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Wyeth vs. Levine: Should Drug Label Standards Be Determined By Juries?

It is with some degree of trepidation that I enter the fray on the Wyeth vs. Levine case. I’ve been watching the media frenzy about the lawsuit with interest – mostly because (for the first time in a while) I think that the pharmaceutical company is in the right on this one – and that most journalists (and even medical journal editors) have missed the salient points.

I think that a close review of the case is instructive in two ways. It shows: 1) the dangers of making legal decisions based on the perspective of the victim (a risk of harm equal to 1 in 20 million is unacceptable to that one person who suffered the consequence, but tolerable to the other 19,999,999 others) and 2) that a simple case of medical malpractice has made it all the way to the US Supreme Court because (as I discussed in my last post) a democratization of knowledge (juries reading a drug label) was believed to democratize expertise (how a physician would understand the label).

Background

My research for this blog post included the following: a review of the 66 page transcript of the opening arguments presented at the US Supreme court on November 3rd, careful consideration of an editorial written by Catherine DeAngelis in JAMA, an opinion piece published in NEJM, and several perspectives from bloggers whom I admire (including Maggie Mahar and the Wall Street Journal), and a 1:1 phone interview with Wyeth’s attorney Bert Rein. While it’s true that I did not have the opportunity to personally interview the opposing counsel (for Ms. Levine), I did review his arguments via the Supreme Court transcript. I am not an attorney, and have done my best to understand the facts in this case. Feel free to correct me if you believe I am in error.

First, let me say that it’s very easy to become emotionally involved in this case and let that color one’s view of the facts. A musician lost her arm in a tragic manner – a physician assistant accidentally administered phenergan into (or around) her artery, rather than vein, as part of a narcotic and anti-emetic treatment for a migraine headache. The result was localized tissue necrosis, gangrene and eventual amputation of her arm. I have the utmost sympathy for Ms. Levine and I’m sincerely sorry that this happened to her. However, it is estimated that phenergan has been successfully administered (without incident) over 200 million times in the US. Ms. Levine had a one in a 20 million chance of a gangrenous adverse reaction, and those are really low odds.

However, Ms. Levine is arguing that Wyeth should have included stronger warning labeling language in the phenergan box – because the drug company should have known that providers could mistakenly inject the drug into an artery, and that they should have forbidden the drug from being injected via IV push (into veins) to completely protect against this potential error. She argues that the risk of administering phenergan via IV push outweigh the benefits to the point where IV push administration should be contraindicated by the manufacturer.

Furthermore, the state of Vermont has ruled that a jury can hold the drug company liable for damages because it failed to adequately warn physicians about the dangers of phenergan, even though the label was approved by the FDA in full knowledge of the risks.

The US Supreme Court

In the opening arguments made before the Supreme Court, Ms. Levine’s counsel argued that 1) the FDA did not specifically consider the potential risks of an IV push versus IV drip administration of the drug – he argued that it didn’t happen because they could find no correspondence specifically mentioning this analysis. 2) Wyeth should have strengthened the warnings on the label without obtaining the FDA’s input – because that is the company’s “duty of due care.” 3) Wyeth’s attempts to strengthen the drug label warning (which were rejected by the FDA because there was no new information to require a change in the label) were not substantive or sufficient. 4) Because Pfizer’s anti-nausea drug (vistrol) had caused gangrene when injected into arteries, which resulted in Pfizer’s contraindication of IV push administration, Wyeth should have lobbied for a similar label change.

Justice Scalia responded that if Ms. Levine felt that the FDA acted irresponsibly, she should consider suing the FDA rather than Wyeth. Justices Breyer and Alito clarified that the FDA required new information to justify changing the warning on a label, and that Ms. Levine’s case of gangrene did not represent a change in the average frequency of this adverse event. Scalia also argued that overturning the FDA’s decision on adequate labeling (in the absence of new information) would be a slippery slope.

The preemption law (the argument that federal law supersedes state law) applies to cases where no new information is available. In other words, if new information becomes available (either a previously unrecognized harm or a harm undisclosed by the drug company), patients have the right to sue the drug company (at the state level) for damages. If there is no new information, then the federal law stands (a point made by Scalia, but not clearly acknowledged by the recent NEJM article on the subject). Scalia argued that removing preemption (in cases of known harms) would result in drug companies listing all possible damages (in an attempt to protect themselves from lawsuits) and put an undue burden on the FDA to investigate and weigh all of them. The result would be extreme risk aversion and reduced choice for consumers.

