More Allegations of the Mis-Management at the CDC

The Atlanta Journal-Constitution last weekend published another report alleging management mis-steps at the US Centers for Disease Control (CDC). To summarize, the article reported that an unpaid advisor to the Director of the CDC recommended the agency contract with a consulting firm, Celerant Consulting, with which he appeared to have a personal relationship. Then, allegedly, CDC managers manipulated an existing contract that really did not cover the sort of consulting it wanted the firm to do to hire the firm, and after that contract ended, had the company keep working without a contract. The latter action could possibly be a violation of federal law.

To quote from the article (with some re-ordering):

The road that led to the CDC's hiring of Celerant began with an introduction made by Atlanta businessman Kent 'Oz' Nelson, who at the time was board chairman of the CDC Foundation, a nonprofit that supports the agency.

Nelson, former chairman and chief executive officer of United Parcel Service, became a key [CDC Director Julie] Gerberding adviser after she was named CDC director in July 2002. Nelson, among other things, worked to identify business consulting expertise to help Gerberding chart a new strategic vision and reorganization of the agency.

'I told her I'd be glad to help and began searching for someone. Coincidentally, around the same time, I got a phone call from Jim Down,' said Nelson in an article in the CDC Foundation's 2002-2003 annual report.

In an interview, Nelson said he knew and respected Down from Down's work years earlier as a UPS consultant. Down 'was extremely effective in strategic planning,' he said.

Nelson said he set up a meeting between Down and Gerberding. 'They hit it off very well,' he said. And Down agreed to provide his help and expertise for free, flying between Massachusetts and Atlanta nearly every week, Nelson said. The CDC reimbursed Down only for expenses, Nelson added.

In June 2003, while Down was serving as Gerberding's adviser, Celerant Consulting issued the press release announcing that Down had been appointed to the company's advisory board.
Around October 2003, CDC officials began discussing the need to overhaul the operations in its procurement and grants office. Down recommended Celerant for the job to CDC Chief Operating Officer Bill Gimson, said James Seligman, the CDC's chief information officer, in an interview Friday.

Gimson said Down did not mention any potential conflict of interest when he recommended Celerant. 'Jim's conversation, as a matter of fact, was extremely brief,' Gimson recalled Saturday. 'He said 'I would like to introduce you to a company I think would do great work for CDC.'' After the agency became interested, Gimson said, Down had no further involvement.

After examining Celerant and interviewing company officials, CDC decided to hire the firm, CDC officials said.

Rather than open up the consulting contract to competitive bidding, CDC executives went looking for an existing contract elsewhere in the federal government that would allow them to hire Celerant directly. Seligman, Kotch and Gimson said this is a common and accepted practice. 'Government agencies are encouraged to use government-wide contracts when they're available and appropriate,' said Seligman.

Seligman called contracting officials at the National Institutes of Health, who he said identified a pre-existing contract that would work. According to the NIH Web site, this particular contract, called ECS III, is for the purchase of computer hardware and software to satisfy your agency's desktop computing needs. CDC officials said it also allowed for the purchase of 'services.'
And, most important for achieving the agency's goal of hiring Celerant, one of the prime contractors had as a listed vendor Novell, the computer software giant, which at the time owned Celerant.

'This is a common abuse of IT hardware and software contracts,' said Christopher Yukins, associate professor of government contracts law at the George Washington University Law School in Washington. 'In this case you have an information technology — really a hardware/software contract — being used for consulting services that have little to do with information technology.'

Regardless, the NIH contract is the mechanism CDC used from about December 2003 to February 2004 to hire Celerant to do an initial assessment of how to fix the agency's procurement and grants office. The cost of this initial phase was about $580,000, Seligman said.

The CDC was pleased with Celerant's initial work and wanted the company to go ahead and implement its overhaul plan, at a cost of $10 million. Although the first contract had ended, Seligman said CDC let Celerant continue working and incurring costs while the agency sought NIH approval to again link to the IT contract.

Celerant worked without a contract in place for three months, Kotch said.

Yukins, the government contract law expert, said: 'The federal government takes work done without a contract very seriously. ... It's a violation of federal law, [and] technically speaking it is a criminal violation of law.' While prosecutions are rare, he said, it is a very serious matter.

In April 2004, an anonymous letter arrived at the U.S. Department of Health and Human Services, the parent agency of both the CDC and the NIH, alleging improprieties in the Celerant contracting process. Gimson said that when HHS notified him of the letter, he immediately sent a memo to HHS asking that it conduct an independent inquiry.

By July 2004, HHS officials were sufficiently concerned about the appropriateness of the contract that they issued a formal stop-work order. HHS officials would not grant interviews on the matter.

In September 2004, the CDC said HHS officials allowed the Celerant contract to be reinstated, but required the CDC to take over managing it. They also required the CDC to renegotiate the terms, which resulted in Celerant reducing its costs by $500,000, to $9.5 million. And the CDC set the effective date back to cover the February-May period when Celerant was working without a contract, the agency said.

A CDC public relations risk-management analysis obtained by The Atlanta Journal-Constitution identified several 'threats' to the agency, including 'significant procurement mistakes' and an 'inappropriately backdated' contract document.

The circumstances described in that risk analysis — which CDC officials now seek to discredit as merely 'conjecture' — raise questions about serious and potentially criminal violations of federal procurement law, according to government contract experts.

We have posted before about CDC management here. In that post, we noted that the agency was paying CDC managers, especially those within the Director's office, large bonuses in comparison to those paid to health care professionals at the agency. The rationale was the need for "management transformation" at the agency, and then to retain the top quality managers hired with that goal in mind.

However, the current case suggests that CDC managers at best seemed to be putting expediency and personal relationships ahead of careful business practices. Was this the sort of management transformation meant above? Now tell me again why it is so important we put managers and bureaucrats, rather than health care professionals, in charge of health care organizations?

NIH Leader Indicted for "Criminal Conflict of Interest" for his Relationship with Pfizer Inc.

We have posted a lot about the story of wide-spread conflicts of interest affecting top leaders at the US National Institutes of Health (NIH). After the NIH conflict of interest rules were relaxed in the mid-1990's, some top NIH managers received five- and six-figure consulting payments from pharmaceutical and biotechnology companies. Some failed to disclose these payments, even when writing journal articles favoring the products of the companies for which they worked. Since then, NIH Director Zerhouni made the organization's conflict of interest policies much more stringent, although not without opposition from some of his staff (see post here).

Most recently interest has focused on two cases. Dr Trey Sunderland, a leader within in the National Institute of Mental Health (NIMH), part of the US National Institutes of Health (NIH), provided tissue samples to Pfizer Inc while receiving consulting fees from the drug company. (See posts here, here, and here.)

So today, while newspapers were filled with stories of Pfizer's withdrawal of torcetrapib, a drug it had hyped as a new kind of treatment to prevent heart disease, a striking follow-up about Sunderland's relationship with Pfizer Inc. appeared with much less fanfare. Per the Associated Press (as available here from the Boston Globe), Dr Trey Sunderland has just been indicted for "criminal conflict of interest." The Globe reported (somewhat re-ordered):

In a rare federal prosecution, a leading government Alzheimer's researcher was charged Monday with a criminal conflict of interest for performing lucrative private drug company work that overlapped his official duties.

Prosecutors alleged Dr. Trey Sunderland of the National Institutes of Health received $285,000 in improper consulting fees and travel expenses from Pfizer, Inc., for work on early indicators of Alzheimer's at the same time he also oversaw similar NIH business with the drugmaker.
The private consulting 'directly related' to his government job, and Sunderland failed to obtain the proper approvals from his supervisors or disclose the work to NIH, according to papers filed in U.S. District Court in Baltimore.

The felony charge carries a maximum sentence of one year in prison and a $100,000 fine. Prosecutors filed the charge as a criminal information, instead of indictment, signaling the possibility of a plea deal.

The prosecution is believed to be the first such case against a federal scientist since the early 1990s.

Sunderland refused to testify before Congress last June, citing his Fifth Amendment right against self-incrimination.

