Wednesday, February 28, 2007

The Plight of the Whistleblower in the UK Illustrated: The Case of the Missing Brain Tissue

We recently discussed the plight of health care whistle-blowers in the US.

From the Guardian (UK), yet another story of the fate that awaits health care whistleblowers in the UK,

Allegations that patients at a Liverpool hospital had parts of their brains removed for medical research during neurosurgery without consenting to the procedure, can be revealed today.

The University of Liverpool is accused of covering up the procedures, alleged to have resulted in at least 12 patients having brain parts removed. Its medical school, which was embroiled in the Alder Hey organ retention scandal, is facing claims that it tried to silence a senior hospital whistleblower who raised the alarm about alleged misconduct by a leading brain surgeon.

Until 2005, the university employed Professor Peter Warnke, who was chair of neurosurgery and operated at the Walton Centre hospital. In 2002, allegations surfaced that Warnke had been taking tissue from the brains of living and dead patients at the Walton Centre without obtaining consent.

Warnke is alleged to have taken samples of brain tissue during surgery, freezing them in liquid nitrogen, marking them with a black dot and sending them to Genpat 77, a private biotechnology company in Germany. The samples were used to test a new treatment for brain diseases involving an antibody called TIRC 7. Warnke was a joint owner of the patent taken out on TIRC 7, along with the founder of Genpat 77. Warnke has always vigorously contested claims of wrongdoing. The Observer has established that, at around the same period, Warnke attempted to obtain tonsils that had been removed from patients at the Aintree Hospital in Liverpool for use in associated research. Elizabeth Preston, the hospital's medical director, said: 'I can confirm that Professor Warnke did ask for tonsils, but a nurse questioned whether he had ethical consent. He was refused and as far as I am aware he never had access to any tissues from Aintree.'

Both the nurse and a surgical colleague of Warnke's raised questions about his conduct with Dr Marco Rossi, who then chaired the regional ethics committee set up to improve research standards after the Alder Hey scandal, where hundreds of children's organs were retained without parents' consent. Rossi, who was a consultant neuropathologist at the Walton Centre, claims that when he began investigating the allegations against Warnke he suffered threats from senior staff at the university's medical school. He claims that the level of intimidation made him ill and he was unable to continue his work.

Rossi is suing the Walton Centre, the University of Liverpool and the strategic regional health authority for breach of contract. He argues that as a senior employee and whistleblower they should have protected him, and claims that senior medical school staff were more concerned in covering up a potential scandal. He alleges that he was subjected to a campaign of bullying and harassment in an attempt to get him to withdraw his accusations. In court, the university has argued that Rossi's allegations about Warnke were irrelevant and should not be heard.

Last week, a judge rejected this and ordered the university to hand over its dossier on the affair, including an internal investigation into Warnke's conduct. The court has heard that Rossi alleges that dozens of ethical consent forms used by Warnke for his research were either incomplete or inaccurate.

Although Rossi left in 2002, no action was taken against Warnke until April 2005, hours after Rossi launched his legal action. Warnke was suspended and later resigned. In November 2006 he was appointed chief of neurosurgery at the Beth Israel hospital in Boston, part of Harvard Medical School.

The British law firm Weightmans, which is acting for Warnke, issued a statement to The Observer rejecting Rossi's claims. It said the allegations against Warnke were 'brought by a disgruntled former employee and a colleague of our client'.

Also see the BBC coverage here.

As in the recent US case which we discussed, note that it was the person who came to the aid of the original whistle-blowers who allegedly found himself in even hotter water than they did.

It seems that many types of health care organizations in many countries lack a mechanism to give whistle-blowers a fair hearing, investigate their complaints, and protect them from the wrath of those they accuse, and from institutional leadership which fears those who would rock the boat, even if it is in an effort to alter course away from the iceberg.

Monday, February 26, 2007

Ghost-Filming? - Biotech Commissions a "Documentary"

A while back, we posted about how a pharmaceutical industry group sponsored the writing of a novel that would support the group's negative point of view about reimportation of drugs from other countries. This seemed at the time to be an audacious example of stealth marketing in health care.

Now, one biotechnology company has sponsored the making of a "documentary" movie, just released in theaters, that just happens to underline the suffering that having particular diseases entails, diseases that are now remarkably treatable by drugs that include the company's product. Per the Philadelphia Inquirer,

Pharmaceutical promotion is going undercover to a theater near you.

Starting next month, moviegoers in select cities will be able to see the heart-wrenching real stories of three people suffering from immune diseases - rheumatoid arthritis, psoriasis and Crohn's disease - in a new kind of documentary.

What viewers will not see, unless they wait for the last line of the ending credits, is that the film was produced by Centocor Inc., the Horsham-based biotechnology subsidiary of Johnson & Johnson and maker of the No. 1 treatment for those diseases.

Nor will they hear the name of Centocor's drug, Remicade, or about its high cost
, even though the patients are shown getting the treatment and talking about their recoveries.

The film, titled Innerstate, is the drug industry's boldest foray into a form of indirect promotions called "patient education" or "disease awareness," as opposed to more explicit drug ads on TV, infomercials or pitches to doctors.

In this case, Centocor's director of public relations, Michael Parks, actually served as executive producer and personally sifted through the stories of 40 patients to pick the three for the documentary. He is overseeing its theatrical release.

"This is not about Remicade. It's about elevating public awareness of these conditions," said Parks, who declined to say how much the project is costing.

Alexander Sugerman-Brozan, director of the Boston-based Prescription Access Litigation Project, which opposes "ridiculous, questionable or manipulative" drug advertising, said the film represented a questionable trend in health information.

"We need to be skeptical of disease-awareness campaigns that come from a company with a vested interest," said Sugerman-Brozan, who has not yet seen the film. Industry advocates call "patient education" a powerful way to push valid health information to a jaundiced public - even if it means omitting the sponsor and product name.

"It's about building trust in the message," said Barbara Pagano, a senior vice president at HealthEd Inc., a Clark, N.J., patient-education consulting firm, which had no role in the film.

"It's ironic, yes, but with the reputation that the pharma industry has, it makes a difference if the sponsor is identified. If Centocor's name was on top, people wouldn't watch it. People would think it's a commercial," Pagano said.

Even without naming Remicade, Centocor stands to gain from increased disease-awareness because, as the market leader, it tends to capture most new prescriptions.

"Anything that benefits the overall market tends to benefit the market leaders the most," Pagano said.

So, let's see, a biotechnology company produces a film that highlights the suffering produced by particular diseases, and the wonders of new treatments, one of which happens to be made by the self-same company. By the way, the company's director of public relations was the executive producer, and is overseeing the film's release. Yet the name of the company, or its product, never appears in the film until the end of the credit-roll.

Why make the film if not to increase sales of the drug? But, the film was made to look like a documentary, not an advertisement, and its ties to the company that makes the drug were made as inconspicuous as possible.

So clearly, this appears to be the latest form of marketing based on deception, that is, stealth marketing.

If Centocor thinks its message is so strong and important, why didn't it attach its name overtly and proudly to the message? How much should one trust a company that won't put its name on its own marketing messages?

Blowing Our Own Horns: Health Care Renewal Bloggers at SGIM Annual Meeting

Health Care Renewal bloggers Wally Smith and Roy Poses will be giving a "pre-course" at the annual Society for General Internal Medicine (SGIM) meeting in Toronto, Ontario, Canada. Our session is on Wednesday, April 25, 2007, from 1:30 -5:30 PM, entitled "Changing Physician Behavior - When to Do It? How to Do It? and How Not to Do It?" The latter topic may be of special interest to Health Care Renewal readers. The complete course description is here under PR07. Please note that the course description in the official printed program (available here) was both truncated and garbled.

