Law and Order? - Bristol-Myers-Squibb Settles Case Alleging Fraud and Kickbacks, No Admissions of Guilt, No Individuals Charged

Introduction 

Donald Trump, Republican candidate for the US presidency last week announced he is the "law and order" candidate, accompanied by then vice presidential contender and New Jersey Governor Chris Christie.



I wonder if all this interest in law and order will lead to increasing the effectiveness of enforcing laws when large US health care corporations are accused?

For years, we have been watching a parade of legal settlements made by big US health care organizations.  These have included the biggest drug companies, biotechnology companies, device companies, insurance companies, etc, etc.  Many involved accusations of fraud, kickbacks, and other seeming crimes.

In many cases, the alleged white collar crimes could have resulted in harms to patients.  For example giving physicians kickbacks to promote particular drugs or devices could have led them to prescribe treatments that could have been useless for particular patients, yet subjected those patients to risks of adverse effects.

Yet few of these cases were resolved with findings of guilt.  Many resulted in financial penalties for the accused organization, but which were tiny compared to that organization's revenue.  Almost none resulted in any consequences for the people in the organization who might have individually profited from the alleged actions, particularly the top executives who were making millions of bonuses, suggesting their apparent impunity.

This parade of settlements does not look like instantiation of law and order to me, in my humble opinion.

Bristol-Myers-Squibb Settles Allegations of Kickbacks

And the parade continues.  The latest case, which barely was noticed in the media, involved huge pharmaceutical company Bristol-Myers-Squibb.  It was best documented by Ed Silverman in Stat,

After nearly a decade of litigation, Bristol-Myers Squibb on Monday agreed to pay $30 million to settle charges by California officials of paying kickbacks to induce doctors to prescribe several of its medicines.

The settlement with the California Department of Insurance stemmed from a whistleblower lawsuit that was filed in 2007 by three former Bristol-Myers employees. They alleged that from 1997 through 2003, the drug maker used a wide variety of inducements to generate revenue. The state later joined the lawsuit in 2011 and, last year, the former employees were dismissed from the case by a state court.

The kickbacks included box seats at sporting events where doctors were given food, drinks, and parking; enrollment in a Los Angeles Lakers basketball camp for doctors and their children; prepaid golf outings at luxury courses; tickets for doctors and their families to see Broadway shows in California cities; and lavish dinners, resort hotel trips, and concert tickets for doctors who were especially big prescribers.

Among the many medicines for which doctors were persuaded to write more prescriptions were the Pravachol cholesterol pill; the Plavix blood thinner; the Abilify antipsychotic; the Glucophage diabetes treatment; and the BuSpar antianxiety drug.

A Bristol-Myers spokesman wrote us that the company denied any wrongdoing, but also noted that the firm began adhering to a voluntary industry marketing code in 2002. 'We are pleased to put this matter behind us so that we can focus on making transformational medicines for patients battling serious diseases,' he wrote.

Note that in this case, as is typical for such cases, the financial penalty seems to be minimal compared to the company's total revenues (more than $16.5 billion according to Google finance.)  The company was allowed to deny wrongdoing (although in absence of same, why should it pay a fine?)  No individuals who might have personally profited from the actions in question suffered any negative consequences.

Why Not More Severe Penalties for a Repeat Offender?

Furthermore, the outcome seems to have nothing to do with the accused's track record.  Anyone who follows the news knows that in general, penalties in criminal cases are likely to be different for first offenders and habitual criminals.  Penalties in civil cases also may depend on the defendant's track record.

However, this case, like most other cases involving big health care organizations, seems to have occurred in a vacuum, separate from the company's track record.  Yet a bit of searching reveals that BMS, like many other big health care corporations, seems to have a pretty bad record.


- In 2003, for $617 million, BMS settled suits alleging it tried to prevent competition from low cost generic versions of its products Taxol and Buspar (per the NY Times).
- In 2004, for $150 million, BMS settled suits by the SEC alleging accounting fraud (per the NY Times here).
- In 2007, BMS paid a $1 million dollar penalty while pleading guilty to lying to federal agents about a deal with the Canadian drug company Apotex (per Law360).   In 2009, it paid additional financial penalties in response to a US Federal Trade Commission charge about this case (per the FTC).
 - In 2007, for $515 million, BMS settled a suit alleging it used kickbacks to induce use of Abilify for dementia and by childeren, despite evidence that the drug was not suitable for either.  The settlement included a five year corporate integrity agreement.  (Look at our post here).
 - In 2014, BMS settled allegations its subsidiary Lantheus Medical Imaging Inc evaded state taxes (per the Corporate Crime Reporter)
 - In 2015, Bristol-Myers-Squibb settled allegations by the US Securities and Exchange Commission (SEC) that it bribed physicians in China to induce them to prescribe its drugs.  (Look at our post here).