The Media Gets It Wrong

Some members of the media have erroneously compared Wyeth vs. Levine to the Vioxx case. Wyeth vs. Levine is not the same because the Vioxx case involved a drug company withholding knowledge of potential risks from the FDA. Patients sued Merck for undisclosed risks that harmed them. But Wyeth didn’t fail to disclose harms or risks in this case. Nonetheless, Catherine DeAngelis incorrectly argued that if Wyeth wins this case, patients will be preempted from suing for drug-related injuries in the future. The truth is that the oral arguments presented to the Supreme Court specifically outline that this case would not, in fact, influence a patient’s right to seek damages from drug companies in the case of undisclosed or newly discovered harms. The issue is whether or not a local jury has the right to reinterpret drug labels and overturn FDA rulings on adequate warnings in the face of full disclosure by drug companies and without new information about harms.

Litigation Frenzy And Deep Pockets

In my view, the Wyeth vs. Levine case is a malpractice suit gone wild. The risks of the drug were fully known, the drug’s label made it very clear that phenergan was not to come in contact with arterial blood (through injection or extravasation) or else severe tissue damage could occur (feel free to read the drug label in its entirety here). The FDA approved the drug label’s description of the known risk, and a physician assistant accidentally injected the drug into Ms. Levine’s arm with tragic consequences.

Ms. Levine settled the malpractice case out of court for $700,000. She then sought damages from Wyeth in the Vermont Supreme Court, and the jury ruled in her favor – arguing that juries should be able to hold drug companies to different labeling standards as they see fit. Ms. Levine was awarded $7 million. Wyeth appealed the case to the US Supreme Court. The final ruling will likely be decided in several months’ time.

Who Should Perform Risk Benefit Analyses: Drug Companies Or Physicians And Patients?

No drug is without risk. Every time we receive a therapy, we must engage in a risk benefit analysis with our healthcare professionals, and choose to accept the known risks in favor of the known benefits. Ms. Levine had a 1 in 20 million chance of tissue necrosis. She and her doctor (assuming that her doctor reviewed the risks and benefits with her as he should have) believed that the rapid migraine pain relief was worth that risk. Due to a PA’s error, Ms. Levine suffered an extremely rare consequence. As a result, Ms. Levine is now arguing that a drug company should be required to make the risk benefit analysis for patients and physicians, thus limiting their individual choices.

Some sources argue that states should be able to hold pharmaceutical companies to their own standards because the FDA cannot possibly catch and categorize all the possible risks of a drug when it first comes to market. That’s an interesting argument – but irrelevant in Wyeth vs. Levine because it is NOT a case of a risk missed by the FDA. The phenergan toxicity was a known risk – no new information about risk was raised by this case.

The Final Analysis

So it boils down to this: should we allow juries to set drug labeling rules at will, or should we rely on a federal agency with clear scientific expertise to manage it? Of course the FDA is not perfect and it has its limitations (post market surveillance of each of the 10,000 FDA-approved drugs is a challenge with finite staffing – which is precisely why pharmaceutical companies should be incentivized, not penalized, to bring forward new risk information when it becomes available). But if I had to choose between a group of non-professionals trying to figure out what’s appropriate for a drug label (and awarding unlimited millions to anyone who experiences an adverse outcome), versus a team of scientists who have been provided with all the facts to make a judgment… I think I’m going with option B.

If Wyeth loses this case there could be an increase in lawsuits which would trigger pharmaceutical risk aversion, decreased patient access to medications, and give inappropriate decision-making power to untrained juries. It is the beginning of a slippery slope that would potentially condone legal action against pharmaceutical companies for any known drug side effect.

The risk of taking a medication is never zero. Avoid taking them if you can, understand your risks if you do, and feel free to sue pharmaceutical companies if they are intentionally deceptive or withhold information about your safety. I do not see compelling evidence of either in the Wyeth vs. Levine case. Do you?

