Conflicts of Interest at the Transcatheter Cardiovascular Therapeutics Conference

Business Week last week reported the latest complicated tale about interactions between physicians, research, and commercial firms. The story centered on Dr Martin B Leon, Associate Director, Center for Interventional Vascular Therapy, Columbia University Medical Center, who also is the chairman of the Cardiovascular Research Foundation, which runs the Transcatheter Cardiovascular Therapeutics (TCT) conference. Leon was co-founder of the CTC in 1988. Businessweek summarized his relationships with some device manufacturers.

Leon's first consulting arrangement with a company grew out of the inaugural TCT in Washington. Marvin Woodall, who headed Johnson & Johnson's new cardiac-devices division, asked Leon to serve as the unit's paid ex-officio medical director.

Through the 1990s, Leon and other interventional cardiologists had links with companies they didn't routinely acknowledge at the conference.

Leon and TCT have provided a launching pad for many small companies. 'It is the premier forum for the introduction of new technology,' says Howard Leonhardt, CEO of Bioheart Inc., which is developing several cardiac devices. Leon agreed to serve on the company's scientific advisory board in 2000. 'He introduces us to the right people,' Leonhardt says. 'He's a prominent leader at the cutting edge.'

In 1999 he co-founded a company called Percutaneous Valve Technologies Ltd. (PVT), which developed a cardiac valve that could be implanted by a catheter snaked through an artery, rather than open-heart surgery. When Edwards [Lifesciences], based in Irvine, Calif., bought PVT for $125 million in early 2004, Leon collected his roughly $6 million. In addition, he and other PVT shareholders were promised a total of three $10 million payments upon the achievement of three milestones: the successful treatment of 50 patients, regulatory approval in Europe, and limited approval in the U.S.

To comply with Columbia's policies, Leon has recently simplified his web of financial relationships. Earlier this year, he says, he donated his rights to the Edwards milestone payments to a school in Manhattan, which he declines to identify. That is so he can participate in current clinical trials for the PVT valve, which has been refined since the 2004 live case. And in 2005 he gave up the $257,679 annual salary he had been drawing from his foundation. But he makes no apologies for accepting payments from manufacturers. 'If you expend a significant amount of time and effort' helping a company develop a new device, he says, 'there will be financial remuneration.'

Another complicated Leon relationship concerns Abiomed, a company in Danvers, Mass. In 2005, Leon's incubator, Accelerated Technologies Inc., sold a small company called Impella to Abiomed for $42.2 million in stock. Impella had invented a tiny pump that helps the heart do its job and can be implanted in minutes. Three versions of it are on sale in Europe, and the company is conducting clinical trials in the U.S. Leon received stock then worth nearly $1 million, plus the opportunity to receive a small share of up to $16.75 million in milestone payments, based in part on Abiomed's regulatory approvals and units sold.

Businessweek raised questions about how the products of companies with which Leon had financial relationships were presented at TCT, the conference he runs.

n September, 2004, with thousands of doctors at the conference watching live by satellite on giant screens, a cardiologist in Milan inserted an experimental heart valve into a gravely ill patient. Suddenly the patient's heart began to fail. For 45 minutes the stunned audience watched a series of desperate life-saving attempts, until finally the satellite transmission was cut. The patient died later that day. 'It was harrowing,' says Dr. Martin B. Leon, the New York heart specialist who started the influential conference 18 years ago. 'That was a very difficult thing for us.'

Leon's anguish over the incident remains palpable, but he also had a financial interest in seeing the valve work. He co-founded the small company that invented the device. That company was sold to Edwards Lifesciences....

At TCT ... in 2004, Leon disclosed the relationship simply as 'PVT-Edwards,' one entry in a list of 26 companies from which he received equity, consulting fees, or research grants. He didn't spell out the potential milestone payments in the TCT materials. Doctors who watched the live procedure that ended with the death of the patient in Milan might not have known that the conference's leading figure had an intricate and continuing relationship with the manufacturer of the device being implanted.

Did Leon's financial stake in the experimental device play a role in its being promoted at an important conference where he is the most prominent figure? 'Absolutely not,' Leon says. The question, he adds, 'borders on being offensive.'

[However,] 'Things that Marty is part of get exaggerated attention' at the conference, gripes the CEO of one device startup. The CEO declined to be identified out of fear he would offend Leon and imperil his company's treatment at TCT.

Mostly undisclosed until six years ago, the tangle of physicians' financial interests at TCT is now acknowledged in a booklet distributed to participants. In 2005 no fewer than 345, or 44%, of the more than 750 doctors and researchers who made presentations at TCT had received compensation from companies, some of whose products they evaluated at the conference.

Beyond the danger that conflicts may distort individual clinical decisions, some TCT observers worry that the event engenders a general excess of enthusiasm for complicated device-based procedures.
TCT undeniably stirs excitement about devices. When new products perform well in the live cases--real-time procedures beamed in from hospitals all over the world and viewed at the conference--a crowd of animated doctors and investors typically gathers around the booths of the relevant manufacturers. 'Marty turned the medical meeting into the auto show,' says Dr. Stuart F. Seides, associate director for cardiology at the Washington Hospital Center.

At TCT, Leon makes speeches, presents data, and comments on some live cases. He is "a mixture of teacher and showman," says Dr. Patrick W. Serruys, chief of interventional cardiology at the Thoraxcenter-Erasmus University in Rotterdam....

[After Leon received Abiomed stock and the opportunity to receive milestone payments,] Six months later, [the Abiomed device] Impella was featured in two live cases at TCT. At the same conference, Abiomed co-sponsored an evening event featuring doctors talking about heart pumps. Leon, who was the keynote speaker, noted briefly in the disclosure booklet and on a slide that preceded the presentation that he was a "major shareholder" of Impella-Abiomed.

This latest case raises the same sort of questions about conflicts of interest raised by other recent cases (for example, see this recent post). But first I ought to deal with the objections raised by Dr Leon above to the notion that his financial relationships may have affected what he said or how he ran to the conference. As we have noted before, people may not realize at a conscious level how conflicts of interest affect their thinking. But, " people who have conflicts of interest often find giving clear advice (or opinions) particularly difficult" (see post here). Furthermore, if a physician receiving a pen or coffe mug with a company logo may create a conflict now considered unacceptable at some academic institutions (see posts here and here), then why would a researcher or academic having relationships worth tens or hundreds of thousands of dollars be acceptable?

So, is Dr Leon's work at the Cardiovascular Research Foundation and the TCT only educational and scientific, or does he also act as a marketer for the many companies he also works for? Should the sorts of presentations at TCT described above be taken as just scientific and educational, or also as marketing? Does the Cardiovascular Research Foundation only do research and education, or does it also do marketing? Does marketing in the guise of impartial education and research peformed by disinterested physicians and researchers lead to an "excess of enthusiasm?" Finally, are the physicians, educators, and researchers at TCT misusing the trust placed in them by the physicians and scientists attending the conference, and the public at large, by working for commercial device manufacturers as well as academic institutions?

Health Care Renewal Bloggers to Present at International Meetings

Just a small toot of our own horn...

Health Care Renewal bloggers will be presenting at two major upcoming international meetings.

This is short notice, but I will be presenting during a workshop on Health and Corruption, coordinated by Roger Bate, at the 12th International Anti-Corruption Conference (IACC), to be hosted by Transparency Internationl and held November 15-18 in Guatemala City, Guatemala. My particular topic will be health care corruption in the developed countries, particularly the US. Maureen Lewis will talk about corruption in health care sectors in developing countries, and Roger Bate will talk about the link between tariffs on medical interventions and corruption, and corruption in middle-income and poorer countries. The conference will also feature a Presidential Panel for seven Latin American and Caribbean Presidents.

Dr Wally Smith and I will be giving a "pre-course" on Changing Physicians' Behavior at the Society of General Internal Medicine Annual Meeting in Toronto, Ontario, Canada, April 25-28, 2007. The course will include a section on "when not to change behavior," that will address coping with ill-justified or ill-intentioned attempts to change behavior, especially those driven by vested interests.

