White House Backs Preemption In Wyeth Case
64 CommentsBy Ed Silverman // December 27th, 2007 // 11:03 am
Once again, the US Solicitor General has lined up in support of preemption, a concept that, essentially, states FDA approval of a drug preempts state law claims challenging the safety, efficacy, or labeling. At issue is whether patients can sue a drugmaker through state law when a product has already been approved by the FDA, a controversial notion that is now making its way to the US Supreme Court.
In a related action, the Bush administration recently told the Supremes that FDA-approved medical devices are shielded from product-liability lawsuits in state courts. That position backs Medtronic in a case that has broad implications for devices makers. Unlike medical devices, however, there is no statute providing for preemption for drugs.
Nonetheless, drugmakers and the FDA argue that premption does, indeed, exist by maintaining that the agency’s actions are the final word on safety and effectiveness. The issue has become so contentious that the Supreme Court will, in fact, review a preemption case involving the Rezulin diabetes drug in February. For this reason, the Solicitor General’s brief in a case involving a Wyeth drug was widely anticipated. [UPDATE: On Dec. 28, a loyal reader pointed out that former FDA commish David Kessler and David Vladeck, a Georgetown University law professor, penned this recent essay arguing against preemption.]
In its latest opinion sent to the Supreme Court (here it is), the Solicitor General disagrees with a ruling by a lower court - in this instance, the Vermont Supreme Court - that supported a patient’s right to sue Wyeth over the labeling for Phenergan, an injectable drug. Diana Levine, a professional musician, went to the hospital for treatment of a headache and, after being injected, was left with injuries that led to the amputation of her right arm.
Levine successfully argued that, even though the Phenergan labeling complied with FDA requirements, the adequacy of the warning still wasn’t established. 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, by the way, was awarded more than $6 million.
The Solicitor General, however, sides with Wyeth. “If manufacturers were free to make unilateral changes to labeling the day after FDA’s approval, based on information that was previously available to FDA, the approval process would be greatly undermined and the agency’s careful balancing of risks and benefits thwarted,” the Solicitor General writes.
Nonetheless, the Solicitor General recommends that the Supremes hold off on granting Wyeth’s request to hear the case until the Medtronic and Rezulin cases are decided.
Hat tip to Drug and Device Law
Justice in Michigan
Thanks, Ed. As the DDL guys agree, the Wyeth case is “the big one” as far as FDA labeling preempting all failure-to-warn claims in the drug arena are concerned.
In case there’s any uncertainty, “state law,” in this context, mainly means the right to bring suit against a drug company for failure to warn.
So the preemption argument is premised on the notion that FDA labeling is sufficient to trump whatever else may turn out to be true - delay in reporting, spinning reporting, cat-and-mouse reporting, warning letters over “false and misleading” info dispensed (”cardio cards” etc.), suppressed internal studies, camoflaged reporting intimidating researchers, changing endpoints after the fact, etc.: All the kinds of behavior that now figure into a company’s potential liability - would be irrelevant.
Instead, a company would be fully shielded, with the possible exception of felony fraud, which the DOJ would have have to take upon itself to (a) discover (which usually happens through whistleblowers) and (b) prosecute (almost always settled beforehand). So, as far as a day in court for legitimate claims - Sayonara.
Below is the relevant section of the FDCA about which there is debate re: whether a company can take it upon itself to issue a warning prior to a formal FDA labeling change [my emphases].
Preemptors find a hundred ways to say it doesn’t say what it clearly says {”depends what ‘is’ is,” etc.). Anyone see any ambiguity?
21 USC 201.57 (e) Warnings. Under this section of the section heading, the labeling
shall describe serious adverse reactions and potential safety hazards, limitations in
use imposed by them, and steps that should be taken if they occur. The labeling shall
be revised to include a warning _as soon as there is reasonable evidence of an association
of a serious hazard with a drug_; a causal relationship need not have been proved.
21 USC 314.70 (c) Supplements for changes (in labeling) that may be made _before_ FDA approval “Special Supplement-Changes Being Effected.â€. . . (2) changes labeling to accomplish any of the following:
(i) to add or strengthen a contraindication, warning, precaution, or adverse reaction;
(ii) to add or strengthen a statement about drug abuse, dependence, or over-dosage;
Or
(iii) to add or strengthen an instruction about dosage and administration that is
intended to increase the safe use of the product;
(iv) to delete false, misleading, or unsupported indications for use or claims for
effectiveness.
Nathan
Obviously for those of you familiar with my posts, I’m biased. I work at a drug company. That said, I think it is just stupid to allow state lawsuits against a drug company that is clearly complying with FDA policy. If the policy isn’t strict enough, then tighten up the FDA approval/labeling policy (this already seems to be happening). If I’m not mistaken, federal law always trumps state law. Why should it be different for drug manufacturers?
If we (the drug companies) are clearly in-line with FDA policy and we have not commited fraud, then we should be exempt from product liability lawsuits.
Justice in Michigan
Nathan - Believe it or not, I agree with you. FDA compliance is _already_ a part of almost all “failure-to-warn” lawsuits, and it should be.
The issue comes down to what “clearly complying” means. As you know from the inside, there is a lot of “wiggle room.” Unless one had a Stalinist-sized FDA (which no one wants), the agency itself could never cover all of this. The question becomes when a “wiggle” rises (or falls) to the level of reasonable liability.
No, re: federal law and state law, there is a “presumption against preemption” constitutionally. Thus, all the things that states regulate on their own - licenses, etc.. The “supremacy clause” (fed preempts) comes into play when there are clear constitutional circumstances (e.g., states can’t reinstitute slavery) or - and this is mostly the argument here - when there are “implied” reasons to assume fed law preempts based on an interpretation of the will of Congress. That’s way over-simplied, but hopefully it conveys the gist.
BTW, the people I know within industry are split on this question. Some argue as you do. Others see the potential havoc that could result if we relied _solely_ on FDA regulation. That is usually because they have seen - in their own experience - how easy it is, in actual practice, to “sneak one by” the agency. And how, inevitably, it always will be for those companies that are inclined - hopefully, more and more rare.
That is clearly true with the FDA we have. As above, it would be true (if to a lesser extent) with a better one. That is why (until the current administration) FDA itself argued for _both_ state tort liability and FDA regulation as generally complementing consumer protection.
Both systems are _very_ far from “perfect.” So the core is whether, overall, citizens are better served by having both in this arena rather than only one.
henry
The FDA is not independent of political influence or special interests, which is not a great surprise, since it is a government body. however the law (the written word) is supposed to be balanced and unbiased. the only way patients with legit cases can get justice is to go to court. If this right is taken from us, what alternative do we have. Will the FDA take it up with the pharmaceuticals who pay them? So far they have not.
Nathan
Henry,
I’m not suggesting that people not be able to go to court. I’m suggesting that they due so in FEDERAL court rather than state court. The Federal government sets the standards for drug approval and drug safety. Therefore, violations of that standard should be tried in a federal court. Am I missing something?
Matt
And we all know whose best interests the FDA serves…
todd
Yes Matt, the population of the US. Otherwise we would have a life expectancy of 45 years old, like we did before the innovation of pharma was introduced to the world.
Is it perfect? No. But show me ANYTHING that involves more than 1 person in this world that is perfect (my house excluded of course). Should we try to improve it, of course. Should we try to develop alternate energy sources, of course. Should we try to eliminate racism, bigotry, and sexism, yes. Should all NFL games be on free TV, yes.
See, we could do this all day. From the big issues to the little ones, perfection is never achieved.
