Glaxo And Pfizer Win Preemption Cases
A federal appeals court has decided that the drugmakers can’t be held liable for a pair of suicides that were blamed on antidepressants and an alleged failure by the manufacturers to include sufficient warnings about links to suicide. The ruling comes just months before the US Supreme Court is scheduled to review preemption and whether the concept should apply to prescription drugs.
The preemption debate centers on an argument by the FDA and drugmakers that agency approval of a drug supercedes state lawsuits challenging safety, efficacy or labeling. FDA officials, who once viewed litigation as a tool for aiding oversight of safety issues, now maintain that state lawsuits could lead to an overlapping patchwork of rules that would burden drugmakers and might discourage patients from taking useful meds.
In this latest decision, two of three judges on the US Court of Appeals for the Third Circuit ruled against the family of Lois Colacicco, 55, who took a generic version of Paxil sold by Apotex in October 2003 and committed suicide less than a month later, and the family of Theodore DeAngelis, 64, who in January 2003 took Zoloft and committed suicide eight days later. In doing so, the court dismissed arguments that the drugmakers possessed undisclosed data closely linking their antidepressants to suicide and the FDA’s subsequent warnings for youngsters in 2004.
“Our holding is limited to circumstances in which the FDA has publicly rejected the need for a warning that plaintiffs argue state law requires,” the court wrote in its 58-page decision. “Even when it began to reevaluate its position regarding the association of antidepressants with pediatric and adolescent suicidality, the FDA continued to announce its rejection of adult suicidality warnings for SSRIs as it had for the decade before the prescriptions and deaths at issue in this litigation.”
UPDATE: An attorney for the Colacicco family says that “we read this to be a narrowly tailored decision dealing with only those cases where the FDA has reviewed the issue. In this case, it was SSRIs and suicidality. It doesn’t deal with all drugs.”
“Just months prior to Lois Colacicco’s death, the FDA publicly stated that Paxil was not associated with a risk of suicidality in adults. Similarly, four months before DeAngelis’ death, the FDA filed a public brief stating its position that scientific evidence did not support the addition of a suicide
warning on Zoloft’s labeling.
“The FDA explains in the amicus brief that ‘the basis for federal preemption is not the (labeling) guidelines themselves…, but rather FDA’s repeated determinations prior to October 2003 that there was insufficient scientific evidence of an association between adult use of SSRI and suicide or
suicidality to permit a warning on the labeling for those drugs…
“The FDA’s view that ‘the imposition of liability under state law for defendants’ alleged failure to warn would interfere with FDA’s accomplishment of regulatory objectives,’ is in ourview entitled to at least as much deference, if not more, as the FDA’s view of its preemption authority.”
In a dissenting opinion, Ambro wrote that “Allowing the plaintiffs’ cases to proceed beyond the motion-to-dismiss stage means instead that the state courts and federal district courts applying state tort law may eevaluate - provide a check on - whether the FDA struck the right balance in the precautions and warnings it required for SSRIs.”
Lisa Van S
Im curious, as to why the Deangelis case wasnt heard in New Jersey!
M Helm, MD
I wonder how this concept may affect pending lawsuits relating to off-label uses and “defective” product claims, etc. pending against marketers of atypical antipsychotics (and/or other medications) by State’s Attorneys General? (While I’m wondering things… is “State’s Attorneys General” correct according to the stylebook?)
Would it make a difference that the populations believed to be harmed by alleged off-label promotion and/or use were not among the groups for which the medications were considered safe and effective?
Does preemption (which gets the maker off the hook and seemingly dilutes the concept of product liability) shift all responsibility and legal liability for bad outcomes back to the prescriber alone? Would this be a reasonable assignment of liability if there is some inkling that the manufacturer may have been aware of problems, but “failed” to make the public (FDA and physicians)aware?
