November 11, 2008

The Supreme Court Hears Arguments That Warning Labels Should Include Things Done Correctly

A handy rule of thumb, good for reading published clinical trials and court cases is this: if you can't understand the basics in fifteen seconds, you are being lied to.


Diana Levine had a migraine, and at the doctor's office a physician's assistant gave her a Phenergen injection, IV push.  Unfortunately, it resulted in gangrene, and the arm had to be amputated.

Inexplicably-- and I'll explain "inexplicably" in a moment-- she chose to sue Wyeth for an inadequate warning label, specifically that it should prohibit IV push because it could lead to gangrene.  As it stood, the FDA warning label only warned against IV push and gangrene.

Wyeth's response was: um, why would we prohibit the use of something that is approved by the FDA for that use?   The FDA knew the risks of gangrene and IV push, and approved IV push, with the warning of gangrene.

She won the case and $6.7M.  (Why? Vermont.)  It was upheld in appeal: FDA standards are a minimum, and if the company sees reason to have a stronger label, they do not need new FDA approval to put one on.  Wyeth should have known IV push was dangerous, and prohibited it even though the FDA approved it.

It is now being argued before the Supreme Court.  The legal question is whether federal regulations preempt state requirements; i.e., if it's good enough for the Feds, should it be good enough for the states?   This is already true for medical devices. If it is, then Levine should never have been allowed to sue in state court in the first place.

So far, the Justices have bantered about whether FDA review is adequate, or if it could ever be adequate enough with such a major side effect as gangrene.  Scalia observed that if the doctors at the FDA made a risk benefit analysis for IV push, a jury of laymen shouldn't be in a position to second guess it.

Justice Souter disagreed: "Wyeth could have gone back to the FDA at any time and said, either based on experience or just our rethinking of the data that we have, we think the label ought to be changed to say, 'Don't use IV push.'" Of course, that implies Wyeth thought that IV push was actually dangerous, which it didn't.

I am not a Supreme Court Justice yet, and it's likely President Obama will not choose me; but while everyone is arguing the relative dangers of IV push, a simple and important fact is being ignored: the drug went in an artery.


Clearly, what happened here is that the PA made two mistakes: wrong injection; wrong administration.  Why didn't she simply inject it into the muscle like everyone else on the planet does?

It's not wrong to do IV push, it happens in hospitals when an IV is already in place, but why bother to do it in an office?  Let me be as clear as possible:  the gangrene wasn't a result of IV push, this is not the rare case of IV push induced gangrene-- the med was not administered IV push.  This is a case of medical malpractice.   The PA messed up.  Exactly how is that Wyeth's fault?  Oh, I know: it's their fault because they're rich and we're in Vermont.  Got it.


So now the discussion about warning labels actually has a deeper meaning.

When the various people argue about the "risks of IV push," they are including in that risk the risk of not doing IV push.  In other words, the manufacturer is asked to be responsible for the incompetence of the clinician.  Here's an example: many meds are clearly labeled "Do Not Crush."  Crushing it, for example, could release all of the chemical into your body too fast.  Following Levine's logic, this drug should not only carry a warning label "Do Not Crush," but the drug company should say it shouldn't be used orally at all, because someone might  crush it.

Amazingly, in regular news articles I have not seen this argument anywhere.  All reporting and discussion never even asks whether this is the PA's fault, and not Wyeth's.  I do, however, see that every single article talks about how she is a guitarist.  Is that relevant?   Actually, it is: it makes a good enough story to get 9 people to award her $6.7 million.


Leave it to the crypto-socialists at the New England Journal to recast med mal into a call to arms against corporate America.

Dr. Drazen, editor-in-chief of the NEJM, wants the court to side with Levine.  He says he needs state level product liability suits, for two reasons. 

1. Drazen writes in "Why Doctors Should Worry about Preemption" that product liability litigation is important as information:

Through the process of legal discovery, litigation may also uncover information about drug toxicity that would otherwise not be known. Preemption will thus result in drugs and devices that are less safe and will thereby undermine a national effort to improve patient safety.

It is beyond human capacity to comprehend how an editor-in-chief of the NEJM can argue that he needs lawsuits to get information about a drug.  Does he expect lawyers to gather the required information, and laymen jurors to properly evaluate it, and then off to his desk for approval?  Drazen isn't satisfied with 50 years of Phenergan use, research, and data.  He needs to check with lawyers. I'll add that it simply isn't true that litigation has provided medicine with new information.

