Were Late Stent Thromboses Really So Unexpected? Why depend on device companies and others to find out?

In "Were Late Stent Thromboses Really So Unexpected?" Roy Poses concludes that:

The lessons, again (see previous post), are that physicians must be very, very skeptical about the results of research sponsored by those with vested interests in the research turning out a certain way, and/or by research done by investigators with financial interests in organizations with such vested interests.

I have a more active solution than mere skepticism: building information systems of, by and for the clinicians to give a degree of independence from clinical trials that might be influenced or tainted by vendors or others with conflicts of interest.

An example of this type of endeavor is the Invasive Cardiology Clinical Database (ICCD) project I re-engineered at a 1,000+ bed medical center as Director of Medical Informatics, along with its executive sponsor, now Executive Director of Cardiology Services at a large healthcare system in the western U.S. The project, ineptly led by IT, was failing - to say the least. I took over at the request of the powerful Sr. VP for Medical Affairs, who apparently managed to outmaneuver internal opposition and got me hired.

I led a data model, application design and clinical implementation remediation process. The goal was an information system that met the needs of the clinicians regarding the way they practiced invasive cardiology (6,000 procedures/year), and that was also compliant with ACC and other standards for national reporting so the data could be shared via national registries.

This ICCD system enabled results reporting, outcomes and best practices analysis, and internal and external benchmarking. It contained items facilitating research such as definitive interventional procedure per lesion, catheter and stent performance and issues, great detail regarding lesion morphology and location, and followup data, all recorded at a high level of precision (several hundred well-defined data points in all). The dataset was developed in true collaboration with the clinician domain experts to meet their needs. This information system had the capability to provide independent confirmation of the performance of the new modalities in cardiology, on an ongoing basis.

An article by the executive sponsor and myself on this initiative is here.

Or, I should say, the "politically correct" version is at that URL. The less politically correct version is here ("MIS inadequacies in tough clinical environments: an invasive cardiology example.")

The major issue in this story is the performance of hospital's IT department, turning the clinicians' desire for such an information system into a clinical and political nightmare over a period of several years, as well as interference and obstructionism by the IT department and its CIO and COO (who IT reported to) in the remediation efforts I then led after my hire as Director of Informatics. The IT department and some excutives acted as an active enemy to this project, in large part due to turf and ego issues, as well as executive fears of "empowering the doctors" with respect to administration.

I recall frequent attempts to impede progress of our remediation initiative. I quite literally had to use strong-arm tactics I'd learned early in my career as Medical Programs Manager and Medical Review Officer (drug testing) in a large municipal transit authority's medical department in order to move this project to success.

It is my recommendation that every invasive cardiology/cardiac surgery center performing a good number of cases acquire or build this type of information system and do their own research on outcomes, and provide the data to specialty societies for pooling so as to maximize independence from those with pecuniary or other incentives to hide bad data.

However, strangely and regrettably, clinicians should be aware that doing so may entail potential warfare with those whose interests are in preserving their own healthcare "territory." That this is so is absolutely crazy, considering the stakes, but occurs nonetheless. The difference in ideology between clinicians and non-clinicians was never more clear to me than during this project. If I'd had firing authority, a house cleaning of that IT department would have been my first priority.

I should also note that the COO in question is now CEO of a major municipal hospital system. I can only hope that person has learned something about clinical informatics since the time of the aforementioned project.

-- SS

Medicine at war with ... the I.S. department?