(Parenthetically, I apologize that many of these previous cases have not been previously mentioned on Health Care Renewal.  For that I apologize.  Yet some simple Google searches were all that were required to find them.)

Why did none of the law enforcers involved in the later cases do similar searches, and why did the company's track record not figure into how the current case was resolved?

Chris Christie and the Rise of the Deferred Prosecution or Corporate Integrity Agreement for Too Big to Jail Organizations

The answer to that will not be easy.  At best, it now seems to be standard operating procedure for law enforcement to treat big health care organizations very gently.  However, there is one clue in BMS track record that it might be helpful to discuss in this political season.


Note that in one of the biggest settlements listed above, BMS agreed to a corporate integrity agreement.  According to a 2015 article in Time, the use of such agreements, coupled with apparently large fines but no other penalties, for corporate offenders was pioneered by none other than then US Attorney Chris Christie, (who spoke in the video above).

Christie was apparently horrifed by the criminal prosecution of Arthur Andersen, a big accounting firm, in the wake of the Enron scandal.  At that time, federal prosecutors acted so that

The company itself—not its employees who might have been responsible—was indicted and found guilty. The trial put the company out of business. The conviction was overturned on appeal, but not before the company’s reputation was destroyed and its employees forever branded with a Scarlet Letter, representing Andersen, not Adultery.

The article described Mr Christie's response:

Christie had watched wall-to-wall coverage of the case, and it made him uncomfortable. He decided he did not want to run his office in that way. Instead of bulldozing New Jersey companies facing smaller-scale fraud cases and leaving their employees out of work, Christie preferred to build a case against the firms and then bring their leaders in for a take-it-or-leave-it chat. Ultimately, seven New Jersey corporations accepted deferred prosecution agreements, or deals with the government that let them avoid trial in exchange for the companies hiring independent monitors to oversee operations and put in place guards against future wrongdoing.

Christie often was relieved they were open to the deals. 'Put the company itself out of business? Lose all the jobs?' Christie asked when asked about the alternatives. He pointed to a corruption case he built against St. Barnabas Health Care System, the state’s largest, for double- and over-billing Medicare and Medicaid services. St. Barnabas paid $265 million to settle the case. 'What are you going to do?' Christie asks. 'Close the hospital, the largest hospital that serves the poor?'

Neither Time, nor Mr Christie seemed to notice that this reasoning involved a logical fallacy, a false dilemma.  True, there are two options:
1) criminally prosecute the whole company
2) allow the company to operate under a deferred prosecution or corporate integrity agreement.
But there is a third option:
3) Criminally prosecute the individuals in the company who were most involved in and most benefited from the bad behavior.

So in the St Barnabas example, what he could have done was prosecute the people at St Barnabas who were most responsible for the over-billing, and let the hospital itself go with a fine. Mr Christie for some reason never seemed to think about that option.  Neither have most other US law enforcers who have dealt with large organizations since.

Ironically, Mr Christie has got himself into some ethical hot water because of how he managed corporate integrity or deferred prosecution agreements involving BMS and other health care organizations.  Some have alleged that Mr Christie found some other advantages to using such agreements, advantages that accrued mainly to Mr Christie and his cronies.  As the Time article noted, re BMS

As part of its penance, the company also proposed paying for a professor of business ethics at a law school. The company initially offered to pick up the tab at a school in New York. No way, Christie said. 'This is a New Jersey case. Pick a New Jersey school,' Christie replied. Rutgers already had such a program, and there was only one other law school in New Jersey. It just happened to be Christie’s alma mater, Seton Hall. 'It couldn’t have mattered less to me,' Christie says. 'I didn’t get anything out of it. I was long graduated from Seton Hall.' (The Justice Department signed off on the agreement, but would later limit U.S. Attorneys’ ability to negotiate such deals.)

