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Derek Lowe The 2002 Model

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Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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March 5, 2009

More on Wyeth v. Levine and Preemption

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Posted by Derek

For those who want it, I have more thoughts on the Wyeth v. Levine pre-emption decision over at The Atlantic's business site. Reading the decision, it looks less like a loss for the drug companies than a loss for the FDA, but see what you think.

Comments (9) + TrackBacks (0) | Category: Regulatory Affairs


1. Hap on March 5, 2009 4:42 PM writes...

I could be out in left field (again) here, but I wonder how you found the Alito/Scalia/Roberts dissent. I didn't think it was very intellectually honest, myself - I thought that their implication of Congressional preemption intent based on the complexity of product labeling regulations (in the lack of an actual direct statement) was particularly questionable, and that they seemed to overly rely on a single case to make their argument. Their logic didn't seem to make much sense to me, other than as a means to justify their desired policies, which would seem to be the operational definition for activist judging. (It's also possible I missed something large, which would negate the implication of the second clause). The list of IV pushed drugs at the end, though, was more interesting - I wonder if Wyeth could have done better (or had already tried) to use the argument that their labeling was already good enough rather than relying on preemption as their main weapon, based on the labeling for other, more toxic drugs (or does Phenergan have a very specific IV push toxicity that the listed drugs do not?).

Tort law is a crappy way to make drug regulations, but in its presence it provides (along with state law) the possibility of self-correction to government regulation, while an FDA with preemption seems to provide very little such possibility.

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2. CMC Guy on March 6, 2009 11:50 AM writes...

The logic of the majority who upheld the liability of Wyeth is what escapes me. I know from experience that legal and regulatory logic are not the same as science logic I am used to (all of which many be oxymoronic) but if you read details of the case there is a disconnect in the outcome (don't have links handy assume can get US and/or Vermont Supreme Court Briefs on-line). The Packaging Insert (i.e. Label) did contain a number of statements warning about injection into arteries and even believe had cautions with bolus admin. The potential consequences (gangrene) were even listed. The nuance was that there was not a specific "Counter Indication" for a particular method of delivery that indeed would have been a louder and clearer message. So the argument was the level/strength of the warnings and then (by Wyeth's legal strategy) who controls that info (Company or FDA). [I don't diminish the tragic results but to shift the blame to drugmaker form a mistake by a PA (I forget how much PA/Hospital settled case for but relatively a lot less I think) is not logical, except a deep pockets reach through and emotional need to punish].

Analogy I offer for level of warning is like a road that ends at a cliff. There are signs to slow down and signs for a dead-end but (bad) drivers still go over the cliff. Must a 20 foot Billboard (flashing as to a srp post) be erected to solve the problem? (Unfortunately in the US legal system the answer is probable yes, as "Do not dry your Cat in the Microwave" labels).

As to who ultimately controls the Drug's Label again my experience suggests that the FDA is mostly in the Drivers seat. Companies do try to intentionally navigate to roads for favored scenery but do not decide in the end what route taken. After an arduous journey attempting to go on another trip has high activation energy and if Company tries to go by themselves they are likely to get in very hot water so process if bogged down. That does not necessary favor preemption, and may be against it since relies on FDA competency and responsiveness (which are questionable IMO). That is the context in which Pharma works and to ignore how it influences the details, as seems to have won out in this case, seems to stretch beyond practical aspects.

Hap is correct (for a change :)) when he says that Tort law is crappy mechanism but the balance/low bar leans more so now encouraging lawsuit mania that impact will be felt in R&D with accelerated push for reductions or offshoring of jobs.

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3. Hap on March 6, 2009 1:42 PM writes...

Outsourcing won't make it harder to sue but probably easier - when the jobs you might remove are yours (and the resultant tax receipts), you might be more careful in adding costs to businesses, while if they aren't, then you probably won't be as careful. As long as drug companies rely on the US for their sales and profits, whoever determines liabilities and safety here is likely to call the shots. If you can't get any money out of foreign companies, you can surely cost them some (by refusing to allow the offending products to be sold).

I thought Thomas's concurrence was actually OK, though I don't know (either about law or the consequences of my own preferences) whether I think that only the text of the law should be the only source for determination of Congressional intent. It did argue for a consistent approach to preemption which the dissent probably didn't (and which it could be questioned whether the majority did). I haven't heard much good from him (and the one other case I remember reading didn't help), but this opinion seemed good.