In addition, bloggers Russ Maulitz, Smith, and Poses (and also not a blogger Robert Crausman MD) will be presenting an oral abstract during the first abstract session (session A), in the Health Policy section, entitled, "Selling Them the Rope: Prevalence of For-Profit Health Care Corporate Directors Among Academic Medical Leaders." This should be of special interest to Health Care Renewal readers.

Finally, I will be chairing a meeting of the Professionalism Sub-Committee of the SGIM Clinical Policy Committee during the annual meeting (time not yet known). This sub-committee's mission, to uphold physicians' professionalism, especially against external threats, including those due to concentration and abuse of power in health care, should be of particular interest to Health Care Renewal readers. If any SGIM members who are not members of the sub-committee are interested in joining, and/or want to attend this meeting, please contact me, Roy Poses, directly. (roy underscore poses at brown dot edu or rposes at firmfound dot org).

Friday, February 23, 2007

From the British Medical Journal: Financial Links Among the World Health Organization, Patient Organizations, and Pharmaceutical Companies

We have posted frequently about questionable financial links between commercial firms that produce health care goods and services (for example, pharmaceutical, biotechnology, and medical device companies) and not-for-profit organizations and government agencies that provide or regulate health care (for example, hospitals, academic medical centers, and government agencies). The latest example of such links, and one with global implications, comes from one of my now favorite outlets for investigative journalism, the British Medical Journal. [Day M. Who's funding WHO? Brit Med J 2007; 334: 338-340).
Serious questions have been raised about whether the World Health Organization is using patient groups as a conduit for receiving proscribed donations from the pharmaceutical industry. Email correspondence passed to the BMJ seems to show that in June 2006 Benedetto Saraceno, the director of WHO's department of mental health and substance abuse, suggested that a patient organisation accept $10 000 (£5000; {euro}7000) from GlaxoSmithKline (GSK) on WHO's behalf. The sum was then to be passed on to WHO—ostensibly with the intention of obscuring the origins of the donation. GSK withdrew its offer of funding when it learnt that acceptance was conditional on obscuring its origin. However, the email exchange indicates that other sums of money originating from drug companies may have already been channelled to WHO through patient groups.

When asked about this correspondence, Dr Saraceno told the BMJ that his email to the patient organisation was 'clumsily worded' and that he had 'never intended to solicit donations from the pharmaceutical industry through' the patient organisation. In the email dated 16 June 2006, Dr Saraceno thanks Mary Baker of the European Parkinson's Disease Association (EPDA), for raising the $10 000 'requested by the WHO.' The money was to have funded a report on neurological diseases, including Parkinson's disease, for which GSK produces treatments.

Dr Saraceno then seems to advise Mary Baker on how to get round the WHO's rules forbidding drug industry funding. 'Unfortunately,' he says, 'WHO cannot receive funds from pharmaceutical industry. Our legal Office will reject the donation. WHO can only receive funds from Government agencies, NGOs, foundations and scientific institutions or professional organisations. Therefore, I suggest that this money should be given to EPDA and eventually EPDA can send the funds to WHO which will give an invoice (and acknowledge contribution) to EPDA, but not to GSK.'

According to paragraph 13 of the WHO's guidelines on interactions with commercial enterprises, which deals with cash donations, WHO should avoid indirect collaboration (particularly if arranged by a third party acting as an intermediary between WHO and a commercial enterprise).' Paragraphs 15 and 16 of the guidelines state that funds may not be sought or accepted from commercial enterprises that have a direct commercial interest in the outcome of the project and that caution should be exercised even when the business has an indirect interest. And paragraph 27 says that for reasons of transparency, contributions from commercial enterprises must be acknowledged.

Richard Nicholson, editor of the Bulletin of Medical Ethics, said: 'It would be very bad indeed if the WHO were trying to obtain money surreptitiously from drugs companies. Unfortunately it's also under-funded, and sadly there's always going to be the temptation of senior officials who ought to know better than to accept such money. But they should remember that there's always a price attached to such funding.'

He adds: 'This is in line with what we have done so far with other contributions to the report which all are coming from other professional organisations,' — suggesting that less than transparent transactions were the norm for this fundraising operation.
It turns out this has not been the first time that WHO was accused of being caught up in commercial entanglements.
Ralph Edwards, the director of the WHO's drug monitoring centre in Uppsala, Sweden, warns .... 'These days it's so hard to find anyone completely free of the pharmaceutical industry. A couple of years ago we wanted to publish a safety report on Lapdap [chlorproguanil-dapsone], the combination malaria treatment. The WHO's tropical disease research group had developed the treatment jointly with Glaxo, but Glaxo weren't happy with what we wanted to publish.'

'This was a bad situation and it was very, very difficult. We raised the issue with WHO because we thought that there had not been enough safety studies done. We managed to get the report published eventually, after a lot of lobbying and pressure—but it was delayed for more than a year,' said Dr Edwards.

'It's an example of how tortuous it is working with pharmaceutical industry money.'
This story is yet another reminder of how globally pervasive are financial ties amongst various health care organizations that naively physicians and the public may think are supposed to work at arms' length. However, if we want health care that puts the needs of patients first, we have to align the incentives with the mission, and eliminate opportunities for well-heeled vested interests to pay for increased influence.

Wednesday, February 21, 2007

The Plight of the Whistleblower Illustrated: the Stratton VAMC Story Revisited

Two years ago, we discussed the troubling case of Paul Kornak and the Stratton Veterans Affairs Medical Center (SVAMC) in Albany, New York. Kornak was apparently hired despite having lost medical licenses in several states due to forged credentials, and a felony fraud conviction in Pennsylvania. Although Kornak apparently never completed medical training, the Stratton VAMC allowed him to perform physical examinations and identify himself as "doctor." The FDA found that Kornak had falsified patients' medical records in several drug studies, allowing patients to enroll in studies even though they should have been excluded. Kornak plead guilty to fraud and negligent homicide for the death of one patient in a chemotherapy study.

Our post in 2005 was based on a New York Times article that suggested that Kornak's actions were part of a much larger problem, and that whistle-blowers who tried to alert the government to Kornak and these other problems were discredited and punished.

I just found another article, published last year in a health care journal, [Fudin J. Blowing the whistle: a pharmacist's vexing experience unraveled. Am J Health-Syst Pharm 2006; 63: 2262-2265.] and now available on Medscape, which reveals more troubling details about the case. Its author was a key whistle-blower in this case.

Fudin first noticed in 1994 what he felt were important problems with cancer research studies, such as enrollment of patients without informed consent, enrollment of patients who did not fit study criteria, and coercion of patients to enroll.

As I climbed the chain of command to report my observations, it became painfully obvious that institution officials were angered by my 'protected' disclosures. I felt obligated to bring my concerns to an outside agency, the VA Office of Inspector General (VAOIG).

After putting these concerns in writing, I was threatened. The exact words still ring clearly in my ears, 'Fudin, I will bury you.'

After Fudin noticed more research problems in 1995,

I wrote a report of my findings and sent copies to several administrative medical personnel in March 1996. It included my refusal to participate or comply with any physician orders to dispense these medications, at unstudied dosages in unstudied combinations, to patients. Within two days, I received a memorandum charging me with 'patient abuse for failure to dispense medication as required by the oncologist.'

