Lilly Should Have Warned About Zyprexa In 1998
41 CommentsBy Ed Silverman // March 8th, 2008 // 1:51 pm
That’s what an expert witness told jurors yesterday in a state court in Alaska, where the drugmaker is defending charges brought by state officials in a lawsuit claiming hidden Zyprexa side effects caused many mentally ill people to develop diabetes and cost the state Medicaid program millions of dollars, The New York Times reports.
Instead, Lilly hid Zyprexa’s risks from doctors to protect the drug’s sales, according to the witness, Dr. John Gueriguian. Lilly waited until 2007 to add strong warnings to Zyprexa’s label to reflect the drug’s tendency to cause severe weight gain and blood sugar changes.
Lilly put “profit over concern of the consumer,” Gueriguian testified, saying the drugmaker could - and should - have warned docs as early as 1998 about the link between Zyprexa and diabetes. For its part, Lilly says it did nothing and fully disclosed what it knew about Zyprexa to the FDA, the Times writes.
Gueriguian, a specialist on diabetes and a former medical reviewer for the FDA for 20 years before retiring in 1998. is testifying on behalf of the State of Alaska, which has sued Lilly to recover its costs for treating Medicaid patients who developed diabetes after taking Zyprexa. At the FDA, he recommended against the approval of Rezulin, a diabetes drug that was later withdrawn for causing severe liver damage in patients, the Times notes.
Under examination by Tommy Fibich, a lawyer from Houston who is representing Alaska, Gueriguian reviewed about a dozen documents in which Lilly scientists and execs discussed potential links between Zyprexa and diabetes. Zyprexa was introduced in September 1996 and hailed as a breakthrough medicine for the treatment of schizophrenia, but docs quickly began to report to Lilly that patients suffered severe weight gain, high blood sugar and even diabetes after taking the drug.
By the fall of 1998, the combination of adverse-event reports, clinical trial data that showed hyperglycemia and weight gain, and problems in animal studies should have been enough for Lilly to warn doctors about Zyprexa’s links to diabetes, Gueriguian testified. Instead, the Times writes, the company did nothing.
Documents from 1999 and 2000 also showed that Lilly was accumulating evidence of Zyprexa’s risks but not sharing it with doctors, he testified. And in 2002, only 10 months after Lilly began selling Zyprexa in Japan, medical regulators in that country required Lilly to warn doctors against using Zyprexa in diabetic patients.
But Lilly didn’t issue a similar advisory to doctors in the US. Instead, the drugmakers advised its sales reps not to discuss diabetes with docs unless the docs brought it up first, according to another document presented at trial. “We will NOT proactively address the diabetes concerns,” the document, an internal Lilly memorandum, said.
A lawyer for Lilly said after Gueriguian’s testimony that the drugmaker shared all it knew with the FDA and the link between Zyprexa and diabetes was still a subject of scientific debate. Lilly gets a crack at Gueriguian on Monday.
Justice in Michigan
Genuine question.
Clearly, the materials that have come out about Zyprexa marketing, especially in the NYT, read to the average person as pretty damning.
Other than simply asserting quotes were “taken out of context” (there is nothing anyone has ever said or written that was not taken out of some context), is there a way a reasonable person could understand this material differently? Would Lilly have to supply more of the “context”? As far as I know, they do not appear inclined to do so.
As above, genuine question. When we discuss the decline in public trust in the industry since ‘97, it is obviously stories like this that accelerate the erosion.
Dan
Agree greatly with the above comment.
True story: due to some issues I’ve experienced lately, primarly some depression and anxiety, I had a doctor insist that Zyprexia would be my panacea. Like others such as the author of the above quote, I refused to take this drug, or others doctors seem to believe honestly about thier benefits, based on everything but the science behind such drugs, which in some cases, could potentially worsen the health of its users, and this concerns me.
While not a doctor or a health care industry executive, I have been working in the health care arena in a large variety of health care settings for over 20 years. Historically, I have had genuine respect for most of the doctors I have encountered in the past for several reasons, and believe thier clinical decisions are for the ultimate for thier patients. Yet presently, I find myself respecting more those who truly care for such patients, such as those dedicated health care workers possibly in ancillary care departments and other patient care givers. Thier intentions seem more authentic, yet I still hold on to the belief that many doctors are dedicated to the well being of thier patients. Yet doctors today face unpleasant facts about thier vocation that have not always existed, from malpractice to managed care. So thier demoralization is understandable, yet thier ability and dedication should still remain fully intact, or the atrophy will continue progressively in the health care system.
