A New Jersey appeals court decided last week that a trial court should reconsider whether an expert should be allowed to testify in a lawsuit alleging the Accutane acne drug causes depression. And the move, which comes as part of long-standing litigation over the issue, may cause some controversy. The New Jersey trial court, where hundreds of lawsuits allege Accutane is tied to depression, had ruled that Emory University professorDoug Bremner should not be allowed to offer expert testimony due to what was considered a flawed study. His study was funded by Accutane plaintiffs and lawyers, and published in a peer-reviewed article in the American Journal of Psychiatry in 2005. Accutane, by the way, was withdrawn last year, although generics are still available.
Using positron emission tomography scans, Bremner found metabolic changes in the brains of acne patients treated with Accutane that were not present in those given antibiotics. The area affected was the frontal lobe which is associated with depression, The New Jersey Law Journal writes. Based in part on the study, Bremner provided a report concluding Accutane can cause depression and suicide. Roche, which sold the drug, challenged the report and a subsequent hearing found missing data, inaccurate data and that Bremner failed to follow methodology he claimed to have used. A trial judge decided his study was central to his opinion and dismissed the case.
Now, though, the appeals court decided the study comprised only a portion of Bremner's opinion and he may yet testify, although the study itself won't be introduced (see here). Meanwhile, the Drug & Device Law blog calls the decision "amazing," and labeled the study "junk science" and "litigation-inspired trash," likening it to the scandal over Andrew Wakefield and his autism research in The Lancet (see here). In turn, Bremner writes on his own blog that the study was largely funded by a parent not directly connected with the litigation (although the parent's son committed suicide while on Accutane) and attempts to explain problems with the reported data which, he notes led to a single-line correction, not a retraction.
The links offered in our post, notably the ruling, provide some context, so please take a look. And then tell us what you think...
Did The Court Make A Mistake By Saying Bremner Can Testify?
- No (73%, 93 Votes)
- Yes (27%, 34 Votes)
Total Voters: 127
50 Comments
I voted "NO"... Congratulations Dr. Bremner.
I voted "NO"
"should not be allowed to offer expert testimony due to what was considered a flawed study"
So the drug company lawyers wants to pick and choose which flawed study can be used in court?
I'm little befuddled; especially considering the Pharma industry's record related to flawed and tainted drug studies. This whole issue appears somewhat ludicrous and rolling on the floor hysterical as a defense tactic.
Gee, Paxil Study 329 rings a bell...
Great post, Ed. Any parent of a son or daughter with scarring-type acne should pay special attention to this one. Nothing we do in medicine is not without some risk. Sorry about the double negative. I intend to look at the functional brain imaging study in detail (so many projects, so little time). The study design is everything. Sometimes pilot studies are done simply to know whether to look at the question further. Quite a few teenagers become depressed because of their acne, independent of treatment.
This really goes to the wider question of the criteria for any expert witness--a question about which I have no knowledge!
I'm wondering if folks who testified, in Vioxx, that VIGOR could be explained by the cardioprotective effects of naprosyn would also be accused of "junk science" by DDL. Certainly, they were so accused by FDA.
That was a pretty unprofessional rant from the drug & device law blog, wonder where they get their funding from?
Obviously only physicians in the employ of pharma have the requisite skills to properly interpret the data. Outside experts need not apply .Than again there is always preemption
Ed, I also commented on the court's decision, which uncovered some disturbing facts about the study--namely that Bremner et al didn't do what they said (or implied) they did and that one outcome was negated because of discovered errors in data entry. Without the pretrial hearing, this information would not have come to light--despite the fact that the study was peer reviewed (a necessarily limited--even potentially meaningless--stamp of approval).
Bremner now evidently bases his argument associating Accutane with depression on other data--which, frankly, I find pretty slim. His inclusion as an expert witness in the trial is apparently being treating here as something of a validation of his worthiness and/or the plaintiffs' stance. But the soundness of the Accutane-depression association remains to be seen. Bremner's reputation, because of the court's opinion, has already been tarnished where it counts--and that's not in the blogosphere.