Conflicts of Interest and the Marketing of Requip

The Wall Street Journal recently reported (link requires subscription) on the marketing campaign by GlaxoSmithKline (GSK) to sell more Requip (ropinirole) for restless legs syndrome (RLS). Having seen far too many direct to consumer (DTC) advertisements on television about this disease, my first response was to groan, "not more about restless legs," but in fact the WSJl article was revealing. It also referred to an important scholarly article by Steven Woloshin and Lisa Schwartz in PLoS Medicine (Woloshin S, Schwartz LM. Giving legs to restless legs: a case study of how the media helped make people sick. PLoS Medicine 2006; 3(4): (e)170)

The Requip marketing campaign was very succesful. As the WSJ reported, "Requip is on track to post sales of $500 million this year, making it one of the fastest growing drugs in Glaxo's portfolio." Both articles focussed on how Requip was advertised directly to consumers, and how the media addressed the drug. However, I wanted to focus on how GSK employed conflicts of interest to market its product:

Conflicts of Interest Affecting Physicians - According to the WSJ, "Glaxo began its blitz by advertising the disorder to doctors in medical journals months before the company had regulatory approval to begin selling Requip for RLS. Then, it sent specialists to discuss the disease with general practitioners, who usually see RLS sufferers first." Furthermore, "soon after the FDA approved Requip as an RLS treatment in May 2005, Glaxo hired an army of sleep-disorder specialists and invited general practitioners to dinner at fancy restaurants across the U.S. to hear them speak about Requip, some specialists say. Philip Becker, medical director of the Sleep Medicine Institute at the Presbyterian Hospital of Dallas, says he has delivered about a dozen such talks in Texas. Dr. Becker, who has treated RLS for 25 years, says he thinks his talks have persuaded some doctors to take the disorder more seriously and to try Glaxo's drug."

Conflicts of Interest Affecting Disease Advocacy Not-for-Profit Organizations - According to the WSJ, "Awareness of the syndrome rose within months of Glaxo's first TV ads, says the Restless Legs Syndrome Foundation, in Rochester, Minn. It had about 2,600 visitors a day to its Web site before the Glaxo ad campaign. Two months later, about 4,500 people a day were visiting, says Georgianna Bell, executive director of the foundation." Even this WSJ article left something important out here. Woloshin and Schwartz wrote that one-fifth of the media articles they surveyed "referred readers to the 'nonprofit' Restless Legs Foundation for further information; none reported that the foundation is heavily subsidized by GlaxoSmithKline." The Foundation's 2005 annual report lists GSK as a "corporate gold partner," meaning that the company contributed at least $250,000. It is the only corporate partner listed, and the only donor making a contribution of more than $10,000 listed.

Reports of how commercial firms market health care products through apparently disinterested, respected intermediaries, like academic physicians and disease advocacy not-for-profit organizations, are becoming distressingly routine. For instance, we have recently discussed allegations about how Amgen supported the development of guidelines for the use of Epogen by the National Kidnesy Foundation (here), and how Eli Lilly marketed Xigris by providing grants to physicians and bioethicists to address rationing of health care (given that Lilly marketers apparently believed that Xigris was being rationed), and by supporting the Surviving Sepsis campaign and its development of relevant guidelines (here).

So I thought I would raise some questions about these marketing practices.

To physicians and academics paid by commercial marketers to give talks or write papers favorable to their products -

• Did you tell your audience that this was a marketing effort?
• Did you tell your audience that you were paid by to market the product?
• If not, were you being honest?
• How else would you describe your actions?
• Do you consider yourself a part-time marketer?
• If not, what would you call your role?
• Is being a part-time marketer in conflict with your values and mission?

To not-for-profit organization leaders paid by commercial firms to support their marketing efforts -

• Do you announce that you are funded by marketers to support marketing efforts?
• If not, are you being honest?
• How else would you describe your actions?
• Do you consider yourself a part-time marketer?
• If not, what would you call your role?
• Is being a part-time marketer in conflict with your organization's mission?

As we have discussed before, conflicts of interest cause people to fail to think clearly, or " people who have conflicts of interest often find giving clear advice (or opinions) particularly difficult" (see post here). Those with such conflicts, however, need to think particularly clearly about what they are really doing. And we all need to think about how Transparency International defines corruption (in the ethical, but not necessarily the legal sense) - "Corruption is operationally defined as the misuse of entrusted power for private gain."

Short Takes: More Mystery and Meyhem in Health Care

Two readers of Health Care Renewal recently told me that they had no idea of the pervasiveness of bad management and misbehavior in health care until they started reading the stories compiled in the blog. Just to add to that volume, here are a few short takes on health care shenanigans reported this week...

Medco Settles for $155 Million
According to the Associated Press (via the Houston Chronicle) "Prescription-benefits manager Medco Health Solutions Inc. has agreed to pay $155 million in fines to settle fraud, kickback and other charges brought by federal prosecutors in Philadelphia in a whistleblower case dating to 1999." Said US attorney Pat Meehan, "Hidden financial agreements between PBMs and drug manufacturers and health plans, along with the bottom-line pressures of management, can influence which drugs patients receive, the price we all pay for drugs and whether pharmacists serve patients with their undivided professional judgment." Medco denied all wrong-doing, but "Among other charges, Medco was accused of paying health-insurance plans kickbacks to obtain their business and of soliciting kickbacks from drug manufacturers to favor their drugs over competitors' products, partly by illegally pressuring pharmacists and doctors to switch prescriptions. Medco also was accused of destroying patient prescriptions when its mail-order pharmacies did not fill them as quickly as required by its insurance plan contracts." In addition to paying the fine, "Medco also must set up a strict program to ensure it complies with all Medicare requirements and pharmacy practice requirements, with both an independent reviewer and the U.S. Attorney's Office reviewing its records annually for five years." According to Bloomberg News, this is only the fourth largest settlement of a health care false claims act case in 2006. Note that although the company had to pay a substantial fine and upgrade its compliance practices, no individual manager was punished.

California Suspends Managed Care Regulator Over Conflict of Interest
According to the Los Angeles Times, "The Schwarzenegger administration is moving to fire a top HMO regulator who held stock in UnitedHealth Group Inc. when he helped review the 2005 acquisition of PacifiCare Health Systems Inc." It turns out that the Deputy Director of the California Department of Managed Care reported that he held between $10,000 and $100,000 stock in UnitedHealth Group. However, he failed to recuse himself from "participating in the merger approval process, based on the fact that he had a financial interest in UnitedHealth," said a spokesperson for the Department. The Deputy Director "is fighting the move, saying he complied with California disclosure laws and played no role in the state's decision to approve the deal. He said the Schwarzenegger administration had decided to approve the acquisition before he was involved." However, "The department described Donohue as its point person in a final round of negotiations that sought to ensure that the 3.2 million members of Cypress-based PacifiCare would not see their benefits reduced or premiums increased to pay for the controversial acquisition by the 22-million-member UnitedHealth of Minnetonka, Minn." According to the Times, "Donohue was integrally involved in Managed Health Care's review of the proposed acquisition and the agency's negotiation of conditions for approval. He also headed some of the hearings to solicit testimony on the potential effect of the acquisition on consumers and the state's healthcare network. Consumer advocates said Donohue seemed particularly tough on patients at public hearings. 'He was argumentative with anyone who criticized the [health] plans,' said Jerry Flanagan of the Foundation for Taxpayer and Consumer Rights in Santa Monica." A la Indiana Jones, "United, why is it always United?" One wonders why somebody whose primary job is regulating managed care would choose to hold a fairly large position in one of the country's largest managed care companies?

Medical School Dean Resigned After Her Husband Was Violently Attacked
A brief article in the Houston Chronicle revealed that the former Dean of the University of Texas Medical Branch in Galveston, Dr Valerie Parisi, "left the job after her husband was attacked outside the couple's home in July during a controversial period of hundreds of layoffs at UTMB. Strong told police his attackers told him to tell his wife 'she doesn't know who she's (expletive) with.' Parisis said she resigned to protect her family.
Police never identified the masked men who attacked Strong as he was walking the couple's poodle." The misbehavior in health care rarely is violent, so this case is exceptional. Nice "business" we are in, eh?

It's a real challenge for conscientious physicians to uphold their professional values while these sort of events are happening all around them. But if physicians want to uphold their values, and the public wants high quality, accessible, reasonably priced health care, we must all figure out how to deal with the conflicts of interest, unethical behavior, and even outright criminal behavior that seems to be everywhere in health care. These problems are systemic, and until we deal with them as such, not just as local aberrations, they will continue and worsen. Furthermore, in my humble opinion, until there are real, tangible, substantial negative incentives to individuals for misbehavior, misbehavior will continue.

IOM "gets it" regarding Medical Informatics

The Institute of Medicine of the National Academy of Sciences has been studying issues of drug safety, drug postmarketing surveillance, and related issues for the past several years.

In its new report “The Future of Drug Safety: Promoting and Protecting the Health of the Public”, the Committee on the Assessment of the US Drug Safety System of the Institute of Medicine has written:

Rec. 4.6: The committee recommends that CDER [FDA's Center for Drug Evaluation and Research] build internal epidemiologic and informatics capacity in order to improve the postmarket assessment of drugs. In recognition of the limitations in human resources in the current employment market to meet this role, a combination of advancing professional skills through continuing education and support for academic training programs is needed.

Informatics experts should track progress on the national health-information infrastructure, look for opportunities to gather information about drug safety and efficacy after approval, coordinate partnerships with external groups to study the use of electronic health records for [drug] adverse event surveillance, participate in FDA’s already strong role in setting national standards and track the development of tools for data analysis in industry and academe, and encourage the incorporation of the tools into FDA practice where appropriate.