Posted in: Pharmaceuticals, Politics and Regulation, Public Health

Leave a Comment (20) ↓

20 thoughts on “Wyeth vs. Levine: Should Drug Label Standards Be Determined By Juries?

  1. A 1-in-20-million risk is too small to worry about. It’s tragic, but I bet the risk of her losing her arm or her life in a car accident last year was greater than the risk posed by this drug.

    It certainly doesn’t sound like the drug company is at fault.

  2. zstuff says:

    Working in the non-profit healthcare space, I see time and time again, states acting to protect the interest of its residents (as they should) by legislating state-specific requirements. These lawmakers however, are myopic and almost never consider the entire landscape (i.e, the national perspective).

    In the case of Wyeth v. Levine does the Vermont jury realize it may be paving the way to 50 different SDA’s (State Drug Administrations)? Do they realize what that would cost their state at a time when states are trying to create efficiencies and reduce the cost of healthcare? Does the Vermont jury realize the potential boondoggle of state-specific regulations that its decision may create for the drug companies to have to navigate?

    I am truly sorry that Ms. Levine lost her arm to a known and labeled adverse drug reaction, but this is clearly a cut and dry case of provider error and nothing else. I know it can’t be easy for a doctor to side with a pharmaceutical company in the shadow of the Vioxx case, so you have my admiration.

  3. qetzal says:

    Thanks for providing such a fulsome analysis of this important case. There is also some interesting discussion in a couple of threads over at Pharmalot. See http://www.pharmalot.com/2008/11/preemption-play-by-play-from-the-court/ and http://www.pharmalot.com/2008/11/read-the-supreme-court-preemption-transcript-here/ – especially the very thoughtful comments by Justice in MI.

  4. overshoot says:

    Chris Hoofnagle over at Denialism recently posted on the evils (or potential evils) of Federal regulatory preemption. He didn’t specifically address Wyeth but I do rather wish you and he could jointly address it from your respective positions.

  5. daedalus2u says:

    In looking at the drug label, it seems to me that it discloses multiple times the risk of side effects leading to amputation. It mentions gangrene 6 times and amputation 3 times.

    It says to not administer it at a rate greater than 25 mg/minute. It would seem that the PA was already violating the directions giving in the drug label, and that giving it by IV push (at a rate greater than 25 mg/minute) already does violate the drug label directions.

    A “drug label” is meant as a communication to the professional with the right to prescribe and administer drugs. It isn’t meant as a communication to members of the lay public without the background and training to understand what it means.

    In order to decide that a label is inadequate the jury needs to have the background to understand such labels and in the settings that they are used in. The “jury of peers” should be limited to medical professionals.

  6. MedsVsTherapy says:

    “In looking at the drug label, it seems to me that it discloses multiple times the risk of side effects leading to amputation. It mentions gangrene 6 times and amputation 3 times.”

    -Daedelus- do you happen to know if the label was changed following the injury and court case?

  7. Mark Sadaka says:

    I would like to say that your article is very well written. With that being said, you rely on two false facts in building your argument. First, is that the FDA maintains some scientific prowess that makes it omniscient. Second, that lawsuits will increase as a result of this litigation.

    The FDA does have experienced staff but it is not equipped to deal with duplicitous behavior of some pharmaceutical companies. The system works only when both sides are honest with each other. In most circumstances, pharmaceutical companies are forthright with the results of clinical trials and open those results to peer review. Litigation stems from those times that a pharmaceutical company does not do this. For example, Merck hid information about Vioxx from the editors of the New England Journal of Medicine. Once word got out as the result of the trials, the NEJM lambasted Merck for their duplicitous behavior. The key here is that the information would never have come to light if not for litigation. In another litigation that I was involved in, the company submitted bad results to the FDA but placed it at the bottom of the pile and did not mention the results in the executive summary. Suffice it to say, the experts in the FDA did not see this “bad data” until 3 and a half years later. I have 100s of these stories that I just can’t share with you because of confidentiality provisions. Again, the injuries that resulted from this duplicitious behavior cost people their lives and it would never have come to light if it wasn’t for greedy trial lawyers and their clients.