Members of the House Energy and Commerce Committee which launched the probe called Monday for Sunderland's dismissal. Otherwise, Rep. Bart Stupak, D-Mich., said in a statement, 'We can only conclude that no one is being held accountable, the system is broken and the public trust has been violated.'

Rep. John Dingell, D-Mich., complained Sunderland had been kept on even after Department of Health and Human Services agencies found wrongdoing in their own internal investigations.

'Will a criminal conviction for conflict of interest be enough to get someone fired from NIH?' he asked.

Ned Feder, a former NIH scientist now with the non-profit watchdog group Project on Government Oversight, said 'in this and similar cases NIH authorities have made it habit of covering up or minimizing wrongdoing. They are still hiding the details of other scientists' conflicts of interest over the past 10 years.'

Experts said the last prosecution of a senior NIH scientist was that of Prem Sarin, who was convicted in 1992 of embezzling a drug company payment to NIH that was intended to help with AIDS research.

Of course, an indictment does not prove criminal guilt. But the indictment of a formerly respected leader within the NIH for "criminal conflict of interest" certainly is a noteworthy step in the process of finally facing up to the conflicts that apparently afflicted a considerable number of the mid- and upper leadership of the NIH. These conflicts, in turn, are only a sub-set of the conflicts of interest that pervade other health care organizations, including medical schools and academic medical centers.

However, this case raises a further question. If Sunderland deserved indictment for taking money as a "consultant" from Pfizer Inc., and delivering to Pfizer samples he obtained while he nominally was working full-time for the NIH on issues related to his consulting assignment, what does Pfizer Inc., or the leaders there who decided to initiate the relationship with Sunderland, deserve?

Another Post-Modernist Attack on EBM: Because EBM is Not a "Vehicle" for Anyone's Political Program?

I make no secret of my support for evidence-based medicine (EBM). According to the Users’ Guides to the Medical Literature, at first the term described "an attitude of ‘enlightened scepticism’ toward the application of diagnostic, therapeutic, and prognostic technologies in ... day-to-day management of patients." Thus, "the goal is to be aware of the evidence on which one’s practice is based, the soundness of the evidence, and the strength of inference the evidence permits."[1] Another way to look at EBM is as a process, [2] e.g.:
1. translation of uncertainty to an answerable question;
2. systematic retrieval of best evidence available;
3. critical appraisal of evidence for validity, clinical relevance, and applicability;
4. application of evidence in practice; and
5. evaluation of performance.

EBM advocates understand that performing this process, however, is difficult and fraught with barriers and pitfalls. These include the shortage of coherent, consistent scientific evidence; difficulties in applying evidence to the care of individual patients; the need to develop new skills; limited time and resources; and the paucity of evidence that evidence-based medicine "works."[3] For discussions of how to cope with such difficulties and barriers, see these relevant articles.[4-6]

Yet EBM has produced negative reactions, some particularly intense, beyond what its well-described short-comings would seemingly inspire. These seem to be getting more frequent airings in the medical and health care literature, and in the media. See, for example, our previous posts on how EBM has been labelled "microfascist," both in a scholarly article (post here), and in an op-ed in US News and World Report (post here).

The latest example of such negative reactions is in an article recently published in Social Science Medicine.[7] This article by Goldenberg, entitled, "On Evidence and Evidence-Based Medicine: Lessons from the Philosophy of Science," like the one by Holmes et al,[8] took a post-modernist stance, with particular accent on feminism.

Like Holmes and colleagues, Goldenberg wrote in an opaque post-modernist style. She made the expected appeals to authority, but although these included the apparently obligatory bow to Foucault, she emphasized feminist authorities, such as Lorraine Code, Harraway, and Nelson. She quoted assertions by such luminaries as truth, without explanation or justification.

Like Holmes and colleagues, Goldenberg seemed to misunderstand EBM, and made arguments based on misunderstandings. For example, she equated EBM to logical postivism.

However, the apparent obviousness of EBM can and should be challenged on the grounds of how 'evidence' has been problematised in the philosophy of science. In this paper, I argue that evidence-based practices maintain an antiquated understanding of evidence as 'facts' about the world in the assumption that scientific beliefs stand or fall in light of the evidence. This understanding of evidence is explicitly positivist....

She then skewered logical positivism, citing how observation is theory-laden, and how theories are underdetermined. By thus discrediting logical positivism, she discredited EBM.

The formal methods promoted by EBM to replace so called 'traditional' medicine's over-reliance on intuition, habits, and unsystematic clinical experience appear to repeat the misplaced effort to separate science from values.

Note that most EBM proponents, of course, advocate the explicit incorporation of values into the EBM process, but they do distinguish values from science.

Goldenberg also wrote, citing Nelson as an authority,

The basic tenets of EBM, it seems, rest on the unquestioned authority of scientific evidence, a position that is now out of step with current post-postivistic thinking.

That might seem almost funny to an EBM proponent, given the amount of effort spent in the EBM process to rigorously critique evidence. EBM, in my humble opinion, is exactly the opposite of accepting "the unquestioned authority of scientific evidence."

Then, like Holmes and colleagues, Goldenberg accused EBM of badness. Although she did not label it "microfascism," her accusation was that EBM is harmful to women.

Feminist critiques of science are driven by a deep concern that the abstractions made in the names of scientific objectivity, generalisability, and predictability harm women. These tendencies appear to resurface in the practice of EBM.

And again,

Feminist insight reveals that the practices of EBM are marked by potential or actual gender bias, which has led at least one critic to argue that EBM is bad for women's health.

(And Goldenberg never questioned that critic's argument.)

Some of these accusations seem to be based on confusion between the messenger and the message. Goldenberg blamed EBM for insufficient representation of women in controlled clinical trials, "because evidence-based clinical decision-making, policy determinations, and the formulation of clinical guidelines rely upon existing clinical research, the movement reflects any gaps or biases that currently exist in medical research." Again, Goldenberg completely discounted how EBM has critiqued current clinical research for, among other things, not using patient populations whose results might widely generalize to the population at large.

Why are post-modernists taking such whacks at EBM lately?

Goldenberg may have provided a clue. She asserted,

A feminist philosophy of science is explicitly political, as science is recognised to be a vehicle for feminism's emancipatory programme.

I propose that one important reason that EBM may generate opposition is that EBM potentially challenges ideas, programs, and products in which people believe, or in which people have vested interests. If you really believe gizmo X works, or if you make a lot of money selling gizmo X, you may not be enthused about a rigorous review of the evidence that suggests that maybe gizmo X doesn't work so well.

In fact, EBM advocates suggest that EBM teaches people such new skills as "distinguishing evidence from propaganda (advertisement); probability from certainty; data from assertions; rational belief from superstition; and science from folklore."[2] Teaching people to distinguish evidence from propaganda and advertisement could offend the vested interests which increasingly dominate health care.

Goldenberg may have been particularly offended because EBM may not reliably support "a feminist philosophy of science [which] is explicitly political." Although Goldenberg asserted that "science is recognised to be a vehicle for feminism's emancipatory programme," EBM is not a vehicle for anyone's political program, no matter how well-intentioned.

Although some aspect of Goldenberg's political program may be worthwhile, for all I know, (which is little, since she did not explicitly describe this program), I think it is valuable to have a process like EBM which is hard for political advocates, as well as corporate executives and government bureaucrats, to manipulate.

Post-Script

Post-modernism has important influence in the humanities, and to some extent, the social sciences, in many US and other Western countries' academic institutions. Although post-modernists often claim that their work is supported by vast numbers of authorities and multiple weighty tomes, there have been a few well-written efforts to de-bunk the field. See in particular:
Hicks, SRC. Explaining Postmodernism: Skepticism and Socialism from Rousseau to Foucault. Tempe, AZ: Scholargy Publishing, 2004.
Koertge N. A House Built on Sand: Exposing Postmodernist Myths about Science. New York: Oxford University Press, 1998.
Sokal A, Bricmont J. Fashionable Nonsense: Postmodern Intellectuals' Abuse of Science. New York: Picador USA, 1998.
They did a much better job than I could do explaining why post-modernism is, as per Sokal's title, fashionable nonsense. It is too bad it has been slipping into medicine and health care, and now attacks EBM, which may be one of our few bulwarks against the economic vested interests that increasingly dominate medicine and health care.

