Read The Supreme Court Preemption Transcript
25 CommentsBy Ed Silverman // November 3rd, 2008 // 9:40 pm
Want to know what Wyeth’s attorneys told the US Supreme Court justices to justify preemption? Did Diana Levine’s attorney make a good case against preemption? What questions did the justices ask? And which ones seem to favor preemption? Is it really possible to tease out which way the court will vote by poring over today’s big event? Try figuring it out by reading the official transcript.
Justice in MI
My tea leaves below, in the play-by-play thread. It is fascinating reading, even if you are not a preemption junkie. We’ve got some smart folks and genuine characters on the Court, even if I profoundly disagree with some of them.
Justice in MI
Now that I have read through the actual argument in detail, I have somewhat different thoughts than initially expressed. Beyond the question of who should win or lose, or what the Court may actually decide, the case provides a window into what is probably ‘business as usual’ for both FDA and industry when it comes to drugs, like phenergan, that have been used for years, are certainly not blockbusters, and which probably no one ever expected would become ‘headliners’ one way or other.
On the one side, it seems clear that the FDA never did much one way or other to carefully assess the risks, or relative risks, of push IV delivery. While there are some warnings on the label, they appear to be more pro forma than anything else, and do not provide physicians guidance regarding when the risks of push IV might be a reasonable choice relative to other possible choices. So, if there is ‘negligence’ - which is probably the wrong word - we have an agency that is basically coasting the way it usually coasts, and in the context of its usually starved resources.
On the other hand, we have a company that is also essentially coasting. Plaintiffs argue that Wyeth should have known the risks based on a scattering of reports and experiences with related drugs. And that, at some point in time, could have and should have made a unilateral label change. The argument is that CBE regs as they then existed would have allowed such a change, which much of the discussion circled around - did the information have to be “new,” a “new interpretation” of old info, or whatever whatever.
In any event, the company emerges as more or less winging it based on the usual ways company wing it, just as the FDA similarly does. All the stuff we’ve heard about the FDA making careful risk/benefit assessments, or the company doing its version of the same, fades away. And what we end up with is the picture of a company and an agency more or less limping along in the ways to which each has been long accustomed under such circumstances.
Given these realities (as I see them), I frankly have no solid opinions about how this case either should or will go. To give pre-emptive deference to an agency that stays together with duct tape and jerry-rigging (which is as much as Congress has provided0 does not seem to make much sense. But neither does holding a company accountable when they didn’t do more than the usual duct taping and jerry-rigging of their own, with no suggestion of negligence unless the acting in accord with a more or less pitiful status quo, in itself, is negligent.
So I see no demons here. It’s more the banality of imperfection on all sides, coupled with the twin hyperbolic claims of noteworthy irresponsibility on the part of the company and noteworthy competence on the part of the FDA.
Nathan
Justice,
Excellent writing! I enjoyed your summary far more than I enjoyed wading through the first few pages of the transcript.
Are there more arguments scheduled for today? I have no idea how long a typical supreme court case lasts.
Former pharma Marketing Exec
Good Comments Justice,
However, I do have a problem with the idea that this can all be put down to banal indifference and quasi complacency caused by limited resources at the FDA restricting time and effort devoted to such a serious situation.
The problem is that the Doctors, Nurses and other health care professionals must rely on the information in order to work within the strict requirements of their profession.
The fact remains, Wyeth had some information, did not share it entirely with the agency which meant that the information was not shared with the health care professionals so that precaution could be sharpened and more adequate risk information shared with the patient. Levine did not know that agreeing to have the injection to get rid of a migraine, could even remotely, cost her her arm.
The argument here is that this person was denied access to the facts that were known by someone but not fully disclosed for whatever reason, in order to properly make an informed decision on what treatment she should have.
This case does highlight the need for improved funding for the FDA.
In light of what we have heard from FDA employees and the facts of this case and many others like it, we would be doing a great dis service to ourselves and our entire health care system if we put the responsibility solely on the shoulders of the FDA for safety and welfare of our citizens.
