Preemption And Amputation: Diana Fights Wyeth
23 CommentsBy Ed Silverman // February 20th, 2008 // 1:00 pm
Eight years ago, Diana Levine entered the emergency room of a Vermont hospital because of a severe migraine. This had happened before and, as on other occasions, she was given a painkiller and another med to treat the nausea brought on by the first drug. One thing, however, was unusual about this visit - the nausea med was administered differently. And the incident eventually caused Levine, a professional musician, to lose her right arm below the elbow. She later filed a lawsuit against Wyeth, which sells the injectable Phenergan nausea med.
Levine successfully argued that, even though Phenergan labeling complied with FDA requirements, the adequacy of the warning still wasn’t established. This referred to a particular method for administering Phenergan known as IV push. Moreover, Levine’s attorneys contended Wyeth wasn’t prevented from adding or strengthening the warning on the label, even though the FDA rejected a proposed change. Levine was awarded more than $6 million and, despite appeals, the Vermont Supreme Court sided with her. But Wyeth has appealed again and now the US Supreme Court agreed to review the case.
Why? At issue is preemption - a legal notion that FDA approval of a drug supercedes state law claims challenging safety, efficacy, or labeling. Drugmakers and the FDA argue that preemption exists by maintaining the agency’s actions are the final word on safety and effectiveness. The court’s decision, therefore, is being closely watched because its ruling will determine whether patients can sue a drugmaker through state law when a product has already been approved by the FDA. We chatted with Levine, 62, about her plight and the legal battle. This is an excerpt…
Pharmalot: Before this episode, you were a professional musician. What did you do?
Levine: Back in 1989, my husband and I started a label, called Rebop Records, which I did to combine my passion for music and songwriting, and my love for kids. I played bass, guitar and piano. Sometimes, I’d play with my sister, who lives nearby, or my husband in local bands. The label was designed to provide rock and roll that kids and parents could enjoy together.
Pharmalot: But in 2000, you went to the hospital and Phenergan was administered. What happened?
Levine: I have a history of these migraines and, normally, I can manage them, but on occasion, they could be excruciating and debilitating, and I’d get hauled off to the emergency room. Normally, I’d get Demerol for the pain and then Phenergan, because the Demerol would make me nauseous. And it would be intramuscular administration, which was normally a shot in the butt. This time, they gave me a push IV and that’s what caused the problem When I woke up, I was still in pain.
Pharmalot: At what point was your arm in jeopardy?
Levine: This went on for two or three weeks. It’s a bit of blur now. But I was taking bloodthinners and morphine and painkillers. The doctors tried desperately to keep my hand. I’d never been in such pain. There were two procedures, though. The first was to amputate the hand. But it became obvious that the skin (below the elbow) wasn’t going to regenerate and get healthy. The gangrene was still there. So I told them to take as little (of the arm) as you have to. The trauma seemed insurmountable. The best I could say was that I hadn’t died.
Pharmalot: What did this do to your life, and your music?
Levine: Well, it stripped me of my career and my business and my ability to do what mattered most. I had to start from scratch. I’m left-handed and it was my right arm that was affected, so in a way, it was a blessing. Although I tried to do too much and developed over-use syndrome. Anyway, I was eventually outfitted with a prosthesis. And now I can hold a guitar pick and strum and make a chord. I still work with kids, but I can’t tell you how many times they ask what happened. I tell them one is my soft hand and the other is my hard hand.
Pharmalot: What’s your view of Wyeth and its actions?
Levine: They should’ve taken responsibility for changing the label…
…It’s not a bad drug. It’s a good drug, for what it is. But I’d much rather throw up than lose my arm. I think they should’ve come out and said that, under no circumstances should the drug be administered under push IV. They didn’t protect me and ensure my safety…They have strong economic incentives and, sometimes, those things take precedent…They say the FDA is their first line of defense, but if a drug company recognizes there’s something that could hurt the public, they have an obligation to do something.
Pharmalot: What do you think about the Supreme Court agreeing to review your case?