I wasn't going to way in here but I feel the need to clarify the prior statement. The "not doing what they said they did" was related to a questionnaire called the skindex that was an acne quality of life survey not even in the original protocol. It was described as given "before and after treatment" where not all of the subjects got the questionnaire after treatment. The post treatment data was not presented (it was analyzed later and had no impact on the study results) and so it boiled down to the error of saying it had been given post treatment when not all of the subjects got it, which was corrected in the letter of correction which you can now access in the journal. The primary result of frontal lobe brain function was unchanged. A secondary (i.e. not most important outcome) of ratio of frontal lobe to global activity was no longer significant after the data was re-analyzed, as I stated in my post and as is stated in the correction. I'm not sure why pharma has decided to change from my primary (clearly stated in the original protocol) to my secondary outcome, when they have repeatedly changed from primary to secondary (e.g. Paxil 329) when it suited them. As for relying on "other data" that simply is not true. The brain imaging study was always just one part of the extended literature that I used for my opinion. Finally, since Dr. Martin hasn't disclosed that she works as a writer and marketer for pharma I will do that for her here.
Dr. Martin,... Shame on you dear, you should have disclosed your conflict of interest, and by not diclosing, you have ultimately tarnished your own reputation.
Ed, The good ole Dr. Martin is looking for some press time,... I will assume she has an agenda to push. She really should have disclosed her COI..
Given the finding in the Merck Vioxx case that Merck had a "hit list" of doctors "to seek out and destroy where they live", the recent verdict on Dr. Wakefield, and this case the message is clear: publish against phrama and get destroyed. That's just their MO now.
Thanks for the explaination on the error Dr. Bremner.
Oy vay. If you go to my blog, my employment experience is clearly indicated. I have worked in pharmaceutical marketing--although nothing related to Accutane, and I have no vested interest in whether Accutane causes depression or suicide. Dr. Bremner, given that he is a paid expert witness for Accutane plaintiffs, most certainly cannot say the same.
Moreover, my employment history has no bearing on the court's findings and its problems with Dr. Bremner's study. That stands alone--regardless of what I did or do for a living and whether I write about the court's opinion. To cast aspersions on me is a diversion.
If nothing else, the court has shown the shortcomings of the peer-review process (as Jim Beck emphasized), specifically with respect to the publication of Dr. Bremner's study.
If you see it as a weakness of peer review that they don't have two years and a million dollars to comb through every piece of the raw data-- as Roche did in this case-- and pay their experts handsomely instead of asking them to do it for free-- then so be it. I might that after this lengthy process there was no dispute that the primary outcome was the same. After all of this Roche accused me of fraud and I was cleared of those charges by a university committee who had access to all of the data and the legal documents. Finally, I don't see why private citizen Liam Grant shouldn't be able to donate money to support research that he is interested in (the donation did not pay my salary, so I wasn't "paid" to do the study, and the source was disclosed in the 2005 paper) when women in the US can donate money for breast cancer research, or pharma can pay for research that suits its marketing goals.
I would just like to add that "oy vey" is usually spelled that way. There are occasional references to "oy vay," but it has limited street cred. One also sees "oy vai," but pretentiously.
Tradition.
As far as DDL's clients, oy ve (accent aigu).
So when a study includes 1-2 year olds in a "recieved MMR but does not have autism diagnosis" group even though it is virtually impossible to get an autism diagnosis before the age of 2, this is excellent peer-reviewed science that should be unquestioned.
But when someone like Dr. Bremner finds something uncomfortable we've got to look through every detail to find some tiny mistake and we declare the peer-review process worthless.
I get it.
Dr. Martin, You could have easily provided the Pharmalot Readers with a link to your blog and pointed out your financial interests.