While this case doesn’t make a case for preemption one way or the other, the information we have learned because of it surely does.
It is absurd for anyone to be in favor of preemption while the FDA seems to be in such disarray.
Jaynesday
Former, I agree about the absurdity of preemption -
The unaware American people stand in the path of the perfect storm. Corporate immunity disguised as “torte reform”, a hungry industry wolf and the failure of our only protection (FDA and litigation).
What will the aftermath of our health provision look like when the storm is upon us?
harpy
I believe it was Hannah Arendt who first discussed the “banality of evil.”
Justice in MI
Yes, harpy, and Arendt got it wrong. (This is stuff I’ve been teaching about for thirty years.)
My views on preemption haven’t changed. It’s rather that the arguments as given focused on very particular circumstances - some hypothetical - in which preemption might apply. For example, even Levine’s attorney agreed that _if_ FDA had all relevant information and _if_ Wyeth had provided all relevant info they had and _if_ FDA made a careful determination within all those circumstances, preemption ought to apply.
I am less clear than Former that Wyeth did not entirely share the info it had with FDA. There was no claim of that on the Levine side. It was rather that Wyeth ought to have done more with the info they had, regardless of what FDA did or did not have or do.
Earlier yesterdat, DDL called the case a potential “bridgehead” (I think “beachhead’ was a bit more the idea). So preemption certainly has not gone away. If the court does not give the industry the whole enchilada - which could still happen - there will be further cases and interpretations in which there will remain pushes toward negligence, fraud, etc. also be protected by preemption.
For Nathan, the arguments are over. Only lasted a few hours. Decision will come….we don’t know, certainly weeks if not months.
harpy
Sorry, Justice, you’re absolutely right. Bad day here and I prolly just shouldn’t comment. I’d withdraw it if I could.
Nathan
That’s amazing to me that “normal” court cases go on for days and sometimes weeks. Yet this vitally important court case is over in a matter of hours! I guess the difference is that normal cases are directed at uneducated jurors while the supreme court cases are directed at extreamly well educated “jurors”.
jooe
Another issue that needs to be discussed: Currently if someone has insurance or is on Medicare/Medicaid, any money that received in a pharmaceutical settlement, must be repaid. There is a lien put on your claim from insurance companies and Medicare so they can get their money back. If preemption goes through, this can bankrupt the insurance companies and Medicare if they are not allowed to claim any money they paid out for a patient that was injured due to a drug injury.
An FDA Reviewer
Justice,
I haven’t read the transcripts yet, but your assessment of how things work are absolutely correct.
I knew about not giving phenergan IV push and Wyeths labeling 25 years ago and well before ever coming to the FDA.
Even important things just get tossed on the pile and we never get to them.
My fear is not so much this particular case but the way Pharma abuses system to make sure we can’t get to important things. For example by simply running us in circles with busy work. And most importantly that this is really just a strategic case for industry to protect themselves from big big claims in the future about problems that they already know about but that haven’t come out yet because no one has put 2 and 2 together yet, i.e. another vioxx and/or phen-fen.
An FDA Reviewer
Doug Bremner
I am reading the transcript now and am struck by the comment by Justice Alito (can’t help but hear Ted Kennedy in my mind say ‘Alleoto!”): “how can the benefit of nausea reduction outweigh the risk of gangrene?”
How indeed?
Here is another quotable [in response to defendants saying the label is to inform physicians of risks and benefits]:
JUSTICE KENNEDY: The FDA was never concerned with risks versus benefit?