Levine: Well, those nine judges aren’t supposed to be influenced by whatever goes on between industry and the administration (which back preemption). I just have to have faith…If people like me are denied the ability to sue a drug company, well, a drug company has a mind of its own. They know when something is dangerous and they can change it. Think of all the little clinics and emergency rooms that may know as a result of my case. But it’s Wyeth’s responsiblity to let them know, not mine.
I can understand why (Wyeth) is doing this. It’s probably because of all the frivolous case. But don’t punish me or change a sytem that, right now, helps keep people safe. The only way I look at it is that now I have an opportunity to talk to people. Millions are now paying attention to the situation. I’m up on my soapbox and I’m going to create awareness. Hopefully, that’ll lead to change. It’s a shame we have to take this upon ourselves. Why should I have to be the savior? It’s astonishing to me that the Supreme Court took this, but I’m going to make the best of it.
Laurie
“Levine: They should’ve taken responsibility for changing the label…”
This is the key phrase. While the FDA is touted as the “final word” on safety, it is the drug manufacturer who has the data and has to openly provide that data to the FDA for review. The FDA then takes years to “review” the data and act. This is the catch 22 that is created, while the public is at risk.
Nathan
Levine: They should’ve taken responsibility for changing the label… I think they should’ve come out and said that, under no circumstances should the drug be administered under push IV.
Laurie, I disagree. The key question is: Did Wyeth have evidence in-hand to support this second sentence? I don’t know the answer — but THAT is the key question.
Prior to this case, was the company aware of problems resulting from IV pushing? If so, how extensive were those problems and did those problems warrent a COMPLETE ban on IV pushing or just a strong warning against IV pushing?
Ed Silverman
Hi Nathan,
To answer your questions, her attorney noted that there was evidence presented at trial that Wyeth knew. If you would like to read more, I included a link to the Vermont Supreme Court ruling (see the link above), which reiterates the facts of the case.
Hope this helps,
ed
Laurie
The current labeling continues to give instructions on how to administer phenergan IV, when the IM route is obviously safer. Most hospitals have their own internal policies on the use of IV phenergan, and most nurses will refuse to administer it IV due to the extremely high risk.
Justice in Michigan
All preemption, all the time. I like that.
I agree with Nathan’s comment (which may surprise him!). It all depends on what Wyeth knew, when did they know it, what did they do.
As I’ve recently learned, there appears to be much more to these questions than was apparent when the case was first publicized. But I think it is fair to say that the spectrum I mentioned in today’s thread on Medtronic/Riegel - between good faith compliance on one end and fraud on the other - is also relevant here.
If I can be more specific, I will be.
Laurie
“I agree with Nathan’s comment (which may surprise him!). It all depends on what Wyeth knew, when did they know it, what did they do.”
Oh, I totally agree with that too.
Justice in Michigan
This additional bit. As reported in Ed’s summary and in the trial briefs, Wyeth was very aware of the problem and was in negotiation with FDA over a label change that would address this. The report is that “FDA rejected” Wyeth’s proposed change. Personally, I don’t know whether that was because FDA felt the proposed chage was too strong, not strong enough, or had some other flaw in FDA’s view.
From that point on, a year passed and nothing happened. Wyeth, of course, had “deniability” based on the gridlock in label-change negotiation, whatever the reason for it.
We are all familiar with similar stories.
And then Diana Levine lost half her arm and much of her life. The original jury ruled against Wyeth unanimously. I don’t think Vermont is generally on the “judicial hellhole” list, despite Bernie Sanders.
What might have happened? Like many of you, I am aware of a range of situations in which companies do the “right thing” technically, but conscientous employees are very aware that significant safety issues are not being addressed. Often they act to try to rectify such problems. These are the everyday heroes of the industry that we should celebrate, and they are not few in number.
I would not be surprised if there were such people at Wyeth and involved in this issue. Clearly, they did not win.
A victory for preemption is essentially saying to those people - keep your nose clean, keep you head down, look the other way. Get cynical. Because the system supports you not a whit.