The reference for this recommendation is “The Future of Drug Safety: Promoting and Protecting the Health of the Public”, Committee on the Assessment of the US Drug Safety System, Alina Baciu, Kathleen Stratton, Sheila P. Burke, Editors, Board on Population Health and Public Health Practice (BPH), Institute of Medicine (IOM), 2006, page 102.

It is encouraging to see these words in print from the IOM. Others such as Gartner Group, a large IT-related consulting firm, had made similar observations, but don't have the clout of an IOM. Hopefully, the pharma industry will take notice. (There will likely still be resistance in some quarters to this recommendation).

Not to toot my own horn or that of the field of medical informatics, but just prior to the mass layoffs that led to the end of my pharma position managing an internal science research library system and IT group (a position I'd obtained due to a secondary line of research as an informatics postdoc regarding selective information retrieval), I'd emailed the VP over my area about medical informatics.

This company has been struggling with a weak pipeline of new drugs. The VP, a former computer-industry businesswoman with no biomedical experience at all, was directing an entire division of biomedical research computing. As a cost-cutter, she was resistant to ending rationing of critical cheminformatics tools to R&D scientists, despite competitive intelligence data I prepared showing our competitors granted up to ten times the number of R&D scientists at their companies unfettered access to these tools. The cost to end rationing would have been a tiny fraction of the overall corporate R&D budget (assuming that budget could not be increased via a presentation to senior management of the criticality of these tools!)

In my pre-layoff email to the VP, I pointed out that if my area was to be downsized, as information groups often are, my primary expertise in the EMR and its use beyond care delivery for data aggregation, outcomes evaluation, etc. was a strategic skill for this troubled company. I was the only formally-trained medical informaticist (via an NIH-sponsored postdoctoral fellowship) in an international company of ~ 60,000.

Predictably, the VP laid me off along with a number of my staff. The VP also subsequently closed the research library at one of the company's two major R&D sites, something I had explicitly warned against as unwise, up to the highest levels of management.

That VP only lasted a few more years before her contract was not renewed, as I understand it. At last report, the VP was working for a computer gaming-hardware company.

The IOM's observation that there are "limitations in human resources in the current employment market to meet this [informatics] role" does not recognize another layer of human limitation in healthcare management - that of basic insight.

The lesson to be learned is to not hire people lacking biomedical backgrounds and insights into high management positions in biomedical settings. The decisions they make due to lack of expertise, lack of vision, difficulties understanding biomedical risk and the nuances of biomedical R&D (or clinical care in the provider sector), etc., will often be highly damaging.

This basic issue, of course, is often still ignored.

UNOS' Regulation of Organ Transplantation: "A Day Late and a Dollar Short"

The Los Angeles Times just reported on problems in the regulation of organ transplantation in the US by the organization known as UNOS , the United Network for Organ Sharing. "Since 1986, the federal government has contracted with UNOS to oversee everything from how organs are harvested to where they end up." The Times charged that UNOS "often fails to detect or decisively fix problems at derelict hospitals - even when patients are dying at excessive rates." Furthermore, "when it does act, the United Network for Organ sharing keeps findings of its investigations secret...."

The Times article provided bullet points about problems with UNOS operations:

• "UNOS has never recommended that the government close an active transplant program."
• "Even after programs log high death rates, years sometimes pass before UNOS takes meaningful action."
• "UNOS often backs down after being challenged — or even defied — by medical centers it is supposed to regulate."
• "UNOS officials have missed obvious red flags, including troubling transplant center statistics available on its own website."

The article described several cases in which transplant programs succeeded in delaying action by UNOS for a long time, and then only suffered "confidential probation," seemingly not much of a deterrant. "'It seems like UNOS is often a day late and a dollar short,' said Dr. Mark Fox, associate director of the Oklahoma Bioethics Center and former chairman of the UNOS ethics committee."
UNOS described its enforcement role thus,

Adherence to transplant policy is ensured through a comprehensive, systematic auditing and monitoring process. The policy compliance process is designed to maintain the highest standards in patient safety and foster public trust in the transplant network. Any deviation from policy is corrected quickly and thoroughly to protect patients and ensure that their treatment is not interrupted.

The United Network for Organ Sharing (UNOS) is the non-profit organization that operates the Organ Procurement and Transplantation Network (OPTN) under contract with the U.S. Department of Health and Human Services. In this role UNOS coordinates organ transplant policy development and compliance,...

The OPTN provides the most comprehensive health-care oversight program in the country. Transplantation is the only field of medicine in which every case is monitored.

But according to the Times,

'UNOS is not the FBI,' said board member Dr. Gabriel Danovitch, medical director of UCLA Medical Center's kidney and pancreas transplant program. 'It's not a police force.'

'It was never really designed as an enforcement agency,' said Dr. Dale Distant, a former board member and transplant chief at SUNY Downstate Medical Center in New York.

Although federal contracts give UNOS the role of maintaining "compliance," in fact UNOS is a membership organization. The largest number of its members are the transplant centers whose compliance UNOS is charged with enforcing. And, "it's a relatively small world in which colleagues - even friends - end up in judgment of one another."

So,

Such collegiality is built into UNOS' very structure — and that's the problem, some critics say. UNOS isn't just a regulator; it is a membership organization, run mostly by transplant professionals. Centers, in effect, oversee one another.

'UNOS really can't police itself,' said Dr. John J. Fung, director of the Cleveland Clinic's transplant center and a former UNOS board member. 'Everybody is beholden.'

The Times interviewed Judith Braslow,

who oversaw the federal government's division of transplantation from 1990 to 1998, said that although UNOS generally does a good job, it is difficult for the group to be 'completely objective because they essentially wear two hats.'

'In their capacity as the government contractor, they have responsibility to keep the public informed. In their capacity as a membership organization, they have responsibility and loyalty to their members,' she said.

'Those two roles are really in conflict in terms of the policing function.'

So this turns out in some way to be a familiar story. An organizational structure designed in a more genteel age, when hospitals were smaller, more community oriented organizations, threadbare in finances, and run by "superintendents" or "directors" (as per Kenneth Ludmerer's Time to Heal) may no longer be appropriate for an age when hospitals are multi-billion dollar organizations run like "businesses" by CEOs, and other professional (but usually not health professional) managers, to the latest tunes sung by management consultants. In the new bleeding edge world of health care, collegiality can turn into conflict of interest awfully quickly.

"Collegial" mechanisms to ensure compliance may not work too well for organizations no longer run in a collegial manner.

Unless we can re-establish health care as collegial, instead of cut-throat corporate, we will need considerably tougher methods to keep the system honest.

Guidelines in Whose Interest? - Amgen, Epoetin, Medicare, and Chronic Kidney Disease

A number of articles that have come out over the last two months raise questions about the increasingly aggressive use of epoetin for patients with anemia on dialysis for chronic renal failure. Patients with chronic kidney disease often have severe anemia. Epoetin can treat such anemia. Epoetin is manufactured under the trade name Epogen by Amgen Inc. Epoetin is usually dosed to achieve a given target level of hematocrit (Hct) or hemoglobin (Hb). The question is how much epoetin to use to reach what level of Hct or Hb.

The most recent update of the Cochrane review of epoetin in this setting concluded that more aggressive treatment attempting to achieve a nearly normal hemoglobin was not clearly supported by existing evidence from randomized controlled trials, "There was no significant difference in the risk of death for low (<>133 g/L). Lower targets were significantly associated with an increased risk for seizures but a reduced risk of hypertension." (See Strippoli GFM, Navaneethan SD, Craig JC. Haemoglobin and haematocrit targets for the anaemia of chronic kidney disease. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD003967.)

An article in Health Affairs (Cotter D, Thamaer M, Narasimhan K et al. Translating epoetin research into practice: the role of government and the use of scientific evidence. Health Affairs 2006; 25: 1249-1259 ) noted that despite this lack of evidence for more aggressive use of epoetin, Medicare, which pays for most epoetin use for patients on chronic dialysis in the US, has progressively agreed to pay for higher and higher hemoglobin targets. This policy is not based on evidence from randomized controlled trials, as noted above, nor on the US Food and Drug Administration (FDA) suggested targets for hemoglobin.

So, "spending for epoetin therapy is now the single largest Medicare drug expenditure ($1.75 billion in 2005) and is the second-largest source of dialysis facility income (approximately 22 percent)."