The only hole I thought to the majority opinion was in how the warning could have been made stronger without banning IV push altogether - while there was the theoretical possibility of doing so, what could they have done to make that less likely? Unless they advised strongly against injections in the elbow, or had a needle with an artery detector, I don't know what they should have done. There wasn't a suggestion of what a possible warning should have been, and if Wyeth couldn't make the warning more severe (to comply with VT) without banning IV push, could it trigger preemption? (Can VT ban a method of administration?)

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4. Hoping for a Job on March 6, 2009 7:08 PM writes...

to use the argument that their labeling was already good enough rather than relying on preemption as their main weapon,

This is my main question. It doesn't seem like you need pre-emption to overturn this decision. The warning label said "Avoid doing X, because it can lead to Y". How can you sue the drug company when Y happens when you've been warned that it's a distinct possibility.

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5. lugan11 on March 9, 2009 8:57 AM writes...

This really is about doing the IV push incorrectly. Physicians and nurses all know that missing the vein and inadvertently injecting just about anything into the adjacent artery will cause vasoconstriction and necrosis (even NaCl will do this). Had the package insert been written as advised, it likely would have not resulted in a different outcome.

I feel sorry for the plaintiff, that is a terrible thing to happen to her. But IMHO, Wyeth was dragged into this because it has deep pockets. That is the way the tort system in the US works. If her armed had been mauled by a pit bull owned by an irresponsible person without any assets, trial lawyers wouldn't have given her the time of day.

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6. Hap on March 9, 2009 10:06 AM writes...

Why do IV push at all, or at minimum, why there? Assuming there's a medical need to do it, is there another good place other than the elbow, because the elbow is presumbably a crowded place to do it (and why said problems occur).

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7. lugan11 on March 9, 2009 2:05 PM writes...

In many instances of severe nausea/vomiting (as from migraines, as I read the victim was suffering from), oral antiemetics are just thrown back up, and IV is often chosen to administer drugs. I believe that she had gotten IV phenergan before this incident as well.

The antecubital fossa (inner elbow) is used extensively for blood draws and IV line placement because of the (unique) proximity to the skin surface of a rather large vein (cephalic vein). Other access points are riskier. Usually it's not difficult to locate correctly, but can be in certain individuals. I gather in this case, for whatever reason, the rare event occurred, and they hit the radial artery instead.

After this incident, manufacturers may stop supplying phenergan for IV altogether, which had benefitted many persons with intractable nausea from chemotherapy, etc.

As an aside, there is some very nice commercial technology now for visualizing veins for more accurate venipuncture (

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8. Hap on March 9, 2009 2:43 PM writes...

Why use IV push over drip? IV drip was supposed to have been recommended because it was harder to mess up this way, so I assume there is a reason (speed of effect?) to deliver by push over drip. I thought in the decision, they cited material that claimed it was fairly easy to mess up IV push if given in the elbow, while much harder to mess up IV drip.

I assume Wyeth could still sell Phenergan for IV, but require drip rather than push perhaps.

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9. CMC Guy on March 9, 2009 3:11 PM writes...

lugan11 thanks for the perspectives. Clinical people I know have suggested that giving anything by IV push has much greater risk and typically not used commonly except in ER situation (outside of Image Contrast agents and a few other drugs that require quick delivery). This drug may be worse (than average?) if it gets in the arteries however apparently some doctors comments I have seen indicates phenergan can/has be administered by IV push with proper technique and monitoring. (Stats seen is 20 cases of AE likes Levine in 200M uses, caveat that majority likely by IV drip). Again my experience in labeling negotiations suggests drug manufacturer provides extensive core info unless a true high level warning known but leave room for medical judgments/practices to the MD present with the patient.

I agree this may mean pulling some products off the market rather than deal with risk. Likely will directly increase convoluted/complicated labels than exists (and some argue can not have TMI (Too Much Info) which is BS as the more CYA info Legal adds the Benefits/Risks get lost). Not to insult everyone but most MDs/RNs do not really know how to read labels well (since training weaknesses) and its usually the Pharmacist who have the best handle on a drugs use/cautions. Finally as noted above another result will probably be fewer jobs in R&D as companies try to further offset the legal cost (real or projected) by cutting staff or using cheaper labor elsewhere (Neither option positive for innovation we need).

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