Do the payers (Medicaid/Medicare/Private Insurers) have liability because they continue to pay for medications for populations where harms have been identified? Using the example of atypical antipsychotics - does a Medicare Part-D plan share liability with a prescriber in the event of a medication related death of an elderly dementia patient because the Part D plan continued to pay for the medication even after warnings were added to the labeling?
What if a state AG is suing manufacturers for defective product claims/off-label promotion activity (as many are) and the state Medicaid and other insurance programs continue to pay for the uses which are the subject of the suit? This would seem to be the case in the majority of states where suits are pending.
I’m sure that I do not understand how liability suits against manufacturers in State court interferes with FDA “accomplishment of regulatory objectives.” What regulatory objectives would those be anyway? If there is a problem with a drug, which is revealed through a liability case in state court, would it not be valuable to all to know that evidence? I think I miss Dr. Kessler - and I’m not claiming he was all that great either.
Admittedly these questions call for some degree of speculation… I know there are a few legal minds who check this site, what are the thoughts on this?
Justice in Michigan
Hi Doc Helm - I will try to address some of what you raise, but briefly. A number of these issues have been discussed on other threads here, so you could track them via “preemption” or “Justice in Michigan” (since I’m always honking off about it).
Going backward, David Kessler and David Vladeck recently wrote an excellent critique of preemption that Ed cited. So that can also be searched for here. It was originally in Georgetown Law Review.
I do not think preemption will shift liability to provider. It will keep it with companies and the FDA who will be, in essence, fully shielded. I say this only partly in gest. We will all need “FDA Preemption Survival Kits.” The current Public Citizen kind of guidelines re: use of new drugs will be inadequate in a preemption regime, in which much more will be in the dark, and for much longer, re: drug safety.
Suits from AGs over defrauding Medicaid, Medicare, etc. may be impacted somewhat, but should still be able to go forward under misbranding law, particularly when there is very good evidence of fraud. But these will require the Department of Justice’s involvement as well, as I understand things (not my area, so could be wrong).
Re: civil liability complementing FDA, that was FDA’s own position until 2002 - current administration. (People on the other side will tell you that preemption was also argued during the Clinton administration. That is true, but in a much narrower - and essentially irrelevant - context than it has been argued since ‘02.
There was an excellent JAMA article entitled, “The Role of Litigation in Assessing Drug Risk” in Jan ‘07. Kesselheim and Avorn. It makes the case definitively, in my biased view, that civil liability has only added to FDA’s mission, as you suggest.
All can do for now.
Justice in Michigan
Drawing a bit from yesterday’s NYT, Ed summarizes:
“FDA officials, who once viewed litigation as a tool for aiding oversight of safety issues, now maintain that state lawsuits could lead to an overlapping patchwork of rules that would burden drugmakers and might discourage patients from taking useful meds.”
This is a good summary of the preemptors’ arguments, and one more opportunity to point out how silly they are.
All labeling and other regulatory decisions remain the exclusive province of FDA. There are no “rules” whatsoever to which lawsuits could lead that competed with FDA’s. Zilch. Nada. Nothing. It _is_ possible - and has happened - that lawsuits lead to the uncovering of suppressed or skewed data. This may later contribute to an FDA decision on a label change. That can only be to the good.
In the meantime, as noted before here, there are already differences in different state’s Medicaid formularies, for example, and which, by law, are based on relative safety and efficacy (not cost except when felonious kickback schemes are uncovered). That is why Washington, Oregon, and a few other states were much tighter with criteria for approved use of coxibs.
I’m still waiting for to hear evidence of someone on Medicaid in northern California or western Idaho who became “confused” because of the different guidelines across the border.
Viz: The argument is horse hockey.
HorusCat
Dr. Helm,
It seems to me that you are mixing up a few issues here. If a prescriber chooses to use an atypical off-label, as in your example of the elderly patient, and a bad outcome occurs, then it seems to me the physician would be the one to whom the family may turn for liability, because it is ultimately the physician who has made the prescribing decisions. Common sense dictates that the company could be held liable only if they were urging off-label use and covering up data that showed probable harm. That being said, physicians are protected somewhat by the Standard of Care defense. That is, if it is standard practice to use atypical antipsychotics to control certain behaviors in the elderly, then making that prescribing decision would probably not be viewed as negligent or malpractice.
