MadInAmerica.Com recently reported on Abbott Laboratory’s $500 million sentence as a result of pleading guilty to illegal off-label marketing of Depakote and this caused me to root around on the federal courts’ electronic filing database to see what I could find out about details not reported in the media. Included among the 725 pages comprising the plea agreement (55 megabytes), was an Agreed Statement of Facts. It is a primer on many of the fraudulent and illegal ways in which drug companies boost their sales.
The above links take you to the source documents, which PsychRights has posted on its website for convenience, and I will discuss some of the items to which Abbott admitted in the Agreed Statement of Facts.
To start with, Abbott admitted that Depakote has never been approved by the Food and Drug Administration (FDA) as safe and effective for agitation and aggression in patients with dementia or for the treatment of schizophrenia.
Illegal Promotion of Depakote for Use on the Elderly in Nursing Homes
In 1999, a study of the use of Depakote in the elderly was terminated because of serious adverse events. In spite of there being no scientific justification for its use, from 1998 through 2006, Abbott illegally promoted the use of Depakote on the elderly to control agitation and aggression. If a doctor asked about the terminated study, Abbott trained its sales force to minimize these safety concerns by saying the dosages used in the study were too high.
Abbott also trained its long term care sales force to promote Depakote as safe and effective for this unapproved use, including that it didn’t have the same side effects as neuroleptics. Abbott paid bonuses to its sales force for garnering sales of Depakote for this unapproved use. Abbott also funded a prescribing “guide” from a supposedly legitimate source that promoted the use of Depakote in the elderly, with Doctors being able to earn continuing medical education (CME) credit by taking a test at the end of the guide. Abbott paid millions of dollars in rebates to Long Term Care Pharmacy Providers based on increases in the use of Depakote to their nursing home patients.
Illegal Promotion of the Use of Depakote on People Diagnosed with Schizophrenia
The “MD99-010 Study” was conducted to show the safety and effectiveness of Depakote together with neuroleptics to treat patients with “acute exacerbations of the symptoms of schizophrenia,” but it did not result in significant improvement after 28 days as compared to the use of neuroleptics alone. A consultant then told Abbott that while the study “does not support combination use (as defined strictly the combination being superior to each [neuroleptic] alone), we could still argue for [the study’s] applicability to add on” therapy. Maybe this is some medical language I don’t understand, and I am just a bush lawyer, but to me it is completely gobbledy gook. I guess they couldn’t say it was okay for “combination” therapy, but could for “add on” therapy. Maybe that is because there isn’t a definition for “add on” therapy.
There was another study, “M02-547” that also did not show a statistically significant treatment difference when Depakote was combined with a neuroleptic, but did show that somnolence, weight gain, and urinary incontinence were significantly higher for patients receiving Depakote ER combined with a neuroleptic than those treated with a neuroleptic alone. Following the completion of this second study, one of Abbott’s vice president, after stating there were no systematic problems with the study, concluded that “there is not an obvious benefit of adding Depakote to [neuroleptics] in acute schizophrenia.”
In spite of these negative studies Abbott promoted the use of Depakote as a treatment for schizophrenia. Doctors were paid $2,500 to attend a “Depakote Psychosis Speaker/Facility Development Meeting,” in which the M99-010 Study was portrayed as positive, and presentation slides given to the doctors. Abbott also organized programs at an American Psychiatric Association (APA) meeting to provide the M99-010 Study data to promote Depakote for the treatment of schizophrenia. Abbott did not present any information about the M02-547 Study.
When Abbott conducted a survey about the effectiveness of these illegal off-label promotion activities, it found a majority of surveyed providers recalled that, during their most recent visit with an Abbott sales representative, the sales representative had discussed the off-label use of Depakote as combination therapy for the treatment of schizophrenia.
Abbott funded and organized “Psychiatry Consultant Meetings,” which were used to provide information about the results of the M99-010 Study to healthcare providers. Abbott paid a $500 “honorarium” and travel expenses for each psychiatrist’s attendance. Abbott continued to present a false impression of the M99-010 Study in its promotional activities, while not presenting any information about the M02-547 Study.