    Second, there are many drug related lawsuits out there. A ruling against preemption would not spur anymore litigation then would have come about naturally. People are mistaken when they think that a ruling in favor of the plaintiff will lead to more lawsuits. That is just not true. A ruling in favor of the plaintiff will just allow drug related lawsuits to continue. It does NOT open a new avenue of litigation.

    Visit my website at pharmawatchdog.com for more information.

  8. Val Jones says:

    Mark Sadaka,

    Thanks for the compliment about my writing. I appreciate the time you took to respond and can certainly sense your passion about keeping pharmaceutical companies honest. That is a very good thing.

    However, I do think that this case is a really poor example of pharmaceutical wrong-doing. The fact of the matter is that Wyeth did indeed make the risk of gangrene very clear on the label, and that the accidental administration of the drug into Ms. Levine’s artery resulted in very sad but predictable consequences. The risks were well documented by the FDA-approved label. The providers are the ones at fault for the error.

    In the Supreme Court hearing, the justices made it clear that patients are permitted to sue drug companies for harms that are not disclosed clearly by the label. In cases where new information becomes available, it is the drug company’s duty to warn the public and alert the FDA. Ms. Levine’s accident was nothing new – just terribly tragic.

    If Ms. Levine wins this case, it establishes a few precedents: 1) that patients can sue drug companies for known risks of the drug – and potentially even unwanted side effects 2) that juries have the right to override FDA decisions about drug label safety warnings, without new evidence of harm.

    It would be cost prohibitive (and a logistical nightmare) for all 50 states to create their own oversight agencies for drug labels. Allowing patients to sue drug companies for known risks of using the drug would essentially require that all drugs be 100% safe – which is impossible. Drug companies would have no incentive to disclose new harms that come to light post-market – since it would only be grounds for a lawsuit.

    If Wyeth wins, patients will still be able to sue drug companies if they experience a new or undisclosed harm. However, drug companies will be encouraged to be forthcoming with potential risks so as to avoid being sued. This will incentivize full transparency and rapid reporting of any new information related to risks of harm or safety matters.

    Ironically, a win for Wyeth is a win for the majority of Americans. It’s only that 1 in 20 million who won’t be pleased.

  9. Mark Sadaka says:

    Val,

    A failure to warn case is what is at issue here. A product can be defective if the warning fails or inadequately warns about the risk of a side-effect. An inadequate warning is the same as failing to warn at all.

    I can sit here and write a list of all the various aliments in the world and place it into a label. What effect is that going to have for the prescribing doctor? Nothing. He or she will ignore it because it is viewed as filler. A proper warning for a serious side effect must draw the doctor’s attention.

    The jury in the Wyeth case did not override the FDA’s decision about warnings. They decided that the warning was not adequate after listening to expert testimony from both sides. The availability of this type of lawsuit is essential. For example, take the Ortho Evra patch litigation. There is a clear warning in the label, like in all low dose birth control labels, that says that there is a risk of DVT and stroke. Was that warning adequate when it was found that the patch released 60% more estrogen into a woman’s body than a typical low dose birth control pill? Estrogen is the component that causes the strokes and the DVTs. Shouldn’t a woman know that the patch releases 60% more estrogen than a typical pill? Shouldn’t a woman know that the patch she is using is releasing the same amount of estrogen as what was found in the pills out in the 1970s? A decision for Wyeth will take this type of lawsuit away.

    Furthermore, it was only recently that the FDA was granted power to change a drug’s label. The label is the property of the pharmaceutical company. What goes into a label is a complex negotiation between the FDA and the pharmaceutical company, usually the marketing department or “medical affairs”.

    The point is that Plaintiff’s have always be able to sue pharmaceutical companies for inadequate warnings and it hasn’t stopped innovation. Are their 50 SDAs? No. This is a case about taking something away, not adding. There is no new avenue of litigation being created here.

    Finally, drug companies are required by law to share their adverse event data with the FDA. The FDA also collects its own data and can see spikes in reporting.

    Most problems that are found in these drug lawsuits comes from a rogue department or group within a department and not the company as a whole. The company itself wants to comply with the law and submit adverse data to the FDA. Preemption will not incentivize a rogue department or group to comply with their obligations.

  10. daedalus2u says:

    Mark, correct me if I have misunderstood your position, but according to your “logic”, if a provider wrongly administers any drug the drug manufacturer is at fault because the label did not provide proper warning. If the label had provided proper warning, the provider mistake would not have happened.

