Washout Or Whiteout? Paxil And Placebo Suicides
15 CommentsBy Ed Silverman // June 16th, 2008 // 8:01 am
Last week, US Senator Chuck Grassley called for a probe into Glaxo and the FDA over their handling of the Paxil antidepressant. At issue are the long-standing allegations that the drugmaker knew about suicide risks in children for nearly 15 years but obscured evidence.
In demanding the probe, Grassley cited a report prepared by Joseph Glenmullen, a Harvard psychiatry professor, for litigation in federal court in California over Paxil side effects. The report was unsealed earlier this year, but was missing some pages. Last week, those pages became available and include a section that describes in some detail how Glaxo allegedly manipulated so-called placebo suicides.
These are deaths that occur among patients who are taken off other meds so they can participate in a trial. “The rationale from washing out all drugs is to prevent them from confounding the results of the study, so that all patients start out the study in similar conditions,” according to the Glenmullen report, which goes on to maintain Glaxo “improperly” minimized the differences between Paxil and placebo suicide data in order to obtain favorable results.
As a result, the actual suicide risk was eight times its risk for patients on placebo. “Glaxo was aware of this risk, and hid it,” the report states, as The Wall Street Journal noted over the weekend in a story that refers to the previously missing pages. Here is the full report and page 47 offers a summary of Glaxo’s efforts. The page to the right, by the way, offers some insight into how suicide data was handled.
Thom
This is all just a big misunderstanding, I’m sure. Just like Tachi Yamada’s call to John Buse back in the late nineties regarding Avandia was just a chat among colleagues and not an attempt to intimidate Buse.
truthman30
Oh indeed Thom..
All just one big mistake by Glaxo..
Surely they couldn’t have intentionally sold a defective and dangerous drug which makes depressed people more suicidal? ..
Of course not, GSK are one of the most etchical corporations out there…
Yeah Right…
BOB FIDDAMAN
If the Ford Motor Company hid a defect in its product they would be hauled over the coals and sued by everyone and anyone who had ever had the misfortune to crash in one of their cars.
Why not Glaxo?
Unless of course, a ‘Don’t be naughty again’ type of letter sent to their CEO from the MHRA is that ‘hauling over the coals’?
Surely anyone with common sense here can see that they deliberately marketed a drug knowing that the suicide rate was abnormally high. This is not about ethics, this is manslaughter!
If only the law were as simple huh?
Instead it takes years of legal wrangling between lawyers that ultimately ends up in a settlement with gagging orders placed on those who have endured unforseen side effects from a drug that should never have been granted a license.
The company, in this case, GlaxoSmithKline offer a compensation payout - compensation that is in essence money they have earned from the sales of a defective drug. Money that could have… would have been better spent manufacturing a pill that actually carried no threat for the patient.
And still this drug is prescribed!
Fid
Justice in MI
This not a comment related to the specific issue of Paxil. Rather, just my usual reminder that in the relatively near future FDA preemption, which the Supreme Court will almost certainly uphold, will prevent any such lawsuits at all.
Ford’s potential accountability as described here will have no parallel - or even anything vaguely resembling - in the arena of pharma.
Sound like a bad idea? This is an election year. And almost none of the candidates (from the top on down) want to talk about it.
Should it not even be part of the national debate about healthcare, consumers’ rights, and the role of torts?
Whatever side you are on, if you believe it ought to be freely and openly discussed, this is the time.
Jaynesday
Justice, I of course agree with you as I too feel that preemption is… well I can’t think of a word.
I’ll go out on a limb. Here is a list of reasons that I know of that people think preemption is a good thing. (probably not complete)
I would like to know if there is any evidence (not a feeling) that any of these are true or if any are absolutely required for a drug/device company’s survival.
*Without preemption new and important drugs have not come to market because it’s too risky to put them on the market.
*Without preemption drug companies will go out of business because liability costs are too high.
*With preemption we will have safer drugs.
*Frivolous law suits are rampant and too many unscrupulous people are taking advantage
*Creative drug design is stifled by the need for safer drugs/devices
*An emotional jury can not correctly judge damage liability
*The FDA has enough capability to adequately protect the public from poorly designed/manufactured drugs and devices and doesn’t need the help of tort.
