used to get to Caronia, who was used to get to Gleason, so they could get the company.

We know what happened to Caronia.  What happened to Gleason?

Dr. Gleason ultimately pled guilty to a misdemeanor of engaging in interstate commerce of a misbranded drug and got 1 year probation.  Probation ended January 29, 2011.

He hung himself 10 days later.









Comments

hanged. duh.... (Below threshold)

December 8, 2012 10:41 PM | Posted by Anonymous: | Reply

hanged. duh.

Vote up Vote down Report this comment Score: 11 (33 votes cast)
the last psychiatrist is th... (Below threshold)

December 9, 2012 1:41 AM | Posted by Anonymous: | Reply

the last psychiatrist is the shit. . . foh real yo!

Vote up Vote down Report this comment Score: 14 (18 votes cast)
What are the cons?... (Below threshold)

December 9, 2012 2:23 AM | Posted by Jeremy Bentham: | Reply

What are the cons?

Vote up Vote down Report this comment Score: 6 (8 votes cast)
"He received $450 to visit ... (Below threshold)

December 9, 2012 2:29 AM | Posted by Or: | Reply

"He received $450 to visit a doctor in the office, $750 for speaking at a luncheon and $1,500 for a dinner speech. He made as much as $3,000 a day, he said. Although he continued to see some patients, the Xyrem talks gradually became his primary source of income."

I have to wonder how much of that mad cheddar he spent on hookers and blow if "a public defender... took over the case after Dr. Gleason determined he could not afford a private lawyer."

Vote up Vote down Report this comment Score: 8 (10 votes cast)
that's why you go to school... (Below threshold)

December 9, 2012 5:02 AM | Posted by Anonymous: | Reply

that's why you go to school for all those years, . . . so you can pull in the easy money down the line.

Vote up Vote down Report this comment Score: -2 (6 votes cast)
So, I guess, the takeaway i... (Below threshold)

December 9, 2012 1:51 PM | Posted by bbrodriguez: | Reply

So, I guess, the takeaway is, if you're talking to the feds, come what may, make sure you wear a wire?

Jesus fucking wept, "engaging in interstate commerce of a misbranded drug"?

Did anybody reading this actually know that that was a criminal offense?

Conrad Black, who, I have no great love for, has written extensively about this sort of thing. He points out that a 95%+ conviction rate should be cause for concern.

Vote up Vote down Report this comment Score: 15 (21 votes cast)
This is fucking mad. An sad... (Below threshold)

December 9, 2012 2:34 PM | Posted by Arthur: | Reply

This is fucking mad. An sad.

I bet the feds never thought they were about to change the world when they procecuted the poor man to get the company.

This reminds me of the wire. The guy wants to show some work, maybe even thinks he's right, or finds somethings suspicious, or really wrong with a company. He starts to do shit to get to the comp.

A guy dies in the way, and suddenly the whole law gets changed because of a bullshit charge he pinned on someone just to get to the company.

Vote up Vote down Report this comment Score: 3 (3 votes cast)
More like this, please.... (Below threshold)

December 9, 2012 8:11 PM | Posted by sunny day: | Reply

More like this, please.

Vote up Vote down Report this comment Score: 2 (4 votes cast)
Opa Pharma Style. . . . . .... (Below threshold)

December 9, 2012 9:36 PM | Posted by Anonymous: | Reply

Opa Pharma Style. . . . . .heeeyyyyyyyyyyy, fuck the labels,. .. oppp oppp opppp opppp Opa Pharma Sytle

Vote up Vote down Report this comment Score: 5 (23 votes cast)
anony,I believe Hu... (Below threshold)

December 9, 2012 11:43 PM | Posted by 8==D: | Reply

anony,

I believe Hung is the right word as the next article will attest this was off label uses for penis enlargement ;)

Vote up Vote down Report this comment Score: 5 (5 votes cast)
well, with all the penis en... (Below threshold)

December 9, 2012 11:45 PM | Posted, in reply to Or's comment, by 8===D: | Reply

well, with all the penis enlargement pills, he was also given viagras....

Vote up Vote down Report this comment Score: -2 (2 votes cast)
I don't get the picture tha... (Below threshold)

December 10, 2012 8:33 AM | Posted by dumbass: | Reply

I don't get the picture that accompanies this article... is that the oil pipeline? and how does that relate to pharma? i think I need more meds!

Vote up Vote down Report this comment Score: 0 (2 votes cast)
Of course they just had to ... (Below threshold)

December 10, 2012 8:34 AM | Posted by Wyj: | Reply

Of course they just had to do this setup with a drug as controversial as Xyrem, no better way to spark moral outrage.