Secondly, Dr. Bremner has also been a paid Clinical Investigator for GSK, and the antidepressant paxil so to state he is solely a plaintiffs Doc is false.
So, what expertise in suicide and depression do you have to bring to the table?
Oh, I got it now, the good ole Doc is a ghostwriter.
what about all the drug company studies that leave out the people who got worse or even died? drug companies falsify their research everyday to get their drugs through the FDA (hopelessly easy) and onto the market as fast as possible where millions of unsuspecting Americans can pay for the privilege of being "lab rats" in stage 4 post marketing studies. when the body count gets so high that even the FDA begins to suspect cause and effect, then the drug might be withdrawn from the market but only after a replacement one has been introduced or the patent protection period is over. more people were killed by VIOXX than died in Vietnam and yet i don't recall seeing mass protests against the war being waged on Americans by drug companies. of course Dr. Bremner should testify and his studies should be allowed as evidence as well!
Ha ha ha I love it when someone gets outed as a pharma employee online and then they come back and act like it's no big deal.
Dr. Martin what is your interest in this if not to help pharma? Do you have bad acne or something?
If I were involved with pharma I think now would be a time when I would be afraid to open my mouth what with all the news that just keeps flooding out everywhere about people under investigation and being sued or prosecuted etc. But that's just me.
Oh, Dr. Martin, what tangled webs we weave.
Hi Barbara,
A belated acknowledgement of your own post on your blog. Since you didn't include a link, I'll do so for you...
http://www.pathophilia.com/
Thanks for stopping by and engaging the crowd.
Regards ed
Hi Ed,
In general I like your posts but I think you have done a disservice with your statement "what was considered to be a flawed study" which is an echo of the comments on Andrew Wakefields MMR vaccine study for which a link was made by the DDL blog. I don't think that anyone other than the supporters of Roche would consider the study "flawed" (although there were data entry errors which were corrected)
This discussion has become sublime. We can now compare the two studies in question (Wakefield’s and Bremner’s) directly, hold them up side by side for comparison and analysis. There are differences.
http://ajp.psychiatryonline.org/cgi/reprint/162/5/983
http://www.generationrescue.org/pdf/wakefield2.pdf
Thanks for posting the link to my blog, Ed. Although, as you know, your comments section allows one's link to be embedded in one's name. (Sigh. I guess the traffic is welcome.)
As for "engaging the crowd," as you put it, I'm not sure the diverting pile-on will induce anyone with anything but a complete anti-pharma stance to post here. Too bad a more intelligent and on-point discussion of the subject--one that avoids the production of rabid foam--isn't possible.
KUDOS to bmartin for her articles at her pathophilia.com blog:
Litigation-Driven Research: Getting Over the Ick Factor By bmartin on February 8, 2010
Accutane-PET Study Discredited in Court Opinion By bmartin on February 5, 2010
I support Dr. Bremner, I voted NO
I voted no, Dr. Bremner would be a breath of fresh air in and maybe bring some wisdom to my home state.
I support Doug Bremmer, and all the brave pharma warriors like him.
Now that so many drug cases are finally seeing some public legal action, I find it interesting that so few of the highly paid KOLs are showing up on the expert witness lists of the drug companies.
Might there be a few credibility problems? I think this issue would make for a more interesting point of discussion.
I'd sure hate to see Paul Offit, M.D. as an "expert" witness.
"a child can tolerate 10000 vaccines"
Credibility problems? No kidding!
are we surprised that the voting is 3 to 1 in favor of Dr. Bremner? NO! it's high time the citizens of this once free nation woke up and realized that they are being maimed and murdered in the name of profits
I'm sure that none of the pharma hacks are foaming at the mouth since they probably all got their rabies vaccines already. Every year.
By the way, I agree with Evelyn. It's been All Quiet on the Western Front Groups lately. No news of judges excluding witnesses in litigation like, um, I don't know - Zachary Stowe of Emory, Wisner, Biederman, etc? Gee I wonder why the attorneys for pharma defendants don't try to offer them up as experts?