*Without preemption drug companies will have to adhere to conflicting requirements of state and federal law.
*others?
If I’ve missed any reasons for preemption please add to the list. If anyone has evidence (not a feeling) for any of these statements please also provide.
HorusCat
Jaynesday,
I think a middle ground exists that avoids the kangaroo court that a jury trial can become. While Justice maintains that the truth usually reigns supreme in these cases, I respectfully disagree. One example is that Vioxx case where a member of the jury finally admitted he was loaned money by the plaintiff. Another is the asbestos debacle that has taken place over the past three decades. It got to the point where no harm had to be proven–the companies just paid and paid until they were bankrupt. Finally, one can point to a multitude of medical malpractice cases where a jury acted on the feeling that “someone should pay,” regardless of actual culpability. (John Edwards seems to have mastered this manipulation.)
We need a process that accurately determines actual fraud or negligence. Then we need a process, probably a criminal one, that punishes the individuals involved–while not irrevocably harming those whose lives depend on their continued employment. Merck didn’t perpetrate the Vioxx damage, if you think of Merck as the tens of thousands of employees and stock holders that make up the corporation–from the janitors to the cafeteria workers to the reps who didn’t even sell Vioxx. A punitive process that significantly damages or even bankrupts a company doesn’t just affect the employees of that company, either–it affects all those people whose lives intersect with those employees: their hairdressers, dog walkers, babysitters, realtors, etc, as well as the stockholders (old people, pensioners, blue collar workers, teachers) whose retirement in part depends on that company.
laura
So, HorusCat, I hear you saying that another reason for preemption to add to Jaynesday’s list is…to keep employees of medical device and drug companies employed. Is that truly the responsibility of the consumers or is it actually the responsibility of the medical device or drug companies? If they provide safe devices and drugs that don’t warrant massive lawsuits, they won’t have to be concerned with significant damages and bankruptcy. I truly apologize, but I don’t feel sorry for a corporation that makes millions of dollars off of a given drug or device and is then held accountable for harm or death that their product inflicts upon a consumer. And if they let the damages multiply without determining how they need to change their product to make it safer, and they end up with, horrors of all horrors as far as they’re concerned, a class action lawsuit, that’s they’re fault, not mine or yours. All companies have to be accountable for their products. What gives medical device and drug companies the right to be free of this very basic responsibility? I know you say that everyone has to be aware that they can be harmed and killed by medical devices and drugs and that’s a risk that we all take by using them. I say that medical device and drug companies are selling products that not only provide great benefits, but also have the potential of providing great harm and it is their duty to fairly warn of that harm without concern for how that will affect their bottom line. If they do this, they won’t have to be concerned about losing their profits to lawsuits.
Justice in MI
Jaynesday - I wish I had time to respond adequately to your points. But I would refer you to some of the pieces mentioned here by me and others: David Kessler and David Vladeck’s piece in the Georgetown Law Review; the NEJM editorial condemning preemption; the JAMA commentary about litigation and drug safety; most of the statements at the recent Congressional hearings that the Committee on Oversight (Chaired by Waxman) had. Many of this material has benn cited by Ed, me, or others on the ‘Lot. If you need references, just let me know.
Re: HC’s comments, I think we are better off with both civil liability and the FDA than either one alone. That would be a fair statement of my views. They are both imperfect systems. They have worked reasonably well together for the last hundred years, as FDA itself has reiterated many times. So I believe there is room to improve both - a lot of room. I also agree with what Senator Leahy said on Friday - to nuke civil liability entirely, which is what FDA preemption means, is a pure power grab. If you favor preemption, you favor that nuclear option. As someone who writes with seemingly libertarian leanings, I have been surprised you would even consider ceding such sole and exclusive power to a government agency. But I guess we are all entitled to inconsistency.
Re: Jaynesday’s list, I have to be super brief. So please don’t take this as a substitute for the references above.
*Without preemption new and important drugs have not come to market because it’s too risky to put them on the market.