Government Enforcement Actions Against the Drug Companies Are Ineffective
From my PsychRights work it is my observation that the use of Depakote in combination with one or more neuroleptics has become ubiquitous. Clearly, Abbott’s illegal promotion of Depakote was successful from a profit perspective. Depakote is an anti-seizure drug that would normally have a very limited market, yet from 1998 to 2008 Abbott’s gross sales of Depakote were approximately $13.8 Billion. The $500 million paid by Abbott as a fine for its criminal activity in promoting Depakote for use in the elderly and for schizophrenia was a small price to pay — just a cost of doing business.
Does anyone expect that the use of Depakote on the elderly, and people diagnosed with schizophrenia will plummet? I don’t. Why haven’t the past revelations of drug company fraudulent marketing causing tremendous harm to millions of patients without benefiting them resulted in any meaningful change in prescribing practices? I would suggest that the Agreed Statement of Facts should be required reading before any doctor prescribes Depakote for one of these uses. Fundamentally, the psychiatrists prescribing these drugs in this way have breached the trust that society has placed in them in exchange for granting them monopoly power over legal access to these drugs, i.e., prescribing privileges.
There is the further question of why the Government continues to pay for these off-label prescriptions, when neither Medicaid nor Medicare properly cover such uses? As succinctly stated by the court in US ex rel Rost v. Pfizer, 253 F.R.D. 11, 13-14 (D.Mass. 2008):
Medicaid can only pay for drugs that are used for a "medically accepted indication," meaning one that is either approved by the FDA or"supported by citations" in oneof three drug compendia, including DRUGDEX.
In a May, 2011 report, the Inspector General of the Department of Health and Human Services confirmed that Medicare has the same restriction:
Medicare requires that drugs be used for medically accepted indications supported by one or more of three compendia to be eligible forreimbursement.
The big fines paid by the drug companies are not effective, yet the government is ignoring the simple solution of enforcing Medicaid and Medicare’s restrictions to drugs that are prescribed for medically accepted indications. It is hard to take seriously the government’s stated commitment to rooting out fraud when this massive fraud is consciously allowed to continue. I know it is consciously allowing the fraud to continue because the government has been antagonistic to our whistleblower cases raising this point. Massive harm is not enough to cause government action. Massive fraud when the government is drowning in red ink is not enough either. What is it going to take?
Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own.
Thanks for this explicit argument, Jim. You are raising the points that reflect the state of ineptitude within the APA. The guidelines for the safe practice of prescribing psychotropic drugs should be forthcoming from the professional organization that exists to legitimize the practice of psychiatry in America. Long overdue …
Starting with “The Agreed Statement of Facts” as an example of required reading before prescribing Depakote, there is an opportunity to focus on the crux of the matter that is somehow ignored when the cases of “illegal off-label marketing” by pharmaceutical companies are reported. The dissemination of false and potentially harmful information to psychiatrists is the crux of the matter. An education campaign should be launched by the APA, along with requirements for retaining prescribing rights implicit in the successful completion of these education courses. REQUIRED CME’s for retention of the license to practice psychiatry, is what I am talking about. A professional organization concerned about safe practice, or rather, protection of trusting patients, would definitely take these measures at this time.
Incorporating the factual information that dispels the widespread acceptance of what is proven to be “illegal off-label marketing” should be immediately included in the examination for “Board Certification” of psychiatrists.
I believe that in the absence of a reasonable response from the APA regarding the evidence provided in the civil and criminal cases against pharmaceutical companies, there is reasonable cause for concern that there is no organized group of academic medicine based psychiatrists, or even any practicing psychiatrists to challenge the deaf and blind leaders of the APA, who are simply ignoring what the public is becoming more aware of. Those sitting comfortably in their seats of authority, either in academic medical centers or behind their desks, are either criticizing their opponents (us), or silently condoning the lack of response to their opponents (protecting each other). Some psychiatrists in this category, blog on MIA. I hope they reflect on their role in failing to challenge the APA, and academic based psychiatrists- DIRECTLY, as they get cheers from the MIA audience who has zero influence with either of the sources of this scourge.
From my vantage point I notice that there is precious little concern over the unsafe practices of prescribing psych drugs for children in the medicaid system or the elderly on medicare. This, unfortunately, illuminates the darker aspects of our society’s failure to protect children and the elderly from abuse, while claiming to be resolving the behavior problems in this ‘cast aside’ population. The humanism required to address the actual behavioral ‘problems’ is lacking. This is very hard to address without becoming a target. The self proclaimed martyrs in the positions within the social service agencies that can effect things like drug prescribing policies, are more likely to contend that they are employing the best approach to dealing with an impossible set of circumstances. They whine. They get hostile when criticized. They unit for the expressed purpose of removal of anyone who is making them feel badly about their shortcomings and weaknesses of character. I totally support activism within these social service agencies. It is just a very slow process riddled with numerous obstacles so long as the ‘prescribers’ continue to be criminals at large with no fear of punishment!