Laurie
“The company has said it did nothing wrong and fully disclosed what it knew about Zyprexa to the Food and Drug Administration.”
This is the statement that bothers me the most. IF this is true, which has yet to be determined…this is a HUGE argument against preemption. If, and that’s a big “if” right now, the FDA did know about these risks, what did they do about it? Are they going to claim that Lilly “owns” the labeling, therefore the ball is back in Lilly’s court”. The whole debacle is a catch 22 of who knew what and when AND what the did about it, which is this case was nothing.
As we see more and more of these type problems come up, the one thing that continues to come to light is the lack of effective regulation by the FDA. They are supposed to be there to prevent situations like this, and they have proven that they are not able to regulate as they are mandated to do.
Chad Shanks, RN
Lilly is simply following the well-established cost-benefit analysis business plan. When it comes to human life, this is a very hot ethical issue. However, it is absolutely nothing new. Lee Iaccoca and Chrysler were caught up in the same sort of issue with the Ford Pinto in the 1970’s; where it would have cost them less than $5 per car to place a plastic safety device which would have prevented the gas tanks from exploding on impact. Even if Lilly loses the case, don’t count on them changing their game plan anytime soon.
Dan
A debate possibly needs to occur that asks the question if the health care industry needs to be segregated from other industries that rely on such terms desribed above such as cost-benefit analysis, as the industry of health care deals with complex issues quite a distance from tangible, faulty items, that occur at times with other industries. Questions need to be asked…. are tactics developed and implement with deliberate intent in the health care industry? Do such tactics involve deliberate ignorance and reckless disregard?
Dr. Incognito
Debates on such issues do occur. However, are you aware that the idea of cost-benefit-analysis infiltrated the government itself when Secretary of Defense Robert S. McNamara joined our government’s ranks. He brought it with him when he came over from the Ford Motor Company. It’s been in use as a government tool ever since.
Dan
Dr. Incognito,
Thanks for the information.
This assesment of the analysis, as it relates to human health, perhaps requires a guardrail not intended to be penetrated that is unique and without presence in other industries, perhaps, while fully agreeing with you and others that the analysis is an established disipline of the U.S., yet it would be to the benefit of public health if such analysis occured with minimal frequency.
Robert Wilkens
I hate to be the bearer of bad news, especially since if it is true, I lose my disability benefits: Mental Illness does not exist. Zyprexa and similar drugs may fit some ‘cost-benefit-analysis’ criteria, but at the heart of it, they see the ‘benefit’ as the ‘control of the population’ i.e. sedating them, making them fat and lazy, stopping them from demanding change, and the like. I’ve been through the ’system’ enough — with diagnoses ranging from Bipolar, to Schizophrenia, with a stop in between at Schizoaffective disorder. There’s nothing wrong with me that a simple psychologist, or perhaps some other technical (non-chemical) solution could have been used to fix. I’d like to re-state something earlier stated by myself elsewhere, and that is the the breakdown of the word ’schizophrenia’ comes down to ‘Schiz’ which is ‘broken’ or ’shatterred’ and ‘phrenos’ which is a word meaning ‘heart’ (sometimes translated incorrectly as ‘mind’, as they once thought the mind was in the heart, when they created that word). There are psychological tricks you can use to ‘cure’ these problems, I can’t even perceive a way in which some ‘magic pill’ could cure a thought disorder.
Lisa Van S
1998 appears to be a Magic year for Industry,..GSK’s silence on Paxil maimed and killed thousands of children
Justice in Michigan
I’m still holding out for my original question.
Is there a way of understanding the Zyprexa story _other_ than what most reasonable folks would conclude based on NYT stories and related?
It remains a real question.
Justice in Michigan
Another way to ask it is this:
When industry folk read about Zyprexa, do they say: These are the kind of people and pratices who/that are ruining it for all of us?
Or do they say, this is almost certainly the NYT and related unfairly sticking it to pharma again?
Dan
While such articles such as the one mentioned in this post by the NYT can be incomplete and lack objectivity, It is, I believe, the discretion of the reader to judge the subjects of such articles, based on thier interpretation, just like anything else that we may hear or read, such as these posts on this blog.
Ed Silverman
Dear Justice,
It’s hard to know what many people think after reading one or more stories, whether it’s in the NYT or elsewhere (let’s set aside discussions about NYT criticisms for now, since we cover pharma not John McCain).
The Zyprexa documents made for interesting reading, and it so happens they were leaked to the NYT, so that became, for awhile a primary source, and since then, something of a benchmark for coverage.