References

1. Guyatt G, Rennie D, editors. Users’ Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice. Chicago: AMA Press, 2002. P. xiv.
2. Dawes M, Summerskill W, Glasziou P, Carabellotta A, Martin J, Hopayian K et al. Sicily statement on evidence-based pratice. BMC Medical Education 2005; 5: 1.
3. Straus SE, McAlister FA. Evidence-based medicine: a commentary on common criticisms. Can Med Assoc J 2000; 163: 837-841.
4. Haynes B, Haines A. Barriers and bridges to evidence based clinical practice. Brit Med J 1998; 17: 273-6.
5. Poses RM. Money and mission? - addressing the barriers to evidence-based medicine. J Gen Intern Med 1999; 14: 262-264.
6. Norman GR. Examining the assumptions of evidence-based medicine. J Eval Clin Practice 1999; 5: 139-147. 7. Goldenberg MJ. On evidence and evidence-based medicine: Lessons from the philosophy of science. Social Science & Medicine 2006; 62(11):2621-2632.
8. Holmes D, Murray SJ, Perron A, Rail G. Deconstructing the evidence-based discourse in health sciences: truth, power and fascism. Int J Evid Based Healthc 2006; 4: 180-186.

Report from the 12th International Anti-Corruption Conference: "Corrupting Health"

Last week, I was privileged to attend the 12th International Anti-Corruption Conference in Guatemala City, Guatemala. It was gratifying to be at a meeting of over 1200 people from over 100 countries who were all focussed on challenging corruption wherever it may be found. Some of the attendees had truly risked their lives to this end. One vivid example was the recipient of the 2006 Transparency International Integrity Award, Peruvian prosecutor Dr Ana Cecilia Magallanes Cortez, who fought corruption at the highest levels in here country's government, leading to the arrest of former president Alberto Fujimori.

A considerable amount of the meeting's program content seemed relevant to the issues we discuss on Health Care Renewal. I will report back on some particular issues in this regard in the near future.

I was also privileged to to participate in a workshop at the meeting on health care corruption. Our workshop leader, Roger Bate, has kindly posted a summary of what we were up to on TechCentralStation, entitled "Corrupting Health."

The summary rightly emphasized the substantial problem of government-focused corruption in developing countries, based on one definition of corruption used by Transparency International, "the use of public office to further private gains."

I must qualify one statement in the summary attributed to me, that "major corruption is estimated to be low in the US in the health sector." Given the definition of corruption above, and certainly relative to the role of governments in health care in developing countries, that statement is reasonable. However, I would point out that an alternative definition of corruption, ethical rather than legal, found in the Executive Summary of the 2006 Transparency International report on global health care corruption, is "the abuse of entrusted power for private gain." By that definition, corruption in US health care may not be so rare. See Health Care Renewal for examples.

Big employers plan electronic health records (and a manned Mars expedition as a warmup?)

The Wall St. Journal article on this is not yet available electronically, so the article below from the magazine "Red Herring: The Business of Technology" will have to do (perhaps not an inappropriate selection for the purposes of this Healthcare Renewal entry!)

Big employers plan electronic health records - and plan to deliver "a jolt to the US healthcare system", according to the WSJ. Will that "jolt", however, be the jolt that's expected?

Regarding the statement in the Red Herring article below that "... an employer-owned medical database for employees open's a Pandora's Box of privacy and ethical issues", as a former practitioner of occupational medicine in the medical department of a large, unionized municipal transit authority where these issues commonly occurred (e.g., over random drug testing and worker's compensation), I agree.

However, that's the least of the problems. A belief that expertise in computing hardware or in mass-merchandising enables such a venture is quite a quantum leap of faith.

Will the big-corporation approach to EMR work? I'd feel more confortable if the corporations had the complexities of healthcare and healthcare informatics within their core competencies.

See this link for some of the issues that won't disappear due to corporate will, as well as my previous post on Microsoft's clinical information technology venture here.

Also see the issues that are ongoing at Kaiser regarding their plans to be king of the EMR (see here and here , and for an alternate view see here). We report, you decide.

Intel, Wal-Mart Plan to become the Bill Gates of EMR

Companies attempt to heal a system that refuses to heal itself, but is Wal-Mart credible on healthcare?

November 29, 2006

By Cassimir Medford

Red Herring

A coalition of businesses including Intel and Wal-Mart will announce a plan that they believe will spur the development of a massive healthcare database in the United States , a digital Holy Grail that has been under debate for more than a decade.

According to Wednesday’s edition of The Wall Street Journal , Intel, which employs almost 100,000 people, and Wal-Mart, the largest private employer in the U.S. , plan to construct a database that will house the health records of their more than 1 million employees.

Hospitals, pharmacies, doctors, and insurers will have access to the database, which will be able to process the medical cost-sharing based on the health plans of the employees.

The healthcare industry has proven adept at adopting medical technology and a little less adept at adopting new drugs, but information technology has emerged painfully slowly in hundreds of systems that don’t communicate with each other.

For the most part, healthcare information systems have remained paper based, with all the errors involved in paper handoffs among doctors, nurses, hospitals, and pharmacies.

... an employer-owned medical database for employees opens a Pandora’s Box of privacy and ethical issues.

Plus the presence of Wal-Mart as one of the commercial leaders of the online patient’s records movement could present some drawbacks.

"Wal-Mart’s track record on the matter of healthcare benefits for employees has been less-than stellar so they are liable to get a lot of negative publicity for this database," said Charles King, principal analyst with PundIT Research.

... Can of Worms

There are also issues around discrimination from the employer, other potential employers, insurance companies, etc., based on an employee’s health records, which will be digitized, organized, and accessible in one place.

“People understand the benefits, but they are concerned about the Big Brother aspects that are troubling to a lot of people,” said Roger Kay, principal analyst of Wayland, Massachusetts-based Endpoint Technologies Associates.

... Under the Intel/Wal-Mart plan, employees will have ultimate control as to who accesses their records, according to the Journal , and they will have full ownership of those records [easier said than done - ed.]

The coalition hopes the healthcare industry will get on board, which could make the database the first or second phase in the general construction of a national patient health records database.

The UK has been trying this in their Connecting for Health government-sponsored national EMR project. They have not been having the best of luck at it:

Blair's barmy army
Times Online.uk

Critics say the government has blown £70 billion hiring management consultants to do the work of ministers and civil servants — badly. By Bryan Appleyard

Next month the National Audit Office is due to produce a report on government use of management consultants. “Don’t hold your breath,” says Neil Glass. Glass, writing as David Craig, is a whistleblower. His book, Plundering the Public Sector, paints a uniformly bleak picture of consultant greed and government incompetence. Since 1997, he says, consultants have cost the taxpayer £70 billion with either zero or negative returns. He doesn’t expect much from the NAO report because the audit manager, the key figure, of the study is Ron SirDeshpande.

Accenture, one of the giant consultancy firms, employed SirDeshpande for almost eight years before he came to the NAO. For Glass, this means he’s just one of the gang and he won’t dare rock the cosy consultancy boat. A spokesman at the NAO sighs: “I know who you’ve been talking to. Ron SirDeshpande works full time for the NAO and his voice is independent.”

Glass snorts.

On September 28, Accenture pulled out of its £1.9 billion contract with the NHS. Connecting for Health (CfH), a huge computer system, was cutting into Accenture’s profits and threatening its balance sheet with up to $450m in write-offs. Launched in 2002 as a project lasting two years and nine months and costing £2.3 billion, CfH has become a 10-year project with a probable cost of £12.4 billion.

Good luck, Wal Mart, Intel et al.

-- SS

The UMDNJ Mess: A Comment from the Front Lines

We have reported frequently about multiple kinds of misconduct by top leadership at the University of Medicine and Dentistry of New Jersey (UMDNJ). In our most recent post we noted how little had been heard from the long-suffering professionals and academics who have been laboring to fulfill UMDNJ's mission despite the turmoil at the top. In response, we got this comment from one such person on the front-lines, who will remain anonymous:

As a member of 'this long-suffering group,' I think you make a good point about talking to us. We've had a couple of town meetings with the governor, but that was before the latest round of scandals and very little about reorganization was discussed.