After another report by Fudin,

I was investigated for 'practicing outside [my] scope by requiring certain blood work prior to dispensing chemotherapy.'


SVAMC was, however, obligated to convene an internal investigation to determine the legitimacy of my allegations. The investigation was assigned to a pulmonologist named Thomas Ferro. Many of his findings were consistent with my disclosures. But the chief of staff changed the report and ordered Dr. Ferro to sign off on certain edits and to destroy any original documents and computer files. Dr. Ferro admitted this to investigative reporters for a local newspaper and the New York Times.

By July 1995, the chiefs of staff and the department of medicine had approached Anthony Mariano, SVAMC's pharmacy manager at that time. Mariano was ordered to counsel and place me on probation regarding certain alleged 'undesirable professional activities.' A man of high integrity, Mariano refused to succumb to administrative pressures even though this made him vulnerable to retaliation. For supporting me and for making his own 'protected disclosures,' his desk was moved to an empty psychiatric ward where he had no computer, no phone, and no job assignments. He was eventually terminated for allegedly allowing a clinical pharmacist to practice outside an approved clinical scope, a charge that, upon subsequent investigation by several agencies, was dismissed. This cluster of retaliations came from a newly assigned regional pharmacy manager, a pharmacist, who Mariano and I believe was sent to our region by Washington, D.C., officials to remove us from government service. Mariano was forced to resign with no opportunity for a hearing. Just two weeks after my own termination, the regional pharmacy manager was whisked off to a Washington-based job with a promotion, but in December 2001, I prevailed in court and was reinstated to SVAMC by a federal judge.

Fudin alleged that Kornak took the fall to protect worse misdeeds made by more highly placed people.

As a cautious returning SVAMC employee, I watched the 2002 Kornak story unfold in my local newspaper. I knew in my heart that although he deserved punishment for his crimes, he had been used by the government as a convenient scapegoat to avoid accountability for more than a decade of criminality predating his employment.

This experience lead Fudin to help set up an organization to protect US Veterans Affairs whistle-blowers, the Veterans Affairs Whistleblower Coalition. Fudin has posted more details of his story on his own web-site.

Given the anechoic effect, it is remarkable that this story has come out in a health care journal, even so many years later.

This story illustrates the barriers facing anyone who seeks to complain about perceived misdeeds and malfeasance in health care, whether they affect patient care, academics, or institutional finance and governance. The unfortunately usual pattern is that the original whistle-blower is made to pay dearly, as are those who come to his or her support.

This clearly suggests the need for clear and enforced codes of conduct for everyone, including top management, who works in health care; indepedent watch-dog organizations to publicize mission-hostile management, conflicts of interest, and corrupt and criminal behavior in health care not handled by these internal resources; and finally recourse to independent, unconflicted, impartial regulatory agencies when all else fails.

Right now, as illustrated by Fudin's article, most whistle-blowers in the US must survive on their own wits while paying their own legal bills. In a health care sector increasingly dominated by "increasingly aggressive business models," in which even ethicists call for managers to " test the boundaries of legal permissibility" to beat out their competitors, failure to protect whistle-blowers will just put us all deeper into the moral swamp.

Monday, February 19, 2007

Pharmaceutical Stealth Marketing on PBS

Say it ain't so, stealth marketing of a drug on a US Public Broadcasting System (PBS) show, but Broadcasting & Cable (that's a new source for us) reported that:

Glaxo[SmithKline] is underwriting the April broadcast of Fat: What No One is Telling You, the second in the 'Take One Step' series of health-related shows and outreach PBS is undertaking in concert with the YMCA. The series kicked off this week with a show on heart disease, but Glaxo was not a funder, according to a spokeswoman for producer WGBH Boston. But Glaxo is underwriting the 'Fat' show, which debuts April 11.

Jeff Chester, executive director of the Center for Digital Democracy, and a frequent critic of what he sees as the increasingly commercialization of noncommercial broadcasting, has written to PBS ombudsman Michael Getler to complain about what he sees as too lax sponsorship policies.

'We note that funding comes in part from GlaxoSmithKline,' Chester wrote Getler. 'The drug giant just happens to have a recently approved for over-the-counter drug on the market-under the brand name Alli, that is for use by overweight adults along with a reduced calorie, low-fat diet.'

Chester fears the show will effectively be a plug for the new diet drug and that 'Programs on PBS should be free of connections to sponsors who have a vested interest in an issue.'

And Broadcasting & Cable further reported:

PBS ombudsman Michael Getler says he doesn't think PBS should have accepted a sponsorship from drug company GlaxoSmithKline for an obesity special airing next month.

On the PBS Web site, Getler in response says that 'even though GlaxoSmithKline came in late and, under PBS policy, has no say in any of the content, this kind of possible conflict can undermine credibility and, without knowing the financial details, doesn't seem worth it.'

Well, at least one organization has an ombudsman that seems ready to tell it like it is.

This is an illustration of just how pervasive stealth marketing is in health care.

Again, if pharmaceutical companies (and other organizations) want to regain the trust of the public and professionals, they at least should only market their products in situations in which the marketing nature of the activity, and who sponsored it, are clear.

See also a post on the Pharmalot blog. This story does not yet seem to have made it to the more general media, much less, of course, the medical and health care literature.

The Case for "Mission-Hostile Management"? - Should Hospital Leaders Test "Boundaries of Legal Permissibility" to Beat Competitors?

The New England Journal of Medicine earlier this month published a notable article entitled "Regulatory and Judicial Oversight of Nonprofit Hospitals" that is worthy of summary and comment. [Studdert DM, Mello MM, Jedrey CM, Brennan TA. Regulatory and judicial oversight of nonprofit hospitals. N Engl J Med 2007; 356: 625-631.]

The article gave a somewhat dry description of the "legal environment in which nonprofit hospitals operate." The authors started by surveying the US federal law that regulates not-for-profit corporations, section 501(c)(3), and how the US Internal Revenue Service (IRS) has regulated, or failed to regulate the conduct of non-profit hospitals. Importantly, Studdert et al noted that the IRS historically could only use a very blunt negative incentive against misconduct by not-for-profits, eliminating their not-for-profit status. However, in 1996 the IRS developed "intermediate sanctions," "financial penalties on influential insiders, such as board members and managers, who frustrate the charitable purpose [of the organization] by reaping impermissible private gains or 'excess benefits' from the corporation. [Yet,] to the best of our knowledge, intermediate sanctions have only been applied once in health care."

The article then surveyed legal issues at the state level. Although they asserted increasing activism by state attorneys general, spurred by developments such as "the spectacular collapse of the Allegheny Health, Education, and Research Foundation in 1998," the authors found "difficulty of discerning any pattern in the way state courts have viewed questions about nonprofit hospitals' compliance with their charitable purposes."

Finally, the article discussed class-action litigation, such as the many recent law-suits that charged "hospitals have shirked their community responsibilities, particularly in failing to provide free care to poor and uninsured patients." However, most federal class action suits have failed, although there have been a few settlements of state level suits.

The article was long on description, and short on policy recommendations. But one recommendation it did make was striking.

In conclusion, the authors suggested that the "convoluted evolution" of law and regulation reflects major unresolved policy questions. They noted sympathetically the "formidable challenges" which non-profit hospitals face, such as "cost increases that will outpace reimbursement," and "growing competition from medical staffs interested in tapping into profits from procedure based-care." The authors asserted that such challenges should cause hospitals to "develop increasingly aggressive business models." Thus, Studdert et al finally concluded that "one might argue that leaders of nonprofit hospitals are failing to act diligently if they do not test the boundaries of legal permissibility by considering every technique that their for-profit competitors use."