Lilly, meanwhile, hasn’t released all of the documents, so if Lilly wants to complain about material taken out of context, Lilly could clear that up by releasing all the documents. The drugmaker has not done so. Whatever its reasons, the drugmaker has itself to blame.
Hope this helps
ed
Dan
If I may add to Ed’s comment noted above, there may be other variables related to documents associated with zyprexa in addition to what has already been stated that are prevented from being disclosed to the public due to possibly some sort of court order. Furthermore, anything presented about zyprexa so far that may have been misrepresented, embellished, or exaggerated would pose libel issues from various publishers who have had similar stories related to this zyprexa issue, and would likely be a catalyst for an immediate response from it’s developer as well, from an image paradigm.
Matthew Holford
Laurie wrote:
“…The whole debacle is a catch 22 of who knew what and when AND what the did about it, which is this case was nothing…”
I think that this is the crux of the matter, and it seems to be important to the industry’s business model that none of these issues are ever resolved (because if these issues were resolved, the discussion would move onto a new level). The current dispute over Seroxat (Paxil), in the UK, looks very similar.
Matt
Justice in Michigan
I think my question is not quite being understood.
One of the privileges of participating in a forum like Pharamlot is that it includes a wide range of people - from industry, academia, health profs, pt. advocates, and beyond and beyond.
Each such group is itself enormously diverse, as we all know.
In any event, for lots of people essentially “on the outside,” it is easy to jump on what we know (or think we know) about Zyprexa and draw predictable conclusions. Those may be accurate. Or they may not be.
The opportunity I was trying to create here was to hear how stories like this are “taken” by people in industry. I offered several options, none of which, of course, are exclusive of the other:
- The NYT selectively released info to make journalistic hay at Lilly’s expense.
- This is the kind of malfeasance (Lilly’s) that ruins it for the rest of us and contributes to the erosion of trust in the industry.
- Or something else, and a range of permutations.
So I’m trying to get beyond what may be “knee-jerk” responses to such stories, whoever’s knees we’re talking about. how does this “play” - especially for those inside the industry?
I am enormously - and genuinely - interested in learning from them about that.
Grieving
Google AHRP.ORG, archives pre 2006, type in Zyprexa, and take a look. This is a March 3, 2002, article by Tim Wheeler in the Baltimore Sun. It tells of the sudden and unexpected death of my only son from profound hyperglycemia from Zyprexa, on which he gained 100 pounds. He was forced onto this drug by Maryland Medicaid having done well mostly on lithium for the previous 13 years. After this and two other front page articles in the WS JNL and NY Times, Lilly got worried that they alone would get fingered for diabetes, and well they should have, but the FDA made all atypicals place a warning for diabetes, hyperglycemia, and death. Eventually the word death disappeared.
This article was the first that I know of that brought this problem to the public, and the first time Lilly lied in public.
Grieving
The article came out in March, 2003, not 2002
Ed Silverman
Hi Folks,
Just to reiterate a point that may not be understood - Lilly can make documents available; no judge can order a company not to make its own documents available. So if Lilly wants to discuss context, it can do so and has had all weekend, as one loyal source reminds me, to find the documents for its arguments.
Hope that helps, at least a little.
ed
Justice in Michigan
Grieving - What happened to your son, and your family, is horrible. Everyone here would feel that.
The “case” against Zyprexa marketing, as it has appeared in the NYT as well as other sources as you cite, evokes a clear response in most people. It is not positive.
But I believe we could all learn, and be served, by learning more about the range of ways people in industry - an enormously diverse group - “take it,” or don’t.
I apologize for coming back to this. The loss of your son obviously means more than such questions.
Justice in Michigan
Thanks, Ed. Yes, I think the ‘general’ view is that the last thing Lilly wants is to have even more internal documents go public, which is how the settlement has been explained.
That may or may not be an accurate analysis. It is related, but separate, from the question that possesses me.
Maybe I should go out and get some exorcise.
Dan
Ed,
Not to continue a debate with you as a layperson when it comes to legal matters, but although no one can prevent you from acquiring documents from a pharma company or created by a pharma company, discussing them to some degree may be prohibited.
Please correct me if my beliefs are inaccurate.
Thanks.
Ed Silverman
Hi Dan,
I was referring to Lilly’s ability to introduce its own documents into the court record, which it could do in state court in Alaska, should it wish to do so.