No one is talking about shutting down the parts of UMDNJ, just the superstructure. The best analogy I can think of is the Soviet Union. The component countries all still exist, they just don't have to worry about the Politburo anymore.

I doubt if you could find one faculty member at the Robert Wood Johnson Medical School who disagrees that UMDNJ should be restructured, and that restructuring should include emancipation of RWJMS from UMDNJ. If they shut down UMDNJ central administration completely, that would have the added benefit of saving money and electricity and relieving traffic congestion and parking around University Hospital in Newark.

We have often suggested that health care organizations require and deserve more representative, transparent, accountable and ethical governance.

In particular, despite being staffed by hundreds of well-trained and accomplished faculty members, it is remarkable how often the governance of medical schools and academic medical centers is top-down, and often in the hands of people with little experience or background in health care. This appears to have been true in the case of UMDNJ.

One wonders if CEOs would stop being "imperial," and would start listening to the talented people who work for them on the front lines, how many problems they would avoid, and how much better their organizations would become at fulfilling their missions?

The American Diabetes Association and Its Pharmaceutical Donors

The New York Times reported last week about potential institutional conflicts of interest affecting the American Diabetes Association. The Times' article's main focus was on the organization's ties to the food industry, especially to makers of highly caloric food:

SnackWell’s Sugar-Free Lemon Creme cookies have nearly as many calories as some sugar-rich cookies. Yet until recently the box featured an American Diabetes Association logo, advertising the cookie as a 'proud sponsor' of the charity’s efforts on behalf of the nation’s 21 million diabetics.

Foods like the Sugar-Freedom Eskimo Pie and Frosted Shredded Wheat have also sported the American Diabetes Association logo over the years. The companies paid the A.D.A. to be associated with a respected voice for healthful eating. The association wanted the money to finance its uphill battle against a widening epidemic of Type 2 diabetes, which is associated with obesity.

To its credit, the ADA has started to rethink its relationship with the food industry.

But in the last year the A.D.A. began rethinking how it raises money from companies, especially from those whose primary business is selling foods and beverages that are high in calories, even if they have created some sugar-free items.

The group has allowed some food company deals to expire and has turned down millions of dollars in new sponsorships.

However, although it received less attention in the article, what may be a more important issue is the ADA's relationships with pharmaceutical companies (quotes below somewhat re-ordered.)

Though they often present the most difficult choices, food companies represent a small segment of the A.D.A.’s corporate support. Pharmaceutical companies remain the largest corporate contributors, but the guidelines have not affected them as much because the A.D.A. has never allowed its logo to be put on specific medicines.

Others remain concerned about the A.D.A.’s relationships with pharmaceutical companies. Their presence is evident throughout the charity, from its annual convention, which is largely underwritten by drug makers, to its board meetings, where pharmaceutical executives have served on the volunteer committees that set policy.

The A.D.A. says its independence is evident because it has often acted against the interests of the pharmaceutical industry. Last month, for example, a panel it appointed to study how to treat people at heightened risk of developing diabetes decided against recommending the use of higher-priced brand-name drugs.

But critics say the drug industry’s influence can be seen in the A.D.A.’s emphasis on the treatment of diabetics, which often involves drug therapy, over efforts to persuade people to change the way they live so that the disease can be prevented in the first place.

Dr. Peter Lurie, deputy director of the Health Research Group of Public Citizen, the government watchdog group, said the influence of pharmaceutical money can be very subtle.

'The question is what happens in the close calls,' he said. 'If you are at more cocktail parties, if you have more mugs from the company in your kitchen, you are just going to be more receptive.'

A.D.A. officials cited an event from several years ago to illustrate their resistance to such influence. An A.D.A. panel found that antipsychotic drugs could help fuel diabetes. The announcement angered a drug manufacturer, Eli Lilly and Company, a longstanding A.D.A. benefactor that stood to lose hundreds of millions of dollars in lawsuits.

Some A.D.A. officials said they believed the company became so angry it sought to have Dr. Kahn fired, a charge the company denies.

Either way, nothing happened. Dr. Kahn, the association’s chief scientific officer, kept his job.

'Show me one instance where money has caused us to do something that is wrong,' Dr. Kahn said in an interview. 'You can’t.'

One starts to wonder whether there is any large US health care non-profit corporation that does not receive a significant amount of funding from the for-proft health care sector.

It may be very hard to prove such relationships have caused not-for-profit organizations like the ADA to do "something wrong," especially if one demands a scientific level of proof of causation.

On the other hand, a not-for-profit that gets a large amount of money from, say, the pharmaceutical industry might be hesitant to be critical of the industry or its products, or prone to give the industry the benefit of a doubt.

But even such relatively subtle biases could put the industrial benefactor's interests ahead of the not-for-profit organization's own mission.

Large, stable funding streams from commercial firms may be tempting, but not-for-profit leaders must ask themselves if they are worth the doubts they ought to raise.

More Fall-Out from Allegations of Faculty Positions Traded for Referrals at UMDNJ

The latest development in the mess at the University of Medicine and Dentistry of New Jersey (UMDNJ) produced some interesting analysis in the media. As we have discussed previously, the university now is operating under a federal deferred prosecution agreement with the supervision of a federal monitor (see most recent posts here, here, here, here and here.) We had previously discussed allegations that UMDNJ had offered no-bid contracts, at times requiring no work, to the politically connected; had paid for lobbyists and made political contributions, even though UMDNJ is a state institution; and seemed to be run by political bosses rather than health care professionals. (See posts here, and here, with links to previous posts.) The latest development (see post here with links to previous posts) was that UMDNJ apparently gave paid part-time faculty positions to some community cardiologists in exchange for their referrals to the University's cardiac surgery program, but not in exchange for any major academic responsibilities.

First, the indefatigable Newark Star-Ledger reported that Dr Jerrold Ellner, the chair of medicine at the UMDNJ Newark campus, was put on administrative leave because he and Ronald Pittore, of the school's legal department, "were identified by the university's federal monitor as key figures in UMDNJ's plan to hire at least 18 local cardiologists as part-time clinical assistant professors."

That event inspired a news analysis article in the New York Times. The points it made included,

As New Jersey’s state medical school has been shaken in the past year by disclosures of widespread financial mismanagement, administrators there have repeatedly defended the institution, the University of Medicine and Dentistry of New Jersey, by insisting that the scandals have affected its treasury but not the quality of care for the more than two million patients it treats each year.

But a federal monitor’s recent accusations that the cardiology unit at the university’s main hospital has been paying kickbacks to doctors for referring heart patients have undercut that argument at a time when the school’s future remains in doubt.

The fact that some of the university’s most prominent doctors now stand accused of taking part in an illegal scheme that involved life-or-death medical decisions is likely to further tarnish the school’s image at a time when state officials are deciding whether to merge the institution with Rutgers University and Robert Wood Johnson University Hospital.

Governor Corzine said on Wednesday that charges about the quality of care being affected by the scandal were deeply troubling — 'It’s really disgusting that the culture allowed for this kind of practice' — but added that he had not decided whether to restructure or disband the school.
But other state officials said the latest round of disclosures would only heighten pressure for a merger.

'This just highlights the disaster of trying to salvage what’s left,' said State Senator Raymond J. Lesniak, a Democrat from Union County who is chairman of a panel examining the future of the school. 'Before, the focus was on enhancing the ability to provide education. But now we’re also talking about direct impact on health care and people’s lives.'

On one hand, it is too bad that this analysis appeared in the Times' regional section. Although one would think that a scandal of this magnitude involving the biggest health care university in the US would attract national attention, as an example of the anechoic effect, it has been treated largely as a regional matter.

On the other hand, the analysis recounts some curious ideas about this case.

The first is that a scandal involving top leaders of the health care university had only financial significance, at least until a top physician leader was involved. Underlying this might be an asumption that the managerial and financial sphere of the university is entirely separate from the clinical and academic sphere. But the mismanagement in the former sphere must have sapped resources from the latter. Furthermore, it is hard to believe that clinical and academic personnel did not sense something wrong in the top management, and at least that the focus was more on the personal interests of the top management than the mission of the university. Such a sense would likely at least have dispirited these personnel, and certainly would not have enhanced their performance.