This is an important article, one that deserves to be read. It provided a nice summary of the legal environment in which US nonprofit hospitals operate vis a vis their nonprofit status. Most of the article was descriptive, not prescriptive. But to call its concluding recommendations discouraging would be understatement.

These conclusions seemed to not to assume any ethical or moral standards for leaders of nonprofit hospitals. Rather, the article finally implied that they should put making money, and "increasingly aggressive business models," before anything else. This amoral approach seemed to spawn the notion that hospital leaders ought to approach and sometimes go over the line separating legal from illegal behavior because that is what their competitors are doing. (How illegal behavior by some for-profit hospital chains have landed them and their leaders in hot water was not mentioned.)

Perhaps this underlying amoral approach is why the article failed to mention any of the ethically questionable behaviors of leaders of not-for-profit hospitals. Some that have been cataloged on Health Care Renewal include: accepting or condoning conflicts of interest affecting physicians and managers, including respected faculty paid part-time by pharmaceutical companies apparently to help market their products, and hospital CEOs paid by vendors for "face-time"; hospital CEOs convicted of federal crimes commited as part of their official duties; and hospitals indicted for federal crimes and allowed to continue operating only under deferred prosecution agreements; etc., etc. These behaviors to me suggest the need for higher ethical standards for hospital leadership.

Current events suggest that the leadership of nonprofit hospitals, like other health care organizations, is all to often mission-hostile. Urging hospital leaders to go up to or over the legal line to beat out the competition may produce even more mission-hostile management. If managers heed this dubious advice, higher costs, decreased access, poorer quality, and more demoralized health care professionals would surely soon follow.

Friday, February 16, 2007

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 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.

Accusations Against AZ

It also was not a happy week for UK pharmaceutical company AstraZeneca.

On one hand, as reported by Bloomberg news, the company is now the subject of thousands of lawsuits about its marketing of the atypical anti-psychotic drug Seroquel (quetiapine). From the Bloomberg report,

AstraZeneca Plc, the U.K.'s second- largest drugmaker, has been sued by almost 10,000 people in the U.S. over claimed injuries from defects in the company's antipsychotic drug Seroquel, according to a court filing.

Patients claim in their complaints that AstraZeneca didn't adequately warn of possible side effects, including severe weight gain and risk of diabetes. Many of the suits contend the London- based company and its affiliates promoted the drug for unapproved uses, contrary to U.S. Food and Drug Administration regulations.

The lawsuits are similar to claims filed over injuries from the antipsychotic drug Zyprexa against Eli Lilly & Co., which has settled more than 28,000 cases for as much as $1.2 billion.

The growth in sales of the drug, from $66 million in 1998 to $2.75 billion in 2005, was spurred by 'AstraZeneca's aggressive marketing of Seroquel,' according to these patients, whose cases have been transferred to federal court in Orlando.

The marketing 'consisted chiefly of overstating the drug's uses and benefits (including massive off-label promotion), while understating and consciously concealing its life-threatening side effects,' their complaint said.

There are no defects in Seroquel, and AstraZeneca doesn't intend to settle the suits, company spokesman Jim Minnick said.

'We are vigorously defending them all,' he said in an interview. 'We believe Seroquel is safe and effective.'

On the other hand, the company was just accused of being one of the many companies, including some prominent pharmaceutical companies, involved in the oil-for-food sanctions scandal. According to the UK Guardian,

The Serious Fraud Office has launched an investigation into allegations that a number of major UK-based firms paid bribes to Saddam Hussein's regime in Iraq. The firms being targeted include the drug giants GlaxoSmithKline (GSK), AstraZeneca and Eli Lilly. The international oil traders and UK bridge-builders Mabey and Johnson are also to be investigated.

They are on a long list of international companies accused in a UN report of paying kickbacks under the discredited oil-for-food sanctions regime, which enabled Saddam to illicitly amass an estimated $1.8bn. Ministers have agreed to fund the investigation with £22m over three years.

The inquiry was ordered last week by the SFO director, Robert Wardle. Yesterday the agency confirmed: 'The director of the SFO has opened an investigation centred on alleged breaches of sanctions in respect of the UN oil-for-food programme.'

The investigation - the first official inquiry into the oil-for-food scandal - was urged on the British government by Paul Volcker, a former chairman of the US Federal Reserve, who compiled a UN report, delivered two years ago, into abuses of the programme after investigating the sanctions regime that enabled Saddam to survive for so long.

Mr Volcker said the programme - in which Iraq was only allowed to sell limited amounts of oil abroad to buy food and medicines - had become corrupted as the Saddam regime demanded kickbacks from foreign companies in return for the contracts. He identified French and Russian politicians as the chief culprits.

Mr Volcker said the kickbacks were disguised by various subterfuges. Contracts were inflated, usually by 10% to cover so-called "after-sales services" fees. More than 2,200 companies were listed, using evidence drawn from banking records and Iraqi government documents.

The inquiry will draw on Mr Volcker's evidence. He accused GSK of paying kickbacks worth $1m to win nine contracts valued at $11.9m to supply medicines. Yesterday GSK denied any wrongdoing.

AstraZeneca was named as having paid bribes of $162,000 to secure three contracts worth $2.9m. The company said: 'We deny any allegation of unethical behaviour on our part in our trading relationships with Iraq.'

Another company, Eli Lilly, was accused of securing a $3.2m contract with a bribe of $343,000. It said: 'Eli Lilly and Company ... denies any wrongdoing with regard to the oil-for-food scheme.'

It's odd how the companies mentioned in this report have all been recently accused of questionable marketing practices employed to promote blockbuster psychoactive drugs. (See our most recent post on GlaxoSmithKline and Seroxat or Paxil, and our most recent post on Eli Lilly and Zyprexa.)

Again, if the pharmaceutical industry wants to improve its reputation for marketing excess, the companies involved need to resolve these current accusations quickly, and start reassuring patients and health care professionals that they will clean up their marketing act. Maybe they should consider shifting their balance of internal power from the go-go marketers, back to the scientists and physicians within the companies?

Wednesday, February 14, 2007

New Black-Box Warnings and Congressional Hearings on Ketek: "Whose Interest is Being Protected?"

It has not been a happy few days for the pharmaceutical industry.

We previously posted (also here) about the ill-fated clinical trial, study 3014, of the antibiotic telithromycin (Ketek) made by Sanofi-Aventis, run by Pharmaceutical Product Development Inc. (PPD). Problems with the trial included fabrication of data at one clinical site, and allegations of manipulation of data at another. The physician in charge of the first site was convicted of mail fraud, and the physician in charge of the second had his license suspended. Although the results of this trial were never published, it still crept into the clinical literature: it was cited in a review article in the New England Journal of Medicine. Nonetheless, the US Food and Drug Administration (FDA) approved Ketek for use in even relatively mild infections. Back in June, 2006, US Senator Charles Grassley (R-Iowa) announced his intention to figure out why.