In federal court in NY, Lilly reached an agreement to keep certain documents under seal as part of the product liability litigation. Some of those documents were the subject of the NYT stories more than a year ago and the subsequent controversy over the publication of those documents. The federal judge overseeing that litigation was quite angry over the fact that those documents were leaked.
To read more about that brouhaha, go to the little search button on the upper right corner of the screen on my main page and type in ‘egilman,’ berenson, ‘weinstein,’ and ‘gottstein.’ These were the key individuals figuring in that episode.
Hope that helps,
ed
nathan
Justice,
First, I have no knowledge of Zyprexa beyond what is in this article. However, the way understand it, Dr. John Gueriguian was examined by the prosecution on Friday. He hasn’t been cross-examined by the defense yet. As far as I can tell, Lilly has not had an opportunity to put any of the documents into context. Since there is an ongoing trial, they are certainly not going to PUBLICLY put those documents into context — that would be grounds for a mistrial. Wait till Monday and see what cross-examination takes place and see what new evidence is introduced. Lilly cannot introduce evidence in its defense until cross-examination begins.
But I’ll admitt that on the surface it looks pretty damning to them…
Bob Freeman
Nathan, good points–I had not thought of that: Lilly not having an opportunity to cross-examine the witness and, therefore, their inability to respond.
Back to Judge, I generally don’t form opinions about a newspaper’s motives in publishing a study, nor do I draw a conclusion about Lilly’s guilt or innocence in the short-term.
Yet, I also agree it doesn’t look good so far.
Dan
Ed,
Thanks for the clarification and I do recall he NYT Lilly story regarding exposed documents that were sealed.
But if you think about it, how many others have access to such documents, so it was somewhat of an empty threat by the judge, yet he appreared rather vexed at the exposure. If true, than no one can be directly blamed for leaking most documents that may be under seal.
Ed Silverman
Hi Dan,
Well, until the documents were leaked and circulated, no one had access because of the seal. And despite his anger at what he called a conspiracy, the federal judge didn’t require various web sites to return what they received. So in that way, Zyprexa documents remain accessible. But you should go back and read the chain of events if you want to digest the reasons for why the judge laid blame where he did.
ed
Laurie
“until the documents were leaked and circulated, no one had access because of the seal”
Key point…if these weren’t leaked the public would have no idea that they even existed. Would the diabetes risk been pushed to the point it has if these documents weren’t out there? I don’t think so.
That’s what’s so distressing about the whole situation. I understand corporate “secrets”, but when they effect an individuals health all bets are off..and should be!
Lisa Van S
Ed,
Why would the Zyprexa documents be any different from Paxil and Viox. Lill is concerned with one thing, and one thing only,their profits. If the have nothing to hide, then they should release the raw data for all to see. Until then they shouldnt ask to be trusted. Look how long they played down the Murder/suicide side effects of Prozac. Hiding behind Trade Secrets is the Coward man’s way out.
Lisa Van S
Hopefully the suicidality relating to Zyprexa will rear its ugly head during this trial!!!!
Former pharma Marketing Exec
To JIM:
You asked about NYT and what the industry thinks - from my perspective, this is interesting. The NYT is usually a little more biased towards pharma - I know I am rattling some cages again. This is because we buy lots of advertising, which pays the bills. Sometimes it is hard for them to keep their objectivity.
If you watch NBC nightly news - just about every commercial is an add for a drug. Have you seen them ever do a full blown investigative report? I can’t remember seeing them do it. 60 minutes does…
We in the industry are suppose to monitor ourselves when it comes to marketing practices. There are mechanisms in place which I am sure you all know about. There are regulatory requirements that we are supposed to follow.
How does the industry feel about these types of incidences, yes some of us do realize that these situations harm us collectively as an industry.
Lisa, I agree with you about releasing the raw data. Primary investigators do not get to see the entire raw data themselves and very often the studies are written by hired medical writers or employees of the company and you know what that means.
After so many years in the industry I often wonder how it is that people actually think they will get away with this.
You all know how I feel about this. This case is really outrageous (they all are) but they knew about this for quite some time..
I hope there is a class action lawsuit…This is the problem, patients will now get stuck with the bill for the drugs and treatment to control their diabetes. They need to get full compensation for this, but this does not make the situation better.