Justice in Michigan
Hi Nathan - If FDA preemption is upheld, there will be no civil liability for “failure-to-warn” in any court, state or federal. I know - it’s hard to believe, given what we have taken for granted as the justice system.
There would probably be some version of a “fraud exception,” but - for reasons I won’t bore you with (unless you ask) - it would be de facto meaningless.
The most one could anticipate as far as compensation in a very large case (larger than anything we’ve ever seen) might be some version of the way the asbestos litigation was finally worked out. But that is entirely speculative on my part.
henry
State laws can dictate conduct of clinical trials. clinical trials are the basis of the benefits and risks data, which the FDA base their approvals and warnings on. In my experience, drug companies hide high risk data, they have a number of ways of doing this, political friends, KOLs, computer programming, outsourcing. I would assume the federal courts come into play when freedom of speech or information are argued, rights to access safety data (commercial interest) which currently the federal government and drug companies hide behind. I am not a lawyer so I could be wrong.
Perfection is not the answer. However, if a marketing campaign orchestrated by a pharmaceutical company injures one person because data is supressed it is a criminal act… “intent to harm”.
Justice in Michigan
Hi Henry - It is my understanding that the conduct of clinical trials is regulated by the FDA, and is thus under federal, not state, overview. Whether data is hidden, fudged, etc., would also be under FDA’s Office of Regulatory Affairs; potentially, the Office of Criminal Investigation and the Department of Justice if fraud is suspected.
History suggests that FDA virtually never moves to prosecute intentional fraud, which is a criminal felony. This is understandable. Their mission is public health, not law enforcement. Thus they have been ready to make settlements in which companies admit no wrong-doing, a label is changed or a batch withdrawn, perhaps a small fine (relative to industry revenues) is levied, and there is no attempt to prove “intent” and no prosecution. (So these end up being misdemeanor, not felony, charges). Likewise, FDA, of course, has nothing to do with compensating whomever may have been injured.
The latter has been the role of the courts. And thus FDA has relied on civil liability (unfortunately, from the perspective of preemptors) to levy more significant penalties, hold companies seriously accountable for serious misdeeds, and compensate victims.
If FDA preemption is upheld - as it may very well be in the Roberts court - the three items listed in the prior sentence will, essentially, disappear.
ol cranky
Henry:
The states don’t review and rule in on clinical trial design or conduct. Trials in the US are performed in accordance with CFR (as well as ICH) and are approved by local and/or central IRBs that meet DHHS assurance requirements. There may be some state limitations that impact Clinical Trial Agreements and/or the Informed Consent Forms, and I think some states may consider requiring certification of physicians to conduct trials, but these don’t provide any support for any argument against federal preemption.
BTW, am I the only one confused as to why the Levine case is even one in which the manufacturer (and labeling) are to blame? Just like the case with the Quaid twins’ heparin overdose, this was a case of HCP error leading to injury.
Justice in Michigan
OC - I agree it’s not the greatest case from the litigant’s perspective. Personally, I would much rather see preemption tested within one of the high-profile sagas - like Vioxx, Rezulin, or Baycol - where you have both FDA compliance (despite a few warning letters) and the question of whether that fact should shield the companies from liability more finely drawn.
Lisa Van S
NJ Law has a very stringent “failure to warn”. With that said, maybe abortion should be outlawed… May the debate begin!!
Hank
Hi Lisa - OK, I give up. I don’t get it. Is it a girl thing?
ol cranky
Lisa:
Are you saying that the patient(s) are not being adequately warned of potential side effects? If so, unless you manufacturers are routinely hiding reported serious/significant AEs reasonably considered to be related to a treatment, it’s very much an FDA issue. FDA does a bottom up review - they get the data sets and have been known to analyze the data often using different statistical methodology than planned in trials. While I do think there are examples of companies playing foot-loose and fancy free with safety data, I don’t think it’s the norm in analyzing clinical trial data or review of the ISS.
In the absence of overt fraud, in the Levine case, failure to warn would be a matter of lack of informed consent by the patient. This is a burden of the HCP.
University Update - Georgetown University - White House Backs Preemption In Wyeth Case
[...] Virginia University White House Backs Preemption In Wyeth Case » This Summary is from an article posted at Pharmalot » News, Comment and Conversation on [...]
Ilena Rosenthal
The FDA recently chimed in on it’s own inability to do it’s job. It illlustrated that perfectly by giving silicone breast implant manufacturers a green light.
Here’s an excellent new report on FDA impotency.
EXCERPT:
The FDA cannot fulfill its mission because its scientific base has eroded and its scientific organizational structure is weak.
Complete report here:
http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4329b_02_01_FDA%20Report%20on%20Science%20and%20Technology.pdf
Ilena Rosenthal
Just read some of your comments on ‘clinical trials.’ Very interesting.
In the breast implant debacle, in some of the so called ’studies’ only around 5% of the women had follow up.
These studies were easily skewed, for example, when a woman removed her implant for any reason, she was dropped from the study.
And although there were ‘conditions’ put on the plastic surgeons, there is nothing in place to see that they are followed. Once a woman has been implanted, there is nothing to encourage the plastic surgeon to report failures and illnesses, nor see that she pays for and undergoes the MRI’s the conditions require.
Justice in Michigan
Yes, another of the big FDA studies of the past few years all of which have essentially said the same thing. Most of the responsibility resides in Congress, which every now and then adds mandates or powers to the FDA but not the means to carry them out. Responsibility also resides in several of those in FDA senior management.
Re: preemption - where this thread began - I think the more encompassing point is as discussed above. FDA regulation and civil liability do not cover the same ground, and ought not try to. Both are far from perfect. But, at their best, they provide complementary instruments of accountability and protection that neither one could provide alone.
henry
the state does not rule on clinical trials or conduct (who does? the IRBs!!), but there are individual state laws enacted that address patient liability, informed consent, insurance and HIPAA. This is becoming an issue for corporations it appears (the case above is post-marketing -different but related) and the feds have intervened, if I understand the opinion.
The CFRs are technical and deal with the operations of the trial and drug applications/labeling etc. This case highlights how patient safety is ignored while the courts and corporations bicker over outdated laws.
It is the responsibility of the FDA to provide the general public and their doctors with the results of scientific research, which is fairly accurate, (we are not asking for much). If the FDA becomes aware that data was comprised, it is their responsibility to investigate and report (to who? I don’t know!), maybe the DOJ which is also a political body and will ignore (CIA tapes comes to mind)! So it comes down to individuals and hopefully the state (only hope) vs. (special interests) pharma, the FDA, DOJ, OIG, Bush administration and in one year the democratic administration
ol cranky
Ilena:
I’ve never worked on a cosmetics program but in many clinical trials of drugs and devices, subjects are discontinued from the study when they discontinue the treatment under evaluation - follow-up post last exposure to the study treatment depends on things like half life, etc. Onset of new Serious Adverse Events are reported if discovered by study staff (at the enter following the study subject); SAEs that are considered possibly related to the treatment under study and any non-serious AEs that are considered possibly related are entered into the safety database and are to be followed through resolution of achieving a new baseline. These are addressed in the clinical study reports and/or IND annual reports and/or integrated summary of safety submitted to the FDA. Staff at the study center (including, but not limited to the principal investigator) are the first line to make sure that information is documented and reported. For the record, we do at least try to actively follow up with study subjects who discontinue due to an adverse event and the FDA has actually been a little more stringent with companies to document reason for any withdrawn consent to continue study participation since this can mask possible adverse events that hasn’t been reported.