Cotter et al alleged that Medicare based its decisions on published practice guidelines, in particular, the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, " in numerous policy instructions, the CMS has cited KDOQI’s target hematocrit recommendations as the basis, in part, for its epoetin Medicare policy." But,

Amgen sponsored the Kidney Disease Outcomes Quality Initiative (KDOQI) of the National Kidney Foundation (NKF), an assessment process that purported to be an evidence-based approach to evaluating the medical literature. However, a rigorous review of the evidence used to support KDOQI’s 2000 'Guideline 4: Target Hemoglobin/Hematocrit for Epoetin' recommendations yielded major deficiencies. Notably, the priority scores (that is, the weights) for cited studies were never published, and the evaluation techniques did not elicit 'linkages in the causal pathway between intervention and outcome.' Specifically, KDOQI 2000 used a few randomized clinical trials (RCTs), expert opinion, and numerous industry-sponsored observational studies based on Medicare claims and other administrative data that suggest, for any given snapshot of the treated population, that patients who achieved higher hematocrits tended to have better clinical outcomes. Thus, both researchers and guideline developers have interpreted the evidence of an association between treating anemia with higher epoetin doses and improved clinical outcomes as an indicator of causality.

Last month, Christopher Rowland writing in the Boston Globe suggested that there is additional evidence against the use of higher hemoglobin targets. He reported that a trial,

called CHOIR, was intended to document the benefits of larger Epogen doses. Instead, safety reviewers halted testing because participants were dying at an unexpectedly high rate.

Patients given the highest doses of Epogen suffered 16 more deaths -- 72 out of about 700 patients -- than those treated within FDA guidelines, who suffered 56 deaths. The results have not been published in an academic journal.

The CHOIR study focused on Procrit, a drug virtually identical to Epogen, and involved 1,432 subjects. It was sponsored by Procrit's manufacturer, Ortho Biotech Products LP , a unit of Johnson & Johnson . The intent was to determine whether patients had lower death rates and fewer cardiovascular ailments if their red blood cell counts were elevated to 13.5 grams per deciliter.

Furthermore,

The CHOIR trial was not the first to show higher doses of Epogen carried risks. Fatal heart attacks, strokes, and other problems forced clinical investigators to suspend at least seven other trials using Epogen or similar drugs to treat kidney and cancer patients.

He also noted that "Epogen was the primary reason Amgen became a global powerhouse. In 2005, it earned $3.7 billion on $12.4 billion in revenue...."

Finally, a recent Forbes article critical of Amgen also reported the company's influence on the development of the guidelines which seem to have been Medicare's primary rationale for paying for aggressive use of epoetin,

Dr. Barry Straube, Medicare's chief medical officer, defends the Epogen guidelines.

But Straube admits that the Medicare decision on epoetin dosing is based on clinical habits and industry-promoted guidelines, not the results of randomized clinical controlled trials.

Some of the guidelines that Medicare relies on were set by a committee of the National Kidney Foundation, whose work was principally funded by Amgen. 'Amgen essentially purchased the pseudoscience that went into raising these hematocrit guidelines in the medical literature,' bristles Merrill Goozner, a director at the Center for Science in the Public Interest.

Thus this appears to be a second example this week of how 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. (See recent post here.) At best, this can lead to excess costs and treatment that does patients little good, and risks harming them.

This is a reminder that 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.

The Latest Stealth Marketing Story: Eli Lilly and Xigris

The latest alleged example of stealth marketing of pharmaceutical products appeared in a commentary the New England Journal of Medicine this week. (Eichacker PQ, Natanson C, Danner RL. Surviving sepsis - practice guidelines, marketing campaigns, and Eli Lilly. N Engl J Med 2006; 335: 1640-1642.) I will summarize the main points using quotes from the article:

In 2001, the Food and Drug Administration (FDA) approved Eli Lilly's Xigris (recombinant human activated protein C, or rhAPC, also known as drotrecogin alfa [activated]) for the treatment of sepsis. This approval was based primarily on a single phase 3 randomized, controlled trial — the Recombinant Activated Human Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study, published the same year — which showed a significant overall survival benefit at 28 days. The FDA acknowledged that there was controversy surrounding this decision, and half the members of the agency's advisory panel, pointing to methodologic and other important problems with the PROWESS study, voted to require that a confirmatory trial be performed before approval was granted.

To improve sales of rhAPC, in 2002, Lilly hired Belsito and Company, a public relations firm, to develop and help implement a three-pronged marketing strategy. First, the product's sales were to be supported by marketing initiatives targeted to physicians and the medical trade media. Second, because rhAPC was relatively expensive, word would be spread that the drug was being rationed and physicians were being "systematically forced" to decide who would live and who would die. As part of this effort, Lilly provided a group of physicians and bioethicists with a $1.8 million grant to form the Values, Ethics, and Rationing in Critical Care (VERICC) Task Force, purportedly to address ethical issues raised by rationing in the intensive care unit. Finally, the Surviving Sepsis Campaign was established, in theory to raise awareness of severe sepsis and generate momentum toward the development of treatment guidelines.

In the second phase [of the Surviving Sepsis campaign], launched in June 2003, international experts in critical care and infectious diseases were convened to create guidelines for sepsis management, which were published in Critical Care Medicine in March 2004. Lilly provided more than 90% of the funding for these two phases, and many participants had financial or other relationships with the company. According to the Council of Public Relations Firms, Belsito helped to assemble the VERICC Task Force and launch the campaign, and initiated a media-outreach program to 'raise awareness' of alleged rationing in severe sepsis with the intent of generating demand for rhAPC.

[In the guidelines,] rhAPC was given a highly favorable rating (grade B), whereas established therapies for sepsis (such as antibiotics, fluids, and vasopressors), though included in the recommendations, received lower ratings (grade D or E), because most had not undergone randomized, controlled trials owing to a lack of equipoise.

This imbalance is made more troubling by the campaign's failure to discuss persisting concern about rhAPC, which has been reinforced by recent trials. After the PROWESS study, which had demonstrated an increased risk of serious bleeding, two other controlled trials — the Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) study and the Resolution of Organ Failure in Pediatric Patients with Severe Sepsis (RESOLVE) study — both of which were terminated early because they were deemed unlikely to show a significant difference in their primary end points, confirmed that increase in risk and resulted in warnings submitted by Lilly to the FDA regarding the use of rhAPC. ...No mention of the [ADDRESS] study was included in a supplement to the Surviving Sepsis Campaign Guidelines.... Although data from the ENHANCE trial were available and are included in the guideline supplement, the possible magnitude of this increased risk (a 28-day incidence of serious bleeding of 6.5%, as compared with 3.5% in the PROWESS study) is not noted.
The Infectious Diseases Society of America (IDSA), however, declined to endorse [the guidelines].... According to Dante L. Landucci, an intensivist at East Carolina University, Critical Care Medicine, which published the guidelines, removed mention of the IDSA's rejection from his invited editorial on the subject that appeared in print 3 months after the guidelines did.

As part of the third phase of the campaign, Lilly awarded unrestricted grants for an 'Implementing the Surviving Sepsis Campaign' program. The main goal of this phase, launched in mid-2004, is the creation of performance bundles based on selected recommendations from the campaign guidelines. Again, many participants have self-reported financial or other relationships with Lilly. Despite the persisting scientific controversy surrounding its safety and efficacy, rhAPC is included in one of these performance bundles. Neither the campaign's manual on bundle implementation nor a cover letter from the president of the Society of Critical Care Medicine mentions the ADDRESS and RESOLVE trials or the warnings they precipitated. In formulating and promoting the bundles, the campaign sought to collaborate with public, not-for-profit arbiters of the quality of health care, including the Voluntary Hospital Association, the Institute for Healthcare Improvement, and the Joint Commission on Accreditation of Healthcare Organizations.
Implementation of the bundles is being advocated nationally in workshops organized under the auspices of the Society of Critical Care Medicine and funded by Lilly. Furthermore, the campaign has lobbied state governments to adopt the bundles. Efforts to institute these measures internationally are being promoted in a program called the "Surviving Sepsis Campaign Roadshow," also subsidized by Lilly.

The authors' conclusions were:

Professional societies and other stakeholders must work together to promote a consistent guideline-development process, a robust rating system for guidelines that is applicable to all subspecialties, and a policy that prohibits the pharmaceutical and medical-device industries from directly or indirectly funding or influencing practice standards. The challenges involved in producing first-rate guidelines and performance standards are only exacerbated by the intrusion of marketing strategies masquerading as evidence-based medicine.

We have previously discussed how guidelines may be written by authors who have financial interests in relevant products (here and here). This current case suggests how this may come to pass in the context of a detailed stealth marketing campaign (and see posts here and here about stealth marketing.) It is particularly notable that these issues are now appearing in the most mainstream of mainstream medical journals.

Maybe with increasing realization how pervasive conflicts of interest fuel deceptive marketing and promotion will come some increased skepticism and a will to address this problem.