Dr. Sal Giorgianni
This is a very important case. It has implications across many areas, not the least of which is one of the most important notions of our nation and that is interstate commerce. One possible outcome of a finding against the manufacture (that is a state can mandate its own terms for labeling – or a manufacture may provide labeling to protect itself from litigation in defiance of an ongoing FDA review or negative ruling) could create chaos. If states can mandate more stringent labeling – either directly or through a court ruling and thus uniform national labeling standards are put aside interstate commerce could be thrown into chaos. If a manufacturer creates and publishes any statement prior to FDA approval, regardless of the reason, it would be in violation of fundamental regulatory precepts and severe penalties could be imposed, including jail time. There has been a relative view of a safe-harbor for package labeling that has been in-tact for decades to insure the smooth course of interstate commerce and a scientifically valid regulatory process. To dismantle it would cause chaos and put the health and welfare of the public in jeopardy.
In the Know
Dr. Sal is fundamentally correct regarding the legal Catch-22 manufacturers find themselves in. Of equal importance, however, are facts regarding the Phenergan package insert (directed to physicians) that are omitted from this discussion. Phenergan is an established drug with several manufacturers servicing the healthcare community — it is not a money-maker for any of the manufacturers. The preferred method of administration is intramuscular, however, there are instances where physicians need the ability to quickly administer a therapeutic dose which is why the label has clear warnings regarding intravenous administration. There are at least three sections in the package insert that clearly warn healthcare professionals — in bold letters — to use extreme care when administering intravenously and to avoid administration into an artery (either directly or through extravasation, piercing a vein and unintentionally hitting a neighboring artery). Healthcare professionals are cautioned to cease administration if the patient experiences pain at the injection site. The package insert then clearly states that the end result of administration into an artery is irreversible gangrene and potential amputation of the affected limb.
You may be asking yourself why such a “dangerous” drug or method of treatment would be allowed to stand. The simple answer is that sometimes sick people need aggressive treatments to afford comfort or to improve their quality of life and it is up to their physician to use their judgment, experience, knowledge and care to treat their patients. It is often stated that chemotherapy and radiation treatments are more debilitating than the underlying cancers themselves. Unfortunately for Ms. Levine, her healthcare providers — in their rightful zeal to provide her immediate relief — failed to exercise the proper standard of care ultimately leading up to her significant and life-altering injury. It is truly a tragic circumstance but the blame cannot lie with a manufacturer that provided clear warnings and worked within the framework set forth by the FDA. To attempt to satisfy a patchwork of differing state standards and discharge FDA obligations simultaneously would, as Dr. Sal opines, cause chaos.
ol cranky
Most hospitals have their own internal policies on the use of IV phenergan, and most nurses will refuse to administer it IV due to the extremely high risk.
Gonna take an unpopular stance here. . . if the nurses are acutely aware of the extra risk to refuse IV, one would expect physicians are also aware - even without a change in the labeling. This is a horrible thing that happened to Levine but, unless she can prove that the manufacturer overtly and actively encourages administration by IV or touts IV as safe as IM, this is a case of HCP error/malpractice.
Bob Freeman
Frankly, I’ve been thinking about the same thing. From my one hospitalization had I not been an informed patient (consumer) I would have experienced at least two significant medical (not medication) errors.
Not to dig into the SSRI debate I recently attended a grand rounds presentation of SSRI toxicity as the result of one particular antibiotic used to treat MRSA. Physicians are clearly aware of SSRI toxicity but can’t wait for the drug to wash out of the patient’s system based on the need to treat the infection. Part of the problem is the cases series study is used, not a case-control or cohort analysis, so one cannot have a definitive diagnosis of SSRI toxicity.
Justice in Michigan
Quick response to Dr. Sal.
The reality is that we have lived well with FDA regulation and civil liability for one hundred years. The chaos you suggest has never happened, no state has ever imposed (or sought to impose) its own labeling, and no manufacturer has ever been penalized in any way whatsoever for trying to defend itself from this imagined state requirement that never happens.
The scenarios you describe have no basis in reality - either present or conceivable.
Nathan
Justice,
Another question for you: (this may be a long one - sorry)
The way I understand it, there are three current supreme court challenges that utilize preemtion as a primary defence. One of those was just decided. The other two are pending later this year.