Drazen has the audiacity to cite Vioxx as an example of a drug that got FDA approval when the risks were not known, that resulted in litigation. Never mind that doctors continued to prescribe it even after the risks were known.  Never mind that the NEJM, with its crack squad of peer reviewers, is the journal that let the flawed Vioxx study that minimized the risks get published in its pages.


Preemption will undermine the confidence that doctors and patients have in the safety of drugs and devices.
How confident do you want doctors to be?  So confident that they don't have to worry about the difference between a vein and an artery?  Not surprisingly, Drazen nowhere mentions "artery" or any negligence on the part of the PA; he doesn't even mention the name of the drug.  Becuase to mention any of these real things would ruin his sophistry. 

It's hard to be simultaneosly hypocritical and ignorant-- hypocrisy requires at least some awareness of reality-- but Drazen pulls it off.   In pretending to be for the "consumer" by worrying that:

In stripping patients of their right to seek redress through due process of law, preemption of common-law tort actions is not only unjust but will also result in the reduced safety of drugs and medical devices for the American people.
He hides the fact that the real risk to patients-- to Levine-- isn't bad or unsafe drugs (that are 50 years old), but egregious mistakes by clinicians.  Not to mention preposterously biased and uninformative medical journals.

I suspect the Supreme Court does not read this blog, but if you see them at lunch please pass this along: find for Wyeth.  This case is not really about preemption, and they should make that clear.  Otherwise this case will become a dinner table anecdote for Big Business, not to mention conservatives, to seethe over, so that the moment they get power back-- think Newt Gingrich in 1994-- they unleash a backlash of tort reform so dizzyingly vicious you'll beg for Pherengan IV.


Hey Alone,This is ... (Below threshold)

November 11, 2008 12:22 PM | Posted by Jeffrey Lacasse: | Reply

Hey Alone,

This is a very interesting post and I have not seen this point of view in the mainstream media either.

Would you agree, though, that the process of legal discovery has uncovered useful information on antidepressants and atypical antipsychotics? Or, related information, such as the documentation of ghostwriting (CMD communications report that) David Healy found it Motus v. Pfizer?

This may not be a valid argument regarding this preemption decision, but it seems to me there are some facts regarding SSRIs and antipsychotics that came out because of legal processes (including, for instance, exactly *when* pharmaceutical companies knew that SSRIs could cause agitation, for instance).

What do you think?

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The NEJM used to be [way lo... (Below threshold)

November 11, 2008 7:25 PM | Posted by Jack Coupal: | Reply

The NEJM used to be [way long ago] considered The Bible of American medicine.

It looks like Dr. Drazen is carrying on the bizarre editorial stance from the eminent Dr. Marcia Angell, who was hell-bent on driving NEJM into the ground credibility-wise while she was editor.

The current mantra at the Journal is that corporate is automatically bad, and that the helpless public (including physician assistants) needs only governmental help to protect it.

Must be a New England thing. The Boston Tea Party could never happen today.

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I agree that the argument t... (Below threshold)

November 12, 2008 4:35 AM | Posted by Anonymous Hero: | Reply

I agree that the argument that academic medicine needs discovery to accurately assess the health implications of drugs is ludicrous.

Discovery will almost always be useless for this as there are strict conditions attached to the use of documents that are discovered and usually they cannot be used for any purpose not associated with the litigation for which they were discovered.

Just consider the extraordinary lengths that people went to to provide access to the Zyprexa documents and if not for the NYT and the incredibly censorship resistent internet they would never have seen the light of day.

You are probably right that Levine's claim lies not against Wyeth but against her doctor but patients in general are loath to sue their personal doctors, it's much easier (emotionally anyway) to sue a large faceless corporation.

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Minor correction on the Lev... (Below threshold)

November 12, 2008 11:11 AM | Posted by marcia: | Reply

Minor correction on the Levine malpractice case. The phenergan was actually accidentally administered IA (intra-arterially) because the nurse didn't establish an IV line, but only inserted a butterfly, which ended up in an artery, rather than a vein.

A malpractice case arose from this against the health care provider and hospital, and was settled in Levine's favor.

Wyeth v. Levine became a product liability case because Levine's attorney argued the package insert should specifically state that, when administering phenergan intravenously, an IV should be established first, and that such action would have prevented the patient's gangrene and amputation.

The package already discourages administration via IV push, but does not prohibit it. Gangrene is a known and documented side-effect resulting from injection. Apparently the actual incidence of this occurrence is rare.

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Ah, sorry. I see that you s... (Below threshold)

November 12, 2008 11:16 AM | Posted by marcia: | Reply

Ah, sorry. I see that you stated the medication went in an artery. Don't know how I missed that on the first read.