[aside: as a physician I see no reason why they didn't put in an iv, which would have eliminated the risk, but that is beside the point of the Supremes ruling on preemption]
Justice in MI
Hi Doug - Your last point is relevant to preemption because it speaks to the question of how thoroughly FDA reviewed the risk in question. As FDA Reviewer seems to confirm, just because something is on the label doesn’t mean there has been much attention paid. Sharkey argues - and I tend to agree - that if FDA wants pre-emption there has to be more evidence that the relevant risk was seriously reviewed. Probably the ideal solution, and it could happen, would be to remand the case back to Vermont. Otherwise, even though I don’t think Wyeth’s delinquencies were large (compared with other delinquencies we often consider), I don’t like the idea of preemption getting a “beachhead” either…
Harpy - I was bit snappy. I did deliberately use the word banality because I was thinking of Arendt. And, indeed, bad things often do result from trivial causes. I just think she was wrong about Eichmann and company, which she was writing about. They were not “ordinary bureaucrats” as she suggests. But that is another topic….
Nathan
Doug writes: “how can the benefit of nausea reduction outweigh the risk of gangrene?” How indeed?”
Let me ask you another related question: How can the benefit of headache relief outweigh the risk risk of major GI bleeds?
(think ASPRIN)
Here’s another: How can the benefit of convenient travel outweigh the risk of death in an auto accident?
We make these “calculations” all the time in the privacy of our own minds.
Just A Thought
I have a question based on the following (pg. 24- lines 2 through 6):
JUSTICE SCALIA: You can supplement only when there is new information?
MR. KNEEDLER: When there is new information and even then, it has to be in the form of a new drug –a supplemental drug application to the agency.
Would a “supplemental drug application” include a supplemental abbreviated new drug application?
It is obviously not for the purposes of the Levine case that I question.
Doug Bremner
Ah, Nathan: First off, I think it is spelled “Aspirin”. Second, I think the more relevant comparison would be: comparing the risk/benefit ratio of giving phenergan iv push versus through an iv. The excess risk of putting in an iv is essentially zero, and it would eliminate the risk of gangrene, which as “juryman” wrote on this site earlier, the Vermont trial revealed that you don’t have to be in an artery to get gangrene from iv push, so not putting in an iv is simply irresponsible.
Which gets me to my next point. The fact that the FDA did not say DO NOT GIVE BY IV PUSH means that they cannot be expected to handle every detail related to prescription drugs, especially since their staff is being hounded to approve drugs as soon as possible, via pharma pressure. I think this is the BEST argument against preemption of state law by FDA approval.
An FDA Reviewer
Thought,
An sNDA would NOT include an ANDA. The labeling of an ANDA has to be virtually identical with the labeling of the holder of the reference product.
For others an ANDA is a generic drug.
Another comment. I disagree with Formet Commissioner Kessler’s comment the other day that labeling is fully revealing at initial approval because the company is told that they are not allowed to change any wording or the drug will be misbranded. At approval the labeling is a product of negotiation and FDA often doesn’t get everything it wants. The warning is really to tell the sponsor to not try to pull a fast one and change the negotiated wording to make it more sales friendly, and thus this a warning that this is the bare minimum we will accept.
I’ve seen too many times where sponsor send us back mockups of supposedly negotiated labeling and it’s been changed. Or in supplements things get changed and we’re not told so if might approve some change we’re not even aware the company did.
One of the most surprising things I ever heard is when one of the biggest companies around told me during labeling negotiations, “but if we put that in the labeling it’ll decrease our sales by 10%”.
Isn’t it up to the patient and the physician to have an informed opinion so they can decide the risk vs. benefit of use.
(This wasn’t as surprising as when a company representative yelled at us in a meeting, “But we paid for an approval!”)
An FDA Reviewer
Just A Thought
FDA Reviewer,
The reason I ask is because, according to the VA, Dilantin NMP was approved via sANDA.
If Dilantin NMP was not an ANDA or a sNDA, then what exactly was it? I understand that Dilantin NMP was not approved under the usual circumstances of an ANDA.
So based on Kneedler’s comment, it seems reasonable that anyone privy to post-marketing information should do something. Otherwise we were not even being involuntarily harmed for the greater good.
I do wonder how it is that the agency thinks it can ensure proper warnings when testing is so limited that it does not exclude long time users with a NTI. This was a dramatic change that caused serious harm. A change such as this leaves us wondering how our doctors can ever know what they are prescribing. This approval also made the DAW pointless.