Seen at the HISTalk web site, a site designed primarily for Healthcare's IT (computing) personnel, from an anonymous poster. I have been posting views on that site about the need for more clinician and medical informatics-based leadership of clinical computing projects:

From Anony-Mouse : "Physicians who haven't practiced often go right into sales or thought-leader positions expecting to earn the respect of their colleagues with their MD credential and 'been there, done that' claims, but they often develop overly complicated 'solutions' that no one uses. I enjoy Scot's perspective and find his articles thought-provoking, but I don't see anything in his credentials suggesting he's 'been there,' other than being involved in one EMR project. To imply that his skills or those of other informaticists are superior to those of lowly, undisciplined IT types is a fine example of his own rant, one whose tone and attitude furthers the narrow-minded and silo-creating thinking that plagues healthcare's social systems." (emphasis mine)

I had addressed the "you don't have enough experience" blocking-defense of the clinical IT world in this essay several years ago. Perhaps it is "insensitive" -- from that multi-culti socialist perspective - to imply that people with professional training and experience in two fields (medicine and computing) might perform better in clinical environments than those with training in one. (Patients, on the other hand, might favor the involvement of the former.) Perhaps IT personnel need to stifle their need for "sensitivity" where clinical matters are concerned as well as their argumentum ad hominem reactions to critique, which that posting had a touch of.

Another anonymous poster writes:

Scot - you are welcome to your opinion, wrong as it may be. I've been in this business for over 20 years and I've always said - give me someone with healthcare experience or IT experience...I'll teach him the other. You don't need someone with a PhD to configure an application.

I am not impressed by comments stating an opinion is "wrong" on the "argument from authority" ("I have 20 years of experience") alone. Concerning the "shrinkwrapped mentality" ... I'm not just talking about the tactical issues of installing a software application and configuring it, my concerns are about the strategic issues of clinical IT application design, development, iterative revision and other factors that give the installer something to 'configure.' The superficiality of the IT people wandering the hospital halls is sometimes startling.

Also, about the lack of 'need' for someone with a PhD or MD - I wrote about this attitude before as well at this page back in the late 1990's, partially in response to a large Healthcare IT recruiting company's written statement that "we don't believe a degree gets you anything."

Yet another anonymous poster writes:

... There are as many or more pretenders that are physicians who feign knowledge of the unbounded complications of the IT world merely because they are physicians. A medical degree does not imbue the owner of superior knowledge of IT initiatives, needs, systems, workflows functioning etc. but too often vendors and hospitals make an assumption that MD is identical to leadership and equivalent to information systems knowledge. The very opposite may be more true. Physicians are trained in diagnosing and treating patients but are often times the most unreliable in aligning business process with technology or the myriad of other issue that make up the Healthcare Information systems world.

While a few poster's views are clearly not indicative of a trend, I have more than one information point on this issue, e.g., here in observations from a few years ago, as well as observations by myself and other medical informaticists over the years in the field.

I am beginning - well, not just beginning - to suspect that:

1. In addition to the de facto warfare being conducted upon clinicians by payors, insurers, and various politicians and governmental agencies who control healthcare (not to mention the corrupt within healthcare itself), there may be another enemy: the hospital IT department and the EMR industry.

2. That there are those in hospital IT departments who are highly reactionary and unable to accept critique, and will guard their terroritory by any means necessary. To hell with patient care or clinicians as long as they "make their numbers." Medical informatics experts "don't have enough experience" (ergo, should not be hired).

3. There is a growing phenomenon of everybody and anybody in healthcare telling clinicians what they may say, do and think, what tools they need to practice, and who should give them those tools, and what form those tools should take. Now IT personnel think it's their turn.

This is a very bad trend.

-- SS

An Even More Tangled Web: "Development Cases," "Go-To Men," and Health Care Corporations

The Wall Street Journal excerpted (available here from the Providence Journal with free registration) a chapter from a new book, The Price of Admission by Daniel Golden. The book is about allegations of how major American institutions of higher education actively recruit children of the rich or famous, regardless of their academic qualifications, to enhance the institution's prestige or funding. (See the Washington Post's review of the book here.)

Full disclosure: one of the two universities the excerpted chapter discusses is my own alma mater, Brown University, where I currently have a voluntary faculty appointment.

The chapter otherwised focused on Duke University, and in doing so suggested yet another dimension of financial entanglements between universities, their top leaders, and health care corporations.