Ans: There is simply no evidence for this. Drugs that fail at stage III or earlier do not do so because of liability but because manufactuers realize they just won’t fly. To suggest they are only or even primarily worried about liability is to rate the integrity, and smarts, of pharma companies much lower than I would.
*Without preemption drug companies will go out of business because liability costs are too high.
Ans: A while back, I referenced a Business Week piece on the alleged “tort tax.” But just think of recent cases - Lilly/Zyprexa, Merck/Vioxx, GSK/Paxil. In the contexts of these comapanies’ budgets, the settlements they have made were about as far from threatening their future survival as a bad thunderstorm.
*With preemption we will have safer drugs.
Why would that be? According to Kesselheim/Avorn in JAMA, civil liability has played a critical role in drug safety. I
*Frivolous law suits are rampant and too many unscrupulous people are taking advantage
Ans: I actually agree with HC that the asbestos litigation got out of hand and was resolved appropriately. But most of the “frivolous lawsuit” lingo is pure political rhetoric. The reality is that both the number and cost of lawsuits have been decreasing. Most suits involving pharma are not from plaintiffs but companies suing each other over patent infringement, etc..
Is there a Pfizer person out there who believes their action against Rambaxy was “frivolous”?
*Creative drug design is stifled by the need for safer drugs/devices
Ans: I think this covered above. It is more likely that the support of safety managers that liability provides _increases_ the development of safer drugs/devices
*An emotional jury can not correctly judge damage liability
Ans: Juries work hard but, yes, do not always see the whole picture, and some are more “swayable” than others. It works both ways. To trash “juries” as a whole is really to trash ourselves - that’s who we are. There is some excellent work on the social psychology of jury decisions that deserves consideration.
If you read Cass Sunstein, Law Professor at U-Chicago, the big problem has to do with punitive damages. Juries just don’t have good ways to equate harm with with damages. This is an area where I believe real reform is needed. Jury-trashing more generally is a kind of knee-jerk anti-populism. Mostly thoughtless with without supporting data.
*The FDA has enough capability to adequately protect the public from poorly designed/manufactured drugs and devices and doesn’t need the help of tort.
Ans: Holy Cow! Here, I can only quote Andy Von E. himself - “Peril exists.” As you well know, every other week it seems another major study comes out that tells us how deperately limited are the resources and regulatory culture/means at FDA - IOM, OIG, FDA’s internal studies, you name it. As I wrote in the New York Times (blush), there is a kind of Alice-in-Wonderland quality in talking about FDa preemption in this context.
Once again, see the Kesselheim/Avorn article in JAMA. They document very well how the two systems work together.
*Without preemption drug companies will have to adhere to conflicting requirements of state and federal law.
Ans: There are _some_ instances where it gets tricky. I think the Wyeth case may be once of those, which is why our current Solicitor General - in my view - pushed it to be the poster child case on preemption. Given the amount of scuzzery in cases like, for example, fenphen, Baycol, or Rezulin, it would have been much harder to make a reasonable case for preemption in those instances.
Bottom-line: No civil case requires _any_ requirements of a company. That remains solely within FDA’s jurisdiction. What history suggests is that civil cases have most often _led_ to changed FDA labelling requirements, and even withdrawal in some instances, because of what emerged in the discovery process (suppressed studies, etc.) That is why the two systems have been viewed as complementary rather than contesting.
*others?
Ans: Yeah, I have ten more pages of the pro/con arguments, with answers, answers to answers, and on and on. But I don’t think anyone really wants to see all that here.
I’ll just put in one - the bogeyman that lawsuits remove safe and “life-saving” drugs from the market that would otherwise be available.
As far as I know, there is only one case in which some version of that happened. This was the drug, Benedectin, which was used for morning sickness. That is why preemptors always repeat, “Benedectin! Bendectin! Benedectin!”
But guess what - This “life-saving drug” was actually a combination of doxylamine succinate (the active ingredient in Unisom) and vitamin B6. Both ingredients were available OTC at the time of the Benedectin withdrawal. There have even been articles by Ob-Gyns about how to make “home-made Benedectin” if anyone was so inclined.