If a company marketed off-label (as I think BMS did with Abilify and long-term care patients), then a State Attorney General could go after them for Medicare fraud. I suppose, but would have to yield to Justice, that if a company had evidence of poor outcomes in these patients and covered it up, then they could be liable criminally?
It seems that preemption only applies for liability assigned to a pharma company for harm arising from the use of a product. It does seem fair to me that if the FDA has approved the use of a medication and there has been no cover-up or fraud, the company should have some protection from random liability claims, especially if the product is adquately labelled. There are always going to be adverse events associated with prescription medications–that is why they are prescription.
HorusCat
Let me clarify–if an adverse event occurs that is clearly discussed in the labelling, it seems that a company should have some protection.
Justice in Michigan
HC writes: “It does seem fair to me that if the FDA has approved the use of a medication and there has been no cover-up or fraud, the company should have some protection from random liability claims, especially if the product is adquately labelled.”
I agree with HC on this. As has been discussed, FDA preemption as it is being makes no exception for cover-up or fraud. Companies would still be shielded from lawsuits brought by patients (or their survivors) who believe they were injured.
Companies _would_ be theoretically liable for action taken by the Justice Department and the FDA’s Office of Criminal Investigation. But, as has been reiterated, (a) such actions almost never happen, (b) the results are most often slaps on the wrist when they do, and (c) the injured or their survivors would have no means of reparation for injury as things stand.
Keep in mind, too, that, legally, the “label” includes marketing materials. Merck, for example, was warned twice about “false and misleading” such materials in about as strongly worded warning letters as such letters get.
So some of this also depends on what you call the “label” - just the package insert or the various other communications a company might make about their product.
The FDA concluded in these instances that Merck’s promotional material was demonstrably false. And had the grounds to show it was deliberately so. But, as typical, nothing happened except the warning letters.
What do people think - was the “cardio card” distributed to physicians shortly after VIGOR fraud, as the FDA itself concluded?
Or wasn’t it?
Justice in Michigan
In case folks don’t remember, here is an excerpt from FDA’s second warning letter in September, 2001. As they note, it was, indeed, a second warning about similar behavior.
Question especially for people in industry. If the facts are as the FDA represents them, do you believe that they should have figured into any potential liability?
Alternatively, do you believe that misreprentation in marketing to physicians is the kind of behavior that should appropriately be given a good deal of leeway?
When FDA wrote that Merck’s actions raised “significant public health and safety concerns” do you believe this was appropriately stated? Do you believe that the FDA describing promotional materials that “misrepresented Vioxx’s safety profile” reflects a misunderstanding of legitimate business practice?
These discussions are particularly useful when there are particulars to deal with. We rarely do that.
********************************************************
FDA Warning Letter to Ray Gilmartin
You have engaged in a promotional campaign for Vioxx that minimizes the potentially serious cardiovascular findings that were observed in the Vioxx Gastrointestinal Outcomes Research (VIGOR) study, and thus, misrepresents the safety profile for Vioxx. Specifically, your promotional campaign discounts the fact that in the VIGOR study, patients on Vioxx were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator non-steroidal antiinflarnmatory drug (NSAID), Naprosyn (naproxen).
Although the exact reason for the increased rate of MIs observed in the Vioxx treatment group is unknown, your promotional campaign selectively presents the following hypothetical explanation for the observed increase in MIs. You assert that Vioxx does not increase the risk of MIs and that the VIGOR finding is consistent with naproxen’s ability to block platelet aggregation like aspirin. That is a possible explanation, but you fail to disclose that your explanation is hypothetical, has not been demonstrated by substantial evidence, and that there is another reasonable explanation, that Vioxx may have pro-thrombotic properties.