Over more than 20 years, Duke transformed itself from a Southern school to a premier national institution with the help of a winning strategy: targeting rich students whose families could help build up its endowment.
What makes Duke and Brown, among other institutions, stand out, is the way in which they ramped up and systematized their pursuit: rejecting stronger candidates to admit children of the rich or famous, regardless of their ties to the university.

Both schools had a behind-the-scenes power broker, a go-to man for prominent parents seeking to fast-track their children's applications. Duke had Joel Fleishman, 72 years old, a wine connoisseur who sits on boards of companies run by Duke donors and the parents of Duke students.
In the world of higher education, children of the rich and famous are known as 'development cases,' pursued by presidents and fund-raisers often to the dismay of admissions staffs. Duke landed the children of fashion mogul Ralph Lauren and other corporate titans. Some of them became major donors, helping boost Duke's endowment from 25th in 1980 ($135 million) to 16th in 2005 ($3.8 billion).

Mr. Fleishman has held numerous titles at Duke, from senior vice president to professor of law. His power at the university stemmed in part from a long association with Mr. Sanford, which dated to the president's days as governor. Mr. Fleishman's résumé also includes a variety of affiliations with nonprofit foundations and companies.

What it omits is his role at the vortex of development and admissions. Mr. Fleishman, who served as chairman of a 1983-92 fund-raising campaign that raised $221 million, courted potential donors and pushed to admit their children.

Mr. Fleishman also sits on the board of Boston Scientific Corp., whose chairman, Duke alumnus Peter Nicholas, is one of Duke's biggest donors. His three children graduated from the university.
Mr. Fleishman sits on more corporate boards 'than a lot of people, especially nonpresidents,' says J. David Ross, a former vice president at Duke. Mr. Ross says he believes the directorships weren't payback for admissions. Duke spokesman Mr. Burness says Mr. Fleishman 'is a person of considerable distinction and accomplishment, and it's no surprise that a number of leading nonprofit and corporate organizations have invited him to share his wisdom as a member of their boards of directors.' Boston Scientific declines to comment.

The entanglements in this case are clearly even more complex than those in the case of a medical school leader simply sitting on the board of a health care corporation.

Again, most of the public discussion about conflicts of interest in health care has been about practicing physicians getting pens and coffee mugs with company logos or take-out lunches from company representatives. Some has been about faculty members getting thousands or tens of thousands from consulting relationships or speakers' fees. These conflicts are very important.

Yet more complex and intense entanglements affecting top medical school officials and the university leaders to whom they report have up to now received almost no attention. Maybe they will now.

NIH Internal Audit Finds"Serious Misconduct"

We have posted frequently, most recently 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 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.

David Willman just wrote another article for the Los Angeles Times on the conclusions of an internal NIH investigation of Walsh. According to the article:

The internal review, conducted by lawyers and other ethics specialists within the office of the NIH director, found that from 1999 to 2004, Walsh received fees totaling $100,970 from pharmaceutical and biotechnology companies. He accepted fees from 25 companies and has led government-sponsored research involving some of those companies' drugs.

For Walsh, the first questions from NIH ethics officials centered on his arrangements with Merck. The NIH's internal review found that, at the same time Walsh accepted $3,000 in fees for attending separate Merck-sponsored events in 2000 and 2001, he was leading a formal 'cooperative research and development agreement' between Merck and the National Cancer Institute.
Months before his case was referred for possible disciplinary action, the NIH ethics review panel concluded privately that Walsh should not have engaged in the simultaneous government and paid arrangements with Merck.

'The review panel finds that the scientific subject matter of the activities overlap directly with Dr. Walsh's research at NIH,' the agency's chief ethics lawyer, Holli Beckerman Jaffe, wrote in June 2005.

'In addition, while Dr. Walsh was a paid speaker for Merck on two occasions, he was collaborating with Merck, and one of its competitors, in his official capacity,' Jaffe said. 'Accordingly, the panel finds his unapproved outside activities with Merck to be highly problematic.'