Vote up Vote down Report this comment Score: 2 (2 votes cast)
I get it... Dr. Gleason is ... (Below threshold)

December 10, 2012 3:32 PM | Posted by Jess: | Reply

I get it... Dr. Gleason is the pendulum!

Vote up Vote down Report this comment Score: 0 (4 votes cast)
Harvey Silverglate, a well-... (Below threshold)

December 10, 2012 4:48 PM | Posted by altoii: | Reply

Harvey Silverglate, a well-known Boston defense lawyer, has written about these kinds of federal prosecutions in Three Felonies a Day.

Vote up Vote down Report this comment Score: 4 (4 votes cast)
It gets even better. If yo... (Below threshold)

December 11, 2012 12:44 AM | Posted by DensityDuck: | Reply

It gets even better. If you discover something about a drug during a trial--like, maybe, the trial is for melatonin levels but the drug also works like Viagra--then you aren't allowed to report it or discuss that in any way. You need to set up a completely new clinical trial series--all the way back at the "does it kill rats" level--specifically to look for that new thing.

Oh, and if your study objective is "better than" but you only get "as good as", then sorry, your drug is not approved today. Go back to the starting point with a completely new study--you can't use any data from the old study, that would be silly--and this time make sure your study is looking for "as good as".

Vote up Vote down Report this comment Score: 16 (16 votes cast)
yeah he killed himself. a y... (Below threshold)

December 11, 2012 2:20 PM | Posted by medsvstherapy: | Reply

yeah he killed himself. a year of 'probation' is enough of a narcissistic injury to kill off a psychiatrist?

Vote up Vote down Report this comment Score: -1 (7 votes cast)
Sycophancy, 'phychopancy' a... (Below threshold)

December 11, 2012 2:44 PM | Posted by Anonymous: | Reply

Sycophancy, 'phychopancy' and toolism in general are well within the range of the human condition. Not a good thing, but they exist and can come out to a degree in all people.

So what I fight and think about allot is... What is it about life as it stands now, where acting this way is rewarded enough that it can maintain a stable equilibrium. Stable and ubiquitous enough that it is a blog-able topic and everyone can say, "yeah, I know what you mean man."

Yeah, narcissism But why narcissism? Why do I feel like reading and internalizing 48 laws of power are the only way to eek out a respectable (not in the monetary sense) existence? Or devolve to sycophancy, and other fringe-base ways of being?

Is the root just higher affluence than we have evolved to deal with? Even most poor people have more comfort than rich people of not too long ago.

I feel like I have a suitable answer, but I just don't like the answer.

A generation or two needs to fade away and be replaced by another equilibrium, unless we've run too far to get home.

Vote up Vote down Report this comment Score: -1 (3 votes cast)
Yeah, yeah. The off-label u... (Below threshold)

December 11, 2012 11:44 PM | Posted by Anonymous: | Reply

Yeah, yeah. The off-label use of Xyrem is date rape.

Vote up Vote down Report this comment Score: 2 (2 votes cast)
What is all of it, Alex?</p... (Below threshold)

December 12, 2012 5:52 PM | Posted, in reply to Or's comment, by It: | Reply

What is all of it, Alex?

Vote up Vote down Report this comment Score: 0 (0 votes cast)
Dr. Gleason was from Maryla... (Below threshold)

December 16, 2012 2:47 PM | Posted by Punditarian: | Reply

Dr. Gleason was from Maryland, but the railroad station where he was arrested is in Great Neck, New York. So now you know.

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Hehe, a last psychiatrist b... (Below threshold)

December 19, 2012 8:04 AM | Posted by Ben: | Reply

Hehe, a last psychiatrist believing symptomatic conspiracy theories.

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if Pharma can now say whate... (Below threshold)

January 6, 2013 3:07 PM | Posted by harpy: | Reply

if Pharma can now say whatever it likes about its drugs, why have FDA approval at all? I, for one, welcome our new snake oil overlords.

Vote up Vote down Report this comment Score: 0 (2 votes cast)
We should really just try h... (Below threshold)

January 7, 2013 1:29 AM | Posted by Anonymous: | Reply

We should really just try having no government regulation of drugs or medicine. I'm sure we can trust the medical profession to act ethically.

Vote up Vote down Report this comment Score: 1 (1 votes cast)
"Let's agree that peer revi... (Below threshold)

January 7, 2013 10:00 AM | Posted by Anonymous: | Reply

"Let's agree that peer review is the scientific equivalent of Soviet era cronyism"

No, let us not agree anything of the sort. If you were a real scientist, you'd know that.

