Pharmacy Benefit Managers as Pharmaceutical Marketers

We posted a number of times about questionable practices Eli Lilly used to market its atypical anti-psychotic drug Zyprexa (olanzapine). A post from 2007, with links backward, is here, and our most recent post is here. The company remains entangled in litigation over its marketing of this drug. That litigation has lead to the release of numerous internal documents that provide quite a view of Lilly's marketing practices. Bloomberg continued its reporting on these documents, with its latest effort here via the Boston Globe, describing yet another surprising way this drug was sold:

A unit of CVS Caremark Corp. used its access to doctors to market Eli Lilly & Co.'s Zyprexa antipsychotic while it was under contract to bargain with the drug maker on behalf of health insurers, internal Lilly files disclosed in a multibillion-dollar lawsuit by insurers show.

The subsidiary of CVS, the largest US drugstore chain, touted Zyprexa starting in 2003, according to e-mails made public by lawyers suing Lilly for overpayment. CVS's AdvancePCS, a pharmacy benefit manager, or PBM, offered to send 120,000 letters to doctors promoting the drug, Lilly's top-seller with $4.7 billion in sales last year, according to a confidential 2004 proposal. The CVS unit said it would charge $5 per letter.

AdvancePCS, acquired by Woonsocket, R.I.-based CVS in 2007, said in the documents that the direct-mail campaign was 'designed to influence key prescribers' as part of a 'tactical plan for Zyprexa.'

Furthermore,

In AdvancePCS's 2004 pitch to Lilly offering to send out letters promoting Zyprexa, Kevin Aholt, the company's assistant vice president in charge of strategic alliances, said he could target physicians based 'on the most recent AdvancePCS claims data,' according to the unsealed documents.

Aholt also said that one of the 'key issues' in the market for antipsychotic drugs was finding ways to 'accelerate the growth of new patient starts,' according to the proposal.

Also,

Steven Fuchs, an official at the PBM, asked Lilly officials in an April 2004 e-mail whether he should include information about Zyprexa's ability to calm agitated patients in the next round of letters to doctors.

'Would a discussion of that be something you would want to include?' Fuchs asked, according to the document.

Lilly marketing executive Scott Dell responded in an e-mail that officials at the drug maker had discussed asking AdvancePCS to include material highlighting 'the new bipolar maintenance indication for Zyprexa.'

AdvancePCS was not the only pharmacy benefits manager (PBM) that offered to help sell Zyprexa.

CVS rival Express Scripts Inc. also sent out Zyprexa marketing letters, according to the unsealed documents and also isn't named as a defendant in the suits.

So here we have at least two pharmacy benefit managers (PBMs) offering to help market a particular drug, for money, of course. What is the problem here?

CVS's contracts with insurers and pensions meanwhile place it in an adversarial posture with Lilly, requiring it to use its buying power as leverage in drug-price negotiations.

'The problem is that PBMs are negotiating these hidden deals while at the same time telling employers that they represent them at the negotiating table,' said Gerry Purcell, a former PBM executive who advises companies on their drug plans. 'These documents will add fuel to the perception that the companies and the PBMs are in cahoots with each other.'

Also,

While PBMs negotiate on behalf of insurers, most states don't designate them as agents of the benefit plans, said Robert Garis, a pharmacy professor at Creighton University in Omaha who studies the industry. As a result, they aren't legally required to act only in the best interest of their clients, he said. Maine is one of a few states that have specified PBMs as fiduciaries, or agents, he noted.

'The companies have gotten around that by adding language to their contracts that exclude them from having to meet those fiduciary duties,' Garis said.

Apparently, in this case, one PBM said it disclosed its relationship to the drug company to physicians, but it is not clear whether it was disclosed to the health care insurers and managed care organizations which paid the PBM to reduce the costs of drugs:

CVS, which isn't a defendant in the Lilly suit, said that it tells doctors when it has 'financial relationships' with drug makers and that they are free to opt out of mailings.

'To engage in a point/counterpoint in a media outlet rather than in court would not be productive,' said Lilly spokeswoman Marni Lemons.

Lemons declined to answer specific queries about the CVS or Express Scripts letters, whether Lilly paid for the practice, or other questions raised by the unsealed documents....

CVS said in its e-mailed statement that it has 'no active educational programs' related to Zyprexa.

'CVS Caremark discloses to its PBM clients that it may have financial relationships with pharmaceutical manufacturers in connection with these educational programs,' said Christine Cramer, a spokeswoman for the chain. 'CVS Caremark's PBM clients are aware of these programs and have the opportunity to opt out.'

Maria Palumbo, a spokeswoman for Express Scripts, didn't respond to eight telephone and e-mail requests seeking comment.

CVS covers 82 million people, with a market share of 12 percent, and is the largest pharmacy benefit manager, according to Atlantic Information Services. Express Scripts, which covers 55 million people, is the fifth largest. PBMs process about 75 percent of the retail prescriptions written annually in the United States, according to the insurance plans.

The insurance plans sued the drug maker in 2005, contending it used researchers, pharmacy benefit managers, advocacy groups, and public agencies to promote Zyprexa.

Whether or not the PBMs disclosed their relationships to the pharmaceutical company to everyone who might be interested, it does seem that having PBMs who are supposed to help insurers and managed care organizations control drug costs be paid by pharmaceutical companies to market drugs is yet another new species of institutional conflict of interest. Like the many other conflicts of interest, individual and institutional, we have discussed, this one appears to be mutually advantageous to the parties involved. However, it could have adverse consequences for physicians, patients, and the health care system. If the organizations that are supposed to be controlling drug costs are also promoting expensive drugs, the likely result would be excess prescription of expensive drugs to patients who may not derive benefits from the drugs outweighing their harms.

This is another reminder how much we need more sunshine shone on the multitudinous conflicts of interest affecting just about every type of actor within the current US health care system.

Post Title → Pharmacy Benefit Managers as Pharmaceutical Marketers

A Handbook for Ghost-Writing

We posted a number of times about questionable practices Eli Lilly used to market its atypical anti-psychotic drug Zyprexa (olanzapine). A post from 2007, with links backward, is here, and our most recent post is here. The company remains entangled in litigation over its marketing of this drug. That litigation has lead to the release of numerous internal documents that provide quite a view of Lilly's marketing practices. In particular, a Bloomberg news article discussed how the company used ghost-writers:

Ensuring that medical journal articles presented Zyprexa study results in a positive light was one way for Lilly to reach its sales goal, company officials said in its plan, according to the documents.

To do that, Lilly officials hired ghostwriters to prepare submissions to journals such as Progress in Neurology and Psychiatry, according to the unsealed documents.

The article then described how Lilly marketers set up a ghost-written article.