Another (Government) One Bites the Dust: Former FDA Head Crawford Pleads Guilty

It seems to be the season for the public disgrace of leaders of large health care organizations. Multiple news sources have just reported that former US Food and Drug Agency (FDA) Commissioner and acting Commisioner Lester M Crawford has plead guilty to misdemeanor charges of conflict of interest and false reporting. Typical is the report by the New York Times,

Lester M. Crawford, the former head of the Food and Drug Administration, pleaded guilty this afternoon to lying and conflict-of-interest charges in connection with stock he and his wife owned in companies regulated by the F.D.A.
Dr. Crawford, 68, could be sentenced to up to a year in prison and fined up to $100,000 on each of the two counts.

Senior employees of the agency are barred from owning shares in companies it regulates. Dr. Crawford and his wife, Catherine, accordingly sold their holdings in nine companies around the time he became deputy commissioner early in 2002, the government said.

But they retained shares in three others: the food giants Sysco and Pepsico, and Kimberly-Clark, which makes consumer health products and other goods. In addition, Mrs. Crawford held shares in another regulated company, Wal-Mart, but her husband did not list them in his 2002 financial disclosure.

In addition, Dr. Crawford, who is a veterinarian and pharmacologist, exercised options to buy shares in an F.D.A.-regulated poultry biotechnology company in 2003 and 2004, earning almost $30,000 altogether. He did not list them in disclosure filings, as he should have, even though properly reported the transactions on his tax returns, the government said.

The conflict-of-interest charges stemmed from the Crawfords’ ownership of shares in Pepsico and Sysco while he was chairman of the F.D.A.’s Obesity Working Group, which was reviewing calorie-content labeling for soft drinks.

So in the last week, the former CEO of a prominent teaching hospital was convicted of conspirarcy and mail fraud (see post here), the current CEO of one of the largest US managed care organizations agreed to resign after an internal report implicated him in back-dating of stock-options (see post here), and now the former Commissioner of the FDA plead guilty to conflict of interest and disclosure violations.

Might the connection of these very large dots finally be the wake up call that we have a major problem with mismanagement, conflicts of interest, and corruption at the top of large health care organizations? This might have to do with our repeatedly lamented but never succesfully addressed problems with rising costs, declining access, questionable quality, and demoralized health care professionals.

Another (Really Big) One Bites the Dust: CEO McGuire to Retire from UnitedHealth

We have posted repeatedly (see these posts here, here, and here with links backward) about the hugely lavish compensation afforded to the Dr William McGuire, CEO of UnitedHealth Group, one of the largest US insurers/ managed care organizations, and how this remuneration stood in stark contrast to the stated mission of UnitedHealth Group:

UnitedHealth Group is a diversified health and well-being company dedicated to making the health care system work better. The company directs its resources into designing products, providing services and applying technologies that:
- Improve access to health and well-being services;
- Simplify the health care experience;
- Promote quality; and,
- Make health care more affordable.

Most recently, controversy has swirled over the timing of huge stock option grants given to CEO McGuire (see post here). The findings are now in from an internal investigation of the problem, and they are not pretty. Quoting from the Wall Street Journal article by James Bandler and Charles Forelle published October 16,

The scandal over backdated stock options claimed one of corporate America's most successful chief executives, William McGuire of UnitedHealth Group Inc., who agreed to leave the giant health insurer after an internal probe concluded that the stock-option grants that have brought him a huge fortune were likely manipulated.
The probe's findings, released yesterday, provided a detailed picture of how stock-option backdating worked at the company, offering glimpses of cronyism and a culture in which vast sums of compensation were handed out with few controls or written records. Among the troublesome option grants detailed in the report was a massive 1999 award to Dr. McGuire that ranks among the most lucrative ever.

UnitedHealth said Dr. McGuire would immediately relinquish the chairman's post and step down as CEO by Dec. 1. Also leaving is William G. Spears, a member of the board's compensation committee who had deep financial entanglements with Dr. McGuire, which were undisclosed to investors, and David Lubben, the company's general counsel.

At the end of last year, Dr. McGuire's cache of unexercised options was valued at $1.78 billion, a sum far greater than any other U.S. corporate chieftain. Yesterday, UnitedHealth said he agreed to have all of the options issued to him from 1994 through 2002 repriced, likely cutting tens of millions in dollars from their value. But the company left open other financial arrangements with Dr. McGuire, and the exact terms of his departure are likely to be the subject of intense negotiations.

UnitedHealth, which is based in Minnetonka, Minn., and has a market capitalization of $66 billion, also is being investigated by the Securities and Exchange Commission, by federal prosecutors in New York, and by the Minnesota attorney general.

The probe by WilmerHale was headed by William McLucas, a former director of the enforcement division of the SEC. It examined 29 of the largest options grants at UnitedHealth over a 12-year period, and concluded that most likely were backdated to benefit insiders.

Although couched in careful language, the 14-page WilmerHale report suggests that Dr. McGuire misled lawyers conducting the probe of the options grants at issue. To the end, Dr. McGuire insisted that year after year he actually did call or otherwise contact a compensation-committee member to set an options grant in motion on what, in hindsight, turned out to be a wildly favorable day.

'Certain facts run contrary to this assertion,' the WilmerHale report says, citing memoranda Dr. McGuire wrote on or after the purported grant dates referring to possible grants in the future tense.

Additional articles in the media underlined management problems at UnitedHealth. In the New York Times, "a law firm hired by UnitedHealth to investigate the timing of stock options concluded that the company was riddled with poor controls and conflicts of interest." From the Associated Press (in the San Jose Mercury News), "William McGuire ran UnitedHealth Group Inc. like his personal fiefdom, allowing the former CEO and his cronies to gain tremendous wealth with few internal controls to stop them." Furthermore, "the review headed by former SEC top cop Bill McLucas ends up telling a much more important story: That of a controlling leader who put his personal interests ahead of the welfare of the company's shareholders." In addition, "'This shows how a board stopped managing a CEO and just cheered him on,' said Patrick McGurn, executive vice president and special counsel to Institutional Shareholder Services, a proxy advisory firm. 'They just wrote McGuire a blank check.'" In a scathing commentary in the Washington Post, Steven Pearlstein wrote, "Maybe what we have here is the most outrageous corporate scandal since Enron and WorldCom."

Perhaps this is a demonstration of how those ignorant of history are bound to repeat it. Some aspects of the UnitedHealth story now seem strangely reminiscent of the story of the collapse of the Allegheny Health Education and Research Foundation (AHERF), at its time one of the biggest hospital systems in the US, and which became the second largest bankruptcy in the US at the time. Its leader was widely called a "visionary." Later, he was accused of running the system as a personal fiefdom. Yet the story of the fall of AHERF got little national recognition, and almost no recognition in the medical and health care literature, an early example of the anechoic effect. (See my summary of the AHERF story starting on page 5 here.)

So I wonder whether the current UnitedHealth scandal will finally be big enough to open up some eyes about the concentration and abuse of power now pervading US (and global) health care. (For many more examples, just see the archives of Health Care Renewal.)

What has been missing from most of the discussion of the UnitedHealth Group debacle so far is appreciation for its health care context. This is not merely a scandal about lavish executive pay and sloppy management at a big corporation. This is a scandal about mismangement of one of the largest US health care insurers and managed care organizations.

Shouldn't we be wondering if "controlling leader who put his interests ahead of the company's shareholders" also put his interests ahead of the doctors and other health care professionals who had to deal with the company, and most importantly ahead of the patients "served," it that is the word, by the company?

And shouldn't we be wondering if the commercial managed care model, which has failed to control US health care costs, and in this example seemed more devoted to the enrichment of its own executives than saving money for its patients, hasn't been managing care so well, and maybe isn't the model we should be using?

Another One Bites the Dust: Former Roger Williams Medical Center CEO Convicted

We have previously posted about the woes of a local Rhode Island hospital, Roger Williams Medical Center. The hospital's former CEO, Robert A Urciuoli, and a vice president, Frances P Driscoll, were accused of hiring a former state legislator to promote the hospital's political interests. The hospital agreed to a federal deferred prosecution agreement, admitting that the government had evidence of wrong-doing, and pledging reforms. The hospital's board fired Urciuoli and Driscoll. (See posts here and here.)

Urciuoli, Driscoll, and a leader of the hospital's assisted living center have been on trial in federal court in Providence. The verdict was just announced. I will quote relevant details from a Providence Journal story.

A federal jury today returned a mixed verdict in the Roger Williams Medical Center corruption trial that centered on whether hospital executives had abused the honest services of a former state senator -- who became the star witness against them.

After entering their seventh day of deliberations in U.S. District Court, jurors convicted former hospital president Robert A. Urciuoli of conspiracy and 35 of 36 counts of mail fraud. They cleared Peter J. Sangermano Jr., a partner in the hospital's assisted-living center, of the same 37 counts against him. The third defendant, Frances P. Driscoll, a former hospital vice president, was cleared of the conspiracy charge, but convicted of the one other count against her, mail fraud. A conviction for conspiracy carries a penalty of up to five years in prison and a $250,000 fine. Mail fraud is punishable by up to 20 years in prison and a $250,000 fine.