You have also engaged in promotional activities that minimize the Vioxx / Coumadin (warfarin) drug interaction, omit important risk information, make unsubstantiated superiority claims against other NSAIDs, and promote Vioxx for unapproved uses and an unapproved dosing regimen. In addition, in misrepresenting the Vioxx / warfarin drug interaction you also misrepresent Vioxx’s safety profile by minimizing the potentially serious risk of significant bleeding that can result from using Vioxx and warfarin concomitantly.
Your minimizing these potential risks and misrepresenting the safety profile for Vioxx raise significant public health and safety concerns. Your misrepresentation of the safety profile for Vioxx is particularly troublesome because we have previously, in an untitled letter, objected to promotional materials for Vioxx that also misrepresented Vioxx’s safety profile.
HorusCat
Justice,
I do think that the use of false and misleading information such as Merck apparently used should be figured into liability. The assumption the company makes is that marketing materials aid their sales, so if they use misleading materials that make unsubstantiated assertions, they should be liable for that.
There should be some sort of escalating fine for using materials repeatedly–you get one warning letter (because sometimes the pulled material isn’t fraudulent, the FDA just feels it might be interpreted as making a false claim); then if you make the same material claim, you get hit with a big fine.
We’ve occasionally had marketing materials pulled. One recently was some long-term efficacy data that might have been interpreted as implying we have a maintenance indication with the drug. I don’t know if the FDA pulled it or if our DMT did because we are very close to getting the indication and didn’t want to do anything that might jeopardize that. (Ironically, the closer you are to getting an indication, the closer the FDA watches you to see if you talk about it. If you talk about it, then they withhold the indication. That is why sales typically knows so little about new indications and new products–they don’t want us to be able to talk about them and possibly jeopardize approval.)
So was Merck suggesting that the reason Vioxx had a higher rate of MI was because the other NSAID was acting as a cardioprotective agent? They were saying that the Vioxx rate of MI was the baseline, and the other NSAID represented prophylaxis? I can’t believe a phyhsician bought that—we’d all be popping Naproxen and to heck with our tummies.
Justice in Michigan
Thanks HC - I’m glad someone from industry was willing to respond!
Yes, as FDA reports, Merck “explained” VIGOR by saying that naproxen must be cardio-protective. But, as I recall, the “headline” of their materials was something to the effect of Vioxx being shown to be fully safe (and this after FDA Advisory had suggested label change in other direction).
It is hard not to believe that this was knowing misinformation.
My sense is that most physicans just focus on the headline if they are using a drug without problems (or obvious ones) with their own patients. They take it as a bit of reassurance to keep doing what they were already doing, just as most of us do in our work. All is well, etc.. Most of us don’t look for reasons to change course but to stay on them.
Since this kind of thing, in promotional stuff, is extremely common - much moreso, I think, than fraud in clinical trials - my more basic question is whether people put this in the category of “business is business” or believe it appropriate and realistic that companies not only should, but generally do, hold themselves to a higher standard.
Former Pharma Marketing Executive
Justice,
I believe that the misleading information in Mercks packaging materials should be figured in the liability issue.
Additionally, I think that misrepresentation of information to physicians also needs to be addressed. They are doing this to increase sales only and that could lead to potential harm to the patients, as it certianly did in this case with Merck. As I have said before, the downside of all of this is that Vioxx is a really good drug, if Merck would have managed it better and been more transparent with the cardiotoxicity issue, the drug would have continued to do well for them. It was very aggressive and risky behavior on their part and they are paying the price for it.
It is easy for us to play Monday morning quarterback, but clearly the FDA should have taken a much firmer approach on this second warning.
Like the FDA said, Merck should have disclosed the shortcomings of their data. As it was it completely downplayed that what they were suggesting was merely hypothetical.
Can anyone say if physicians learned anything from this? I wonder if post Vioxx, physicians are less inclined to “fall” for these aggressive type marketing campaigns.
In the end the FDA needs to be more strict in its review of marketing material. It was too easy to become complacent and think that if this was approved, somebody must be checking the data?