    The scenarios you bring up, of a rogue department or of different levels of drug absorption don’t seem to be evident in this case.

    Maybe Wyeth’s legal team made a mistake in hanging their legal case on preemption vs adequacy of disclosure in this particular case. That is a problem when non-medical experts (the legal teams, the judge, and the jury) make medical decisions outside of their expertise. The problem with non-medical second guessing is that the “correct” medical decision may be the “incorrect” non-medical decision. That makes the only “correct” business decision to abandon that medical practice if it cannot be practiced in a way that precludes legal liability.

    I don’t dispute that there are rogue elements that have done wrong, even criminal acts, such as the Vioxx case. This case doesn’t seem to be one of them. I get the impression that no matter what the label said the jury was going to find it was inadequate because grievous harm occurred. If that is the case, and no amount of labeling or disclosure can protect a manufacturer from provider error, then the cost of drugs is going to go up a lot, and many will become unavailable.

  11. Mark Sadaka says:

    The scenarios I brought up are directly relevant because a decision for Wyeth will effect our ability to sue pharmaceutical companies where their wrongdoing is a little more clear cut. A woman who suffers a stroke because of Ortho Evra may not be able to sue after this decision even though she was exposed to 60% more estrogen then she signed up for. This is not about Wyeth v. Levine this is a much larger issue.

    You have now discovered why Wyeth choose to ride this case up to the Supreme Court. They knew that the issue of an improper administration will confuse and confound observers and garner support for their cause.

    My logic is this

    1. True – not all improperly administered shots cause gangrene.

    2. True – there are some medications that when improperly administered cause gangrene.

    3. True – it is the duty of the manufacturer of a medication that causes gangrene when improperly administered to warn physicians of the potential of such a serious side effect.

    4. True – not all warnings are adequate.

    The jury in Wyeth made NO scientific discoveries. They did not put on lab coats and conducted studies. They simply decided that the warning label was inadequate. It is quite pompous to think that a jury of our peers could not decide, after weighing the issues, whether or not a label was adequate.

    Don’t be distracted by the dancing monkey in the window. Focus on the real issue. They want to take away your right to sue a pharmaceutical company for inadequately warning about a serious side effect. So people like you say “well, in this case, it is not clear….” See the forest instead of the trees.

    Like I said time and time again – this is a type of lawsuit that already exists.

    -We do not have 50 state fdas.
    -Pharmaceutical companies are continuing to innovate.
    -Drug prices have gone up for issue not related to litigation (FYI -insurance premiums have gone up exponentially while costs due to litigation have dropped. The biggest scam out there but that is another issue).

  12. Fifi says:

    daedalus – To say that the pharmaceutical industry has “rogue elements” is a bit like saying the same thing about the tobacco industry! Pharmaceutical companies are for-profit corporate entites, their main concern as corporate entities is making profit. They do this through selling pharmaceuticals – this leads to the development of new pharmaceuticals which is often a good thing, it also leads to all kinds of situations where profit-making trumps basic ethics. This isn’t to say that there can’t be ethical pharmacists, commercial researchers or pharmaceutical companies, it just seems very naive to attributed the unethical things done by pharmaceutical companies to “rogue” elements. Lobby for direct-to-consumer advertising wasn’t an abberation, neither are most of the other profit-producing but unethical things done by the industry. It may just be a competitive thing or my friends but most academic researchers I know see working for pharmaceutical companies as going over to the dark side.

  13. overshoot says:

    I get the impression that no matter what the label said the jury was going to find it was inadequate because grievous harm occurred. If that is the case, and no amount of labeling or disclosure can protect a manufacturer from provider error, then the cost of drugs is going to go up a lot, and many will become unavailable.

    What you’re describing is “strict liability.” The idea is that the manufacturer of any product is liable if the product causes consumer harm, without regard to whether there was any negligence on the part of the manufacturer. However, even strict liability is not generally applied unless there is a manufacturing defect; the canonical case was a lawsuit where an idiot consumer cut off a foot by misusing a chainsaw and sued the saw manufacturer because the saw was … capable of cutting off limbs. The Court found for the defendant.