Thank you for your reply. I am curious about sANDAs if you have the time.
Just A Thought
“The labeling of an ANDA has to be virtually identical with the labeling of the holder of the reference product.”
Maybe because it was the reference product that was changed there is a new application catagory? Does this change also change the rules for generic makers, to be virtually identical to the new product? Because if the generics we moved to are going to toss us into seizures and toxicities some day soon- it would be helpful to know in advance.
I’ll stop hijacking this thread now. Sorry.
Jim
I thought that the exchanges between Justice Souter and the different parties were the most interesting and that it is my guess that he will write the Majority opinion: What I don’t know is who he will favor. Base upon his questions he seems to be leaning towards ruling against preemption but I would not bet the house on this guess?
I thought the most interesting comment was made By Chief Justice Roberts:
“So, as I understood your answer to be, all we have to do is simply look at the record, and if we think the FDA considered specifically IV push risks as opposed to general arterial exposure, then you lose, and if we determine that they did not, then they lose.”
That would seem to narrow the issue: However I realize just because Justice Roberts asked this question does not necessarily mean that he agrees with the premise.
The other comment by Justice Roberts that I found to be of interest was his comments on the fact that Statutory law includes a preemption for Medical Devices but does not include one for drugs.
I wonder if the fact that there is no express Statutory language favoring preemption will determine his decision?
The fact that Wyeth’s attorney referenced Riegel in his answer doesn’t help here; Riegel was decided on behalf of the Respondent because the Statutory Law did exist.
As to the question on whether Levine’s Attorney presented a good case on behalf of preemption; based upon the transcript I don’t think he did. I thought his answers to the Court’s questions seemed to lack a specific focus. I think his “what did they know and when did they know it argument” will not be relevant in this case as it was acknowledged that the risk was known for years by everyone including the FDA. He testified that Wyeth was aware of the problem as far back as the 70’s; I don’t think this particular testimony helps his case; if the problem goes back that far where are all of the other lawsuits? It just seems to me to reinforce the argument that the problem was with the provider and not the manufacturer.
The other fact is that he pointed to the broad powers granted to the FDA since 2000. Broader authority brings broader responsibility. I can’t help but think that this will favor the industry and bring us right back to Justice Roberts’ Question.
Anon
Agree with everything you said Jim. Perhaps Vyoxx, Premarin and my all time favorite scandal Ortho Evra, should be one of the drugs in this preemption case. With these drugs there is clear evidence that the drug companies knew about the risks and sent in misleading studies to the FDA to get their drug approved.
An FDA Reviewer
Just a Thought,
I have no personal information on this. I think the VA may simply be in error. Dilantin is the brandname of the innovator’s drug product and any changes would have to come from the innovator and would covered under an sNDA. ANDAs are only for generics.
Having said that I found comments on the epilepsy foundation website that the Dilantin produced under the new manufacturing process (NMP) is not bioequivalent when compared under fed conditions (only fasted).
There has been a lot of changes at FDA over the last few years. One is that the manufacturing changes for branded drugs like Dilantin has been removed from the review groups who have always handled them (i.e. the clinical pharmacologists and chemists who work on the original product) and has been handed off to a separate group of chemists who don’t even tell the reviewers who look at the clinical implications what is going on. It has been an incredible mess as they’ve stuck the worst people over there and they have been doing all kinds of things like signing off on changes based on promises by companies that they will show bioequivalency in the future. (I know this has been an issue with the groups who had been reviewing neuro drugs.)
Now the primary review teams are looking at clinical studies and finding out that the studies were done with a totally different formulation that behaves very differently than they thought.
All of these changes in FDA appear to be coming at the request of industry because they simply didn’t like it when FDA reviewers told them that there’s a potential issue with something they wanted to do. (The attitude from industry and even verbalized by upper FDA management is who are we to tell companies anything about what they want to do.) It also causes a lot of excessive work for the primary review team as they have to spend inordinate amounts of efforts trying to stop these problems before they occur. Unfortunately the staff reviewers have been losing these battles and they are just overruled.