Christie’s critics pounced on the $5 million payment to Seton Hall, and to this day are trying to use it as a way to suggest he is another pay-to-play New Jersey politician.

And in two other health care cases:

Christie hired former Attorney General John Ashcroft, his one-time boss, to monitor Zimmer Inc., one of the firms that settled with the government. In turn, Ashcroft’s company charged between $1.5 million and $2.9 million a month to monitor the medical device company. By the time Christie arrived in Washington to answer lawmakers’ questions, The Ashcroft Group had earned $52 million on that case. 'To me, that is outrageous,' Rep. Steve Cohen chided Christie. 'I don’t care what you did. It is not worth $52 million,' the Tennessee Democrat continued. 'Even if you took steroids and hit 70 home runs, it is not worth $52 million.'

Lawmakers also wanted to know why he named David Kelley to a post to oversee the Bristol-Myers Squibb settlement. Kelley two years earlier, as a former prosecutor, declined to bring securities fraud charges against Todd Christie, the future-Governor’s brother. Was this payback for sparing a Christie Family?

Mr Christie defended his conduct in the BMS case:

Christie to this day says he has no regrets about the deferred prosecution agreements, including the professor position. To him, it matters less about whether there was a conviction than whether the illegal behavior ended. 'The goal as the U.S. Attorney is to stop the conduct,' Christie says. 'If you’ve stopped the conduct, you’ve won.'

But of course the current case, and those involving BMS from 2014 and 2015, shows that Mr Christie's corporate integrity agreement did not "stop the conduct" at least in the case of BMS.  That rationale was fallacious too.


Summary

Now that political campaigners are once again shouting about law and order, maybe this is the time to call for effective and equal enforcement of the laws regarding white collar crime in health care.  For years, we have watched perpetrators of small scale Medicaid and Medicare fraud go to jail.  Yet when big companies are accused of big scale crime, almost no one ever goes to jail.

It is time for equal justice for all in health care.

Let me end with a quote from a report by Senator Elizabeth Warren (D - Massachusetts) published in January, 2016, entitled "Rigged Justice: 2016 - How Weak Enforcement Lets Corporate Offenders Off Easy."

 Laws are effective only to the extent they are enforced. A law on the books has little impact if prosecution is highly unlikely.

This country devotes substantial resources to the prosecution of crimes such as murder, assault, kidnapping, burglary and theft, both in an effort to deter future criminal activity and to provide victims with some degree of justice. Strong enforcement of corporate criminal laws serves similar goals: to deter future criminal activity by making would-be lawbreakers think twice before breaking the law and, sometimes, by helping victims recover from their injuries.

When government regulators and prosecutors fail to pursue big corporations or their executives who violate the law, or when the government lets them off with a slap on the wrist, corporate criminals have free rein to operate outside the law. They can game the system, cheat families, rip off taxpayers, and even take actions that result in the death of innocent victims—all with no serious consequences.

The failure to punish big corporations or their executives when they break the law undermines the foundations of this great country: If justice means a prison sentence for a teenager who steals a car, but it means nothing more than a sideways glance at a CEO who quietly engineers the theft of billions of dollars, then the promise of equal justice under the law has turned into a lie. The failure to prosecute big, visible crimes has a corrosive effect on the fabric of democracy and our shared belief that we are all equal in the eyes of the law.

Under the current approach to enforcement, corporate criminals routinely escape meaningful prosecution for their misconduct. This is so despite the fact that the law is unambiguous: if a corporation has violated the law, individuals within the corporation must also have violated the law. If the corporation is subject to charges of wrongdoing, so are those in the corporation who planned, authorized or took the actions. But even in cases of flagrant corporate law breaking, federal law enforcement agencies – and particularly the Department of Justice (DOJ) – rarely seek prosecution of individuals. In fact, federal agencies rarely pursue convictions of either large corporations or their executives in a court of law. Instead, they agree to criminal and civil settlements with corporations that rarely require any admission of wrongdoing and they let the executives go free without any individual accountability.

And end with a video of her speaking on the subject.