'The paper for the Progress in Neurology and Psychiatry supplement has been completed and sent to the journal for peer review,' Kerrie Mitchell, an employee of the public relations agency Cohn & Wolfe, wrote in a Feb. 23, 2001, e-mail to Michael Sale, a Lilly marketing official. The message was among the unsealed files.

'We ‘ghost’ wrote this article and then worked with author Dr. Haddad to work up the final copy,' Mitchell said in the e- mail. Eric Litchfield, a spokesman for Cohn & Wolfe, didn’t immediately return a call seeking comment.

Peter Haddad, a researcher at Greater Manchester West Mental Health NHS Foundation Trust in the U.K., was listed as the article’s lead author. Haddad didn’t respond to requests for comment.

The global Lilly team approved a draft of Haddad’s ghost- written paper in 2000, according to the unsealed documents.

Lilly marketers, rather than articles' putative authors, sometimes exerted pressure to get ghost-written articles published. For example,

Lilly officials e-mailed journal editors to complain about delays in publishing favorable Zyprexa articles, according to the unsealed documents.

In one instance, Lilly employees contacted the Journal of Clinical Epidemiology about delays of an article criticizing a previously published piece linking Zyprexa, as well as the class of atypical antipsychotics, to diabetes.

After Suraja Roychowdhury, Lilly’s senior scientific communications coordinator, wrote to the journal in November 2002, its editor, Andre Knottnerus, replied in an e-mail that it was 'a bit strange to be contacted via the Lilly product team. Dr. Buse and coauthors can contact us directly next time.'

Knottnerus was referring to the manuscript’s lead author, John Buse, a former president of the American Diabetes Association. A copy of the Nov. 22, 2002, e-mail was included in the unsealed documents.

Patrizia Cavazzoni, a Lilly staffer who co-wrote the article, e-mailed Buse on Jan. 9, 2003, seeking permission to send a separate e-mail asking to expedite publication. She also asked Buse if he would prefer 'to send it in your name?'

It isn’t clear from the e-mail chain whether the e-mail was sent by Buse or Cavazzoni.

Finally, Lilly developed a handbook for ghost-writers:

To ensure that ghostwritten Zyprexa articles met Lilly’s standards, company officials issued a guide to preparing them, according to the unsealed files.

The guide, 'Medical Press: Pre-Launch Feature Outline,' was undated. It’s unclear from the documents which teams in Lilly’s top 10 markets for the drug received it.

The primer provided a how-to for writing articles, such as instructing the author to use Zyprexa’s generic name, olanzapine, instead of its brand moniker, according to the documents. Scientists in medical research traditionally refer to a drug’s chemical name.

The guide also offered tips on how to find authors by identifying a 'key opinion leader' and providing them either an outline of the article or a finished copy. Authors could include a study investigator, an advisory board member or “Lilly-friendly” doctor, according to the documents.

A sample article laid out how a Lilly employee may find a doctor to ghostwrite a submission that would 'prepare the market' for the launch of an intramuscular injectable version of the drug. It also offered an outline for the contents of the article, beginning with background on another drug, droperidol, which had been withdrawn from several countries.

The article, with the suggested title 'Filling the Droperidol Gap,' noted that an anti-anxiety drug could be used, before going on to say, 'more advanced IM treatments may soon be available to provide a superior alternative.' The article explained that injectable Zyprexa had just received approval from the FDA, and recounted its clinical trial history.

'The anticipated forthcoming availability of atypical antipsychotics in an IM formulation could be a major step forward in the treatment of acute agitation associated with schizophrenia,' the sample article concluded.

We addressed ghost-writing frequently when we started Health Care Renewal, and have returned to the topic periodically (see these more recent links, from 2008, here and here). The most striking feature of this newest case is the use of a "ghost-writers' handbook" denoting how systematized the practice has become. With each new case, it becomes clearer how common the practice may be. Since the parties involved seem ashamed enough of the practice to try to keep it well hidden, it may be that ghost-writing is even more common than we now realize.

Nonetheless, while the practice may be common, and mutually advantageous for ghost-writers, the academics who front for them, and the marketers who hire them all, as we and others have said before, ghost-writing is dangerous to health. It deludes physicians and patients into thinking health care products are more beneficial and less risky than they really are. Ghost-writing also undermines science by shifting the agenda away from interesting and important questions to questions whose answers may mainly benefit vested interests. Finally, on a personal note, ghost-writing demoralizes honest academics who must run their own studies, write their own papers, and manage the logistics of paper submission in competition with fake authors backed by corporate money and corporate staff. Scientists and academics who allow and front for ghost-writers ought to be ashamed of themselves.

See also comments in the Clinical Psychology and Psychiatry blog, and discussion of some of the other recent revelations about Zyprexa marketing in the Hooked: Ethics, Medicine and Pharma blog.

ADDENDUM (14 June, 2009) - Also see comments by Prof Margaret Soltan on the University Diary blog on the "Stockholm Syndrome" as manifested by "key opinion leaders" in the pay of health care corporations.

ADDENDUM (15 June, 2009) - Furthermore, see comments by Dr Howard Brody in the Hooked: Ethics, Medicine and Pharma Blog.

Post Title → A Handbook for Ghost-Writing

Everything that Rises Must Converge: University of Texas High Living Executives and Eli Lilly's Marketing of Zyprexa

Recently we posted about some dubious practices at the University of Texas Southwestern Medical Center that seemed to contradict this proud academic medical institution's mission. First, there was the case of the "A-list" of local notables who were to have special access, including enhanced access to physicians (see posts here and here). Then, there was the report of how medical center executives seemed to be living the high life funded by charitable donors (see post here).

Also, more than a year ago, we posted about how Eli Lilly and Co. was alleged to have marketed its atypical anti-psychotic Zyprexa (olanzapine) to minimize its major side-effects, including frequent weight gain and the development of diabetes, and how the company was accused of marketing the drug "off-label" for medical problems and in situations for which the drug had not been approved by the US Food and Drug Administration. Since this story has since got a lot of coverage in the media and blogs, we have not returned to it for a while.

Now I have appeared to be guilty of a non sequitur. What is the possible connection between these two issues, other than they both seem to involve questionable decisions by leaders of large health care organizations?

Just wait...

Many media outlets have reported how Eli Lilly is under fire for its marketing of Zyprexa. Last month the NY Times reported on a memo that suggested the company's incoming president "appears to have encouraged Lilly to promote its schizophrenia medicine Zyprexa for a use not approved by federal drug regulators." That article noted that the company is also "under federal criminal investigation for the way it promoted Zyprexa and played down the drug's risks to doctors." Many media outlets reported late last month that the company settled a lawsuit by the state of Alaska that again charged that the company minimized Zyprexa's side-effects (e.g., see the Wall Street Journal here.)