A subsequent summary of the NIH's internal review added, 'this situation is one in which a reasonable person could question Dr. Walsh's impartiality.'

The new documents show that when Merck paid Walsh a $2,000 fee in September 2000, it was to discuss the company's new antifungal drug, Cancidas, at a company-sponsored meeting with medical-opinion leaders in Montreal.

Four months later, Merck identified Walsh as a consultant at an FDA advisory committee meeting at which the company made its case for the drug's approval.

Walsh told the FDA committee on Jan. 10, 2001, that, based on his and his government staff's review of data from a Merck study, Cancidas effectively combats a fungal infection called aspergillus. The committee unanimously recommended approval.

Later that month, FDA staff approved Merck's application to market Cancidas. Through 2005, the drug had generated $859 million in U.S. sales.

And, in the months leading up to an October 2001 FDA advisory committee meeting on Pfizer's antifungal drug, Walsh received $12,000 in fees for conferring three times with company representatives, the internal NIH documents show. Walsh has said he did not accept company payment for appearing at any FDA meeting.

In summary,

'Dr. Walsh has engaged in serious misconduct, in violation of the Department's Standards of Conduct Regulations … and federal law and regulation,' the review concluded.

The previously unreported findings shed light on the depth of conflict-of-interest problems that have persisted at the NIH — the government's preeminent agency for medical research on humans. The NIH's handling of disciplinary decisions related to Walsh and other senior scientists is expected to be a focus of a congressional hearing scheduled for Thursday.

'Dr. Walsh fails to acknowledge that the reason for the 'complex set of rules' governing NIH staff in regards to real or potential conflicts of interest is to prevent the integrity of the agency and its science from being called into question,' the summary said. 'His assertions that his reputation is sufficient to dismiss any questions about his impartiality cannot be the standard that he or the agency use in deciding to adhere to well-publicized rules.'

The summary, dated in December, also said that Walsh's 'conduct continued over time and involved 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.'

Walsh's appearances at the FDA meetings — with representatives of Merck, Pfizer Inc., and Fujisawa USA Inc. — are the subject of a newly opened inquiry by the NIH director's Office of Management Assessment, according to people familiar with the matter.

U.S. conflict-of-interest law generally prohibits a federal employee from representing an outside party before a government agency, regardless of whether the employee accepts payment for the appearance.

Reached briefly by phone on Friday, Walsh referred questions to NIH press aides. He earlier declined to answer questions from The Times regarding details of his arrangements with several companies, but also said that he had never served as a representative or advocate for any pharmaceutical company.

The evidence continues to accumulate about the scope of conflicts of interest affecting top officials of the NIH, once the bastion of research integrity.

At least the stringency of NIH conflict of interest regulations has been restored by the current Director.

It would be nice if some of the other organizations that seem to be shot through with conflicted leaders, such as some notable prestigious academic institutions, might think about similarly stringent rules.

Were Late Stent Thromboses Really So Unexpected?

A flurry of report from the World Cardiology Conference in Barcelona, Spain have raised doubts about the safety of the currently very popular drug eluting stent (DES) as a treatment for coronary artery disease (CAD). Stents are used to maintain the patency of coronary arteries that are expanded after angioplasty (use of a balloon to expand the artery). The drugs eluted by the stents are meant to slow the growth of new tissue over the metal stents. Such growth can lead to narrowing of the artery.

However, apparently two studies reported at the Conference suggested that DES are more likely to incur blood clots than the older "bare metal" stents. Per the Newark Star-Ledger, "A Swiss-Dutch study tracked 8,146 patients and found that recipients of drug-coated stents were at increased risk of thrombosis, or blood clots, that occasionally can result in death. Two other Swiss studies, analyses of presented and published information discussed at the cardiology conference, also found that first-generation drug-coated stents had higher links to thrombosis compared to bare-metal stents."