There are conditions put on study investigators and they are followed up and evaluated during routine monitoring (we do actually go out to the sites to ensure the protocol and regulations are being followed as well as ensure accuracy of the data collected, etc.) Outside clinical trials, HCPs are supposed to report adverse treatment reactions (basically any noted adverse event that is considered even remotely related to the treatment) via MedWatch. I’m sure there’s something similar in place for aesthetics/surgical implants/devices.
Another item of note regarding follow up is that you can’t force someone to follow up. I’ve actually worked on long term morbidity and mortality trials in which subjects were still followed up after discontinuing study treatment and some of them get really annoyed (to say the least) when contacted months or years after their last treatment visit but the study was still ongoing.
todd
You don’t think that before this chick got her shot — which BTW she was probably ticked because she was an abuser looking for Demero (personal bias) — that someone somewhere said “Do you want us to give you a shot that might help, there are some side effects but most people get along fine”. You think she then said “Well, tell me every weird thing that has ever happened to anyone who has ever taken this drug - even if it wasn’t proven that the drug caused it”
Does anyone in the world think that anything in the world is pure benefit and no risk? You can’t cross the street without the possibility of getting hit. You can’t eat an M&M without increasing your risk of obesity and thus MI, CVA, etc.
Has anyone heard of an arm falling off because of promethazine? I am assuming this was an IM injection not an IV - which does place the blame squarely on the ordering physician. Although the IV would have lessened the risk of an arm falling off, it would have increased risk of clots and infection. Then the lawsuit could be for death from a emboli because a drug was given IV, but could have been given IM. Everything in life has a risk, the sooner the “less informed” realize this the better. No free lunches in our society (not even for the docs, everything has a price and cost).
henry
Take the drug off the market. risks outweigh the benefits.
Headache, nausea vs. possibility of amputated limb or blood clots-ae just reported.
The company submitted adverse event information following label decision by the FDA.
The doctors have their responsibilities and trained to make informed decisions for the rest of us poor mortals (that is why they spend 10 years in training). Perhaps the patient’s MD was wined and dined by Wyeth, maybe not.
Phenergan is used to treat allergy symptoms such as itching, runny nose, sneezing, itchy or watery eyes, hives, and itchy skin rashes.
Phenergan also prevents motion sickness, and treats nausea and vomiting or pain after surgery. It is also used as a sedative or sleep aid.
Side effects: (Would you take phenergan for a runny nose?)
Angioneurotic edema. Neuroleptic Malignant Syndrome (potentially fatal) has also been reported…
(How many cases, it is not mentioned in the label).
Administration of Phenergan Injection has resulted in nerve damage ranging from temporary sensory loss to palsies and paralysis. Injection into or near a nerve may result in permanent tissue damage. Subcutaneous injection has resulted in tissue necrosis. Injection site reactions including burning, erythema, pain, and edema have been reported. Administration of Phenergan Injection has resulted in abscesses and/or tissue necrosis and gangrene, regardless of the route of administration.
SAEs are subjective, pharma and the FDA think one way, the public have different ideas.
Many patients enrolled in a study have a good relationship with the study investigator, so follow up should not be an issue unless there is an issue.(hidden agendas)
todd
henry, are you serious about the rep “selling Phenergan” - let me look at a calendar, nope it isn’t 1987. someone from wyeth tell me the last decade it was promoted. and then it was the best answer we had. great job in looking in a PDR. look up any drug and see a similar list — especially any parenteral (look it up) product.
So, please look in ANY hospital - it is generic promethazine and has been for years. Instead they will now use a more expensive BRANDNAME produt, about 100 times as expensive. now if the anzemet rep was selling against the ADR’s of phenergan this same group (you) would be complaining about that! i am not disputing that with the current info there are few uses of IV phenergan. but we can say the same about demerol and it hasn’t gone away. there is no reasonable way you can pin this on a manufacturer.
todd
oh henry - when it states cases of “whatever” have been reported -that is not a causality conclusion. and if you haven’t used an antihistamine for sleep induction, a cold, or allergies you are the one guy on the planet.
Justice in Michigan
To Todd - Do you have reason to think this “chick” was a Demerol abuser?
As I understand it, the choice was between an IM injection (which she had) and then progressing to a “push-IV,” which they gave her when the first didn’t work. On one level, the case is about whether the labelled warnings about push-IV of phenergan are sufficient. On another, it’s about whether the FDA-approved labeling on this shields all claims that the company could and should have done more to warn on push-IV, based on what they knew. Whether there is more “background” re:the latter, I have no idea.
As far as “all drugs have dangers,” yeah, we know. Those are never the relevant questions. The questions are:
1. What did they (the company) know?
2. When did they know it?
3. What did they do?
Most people I know don’t want a “risk-free” life. They just don’t want to treated as disposable and f’d over.
Re: Henry’s earlier post, yeah, the it is ideally the FDA’s job to investigate compromised data, and sometimes it does. But often enough it doesn’t, partly because of politics, as you say, partly because of resources, and partly because (as in earlier post above), they are not primarily about policing. Yet again - that is why whistleblowers and civil actions are usually how we find out (and how the FDA finds out).
todd
Justice - I know you are right, I am very biased. I would say, from the hospitals I have worked, 17 of 20 people who come to the ER for a migraine are narcotic seekers. So I really don’t know and it is unfair to say that, but kind of like “reported cases”. In my experience the odds are with a narc addict, but I really don’t know - and I freely admit it.
Let me ask this though - if it was not brand name Phenergan used (which I doubt), why would it be up to Wyeth. Sue Baxter or Hospira (see Randy Quaid) - the likely manufacturer.
If this is the new standard, as soon as any product goes generic the innovator should immediately pull it from the market and let someone else worry about it. I would guess the volume of brand name Phenergan sold is well under $10 million. And when you did use brand name Phenergan it was only because the generic manufacturer had a production problem. So if there were no suitable replacement (as there is in this case), would the manufacturer look bad for pulling their product as soon as it went generic and there was a shortage?
So looking at your 3 questions - if you are a generic manufacturer and not looking for anything are you responsible?
Furthermore, I don’t think anyone could argue that Phenergan is better for N/V than the serotonin agents. The only reason is COST. That then throws it into the hospital formulary and policy and procedures doesn’t it.
I know when the new warning came out about 18-24 months ago (I can’t really remember, it was in the past) - one of the hospitals I consult with had us immediately change ER policy and procedures as well as all standing orders to one of the serotonin agents.
So this happened because people were more worried about $$$ than safety. Again, decide if you want the newest and best for some or affordable health care for everyone.
Justice in Michigan
Thanks for the interesting reply, Todd.
Just on the generic question, I agree it’s complicated. As you may know, there is a an important preemption case out there which is Colacicco v. Apotex (or the other way around, depending on who is appealing, when). It’s about generic Paxil.
So should Apotex be held accountable for what Glaxo _might_ have done or not done? Personally, I don’t think so. ANDA labeling (and I assume any updated, supplemental labeling) are based on what brandname does. To that extent, even if the phenergan was generic, I think _potential_ accountability goes back to Wyeth (again, assuming generic manufacturer did all right things re: labeling which is the issue in this case, and - of course - there is no independent issue of bioequivalence, manufacturing defect, etc)).
Your hypothetical is interesting. If brand went entirely out of business and gave the field over to generics, who would they be responsible for updating potentially new info? No idea!
Also, good question at the end. As I understand it, Levine also sued the ER (successfully) before Wyeth.