The defendants in January were named in a 38-count indictment, charging them with conspiracy and mail fraud. The indictment alleged that Urciuoli, Driscoll and Sangermano hired Celona as a consultant to The Village at Elmhurst, which was partially owned by the hospital, but that Celona's real work was using his public office to influence legislation and perform favors.

The indictment charged that one or more of the defendants directed Celona on various matters, from legislation to persuading municipalities to increase their ambulance runs to Roger Williams to pressuring health insurers with legislation before his Senate committee to increase their reimbursements to the hospital.

In 1998, the indictment charged, Driscoll and Sangermano directed Celona to work against a bill prohibiting health facilities, including the Village at Elmhurst, from offering care for Alzheimer's disease.

As chairman of the Corporations Committee, Celona had the power to advance or kill bills of importance to companies, including Blue Cross and United Healthcare, each of which were embroiled in a dispute with Roger Williams over insurance payments.

Urciuoli and Driscoll are thus new additions to the unhappy roster of health care organization leaders convicted of criminal misconduct in the course of their official duties. (Another relatively recent addition to this roster was the former CEO of Fletcher Allen Health Care, see post here.) Thus, they join the most extreme examples of abuse of power in health care. Yet, as I have said so often, even cases as egregious as these get little attention outside of their local geographic region. So physicians and other health professionals stuck under their demoralizing penumbra often believe that their misery is a local anomaly, not part of a larger pattern.

Hopefully, the litany of cases, big and small, of concentration and abuse of power on Health Care Renewal may persuade some physicians, other health professionals, policy researchers, and policy makers that there are systemic problems that must be addressed.

"Ghosts in the Machine"

We have posted several times (most recently here, with links backward) about the story of Dr Aubrey Blumsohn's dispute with Proctor and Gamble (P&G) and Sheffield University in the UK. In summary, Blumsohn and Professor Richard Eastell had done clinical research on the risedronate (Actonel), sponsored by P&G, the drug's manufacturer. P&G refused Blumsohn access to the original data from the study he was ostensibly running, and hired a ghost-writer to write abstracts in his name. Blumsohn protested to Eastell, who advised him not to make waves because P&G "is a good source of income" for the university. When protests to other university officials produced no results, Blumsohn told the story to the press, whereupon the university suspended him, and he eventually lost his position there.

Dr Blumsohn just wrote a brilliant essay on the integrity of clinical research for the Professional Ethics Report published by the American Association for the Advancement of Science. I will quote from his introduction and then his conclusions. (In the center of his essay is a clear discussion of his case, plus mention of some other important cases, well known and not.)

Pharmaceutical companies sell products under the banner of science and medicine. However, their raison d’être is to make money. If industry gets involved in science, it has to balance genuine hypothesis testing and transparency against commercial interests, bureaucracy of drug regulation, and the financial consequences of dishonesty. This is not in itself a criticism – it is a simple fact.
Universities exist for a different reason – to add to human knowledge and to disseminate that knowledge through publication and teaching. Subtle compromises have allowed the pharmaceutical industry to develop an extraordinary stranglehold over the scientific process, academic discourse, regulatory safeguards and common sense. It is hard to see how safeguards for dispassionate scientific discourse can be sustained when medicine flagrantly disregards them.
The pharmaceutical industry is accused of overturning the usual safeguards of science. The most fundamental of these safeguards is the accountability of authors. Readers of legitimate science expect that stated authors are truly the authors, that they vouch for the work, and that they would be able to defend their findings if challenged. They expect that authors have seen and scrutinized raw data, and would be able to provide that data if asked. That it is necessary to write this indicates how much we have lost.
Industry has been inclined to use universities to give tainted science a veneer of respectability, while denying the very basis of that respectability. 'Ghost-writing' has been repeatedly criticized. However, professional 'medical writers' may sometimes have a legitimate role if clearly acknowledged. By emphasizing the 'writing' aspect, we divert attention from the far more important problem – that of 'ghost science,' of which 'ghost-writing' is only a part.

The usual definitions of scientific misconduct do not apply to pharmaceutical research. In February 2006, Gerald Schatten was accused of research misconduct. His crime was to have coauthored a stem-cell publication with the discredited Dr. Hwang Woo Suk, while shirking the 'responsibilities of verifying the data.' Schatten might have been irked to discover that at the same time, Procter and Gamble Pharmaceuticals (P&G) declared to the media that it was 'standard industry practice' to deny authors access to raw data in drug studies.

Blumsohn concludes:

The ethical challenge in pharmaceutical medicine is to use available data in the best possible way. Data are derived from human participants who subject themselves to risk in the public interest. They have the right to know that the data derived from their assumption of risk are used properly. When data are closed to scrutiny, even by the supposed authors of research, this cannot constitute an appropriate or ethical use of that data. Patients have to be involved in solving the problem.

Most importantly, as academics we need to reassert the importance of data and the
meaning of authorship. We also need to assert “old fashioned” ideas of academic
freedom, our right to speak the truth as we see it, and to allow that truth to be
subjected to open debate.

In the words of George Orwell (1984), 'Freedom is the freedom to say that two
plus two make four. If that is granted, all else follows.'

Bravo!

New Blogs Adding to the Discussion

I just wanted to note a few newish blogs that have been discussing some issues of possible interest to Health Care Renewal readers. I will be soon adding them to our blog-roll. Here they are in alphabetical order.

The Antidote: Counterspin for Health Care and Health News seems to be doing what the title suggests. Some interesting recent posts include a counterpoint to Tyler Cowen's praise for innovation in the US health care system (sorry, Tyler), and some interesting discussions of health care quality issues.

Clinical Psychology and Psychiatry: A Closer Look has been taking a fresh and skeptical look at what has been going on in this particularly embattled area of health care. See in particular recent posts on whether atypical anti-psychotic drugs work for Alzheimer's disease, an ironic follow-up on the Blumsohn - Procter & Gamble - Sheffield University case, and the new BMJ article suggesting how industry funded meta-analyses may be biased.

Running a Hospital focusses on, surprise, hospital issues. What really is a surprise is the identity of the blogger, Paul Levy, the CEO of the Beth Israel Deaconess Medical Center in Boston. I have to tip my figurative hat to a hospital system CEO with the courage to blog with comments enabled. Furthermore, Mr Levy is willing to take on some controversial issues, and to do so without lapsing into health care management-speak. (See in particular his post on concierge medical practices.) Let's see if any other CEOs of large health care organizations will follow his lead.

$70 million for an Electronic Medical Records system?

Seen on HISTalk News (a popular blog in the healthcare information technology community) on 10/11/2006:

Geisinger Health System (PA) contracts with IBM to build a big clinical data warehouse. They called it "partnering," although I'm guessing that only Geisinger will be writing checks. Nothing interesting in the announcement, other than the little pearl that Geisinger's Epic project has cost $70 million so far and has reached "a quasi endpoint in how far we will get in simple decision support functions." Since they're calling it done, how about sharing the ROI and outcomes data?

Epic is an developer and vendor of healthcare information systems. This story is stunning if the facts are correct - or even near correct. A $70 million figure for a "quasi endpoint", and even more at another healthcare system (UC Davis, link), should scare the daylights out of any healthcare CEO. Just how much does it cost to build an entire hospital these days?

Internal documents show the [UC Davis] project -- with the final bill estimated to be anywhere from $75 million to $100 million -- is two years behind schedule and up to a fifth of the budget went to an outside consulting firm whose expense reports are now the subject of an internal UC audit.

The $70 to $100 million figures also seem concerning on their face. For example, these figures are far in excess of what it costs a trans-national company such as a pharma to implement major research information systems. It represents nearly 10 times the annual budget of my former department in one such pharma, that served the scientific information needs of 6,000 scientists and tens of thousands of others worldwide within the company.

It’s clear that metrics are needed such that a health system’s implementation can be benchmarked to others. What did that $70 million buy? Were the internal resources, expenditures, project management, use of consultants, etc. in line with other organizations? Were the cost/bed, cost/clinician, and other figures in line with what other medical centers experience? Was internal expertise adequate to properly manage the ubiquitous sociotechnical issues, i.e., the change-resistance and friction among all stakeholders including IT, administration and clinicians?

(I’m sorry, hospital CIO’s; your skills in management information systems don’t seem to work well when dealing with those issues in the “hiding in plain sight” invisible complexity of healthcare delivery environments.)

Finally, were vendor or software-created problems a cause of cost overruns, project rework, "peek-a-boo template delays" (a term used by a frustrated healthcare executive some years ago), false go-lives, end user disenfranchisement and other cost-increasing problems?

Without sharing of implementation difficulties and metrics, how can we ever really know if a healthcare IT project was implemented in a reasonable, cost-effective manner, even assuming it functions “successfully?”

What other industry is immune from accountability? Even clinicians are coming under greater scrutiny; a capability facilitated by clinical IT. Why is the health IT industry effectively excused from such scrutiny itself?