The second curious notion was that the involvement of a top physician-leader somehow signifies that the institution is now irredeemable, and the only remaining choices are to merge it into another institution, or shut it down entirely. This seems to discount, again, all the hard-working clinical and academic personnel who have been laboring to keep things together at UMDNJ together despite the bad behavior by top management. Maybe somebody should talk to this long-suffering group before any irrevocable decisions are made about the structure of the institution. And again, for better or worse, all should remember that health care institutions are made up of many dedicated hard-working people, besides the top managers. Perhaps again the underlying assumption is that somehow imperial top management is indistinguisable from the institution, the notion that "l'hospital c'est moi."

This notion must be discarded in favor of health care governance that is more representative of the relevant stake-holders, as well as more accountable, transparent, and ethical.

Bayer's Attempted Suppression of Trasylol (Aprotinin) Data Makes the New England Journal of Medicine

The latest issue of the New England Journal of Medicine includes an article about Bayer's attempted suppression of data from an observational study of Trasylol (aprotinin). [Avorn J. Dangerous deception - hiding the evidence of adverse drug effects. N Engl J Med 2006; 355: 2169-2171] We had first blogged about this case, based on a story reported in September, 2006 in the New York Times, here. Avorn's comments on the case are notable:

The health care system has a hard time performing drug-safety analyses, in large part because it relies on the pharmaceutical industry to conduct most research on the risks and benefits of medications. It is naive to expect companies to voluntarily fund studies that could sink lucrative products, the FDA lacks the regulatory clout to require them, and despite the $220 billion we spend on drugs each year, we apparently can't find the resources to provide public support for these studies, even if the results could be of great clinical importance and save millions of dollars.

Avorn suggested:

A good start would be to make a national commitment to publicly supported studies of drug risks so that no company could take possession of critical findings for its own purposes. The results of that research could be discussed openly at an annual conference on the risks and benefits of drugs.

In my humble opinion, it does not make sense to let pharmaceutical (and bio-technology and device) companies be responsible for performing relatively unmonitored studies on human subjects to test their own products. One solution would be to put scientists, physicians, and organizations who are not beholden to such companies in charge of such studies. Another would be much more intense regulation of any human studies sponsored by commercial firms.

At least this issue has now come out in the perhaps world's most prestigious medical journal, so it is squarely in front of doctors, other health professionals, and health policy makers.

But I now realize that Avorn's article, and, for that matter, my previous post, both seemed to avoid the issue of accountability of the drug, bio-tech, and device companies who are currently performing (or funding, and then at least partically controlling) studies on humans. So let me correct that omission.

Also in my humble opinion, as long as commercial firms (e.g., pharma, bio-tech, or device) sponsor, and to any extent control studies on human beings, these firms should be held accountable for any failure to disseminate study findings, even if, and maybe especially if the findings are not favorable to their product. Because their products affect peoples' health and safety, suppressing data about their products' adverse effects, or failure to provide beneficial effects is an affront to any patient who might take or be subject to such products. There should be severe negative consequences for any company that withholds such findings.

Cyberonics' Top Leaders Forced Out Over Back-Dated Stock Options

We had previously posted about the curious way in which Cyberonics' vagus nerve stimulator device was assessed as a treatment for severe depression by a US Food and Drug Administration (FDA) panel. Although a randomized controlled trial failed to show any improvements due to the device that could not be explained by chance alone, after some emotional patient testimonials, the panel voted to approve the device. One panelist later said it was "nuts."

We also posted about questions regarding the authors of an article sponsored by the company about the vagus nerve stimulator. These questions revolved around undisclosed conflicts of interest, and the extent a ghost-author was responsible for the article.

Cyberonics also came to our attention because of questions about stock-options granted to its top executives. Now, according to the Houston Chronicle,

Two top executives have exited Cyberonics, after it disclosed that its stock options problems are much broader than previously reported.

On Monday, investors bid up shares of the Houston-based medical device maker, which said Chairman and CEO Robert Cummins and Chief Financial Officer Pamela Westbrook resigned.

The duo was replaced, on an interim basis, by three people: Tony Coelho as chairman, Reese Terry Jr. as chief executive and John Riccardi as chief financial officer. George Parker was appointed as interim chief operating officer.

The personnel changes came as Cyberonics reported widespread stock option problems in a filing Friday with the U.S. Securities and Exchange Commission.

Before Friday, the company had acknowledged only one instance where stock options were at issue. Those options were given to top executives in June 2004, on the day before the stock market had a chance to react to positive news about a Cyberonics product. Some analysts have described the 2004 options activity as 'make-your-own-luck' grants. Others have called it springloading. On June 9, the SEC began an informal investigation into the two-year-old options.

On Friday, Cyberonics said a board committee that reviewed the company's stock option grants concluded that 'incorrect measurement dates were used for certain stock option grants made principally during the period from 1999 through 2003.'

Cyberonics estimates its financial statements from that period would need to be adjusted to reflect about $10 million in additional 'noncash compensation charges' because of the backdating activity.

It's funny how questionable financial practices seem to go hand-in-hand with dodgy marketing and strange science. In my humble opinion, cases like this suggest the urgent need for better governance of health care organizations, meaning governance that is transparent, accountable, and ethical. But given the way many helath care organizations are currently run, should it be any surprise that costs constantly go up, access constantly goes down, quality is constantly questioned, and health care professionals are increasingly miserable?

Cephalon's Promotion of Actiq

The Wall Street Journal reported the latest story about allegations of company promotions of off-label use of their pharmaceutical products. The allegations were about Cephalon's promotion of Actiq, a formulation of the synthetic narcotic fentanyl provided in a sweet-tasting lollipop. The US Food and Drug Administration had approved the drug for the treatment of intractable pain in patients with cancer. According to the WSJ, (somewhat re-ordered)

From setting unrealistically high sales quotas to pushing larger prescriptions at higher doses, drug maker Cephalon Inc. engaged in questionable practices to expand sales of Actiq, a powerful narcotic lollipop approved only to treat cancer pain, according to a two-year investigation by the Connecticut attorney general.
Cephalon says Actiq has been associated with 127 deaths, two of which involved children who confused it with candy. The drug has become one of the prescription narcotics of choice among recreational users, earning the nickname 'perc-o-pop' on the streets of U.S. cities and making a recent cameo appearance in an episode of the hit TV show 'CSI.' In the first nine months of this year, Actiq sales reached $471 million.

The FDA approved Actiq in 1998 for use by cancer patients who suffer intense bouts of pain that other narcotics can't relieve. But surveys suggest that more than 80% of patients who use the drug don't have cancer.

The trigger for Mr. Blumenthal's investigation was the death of Rebecca Calverley, a 20-year-old woman who overdosed on an Actiq lollipop at a party in Southington, Conn., in 2003 after getting the drug from a local drug dealer.

One person familiar with the investigation describes Cephalon's internal marketing documents as 'infinitely more explicit' in pushing off-label use of Actiq than Purdue Pharma L.P. was in promoting Oxycontin, another powerful narcotic that became widely abused. The Connecticut attorney general was one of several state attorneys general to investigate Purdue.

Mr. Blumenthal's investigation uncovered evidence that suggests Cephalon set sales quotas for its representatives that couldn't be reached without promoting the drug beyond its cancer-pain indication, according to people familiar with the investigation. Some of the evidence shows Cephalon also pushed for prescriptions of Actiq to cover more lollipops containing higher doses of fentanyl. Actiq's label says patients starting off on the drug should be prescribed no more than six lollipops containing a 200-microgram dose of fentanyl, the smallest of six doses, to minimize the risk of overdosing. Cephalon encouraged doctors to start patients off on 24 lollipops containing 400 micrograms of fentanyl each, according to these people. The higher dose costs more and brings in more revenue.

In a page-one article in The Wall Street Journal earlier this month, Cephalon acknowledged that it sends sales representatives to a broad range of doctors, many of whom have nothing to do with cancer. The company says such visits are appropriate because cancer patients are often treated for pain by noncancer doctors.