On Monday, the US Food and Drug Administration announced that Ketek would no longer be approved for sinusitis and bronchitis, relatively mild infections for which many other antibiotics are available. It also announced more "black-box" warnings for Ketek. (See this report by Bloomberg News, for example.) In preparation for a sub-committee hearing in the US House of Representatives about FDA oversight in this and other cases, Representative Edward Markey (D- Massachusetts) called these warnings "overdue," and suggested there was "no coincidence" about the timing of the FDA announcement prior to the committee hearing. The Associated Press (here via the Washington Times) quoted Markey, "it appears that a healthy dose of congressional oversight has reminded them to do their job and ensure the safety of drugs on the market." The AP also quoted Senator Grassley, "the FDA's action today shows what transparency can do. When a spotlight was turned on the questionable way in which Ketek got approved by the FDA for certain sinus and lung infections, the FDA was held accountable."

Today, reports on the hearings first appeared. Per Reuters,

U.S. lawmakers criticized the Food and Drug Administration's monitoring of the risks of the antibiotic Ketek (Sanofi-Aventis) and some other prescription drugs on Tuesday.

At a hearing on the FDA's drug safety oversight, lawmakers said the agency stifled dissent about the risks of drugs when top managers disagreed. They cited problems with Ketek, Vioxx (Merck & Co. Inc.'s withdrawn arthritis drug) and antidepressants made by several companies.

'With each of these drugs, it appears that the FDA is not seriously questioning whether the risks outweigh the benefits of the new drug,' said Rep. Bart Stupak, a Michigan Democrat who chairs a subcommittee of the House of Representatives Energy and Commerce.

'One must ask, if the FDA is not protecting its client, the American people, whose interest is being protected?' Stupak said.

Iowa Republican Sen. Charles Grassley, a vocal FDA critic, told the committee that 'scientific dissent is discouraged, quashed and sometimes muzzled' inside the agency and 'there's widespread fear of retaliation for speaking up about problems.'

And Anna Wilde Matthews, again in the Wall Street Journal, reported,

A former employee of the Sanofi-Aventis SA contractor that oversaw a clinical trial of the antibiotic Ketek told Congress the drug maker knew there was evidence of a problem with the study before regulators discovered fraud.

The testimony of Ann Marie Cisneros, a former employee of contractor Pharmaceutical Product Development Inc., came as the House Energy and Commerce Committee opened hearings into how the Food and Drug Administration handles drug-safety issues.

Committee Chairman John Dingell, a Democrat from Michigan, called the FDA 'badly broken,' and Rep. Bart Stupak, another Michigan Democrat and chairman of its investigations subcommittee, said the FDA's interactions with the drug industry had become 'incestuous.'

[For balance,] In a statement, Sanofi-Aventis said it was 'unaware at the time' that what appeared to be deviations at the site 'in fact reflected fraud in the conduct of the study.' The company said Aventis 'acted in good faith' in conducting the study and has cooperated with investigations.

The FDA, which had none of its leaders testifying, said in a statement that it 'shares Congress' commitment to drug safety issues' and the agency has announced a number of recent drug-safety initiatives. The agency said it followed 'standard procedures in identifying and communicating risks associated with Ketek.'

Pharmaceutical Product Development said it complied with FDA regulations and its contract with Aventis and reported all issues in the trial to Aventis.

In summary, it appears now that the common wisdom about Ketek was based on "pseudoevidence." (See our relevant post on "pseudoevidence-based medicine.") Unfortunately, these sorts of stories suggest that patients and physicians need to be very skeptical about the integrity of the evidence used to support use of the latest, greatest, and most expensive pharmaceuticals. If the drug industry wants to improve its sagging reputation, it will have to show that it can clean up how it does clinical research. Or perhaps we ought to think about getting drug (and biotechnology and device) companies out of the business of sponsoring clinical research on products in which they have vested interests? Of course, such a change will threaten quite a few peoples' sources of incomes, so we can expect plenty of resistance to it.

Monday, February 12, 2007

The Threat of Pseudoevidence-Based Medicine

Clinical Governance, a respected but not widely-circulated journal from the UK, just published an article (subscription required) entitled "pseudoevidence-based medicine: what it is, and what to do about it," written by Health Care Renewal occasional blogger Dr Wally R Smith. [Smith WR. Pseudoevidence-based meidicne: what it is, and what to do about it. Clinical Governance 2007; 12: 42-52.] The article was featured on the publisher's latest monthly highlights page.

I read (and commented on) an earlier draft of this article, and was struck by its use of the term pseudoevidence-based medicine to describe some of the less healthy trends we have discussed on Health Care Renewal. Some key quotes:

Another, perhaps not new threat to the practice of EBM [evidence-based medicine] has been discovered -- pseudoevidence-based medicine (PBM). PBM can be defined as the practice of medicine based on falsehoods that are disseminated as truth. Falsehoods may result from corrupted evidence--evidence that has been suppressed, contrived from purposely biased science, or that has been manipulated and/or falsified, then published. Or falsehoods may result from corrupted dissemination of otherwise valid evidence. These falsehoods, when consumed as truth by unwitting and well-intentioned practitioners of EBM, then disseminated and adopted as routine practice, may well result not only in inappropriate quality standards and processes of care, but also in harms to patients.

EBM rests on the premises of professionalism in science and medicine. EBM presumes that evidence is produced by scientists who strive to be objective. EBM presumes that those producing evidence have no pre-conceived hopes or goals for what the evidence will show. EBM presumes that producers of evidence have no stakes in what the evidence will show. EBM presumes, or at least strives to assure, that the scientific evidence-production process is free manipulation by people with vested interests with goals other than improvement in patients’ mortality, morbidity, or quality of life.

There are reasons to believe EBM’s presumptions are in question, and that PBM is a “new” threat to EBM. Only two conditions are necessary for PBM to flourish. First, one link in the chain of evidence production, assembly, or dissemination must be purposely corrupted, resulting from a compromise of professionalism in science and medicine. Second, the belief must be promulgated that a given piece of evidence is true and of the highest quality possible, when in fact it is tainted.

Smith attributed the rise of pseudoevidence-based medicine to the conflict between the profit motive and physicians' traditional values.

By definition, pharmaceutical companies, device manufacturers, some health care providers, many insurance providers, and various middlemen and brokers in health care are in business for a profit. And while the profit motive is not itself wrong or dangerous, the profit motive is dangerous when placed in direct competition with protecting and prolonging human life, the precise business in which health care stakeholders should be engaged.

As they say, "read the whole thing."

And I think that we will find the term pseudoevidence-based medicine very useful on Health Care Renewal.

Friday, February 09, 2007

Siemens Medical Solutions USA Pleads Guilty to Obstruction of Justice

The giant German company Siemens AG has been under investigation in Europe for corruption. Now its US medical subsidiary, Siemens Medical Solutions USA Inc has pleaded guilty to a charge of obstruction of justice. Per the Chicago Sun-Times,

A subsidiary of international giant Siemens AG admitted in federal court Thursday that it lied to Cook County officials to win a $49 million hospital contract in 2000 then lied in court during a lawsuit to cover it up.

The subsidiary, Siemens Medical Solutions USA Inc., pleaded guilty Thursday to one count of obstruction of justice and is expected to pay a $1 million fine and more than $1.5 million in restitution to the county, according to a plea agreement the company reached with federal prosecutors. The company would also have to show its plea agreement to all government agencies it is currently doing business with, including the Department of Health and Human Services and the Defense Logistics Agency.

The guilty plea is the latest mark against a company that has been embroiled in controversy around the world regarding its corporate behavior.