The Wall Street Journal just reported that one large Eli Lilly shareholder was increasingly discontented by the company's current management, presumably at least in part due to how it marketed Zyprexa. Now read closely, and you will see that my hands never leave my arms...

California's public-employee pension fund plans to withhold votes for three Eli Lilly & Co. directors up for re-election next month, citing a lagging stock price and poor corporate governance.

The California Public Employees' Retirement System, or Calpers, said Thursday it will withhold votes for John Lechleiter, a long-time Lilly executive who is set to become chief executive next week. He has been on the drug maker's board since 2005.

In addition, Calpers will withhold votes for directors Alfred Gilman, provost at University of Texas Southwestern Medical Center in Dallas; and Karen Horn, a retired executive with Marsh Inc. Mr. Gilman has been a Lilly director since 1995 and Ms. Horn has been director since 1987.

'It was on their watch that Eli Lilly experienced severe stock underperformance, poor corporate governance practices, and was unresponsive to shareowners,' Russell Read, Calpers' chief investment officer, said in a press release.

Lilly said in a written statement it disagreed with Calpers' assessment of the three directors as unsupportive of and unresponsive to shareholders.

Gotcha...

So a director of Eli Lilly that was accused of responsibility for the company's poor performance, poor performance which presumably included its mis-marketing of Zyprexa, also turns out to be responsible for the management of the University of Texas Southwestern Medical Center, currently under fire for maintaining an "A-list" of favored patients, and letting its top executives live the high life on donated funds, practices that go against its mission.

This seems like a good illustration of how conflicts of interest affecting health care leaders may not be good for any of the organizations to which these leaders simultaneously owe allegiance. An academic medical institutional leader who is also a director of a public for-profit company may not be a particularly good guardian of share-holders' interests. A director of a for-profit health care corporation who also is the leader of an academic medical institution may not be a particularly good guardian of that institution's values.

Of course, conflicts like these benefit the conflicted individual, who gets power and prestige from both allegiances, plus, of course, a lot of money. (Note that according to Eli Lilly's 2008 proxy statement, Dr Gilman got $281,448 total compensation in 2007 to serve as director. In addition, Dr Gilman now owns 17,159 shares of Eli Lilly stock, currently valued at $51.76 per share, see Google Finance, for a total value of $888,150.) The conflicted individual in such a situation might well feel himself or herself to be among the power elite. And the conflicted individual in a case like this might be in a good position to help out his or her buddies in both the corporate and academic medical hierarchies.

But in my humble opinion, such conflicted leaders are not good for patients, for academia, for physicians, or for stock-holders, for that matter.

If we are really worried about the conflicts of interest created when physician trainees get pens or coffee mugs with company logos from drug companies, or practicing physicians get pizza lunches for their office staffs from pharmaceutical representatives, (see post here) then we should really worry when leaders of academic medical institutions serve on the board of directors of large health care corporations.

Post Title → Everything that Rises Must Converge: University of Texas High Living Executives and Eli Lilly's Marketing of Zyprexa

BLOGSCAN - An "Infomercial" for Avandia and Zyprexa?

On the Hooked: Ethics, Medicine and Pharma blog, Dr Howard Brody critiqued a newspaper op-ed that ostensibly decried excessive litigation in health care, but also seemed unduly concerned with defending Avandia and Zyprexa, two drugs that did turn out to have more adverse effects than expected.

Post Title → BLOGSCAN - An "Infomercial" for Avandia and Zyprexa?

US States Using Pharmaceutical Company Funded Program to Influence Physicians' Prescribing

The Pioneer Press just reported on how Minnesota, and other US states, use a program funded by Eli Lilly & Co which is meant to reduce physicians' supposedly inappropriate use of anti-psychotic medications. Eli Lilly is also the manufacturer of one such medication, olanzapine (Zyprexa).

One of the nation's largest drug companies is helping Minnesota cut costs and reduce questionable prescriptions of psychiatric drugs to poor and disabled residents.

Officials with the Minnesota Department of Human Services defended the program, which is funded by Lilly but run by an independent contractor, Comprehensive NeuroScience. State officials believe CNS has saved money for Minnesota's fee-for-service health plans, but more important, it has corrected some questionable prescriptions of expensive and powerful psychiatric drugs.

'Cost is an issue, certainly, but what is most important is that we get the right health care for patients,' said Brian Osberg, assistant commissioner of the human services department.

Twenty states have contracts with CNS, which identifies doctors who are prescribing psychiatric drugs outside of recommended guidelines for safety and effectiveness. A common problem is patients taking two or three antipsychotic drugs at once, despite an increased risk of side effects and no evidence that patients benefit by taking multiple drugs.

The states then send warning letters to doctors, who can decide whether to alter their prescriptions.

The article noted that states that use the Lilly program seem to have adopted policies that tend to favor Lilly and its products. In particular, neither Minnesota nor the other states that use the Lilly program uses prior authorization schemes to control drug use.

Opponents believe states are paying Lilly back for this help by keeping its drugs off prior-authorization lists. Such lists prohibit doctors from prescribing drugs without first gaining permission from the state.

Lilly is the manufacturer of Zyprexa, a top-selling antipsychotic drug. Minnesota's fee-for-service health plans spent more than $28 million on Zyprexa in 2005, and $103 million on antipsychotics in general. That more than doubled the 2000 total of $43 million for the plans, which cover 200,000 poor and disabled Minnesotans.

While other states have used prior authorization to curb these soaring costs, Minnesota has not. In fact, none of the states with Lilly partnerships use prior authorization to manage antipsychotic drugs.

Wisconsin had a contract with Lilly until last year, when the state's Medicaid agency placed antipsychotic drugs, including Zyprexa, on the prior authorization list. State officials were informed shortly thereafter that Lilly was canceling the program.

A Lilly spokeswoman acknowledged that the company is trying to discourage states from using prior authorization.

Furthermore, another of Minnesota's policies seems to tilt toward Zyprexa.

In February, Minnesota encouraged patients to split cheaper double-strength pills instead of taking multiple smaller-dose pills, which can save money for the state at the expense of drugmakers.

The 'dose optimization' strategy was required for Abilify, Geodon and Seroquel - which are competing antipsychotic drugs - but not for Zyprexa.

'Pure coincidence that dose optimization and tablet splitting are utilized exclusively for Eli Lilly's competitors?' asked Ben Hansen, who has sued to expose Michigan's partnership with Lilly. 'I don't think so.'

Human services officials replied that there was no financial benefit to placing Zyprexa on the pill-splitting list.

The program has its local critics:

If the state 'asks Eli Lilly to help decide how to buy prescription drugs, or even General Motors to help decide how to buy a car, I guess I'm going to be concerned about that,' said Ronald Hadsall, assistant dean of the University of Minnesota College of Pharmacy. 'That just smacks of conflict to me.'