This is where we in industry can and should scrutinize each others information. If the FDA misses these issues at least our competitors will not. This way patients and physicians stand a better chance of not bein so misled.
Interesting quesitons…
Justice in Michigan
Thanks for word, FME. Under FDAAA, FDA does have more power on paper to levy fines as well as issue warnings for this sort of thing. Whether they have the culture, and the leadership, to do so are entirely different questions. In general, warning letters alone have dropped precipitously over the last eight years - from 70 or so per year to 20 something. I don’t see that trend changing soon.
I hear what you say about competitors, but I’m wondering if there may not also be a kind of compact - “I won’t rat on your misleading promo if you don’t rat on ours.” That would also be in everyone’s “interest” (except docs and patients).
Once again, all of this would be outside the sphere of potentially relevant grounds for liability if/when preemption goes forward. So I am continuing to work on my Post Preemption Survival Kit.
Re: docs, there appears to be more cynicism but it would take a good study to really know. Anybody know of one?
Janet
Companies are required to submit copies of promotional materials to the FDA when they are first used. However, given the volume of materials for review, it is doubtful that the FDA has the resources to review all submitted pieces. Also, you have organizations like Washington Legal Foundation (WLF) complaining about how DDMAC letters impinge on free speech.
http://www.wlf.org/Resources/DDMAC/default.asp
M Helm, MD
J.I.M. and others,
Thanks for the excellent discussion and references to other sources. In answer to the promotional material question, when I was on the PhRMA side of things, we used to seek out the competitors promotional material and “home-made bread” to point out any misleading claims to DDMAC. The same was done to the companies I worked for. The rationale for this was not to ensure that physicians were not mislead or confused or to protect patients, it was merely to mess with the other guy’s marketing and sales operations.
Here’s a slightly different scenario: an atypical antipsychotic is promoted shizophrenia and bipoar disorder to a group of physicians - pick any one of the following: Child and Adolescent Psychiatrists, Pediatricians or Family Practitioners. Samples are left, even though these physicians never treat an adult patient who would fall into a category where there was an approved indication?
Is that misbranding? Is the prescriber left entirely holding the liability bag? Lets say a child is allegedly injured due to the prescribers decision to use the medication for presummed Bipolar Disorder in a preschooler. If the prescriber’s medication choice was made in part because samples are available and the prescriber was detailed on the drug, hasn’t the company invited a liability suit if the company directed the reps to call on and sample the phsycian?
To me it seems they have.
This is one of the several reasons, I typically avoid prescribing a new drug for several years. I don’t want to be the one using it incorrectly when there is not much know about it in clinical practice.
M Helm, MD
Oh, one other comment about MDs and whether or not we have learned anything since Vioxx… Did the prescribing community learn any thing from Baychol, Rezulin, Seldane, Trovan, Ketek, Propulsid, Zelnorm, etc. ad nauseum?
I still hear of MDs who believe that celecoxib is safe (according to some, the only safe option) with warfarin. There is clear documentation to the contrary, including in the prescribing information. However, though acetaminophen, opiates (not desirable) and non-acetylated salicylates (which hardly anyone even remembers) are still reasonable choices - safer and cheaper - no one likes to be reminded of that.
This does not mean that physicians as a group are stupid; rather, I think, hopeful, trusting, willing to please, and a little less skeptical than would be healthy for everyone involved. Kind of like the human equivalent of black lab retrievers - though with generaly less drool.
Justice in Michigan
Great comments, Doc.
Re: Janet’s point, yeah, lots of factors. As has been pointed out many times, and especially during the current administration, by the time DDMAC reviews material it is often no longer in use. Not much control there….
Does the WLF believe that promotional materials are OK even if they directly contradict facts known by a company, or, indeed, by FDA?
This was my initial question - whether “false and misleading” in a promotion to docs context ought to be viewed differently (as far as liability) than knowing misinformation in clinical studies?
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