MEDSCAPE'S CME ETHICS, PART II

19 June 2008

MEDSCAPE’S CME ETHICS, PART II

A few days ago I discussed Medscape’s parasitic use of professional organizations to embellish its mediocre CME offerings – “highlights” of the closed 2007 ACNP annual meeting, for example. One of the responses to my post called attention to Dr. George D. Lundberg’s video editorial of 13 June 2008, denouncing attacks on commercially sponsored CME activities. Among other claims, Dr. Lundberg, a past editor-in-chief of JAMA, stated that Medscape “follow(s) rules that prevent bias and improper influence.” He went on to boast that Medscape is “the largest single source of CE for health professionals” and that “We are just going to keep doing what we are doing. It is good. We are clean. Our work is transparent…. We welcome analysis and criticism. We function in the best interests of patients …” These words were spoken before Daniel Carlat and I published our critiques of Medscape a few days later (see here and here and here).

There seems to be a right hand – left hand problem at Medscape. Though I take Dr. Lundberg at his word about his intentions, I invite him to defend the products that actually appear under his oversight as editor-in-chief. Let’s look at a case study of an “Expert Interview” published on-line June 9, 2008 under the tagline Medscape Perspectives on the American Psychiatric Association (APA) 161st Annual Meeting, May 3-8, 2008, Washington, DC. A boilerplate legal disclaimer noted, “This activity is not sanctioned by, nor a part of, the American Psychiatric Association. Conference news does not receive grant support and is produced independently.”

The “Expert Interview” for our case study is titled “Pharmacologic Options for Treatment-Resistant Depression…” The featured expert is Charles Nemeroff, chairman of Emory University’s department of psychiatry. Dr. Nemeroff is well known for ethical controversy. In 2003 the Nature Publishing Group revised their policies on disclosure of financial conflicts of interest in the wake of Dr. Nemeroff’s widely publicized nondisclosures. In 2006 Dr. Nemeroff resigned as editor of the journal Neuropsychopharmacology after he failed to disclose conflicts pertinent to a review article he co-authored and placed in his own journal. As is always true of case studies, the devil is in the details if we wish to understand just how sly and subtle was the spinning. Here are some of the issues that arise from Dr. Nemeroff’s Expert Interview on Medscape.

1. Internal contradiction. The legal disclaimer noted above states that there was no grant support and that the conference news items were produced independently. However, Dr. Nemeroff’s featured item prominently acknowledges an unrestricted educational grant from Bristol-Myers Squibb Company and Otsuka America Pharmaceutical, Inc. These two companies jointly market aripiprazole, a member of a drug class highlighted by Dr. Nemeroff in his Expert Interview.

2. Infomercial format. The Expert Interview by Dr. Nemeroff resembles nothing so much as Lindsay Wagner promoting the Select Comfort Sleep Number Bed in television advertisements. Promotional statements are made without scientific backup.

3. Disease mongering. In this interview, Dr. Nemeroff backed away from his earlier strict definition of treatment-resistant depression (TRD), proclaiming that in his current view 40% to 50% of depressed patients have treatment resistance. This sleight of hand naturally expands the market for the agents he later promotes as augmenting agents.

4. The primary care “hook.” Dr. Nemeroff introduced a professional “hook” to primary care physicians, emphasizing the association of depression with cardiovascular disease. This strategy is a component of disease mongering. Dr. Nemeroff’s discussion of this association had approximately zero educational value. Why did Medscape not insist on more substantive content?

5. Inappropriate drug recommendation. In discussing the switch strategy from one antidepressant class to another for resistant depression, Dr. Nemeroff included a recommendation for nefazodone. That drug was withdrawn by Bristol-Myers Squibb Company several years ago because of hepatic toxicity. What kind of “expert” makes such a recommendation? And what kind of editorial oversight by Medscape waves through such an incompetent statement?

6. Uncritical reliance on uncontrolled studies. In discussing switch of antidepressant drugs, Dr. Nemeroff noted that in phase II of the STAR*D trial 25% of patients switched from citalopram to sertraline responded. Dr. Nemeroff’s discussion of that result was inadequate. He invoked a dubiously relevant effect of sertraline on the dopamine transporter (when you are stuck for an answer, invoke neurochemical mythology) but he ignored the default hypothesis that 25% would have been the placebo response rate had STAR*D been designed to include placebo control groups. This default hypothesis assumes that all SSRI drugs are basically similar in terms of efficacy. For an educational item in Medscape or anywhere else, this aspect of the Expert Interview falls short of expected standards.