The company admitted in its plea agreement to lying to Cook County officials that it was setting up a joint venture with a minority business as a true partner to provide radiology equipment to John Stroger Hospital. In fact, instead of cutting the business, Faustech Industries, into the deal with a share of the profits, Siemens Medical had agreed to pay a much lower flat fee to the company to lend its minority status to the deal.

A Siemens Medical manager called the joint venture nothing more than "a shell," according to the plea agreement.

Siemens Medical acknowledged failing to tell county officials about the arrangement because Siemens Medical officials believed their bid would not have been accepted if the county knew the truth.

In 2000, a rival bidder on the radiology equipment contract sued Cook County, challenging its award of the deal to the joint venture, and Siemens Medical repeatedly produced misleading documents and false testimony in court to cover up the true nature of what it was doing, according to the plea agreement.

Note that we first discussed this story back in 2005, and again in 2006.

Well, was it Jimmy Durante who said, "everybody has got to get into the act?" It seems like every kind of health care organization has got to get into the shady business practices act.

How many of these stories will it take for health care professionals and health policy makers to admit we have a systemic problem with the leadership and governance of health care organizations?

We clearly need to admit we have a problem. We need to develop watch-dogs and oversight mechanisms beyond a few people in the blogsphere. We need new regulatory mechanisms adapted to the brave new world of health care, rigorous enough to root out the leaders who would line their pockets at the expense of their organizations' missions, and even more outright corruption, yet flexible enough to allow innovation and progress. It won't be easy, but it won't begin to happen until we can at least admit we have a systemic problem.

Guidelines in Whose Interest? - Smoking Cessation

Physicians are frequently exhorted to follow clinical practice guidelines. Guidelines are now being given "teeth" by the currently fashionable "Pay for Performance" (P4P) movement. Yet, as we have discussed, guidelines may be written by people with financial ties to organizations that have vested interests in products or services that the guidelines might recommend.

The latest example of this comes from an article in the Wall Street Journal. The Journal reported that US government sponsored guidelines about smoking cessation (helping people quit cigarettes) were written by people with financial ties to companies that make drugs intended to aid smoking cessation, and that the guidelines recommended these drugs as first line therapy.

Michael Fiore is in charge of revising federal guidelines on how to get smokers to quit. He also runs an academic research center funded in part by drug companies that make quit-smoking aids, and he personally has received tens of thousands of dollars in speaking and consulting fees from those companies.

Conflict of interest? No, says Dr. Fiore, who has consistently declared that doctors ought to use stop-smoking medicine. He says his opinion -- reflected in current federal guidelines -- is based on scientific evidence from hundreds of studies.

The Public Health Service, part of the Department of Health and Human Services, issued guidelines in 2000 calling for smokers to use nicotine patches, gums and other pharmaceutical aids to quit, with a few exceptions such as pregnant women. Dr. Fiore, a University of Wisconsin professor of medicine, headed the 18-member panel that created those guidelines. He and at least eight others on it had ties to the makers of stop-smoking products.

The panel is now working on a revision of the guidelines, scheduled for completion early next year. Dr. Fiore, an internist, is again chairman. He says this time only seven of 26 members have industry ties.

As the federal government weighs the data in making new recommendations, many of its advisers are receiving money from companies with a stake in the outcome. Dr. Fiore holds a chair at Wisconsin that is funded by GlaxoSmithKline. He directs a tobacco research center that received nearly $1 million in funding from makers of quit-smoking medicine in 2004 and $400,000 in 2005. Between 1999 and 2004, Dr. Fiore personally pocketed $10,000 to $40,000 a year from the quitting-aid industry for honorariums and consulting work. He says he stopped such work in 2005.

However, the evidence that supports using drugs to help people quit smoking may not be so clear. First, as the Wall Street Journal article pointed out, new observational studies have failed to show that using drugs leads to higher quit rates in the long run. These studies, however, can be confounded by differences among people who choose to quit "cold turkey" versus those who choose to use drugs.

Second, the evidence from controlled trials of drugs versus placebos may not be unequivocal. For example, I reviewed a prominent article that reported a trial that compared placebo with the nicotine patch, sustained-release buproprion, and both the patch and buproprion. [Jorenby DE, Leischow SJ, Nides MA. A controlled trial of sustained-release buproprion, a nicotine patch, or bot for smoking cessation. N Engl J Med 1999; 340: 685-691.]

The article had two major problems. First, it excluded patients with any serious medical problems, who were on any psychoactive drug, or who had substance abuse problems. Thus the study's results may not apply to many of the patients who most need to stop smoking.

Second, many patients enrolled in the study dropped out before completion of follow-up. Fully 19.8% were completely lost to follow-up. We do not know whether the patients who dropped out quit cigarettes in the long run, and whether the quit rates in such patients randomized to different treatments may have varied. Thus, given that the magnitude of the drop-out rate was similar to the magnitude of the difference in the quit rates among the treatment groups, it is possible that were we to learn whether the patients who dropped out quit, this data could completely reverse the results.

For example, the one-year quit rates for the patients who stayed in the study were 15.6% for the placebo group, 16.4 for the nicotine patch, 30.3 for buproprion, and 35.5 for both buproprion and the patch. Suppose that all the patients on placebo who dropped out quit long term, and that none who were on buproprion and the patch who dropped out quit. Then the quit rates for those two groups would have been 64.4% versus 35.5%, a complete reversal compared to the published results. Such a high drop out rate appears to be a fatal flaw in this study.

Finally, the Wall Street Journal article noted that many experts in smoking cessation have failed to reveal their financial ties to companies that make smoking cessation drugs when speaking or writing. For example,

Those who advocate medication sometimes fail to disclose that they have financial ties to companies. In an article on Voice of America's Web site last year, Jack Henningfield, identified only as a smoking-cessation expert, urged smokers to 'go to the consumer-friendly Web site that I like, which is'

Dr. Henningfield is a principal of Pinney Associates, a consulting firm whose largest client is GlaxoSmithKline, operator of the site. Other articles citing Dr. Henningfield's views on smoking have identified him as a professor at Johns Hopkins School of Medicine without mentioning the GlaxoSmithKline connection. Dr. Henningfield, who holds a doctorate in psychology, is an adjunct professor at Johns Hopkins. He says only 10% of his income comes from Hopkins.

Dr. Henningfield says he always tells journalists about his financial ties to industry. But in an interview with The Wall Street Journal last summer, Dr. Henningfield promoted the use of stop-smoking medicine without volunteering any information about those ties. He says he thought GlaxoSmithKline's public-relations firm had already provided the information.

In at least two medical-journal articles that Dr. Fiore wrote or co-wrote promoting the use of stop-smoking medicine, no mention was made of his financial ties to the makers of those treatments. Dr. Fiore says the editors of those journals may have ignored his disclosure or he may have failed to provide it. If the latter, 'I am sorry about that,' he says, adding that those are two of more than 150 medical-journal articles he has published.

In summary, some authors of the guidelines for smoking cessation had financial ties to companies that make drugs used to help smokers quit. The guidelines favored first-line use of these drugs, yet the evidence supporting such use may not be crystal clear. Smoking cessation experts have failed to disclose such financial ties when speaking or writing about relevant issue.

As I have concluded before, just because a set of recommendations is called a guideline, or is written under the auspices of some august academic or scientific organization does not guarantee that its recommendations are based on the best evidence, or are not influenced by vested interests.And yet guidelines remain a buzz word for those who say they want to control health care costs, and improve quality and access. And giving guidelines teeth, otherwise known as "pay for performance," (P4P) is now the most fashionable solution to the cost, quality, and access problems. (See post here.)We need to remain very skeptical about how guidelines are developed, and whose vested interests they may serve, and very careful about giving guidelines teeth through P4P.