In discussion with my renegade colleagues, we come down to these questions:
1) How long can a psychiatrist’s ignorance of the factual information on these drugs be excused?
2) Who is responsible within psychiatry to establish the factual, scientific basis for the practice? The authors of the Board Certification exams? (Medical Board of Examiners); The reviewers who certify that a psychiatrist has met the requirements to retain his/her license? The APA? Harvard Medical School Department of Psychiatry?
3) What is a reasonable amount of time to lapse between irrefutable, established evidence of the harmful effects of of acting on the “fraudulent claims made to secure profits” by drug companies and responsible accountability by the leading psychiatrists in America?
4) When does ‘ignorance’ become ‘malicious intent’? or collusion become established between the APA and the headline making, cited for illegal off-label marketing for the sake of their own financial gain, drug companies?
5) IF the APA will not take action to regain the public trust in their medical practice as a ‘first, do no harm’ , patient -centered practice., should we hope that the legal profession will step up to the plate and prosecute the protective guardians of psychiatry as criminals?
I am deeply disappointed and thoroughly disgusted with the unabated corruption in academic psychiatry, the APA and NIMH. I think there has been adequate time for more than sufficient evidence of life endangering harm to evoke strong action from all three. The lack of action reflects an undeniable breach of the public trust, and because it is clear that financial gain is the only common denominator supporting a shared motive, I say …
“Book ’em, Jim!”
The sooner the better…
Why would the government want to stop it? This is yet another hidden tax. The government allows illegal reimbursements by medicaid which is paid for by U.S. tax dollars and then the government sues the drug companies to take a percentage of that money.
In regards to:
“consultant then told Abbott that while the study “does not support combination use (as defined strictly the combination being superior to each [neuroleptic] alone), we could still argue for [the study’s] applicability to add on” therapy. ”
I’d translate it to this, and this is from experience reading grant applications:
“Depakote’s not good for combination use. I’ll admit that. But we can bookmark this study. It has value, even though all it proves is that Depakote’s not good for combination use. The study has value in considering what to add on to an antipsychotic regimen by excluding Depakote. That’s what this study is still good for.”
If you don’t read it that way, I’d be interested in your read.
Now the *motive*. The motive is political in intent. It’s one writer’s last attempt to wring some positive light out of the reader’s confusion onto the star product by masking “rule out” with “applicable to add on therapy”. It’s deceptive.
Peer Specialist (Community Health Worker)
As someone from Australia it is amazing to watch what we want to happen here, being debated overseas. The problem here is that we are not allowed to know what drug companies spend money on and the maximum they can be fined is a mere $50,000 per drug. Our $ values are about equal with the US $!! Just trying to allow the community to even have the right to know how drug companies pay doctors and community organisations would be a start for us, but I wonder, when we will still have off label prescribing.
Like many countries we have a public health system and so all of our medications are subsidised by the government. Technically we are supposed to have two levels of checks for medications. In order for them to be allowed into Australia, they must first be approved by the Theraputic Goods Administration – our FDA. They approve them for age groups and conditions. Then if they reach a higher level of approval and there is proof the medication will be of benefit to the community they can be approved for use on the PBS (Pharmacueitcal Benefits Scheme). This is usually a really good thing and for most conditions it works great. You can usually take medications involved in medical trials, but you must be part of that trial or you must pay the full cost of the medication, and paying the full cost, means you know they are not approved for use. Except we have a loophole. ANY psychotropic medications are available under the PBS for anyone at all. We have infants under 12 months taking antidepressents and thousands of toddlers on antipsychotics. Almost every coroner in the country has demanded that nursing homes not be allowed to prescribe antipsychotics to those with dementia. The government has defended the right of these drugs to be used off label in that way and are denying families the right to make those decisions themselves.