    Applying a stricter standard to drugs than to chainsaws would, as you note, be a good way to take a lot of useful pharmaceuticals off the market. What happens if some rocket scientist decides to drink the disinfectant?

  14. Harriet Hall says:

    I find it ironic that a rare adverse event after written warnings brings on the lawsuits, while a less rare adverse event with no warning doesn’t. A woman was written up in my local newspaper for a rare “foreign accent” syndrome after a stroke. Buried in the body of the article was the admission that she’d gone to a chiropractor for back pain, had her neck manipulated, had immediate pain and swelling in the neck, and she apparently recognizes that that caused her problem. But she says she “can’t blame the chiropractor” because he didn’t deliberately intend to harm her.

  15. daedalus2u says:

    Fifi, the pharmaceutical industry is fundamentally different than the tobacco industry which sells a product with no redeeming attributes. Those in the tobacco industry are merchants of death. They profit solely to the detriment of others.

    I am not attributing all harms from pharmaceuticals to only those from “rogue elements”, but how can an ethical pharmaceutical company protect itself from cases such as this? How can a pharmaceutical company without “rogue elements” protect itself? I don’t see that they can. To me it seems as they are fundamentally at the mercy of the whims of a jury.

    How can a pharmaceutical company label a drug such that the label can not be considered “defective” as occurred in this case? The provider who administered the drug didn’t follow the label as it existed. What reason is there to think that a different label would have led the provider to behave differently and administer the drug appropriately? Other than the self-serving statements of the clinician who violated the directions in the existing label? (but according to plaintiffs attorney that “had no bearing”).

    ”JUSTICE SCALIA: No. No. Wait, wait. He administered a — a level of the drug that was vastly in excess of — of — of what the labeling said could safely be used for IV push.
    MR. FREDERICK: And the testimony at trial showed that that had no bearing on her injury, because -
    JUSTICE SCALIA: Had no bearing. Are you serious?
    MR. FREDERICK: Yes. It did. The testimony at trial from Dr. Green disputed that point. Both courts below rejected that notion.”

    I suspect that since the provider settled out of court for a modest sum, a requirement of that settlement may have been to assist in going after the deeper pockets of the pharmaceutical company.

    If it is the label that is defective, then those who are finding the label to be defective should be able to provide a label that is not defective. Can they? If the jury has sufficient expertise to find a particular label is defective, can they provide a label that is not defective?

    Mark Sadaka has articulated the standard he wants, omniscience on the part of those making these decisions. Since the FDA is not omniscient, review by the FDA can’t be good enough. Now the omniscient Supreme Court will make the decision. The Supreme Court is omniscient because by definition they are the final arbiters of US law. Whether their decision is good law or bad law doesn’t matter, it will be correct law because by definition what ever the Supreme Court says is correct. It goes without saying that their decision won’t be about science. Decisions by a group defined to be omniscient (i.e. juries and judges) can’t be about science. It is not pompous for me to state that fact.

    Harriet, I think the reason is because these lawsuits are not about “harm” or “justice”, they are about money. The chiropractor doesn’t have the same kind of deep pockets that a pharmaceutical company has.

    This drug has been off patent for over 40 years. It is available over the counter in the UK. I presume it isn’t a big money maker.

  16. Glazius says:

    It is quite pompous to think that a jury of our peers could not decide, after weighing the issues, whether or not a label was adequate.

    Labels are meant to provide instructions to the people administering medication, not necessarily the general public. For drugs only used in a clinical setting, this means the general public is not the intended audience of a label.

    Besides, think about what you’re saying here. It’s the drug company’s fault when someone administers the drug wrongly because the label didn’t contraindicate it expressly enough? That might fly with over-the-counter medication, but this one was administered professionally, and professionals are paid to know many things, including how to read labels and make treatment decisions based on them.

  17. Mark Sadaka says:

    Glazius – correct – the warning is for the physician. Are the words “warning” and “precaution” different to you? (presuming you are not a doctor) If they are to you they are to a physician. Are the words “Black Box Warning” and “Warning” different to you? The point is that physicians need to be made aware of the seriousness of a warning. Like I said previously, every side-effect in the word could be listed in a label but does it really help when warning against a specific serious condition? Is headache the same as gangrene?

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