Speaking of "flawed" studies - there are plenty of bogus B.S. articles floating around saying that it's safe to drug your baby with Zyprexa and SIDS is caused by a Prozac deficiency.
Seems like the good people who actually care and want to do something about drugs when they start killing people will endlessly be on the receiving end of attacks.
Some people have to learn the hard way and I say bravo to everyone who tries to warn others before it's too late for them.
Martin says she has no vested interest in whether or not the drug causes depression or suicide. She obviously means this in the strict sense of potential financial gain. I get that. Still, the phrase stopped me cold and has bothered me enough to provoke this post. In the more general sense of the term, it seems to me that every person should have a vested interest in that degree of potential harm. That sentence speaks volumes about an underlying problem. As long as drugs and their developmental pipeline are profit driven, the potential for all manner of malfeasance is huge. The only way an honorable person can participate in the enterprise is to compartmentalize their involvement in this sort of narrow way. If they were to consider their personal involvement as ethically consequential, demand for sleep-inducing drugs would skyrocket to allieviate all that tossing and turning. In the interests of full disclosure, I have no connection to either "side" in this debate. That said, a post that contains "rabid foam" sorts of hyperbole in an attempt to be clever is, sadly, outside of rational, thoughtful discourse.
I pledge to donate the majority of my future earnings as an expert witness in Accutane litigation to a non-profit institute for transparency in medicine as a counter-balance to the pharma marketing driven information that floods the US medical field and educational system at the current time.
Well I guess that's better than saying you'll donate it all and then end up only giving half.
mwhahh! love you sweets!
I'd like to address Dr. Martin's comment in regards to those of us she considers anti-pharma, who spew rabid foam.
First of all Dr., I am not anti-pharma, I am a mother, of a child, who was harmed by an unsafe drug, and not someone who is trying to finacially benefit from the misery of others.
Did you truly believe, that poisonous venim that spewed from your mouth was gonna go uncontended. Personally,.. you should be stripped of your title of Dr., best if you stick to blogging because your bed side manner is unprofessional and quite disturbing.
Did you truly believe, that poisonous venim that spewed from your mouth was gonna go uncontended. Personally,.. you should be stripped of your title of Dr., best if you stick to blogging because your bed side manner is unprofessional and quite disturbing.
Read that first line again - Venim???? Wasn't Venim in a Batman comic? So you have a child that was hurt by an unsafe environment.... I mean your daughter had problems serious enough to require treatment by a physician, but all her problems were caused by meds. I mean those drugs are venim-ous (sic)?.?.?. If you aren't antipharma I really don't have a descriptor. Maybe venim to medications?
Typo,.. so crucify me!!! LOL
Hey,.. at least I like my own name, and "I", dont have to hide behind the "raw data"...
Hi Folks,
I'd like to gently remind everyone to please stick to the issues and topics at hand.
As I've written before, this forum is like a garden party at a large estate, where you are free to flit from group to group, stopping to listen and participate when the moment strikes. But the verbal equivalent of throwing glasses or chairs will make the environment uncomfortable for everyone.
A civil dialogue, in other words, allows everyone to benefit.
Thanks Ed
Ed, I dont believe I was being uncivil, and actually, I do believe I was on topic, and its a shame that when one cant defend their actions, they have this tendency to attack the child/patients. If they want to make fun of my typo, thats fine, but, children should be off limits.
Isn't true that Roche lost seven accutane cases in a row in Florida for IBD related issues over the past two years or so? But then, a state appellate judge overturned all the rulings in favor of Roche. If I remember reading the information correctly, four different sets of jury’s had been used in four different trails which all favored the plaintiffs claims of harm done due to accutane, but still, the state appellate judge found some flaw with some expert witness which they claimed gave him/her the right to overturn all these judgments. Do I remember that correctly? How can one judge overturn something that 30+ random jurors found them guilty of? Sounds fishy to me!