While I want and we need for truth of what drug companies are doing here, and we need bigger fines I can also see from this that that alone will not be enough. We must stop the off labeling prescribing that is happening through the public health system and at taxpayer expenses. Although I do at times wonder how much it would change. The amount of people now taking and paying millions of dollars for off label prescriptions if huge, and private health insurance is now footing the bill for it, so most people assume if they are willing to pay it must be OK.
The fact remains though that throughout the world psychiatry is working hand in hand with drug companies and fines, even big ones make no difference at all to what they are doing. While it is questionable as to what most of these drugs do for conditions that are on label, to pay for someone to take them off label is even more pathetic.
I do however wonder if psychiatry will simply solve the problem of no government funding of off label prescribing by simply changing the diagnoses they give people, since they manage to give them out at the whim of a hat anyway. I and many others in Australia have already had that happen. I for over 10 years had a psychiatrist ring up and tell the authorities that I had schizophrenia, she said it was necessary as while the research proved that these drugs worked for PTSD they did not understand the research and would not fund them. It is so so so common here, and I can imagine the same would happen in the US. It is not as though they have any proof that we do or do not have said condition. When they fail to be allowed to prescribe it off label, simply change the diagnosis, it works wonders for drug companies and psychiatrists, just not for the individuals concerned.
Great post Jim.
Consciously! What seems perfectly obvious, is an economic motivation to outrageous dysfunction in the management of human affairs? Surely its all about the money, “we think.”
“The $500 million paid by Abbott as a fine for its criminal activity in promoting Depakote for use in the elderly and for schizophrenia was a small price to pay — just a cost of doing business.
Does anyone expect that the use of Depakote on the elderly, and people diagnosed with schizophrenia will plummet? I don’t. Why haven’t the past revelations of drug company fraudulent marketing causing tremendous harm to millions of patients without benefiting them resulted in any meaningful change in prescribing practices?
The big fines paid by the drug companies are not effective, yet the government is ignoring the simple solution of enforcing Medicaid and Medicare’s restrictions to drugs that are prescribed for medically accepted indications. It is hard to take seriously the government’s stated commitment to rooting out fraud when this massive fraud is consciously allowed to continue. I know it is consciously allowing the fraud to continue because the government has been antagonistic to our whistleblower cases raising this point.”
Yet is the real motivation far more “unconscious” than we care to admit to, and are we all guilty of collusion when it comes to the denial of our emotive-motivations? “We have permission to up their medication dosage, to make them easier to manage,” a psych nurse once told me on our blind date.
IMO Its the management of comfort & ease that “unconsciously” motivates human behaviors, like our uncanny ability to “turn a blind eye?” IMO Society operates on an emotional-dynamic far more than it does in any rational or objective way. Fear & shame motive our reactive urges more than objective rationality, in the rank and status structure of society. Hence highlighting the facts of obvious dysfunction in “the system,” always meets a predictable sweep-it-under-the-carpet response, with appeals for justice meeting the most common form of ignorance, ignore-it?
We all love to pretend that we are fully conscious human beings who “know” what we are doing? Yet judging by the state of affairs that Jim reports on, are we perhaps still waiting for the fully conscious generation to emerge, or in that other term for God, “evolve?”
Is there an unconscious cost to doing business? An emotional dynamic, as much involved in normal human motivations, as the so-called pathology of mental-illnesses? Please consider;
“Challenge to and Regulation of Homeostasis (comfort & ease)
(“The cost of doing business”)
•During the first 6-months of life the measurement of vagal regulation during feeding provides an early marker of the developmental status of the neural platform for social behavior.
•During the first year of life, cortical pathways develop that regulate the striated muscles of the face and head and the vagus continue to myelinate to form an integrated social engagement system – the same circuits involved in feeding (ingestion) and state regulation.
•As the infant matures, social context displaces feeding as the most important regulator of behavioral state.” http://ccf.nd.edu/assets/32275/porges.pdf
“social context displaces feeding as the most important regulator of behavioral state.” Consciously, my comment reply would appear to be way off-topic in regard to Jim’s post, yet consider my previous comments about how we unconsciously project “the system” onto the world “out there?” Does the above mention of the term “feeding” resonate with the emotional nature of the way human beings actually react to each other? As some cynical philosophers
note, “the cost of doing civilization, is human misery.”
“Massive harm is not enough to cause government action. Massive fraud when the government is drowning in red ink is not enough either. What is it going to take?”
More honest self-realization, and far less intellectual pretense, perhaps?