A state's program to make physician prescribing more appropriate already threatens physician autonomy, but could be justified if physicians' relevant current prescribing is clearly not in patients' best interests, and if the program would clearly suggest prescribing more in patients' interests. However, the threat to autonomy cannot be justified for the sake of a program supported by a single drug company which seems to tilt the playing field in that company's favor. The state's use of this program seems to be participation in a stealth marketing scheme, made worse by its association with the aura of government power

Hat tip to Kaiser Daily Health Policy Reports.

Post Title → US States Using Pharmaceutical Company Funded Program to Influence Physicians' Prescribing

Data About Zyprexa's Adverse Effects Still Lost in the (Legal) Fog

We have posted (most recently here , here, here, and here) about allegations in a New York Times series that Eli Lilly and Company had used questionable marketing tactics to promote its atypical anti-psychotic drug Zyprexa (olanzapine), and especially that the company had suppressed information suggesting that the drug had more adverse effects than previously reported, and then how the company tried to restrict publication of the internal memos on which these allegations were based.

Last week, Alex Berenson in the NY Times reported again concerning the continuing controversy about whether Eli Lilly & Co suppressed data about the adverse effects of Zyprexa. Now the US Food and Drug Administration (FDA) seems also to have doubts about whether Lilly provided it was accurate data.

Per the Berenson article,

The Food and Drug Administration is examining whether Eli Lilly & Company provided it with accurate data about the side effects of the antipsychotic drug Zyprexa, a potent medicine that has been linked to weight gain and diabetes.

The F.D.A. has questions about a Lilly document from February 2000 in which the company found that patients taking Zyprexa in clinical trials were three and a half times as likely to develop high blood sugar as those who did not take the drug.

That document was not submitted to the agency. But a few months later, Lilly provided data to the F.D.A. that showed almost no difference in blood sugar between patients who took Zyprexa and those who did not.

The F.D.A. confirmed its inquiry in response to questions from The New York Times. The agency said it had not yet decided whether to take any action against Lilly.

'The F.D.A. continues to explore the concerns raised recently regarding information provided to the F.D.A. on Zyprexa’s safety,' Dr. Mitchell Mathis, a deputy director in the psychiatry division of the agency’s center for drug evaluation and research, said.

The Zyprexa document that has aroused the most interest at the F.D.A. is a Feb. 21, 2000, paper in which Lilly scientists discussed whether Zyprexa’s label should be changed to alert doctors of the risk of hyperglycemia, or high blood sugar, associated with the drug.

The paper showed that 154 of 4,234 patients, or 3.6 percent, who took Zyprexa in clinical trials developed high blood sugar. Only 1.1 percent of patients who took a placebo developed the condition.

Doctors have said that difference is worrisome because most patients in the clinical trials were taking Zyprexa for only a few weeks or months.

The data that Lilly provided to the F.D.A. was notably different from the results discussed in the February 2000 paper, with the gap between the two patient groups much narrower. The company told the agency that patients taking Zyprexa developed high blood sugar at a 3.1 percent rate, while those taking the placebo had a 2.5 percent rate.

[Lilly spokesman] Mr. [Phil] Belt said that after the February 2000 paper, Lilly performed a final quality check of the data and discovered that some patients had been incorrectly included in the analysis, while others had been excluded.

'The original data referred to in the memo was a preliminary analysis, not the final accurate analysis that was provided to the F.D.A., and is therefore very misleading,' he said.

The rebuttal by Lilly mirrors that found in a press release of December 21, 2006. The Lilly press release does not provide further explain what precisely was wrong with the data that apparently showed an excess of hyperglycemia associated with Zyprexa, or how the errors were rectified. Nor did it explain why the company produced the internal 2000 document detailing data that was so quickly proven to be preliminary and error ridden. The latter document may be in the cache of more than 300 documents that is still publicly available (here), but I cannot readily determine which one it is.

Thus we are in an evidence limbo. The very limited evidence that has appeared in public is insufficient to judge whether there was good reason to think in the year 2000 that Zyprexa caused hyperglycemia and diabetes, and whether Eli Lilly withheld data that would have been supported this conclusion.

Apparently evidence sufficient to clear up this conclusion exists. But it remains in the hands of Eli Lilly, which so far has not seen fit to release it. Instead, apparently Lilly is continuing to persue a legal case against the people who first released its documents to the public, thus ensuring that the evidence remains obscure. As reported by Nature this month [Giles J. Court case to reclaim confidential data. Nature 2007; 446: 838-9],

A public-health expert in the United States is facing a potential jail term or a hefty fine after distributing documents that contain safety data on a blockbuster drug. The material came to light during initial negotiations in an ongoing lawsuit over the drug, and its manufacturer says that the information should have remained confidential.

The case, which could result in charges of contempt being levelled against the expert, shines light on the murky debates that go on between lawyers before drug liability cases get to court.

The latest incident centres around David Egilman from Brown University in Providence, Rhode Island, who is a frequent critic of the pharmaceutical industry....

Egilman had access to 15 million pages of confidential documents containing clinical-trial data and details of marketing plans that Lilly had released to lawyers during pre-trial negotiations, known as the discovery phase. But because the cases were settled before they reached court, the material was bound by confidentiality agreements.

[An] attorney, James Gottstein of Anchorage, Alaska, subpoenaed Egilman for the Zyprexa documents and then forwarded them on to the [NY Times] reporter [Alex Berenson].

Although Egilman was subpoenaed to release the documents, he and Gottstein could face jail terms or be required to contribute to Lilly's legal bills if the contempt proceedings proceed and are upheld.

Thus, the evidence that would allow physicians (and patients) to decide whether Eli Lilly suppressed data about adverse effects of Zyprexa remains tied up in legal proceedings. The company has not made any effort to make any of this evidence public. Of course, continuing to suppress evidence about the suppression of research evidence can only raise further suspicion that the latter (and first-order) suppression of evidence did, in fact, occur.

And pharmaceutical executives seem to always be baffled about why the public may not trust them?

If Lilly wants to be better trusted, company executives should try a big dose of transparency. Why not clear up the fog, and fully release the February, 2000, document, and details of why its data was erroneous, how it was corrected, and how the corrections turned out?

Meanwhile, maybe the FDA will be able to figure it out for us.

NOTE: See further discussion of the latest wrinkles in the Zyprexa case here on the Clinical Psychology and Psychiatry blog.

NOTE (May 1, 2007): See this post on Furious Seasons which links to the February, 2000 document in question above. On quick review of this document, I found that it did summarize data that the rate of "treatment-emergent" hyperglycemia in the (apparently pooled) group of patients who were given Zyprexa in multiple clinical trials was 3.6%, versus the rate in the (apparently pooled) placebo group of 1.05%. However, the document did not give much explanation about where this data came from, how the trials were done, or how the data were pooled.