7. Pushing dangerous drugs. Dr. Nemeroff has been a leader in promoting use of second generation antipsychotic (SGA) drugs as augmenting agents for resistant depression. I have commented previously on his promotion of risperidone for this purpose, here and here. Others have raised serious questions about his reports. Overall, Dr. Nemeroff promotes these drugs by exaggerating their efficacy and glossing over their toxicity in resistant depression.

8. False statements. In this Expert Interview, Dr. Nemeroff leads off his discussion of SGA drugs for TRD with an endorsement of risperidone. The 2 published references to risperidone in TRD have major scientific flaws. Indeed, the study by Rapaport et al (reference 12 in this interview)was retracted. Nevertheless, Dr. Nemeroff still claims this study supports his position on SGA use in TRD. Does Dr. Nemeroff not read the retractions of his own publications (by his own “research team”)? How naïve are Medscape’s editors to be ignorant of these retractions?

9. Talking up the sponsor’s product. In reviewing the toxicity of SGA drugs for TRD, Dr. Nemeroff found something negative to say about the side effects of olanzapine, quetiapine, and risperidone. However, he made no mention of aripiprazole’s side effects, even though he emphasized its recent approval by the FDA for TRD. How convenient, as BMS-Otsuka sponsored his Medscape spot. Where were Medscape’s editors, described by George Lundberg as working to prevent bias and improper influence?

10. Glossing over weak efficacy. Though Dr. Nemeroff endorsed aripiprazole for TRD, he neglected to discuss the weak efficacy of this drug. The Number Needed to Treat for remission with aripiprazole in TRD is a disappointing 10. The studies cited by Dr. Nemeroff only compared aripiprazole against placebo. Dr. Nemeroff surely knows that just beating placebo does not qualify a drug as clinically useful. Dr. Nemeroff neglected to address the comparative efficacy of aripiprazole versus established treatments of TRD, such as lithium augmentation. The available evidence suggests that patients will do better on lithium and that aripiprazole would not be the first line choice, especially in primary care. Where were Medscape’s editors?

11. Reckless promotion of SGAs early in the course of TRD. Dr. Nemeroff emphatically stated he is not opposed to the early use of SGAs for TRD. Here especially he resembled Lindsay Wagner. A conscientious educator would weigh the risks and benefits of the early and broad use of SGA drugs in TRD. Dr. Nemeroff did no such thing. He simply opined. Why did Medscape’s editors allow him to get away with this reckless promotion? There does not appear to have been any effective editorial oversight of this publication.

12. For Dr. Nemeroff to promote early use of SGAs in TRD is reckless because of the serious toxicity associated with these drugs. Where is the discussion of akathisia (26% in the most recent study of aripiprazole in TRD)? Where is the discussion of emergent suicidality associated with akathisia in depression? Where is the discussion of tardive dyskinesia caused by aripiprazole (5% within 12 months in schizophrenia, and quite possibly higher in mood disordered patients)? Where is the discussion of neuroleptic malignant syndrome associated with SGAs like aripiprazole? Where is the discussion of weight gain with aripiprazole in TRD (significantly greater than with placebo)? Where is the overall analysis of risk versus benefit? Where were Medscape’s editors? Who at Medscape was looking out for “the best interests of patients”?

13. Incomplete disclosures. Dr. Nemeroff has a long history of recidivism concerning failure to disclose pertinent financial conflicts of interest. His record in this instance continues that sordid tradition. He failed to disclose that he is currently chairing a national series of CME meetings promoting aripiprazole for TRD, sponsored by, you guessed it, Bristol-Myers Squibb/Otsuka. Perhaps he thinks that because the money is laundered through a Medical Education Communications Company he doesn’t need to disclose it. Tell that to Joseph Biederman, who was called to task last week by Senator Grassley’s Senate Finance Committee for exactly that obfuscation. Dr. Nemeroff also failed to disclose his support from Janssen for studying risperidone in TRD. He failed to disclose his association with CeNeRx, that is developing MAO inhibitors, mentioned favorably in his interview. There is more, but these examples will suffice. Doesn’t Medscape know by now that Dr. Nemeroff cannot be relied on to report his conflicts appropriately? Does Medscape have knowledgeable professionals or ciphers in its editorial office?