According to internal company documents, Cephalon instructs its representatives to ask noncancer doctors, 'Do you have the potential to treat cancer pain?" Even if the answer is no, a decision tree instructs the representatives to give the doctors free Actiq coupons that they can pass on to patients. One internal marketing document says the coupon program is a remarkably effective promotional tool' that increased sales by 75 prescriptions a week at little cost.

Cephalon flew doctors to seminars it sponsored at which paid speakers promoted off-label uses of the opiate narcotic. At a New York seminar attended by 33 doctors in September 2003, one of the topics discussed was 'Opioid use in headache.' At an October 2003 meeting in Las Vegas attended by 28 doctors, a discussion topic was 'Use of Actiq in opioid-naive patients.' Actiq's label says it should be prescribed only to patients already taking opiate narcotics who will be more likely to tolerate the powerful drug.

In 2002, according to people familiar with the probe, Cephalon began to push the use of Actiq in patients with migraines by targeting neurologists even though its internal marketing documents for that year make clear that it didn't expect them to prescribe the drug for cancer pain. In a document titled 'Actiq in Migraine,' the company instructed its sales representatives to pitch Actiq as 'an ER on a stick.'

What is distressing in the series of stories about promotion of off-label use of drugs (e.g., see our most recent post on the promotion of Neurontin) is the participation of physicians as paid pitch-men, or women. It is true that physicians are free to advocate for any off-label use of drugs they favor. But how can a physician who is paid by a company to give a talk that promotes off-label use of that company's drug deny that he or she is acting like a paid marketer?

At the very least, physicians giving such talks should disclose that they have been paid by the manufacturer to promote their drug. If they find doing so embarassing, maybe they should re-consider why they are giving such talks in the first place. (I would further suggest that promoting narcotics for pay may be particularly embarassing.)

Obviously, physicians in the audience should be properly skeptical of all pharmaceutical, bio-technology, and device marketing, whether it is done by former cheer-leaders or medical doctors.

Death of an Autistic Child: Chelation without Indication

The Pennsylvania State Board of Medicine has brought a formal action against Roy Eugene Kerry, MD, the practitioner alleged to have treated a five year-old autistic child with “chelation therapy” last year, resulting in the boy’s death. According to the Board, Kerry treated the 42 lb. boy on 3 occasions with disodium EDTA, 1 gram, given by “intravenous push” over 5-10 minutes. The boy died during or shortly after the third infusion, reportedly from hypocalcemia—as was predictable based on the action of the drug and the warnings contained in its product information.

HCR has previously commented on the case here, making the point that the boy appeared to have been a victim of “CAM,” not merely of an inadvertent drug error—contrary to what a CDC expert had suggested; and here, adding that the chelationist had almost certainly intended to use disodium EDTA (Na2EDTA), not the calcium-disodium EDTA (CaNa2EDTA) presumed by the CDC expert, because it is the disodium form that is preferred by the American College for Advancement in Medicine (ACAM), the major advocacy organization for such treatments.* Dr. Kerry is a member of the ACAM.

The PA Board order’s Factual Allegations support our contention: “Respondent stated…that Disodium EDTA is the only formula of EDTA he stocks in his office”; he “admits that CaNa2EDTA is available but that he has never used this agent.” The order also suggests that Dr. Kerry failed to establish a diagnosis that would have justified the use of either form of EDTA: hypercalcemia or digitalis toxicity to justify Na2EDTA; lead toxicity to justify CaNa2EDTA.

The order quotes from the boy’s medical chart “maintained by Respondent.” The chart describes the boy as “very energetic” and a “Happy child.” The “current complaint notation reads ‘wants to have iv…edta injection..mother states Tariq autistic due to immunization shots…’” The chart refers to another physician, Dr. Usman, who is said to have told Dr. Kerry that the boy had “a very high aluminum and has not been responding to other types of therapies and therefore she is recommending EDTA, which we do on a routine basis with adults. We therefore checked him to it [sic]…But on testing for the deficiency indicator we find him only indicating the need for EDTA at the present time. Therefore we agree with Dr. Usman’s recommendation to proceed with the treatment.”

We are not told what “testing for the deficiency indicator” means. There is no evidence for the unlikely claim of “very high aluminum,” nor is EDTA the preferred treatment for aluminum toxicity. There is no documentation of mercury toxicity, frequently offered by “alternative” practitioners to justify their contention that immunizations cause autism. EDTA, in any case, is not effective in removing mercury. Nevertheless, Dr. Kerry administered Na2EDTA to the boy “with 3 other assistants and mother controlling him and the papoose board.”

After the first infusion Dr. Kerry sent a “post-provocative” urine sample to a lab. This revealed, according to the Allegations, “minimal elevation of his lead level”—as would be expected for a healthy person following an infusion of EDTA. Kerry recorded his “Initial Impression: Autistic Syndrome, Heavy Metal Toxicity, Candidiasis, Multiple Food Allergies…” There is no documentation to support any of these diagnoses. “Heavy metal toxicity,” “candidiasis” and “multiple food allergies” are conditions freely cited among a small subculture of practitioners as explanations for numerous complaints. We wonder if “testing for the deficiency indicator” refers to the use of an “electrodiagnostic” device, a popular method for making such pronouncements appear legitimate to scientifically naïve patients.

As good a job as the Pennsylvania Board seems to have done in investigating this case, there are some unfortunate misstatements. We wonder if the Board was misled by the CDC’s Dr. Mary Jean Brown, the author of the inadvertent drug error theory. In paragraph 83 the Board charges that “the drug used was the incorrect formula of EDTA in that it did not contain calcium.” In paragraph 85: “the drug used was the wrong type…the patient had a minimally elevated lead level.” Paragraph 86: “…used disodium EDTA to chelate Tariq for metal toxicity which should be treated with CaNa2EDTA instead.” Paragraph 91; “Respondent did use disodium EDTA to chelate Tariq for metal toxicity that should be treated with CaNa2EDTA.”

But these allegations either miss the point or are plain wrong: Kerry didn't give the "wrong type" of chelating agent. He gave the more dangerous of two very wrong agents, and he gave it in the most dangerous possible way. No form of EDTA should have been used because there was no indication for it. To treat an autistic child with EDTA in the absence of demonstrated indications, based on the claim that autism is caused by “metal toxicity,” is without basis in medical knowledge. And there was no evidence, as explained above, that the boy had even a minimally elevated blood lead level or any other “metal toxicity.” By not making these distinctions the Pennsylvania Board, however unwittingly, has offered “plausible denial” of responsibility to those who continue to advocate EDTA for dubious indications.

It is probable that if Dr. Kerry had used CaNa2EDTA instead of Na2EDTA, or even if he had given Na2EDTA as directed by its package insert (slowly over 3 hours), the child would not have died suddenly. But this should not distract the Board, the medical profession, or parents from the real point of the case: quackery killed the boy. Quackery also occurs every time EDTA is given in similar circumstances, no matter which EDTA salt is used, no matter how slowly it is infused, no matter how sincerely the chelationist believes in it, and whether or not it kills its recipient. Ironically, this conclusion would have been unmistakable a mere 17 years ago, when the history of laetrile was still fresh in the minds of most physicians, when “chelation” was on the FDA’s Top Ten Health Frauds list, and before the euphemisms “alternative” and “complementary” had replaced accurate descriptors.

* Rozema TC. The Protocol for the Safe and Effective Administration of EDTA and Other Chelating Agents for Vascular Disease, Degenerative Disease, and Metal Toxicity. Journal of Advancement in Medicine. 1997;10, 1:5-100

IS THERE A BASIC SCIENTIST ON THE BENCH?

One of the innovations in stealth infomercials that pharma has developed is the basic science play. Here’s how it works, illustrated in masterly style by the good people at Corcept Therapeutics.

Since 2001, Corcept has been touting a drug called mifepristone (that’s right, RU486) for treatment of patients with psychotic major depression (PMD). The drug blocks cortisol receptors, and high cortisol was theorized to be a cause of the delusions and hallucinations experienced by patients with PMD.

