AstraZeneca Settles

Here is the latest in the parade of legal settlements of cases of alleged wrong-doing by health care organizations.  As reported by Duff Wilson in the New York Times,

The pharmaceutical company AstraZeneca said Thursday that it had reached a $520 million agreement to settle two federal investigations and two whistle-blower lawsuits over the sale and marketing of its blockbuster psychiatric drug Seroquel.

One of the investigations related to 'selected physicians who participated in clinical trials involving Seroquel,' AstraZeneca disclosed in a government filing. The other case related to off-label promotion of the drug.

Seroquel was the top-selling antipsychotic drug in America. It had $17 billion in sales in the United States since 2004, according to IMS Health, a research firm.

Tony Jewell, a company spokesman, declined to be more specific about the physicians or clinical trials under investigation. He said the company was in final negotiations to settle the whistle-blower suits and reach a corporate integrity agreement with the Justice Department.

The name of the whistle-blowers and other details of the suits remained sealed in federal court. Stephen A. Sheller, a lawyer in Philadelphia for the whistle-blowers, and Patricia Hartman, a spokeswoman for the United States attorney in Philadelphia, both declined to comment.

Here we go again. As the Times article noted,

AstraZeneca, based in Britain, joins a list of drug makers that have paid billions to settle inquiries initiated by complaints from former company insiders.

Earlier this year, Eli Lilly & Company paid $1.4 billion over its marketing of Zyprexa, another antipsychotic drug. And Pfizer announced it would pay $2.3 billion, including a record $1.195 billion criminal fine, mostly over its painkiller Bextra, which has been withdrawn from the market.

Does anyone really still believe that integrity agreements, and settlements assessed against huge corporations deter such profitable bad behavior? A half a billion dollar one-time settlement is just a small cost of doing business for a company that sold $17 billion worth of the offending drug in the last five years. As in the case of many other previously announced settlements, it appears that nobody who authorized, directed, or implemented the bad behavior that led to the settlement will suffer any sort of negative consequences.

We previously discussed allegations that AstraZeneca manipulated and suppressed clinical research, and organized deceptive marketing campaigns in support of Seroquel sales (here, and here).  If we do not discourage such practices, they will continue to bias the clinical evidence making expensive drugs and devices seem more effective and less dangerous than they really are.  Is it any wonder that we over-use and over-pay for these products?  Anyone seriously interested in reforming health care to improve quality and access while moderating costs ought to pay attention to behavior that leads to such over-use and over-payment. 

(However, there may be hope.  Perhaps in the future there will be more effective deterrence.  A recent indictment named not only the device company Stryker Biotech (a subsidiary of Stryker Corporation), but also its former CEO and three managers.)

Nemeroff, Seroquel, and ACCME

Nemeroff, Seroquel, and ACCME

Roy Poses has discussed the atypical antipsychotic drug Seroquel (quetiapine) several times on this site, pointing out manipulation of clinical research results to enhance the appearance of efficacy, and suppression of studies with unfavorable results. I call this augmenting the marketed profile of the drug. Daniel Carlat has commented on published Seroquel data here and ClinPsych here.

AstraZeneca, the marketer of Seroquel, has also been busy with continuing medical education (CME) programs that augment Seroquel’s profile. Last December 8, one such program went on line, aired by the provider CME Outfitters. The program’s title was “Atypical Antipsychotics in Major Depressive Disorder: When Current Treatments Are Not Enough.” The corporate logo for CME Outfitters is Education with Integrity. I will allow readers to decide if the company is meeting its mission statement in this respect.

The key opinion leader engaged by CME Outfitters to discuss Seroquel and other atypical antipsychotic drugs was Charles Nemeroff of Emory University. He was joined by 2 KOLs-in-training, whom I will not name. The corporate sponsor that paid CME Outfitters and, indirectly, these presenters was AstraZeneca. I do not need to rehearse here the ethical issues that have surrounded Dr. Nemeroff for the past several years. Suffice it to say that, as a result of those issues, Dr. Nemeroff is no longer chair of the department of psychiatry at Emory University, he is no longer editor-in-chief of the ACNP journal Neuropsychopharmacology, he was removed from involvement with ongoing federally funded research grants at Emory University, and he was put on a short leash by the Emory administration.

On December 23, 2008 I filed a formal complaint about Dr. Nemeroff’s program with ACCME. My bill of particulars was lengthy, detailed, and backed up by extensive
materials. In due course, ACCME investigated the complaint and found that the program did violate ACCME standards. With respect to content, ACCME determined that Dr. Nemeroff’s program lacked sufficient information about possible adverse effects of treatment with atypical antipsychotic drugs; and failed to emphasize sufficiently the efficacy of alternative treatments. With respect to commercial bias, ACCME determined that bias existed as a result of the absence of contrasting therapy data, and through downplaying the drawbacks related to treatment with atypical antipsychotic drugs in depressed patients.

Following these findings by ACCME, the provider was notified of the violations in early September 2009, and the program was removed from the provider’s website. The sanitized statement of violations determined by ACCME does not capture the nuances of deceit, ineptitude, and deficient educational content in Dr. Nemeroff’s program. One remarkable example was Dr. Nemeroff’s citation of data, from one of his own publications, that were previously retracted. Did he think no one would notice?

A second example involved biased presentation of the sponsor’s data for Seroquel. Two doses of Seroquel (150 mg and 300 mg) were tested. Only the results for the 300 mg dose were statistically significant. Nevertheless, in the video presentation one of the junior presenters stated very clearly that there was “significant improvement in both response and remission with both doses” of Seroquel. That is a falsification of the scientific record. That falsification does not meet ACCME requirements for fair, balanced, truthful, and honest teaching. As moderator, Dr. Nemeroff was required to correct this false statement made by his junior assistant, but Dr. Nemeroff failed to do so.