TOdd
Justice, thanks for the legal side of things. Very helpful for this post and site! Happy New Year’s everyone, see your posts in a week (or so).
Dianne
Justice in Michigan Re: preemption - One has to ask who benefits from preemption. Not the consumer. We need the checks and balances that our tort laws were intended to provide. If a federal agency alone is allowed to make the law, change the law, and adjudicate the law–who is doing the checking, where is the balance?
Justice in Michigan
Hi Dianne - Well, it’s always interesting to play the “devil’s advocate” (devil in eye of beholder).
Checks and balances usually have to do with different braches of the fed gov - exec, judiciary, legislative. Whether the model can be stretched to include FDA and civil liability is at least a question. The FDA is a rather strange creature of all three of the “usual” branches. Congress makes the laws that govern it and supplies its funding (now in collaboration with industry via PDUFA). It is under Health and Human Services, and thus part of the Exec. And has much to do with Judiciary via its (often sadly inadequate) Office of Criminal Investigation and, of course, its recent promulgation (back to the current Exec. branch) of preemption
In any case, with regard to preemption, I would say it is mainly an issue of two systems _complementing_ each other, and each covering arenas that the other does not. But that may be semantics. Either way, we agree that, for all its warts, the system as we’ve known it is better than killing off a key part of it - better for legal rights, and better for public health.
The real core of the “other side” is that allowing _any_ lawsuits is, de facto, a bad thing. Thus there are still those who argue that “a few thalidomides” here and there are a “small price to pay” for keeping keeping those trial lawyers out of industry’s way. That’s basically the ideology behind most of the “Judicial Hellhole” crowd (and their sponsors).
Everyone should hang out with the other person’s ox. Then we’d see who is truly ready to accept being gorged with impunity.
Justice in Michigan
Whoops - a holiday season slip. The ox was gorged rather than gored. Bon appetit, Ox!
Dianne
Agree, however, I am referring to the FDA’s preemption policy that individuals injured by FDA approved drugs would not be compensated, state law would be invalid, and the drug companies would only answer to the FDA. If that, in fact, becomes the case, then the FDA rules. There will be no recourse. Tort laws bring balance as it keeps big business and big government in check.
“Why have states always supplied a body of law that enables one person to sue another for wrongs? Law professors today tend to suppose that tort law functions as a disguised form of safety regulation (one that deters unsafe conduct with the threat of liability), or a disguised form of localized disaster relief (one that provides compensation to injured victims). Attending to tort law’s place within our constitutional order helps us to see that these accounts are misguided. Access to tort law has been constitutionally guaranteed in part because it does something that safety regulation and disaster relief schemes do not: It identifies duties not to injure that citizens owe to one another, and, at least in principle, it arms each beneficiary of such a duty with the power to demand redress from one who has breached it.†- —John C. P. Goldberg is Associate Dean for Research and Professor, Vanderbilt Law School.
Justice in Michigan
Onward, Dianne. I agree with Goldberg, but I also think civil liability _also_ has to do with deterrence of misdeeds (fraud, etc.).
In the specific case of drugs, civil actions have additionally unearthed important safety data not otherwise known. See the article by Avorn and Kesselheim in JAMA from January 16, 2007 - “The Role of Litigation in Defining Drug Risks.”
They specifically discuss what we learned about Vioxx, Baycol, Zyprexa, Paxil, Rezulin, and other drugs that would almost certainly not have come to light without litigation. That is in _everyone’s_ interest, not only those injured and who deserve redress.
(The JAMA piece, btw, was written specifically in response to FDA’s wider claim of preemption in January, 2007. If I may say, it means something when you see a pro civil liability commentary even in JAMA!)
henry
All experiments are subject to analysis. If companies do not release important safety data this is not science, it is marketing.
There is a place for pharmaceuticals and scientific research, but please take the money out of it, they don’t mix. how much does a limb cost? please don’t distract with attacks on character and generics. Have the guts to argue the case. Scientists have a different ethos than wall street, not a surprise. The law (not science) will decide. Either way we have to live by it.
Justice in Michigan
Maybe this will serve as an appropriate coda to some of the discussion.
I have been working against FDA preemption - and the odious form it has taken in our own state, Michigan - for a number of years.
A couple of years ago I was at a conference in which preemption was discussed. The panel included three pro-preemption people - including Dan Troy, fromer FDA chief counsel and the “godfather” of preemption under the Bush administration - as well as one panelist who raised moderate questions about preemption (the program was organized by the Federalist Society, a conversative group that has been radically pro-preemption).
In any case, the panel was civil and decorous, as these events usually are. After it was over, the moderate guy came up to me afterward (he didn’t know who I was except that my question from the audience indicated I was anti-preemption) and whispered this: “Forget most of what I said up there. Preemption? We know what is it really is. It’s just an f’ing power play.”
Perhaps that’s enough said.
Brian
Money and science will always go together. The scientists need funding..Big time funding. It’s the folks on the other end that don’t understand when they are asked to pay for the result. Man made laws are pretty weak when compared with the laws of nature.. This discussion is way off base
Justice in Michigan
Pretty cryptic for me, Brian. Could you explain how what you write bears on anything specific that has been discussed (there has been a lot), who are “the folks on the ohter end” (are you on a different end?), and what precise bases have been missed?
Genuine questions.
Justice in Michigan
Maybe this will help sharpen things. As noted further up in the thread, there are people who believe - and who say explicitly - that “a few thalidomides” are the inevitable price we pay for progress. And that virtually any kind of regulation as well as civil liability only retard new, innovative drug discovery and development.
It parallels the argument about manned space flight. If we’re going to get to Mars and beyond, we have to accept a few Challengers and Columbias blowing up along the way - inevitable and unavoidable “collateral damage.” (Not that the dead and deformed thalidomide babies volunteered to be pharmanauts, but the “price of progress” idea is the same.)
Is that your point?
TOdd
Justice,
I agree with many of your points, and again thank you for providing an intelligent viewpoint and many valid things to think about.
Specifically, looking at the statement that the : Vioxx, Baycol, etc would not have come to light if lawsuits didn’t appear. I do not disagree that it likely sped up the process, but playing devil’s advocate I will say it might have slowed down recognition as well.
The data was there if you looked for it. When Vioxx launched, the Vigor study was in the PI and to me showed a trend that it should be used with caution and could cause some CV events. I think eventually clinicians would have woken up and looked at the data objectively.
On the other hand, isn’t this similar to reporting mistakes by clinicians. When the threat of billion dollar lawsuit approaches, the immediate result is pure defense and spinning the data your way. If there were less risk in admitting a problem and correcting it, maybe Merck would have come out with a warning much earlier in the process. Maybe even pulled it off the market on their own. It seems to me (again, non-legal type), that by pulling a drug on their own, or putting out their own warning they are really just dooming themselves to losing billions of dollars in lawsuits.
Not saying this is what happened or that it is right - just my feeling. Do you feel this is any way similar to health care practitioners that make an honest mistake, but can’t admit guilt, or even apologize and recognize it for fear of malpractice.
Great to have you on the board - I love intelligent conversation and hope you will continue to check in.
Justice in Michigan
Thanks for the kind thoughts, Todd, and also for your good commentary.
Of course, none of us knows what might have been. Certainly, VIGOR was “out there” in 2000, and FDA Advisory Committee recommended label change in February, 2001, to take account of it. Then the famous 14-month gap before the new label appeared in 2002. Was VIGOR already there in some form on the pre-2002 PI? I don’t recall.