An FDA Reviewer
An FDA Reviewer
PS to Just a Thought
For new drugs these issues really take a collaborative approach from medial reviewers, chemists, and clinical pharmacologists working together.
Management has been playing musical chairs with us with the move to the new campus. Now the medical reviewers are in one building, the chemists in another, and the clinical pharmacologists in another. So that it’s a 20 minute fast walk to collaborate. Forget it. With all the new inexperienced reviewers being hired they don’t even know what other review disciplines even do.
Plus the clinical pharmacologists have now been told to not even look at how changes in formulation and manufacturing during development of new drugs alter drug effects. Without this you can’t tell if you should even expect a possible problem with changes after approval.
The moves appear to be intentional or as one senior manager put it “divide and conquer”.
For example back the Clinical Pharmacology staff was moved last april first into a new building because they had just the right number of staff members and the Office of Generic Drugs who were supposed to move into this space were going to have too many based on the plans to higher more reviewers to review generic applications. Within days of the move into the new building the plans to hire all these new reviewers to review generic drugs was canceled. Not only that but the building that had been designed 10 years ago had special computer rooms for the new drug-disease modeling etc. under an ex-Pharma VP. Plus there were rooms for all these new fellows that Von Eschenbach just announced he was going to hire.
An FDA Reviewer
Just A Thought
FDA Reviewer,
You are very kind to lend me an ear.
I think the VA’s confusion (if there is any)comes from Dilantin NMP being approved by the Office of Generics- according to an FDA spokesperson- which might have caused the sNDA to be considered a sANDA.
As for the fasting requirement for bioequivalency, that was not the only problem, just the only one that a simple AUC comparison might indicate.
Our pharmacists were instructed by our physicians to give us Dilantin (DAW) no matter what Dilantin was at the time. There was no additional warning for fed/fasted requirements on the packaging insert initially (not that I got anyway). The pharmacists in my area were oblivious to the change.
Epilepsy drugs often require weeks of careful titration. There is no way we would have put ourselves at risk if all it took to avoid those risks was to reschedule our meal/dosing times. We would not have gone through (often failed) attempts with other drugs. Switching is and has been dangerous.
We were told that the product was the same except for the appearance. Pfizer even called it “New Look” which implies just that.
Please read this article and take note of the statements made by the FDAs spokesperson about how it was approved:
http://www.pharmalot.com/2008/05/a-new-version-of-dilantin-is-giving-pfizer-fits/
I do hope our reports are still on record somewhere in the MedWatch system and that someone will take another look. New and increased instances of AEs in long time users deserves some sort of action.
FDA Reviewer, I do understand your explanation of changes in the agency, but where does that leave us? Pfizer blames the FDA saying that it was on FDA request that they changed their product. I could possibly accept taking a new drug and finding out it is harmful, but we had successfully taken Dilantin for many many years (some for decades) and were blindsided, along with our doctors and pharmacists. Left without our treatment to even go through a safe transition. These kinds of drugs need thorough evaluation for approval. Otherwise the agency is making the statement that our demise or loss of wellbeing is unimportant.
Thanks for your time.
formermarketingexec
O.k. I can’t resist any longer.
I must admit that I was given this drug 4 times in a five year span for persistent migraine headache. I am happy to report I have all my limbs. Why? because it was always through an IV drip and never through an IV push. I confess that on more than one occasion I asked why it wasn’t through a IV push as the drip seemed to take so long, “they” said it would be dangerous through a push, although it wasn’t indicated so clearly on the package insert ( I read everything…).
When you have suffered through a few days with a horrible migraine, you will seek any means that sounds reasonable. I can relate to Levine.
I wasn’t in the US when I received this drug through and IV drip.
Like I said before, this isn’t a great case for preemption and Levine should continue to look forward to what she was awarded.
I wouldn’t joke about this…