Thursday, February 08, 2007

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?

Wednesday, February 07, 2007

Jeanne Lenzer Reviews Peter Rost's The Whistleblower

We have posted frequently about actions by Pfizer Inc., the world's largest drug company. For example, most recently we noted the company's apparent foray into "stealth lobbying," which involved recruiting patients to send letters to legislators in favor of Pfizer's interest.

In the latest British Medical Journal (which seems to be now the most quoted journal on Health Care Renewal) is a fascinating review by Jeanne Lenzer of Peter Rost's new book, The Whistleblower: Confessions of a Health Care Hitman. (Lenzer J. Telling the inside story? Brit Med J 2007; 334:261.) (We posted about Rost here and here.) Lenzer summarized Rost's somewhat bizarre career with Pfizer Inc and its predecessors:

Peter Rost, erstwhile drug company executive, self proclaimed whistleblower, and now book author, first became a cause célèbre in August 2004 when he wrote an endorsement of The Truth about the Drug Companies, the book by former New England Journal of Medicine editor Marcia Angell. He posted a commentary on, saying, 'I should start with a disclaimer. I'm a vice president within one of the largest drug companies in the world and I have spent close to 20 years marketing drugs. So I guess I'm not supposed to like this book. But the truth is I thought it was fantastic.'

Rost's posting was picked up by the media and he became a much sought after guest on television and radio shows. He took up the cause of drug reimportation, a practice that would allow foreign drug companies to sell drugs in the United States. Reimportation, argued Rost, is widely practised in Europe and could drastically reduce drug prices in the US. His position was in sharp contrast with that of his employer, Pfizer, and to virtually all major US drug companies, which vehemently argued that reimportation would allow unsafe drugs to enter the US and would threaten the health and safety of its citizens.

But Rost began to run into trouble long before he became a public advocate of reimportation. In 2001, as the new head of the endocrine care division of Pharmacia, he learnt, according to his account, that the division's flagship drug, Genotropin, a synthetic form of human growth hormone, was being promoted for off-label uses. Off-label promotion of growth hormone is a felony under federal anti-doping laws. Pfizer, which bought out Pharmacia in April 2003, failed to put a stop to the off-label promotions, says Rost.

Rost alleges that it was his complaints about the marketing of Genotropin that led Pfizer executives to fire him. He was first informed in an email message on 3 February 2003 that he was to be sacked, but he managed to hold on to his job for two and a half years, until 30 November 2005.... Rost filed a qui tam, or whistleblower, lawsuit against both Pharmacia and Pfizer in December 2005. In the suit and the book, Rost claims to describe some of the inventive marketing techniques used by the companies to promote sales of Genotropin to "anti-aging" clinics and for the treatment of short children who did not have growth hormone deficiency.

Lenzer was not enchanted with many aspects of the book, including Rost's defenses of some his own actions which Lenzer found indefensible. Nonetheless, she concluded,

Rost's book claims to chronicle problems in the way the drug industry manages to circumvent rules prohibiting off-label drug promotions. In addition, Rost's endorsement of reimportation is perhaps one of the most articulate defences made in the US. The Whistleblower may also reach some lay readers who were not moved to pick up any one of a number of more academic books on the drug industry. Finally, his overview of serious violations by nine top drug companies in his chapter 'How corrupt is the drug industry?' should make one thing crystal clear: fines simply don't work. They are, as has often been said, simply the price of doing business.

'Working for a corporation,' writes Rost, 'is like running with a wolf pack. Everyone helps out and is friendly as long as it benefits the group, but each wolf cares only about himself and will do anything to survive. Compassion, loyalty, caring . . . these are all buzzwords invented to control the masses.' Rost's take on the nature of industry might leave one wondering whether Rost isn't simply a very clever wolf himself.

The good news is that when the titans do battle—the fallout can be instructive.

Note that Rost has become a prolific blogger. Seem more of his provocative writing on Question Authority.

Monday, February 05, 2007

Allegations of Lavish Spending by Leaders of Global Fund to Fight AIDS, Tuberculosis, and Malaria

The Boston Globe just published a story about allegedly lavish spending by the leadership of the Global Fund to Fight AIDS, Tuberculosis, and Malaria. The fund is a large non-governmental organization (NGO), a foundation under Swiss law, that spends billions to fight infectious disease in less-developed countries.

The Boston Globe article was based on an internal report by the Fund's Inspector General, and a separate investigation by the World Health Organization (WHO). The article focused on spending by the Fund's outgoing director, Dr Richard G A Feachem. The report apparently said that his spending entailed "potential risks," and "could be perceived as unnecessarily lavish by donors." Details included spending "between $91 and $930 a day for limousines in London, Paris, Rome, Washington, and San Francisco, averaging $376 a day," also he spent "typically $50 to $100 per person" on meals, and also spent money on such things as renting a suit of clothes ($225). The report also included "flowers for staff members," "$8780 for a boat cruise on Lake Geneva in Switzerland," etc. Thus, it concluded, "senior management failed to convey and reinforce the need for careful and prudent use of donor funds."

The Globe article also noted that Feachem's pay is relatively high for a leader of a public health organization whose mission is to help people in poor countries. Feachem got $320 K a year, tax-free, which included a $70 K housing subsidy.

Furthermore, "Global Fund leaders went to great lengths to keep both reports secret. The full board was not given copies of the inspector general's report, according to members. They said they were allowed to read WHO's report for just a few hours in a room and could not keep copies."

The Globe article quoted Allan Rosenfield, dean of Columbia University's Mailman School of Public Health, "The board has allowed this to happen. They should be held accountable as well." Also, said Willem Landman, CEO of the Ethics Institute of South Africa, "I'm familiar with the cost of limousines in New York City, but this is beyond the pale."

Spokespeople for the Global Fund disputed the Globe's allegations. The Fund's web-site also has a rebuttal posted. Spokesman Jon Liden said, "when you read through the entire report, it becomes clear we are dealing with a report of extraordinarily poor quality in terms of accuracy, context, and fairness." Keep in mind, however, that he is referring to the report by the Global Fund's own Inspector General, not the Boston Globe news article. Lieve Fransen, Deputy Chairwoman of the Fund's board, defended keeping the report secret, "making these reports public would undermine people's dignity, credibility, right to defense, and would undermine the credibility of the Global Fund."

In my humble opinion, for the leaders of an NGO whose mission is to fight infectious diseases in poor countries to use the organization's money for limousines, expensive restaurants, and relatively lavish salaries does not engender confidence in their dedication to the organization's mission. Neither does the leadership's criticism of the work of their own Inspector General, and their attempts to keep his report secret.

The inclination of leaders of many health care organizations to put their own pocket-books and comfort ahead of the organization's mission seems to be an important reason why health care is so expensive, yet produces relatively so little value for the amount spent. It is particularly grievous when people who are already disadvantaged receive poor value for what little is spent on them.

Sunday, February 04, 2007

International Campaign to Revitalise Academic Medicine Calls on Leaders of Academic Medicine to Uphold Their Organizations' Core Values

Last week's British Medical Journal featured a remarkable "Open Letter to the Leaders of Academic Medicine," by the leaders of the International Campaign to Revitalise Academic Medicine (ICRAM). [Ioannidis JP, Ahmed T, Awasthi S, Clarfield AM, Clark J, Landona L et al. Open letter to the leaders of academic medicine. Brit Med J 2007; 334: 191-193.]