I have never completely understood why Merck fought so hard over that warning. I understand that Celebrex was the competition and had no such warning at that point, and that must have been at the core. Still, given what we know about the impact of PIs on Rx’ing - which was, indeed, shown again when the 2002 revised PI made no difference at all in Vioxx sales - one wonders why they were so preoccupied with it. This is retrospective, of course, but their delaying ended up making the pre-2002 cases against them much stronger than they would have been.
There are, indeed, some who argue that Merck’s withdrawing Vioxx was “blood in the water” for liability suits, and - as you suggest - that that risk can have the perverse effect of keeping companies from withdrawing drugs that they might otherwise.
This is tough to prove. For me, it’s hard to imagine they could have viably kept it out there post-APPROVe results (and especially since the 18-month theory would not have held up, which I believe they knew). And also despite the fact that they could probably have garnered FDA support to keep it out there, although with enough warnings and restrictions that the “blood in water” would, I’d judge, have been even thicker. So, from a purely self-interested perspective, one could suggest their timing was just about right - kept Vioxx alive (and still making $2+ billion per year) through most of 2004; pulled it before liability might have _really_ skyrocketed had they pushed beyond that point. Maybe one day we’ll hear the story from the players.
One could also ask what the actual litigation results suggest about all this. By most accounts, Merck ended up doing quite well. Early estimates were that they stood to lose $15-20 B, possibly go bankrupt and even be bought out by Pfizer. Assuming the current settlement offer goes through, they essentially lost the equivalent of the last two years of Vioxx sales - nothing like the disaster predicted. And the verdicts, most of which they won as you know, don’t suggest the Hellholes are quite as hot as some would suggest!
I think your clinician analogy makes sense. Indeed, companies like this have even more reasons to deny and delay than individuals - shareholder wrath, the scale of the investment, the enormous success of Vioxx (which itself required record marketing investment) from the start, and so on. Pretty hard to pull the plug!
In that context, it’s hard to know how/where anticipated litigation would figure in. For example, if they were shielded from litigation, but they were making blockbuster sales as they were, my sense would be that the other factors - facing shareholders’ dismay (and maybe even lawsuits on that side), failure after enormous initial success, forgoing more return on investment for everyone involved (including psychological return), might have been at least as much disincentive to withdraw as lawsuits.
It’s a worthy question.
Justice in Michigan
p.s. Personal footnote - Because of a sprained hip, I myself was given Vioxx samples in 03. (I didn’t ask for it.) This was by a physiatrist who is considered the best in our area - his practice has been closed for almost twenty years.
VIGOR and precautions were certainly on the PI by then. But the doc never once asked me about CV risk factors (it happens I have a few) nor did have have any other info on me in that regard one way or other. (Except that my mother had two MIs in her 50s, which clearly did not figure into what he gave me.)
Of course, the actual risk of my having a problem was very small. But, being the obsessive guy I am, I read the PI myself. That made the case for me - no Vioxx. But how many _pts_ read PIs? 1 in 20,000?!
It’s one anecdote, but perhaps speaks to the question you raised at the start about how much what clinicians know on this level actually impacts what they do, especially when there are some samples sitting around, and a favorite pt. (we have an excellent relationship) sitting in front of them.
TOdd
Justice,
Thanks for the thoughts. Trying to digest them, but until then…..
FYI - The 6 month VIGOR data was in the original PI, and what MRK used in the fight against Celebrex with their CLASS data. Although the 6 month data was not nearly as damning as the 12 month period, the trend was certainly there.
Celebrex is not as good of a COX2 inhibitor as Vioxx was. And it was interesting how the 2 trials were set up. Vioxx did not allow ASA use in pts - which made their GI ulcer data look better than Celebrex and really allowed them to dominate the market. CLASS (celebrex) allowed ASA and the results showed more ulcers but less GI protection.
If you break out the CLASS data you can see those on Celebrex + ASA were equivalent to a traditional NSAID in both GI protection and CV events. The equivalent of a $150/month naproxen prescription - but I don’t think they adopted that as a marketing slogan. Celebrex alone had fewer GI events but increased CV risk, a trend that I think the warnings are now on all NSAIDs that they can cause CV risk. Am i Correct on that warning?
Now I have my own strategy to provide an NSAID with no added CV risk and protect the appropriate pts with gastroprotection - I won’t get into that here, very off topic. My consulting business helps small hospitals and LTC’s implement intelligent formularies and policies. I can say we never endorsed any of the COX2 for adoption. Certainly it was a challenge as MANY pts were on these meds a few years ago and fought the battle against the drug companies, physicians, hospital administrators, risk of losing accounts, etc. But in the end we always felt that pt care would win out in the end, and it did. In fact I would say our stance won some respect when the saga finally played out. So there are people looking out for patients. I guess you can argue there are not enough and as a patient I can understand how it would be hard to find the right doc. But I guess I don’t have the answer to fix that problem either. I think the most important thing you can do is research, but we all have knowledge gaps and as you state very few pts read PI’s. But at the same time, if the uninformed did read a PI they would be scared to death. Now this doesn’t mean there shouldn’t be informed consent and discussion. So I can’t come up with great pt education pieces without either being too vague (i.e. a lot of “talk to your doctor” lines) or too scary. I guess just like many things in life it is a fine line and we try to find it on a daily basis.
Do you have any opinion on Crestor’s potential future liability given additional adverse effects over other statins but superior lipid lower profile? We believe it has a place, but a very small place. I don’t want to see it off the market, but at the same time as market share I believe is increasing. This suggests to me that more inappropriate patients are being exposed.
Thanks and have a great New Year’s - and get some sleep!
TOdd
As a second thought - now that I walk the line between my consulting and as an industry type I have noticed a few things.
Yes, people can point out the bad marketing that pharma does etc. But at the same time, I have seen where appropriate guidelines were disseminated and adopted by the medical community MUCH more quickly than say the AHA/ACC (american heart/college of cardiology) can get the message out. Again, fine line and the importance of having medical people with integrity in these organizations to influence the marketing/promotion is very important. So there is bad marketing and reps that should not go into docs offices, but if that happens some important advances might go unnoticed by the medical community - hard to draw that line as well.
Chris
Are you aware that the ‘appropriate guidelines’ are often biased efforts by pharma companies? We had a vendor draft the desired guidelines and then convene ‘advisory boards of advocates’ to endorse them. The reason that they are disseminated rapidly and adopted by the medical community is that this is what the vendor was paid to accomplish. Uptake was increased by making sure these same messages occurred in multiple different locations (’independent’ websites, etc.)
TOdd
The ones you refer to are a joke and not taken seriously by anyone. I am referring to national groups : AHA, AGA, APhA, ACOG, etc. These are peer reviewed and published in the big reputable journals - JAMA, NEJM, etc. Consensus guidelines, not special panels are what we look are looking for.
chris, keep getting your paid “pharma whores” to endorse your messages, but they get thrown away faster than it hits the desk. “independent websites” - are you for real? with all the info out there why would a HCP go to a pharma recommended site - they are also kind of busy. Love to see the hit data for those sites.
Chris
The ones I am referring to are published as ‘consensus guidelines’ and are published in well-known journals. These projects were specifically set up to look like independent efforts. As part of the projects, the vendor used many different avenues to communicate the desired messages in ways that appear to be independent, thus encouraging the perception of widespread support. (I will say there have been efforts in the past couple of years by the vendor to clean up these projects to make them more independent and less biased.)
Justice in Michigan
Just a couple…we’ve certainly moved beyond FDA preemption.