So the next time you hear about Benedectin - and undoubtedly you will, since it is the only example preemptors have - take a Unisom and have a good snooze.
HorusCat
JiM,
I always enjoy the depth and breadth of your knowledge. I like “Peril exists!” My sister and I usually say, “Danger is everywhere!” (ok, mostly to laugh at her in-laws), but PE is more succinct.
I don’t think I was advocating abandoning governance solely to the FDA. Rather, I was suggesting that there is a better method than civil jury trials, which I think are a blunt instrument that is too easily manipulated by dodgy defense attorneys. (But my aversion to attorneys has deep roots in my childhood as a doctor’s daughter, so perhaps I am not objective.) I was suggesting a criminal process that would actually get the perpetrators, rather than a civil process that slays the whole dragon, so to speak. And in conjunction with that, a screening committee that weeds out the malingerers and the money-grubbers. And I agree with you that the whole punitive damages thing is not a tool meant for the hands of the populace. Besides, being a libertarian is not synonymous with being a populist, unless one is allowed to insist on personal responsibility first and foremost, with government intervention only a last and infrequent resort.
Time to go to bed. I have had my glass of red wine to raise my HDLs and do all the good things for longevity that red wine is supposed to do (and it tasted good). Now I must do a crossword puzzle to exercise my brain and ward off Alzheimer’s. Good night all.
P.S. Jaynesday and JiM, I can’t tell you how much I value the reasoned discourse coming from you, Nathan, Sal and others. I can’t resist mixing it up every once in awhile with a few of our more emotional comrades, but I do sometimes emerge a little dizzy from the pummeling. My husband doesn’t understand why I do it…it’s one of those things “that make you go ‘hmmm.’”
Justice in MI
HC - I hoist a vin rouge with you (see, I’m no populist!). Rather, one of those pinhead intellectuals that Spiro Agnew (probably before your time) got so worked up about (until he got busted).
The “peril exists” line actually comes from Andy Von E. himself (soi-meme). So I find it particularly quoteable.
The grace of this site is the fact that people who almost never talk with each other, and genuinely engage with each other, have the change to here. It’s like breaking through a mirror and allowing us to see things from a perspective that is not one’s own. We may not agree, but at least we have the chance to consider. That’s the ballgame, as far as I’m concerned.
Salut!
Justice in MI
Having spent the evening replying to Jayneday’s post, I offer this comment only to keep the thread from disappearing forever.
So sue me.
Jaynesday
Thanks JiM, Thanks for your input. I really appreciate the deep thought you give to this subject and especially your ability to keep emotions at an arms lenth. For some of us, including myself emotions are much harder to hold back and almost always end up causing us to say things that we regret. I always look for your posts.
Concerning these last posts I don’t have time to respond but what could be said that hasn’t already been better said?
HC, I am so glad that you are here to give us a reason to question ourselves. We aren’t always as smart as we think. And Laura, I think you are pretty smart.
So with that I go on to greet the day. Have a good one.
Justice in MI
Jaynesday - Thanks for the kind thoughts, and cheers to what you said about others and more generally.
Truth is, I don’t keep emotions at arm’s length. I genuinely believe we are heading over a cliff - the industry and, in concert, all of us - if/when preemption is upheld. But there is a point at which screaming, “CLIFF AHEAD!”, just doesn’t help. The sad reality is that we will probably find ourselves in the ravine, look back and up, before we realize how large a mistake we’ve made. There’s some emotion for you!
Beyond that, I do truly believe that this board provides an amazing opportunity - this is not sentimental BS - for learning. Mutual flaming between industry “critics” and “defenders” is something you can get anywhere. The chance to really engage, and try to understand contexts and realities that one doesn’t know, is unique.
There is no way I can teach about this (which is part of what I do) if I don’t try my best to understand how it looks “from the inside” and how many different and complex perspectives “on the inside” there are.
James
Justice,
I’d like to get in touch with you directly, but I don’t feel comfortable putting my email address up here. Would you be comfortable putting yours up here, or if not, perhaps we could rope Ed into passing a note for us in class?
Justice in MI
James - No problem; I’ve included it before. It is justiceinmich@gmail.com
Look forward!