Corcept got fast track approval for their drug from the FDA on the somewhat specious ground that there are no FDA-approved treatments for PMD. They have published a series of small clinical trials that had negative outcomes. One tiny study (N = 5) had no statistically significant result. A second study of 30 patients had no statistical analyses whatsoever. In another study of 30 patients, the statistical analysis was incorrect. These failures did not stop the Corcept team from talking up the drug’s potential in review articles, book chapters, Continuing Medical Education programs, news reports, and press releases. In quite a few of these promotional “product placements,” the financial ties of the authors with the company were not disclosed.

All that is pretty much par for the course in the academic-industrial complex: clinical key opinion leaders were bought and paid for long ago. Now comes the basic science play. In the August 2006 issue of Journal of Neuroendocrinology, a report describes how Corcept’s drug can reverse the deleterious effect of high glucocorticoid levels on neurogenesis in the hippocampus of rats (1). This finding ties in with some inconclusive evidence that some patients with depression may have reduced hippocampal volume. So, this new basic finding is potentially a big deal for Corcept. Indeed, Corcept provided funding for the study. One fully expects that the company will highlight this new information in future statements.

Looking at the new report, one sees in the Acknowledgements that the first author was supported by Corcept. One also sees that a co-author, E. Ronald de Kloet, failed to disclose his relationship to the company: he is a member of Corcept’s scientific advisory board and, unless he has sold any, the owner of 60,000 shares of Corcept stock. One also sees that this basic science article is careful to follow the company’s marketing message and branding language on the putative efficacy of mifepristone for PMD. For instance, it states, “The glucocorticoid receptor antagonist mifepristone has been shown to rapidly and effectively ameliorate symptoms of psychotic major depression.” These basic scientists also stated, “recent clinical studies have shown that the glucocorticoid-receptor (GR) antagonist mifepristone relieves symptoms of psychotic depression after a remarkably brief treatment period of 4 or 8 days.” None of the cited studies shows anything of the sort. We then read, “… similarly to its clinical efficacy, mifepristone’s effects on adult neurogenesis are rapid and positive, and may therefore be important for its mechanism of action.”

What’s going on here? Could it be that one of Corcept’s basic science consultants has been pulled off the bench to pinch hit for the company? The usual readership of Journal of Neuroendocrinology will know nothing about the clinical trials of the drug and will accept at face value the exaggerated statements of mifepristone’s efficacy in PMD. And now the clinical spokespeople for Corcept can point to a new piece of basic science “validation” of their product. Look for it to be highlighted in the next round of book chapters, review articles in clinical journals, CME events, and press releases.

The company needs pinch hitters right now because they have recently had to announce that two large Phase III trials failed. The house of cards is collapsing: they have been informed by NASDAQ that the company is in danger of being delisted because the share price has gone from $12 at issue in April 2004 to around 80 cents today. All in all, Corcept is a case study in bad outcomes for academic entrepreneurs and their backers. Many investors have been burned. Worse, after going through around $95 million of venture capital and IPO proceeds, not to mention several million dollars of NIMH funding, they have failed to answer the original question: does mifepristone help seriously ill patients with PMD accompanied by elevated cortisol production? Now, as the company enters what may be its final spasm of activity, comes this new corruption of the basic medical science literature.

We have long known that citations of the medical literature are not holy writ, but now they are becoming advertising copy. As George Winokur, former chair of psychiatry at the University of Iowa, liked to joke, the medical literature is like the Bible: people can find in it whatever they are looking for. Some of us learned in our training that when we cite an article in one of our manuscripts, we need to actually read that article, understand its methods, and agree with its conclusions. Had the authors of this stealth infomercial in Journal of Neuroendocrinology scrutinized the clinical trials reports that they cited, even as basic scientists they would have recognized the weakness of the evidence. Thus does the corporate mandate to put lipstick on the pig vitiate even the basic medical science literature.

Reference

(1) Brief Treatment With the Glucocorticoid Receptor Antagonist Mifepristone Normalises the Corticosterone-Induced Reduction of Adult Hippocampal Neurogenesis. By: Mayer, J. L.; Klumpers, L.; Maslam, S.; de Kloet, E. R.; Joëls, M.; Lucassen, P. J.. Journal of Neuroendocrinology, Aug2006, Vol. 18 Issue 8, p629-631, 3p, 1 graph; DOI: 10.1111/j.1365-2826.2006.01455.x; (AN 21447609)

Guidelines in Whose Interest? - Epoetin Revisited

We previously posted about how influential guidelines that suggested aggressive use of epoetin to increase and try to normalize hemoglobin levels in patients with anemia and chronic liver disease were funded by Amgen Inc., the maker of one version of epoetin (Epogen). These guidelines appeared to have influenced the US Medicare program to pay handsomely for aggressive use of epoetin, even though the evidence supporting high doses of the drug was not very clear.

This week, the results of two new randomized trials of other versions of epoetin were published in the New England Journal of Medicine.

Preliminary results of the CHOIR study had been mentioned in our earlier post. In short, CHOIR (Correction of Hemoglobin and Outcomes in Renal Insuffiency) was a randomized controlled trial of epoetin alfa dosed either to normalize hemoglobin (target range of 13.0 to 13.5 g/dl) or maintain it in the 10.5 to 11.0 range.(1) The rate of a composite endpoint (death, myocardial infarction, hospitalization for congestive heart failure, stroke) was statistically significantly higher in the more aggressively treated group (17.5%) than in the less aggressively treated group (13.5%). The rates of death and hospitalization for congestive heart failure were numerically higher in the more aggressively treated groups, and the differences were almost statistically significant. Thus this trial suggested that aggressive use of epoetin actually increased the risk of cardiac complications and possibly death.

The CREATE (Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta) trial was a randomized controlled of epoetin beta dosed either to normalize hemoglobin (13.0 -15.0 target) or maintain it in the 10.5 - 11.5 range.(2) The rate of a somewhat more complex combination endpoint (including cardiac and vascular events, as well as death) was numerically higher in the more aggressively treated group, although the difference between groups did not achieve statistical significance. The death rate was also higher in the more aggressively treated group. The study did show that more aggressively treated patients had somewhat better scores on measures of health status, although their improvements did not appear very large. Thus, this trial at best suggested no advantageous effect of aggressive use of epoetin on death or cardiac events, and was consistent with the possibility that it may have had a disadvantageous effect.

Combined, these two studies raise even more concern that aggressive use of epoetin for patients with anemia and chronic renal disease may do more harm than good.

Following the publication of these articles, the Boston Globe reported that the US Food and Drug Administration (FDA) officially warned against excessively aggressive use of epoetin.

This new data underscores the concerns we raised earlier. Guidelines developed with financial support of pharmaceutical or biotechnology companies may favor aggressive use of those companies' products, even in the absence of strong evidence for such use. At best, this can lead to excess costs and treatment that does patients little good, and risks harming them. In this case, we have now gone from a situation in which there was an absence of strong evidence for aggressive use of epoetin to one in which there is evidence suggesting such aggressive use may be actively harmful.

So the bottom line should be just because a guideline advocates something does not mean physicians should obey. Not all guidelines are created equal. Guidelines that have not been rigorously developed using evidence-based medicine principles, especially when they may also have been affected by conflicts of interest, should be viewed with extreme skepticism. Yet, turning such guidelines into "pay for performance" (P4P) incentives is the latest rage in health care management circles (see post here). Such a rage, however, can be bad for patients and doctors.


References

1. Singh AK, Szczech L, Tang KL et al. Correction of anemia with eopetin alfa in chronic kidney disease. N Engl J Med 2006; 355: 2085-98.
2. Drueke TB, Locatelli F, Clyne N et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355: 2071-2084.

"Sponsored Editorials?"

The blog Clinical Psychology and Psychiatry: A Closer Look just noticed a new pheonomenon, the "sponsored editorial." Apparently, these have appeared in the July and November issues of the Journal of Clinical Psychiatry's paper edition (although not on the web). A jpeg reproduction appears in this Clinical Psychology and Psychiatry post.