Vote up Vote down Report this comment Score: 0 (10 votes cast)
"No, let us not agree anyth... (Below threshold)

January 17, 2013 3:34 PM | Posted, in reply to Anonymous's comment, by Anonymous: | Reply

"No, let us not agree anything of the sort. If you were a real scientist, you'd know that."

So, what I'm getting from that is you're not a real scientist (because if you were, you'd understand the truth of the joke), or you are a real scientist who is insecure about the plebs finding out the truth of the joke.

Vote up Vote down Report this comment Score: 2 (6 votes cast)
My wife used to work at NIH... (Below threshold)

January 19, 2013 7:02 PM | Posted, in reply to DensityDuck's comment, by BobNesbo: | Reply

My wife used to work at NIH, and my son has autism. When we were trying to find ways to take care of him, my wife did all the reading. And yes, what Density Duck says here is true. Think of that if you are wondering why they haven't "stumbled" upon a new wonder drug.

Vote up Vote down Report this comment Score: 3 (3 votes cast)
"Let's agree that peer revi... (Below threshold)

January 22, 2013 2:51 PM | Posted by rna: | Reply

"Let's agree that peer review is the scientific equivalent of Soviet era cronyism"

I am a published academic scientist. I really enjoy the wisdom in this blog. However, I think the above statement is not generally correct at all.

Peer review has not specifically kept any paper I know about out of the literature. I'm not saying there has never been a paper kept out of the literature (or a scientist's findings silenced) for political reasons, I'm saying that is pretty rare, and does not generally operate through peer review. I have had experience with unfair reviewers, arrogant reviewers, uninformed reviewers - in fact all manner of unpleasant reviewers. I have even personally have authored a paper or two that some senior scientist made an effort to discredit. In that case the other reviewers were convinced by my responses, and after a few clarifying rewrites, the editor gave my papers the go ahead for publication.

Peer review is an invaluable tool. It usually works as it is meant to - other, anonymous scientists review your work and make comments or suggestions that usually improve your paper. Sometimes, their suggestions will make more work for you, the author. But their comments invite open discourse, and the resulting debate improves and strengthens the quality of the paper.

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yeah, we know what peer rev... (Below threshold)

February 25, 2013 3:14 AM | Posted by Anonymous: | Reply

yeah, we know what peer review is man
i think the cronyism comment speaks to the insular nature of the academic communities which encourages a certain reciprocity that is less than honest

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thanks for such a wonderful... (Below threshold)

April 10, 2013 2:23 PM | Posted by podiatry instruments suppliers: | Reply

thanks for such a wonderful detail on Pharma Pendulum Swings Back The Other Way. keep it good work

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Re-visit your site wonderfu... (Below threshold)

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Very powerful post, thank y... (Below threshold)

May 1, 2013 10:28 AM | Posted by Melany Dalton: | Reply

Very powerful post, thank you for sharing this. It made me very sad though. I hope that needful changes will be done soon in the medical industry.

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"Peer Evil – the rotten bus... (Below threshold)

June 25, 2013 6:35 PM | Posted, in reply to Anonymous's comment, by Anonymous: | Reply

"Peer Evil – the rotten business model of modern science
Posted on June 25, 2013 by Guest Blogger

Guest essay by Abzats.

The most exciting period in science was, arguably, 1895-1945. It was marked by discoveries that changed the foundations of modern science: X-rays, quantum mechanics, superconductivity, relativity theory and nuclear energy. Then, compare this with the next 50 years in science. Incomparable. Nothing of that scale or impact. Yes, technology has advanced, but fundamental science – has come to a crawl. Have you ever wondered why? What changed as the 20th century grew older? Among other things, research budgets and the number of PhDs increased exponentially. This cannot be bad.

..."

http://wattsupwiththat.com/2013/06/25/peer-evil-the-rotten-business-model-of-modern-science/

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I worry that we are failing... (Below threshold)

June 26, 2013 1:59 PM | Posted by essay writing: | Reply

I worry that we are failing to include actual clinicians...clinicians cannot afford to take the time to participate because they earn their money treating patients. Also, clinicians' their med mal carriers likely would warn them that they are at higher risk of being sued over errors and ommissions if they participate as an expert panelist and work to fix our broken system.

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Let us not swing back to th... (Below threshold)

June 26, 2013 2:01 PM | Posted by Robert Hill: | Reply

Let us not swing back to the deregulation of the Reagan era and its dangerous consequences. Let us also remember how corporate America is buying today's elections. And giving the FDA more power to grant waivers is ludicrous. As it is the FDA, whose decision makers on new drugs are on Big Pharma's payroll, is heavily influenced by corporate America. This site helps me in my essay writing process.

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October 11, 2013 5:39 AM | Posted by PPLIC: | Reply

Nice article. very interesting, thanks for sharing.

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