The letter was mainly about the leadership of academic medicine, or lack thereof. Although written with considerable humor, the effect was scathing:

We are not sure who you are. Unsubstantiated rumours suggest that you may not exist at all. We wonder where academic medicine is getting its lead from. Is it some of the many serious scientists, clinicians, and educators? Is it people with illnesses, those who wish to remain healthy, or society at large? Is it political leaders of uncompromising principles and vision? Is it selfless benefactors and visionary entrepreneurs? Or is it self interested compromisers carrying embellished titles acquired through anything but merit? Maybe it's corporate industry escorting academic medicine to the dance tonight?

The letter then noted the problems that afflict health care world-wide.

The pursuit of health is a global priority. Health care consumes an ever increasing proportion of gross national products. However, even in the countries that devote the largest resources to health, provision is beset with the serious problems of poor quality, danger, limited access, poor usability and responsiveness, low productivity, and lack of affordability.

It then pleaded for leadership with a vision that would end the current complacency, and worse.

Assuming that you do exist and that you have the ethos and, yes, the power to change things, we ask with respect and curiosity what is your vision? We've repeatedly heard the standard promotions for academic centres: 'We do the best research, we offer the best care, we are the best teachers, our discoveries shake the world, we save lives, we create medical superstars ....' Please, can we send the public relations people for a break and try to agree. How much can be achieved? What are our priorities?

Provided that you have a vision and that you are not some kleptocratic rogue appointed by a dictator at the Ministry of Health, you need to decide what you want.

A compelling vision requires the right people to materialise it. We don't want to see academic medicine replete with stagnation, compromise, pettiness, opportunism, selfishness, monolithic dogma, and intellectual narcolepsy. We don't want academia to provide authenticity to rotten societies with debased, non-humane values.

Finally, the letter suggests that we have reached our current state because of the failure of the leaders of academic medicine to uphold the core values of their institutions.

The smallest gap between rhetoric and reality rapidly undermines any institution. Too many institutions have damaged themselves by becoming strangled by business. It is by no means wrong to interact with the private sector (and some institutions might make this their primary focus), but a successful institution should be clear about its values, live by them, and never debase them in the pursuit of short term gain. Not every institution will have the same values, but some values seem fundamental to all. Perhaps the most basic might be the pursuit of truth, wherever it might lead, and the genuine interest to help people and our communities.

Political, religious, and corporate dogmas cumulatively undermine both academic and community freedom around the world. The malaise that affects academic medicine has much to do with losing healthy contact with stakeholders.

In some languages academic has become synonymous with something so remote that most people would not have any interest in it. Enhanced interaction is likely to benefit all, especially when guided by transparency, meritocracy, respect for both individual talents and teamwork, and pursuit of the common good.

It ends with a plea,

Dear potential leader of academic medicine, we don't know whether you exist, but we sincerely hope you do.

You can be a true leader regardless of your formal title or lack thereof. We have no doubt that you will succeed if you invest in an uncompromising yet positive vision.

The ideas in this cleverly written letter should be familiar to readers of Health Care Renewal. (We have posted about ICRAM before.) We have certainly written about how leaders of health care organizations may fail to uphold their organizations' values, and how such failures may lead to the ongoing problems in health care, including rising costs, declining access, stagnant quality, and demoralized health care professionals.

What is striking to see such a vigorous, albeit humorous exposition of them in one of the world's leading medical journals, and an exposition that underlines that the crisis in health care leadership is global, not just confined to the US, or to English speaking developed countries.

So let's see who is paying attention.

Thursday, February 01, 2007

HRDI Story Remains Mainly Anechoic

We recently posted about the settlement between the Healthcare Research and Development Institute (HRDI) and the Connecticut Attorney General Richard Blumenthal. HRDI is a for-profit owned by a number of the top executives of some of the US best known hospital systems and academic medical centers. According to an article in the NY Times, HRDI gives a limited number of drug, device, and biotechnology companies access to these executives, for a stiff fee (see earlier post here). Announcing the settlement, Blumenthal called HRDI "an anticompetitive, secret society, an elite and exclusive club of premier hospital executives and select hospital supply businesses that restrained competition to the detriment of patients and providers."

In our last post, I speculated whether this story, which noted the involvement of the leaders of some of the US most prestigious hospitals and health care system in such a "secret society," would lead to any further investigation of these leaders' roles, or any repercussions. Based on our observations of the "anechoic effect," the lack of echoes usually produced by stories about mismanagement by, conflicts of interest affecting, or corrupt behavior of leaders of health care organizations, I predicted that not much would happen.

So far, my prediction seems to be holding. Of the 30-odd leaders who were members of HRDI, local media have addressed only 3, although these efforts were revealing.
  • In Texas, television station KGBT tried to interview Joel Allison, President and Chief Executive of Baylor Health Care System in Dallas, but Allison had "no comment," and that is as far as that story goes.
  • In Tennessee, the Memphis Commercial Appeal interviewed Stephen C Reynolds, President and CEO of Baptist Memorial Health Care, and chair of HRDI. Reynolds asserted "there was no wrongdoing found," apparently because there have been no criminal charges, denied HRDI was secretive, explained the rule that allowed only two companies from any sector to participate as a measure to improve "diversity," denied that money he received amounted to a "conflict of interest," because "HRDI has had a strong conflict of interest policy," and declared the high purposes of the organization "to solve common issues in health care and improve services to patients."
  • In Utah, the Salt Lake Tribune independently reported on the involvement of Bill Nelson, the CEO of Intermountain Healthcare. The article stated, "Nelson and Intermountain trustees defended the association as a valuable forum for feedback and for tapping health care's best minds, saying it would have been inappropriate for Nelson not to take part." Nelson also emphasized the lack, so far, of criminal charges, Nelson, noting there have been no charges filed or admissions of wrongdoing, accused Blumenthal of 'creating the illusion of impropriety' where none exists." On the other hand, the article included some new material which challenged Nelson's assertions that there were no problems with his involvement in HRDI. "Mark Leahey, executive director of the Medical Device Manufacturers Association, condemned HRDI for its lack of transparency. Leahey, whose board includes executives of Utah companies, said he had no clue about HRDI or its business model until Blumenthal began investigating. Up until a few months ago, Leahey said, a pass code was needed to access any information on the group's Web site. 'These guys were making $30,000 and $50,000 a year to rub shoulders with top pharmaceutical and medical device companies,' Leahey said. 'They had fiduciary duty to their hospitals and they were essentially getting kickbacks from suppliers.' Furthermore, at least one Intermountain trustee was not happy with Nelson, "The vendors were paying to have these top executives come and consult with them and we knew that. We didn't like the consulting fee, but we didn't require him not to take it."
So far, the HRDI story has had few echoes in the health care media, although the ACP Observer did run a brief item on it.
My first comment is that it is a sad day for health care when hospital and health care systems CEOs assert that they can demonstrate their integrity by the fact that they have not yet been indicted for any crimes. In my humble opinion, the ethical standards for health care leaders, whose decisions affect the well-being and lives of patients, ought to be a bit higher than merely avoiding indictment.
My second comment is that, as expected, there seems to be reluctance in the "main stream media" to take up questionable conduct by the leaders of some of society's most respected organizations. But if these organizations are to deserve the respect they have historically received, their leaders ought to subscribe to the highest ethical standards, not to to be content to assert, to paraphrase one of our less respected former presidents, "I am not a crook."