So here’s my question: Why now? Are these cases being heard because the present (Bush) administration has a favorable view of big-pharma, or is it coincidence? Even if the “preemptors” win these cases, can’t the next administration just appoint FDA officials who will re-write the regulations in order to dis-favor preemption?
I guess I don’t have a good feel about how long the impact (positive or negative) of these cases will be felt. It seems to me that a future administration could just get around whatever decision is made by appointing new people at the head of the FDA. Is that accurate or no?
JM
This is a question for perhaps Justice or other lawyers out there…
What sort of constitutional challenges, if any, have been discussed in this space (e.g., products liability litigation that is federally pre-empted)? Has anyone argued Due Process?
Any information would be appreciated.
Lisa Van S
Preemption Justice Blog
http://www.sskrplaw.com/blog/index.html
Lynn Hadaway, M.Ed., RN, BC, CRNI
I totally disagree that most nurses understand the risk associated with giving any brand of promethazine by the IV route. I am an infusion specialist nurse with more than 35 years experience and I have served as expert witness in many legal cases involving extravasation injury from promethazine. Most nurses regard this drug with a very cavalier attitude because it is an older drug that they have given IM for virtually all of their career. Also, the level of nursing knowledge and skill about IV catheter site selection, placement and monitoring IV sites is extremely low. This is a dangerous drug that should not have the IV route on its labeling, in my opinion. Changing the labeling may not change nursing practice that much because the nurse is not going to read this label before each dose it given. This drug requires the same level of skill when given IV as any vesicant antineoplastic drug! This requires attention from hospital administration to write policies and procedures aimed at decreasing its use and the requirements for safe administration. Just my opinion after seeing the horrible outcomes for many patients.
DV Jr
To Nathan: A Supreme Court decision reflects the law of the land unless a future SC overturns it or Congress passes a (Constitutional) law changing it. A change in administrations would be irrelevant.
To Justice in Michigan: True that FDA & civil litigation have coexisted up to now, but the question of where the 10th Amendment stands on the role of the state courts in litigation has not been determined. If the SC definitively decides in favor of the states, it’s entirely plausible that the chaos described by Dr. Sal would take place.
Laurie
Lynn, I completely agree with what you said. I’ve been lucky two work with very well informed nurses. I sure this is not the case all over.
I have refused to give IV phenergan only to have the ordering doc have a resident give it, not following the necessary safety guidelines.
But, I’m responsible for my practice and I will not give this medication IV. There are to many other drugs that would treat the symptoms with much lower injury risks.
Dr. Sal Giorgianni
Comment to Justice
Several years ago one state, I believe California, attempted to pass legislation that would have created special warning categories for some pharmaceuticals. I cannot remember the specifics (must have forgotten to take my Aricept) but I believe it had something to do with carcinogenicity. This attempt failed but it was tried. Notwithstanding this failed attempt or any other prior attempt that I am not aware of, it is very dangerous to assume that because something has not been successful in the past sociopolitical climate it would not be successful at this or some future time. I am glad “Justice” and I agree though that the standing FDA system HAS worked and prevented chaos and therefore any actions which might jeopardize this greater-good compromise through judicial activism or case law would be a bad thing.
Justice in Michigan
Quick notes - I don’t know if anyone will return to this thread soon.
- First, happy to say that I am not a lawyer. I teach about some of these issues in a policy/politics context.
- For Nathan: Yes, it is clear that the Bush administration has initiated the movement toward preemption. They make no secret of this. It was a change of policy initiated in early 2002, shortly after Dan Troy’s appointment as FDA Chief Counsel. He has been the “godfather” of the movement for several years, including since his leaving the Chief Counsel position in 2004.
Dan (we have slight acquaintance, so I guess I can use his first name) moved quickly as Chief Counsel, specifically inviting companies to bring cases to him - as FDA Chief Counsel - that FDA would then support with an amicus arguing that such cases should be rejected on the basis of FDA preemption. All of this was very out in the open. His famous line, said at a conference, was that companies should “pitch their cases to him as though they were Hollywood scripts.”
So the goal was to get us where we are - have cases work their way through the circuits - where disagreements were virtually certain - so that one or more would eventually come to the Supreme Court. That took about six years.