Returning to that, I welcomed the opportunity to respond to your (Todd’s) query. Reflecting further, I have at least convinced myself (!) that lawsuits are still more likely to support appropriate accountability than otherwise. Indeed, they can be useful to companies who realize it really is time to bail, but have shareholders and others to worry about. Among other things, they can say: “We might have held out. But those greedy trial lawywers are piling on. If we didn’t withdraw the drug when we did, it would have only gotten worse.”
In fairness, I never heard Merck make those arguments (but I’ve heard it from others who “represent” them). After APPROVe, the jig was up.
And, indeed, Merck’s shares did take a huge hit right after the wishdrawal, but almost all of that has come back last I looked - and share price may even be higher than it was.
So I would still conclude that, in the majority of cases (maybe the great majority), liability serves accountability (as well as appropriate compensation and uncovering otherwise suppressed safety data) in several ways and for several reasons. As referenced in earlier post, Alan Goldhammer, Exec VP of PhRMA, publicly acknowledged that at the 2005 IOM hearings. I would also still suggest that Merck’s own litigation experience shows the “Hellhole theory” to be mostly political propaganda dressed up as “information.”
I’ll check back on the pre-2002 Vioxx label - interesting. Of course, I’m familiar with the famous CLASS 6-months of data publication episode. (My favorite one-liner from that was when FDA’s Bob Temple said that the JAMA “hype” [his word] probabably “has more influence than our labeling does.”
In any event, still wonder why Merck as preoccupied with label as they were. Rx’ing only increased after change, regardless of what was “out there.” I’m not suggesting all pts read PIs. I work with, and have as friends, some of the finest docs in the world. They talk all the time about how hard it is to get genuinely reliable info even on the population level. The indiv. pt. level whole other ballgame. Very glad to hear you played the cox-2s as you did. Some of these docs I mention also did that.
Crestor opens up another issue, perhaps for a later post. I’m far from expert here, but if pts. knew the _actual_ (not relative) risk differences between having having a this or that LDL, they would be a lot less impressed by statins in general for primary prevention (particularly the elderly, women, etc.) When you look at overall mortality/morbidity, it seems clear to me that there is a lot of blind rx’ing - not only of Crestor.
Justice in Michigan
Just on pt. self-eduction. There was a great piece in the WSJ a few years ago that explained, in very accessible ways, the issues of actual versus relative risk, NNT numbers, etc.. I use it in my teaching - something I think is of enormous value to consumers/patients.
Of course, it works for both risks and benefits - whether one hears that Drug X has a “40% increased risk of Y” or “Drug Z reduces the risk of Q by 40%.”
When the actual numbers and percentage differences are out there, I haven’t seen a student yet who wasn’t amazed.
TOdd
agreed. relative risk vs. actual risk reduction are two entirely different animals. What is interesting is I see it on the other side as well. When risk of some adverse event increases from 0.2% to 0.6% I hear the “pt. advocacy groups” announce that the risk increased 200%
It certainly is all relative and up to the patient/physician. I myself have some CV risk, and honestly I want my statin! In my case the very real risk of CV event certainly outweighs the risk of an small chance of liver etc. Plus I feel as if I do have a liver problem, that is likely reversible and won’t kill me. I don’t have the same feeling as an acute MI. But I want Zocor or Lipitor, not Crestor. So you could certainly use number needed to harm to really place things in perspective.
AND CHRIS,
Unless they are from a major independent specialty group, like the ones I mentioned - they don’t even get a second look, no matter where they are published.
Justice in Michigan
Right. I always teach NNT in both directions, with different populations, etc., so my students know that Vioxx is not strychnine and Lipitor is not fairy dust (not that most of them have ever heard of fairy dust).
I don’t know the real studies on Crestor, but I confess that whenever I see the spokesdude walking down the spiral staircase, I wonder if he ends up underground….
On a lighter note … when I see Robert Jarvik Lipitouting, I remind my wife that I have also invented an artificial heart - like the time we went to one of her friend’s choral concerts, and I pretended to have really enjoyed it.
Bless The Truth!
Many of you missed the points. FDA collects user fees from sponsors (big pharma and Boiotech). The CEO’s focus is on dollars for the investors and NOT for the patients. FDA is under-staff, inadequately equipped and with dragging obsolete technology. Even when provided with vivid signals of fraud in clinical trials, they hardly come up with meaningful findings for the patients. What is the use of a “black box label” that details “sudden heart attack” and “even may lead to death”?
Why approving poison for the innocent public, even when there are plenty of alternatives? Many of the scientists trade their scientific expediency for bread and butter, while those who summon up courage to express concerns, are melted with sudden career death.
Having spent over twenty years working in the industry, FDA’s verdict on approval is nothing but a game of numbers. If you want to prove me wrong, then you need to explain to me why so many drugs already approved are withdrawn for safety reasons. It is a mockery of science, integrity and trust. Preemption, give me another word better than FRAUD!
Brian
Luckily, none of you were around to criticize civil war surgeons on the battlefield. We now consider by-pass surgery so routine that we forget to take our medication but as health care costs from hospitals spiral upwards, there needs to be someway to avoid surgery. I think we are obviously ahead of pioneering efforts for treatment of the war-wounded at Gettysburg but obviously it’s still a primitive enterprise. Sorry drugs aren’t perfect and sorry the FDA can’t be good parents to deal with our fears. Despite the length of the opinions on this piece it comes down to comparing man made laws and logic with interpretations of the nature of health and disease. The more mature we become about the plusses and minus of medical treatment with drugs the more rapidly it will advance. Will everyone come through this unharmed?.. I think not. Very few people suffer side effects from new medications so let’s not make that the major focus of our debate. Older drugs that we trust have caused more issue than we wish to admit. The answer is not with the legal opinions of folks who fail to understand science. Don’t line your pockets with valuable research dollars that could progress medicine into the modern era.
Justice in Michigan
Brian - As the history of medicine (and pharmacy) show, they, too, are based on man-made laws about what is best to do under whatever circumstances - leeches, purges, nothing, Celebrex, amputation, coca bean, diet and exercise, a shot of rum, etc..
As a non-lawyer (or plaintiff or physician), my own pockets remain pretty unlined. According to Janet Woodcock (now Associate Commish of FDA), about half of rx-related deaths could be prevented with the right “man-made” FDA, and rx-related deaths are the fifth or sixth leading cause of death in the U.S.
As has already been discussed, the arguments about “all drugs have dangers,” “people want a mommy state,” are only red herrings, irrelevant to the actual topic being discussed.
The topic being discussed is whether comapnies (in this arena or otherwise) ought to be held accountable for fraud or similar delinquencies. Nothing more. Nothing less.
Brian
What you call fraud I call part of the risk and benefit equation. Opponents look at the scientists of the minority opinion as great heroes and whistleblowers when any scientific decision is really made by weighing the risks and benefits of both sides. . Very few recent decisions about launching any drug you care to mention was found to be incorrect. The very few and very vocal side effect suffers know they can gain the attention of the scientifically illiterate to obtain a monetary gain when it was always a risk versus benefit. Aspirin has killed more people than vioxx, it’s fraudulent that no one fights to get this off the market; this lowers your credibility in the search for fraud. The FDA knows as much as the drug company after the results of a clinical trial. The solution you don’t want to pay for is longer and bigger clinical trials. You want other people to be the subjects and you want pharmaceutical companies to pay the bill without offering any concessions. The answer comes out eventually with millions of patients.. On these latter points, I’m sure, we can agree..