Of course, another issue raised in HISTalk that would prevent information sharing about inferior offering and best implementation practices -- that health IT vendors may threaten customers to stay quiet about problems-- is certainly borne out by my observations of almost complete lack of cross-institutional information sharing and publication about health IT problems.

Such a vendor stance makes perfect sense. If institutions don’t or can’t share, it means more business for the vendors – as well as the “remediation consultants” called in to clean up the various messes.

Unfortunately, healthcare doesn’t have the capital for clinical IT misadventures, and I believe when the issues become more public in this industry sector and information flows about mismanagement and abuses (as is happening in the UK ’s Connecting for Health project), the fallout won’t be pretty.

Addendum: on expensive "consultants", a common feature of the health IT landscape: the hospital at which I led the implementation of EMR and development of specialty clinical IT, Christiana Care in Delaware, spent some $500,000 back in the late 1990's for a similar Clinical Data Warehouse engagement with another of the large management consultant organizations.

This project was initiated by senior management without consulting with me, the Director of Clinical Informatics, or my staff. We had experience in this area ourselves.

For $500,000 I could have hired a team of people with specific expertise and built a functional, useful clinical data warehouse.

Additionally, if this had been done, at least there would have been an actual working deliverable, rather than just a pretty spiral-bound consultant's report which, at $500K, works out to about $250,000-per-pound. I'm not sure even weapons-grade plutonium is that expensive.

When healthcare organization leaders start to recognize that it's not OK for others to know their business better than themselves, and that it's not OK to believe it acceptable for others to know their business better than themselves, they will stop the massive waste on dubious external consulting engagements. (Assuming, of course, that there are not other motivators for such engagements, which as readers of HCRenewal know is not always the case).

The American Medical News Reports Stanford's New Conflict of Interest Policy in a Vacuum

This week's American Medical News print edition featured a front-page article on Stanford's new conflict of interest policies (available here, requires subscription.) As we noted earlier, this policy bans all "personal gifts" to physicians, even as small as pens or coffee mugs, from pharmaceutical or device companies; all funding to attend CME events; all direct funding to students and trainees; and sales representatives in patient-care areas or visiting physicians without prior appointments.

The American Medical News article suggested that the only concerns raised at the school about the new policy were related to loss of funding for educational events, and the need for students to learn how to deal with drug representatives.

It contained not a hint that there had recently been other issues raised about conflicts of interest at Stanford.

However, we have previously noted the irony of Stanford's new policy in light of the San Jose Mercury News investigation, written by Paul Jacobs and published in July, which showed that many Stanford faculty and leaders are affected by conflicts of interest that are much more intense than those created by accepting free pens, mugs, and lunches (see posts about this investigation here, here, and here).

Some of the data and cases reported by Jacobs in the series were:

• "The school's 700-plus faculty members last year disclosed 299 potential conflicts of interest related to their research, according to figures provided by Stanford."
• "Potential conflicts occur throughout the school's ranks. More than a third of the school's administrators, department heads and other leaders -- at least 26 out of 67 reviewed by the Mercury News -- have reported outside financial interests related to their research within the last four years. "
• "One researcher has founded six companies, most based on research that came out of his own lab. He is a managing partner of a venture capital firm focused on medical research and sits on the boards of several other companies. "
• "And the physician who until January chaired the department of gynecology and obstetrics is a longtime director of Wyeth, which manufactures controversial hormone replacement therapy for women -- therapy she defended in 2002 when potentially serious health risks were emerging."
• The Associate Dean for Research "holds stock options in and is a consultant to MedImmune, which makes an influenza vaccine he is studying under a federal grant." He also "a paid member of MedImmune's scientific advisory board and holds stock options...."
• The Chair of Psychiatry is currently running a federal grant on mifepristone as a treatment of depression, and has previously been the senior author of two related articles. Although he acknowledged that he helped found and still has a "financial interest" in Corcept Therapeutics, he did not fully disclose that he "took a seat on the board of directors and a part-time post as chairman of the company's scientific advisory board, a job that now pays him $60,000 a year. He and his family were granted 3 million Corcept shares for $1,000 -- today worth nearly $12 million." He had been accused of making exaggerated claims about Corcept's products in scholarly articles which did not reveal the extent of his involvement with the company.

So at Stanford, a junior faculty member will not be able to accept a coffee mug with the Wyeth logo, while a senior faculty member can serve on the board of directors of Wyeth.
I would have hoped that the American Medical News reporter might have dug around a little to determine the background of Stanford's new policy. Juxtaposing it to the results of Paul Jacobs' previous investigative reporting produces a very different impression than simply reporting the new policy in a vacuum.
In my humble opinion, the problem is not that the Stanford policy is too strict. Instead, I submit that the policy is much too tough on students, interns and residents, and junior faculty, given how leniently it treats senior faculty and academic leaders. If the conflict causes by accepting a mug with a company logo is so grievous that it cannot be tolerated, why is it acceptable to serve on the board of the same company?
But maybe the operative slogan was "do as I say, not as I do."
It's a pity that the American Medical News reporter failed to dig up the facts needed to appreciate these ironies.

The Conflicted Defending the Conflicted: Infectious Disease Specialists' Attack on the LA Times Goes Awry

We have posted frequently, (e.g., here and here), about conflicts of interest affecting top US National Institutes of Health (NIH) scientists and leaders. Two months ago, we posted about the case of Dr Thomas J Walsh, Head, Immunocompromised Host Section, Pediatric Oncology Branch, Center for Cancer Research and the National Cancer Institute (NCI). A Los Angeles Times investigation by David Willman had suggested that Dr Walsh, while working full-time for the NIH, had received money from several pharmaceutical companies, and also had had spoken for these companies' products at several US Food and Drug Administration (FDA) meetings.

The Los Angeles Times article (no longer available from the Times, but online here) elicited an extraordinary response. Last month, 109 (one hundred nine) authors wrote a rebuttal in Clinical Infectious Disease. (Full citation: Anaissie EJ et al. Clinical research in the lay press irresponsible journalism raises a huge dose of doubt. Clin Infect Dis 2006; 43: 1031-9.) "To provide a case study for how inaccurate and dangerous the mainstream press can be if articles are not carefully written, as well as to correct inaccuracies and defend honesty in research, we offer our counterpoint to a recent article that questions the various systems of checks and balances that govern the conduct of clinical trials and implicitly accuses one of our infectious diseases colleagues of unethical conduct in 2 clinical trials."

The article by Anaissie et al focussed on two concerns, "selective enrollment of patients and picking doses of antifungals to bias outcomes" of two clinical trials Walsh lead, published in 1999: [Walsh TJ et al. Liposomal amphotericin B for empirical therapy in patietns with persistent fever and neutropenia. N Engl J Med 1999; 340: 764-71]; and in2004: [Walsh TJ et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med 2004; 351: 1391-1402.]

According to Anaissie et al, "The first layer of purported deceit implicitly alleged by Willman's article involved the selection of the type of trial that would have the highest likelihood of securing FDA approval." Walsh had originally advocated testing the drugs on patients with fever and suspected, but not proven fungal infections. Willman suggested that one reason for this was that such patients are more numerous than those with proven fungal infections. Thus, studying the former rather than the latter patient group would speed up completion of trials, and hence possibly marketing of drugs. Anaissie and colleagues made an apparently reasonable clinical argument for empiric anti-fungal treatment in patients with persistent fever and low white blood cell counts despite conventional antibiotic therapy. Curiously, the corroboration they cited came from two guidelines both published after both of Walsh's trials were designed.

Again, according to Anaissie et al, "The second and more serious of Willman's implicit accusations is that Walsh deliberately chose to administer lower, less-effective dosages of comparator drugs in the 2 trials." Their argument in support of the doses of the comparison drugs used by Walsh et al was based on two points. First, the dosage of the comparison drug used in Walsh and colleagues' earlier study was based on "prior studies of empirical therapy that established the safety of this approach." Second, "no evidence of superior outcomes associated with higher dosages .. has ever been published."

Having demolished these straw men, Anaissie et al concluded in a devastating manner,

The Los Angeles Times has failed its readership on all counts. The destructive nature of Willman's implicit allegations and the strong rebuttals made by several investigators and by Walsh's superiors several months before the publication of Willman's article should have prompted Willman's editors to scrutinize carefully the quality of his 'evidence.' Their failure to do so calls into question the credibility of the Los Angeles Times as a serious newspaper. Accordingly, the editors bear responsibility, together with Willman, for this publication. One might ask at what point reporters and editors cross the line of ethical reporting. If anything, this sad chapter should give the public a huge dose of doubt about this newspaper.

Sensational attacks on a respected academic and government employee (and, implicitly, on the entire drug-approval process) and fear-mongering addressed to the lay reader (implying that individuals should enroll in clinical trials at their own risk) may be attention-grabbing ways to sell more newspapers; for this purpose, Walsh served as a convenient scapegoat.