What is being argued before the Supreme Court is the issue of preemption, which the FDA has been pushing, and which means that citizens can't sue a drug company in state courts if a drug has been approved by the FDA, since the federal government "preempts" state law.

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It's hard to argue with you... (Below threshold)

November 12, 2008 1:50 PM | Posted by billy: | Reply

It's hard to argue with your analysis of the details of the case, but you have to remember that the supreme court doesn't give a shit about this lady or her arm. Point blank. Nobody is talking about the guitar playing lady but the newspapers. What is in question here is preemption, nothing more and nothing less. It's a question about the interpretation of the law. Wyeth already blew the part of the trial where they could (and should) pass the buck to the doctor.

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This is what Drazen was ... (Below threshold)

November 12, 2008 10:04 PM | Posted, in reply to Jeffrey Lacasse's comment, by Alone: | Reply

This is what Drazen was trying to say about the Vioxx situation. But in every case I can think of, lawyers only bring to the public consciousness the risks of a med. By the time lawyers are seriously involved, the risks are already heavily discussed by docs. So Yahoo! News had an article on Vioxx in 1999; diabetes started gaining traction post QTC, around 2000-1. Etc.

It certainly is true that cases often expose Pharma for their hdiding data, etc. However, again, even when they are caught hiding the data, doctors already knew about the hidden data. Vioxx is a case in point: NEJM published the study that hid the extra heart attacks (and one stroke on the placebo side.) But the peer reviewers or the editor should have asked for all of the data. That's what they're there for, right? "But peer reviewers aren't supposed to review the data." Why not?

responding to the above two about preemption. Yes, I realize that by the SC stage, the Wyeth/Levine question is largely irrelevant, all they care about is preemption. But they really should never have heard the case (unfortunately for Wyeth) because it's just a bad sounding story, and if preemption stays or goes because of this case, people will be mad on both sides.

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Clinicians wrongly performe... (Below threshold)

November 14, 2008 9:19 AM | Posted by MedsVsTherapy: | Reply

Clinicians wrongly performed the intervention. They knew better. Get what money you can from them. Case closed.

Does a label have to declare each possible way you could wrongly administer some treatment? That would be quite a long label.

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Hi. I'm a pharmacist. In ... (Below threshold)

December 8, 2008 3:34 AM | Posted by Anonymous: | Reply

Hi. I'm a pharmacist. In a hospital. From what I have read here and elsewhere, Phenergan was never given to this patient via IV push. It was given IA. Small difference... humongous implications. Like the loss of a limb. A Supreme Court case. A bad day at the clinic to say the least. Was this physician's assistant new? Why were they not giving the med IM? OK, so you want to give it IV, fine. Why use a butterfly and not a syringe and needle? Was there no tell-tale blood flow from the artery into the syringe?
You can inject promethazine into a lot of different places in the human body, that doesn't mean it is supposed to be done. And certainly doesn't make it the manufacturer's fault.

PS. I'm surprised they were using brand name Phenergan. Generic promethazine is widely available and cheaper. Maybe Wyeth sould just pull the drug from the market. This is the only way they can ensure that it is not used improperly.

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Dr. Drazen may see his argu... (Below threshold)

December 16, 2008 5:48 PM | Posted by AnnJo: | Reply

Dr. Drazen may see his argument against preemption as an anti-corporate stance, but it is the opposite. Only truly giant corporations can dream of surviving in 51+ different regulatory environments. Smaller businesses will necessarily have to throw in the towel and merge into whatever giant gives their products the best protection in the "gotcha!" culture Drazen envisions.

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They shouldn't have heard t... (Below threshold)

March 22, 2009 9:25 AM | Posted, in reply to Alone's comment, by acute_mania: | Reply

They shouldn't have heard the case simply because if they felt that federal regulations shouldn't preempt state regulations, then the federal court has no business reconsidering the verdict of the state court.

Regarding Anonymous' comment, does liabilty for injury caused by a drug rest solely with its manufacturer and not its patent-holder? Does my estate sue Johnson & Johnson or do they sue If I die from a generic preparation of haloperidol? Who is resposible for the package insert, because I notice that the PIs for generics tend to be worded identically to they're branded counterparts, so in that case, are they treated like the work of the patent-holder?

I can see why pharma companies discontinue drugs after they become generic, particularly potentially unsafe ones. It's a huge liability for a product they're not earning any income from.

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Great article and ... (Below threshold)

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