ErnestR
I haven’t read about any suicides related to Zyprexa specifically as the press and law enforcement are
very reluctant to name specific drugs and a mere suicide is hardly press worthy anymore. You really have to go out and kill about 5-10 people now and turn the gun on yourself to get a headline. Of course most of these turn out to be on anti-depressants but there is a growing amount of people doing this on anti-psychotics. William Freund was the first one I noticed. He was being treated for Asperger’s with Geodon and really didn’t start making threatening statements and postings until he got on that drug.
http://www.thetrenchcoat.com/categories/27-William-Freund
http://specialchildren.about.com/b/2005/11/02/teen-with-aspergers-shoots-neighbors-self.htm
A recent case in White Lake Township, Michigan, Mark Ott, being treated for bipolar, just killed his parents out of the blue. No specific drug mentioned but who has bipolar and is not on an anti-psychotic? Unfortunately, there is so much of this going on that will never see the light of day. Media will report these horrific murder/suicides and blame it on guns (much like blaming drunk driving on cars) but Mark Ott used a knife so we probably should ban those too.
Unfortunately nobody gets paid to document or collect up any of these accounts so about the time somebody on an anti-psychotic is doing a major murder/suicide once a week is about the time it will sink into public consciousness. We are just about ready to accept the role anti-depressants play in these murder/suicides but by the time we do, big pharma will have kids all switched over to anti-psychotics and be good for another 10-20 year run of pulling the wool over the public eye.
Justice in Michigan
Thanks to comments from Nathan and FME. As has been noted, a lot of the Zyprexa stuff has been out for some time. But cross will certainly be interesting. Guerigian famous from the his time at FDA, particularly re: Rezulin review which did not meet W-L’s or senior management’s approval.
Had a terrific student who graduated last year. She already had a job with Lilly. She was afraid to read the Zyprexa stuff when it first came out because of what it might say about where she was heading.
This kid is the salt of the earth. Whatever else would be, people like her are certainly part of the solution.
truthman
“Lilly is simply following the well-established cost-benefit analysis business plan”
I think this is standard practice now for Pharma…
They know that even if a drug is defective and shows signs of dangerous side effects in clinical trials , they can suppress that information and deny it for the lifetime of the drug…
They make their billions and pay out a percentage to the inevitable lawsuits which follow decades later later..
What a sick and twisted business model…
truthman
“Hiding behind Trade Secrets is the Coward man’s way out”
Trade secrets may be ok for safeguarding a recipe for apple pie , but when pharma uses it to safeguard its profits as patients die from defective drugs then it is a pathetic and cowardly excuse…
Nathan
“Lilly is simply following the well-established cost-benefit analysis business plan”
Truthman,
This is not entirely evil. Take seatbelts as an example. Have you heard about seatbelts that have killed people? I have. (car into a lake, can’t get seatbelt off) Airbags have killed many, many people. But as a society we accept these inventions. Why? Because the save far, far more lives than they hurt.
I’m not saying that all pharmaceuticals fall into this category. But many do. There is a “cost benifit” analysis that is take by society — and there is a similar “cost benifit” analysis taken by companies.
I’ll end by saying that there is NO PLACE in this buisness for lying and covering up data. That is not part of a “cost benifit” analysis that I’m talking about. Deception is wrong. Cost-benifit analysis is just fine when it’s conducted in the open. The FDA has to make these kind of calculations all the time.
Justice in Michigan
Nathan writes:
I’ll end by saying that there is NO PLACE in this buisness for lying and covering up data.
I think that’s a formulation a lot of us, insiders and outsiders, could live with well. Definitional issues remain, but that is certainly the core.
lemmy
and watch this movie in teh same context, and:
einen schönen Sonntag!
http://plus7.arte.tv/de/detailPage/1697660,CmC=1939990,scheduleId=1932934.html
lemmy
we have a global problem, think so.
Grieving
The individual with bipolar who killed his parents may well have been on lithium and ANTIDEPRESSANTS. The SSRIs have been the main cause of homicide. But there have been plenty of reports of atypicals and suicide which have not made the mainstream media.
I find it highly unbearable that Eli Lilly threw my son’s life away based on lies and a cost-benefit analysis. I’ve seen their budgets - a little line item to pay off (mostly a very measly amount) family members killed by their drugs.
I would like to see a tasteful Vermont-granite or marble sculpture placed in a prominent place in the heart of Washington with a plaque to all the thousands upon thousands of people killed knowingly by prescription drugs. A little consciousness-raising to government and industry - both out of control, and for families - a recognition of their family members’ deaths, all hidden from view, and a place to grieve.
Most times I post, there isn’t even a response….oh no, don’t want to talk about THAT.
Grieving
The Zyprexa papers that were released by Jim Gottstein to Alex Berenson at the NYT can be found on the blog furious seasons. I believe they got a lot of traffic from Lilly lawyers prior to the Alaska trial.