The greatest danger of articles such as Willman's is that members of the lay public do not read medical journals. By contrast, the Los Angeles Times is widely read, is disseminated online, and is perceived as an authoritative news source. Accordingly, there is good reason to fear that the public will conclude, on the basis of Willman's article, that the entire process of drug development in the United States and abroad is corrupt and that they should refrain from participating in clinical trials. We question whether Willman and the Los Angeles Times considered the possibility that future patients might suffer as a result of Willman's irresponsible report.

Now who is fear mongering? I would readily concede that the methodologic issues raised by Willman about the two trials lead by Walsh are complex and debatable. In fact, when writing our first post on the subject, I decided not to dwell on them for those reasons. However, Willman's article raised other issues that Anaissie et al virtually ignored.

These were the questions about Walsh's conflicts of interest. Willman had reported:

• Walsh made favorable comments about an anti-fungal drug made by Merck & Co, Inc to an FDA panel, and in an editorial in the New England Journal of Medicine, while he was consulting for Merck and had served on an expert panel for the company. Walsh did not disclose his relationship with Merck to the the NEJM.
• Walsh also appeared in front of an FDA panel in support of an anti-fungal drug made by Fujisawa USA (now Astellas Pharma Inc) while he was a consultant to Fujisawa.
• Walsh presented information to yet another FDA panel in support of another anti-fungal drug made by Pfizer Inc while he was a consultant to Pfizer.

Willman noted that, "U.S. conflict of interest law generally prohibits a federal employee from representing anyone before a government agency, regardless of whether outside compensation is paid."

Yet Anaissie et al attempted to finesse this issue thus, "Willman further attacks Walsh on the inappropriateness of his advice to regulatory agencies." They argued,

It is entirely appropriate for a principal investigator and data review committee chair to provide advice to both the pharmaceutical industry and the FDA, particularly when he happens to be, like Walsh, an accomplished investigator with almost 600 peer-reviewed scientific publications and service on numerous scientific advisory boards. Being a federal employee does not disqualify Walsh from providing such advice; he is as qualified to do so as any other academic investigator with similar expertise.

The issue, of course, was not whether Walsh should have provided just advice to pharmaceutical companies and the FDA. The issues were, instead, whether it was ethical, or lawful, for Walsh to provide advice to FDA advisory panels while he was working both for the NIH and for the drug companies who made products that those panels were considering, and whether it was ethical for Walsh to be working for drug companies as a consultant while he continued to work for the NIH on projects related to their products. Anaissie et al did not even acknowledge these central concerns raised by Willman's reporting, much less attempt to refute them.

In fact, a few days after the article by Anaissie et al was published, Willman wrote another Los Angeles Times article about the results of the NIH internal investigation of Walsh. This noted that Walsh had received over $100,000 from multiple drug and biotechnology companies, and that Walsh had been getting consulting fees from Merck at the same time he took the lead for the National Cancer Institute (NCI) on a formal collaboration between the NCI and Merck. The report dismissed Walsh's assertions "that his reputation is sufficient to dismiss any questions about his impartiality." The report noted "at least 38 separate instances where he chose not to follow agency procedures. He actively chose not to adhere to policies because it was inconvenient or time-consuming; he knew it was likely his participation [with the drug companies] would have been disapproved. His actions reflected negatively upon the agency." Finally, it asserted, "Dr. Walsh has engaged in serious misconduct, in violation of the Department's Standards of Conduct Regulations … and federal law and regulation."

Although Anaissie et al may have not been aware of these findings when they wrote their article, they were left in the position of defending someone now accused by the NIH of violating federal laws and regulations.

Anaissie and colleagues' article just received a deserved scolding by Ivan Oransky, deputy editor of The Scientist, in the Boston Globe,

Unfortunately, the Clinical Infectious Diseases screed's omission of Walsh's financial relationship with Merck and other companies is consistent with how clinical researchers seem to feel about disclosure.
Message received: Researchers know best. Please stop bothering us with these silly rules and your sensationalist investigations. Sorry, neither Willman's irresponsible report nor the government's alleged heavy-handedness in trying to protect the public are going to hurt patients. What is going to hurt clinical research and patients is the continued lack of transparency by a number of researchers. Like most Americans, I'm a strong believer in the importance of research, clinical trials, and the role of drug companies in improving the public health. But I'm also a strong believer in disclosure. When someone hides something, I want to know why. If there's nothing wrong with financial relationships between researchers and drug companies, why not disclose them?

Olansky makes good points. The NIH internal report certainly suggested that some researchers may believe that their scientific or clinical abilities exempt them from having to deal with "silly rules," including those about conflicts of interest. However, the attempted defense of Walsh by Anaissie et al makes a larger point.

A full one and one half pages of the print version of the Anaissie et al article are taken up by disclosure of its authors' "potential conflicts of interest." Of the 109, approximately 54 disclosed that they worked as consultants to and/or for speakers' bureaus of pharmaceutical and biotechnology companies. Approximately 28 worked for Astellas Pharma US, 35 for Merck & Co, and 44 for Pfizer Inc. (Many worked for more than one company; some worked for more than 10 at a time.)

Thus, isn't it clear why this group had a problem grappling with, even talking about, the allegations of conflicts of interest affecting Walsh's work for the federal government, conflicts arising out of Walsh's paid work for Fujisawa (later Astellas Pharma US), Merck & Co, and Pfizer Inc?

What Anaissie et al succeeded in doing was reminding us all how pervasive conflicts of interest are in academic medicine. They also reminded us that the problem with conflicts of interest is that the people who have them are, well, conflicted. As Joe Collier recently wrote in the British Medical Journal, "people who have conflicts of interest often find giving clear advice (or opinions) particularly difficult." And it is unclear whose interests conflicted peoples' opinions serve.

I think Anaissie et al have demonstrated the glaring need for tough regulations requiring disclosure of all financial (and probably political) conflicts of interest affecting anyone who can make decisions, for individuals or organizations, in health care. Basically similar regulations should apply not only to government agencies and academic medical institutions, but also all other health care organizations, not-for-profit and for-profit included.

WHAT CAN BE DONE?

If you work in a health care organization, push for internal regulation. Write your congressperson about the need to regulate and discl0se conflicts of interest in health care.

Suffering Medical Education: Follow the Money

While pharma seems to have plenty of money to subsidize dubious marketing schemes (see post here), there is plenty of evidence that primary care and medical education are continuing to suffer from too little money. See for example, two recent stories, one from the UK, one from the US.

From the US, the Detroit News published yet another story about the decline of primary care training. This story contrasted the situation in primary care with that in dermatology. I confess being brought up to think of this specialty as necessary, but not particularly exciting, varied or glamorous. But now, "Droves of the nation's most talented medical students are pursuing careers in dermatology, a field that promises good pay, flexible hours and job opportunities hard to come by in other fields. The surge in dermatology interest comes as doctors flee some of the most critical medical fields -- family practice, internal medicine and obstetrics -- for a slew of reasons.... 'We're very lucky in dermatology that we get to pick our trainees from the best and the brightest,' said Dr. Jack Resneck, an assistant professor of dermatology at the University of California-San Francisco. 'We've certainly seen declining interest in primary care and general surgery residencies,' he added." One particular factor in the imbalance of interest in primary care vs dermatology is the vast sea of debt in which many US medical students swim. "Young doctors easily run up more than $100,000 in education costs by the time they're ready to practice, making a good-paying job a priority." Yet, as we have noted before, the very high and rising cost of going to US medical schools seems to contrast with the little financial support given to US medical school faculty members for actually teaching. Where is all that tuition money going? That's a good question.

Meanwhile, in the UK, the Guardian reported that one result of the growing financial crisis affecting UK hospitals is " Millions of pounds that should be being spent on training junior doctors, nurses and midwives are being withheld in a bid to meet the NHS's financial deficit, Britain's most senior surgeon has warned.
Cash-strapped strategic health authorities are "raiding" an average of 10% of the MPET (multi-professional educational training) budget, which should be spent on improving health professionals' skills, Bernard Ribeiro, president of the Royal College of Surgeons, said. That could have a serious impact on patient care at a time when junior doctors' training - and in particular theatre time - is already being slashed by a reduction in doctors' hours caused by the European working time directive, and by a new training system called Modernising Medical Careers, to be rolled out in August, that will see junior doctors become consultants in seven years rather than the current 11 years or more." One issue is that the money for training is not "ringfenced," which I take to mean that the money, although meant for training, need not actually be spent on training. This recalls the situation of the money spent by Medicare in the US on graduate medical education, which is provided to hospitals to support this function, but without any requirements about how the hospitals must actually use the money (see post here).

Figure out where the money goes, and who sends it there, and you have figured out a lot about what is currently wrong with medical education, and more generally in health care.