"I have worked in pharmaceutical marketing–although nothing related to Accutane, and I have no vested interest in whether Accutane causes depression or suicide"
frankly dr martin, i should think that every feeling, moral, ethical, decent human being has a vested interest in whether Accutane causes depression or suicide
Both the Accutane depression linkage and the MMR autism linkage need further validation, even if both linkages ultimately end up refuted. Litigation driven research is not necessarily a bad thing. The legal hurdles required by courts to admit "expert" opinion into the record are high, as well they should be. Private parties do not have the financial resources to fund large, adequate, well-controlled studies of the type that pharma can afford and FDA typically requires. Private parties can typically support only smaller scale, pilot-type studies.
Its fair to say that both the Wakefield study and Bremner study show that such studies must be carefully designed and meticulously executed.
A question that can be asked of both investigators is, to what extent did you use the results of your study to promote the view that your study establishes either an autism linkage or a depression linkage?
"Bremner issued an expert report opining that Accutane can cause depression and suicide."
http://bmartinmd.com/2010/02/accutane-pet-study-discredited.html
"Despite rampant misreporting, Dr. Wakefield’s original paper regarding 12 children with severe bowel disease and autism never rendered any judgment whatsoever on whether or not vaccines cause autism, and The Lancet’s retraction gets us no closer to understanding this complex issue."
http://www.ageofautism.com/2010/02/a-statement-from-jenny-mccarthy-jim-carrey-andrew-wakefield-scientific-censorship-and-fourteen-monke.html
patrons99,
You keep referring to the need to further study the discredited link between MMR and autism. NO! That's a waste of money on something that's already been determined. There have been numerous studies investigating that link and no credible study has ever found a link. Let's put dollars toward treating autism where the money can do some good.
Reality Check
Hey Reality Check, I respectfully reserve the right to disagree. It's not just the MMR that's to blame. It's the stupendous vaccination schedules we have had jammed into our arms since birth. We're shooting holes in our immune systems. I cannot express the view better than Kenneth P. Stoller, M.D., FACHM, when he stated on January 13, 2009,
"The truth that vaccine policy is not about science or safety but about money and politics is finally seeing the light of day."
We're getting so many jabs nowadays, that even vaccine-vaccine interactions are starting to show up, e.g. Zostavax and Pneumovax 23.
Our immune systems have been under continuous assault with every jab, sometimes with overt clinical manifestations, sometimes subclinical, often waxing and waning, just waiting for the straw that breaks the camel's back. These vaccine reactions may well prove to be manifestations of cummulative, synergistic toxicity.
Then there's Paul Offit, perhaps the most widely-quoted defender of vaccine safety.
He's gone so far as to say babies can tolerate "10,000 vaccines at once."
I'll say it again. There will come a day when Dr Paul For Profit Offit has some seriously explaining to do. This is a global public health catastrophe. It's time we all had a reality check. It's not just the metals, adjuvants, and preservatives...what about the risk of the uncertain biologic recombinants?
DISCLAIMER: the view expressed above is simply a former bio-organic chemist's personal opinion and is not intended to be medical advice.
I vote no
Great post, Ed. Any parent of a son or daughter with scarring-type acne should pay special attention to this one. Nothing we do in medicine is not without some risk. Sorry about the double negative. I intend to look at the functional brain imaging study in detail (so many projects, so little time). The study design is everything. Sometimes pilot studies are done simply to know whether to look at the question further. Quite a few teenagers become depressed because of their acne, independent of treatment.
I full agree with the results of this poll, and I'm glad the Judge allowed the testimony of Dr. Bremner.
I believe Accutane is the only non-psychiatric drug that has been been ranked in the top 10 of the FDA AERS database for suicide attempts.
It's caused untold misery for countless families and has been tied to many serious side effects outside of depression and suicide, notably inflammatory bowel disease, Crohn's disease and ulcerative colitis.
Go Dr. Bremner!