The negative findings and sanction by ACCME against Dr. Nemeroff’s program are welcome, though I have to say it took ACCME an inordinately long time to complete their work. I also presented ACCME with several follow-on questions, which the Council is now considering. These are:

• Did ACCME notify the presenters that their program violated ACCME policies? If not, why not?

• Will CME credits be clawed back from physicians and other professionals who obtained credits through the noncompliant program? If not, why not? I believe this would be an effective form of negative feedback to the provider and the presenters.

• Does ACCME have a process to require the provider and presenters to ascertain whether any patients were injured as a result of the violations that created biased and deficient information in this program? If not, why not?

• Does ACCME require the provider to notify physicians and other professionals who completed the noncompliant program that the provider was sanctioned for violation of ACCME standards? If not, why not?

• Does ACCME require the provider to furnish corrective materials to such professionals in order to remedy the bias and incompetence to which they were subjected through violation of ACCME standards, and thereby to remove potential danger to future patients? If not, why not?

• Why did ACCME allow the noncompliant program to remain available long after the complaint was filed? I suggest that ACCME needs to place a hold on programs that are subject to active complaint. Had such a policy been in effect in December 2008, the violating program would not have been re-aired by the provider in early 2009, it would not have remained on-line for 9 months, and the damage to the continuing education community would have been contained.

• Will ACCME issue a public listing of sanctions it has enforced against providers and presenters? If not, why not? State medical boards do exactly that in relation to physicians and other professionals who violate standards of practice.

• Finally, I reminded ACCME that its primary constituents are patients, physicians and other professionals, not commercial or academic CME providers. It seems to me that ACCME was altogether too laissez-faire and dilatory in the way it handled this matter. At the time of my initial complaint last December, I requested expedited review precisely because additional airings of this violating program were scheduled.

The good news is that ACCME seems to have got the message that things need to change. As one of their officers wrote to me recently, “We sincerely appreciate the time and effort you have put into participating in our complaints and inquiries process. You have raised important issues that the ACCME will review and address.” I await their next communications on the remaining questions.

As for Dr. Nemeroff, he is yesterday’s news. The adverse findings by ACCME about his program serve as a reminder to corporate sponsors and CME companies that Dr. Nemeroff is so compromised by now that he has lost effectiveness as a front man for Pharma. Indeed, he is so toxic that he now glows in the dark.

More on the Misleading Promotion of Seroquel

Previous posts (here and here) noted internal documents from AstraZeneca made public during litigation about its blockbuster atypical antipsychotic drug Seroquel (quetiapine) suggesting that the company's marketers manipulated clinical research results to make them appear more favorable to the product, and suppress studies with unfavorable results that could not be easily manipulated.

This week, Bloomberg News reported testimony from one trial about other aspects of Seroquel's marketing. The marketers' claims were at odds with the company's own research results:

AstraZeneca Plc advised its sales force to promote the antipsychotic drug Seroquel as 'weight neutral' four years after company research found 'clinically significant' weight gains in users, internal documents show.

AstraZeneca’s 'global strategy is to demonstrate to consumers that Seroquel has a weight-neutral profile,' Debbie Holdsworth, a marketing official, wrote in a 'dear colleague' letter dated May 14, 2001. The document was produced during a pretrial examination of former executive John Patterson.

'If 45 percent of patients gained significant weight in a year, how could that be weight-neutral?' patient attorney Ed Blizzard asked Patterson, citing a internal 1997 e-mail written by an AstraZeneca doctor, at a hearing in Orlando Oct. 5.

Also, evidence was presented that suggested that company marketers consciously promoted the drug for off-label indications over several years:

Patterson was asked about a 'Seroquel Strategy Summary' issued in December 2000, which described the broadening of Seroquel use 'on and off label' as a sales goal. While doctors are free to prescribe any medicine to treat a given condition, it is illegal for drug companies to promote medicines for uses not approved by the U.S. Food and Drug Administration.

'The company has standards and procedures to ensure its sales representatives do not promote off label,' Patterson testified. Still, the goal of off-label promotion remained in strategy summaries for the years 2001 or 2002, he acknowledged.

Coupled with previous revelations (see posts noted above), it looks like the marketers were employing an integrated strategy combining a variety of deceptions, the sort of broad based stealth marketing approach we have seen employed to promote other health care products.

Such strategies undoubtedly have lead to the prescribing of expensive drugs when other treatments, or no treatment would be better, and have helped support the high prices charged for products that are not necessarily so good for the many patients who have ended up getting them. Of course, the money thus generated has let many executives of the companies that employ such marketing strategies become rich. As Bloomberg reported:

Patterson, who reported directly to AstraZeneca’s chief executive officer, was paid more than $1 million at one point during his tenure at the company. He retired April 1 as executive director of product development, and is the highest- ranking AstraZeneca executive to testify in open court in lawsuits claiming the company withheld information about the risks of Seroquel.

In my humble opinion, if we really want to reform health care in the US (and around the globe), we need to challenge how health care organizations have used their ability to sponsor medical research to manipulate its design, implementation, analysis and dissemination, and when necessary, to suppress its results to favor their vested interests. We also need to challenge systematically deceptive marketing practices designed to make products and services appear more useful than they really are, thus supporting exaggerated prices and prompting overuse. Unless we challenge these and some other causes of excess prices and excess use, attempts to provide universal health insurance and access will bankrupt us all.

(And to preempt anyone in the audience who may recoil from anything that restricts the freedom of action of health care corporations - tell me how manipulation of research, suppression of research, and deceptive marketing is necessary for innovation or for adequate revenues to support good products? I am not arguing for hamstrung companies. I am arguing for honest business practices.)

Hat tip to PharmaGossip.