Post Title → Data About Zyprexa's Adverse Effects Still Lost in the (Legal) Fog

More on the Zyprexa Memos

We have posted (most recently here , here, and here) about allegations in a New York Times series that Eli Lilly and Company had used questionable marketing tactics to promote its atypical anti-psychotic drug Zyprexa (olanzapine), and especially that the company had suppressed information suggesting that the drug had more adverse effects than previously reported, and then how the company tried to restrict publication of the internal memos on which these allegations were based.

The case continues to bubble. The Los Angeles Times (and others) reported that a New York judge ordered the original copies of the leaked memos returned, but will not suppress their continuing dissemination and discussion, especially on the internet.

A federal judge in New York gave websites a partial victory by acknowledging today that when documents are published on the Internet they take on a life of their own, an existence that cannot be reversed by a court.

Senior U.S. District Court Judge Jack B. Weinstein issued a mixed decision in the closely watched case involving documents relating to the drug Zyprexa. The case pitted opponents of the drug against its manufacturer, Eli Lilly & Co., and both sides claimed at least part of a victory.

The Brooklyn jurist ordered that the documents be returned to the proper officials and enjoined eight parties from further distributing the documents, which are part of civil liability cases. But Weinstein noted that the wave of modern communication made it all but impossible to extend a traditional legal remedy such as an injunction to the Internet.

'To extend the reach of the injunction further might involve the court in attempting to control a constantly expanding universe of those who might have, or will have, access by reason of the original breach,' Weinstein wrote.

'That such an amplified injunction could be enforced effectively is doubtful. Even if enforcement were possible, on policy grounds the risk of unlimited inhibitions on free speech should be avoided when practicable,' he said.

So in the spirit of promoting free speech on this issue, we continue...

Meanwhile, Reuters reported that US Food and Drug Administration staff scientist and whistle-blower David Graham also worried about the Zyprexa case.

U.S. lawmakers should investigate the Food and Drug Administration's handling of side effects linked to Eli Lilly and Co.'s antipsychotic medication, Zyprexa, an agency whistle-blower said on Tuesday.

FDA scientist Dr. David Graham told a congressional hearing the drugmaker and the agency knew 'for a long time' about the risk of weight gain from Zyprexa that could trigger diabetes.

While such side effects were eventually added to the drug's prescribing instructions, Graham testified it was not clear how the agency handled the information or made the decision to alter the label.

'FDA did its typical dragging its feet on post-marketing safety issues,' he told Reuters after the U.S. House of Representatives Energy and Commerce subcommittee hearing.

Finally, Slate has started reporting about the troubling content of the Zyprexa memos, and may be the first at least quasi main-stream media outlet to actually print one of the memos after the court order.

Today's memo (which comes via furiousseasons.com and appears below and on the following 12 pages) is from a 2001 campaign by Lilly's marketing department to encourage doctors to prescribe Zyprexa. Part pep talk and part "message" script, the memo instructs sales reps to tell primary care physicians to prescribe the anti-psychotic drug directly to their patients rather than refer them to psychiatrists (see page three) because such referrals are often 'expensive' and 'difficult to schedule.' On Page 9, Lilly sales reps are instructed to say that the most common side effect of Zyprexa is … 'somnolence.'

The memo sounds an awful lot as though Lilly wants its sales reps to tell primary-care physicians to prescribe Zyprexa for off-label uses. The law permits doctors to do so, but Lilly's executive vice president of science and technology, has stated flatly: 'We do not engage in off-label promotion.' That's difficult to square with the script on Page 3. 'Doctor, you know your patients better than any other clinician,' the memo reads, before describing three patient types a primary care physician would commonly see in his office: 'Martha,' an aged widow who is difficult for her family to manage at home; 'David,' who suffers from a probable 'mood disorder'; and Christine, a twentysomething who struggles with 'a history of poor work performance.' None of these hypothetical patients would appear to suffer from schizophrenia or bipolar disorder, which are the only two conditions Zyprexa is approved for.

It sounds like the arguments that Eli Lilly really did try to bury discussion of Zyprexa's adverse effects, and try to get physicians to prescribe the drug off label are getting harder and harder to refute.

I would add that as a primary care physician, I have been troubled by the pushes I have perceived to get us to screen for depression even in patients who do not appear depressed, and aggressively prescribe SSRIs and even atypical anti-psychotics on our own for depression, before and often in lieu of psychiatric attention and treatment. I have gotten the impression that some people thought we are not doing our jobs if we are not handing out SSRIs to just about everyone who felt a bit "down," and using even more aggressive medication in people with more severe symptoms. Now I'm beginning to think the pushes I perceived were there, were at least partially coming from pharmaceutical marketing, and were not just a product about our feelings of inadequacy when treating psychiatric disease.

And to conclude, like a broken record, if pharmaceutical companies want to earn back some of their lost trust, they will have to publicly and clearly forgo these sorts of over-aggressive and questionable marketing practices.

For other opinions on the Zyprexa case, see the Clinical Psychology and Psychiatry blog here and PharmaGossip here and here.

Post Title → More on the Zyprexa Memos

An Ironic Juxtaposition: Continuing Fall-Out from the Zyprexa Memos and Increases in Eli Lilly's Executive Compensation

We have posted (most recently here and here) about allegations in a New York Times series that Eli Lilly and Company had used questionable marketing tactics to promote its atypical anti-psychotic drug Zyprexa (olanzapine), and especially that the company had suppressed information suggesting that the drug had more adverse effects than previously reported, and then how the company tried to restrict publication of the internal memos on which these allegations were based.

The Los Angeles Times ran an op-ed by Richard Zitrin from the Center for Applied Legal Ethics at the University of San Francisco about the secrecy resulting from how Eli Lilly & Co settled the Zyprexa-related law-suits.

DRUG GIANT Eli Lilly & Co. recently settled 18,000 lawsuits brought by people claiming they were injured by the side effects of its biggest-selling drug, Zyprexa, which is used to treat schizophrenia and bipolar disorder. But the $500 million in settlements says less about the dangers of the drug than the dangers of secrecy.

About 18 months earlier, Lilly had settled 8,000 other Zyprexa cases for $700 million. But those settlements required the plaintiffs to return all sensitive documents obtained through the legal discovery process to Lilly — a requirement that kept the strongest smoking-gun evidence out of public view. The plaintiffs also had to agree 'not to communicate, publish or cause to be published, in any public or business forum or context, any statement, whether written or oral, concerning the specific events, facts or circumstances giving rise to [their] claims.'