Justice in Michigan
Thanks for the further word, Brian. Of course, I agree that it’s only with widespread use that we really know. 51% of new drugs show serious AEs post-approval. That is inevitable, and there is no sense whatsoever in which I consider that “fraud.”
Here are a few examples of the sort of circumstances in which I do think accountability out to figure in:
1. A company knowingly and deliberately does not report deaths from acute liver failure to FDA (later saying: this was because they occurred abroad and they “didn’t know” they had to report these). See the Oraflex case during the 80s.
2. A company (or the person responsible therein) counts acute liver failures in such a way as to reduce them by one-third in reporting the number to FDA. The FDA has no way of knowing that happened (until it later comes out in court). That’s one version of Rezulin story.
3. A company suppresses its internal studies of AE rates of their drug relative to others in its class; or - although concerned about the differences - decides not to pursue a study that has been recommended by some inside that company. One version of the Baycol story, and several others.
4. A company directly denies AEs it knows of, shreds records, hires KOLs to give “testimony” in favor of drug, tries to intimidate or bribe (with cash) those who see it otherwise (even at FDA) - thalidomide most obviously, and a number of others too.
5. A company puruses what Jerry Avorn of Harvard calls “passive-aggressive” compliance - data is chronically submitted late; Medwatch reports are “headlined” in ways to disguise or camoflage all that the company knows is going on (requiring FDA’s ODS to find needle in haystack), etc. One version of fen-phen story and several others.
You and I both know examples of this sort could make a very long list. They have nothing to do with scientific disagreement or risk-benefit equations.
TOdd
Ok, not all drugs are perfect and could be better - agreed. Plus, isn’t this originally about Phenergan, a drug older than I am by the way. So I don’t think delaying medication at the FDA for 30 years while people die and are unable to benefit from breakthrough drugs is the answer either. Caution with new drugs - yes. But keep in mind, pharma doesn’t prescribe.
I think if you look at the data, HCP mistakes kill more patients than drugs. Not even talking about docs writing for meds they shouldn’t. Why every hospital in the country is not barcoded is AMAZING to me. Look at the whold Quaid incident - a hospital too cheap to barcode, kills 3 kids and the manufacturer gets sued?!?! So we can talk about drugs because they are the easy “big target”. What about your local hospital that has been making millions for years in your backyard without doing everything possible to improve patient outcomes? I know, not as easy or popular as blaming big drug companies. But believe it or not, hospitals do all they can to make money as well. They are run by an administrator, not a HCP. I would argue that pharma actually is looking after pts better than your local health care system.
TOdd
Justice, not sure where your loyalties lie (Ann Arbor or Lansing) - but the Michigan game is GREAT! Go Big Ten!
Justice in Michigan
Go Blue, Todd. Thanks. Otherwise, truce in the drug wars - we deserve it! Whatever disagreements, I respect the dedication and smarts of everyone involved in this discussion.
TOdd
I am with you, discussion tabled until conclusion of Rose Bowl at least!
Lisa Van S
Ol Crankey,
Failure to Warn,..Lets use Pfizer as an example, shall we. In 1983, before zoloft was approved, a 44 year old man was removed from a clinical trial due to thoughts of killing others, and then himself, Clinical Investigater stated that this episode was due to Study Drug!!. Pfizer reported the AE to the FDA that the gentleman was removed from the clinical trial due to Nausea. In this case pfizer didnt tell FDA the whole truth. Ten years later to the day,..Pfizer draws up the “INFAMOUS PROSECUTORS MANUAL”. BTW,…FDA is a Joke..
Lisa Van S
HANK,
Not a girl thing at all!! Have to be a New Jerseyan to understand, its an inside political thing.
Brian
What I am thinking now is your fault. How can I be compensated? The investigator could not know definitively what caused this deranged man’s thoughts or if he was reporting a falsehood. Could he? and what is it that you know definitively?. You are just happy someone wrote it down but it is not evidence. Nevertheless, It is still our duty to help the mentally disturbed but they are not capable of assisting in their own treatment..
Oliver H. Winn
Amicus Curiae Statement
Oliver H. Winn
Levine vs Wyeth
PREFACE
The premise of my claim for standing before the Court is my unique position as father of the plaintiff and the insights I gained in studying the case from day one. During these studies, my viewpoint broadened from just seeing justice provided my daughter to include recognition that the Court has the opportunity to improve the drug approval system significantly.
The exploration presented here includes short summaries of the development of the drug, the medical procedure that led to the filing of Levine vs. Wyeth, and a revised drug approval process illustrating the improvements. Two of the summaries are presented in narrative form.
There are a few hearsay statements in the descriptions. They don’t attempt to enter new evidence; they only describe how information was received. The submission also contains statements that may not meet the full requirements for classification as common law, but this Friend believes they are logical and common sense.
THE DRUG AND ITS APPROVAL
Wyeth has three versions of the medicine that avoid risk by insulating the drug from arterial corridors. These are a suppository capsule, an oral pill, and a liquid to be injected into the fleshy part of the rump. The dangerous version of the drug used in treating Levine was a convenience form for those care givers routinely using intravenous injection.
The FDA and Wyeth used the standard procedure: the drug company develops the drug and determines its efficacy. The dangers involved in using the drug are carefully identified and warning labels outlining actions health servers must take to avoid dangers are developed and included with the medicine. The FDA monitors this effort and the drug is not approved until both the FDA and Wyeth agree. If any problems are discovered, corrections to the process or the warnings are made.
Many drugs are dangerous. The drug involved in Levine vs. Wyeth is extremely so. To insure that this drug does not cause the loss of limbs and even life, a complex series of steps must be performed perfectly. (1) The liquid medicine must be examined for cloudiness or change in color (damage by light); (2) The drug needs to be diluted to a specified concentration; (3) The proper dosage must be prepared; (4) the rate of flow of the diluted drug must be kept below a defined maximum; (5) The intravenous patch in the wrist must be precisely positioned and inserted; (6) The IV must be proven to be flowing properly; and (7) Drug flow must be stopped immediately if the patient complains of intense pain when the flow starts.
Finally, these conditions and the appropriate warnings of the consequences of failure are recorded in a warning label and included in the drug package.
The process generally works well, but there is no evidence that caregivers have had any part in the approval process. Yet they end up being the carrier of all the risk. Assuming the drug warning label is adequate, they have become the potential “intervening causes” protecting the drug manufacturer from liability. It doesn’t seem quite fair.
At time of treatment of Levine, there was a history of serious maltreatments and the FDA and Wyeth were involved in refining the labeling. Wyeth had proposed a change that the FDA had not approved. There was recognition that the warning label is inadequate, but there was gridlock.
It is at this point that Wyeth took an action negligent almost to the point of grossness. Its action was to take no action. It was tragic and it placed Wyeth at the center of liability.
The proper legal and ethical action was to announce to all users that the medicine was temporarily withdrawn until new and adequate warning labels had been issued and to reopen discussions with the FDA to complete the work.
Instead, Wyeth decided to wait until maltreatment and lawsuit occurred, preferably one like Levine’s where no intervener’s failures have been shown to have occurred. This then would provide opportunity to seek clarification of the FDA/drug company liability (to change the law to shift the ultimate liability to the FDA).
This Friend of the Court vividly remembers a family review session with Levine’s lawyer during which I commented “the only thing that explains Wyeth’s behavior to this point in the trial is that they seek ultimately to change the law”.