Once the Supreme Court rules, there is nothing a new FDA administration can do to reverse or modify it. It is now “the law of the land.” If it were to lead to demonstrably bad results, there is the possibility that Congress could pass a bill that impacted the Supreme Court’s decision. But essentially we’re in a position close to Roe v. Wade. The Supreme Court would have to reverse itself to turn back what happened yesterday. I guess that’s why we do, indeed, call it “the law of the land.”
Dr. Sal - I’ll take your word on that. There are other potentially relevant examples. The Medicaid systems in both Washington and Oregon did not support Vioxx after the 2001 FDA Advisory Committee on it. This was not based on cost but on safety (it is against the law for such formulary decisions to be based on cost in those states). So here, indeed, were cases of states making, in effect, declarations about safety that were contrary to what FDA was then saying, Merck, et. al.
Nonetheless, no chaos resulted.
Dr. Sal Giorgianni
To Justice
The issue in Ca. I referenced was a move to require seperate package insert/label in that state for a particular product. This is quite a different matter than a decision not to allow general coverage for a product or proceedure.
Thanks for taking my word on this matter-of-fact; I worked on many issues in my time and can only sometimes remember generalities.
Justice in Michigan
Dr. Sal - You are right and, as I recall, that came up in an earlier case involving preemption. To me, at least, separate state approval systems don’t make sense.
However, what the preemptors did was to equate an issue like that - where there is truly an indendent “min” FDA in a state - and slid it into preemption of state tort law, which, in itself, has nothing to do with labels.
Still, there’s a great deal we’ve learned about safety issues with certain drugs (that end up in label changes or full withdrawal) through civil liability that it is unlikely we would ever have learned otherwise. See Kesselheim and Avorn, “The Role of Litigation in Drug Safety,” JAMA, January 17, 2006.
In the Know
Dr. Sal & JM:
Although state specific attempts to directly impose labeling requirements on pharma manufacturers are likely to be unsuccessful (there is no argument that FDA preempts the field here), the real world issue is that state law tort concepts have imposed an impossible burden on pharma manufacturers. Taking the Levine case as an example, the manufacturer followed FDA procedures with respect to warnings and additionally lobbied FDA for expanded warnings for its Phenergan product. FDA decided the warnings were adequate and declined the manufacturer’s request for revision. There was thus nothing more the manufacturer could do legally regading warnings on the Phenergan product. The Vermont jury, however, found that the manufacturer did not provide adequate warnings and that Mrs. Levine’s injuries were the direct result of that failure to warn. As a result, the manufacturer bears the financial brunt of an injury caused by allegedly inadequate warnings that it was constrained to maintain due to FDA fiat. This scenario is played out in courtrooms across the country as plaintiffs attempt to convince juries that, “Manufacturers selling pharmaceutical products in (fill in state) have a duty under state law to ensure that their product carries appropriate warnings to protect our citizens. It is not enough to simply have complied with FDA regulations.” The chaos that Dr. Sal references is already in play and the real world consequences are/will be reduced availability of pharmaceutical products on a state-by-state basis which has been a hotly debated issue for years.
Nurses Laurie and Lynn:
I agree that because of the age/familiarity of promethazine, most nurses are unaware of the risks of IV infusion. From the manufacturer’s perspective, however, there is an expectation that the physician requesting said administration is fully aware of a drug’s propensities. Risk-Reward is at the essence of a decision whether and how to administer a drug to a certain patient and the physician is uniquely qualified to make that determination in light of how the patient presents in his/her office. It cannot be controverted that the Risk-Reward analysis can only effectively be made when ALL of the risks have been factored. It leaves everyone empty when a physician testifies (as in this case) that he ordered IV administration because he knew it would provide immediate relief but that he had not recently read the label and did not know of the risk of extravasation. It also leaves everyone empty when the nurse administering the infusion testifies (as in this case) that she did not halt the infusion despite the patient’s cries of severe pain at the injection site in contravention of standard practice. I agree that pharma and the medical community need to write policies and procedures aimed at ensuring the safe administration of pharmaceutical products. These products are, by definition, toxic substances that can have serious unintended consequences if administered injudiciously.