The "sponsored editorial" itself features clinical bullet points on akasthisia, and two pull quotes, in a large type face, from suffering patients. On the bottom appears the AstraZeneca logo. No authors are listed.

I want to second Clinical Psychology and Psychiatry's blogger's motion that by printing this as an editorial, albeit "sponsored," the journal appears to be endorsing a marketing message as if it were substantive content. This appears to be the latest addition to our catalog of deceptive marketing practices, and the latest story about how medical and health care journals seem to be supporting the vested interests of their commercial sponsors at the expense of their independence. Misleading physicians by disguising advertising, in this case, as editorial content in a peer-reviewed journal, is liable to distort their medical decision making, and hence is bad for both them and their patients.

Now Kaiser Permanente Hospital Criminally Charged for Patient Dumping

This is getting painful. After Kaiser Permanente was recently in the news for problems with its new electronic medical record system, and allegations of the poor management of the system development process (see posts here, here and here), now the Los Angeles Times is reporting

The Los Angeles city attorney's office filed false-imprisonment and dependent-care-endangerment charges against hospital giant Kaiser Permanente on Wednesday, the first criminal prosecution of a medical center accused of 'dumping' patients on skid row.

The charges stem from an incident earlier this year when a 63-year-old patient from Kaiser Permanente's Bellflower hospital was videotaped as she left a taxi in gown and socks, and then wandered skid row streets.
In addition to the criminal charges, the city attorney filed a civil lawsuit against Kaiser, using a state law on unfair business practices that city prosecutors usually implement against unscrupulous slumlords to force them to clean up their buildings. The suit seeks a judge's order to forbid all Kaiser medical facilities from dumping homeless patients on skid row or impose financial sanctions if it violates the order.

A Kaiser spokeswoman on Wednesday said she was 'very surprised' by the charges.

'I can't understand how these charges would be levied based on what I know of the incident,' said Diana Bonta, vice president of public affairs for Kaiser Southern California.

She said Kaiser had changed some of its practices since the March incident to better serve discharged homeless patients.

[The patient] Reyes also is being represented by the American Civil Liberties Union of Southern California and Public Counsel. Representatives from both organizations said Wednesday that they planned to file a second lawsuit on Reyes' behalf soon.

'This is the first case in the nation where there is a joint effort by government and civil rights groups to halt the practice of hospital dumping,' said Mark Rosenbaum, the ACLU's legal director.

Rosenbaum said that meetings with Kaiser and hospitals failed to yield reform — and that was part of the reason for the court filings. 'It is like they lit a match to the Hippocratic oath,' he said.

Dan Grunfeld, president and chief executive officer of Public Counsel, the largest pro-bono legal firm in the nation, echoed that sentiment. 'This is as stark a case as you are likely to find,' he said. 'You have a relatively older woman in adult diapers and gown dumped on a skid row sidewalk. That is a pretty profound statement. Ms Reyes is not alone. There are a lot of Ms. Reyes' out there. We hope to achieve a systemic change.'

You have to start to wonder if something has really gone systemically wrong with the upper management of the once proud Kaiser Permanente organization, which is still, as best as I can tell, staffed by quite a few dedicated doctors, nurses, and other health professionals. Of course, what we have so far are only allegations. But the story as reported by the Los Angeles Times is very disturbing, and the city attorney obviously thought this case was egregious enough to merit criminal charges. Stay tuned.

Kaiser Permanente's New EMR - An Alternative View

MedInformaticsMD has posted recently about allegations of major troubles with Kaiser Permanente's new electronic medical record, and the management of its development (see here and here).

A physician correspondent at Kaiser, and someone whose judgment I trust, had an alternative view:

I want you to know that the Epic product for KP, HealthConnect, is a fully integrated and very highly functional software that interfaces with Pharmacy, Inpatient & Outpatient records, imaging, lab..............it's unbelievably useful. Not absolutely perfect, but really extraordinary nevertheless. I personally can research referrals with an ability to track diagnostic images, consults, labs, professional notes including progress notes all on one platform. It has been rolled out to most of the Northern California region where we serve well over 3 Million people, and there is nothing that competes with its usefulness. The down time quoted is a gross exaggeration. It has helped me enormously provide fast, accurate decisions in settings in which, in the old work, I would have otherwise wasted precious time getting the right, important information.
The KP CIS system to which some reference was made by JD is to Epic as the Conestoga wagon was to a Ferrari. The fact that he thinks it was a satisfactory system either reflects a lack of understanding or a willful blindness to the needs of clinicians. Furthermore, KP is a nonprofit in the best sense of the word - its margin is used to build new hospitals as mandated by State law to make hospitals earthquake safe and to improve care by doing things like rolling out KP HealthConnect [the Epic product]. These are spectacularly expensive projects in the best of all possible worlds, and are intended to provide advances in improving access to care for vulnerable patients.

This does not address all the issues in our previous posts, but at least makes clear that there was some reasonable rationale for trying to adapt the system to the Kaiser setting.

I would also note that Kaiser has a reputation as one of the best managed care organizations, and one that has remained not-for-profit and generally tried to maintain its focus on its primary mission. It's goood to see that Kaiser physicians are continuing to adhere to its traditions. We will stay tuned to see what turns out about the other issues raised about Kaiser's expensive EMR project.

UMDNJ's Federal Monitor Charges Cardiology Kick-Back Scheme Reached Into All Levels of Administration

The leadership of the University of Medicine and Dentistry of New Jersey (UMDNJ) seems to just keep digging a bigger hole for itself. As we have discussed previously, The university now is operating under a federal deferred prosecution agreement with the supervision of a federal monitor (see most recent posts here, here, here, here and here.) We had previously discussed allegations that UMDNJ had offered no-bid contracts, at times requiring no work, to the politically connected; had paid for lobbyists and made political contributions, even though UMDNJ is a state institution; and seemed to be run by political bosses rather than health care professionals. (See posts here, and here, with links to previous posts.) The most recent allegations, which surfaced last week (see post here) were that the University were paying community cardiologists as clinical faculty as a reward for them referring patients to the UMDNJ cardiac surgery programs, but not as payment for any substantial teaching duties.

Now the Newark Star-Ledger has just reported that the federal monitor assigned to UMDNJ also averred that "UMDNJ had devised an illegal scheme to pay local cardiologists in private practice for hundreds of patient referrals." But worse,

The report documented nearly $36 million in illegal Medicare and Medicaid payments for procedures on hundreds of patients, in ex change for payments of $5.7 million to physicians since 2002 in ex change for sending their heart patients to UMDNJ's University Hospital.

'Unfortunately, this scheme reached well into all levels of the hospital and University Central Administration, who were complicit first in forming and expediting this illegal plan, and later in covering it up,' said Stern in his report, who said the illegal activity 'persists to this day.'

Noting that administrators were aware of the kickback allegations -- settling a lawsuit for $2.2 million by a whistleblower who claimed he was fired for protesting the illegal scheme -- Stern said UMDNJ violated the terms of the deferred prosecution agreement by not only failing to alert his office to the existence of the whistleblower, but by failing to provide relevant documents and information related to the allegations in the lawsuit.

And still worse,

U.S. Attorney Christopher Christie has begun an investigation into charges that the University of Medicine and Dentistry of New Jersey paid nearly $6 million in illegal kickbacks to 18 cardiologists in ex change for patient referrals.

At the same time, Christie said he was particularly disturbed by findings that UMDNJ had violated a deferred prosecution agreement with the government by failing to cooperate with the university's federal monitor on a five-month inquiry into the matter.

And even worse, the New York Times reported that the federal monitor "accused the university’s interim president, Bruce C. Vladeck, who was appointed by Gov. Jon S. Corzine in the spring to restore credibility, of 'trying to refute, rebut and bury' information about violations of anti-kickback laws. It was the first time that the federal monitor, Herbert J. Stern, had directly criticized Mr. Vladeck."

The hits they just keep on comin' for UMDNJ. The most distressing aspect of the current allegations is that they involve activities that continued after the University agreed to a deferred prosecution agreement, and after the leadership of the University was totally revamped.

If the UMDNJ case do not demonstrate the crying need for transparent, representative, accountable, and ethical leadership of health care organizations, I don't know what case does.