LEVINE’S TREATMENT
The stage is set for the system to take care of Diana Levine. She is in a health Center bed, fighting an extremely painful migraine, her life-long nemesis. She has an IV in her wrist and it has just been used successfully to inject a strong pain killer and sedative. The Wyeth medicine has been prepared and mounted following the procedure outlined in the drug label literature. The care givers hear no complaint of pain as the flow begins.
In less than an hour every capillary in her hand below the IV had closed, dooming the limb. Valiant efforts were made to try to save the hand. Blood thinners so strong that she bled through her skin were injected. She endured weeks of pain as her doctor tried to head off the need for amputation. Finally, gangrene forced two surgeries to remove of her hand and significant portion of the lower right arm.
The state lawsuit against Wyeth is filed and follows a path the reverse of the treatment. First, it was proven that the Wyeth drug was properly prepared and inserted in a functioning IV in full compliance with the label instructions. This determined that the warning label failed to define a path that would prevent injury. Then damages were calculated and assessed.
The jury decided unanimously in favor of Diana. It was confirmed throughout the state court system. Wyeth initiates the subject Federal appeal to the US Supreme court, claiming it was helpless to change the labeling without FDA approval, which had not been granted.
AN IMPROVED PROCESS
This Friend recommends strongly the court go beyond the current label-changing difficulties and examine the initial process that led to the inadequate label. The easiest way to describe the actions that could have produced a satisfactory procedure and label is to consider how the process might have been better. Such a process is described here in narrative form.
First, the FDA doesn’t wait for the drug company to develop the drug handling procedure and propose a label. The FDA, with its special concern for safety review, takes an active role in the procedure from the beginning. Both the FDA and the drug company are fully aware that this drug is very dangerous. Representatives of care-givers of different levels of ability to care are enlisted in the team.
In the initial conversation, when the drug company suggests the care giver should check for light damage to the liquid and dilute the standard concentration to a safe level. The alert FDA examiner says, “Why do we want to take a chance that the checking and dilution may be botched by some nurse? Why don’t you reduce this risk to zero by shipping properly automatically diluted and checked medicine in a ready-to-use condition? The risk for these steps is eliminated. The drug company says “OK, and thanks for the suggestion!”
Drug company: “Next, the drug dosage must be correct and it must be fed at a very low rate. We will specify the rate that must not be exceeded.”
FDA: “Why don’t you deliver the drug as individual opaque dosages instead of bulk? This would essentially eliminate the risks of degraded medicine, concentration, and dosage. The preparation will be accomplished by automated equipment under full quality control at the drug factory”.
Drug Company: “Although the cost of the small packaging and automatic dosage and filling is significant, we agree the elimination of risk would more that justify the investment. As I think about it, I believe we may be able to form the treatment package so that it could control the feed rate, eliminating another significant risk. The drug container could just be hung at the top of the IV line. No care-giver adjustment would be needed. We will examine this possibility”.
Care Giver: “There is another problem with the procedure. We are told to stop treatment immediately if the patient complains of pain. However, the administration of the medicine begins after we have injected a heavy dose of pain killer/sedative. Such pain relief is first priority. It is likely the patient is ‘feeling no pain’. What is needed is a small, safe test kit able to test the intravenous tap quickly. Then we could do a quick proactive test before the painkiller is injected. We would get the patient’s attention and instruct the patient to report any pain at the beginning of the test and before administration of the pain killer or full drug injection”.
Drug company: “It could be done. It is possible it could be incorporated into the capsule, with one end containing the test mechanism and the other providing the medicine feed at the appropriate rate”.
NOTE:
During his initial study of the drug warning label, this Friend of the Court followed a similar pattern of thinking. He then put the conclusions to work by ordering medical glass tubing. Using a small torch, he constructed a sample drug delivery package. It worked fine!
The above narrative demonstrates that a much lower risk process with a very simple label could have been developed with the FDA, Wyeth, and caregiver representatives concentrating on eliminating risks rather than passing the high risks downstream and depending on labeling to prevent the tragic drug failure. In this Friend’s opinion, this was one of Wyeth’s and the FDA’s failures: not concentrating first on reducing risk.
INTRAVENUS INJECTION
This Friend believes the re-oriented team should hold one more discussion, one devoted to the risk of intravenous injection of dangerous drugs. Here is the final discussion.
FDA: “Let’s stop looking at the details and discuss the inherent risks of injecting any dangerous drug intravenously. We all know the needle is injected in a tiny passageway called the carpo tunnel. The channel houses a whole family of tendons, arteries, veins, and nerves. It is packed so tightly that a significant percentage of the population requires surgery to expand the tunnel to avoid loss of the use of the hands. The idea of penetrating this area with a very sharp needle to inject a dangerous medicine doesn’t seem to be a wise practice. Even if the initial insertion is successful, it seems quite possible subsequent motion would cause failure during injection of the medicine.
It seems to me that the only satisfactory warning label would say ‘Don’t inject this medicine intravenously.’ I recommend this version of the medicine not be approved and that we stick with the other forms proven to be safe”.
Other team members, including the drug supplier: nods of agreement.
If this decision had been made and promulgated, all other “generic” producers would have been bound by it.
STATE COURT JURIDICTION
Some have argued that jurisdiction of medical malpractice cases should be moved to the Federal Courts. This Friend believes this would be a tragic move for two important reasons. First, this would place an impossible burden on the Federal Court system. The state courts now are carrying the heavy burdens. Second and more important, States are different and require different practices.
An example of the latter point is the comparison of Vermont and New Hampshire. The emergency medical facility available to Levine in the north central part of Vermont is a local (5 miles) medical clinic that is manned by a Physician’s Assistant during the night. The hospital to which Levine was transferred for sophisticated treatment is right across the river at Lebanon, New Hampshire (about 60 miles southeast). She was moved there from the Montpelier Hospital where adequate care was found to be unavailable.
Dartmouth Hospital is a remarkably competent treatment center. For example, three specialists are assigned full time to circulate throughout the hospital to monitor the condition of intravenous patches, changing them out when they are faulty. Three others are similarly assigned to examine the psychological condition of patients. Clearly it is the responsibility of drug companies to be aware of these differences between care facilities and adapt their practices to serve the full range of caregiver abilities.
The State Courts help to insure this is done. To destroy these services in favor of Federal jurisdiction could be catastrophic.
CONCLUSION
A State of Vermont jury decided, by unanimous agreement, that Levine’s care-giver faithfully followed the procedures described in Wyeth’s warning label. It judged that the label was inadequate to avoid the loss of Levine’s hand. It awarded damages. The decision was validated by the state appellate and supreme courts.
Some truths are self-evident: no one had the right to sacrifice Levine’s right hand in order to test the proposal that the decision of a bureaucrat in Washington could relieve a drug company of liability for the damage done by its medicine. This is exactly what Wyeth has done.
The time has come for the Court to provide justice, justice already delayed for seven years. It can do this simply by confirming the State Court’s actions in the Levine vs Wyeth case. It should do so immediately and not wait to review other somewhat similar cases selected for review.
However, the court should not lose the opportunity to improve the drug approval process greatly by exhorting the FDA to include care-givers in its review team and to remind all participants that the principal objective of the review is to eliminate or minimize risk and not just arrange for distribution of liabilities.
THANKS
It is hard to describe adequately the thanks that this Friend of the Court owes to the Court for allowing this somewhat unusual Friend’s statement to be examined and considered.
Dr. Oliver H. Winn
422 Heliotrope Avenue
Corona Del Mar, CA 92625
owinn@worldnet.att.net
949 675 4016