So, this sleazy example illustrates many of the systemic problems that Medscape will need to correct if it hopes to remain credible. This documentation gives the lie to Dr. Lundberg’s claims that “We are clean. Our work is transparent.” One suggestion is for Medscape to abandon the degenerate form of scientific journalism exemplified by “Expert Interviews” and News items. In their present formats they cannot be truly educational and balanced items. They do not qualify for CME credit, as I verified with the company. They are simply vehicles for promoting sponsors’ products. And the Medscape staff seem to think their job is to ensure that the spin is firmly in place. Does George Lundberg really intend that?

Bristol-Myers Squibb Settles, Enters "Corporate Integrity Agreement"

And here we go again. Reported first late last Friday afternoon, as these things often are, was the huge settlement made by pharmaceutical manufacturer Bristol-Myers Squibb. This story received surprisingly little coverage in the main stream media, although World News Tonight (ABC) lead with it. The most detailed print version was in the Boston Globe,

Bristol-Myers Squibb and a subsidiary have agreed to pay more than $515 million to settle civil suits over fraudulent drug marketing and pricing schemes, including illegally promoting an anti-psychotic drug to children and the elderly, US Attorney Michael J. Sullivan said yesterday.

The settlement between the federal government and Bristol-Myers Squibb and Apothecon Inc. is the third-largest between a pharmaceutical company and the US Attorney's Office in Massachusetts....

The company said it has ... entered into a five-year 'corporate integrity agreement' with the Office of the Inspector General of the Department of Health and Human Services that requires it to develop programs to ensure compliance with the law.

The most notable charges involved unethical marketing practices.

The agreement says Bristol-Myers Squibb gave kickbacks to physicians and healthcare providers from 2000 through mid-2003 to get them to prescribe the company's drugs. The kickbacks came in several forms, including consulting fees and trips to luxury resorts.

From 2002 through 2005, Bristol-Myers Squibb promoted the sale of Abilify, an anti-psychotic drug, for pediatric use and to treat dementia-related psychosis, both "off-label" uses, prosecutors said. The Food and Drug Administration has approved Abilify to treat adult schizophrenia and bipolar disorder but not for the uses marketed by Bristol-Myers Squibb.

Nonetheless, Bristol-Myers Squibb created a special longterm-care sales force that called on nursing homes and promoted off-label use of Abilify, prosecutors said.

A sales force also visited child psychiatrists and other pediatric specialists and urged them to prescribe Abilify.

There were also allegations of pricing hanky-panky.

Bristol-Myers Squibb participated in pricing schemes, including one involving its anti-depressant drug Serzone, that defrauded the Medicaid program, prosecutors said.

Bristol-Myers Squibb and Apothecon also inflated prices for a wide assortment of cancer-fighting and generic drugs, deceiving federal healthcare programs that established reimbursement rates based on those prices, prosecutors said.

Not surprisingly, the company wants to put it all behind it.

Bristol-Myers Squibb is pleased to have resolved these matters from the past and is proud of its commitment to conduct business with the highest standards of integrity in its mission to extend and enhance human life.

Critics of the industry were not impressed.

Dr. Jerome Kassirer, a professor at Tufts University School of Medicine and outspoken critic of drug companies, is skeptical.

'A lot of these companies, when they get sued for a few million dollars, they just consider it loose change,' he said. 'I haven't seen any let-up in what they're doing. Most of the time, when they're caught, they'll often say, 'It was a renegade, someone who wasn't following the instructions. Our policy says we shouldn't do that.' '

Similarly, Thomas M. Greene, a Boston lawyer representing one of the whistleblowers, said the allegations are serious because off-label use has the potential to harm patients.

'What happens when you promote a drug that is not effective?' he said. 'You're depriving sick people of some other effective treatment.'

As in the recent case involving orthopedic device manufacturers, (see post here), so far, despite the huge corporate fine, it is not clear that any individuals, either at the drug company, or physicians, will pay a penalty.

As we noted before, corporate payments of huge fines may not be much of a negative incentive to corporate executives because the impact of the fines can be spread across the entire organization. And such fines clearly have no direct effect on physicians, and will not discourage them from accepting "consulting fees and trips to luxury resorts" on behalf of drug marketers.

How many more examples like this do we as a society need before we conclude that there is a systemic problem with unethical behavior by leaders of health care organizations, and that we need a systemic solution to this problem that goes past civil lawsuits, corporate compliance monitoring, and deferred prosecution agreements?

ADDENDUM - See also comments on BrandweekNRX, and on the Wall Street Journal Health Blog.

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.