Lilly had strong motivation to settle. The documents contained evidence that Zyprexa caused large, often enormous, weight gain in many patients, significantly increasing the risk of dangerously high blood-sugar levels and diabetes. They also showed that Lilly knew about the problems in 1999, largely through its own research. Other documents outlined a marketing scheme to encourage physicians to prescribe Zyprexa for elderly patients with early signs of dementia. This strategy not only had no clinical evidence to support it, it promoted an 'off-label' use not approved by the Food and Drug Administration, a violation of federal law.

When secrecy is the price of a legal settlement, wrongdoers hide their mistakes as if they never happened and continue with business as usual. That's what happened in the Lilly case.

Courts have the power to grant protective orders only to limit the disclosure of highly personal information and legitimate trade secrets. But when all the lawyers in a case agree, judges often grant protection even if the trade secrets in question show how the product does not work, not how it does. Neither lawyers nor judges should ever be party to such agreements. It is simply unacceptable as a matter of public policy to permit secret deals that conceal evidence of dangers to the public.

The civil justice system belongs to all of us, and no one should be allowed to use it to keep the public in the dark.

It is ironic how such continuing criticism of Lilly's attempts to keep unfavorable information about its products or its management actions out of the public sphere is coming out as the same time as this report from the Indianapolis Star.

Lilly's top execs reap rewards
CEO's 2006 compensation was $15.2M

A year after top executives at Eli Lilly and Co. saw their compensation packages fall, the Indianapolis-based drug maker is giving them a reason to smile again.

Lilly raised the salary of Sidney Taurel 4 percent last year and gave him a hefty increase in bonus pay, stock grants and options, bringing his compensation package for the year up 16 percent to $15.2 million.

Other top executives also saw their compensation rise -- some by more than 80 percent -- in what the board said was a way to reward them for the company's performance.

But Lilly's share price has lost ground, falling about 8 percent last year, even as the Standard & Poor's 500 health-care index rose 4 percent. Lilly's stock closed at $54.64 Tuesday, down 3 cents.

'The share price went down, so I don't know how to justify these big raises,' said Les Funtleyder, an analyst at Miller Tabak & Co. in New York.

So let's see, continuing news stories and commentaries suggest Eli Lilly has been trying to hide unfavorable information about its blockbuster drug Zyprexa, the company's share price is falling, and yet its top executives are getting large increases in their already lavish compensation. At a time when physicians are increasingly under pressure to submit to "pay for performance" (P4P) plans, one wonders what criteria for performance are used by Eli Lilly to set the pay of its hired top executives?

Post Title → An Ironic Juxtaposition: Continuing Fall-Out from the Zyprexa Memos and Increases in Eli Lilly's Executive Compensation

More About the Zyprexa Marketing Memos

We previously posted (here, here, here, and here) about allegations in a New York Times series that Eli Lilly and Company had used questionable marketing tactics to promote its atypical anti-psychotic drug Zyprexa (olanzapine), and especially that the company had suppressed information suggesting that the drug had more adverse effects than previously reported, and then how the company tried to restrict publication of the internal memos on which these allegations were based.

More keeps coming out about this topic. The Times (UK) added some information about the internal memos.

Eli Lilly, the American pharmaceutical giant that has consistently denied any link between Zyprexa, its antipsychotic drug, and diabetes, was concerned about the side-effects of the drug as early as 1998, according to documents seen by The Times.

A series of leaked court documents seen by The Times suggested that the company was aware of the risks of weight gain, hyperglycemia (high blood sugar) and diabetes associated with the drug but presented them as common problems across the whole class of schizophrenia drugs and not restricted to Zyprexa.

In one document dated October 9, 2000, Robert Baker, a senior Lilly clinical research physician, e-mailed colleagues about a meeting of an academic advisory board he had attended in Atlanta. It had 'reinforced my impression that hyperglycemia remains quite a threat for olanzapine and may merit increasing even further medical attention and marketing focus on this topic'. Dr Baker added: '[The board was] quite impressed by the magnitude of weight gain on olanzapine and implications for glucose.'

Another internal document dated October 14-15, 1998, described the risk of weight gain as a 'top threat' to Zyprexa.

A statement from Lilly said that the documents represented 'a tiny fraction of the more than 11 million pages of documents provided by Lilly as part of the litigation process. They do not accurately portray Lilly’s conduct nor represent an accurate view of Lilly company strategy or activities.'

It added that the documents were 'selectively and illegally leaked'.

Meanwhile, the New York Times reported on the growing number of investigations of how Eli Lilly marketed Zyprexa.

On Thursday, lawyers from the consumer protection division of the Illinois attorney general’s office demanded that Lilly hand over marketing materials, e-mail messages, and other documents with information about promotion of Zyprexa. Vermont investigators issued a similar order yesterday morning.

The orders are the civil equivalents of criminal subpoenas, according to Deborah Hagan, the chief of the Illinois consumer protection division.

Illinois and Vermont are now part of a coordinated five-state civil investigation into the way Lilly promoted Zyprexa, a treatment for schizophrenia and bipolar disorder. The states are investigating whether Lilly tried to hide Zyprexa’s risk of causing weight gain and other risks associated with diabetes and whether the company promoted Zyprexa for use in patients who do not have schizophrenia or bipolar disorder.

The orders on Thursday and yesterday are the first formal demands for Lilly documents from state attorneys and they indicate an escalation of the investigation, according to Ms. Hagan and Julie Brill, who is an assistant attorney general in Vermont.

In a statement yesterday, Lilly said it would cooperate with the investigations and had done nothing wrong. 'We intend to cooperate with the Illinois attorney general’s civil investigative demand relating to Zyprexa,' the company said. We cannot comment further about this or other ongoing investigations.'

While the investigation being led by Illinois is civil, other investigations into Lilly’s conduct are both civil and criminal. Attorneys general in California and Florida may seek to recover Medicaid payments that the states made for Zyprexa. Medicaid represents a sizable percentage of the drug’s overall sales because many people who take the medicine are disabled and do not work.

Sounding like a broken record (if anyone remembers what that means), patients and physicians need the best possible evidence about benefits and harms to decide on treatments. Any attempts to hide such evidence in support of vested financial interests may hurt patients. A pharmaceutical (or biotechnology or device) company that seeks to quiet the discussion of the benefits and harms of their products should not inspire trust.

See also related comments here on the Clinical Psychology and Psychiatry blog and here and here on the PharmaGossip blog.

Post Title → More About the Zyprexa Marketing Memos

Unringing the Zyprexa Memos Bell

We previously posted (here, here and here) about allegations in a New York Times series that Eli Lilly and Company had used questionable marketing tactics to promote its atypical anti-psychotic drug Zyprexa (olanzapine), and especially that the company had suppressed information suggesting that the drug had more adverse effects than previously reported, and then how the company tried to restrict publication of the internal memos on which these allegations were based.

The New York Times has continued its reporting on the subject,

It all began with Dr. David Egilman of Massachusetts, who was a consulting witness in ongoing litigation against Lilly. Dr. Egilman had in his possession a trove of internal Lilly documents — not all of them flattering to the company — sealed by the court as part of that litigation.

Comes James B. Gottstein, a lawyer from Alaska, who was pursuing unrelated litigation for mentally ill patients in his state. He somehow got wind (and precisely how is the subject of separate legal jujitsu) that Dr. Egilman had some interesting documents.

Mr. Gottstein sends Dr. Egilman a subpoena for copies. Hell begins breaking loose.

In a letter dated Dec. 6, Dr. Egilman informed Lilly’s lawyers, as was required by the order sealing the documents, that he had been subpoenaed. Lilly’s lawyers expressed their deep displeasure in a Dec. 14 letter to Mr. Gottstein, and politely told him to back off. In a response a day later, Mr. Gottstein informed them, among other things, that it was too late, and that some of the material had already been produced.

It seems Mr. Gottstein was also apparently in a sharing mood, which is how hundreds of pages ended up with a Times reporter, Alex Berenson — and about a dozen or so other individuals and organizations.

United States District Judge Jack B. Weinstein ordered Mr. Gottstein to provide a list of recipients to whom he had distributed the contraband pages, and to collect each copy back.

The Times, which politely declined to oblige, has since been left out of the legal wrangling, but on Dec. 29, the court temporarily enjoined an expansive list — 14 named individuals, two health advocacy groups (MindFreedom International and the Alliance for Human Research Protection), their Web sites, and a site devoted to the Zyprexa issue — not just from 'further disseminating these documents.' They were specifically ordered to communicate the injunction to anyone else who had copies, and enjoined from 'posting information to Web sites to facilitate dissemination of these documents.'

That’s right — it appeared that even writing on their Web sites something like, 'Hey, there’s a site in Brazil where you can get those Zyprexa documents,' would run afoul of the injunction.

The order was extended by Judge Weinstein on Jan. 4, and tomorrow the court will revisit the issue at length.

So now there are serious free speech issues (involving the First Amendment to the US Constitution) involved.

While surely painful for Lilly, the online proliferation began flirting with some bedrock principles of free speech and press, as well as some practical realities that looked a fair bit like toothpaste out of its tube.

As Mr. von Lohmann and the Electronic Frontier Foundation see it, the injunction is simply untenable. Whatever the legal merits of Lilly’s claims against Mr. Gottstein and Dr. Egilman for violating the seal, the court’s power to stifle the ever-growing chain of unrelated individuals and Web sites who, after one or two degrees of remove, had nothing to do with the Lilly litigation, cannot extend to infinity. Very quickly, Mr. von Lohmann argues, you are dealing with ordinary citizens who are merely trading in and discussing documents of interest to public health.

There is also a traditionally high bar set for placing prior restraint on the press — which, whether Judge Weinstein recognizes it or not, very much includes a colony of citizen journalists feeding a wiki.

For now, copies of the Lilly documents sit defiantly on servers in Sweden, and under a domain registered at Christmas Island, the Australian dot in the ocean 224 miles off the coast of Java. 'Proudly served from outside the United States,' the site declares. There are surely others.

On his TortsProf blog, William G. Childs, an assistant professor at Western New England School of Law in Springfield, Mass., put it this way in a headline: 'Judge Tries to Unring Bell Hanging Around Neck of Horse Already Out of Barn Being Carried on Ship That Has Sailed.'

I cannot comment on the legal merits of the argument that the Eli Lilly memos about Zyprexa should not have been published.

It does seem to me that any effort to restrict discussion of the case by parties not involved in the case would be a serious general affront to free speech.

Furthermore, to make the best possible medical decisions for individual patients, the patients and their health care professionals need the best possible evidence about the benefits and harms of therapy. Thus, patients, health care professionals, and ultimately the public have a need to know about the benefits and harms of medications like Zyprexa, and about any attempts to suppress or manipulate such evidence by interested parties, particularly the medications' manufacturers.

Although I can appreciate Eli Lilly's interest in having a fair day in court, the company's attempts to corral documents that put its managers in an unflattering light do not enhance trust in how the company is run.

Hat tip (see this post) in the Clinical Psychology and Psychiatry blog.

Post Title → Unringing the Zyprexa Memos Bell

Eli Lilly Threatens Zyprexa Whistle-Blowers with "Very Severe" Sanctions

We previously posted (here and here) about allegations in a New York Times series that Eli Lilly had used questionable marketing tactics to promote its atypical anti-psychotic drug Zyprexa (olanzapine), and especially that the company had suppressed information suggesting that the drug had more adverse effects than previously reported.

The latest issue of the British Medical Journal featured a news article by Jeanne Lenzer about how Lilly has tried to suppress publication of the internal memos on which the Times based its series. [Lenzer J. Drug company tries to suppress internal memos. Brit Med J 2007; 334: 59. ]Lenzer wrote,

The drug maker Eli Lilly instigated legal action against a number of doctors, lawyers, journalists, and activists over hundreds of internal corporate documents and emails said to have been obtained by them regarding the antipsychotic drug olanzapine (Zyprexa). Eli Lilly obtained a court injunction on 29 December ordering 16 individuals and organisations to stop publishing the documents and to remove any copies posted on the internet.

The documents created a furore after they were leaked to the New York Times, which reported that they showed that Eli Lilly "engaged in a decade-long effort to play down the health risks of Zyprexa" (www.nytimes.com/2006/12/17/business/17drug.html).

Eli Lilly disclosed the internal documents to the attorneys for the plaintiffs in a pending class action suit in the US District Court for the Eastern District of New York, but they remained confidential. However, Jim Gottstein, a lawyer representing a client in a separate court case in Alaska complaining about the coercive use of antipsychotic drugs, subpoenaed the documents from David Egilman, a prominent occupational health expert and an expert witness in the New York class action suit.

Alex Reinert, attorney for Dr Egilman, said that his client did not violate the law in releasing the documents under subpoena to Mr Gottstein. Mr Gottstein, who acknowledges giving the documents to the New York Times, said that he didn't violate the law as he was not a party to the confidentiality agreement issued in the New York class action suit.

After the injunction was granted to Eli Lilly the documents rapidly disappeared from the internet. The company was given access to Dr Egilman's computers for three days for 'forensic examination'; and Mr Reinert said that Eli Lilly has indicated that it wants to seek 'all possible sanctions' against Dr Egilman. The consequences, Mr Reinert said, 'could be very severe' and could conceivably extend to compensatory damages and time in jail.

Mr Gottstein said that Eli Lilly has also warned him of possible 'disciplinary action at the bar.'

Eli Lilly, in email messages to the BMJ, states that it is pursuing action because 'these individuals have violated a federal court order by leaking the documents' and that it has not released its internal documents publicly because the company 'has no intention of violating that order by releasing documents ourselves.'

It added, 'We intend to try the remaining cases in court—not in the news media.'

Eli Lilly also states that 'documents that have been illegally leaked to the New York Times are a tiny fraction of the more than 11 million pages of documents provided by Lilly as part of the litigation process. They do not accurately portray Lilly's conduct.'

The leaked documents, says the company, were "only a few hundred of the 11 million pages" and had been "carefully selected by the ‘leakers' to tell a story that the ‘leakers' want them to tell."

Eli Lilly's statement to the BMJ continued: 'These documents do not in any way represent an accurate view of Lilly company strategy or activities. What these individuals are not likely to show you is the millions of other pages of documents demonstrating how Lilly and its employees have worked to improve the lives of people with schizophrenia and bipolar disorder.'

This is a chilling development. It seems to me that patients, physicians, and the public ought to know whether Lilly marketed Zyprexa honestly, or whether it sought to deceive, and particularly whether it sought to suppress or manipulate data from trials on patients who thought that the information about them was to be used for the advancement of science, not commercial marketing purposes.

Lilly, of course, has a right to explain its actions, and defend itself from any allegations about its conduct.

But for a drug company to threaten whistle-blowers with "very severe" sanctions, including jail time, in a case like this does not exactly inspire confidence in their commitment to transparency, or to putting the welfare of patients, particularly patients in drug trials, ahead of marketing concerns.

Post Title → Eli Lilly Threatens Zyprexa Whistle-Blowers with "Very Severe" Sanctions

More on Questionable Marketing of Atypical Anti-Psychotic Drugs

Yet more information is emerging about questionable practices used by pharmaceutical companies to market psychiatric medications.

The New York Times has continued its series about how Eli Lilly and Co. marketed its best-selling anti-psychotic drug, Zyprexa (olanzapine). Yesterday it published an article suggesting that Lilly suppressed data that suggested a relatively high rate of adverse effects from the drug, while releasing data that made the drug appear safer:

For at least a year, Eli Lilly provided information to doctors about the blood-sugar risks of its drug Zyprexa that did not match data that the company circulated internally when it first reviewed its clinical trial results, according to company documents.

The original results showed that patients on Zyprexa, Lilly’s pill for schizophrenia, were 3.5 times as likely to experience high blood sugar levels as those taking a placebo, according to a February 2000 memo sent to top Lilly scientists.

The 2000 memo indicates that it was prepared as Lilly considered changing Zyprexa’s prescription label to provide doctors with more information about the drug’s potential to raise blood-sugar levels.

According to the memo, Lilly scientists initially wanted to propose a relatively straightforward statement on the label that high blood sugar had been observed in patients taking Zyprexa in clinical trials. That change was never made.

According to the memo, Lilly had reviewed data from its clinical trials and found that 'the incidence of treatment-emergent hyperglycemia in olanzapine group (3.6%) was higher than that in the placebo group (1.05%).' Olanzapine is the generic name for Zyprexa.

But when Lilly subsequently discussed the clinical trial results with doctors, it used a different comparison. Lilly told doctors that Zyprexa had caused 3.1 percent of patients — not 3.6 percent — to have high-blood sugar. And it said that 2.5 percent of patients on the placebo — not 1.05 percent — had high-blood sugar. As a result, the rates of high blood sugar in the two groups seemed almost identical in the revised data.
Another Lilly report, from November 1999, shows that Lilly found after examining 70 clinical trials that 16 percent of patients taking Zyprexa for a year gained more than 66 pounds.

The company did not publicly disclose that figure, instead focusing on data from a smaller group of clinical trials that showed about 30 percent of patients gained 22 pounds.

A few days earlier, the Times had published an editorial on Lilly's marketing of Zyprexa.

It was bad enough when studies showed that the newest and most heavily promoted drugs for treating schizophrenia weren’t worth their high cost. Now the disturbing tale of their excessive use has taken a tawdry turn with revelations that Eli Lilly, a pharmaceutical giant, has consistently played down the risks of its best-selling antipsychotic drug, Zyprexa, and has promoted it for unapproved uses.

Although Lilly says the documents present an inaccurate picture, they offer persuasive evidence that the company engaged in questionable behavior to prop up its best-selling drug, which creates almost 30 percent of Lilly’s revenue.

Meanwhile, it was widely reported that Bristol-Myers-Squibb had agreed to settle charges having to do with problems with its sales and marketing practices, particularly of its big-selling atypical anti-psychotic drug, Abilify (ariprazole). Again, from the New York Times report:

Bristol-Myers Squibb has reached a tentative agreement to pay $499 million to settle a federal investigation into illegal sales and marketing activities from the late 1990s through 2005, the company said yesterday.

That settlement, and separate special charges the company also announced yesterday, would wipe out Bristol-Myers fourth-quarter profit.

Bristol-Myers, based in New York, declined to disclose which years, which drugs and which practices the tentative agreement covers. But Jeff Macdonald, a company spokesman, confirmed previous reports that one product involved was the antipsychotic drug Abilify, one of the company’s best sellers.

Bristol-Myers said it also expected to sign a corporate integrity agreement with regulators in the Health and Human Services Department who monitor industry compliance with federal insurance programs.

The antipsychotic drug Abilify covered in the settlement has become the company’s best-selling product outside of its flagship cardiovascular group....

There is increasing reason to fear that the basis of much current thinking about the management of major psychiatric disorders, particularly schizophrenia, is on very shaky ground. More and more of the information that pharmaceutical companies have provided to physicians appears to be dubious. And very recently, allegations surfaced that pharmaceutical companies got far too cozy with state mental health departments to develop treatment algorithms for major psychiatric disease that emphasized the use of the newest, most expensive drugs, even though it is no longer clear that these drugs are so much better than older and cheaper treatments (see post here). Note that these Texas Implementation of Medication Algorithms (TIMA) pushed five new atypical anti-psychotic drugs for schizophrenia, including Abilify and Zyprexa.

To take the best possible care of each patient, physicians (and patients) need maximally accurate and unbiased information about the performance of drugs, devices, and diagnostic tests. It may be in the financial interests of companies that make such products to gimmick the data in their favor, but such manipulation can hurt patients, and surely is an unheralded reason for the continuing rapid rise in health care costs.

It is high time to get pharmaceutical, biotechnology, and device companies out of the business of the clinical testing of their own (or competitors') products. Let these companies sponsor the basic biology research needed to develop innovative new products. Clinical research on patients to evaluate these products should be done by organizations and researchers with no horse in the race.

Post Title → More on Questionable Marketing of Atypical Anti-Psychotic Drugs