Also, data has begun to surface from the stent manufacturers raising the same concerns. "Denis Donohue, vice president of clinical and regulatory affairs at J&J's (Johnson & Johnson) Cordis devices unit, said late stent thrombosis was an issue but there was not a clear safety signal. The company's own data showed long-term mortality rates of 6.5 percent for patients with a Cypher stent against 5.1 percent for bare-metal stents, but this was not a statistically significant difference. J&J submitted its latest data to the U.S. Food and Drug Administration last week, Donohue said."

In addition, according to the Boston Globe, Boston Scientific just revealed that its DES is associated with "a statistically significant increase in such clotting, or 'late thrombosis,' in patients receiving its stent. Compared with patients getting bare-metal stents, an additional one in 200 is likely to develop a blood clot, the company said."

The Globe also noted that Boston Scientific's Taxus stent "has been implanted in more than 2 million people worldwide," and that "the drug-coated stent is one of the most profitable medical devices in the word, bringing in more than $5 billion a year for its two main manufacturers, Boston Scientific and Johnson & Johnson."

It seems like almost every week we hear about some popular drug or device is found to have late adverse effects which no one heretofore expected. But should they have?

I took a quick look at the major published study that compared the Boston Scientific TAXUS stent with the bare-metal stent. (Stone GW, Ellis SG, Cox DA et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med 2004; 350: 221-231.)

The study was a randomized trial. Follow-up was nine-months. Major outcomes included death from cardiac causes, myocardial infarction (heart attack), and the need for a repeat procedure to re-open the vessel. The rate of all cardiac deaths was actually higher in the TAXUS group, 1.4% than in the bare-metal group, 1.1%. The paper did not report total mortality in either group. The article did not specifically address any other possible adverse effects of the stents, the procedure to implant them, or the drugs given to prevent blood clots. The study was funded by Boston Scientific. Five of its authors had financial arrangements with Boston Scientific, and another worked for the company.

So a strict evidence-based medicine reading revealed the study did not follow patients for a long time, so could not assess long term outcomes, good or bad. Furthermore, the article failed to report the total mortality rates of patients receiving different stents. This is a particularly curious omission in a study of a treatment meant to prevent some catastropic events that can be fatal. Thus, not only did the study fail to prove that the DES decreased mortality relative to the bare-metal stent, but it could not refute a hypothesis that the DES increased mortality. Finally, by failing to report various possible adverse effects of therapy, it could not refute a hypothesis that the DES had more adverse effects than the bare-metal stent. In summary, a strict EBM reading of one important article about drug-eluting stents would have raised doubts about whether the benefits of using DES outweighed its possible harms, and about whether DES are superior to other treatments of coronary artery disease.

Furthemore, in retrospect, one wonders why such an incomplete article appeared in print? One wonders whether unintentional bias was introduced because the company which had the most to gain from success of the DES sponsored the study, and because so many of the authors had financial ties to that company?

The lessons, again (see previous post), are that physicians must be very, very skeptical about the results of research sponsored by those with vested interests in the research turning out a certain way, and/or by research done by investigators with financial interests in organizations with such vested interests.

Bernadine Healy Takes Some Cheap Shots at EBM

Bernadine Healy MD, cardiologist and former director of the National Institutes of Health (NIH), writes a periodic health column for the US news magazine, US News and World Report, to which I subscribe. Imagine my surprise when I read her latest column, in which she slams evidence-based medicine (EBM), based on a mish-mash of misunderstandings, innuendo, and illogic.

Misunderstandings

EBM is Based Mainly on Randomized Controlled Trials (RCTs) and Cost-Effectiveness Analysis? -

Healy wrote,

'best' evidence, gleaned mostly from randomized clinical trials and cost-benefit studies, is the basis for what docs should or shouldn't do.

A quick definition of EBM is medicine based on critical review of the best available evidence from clinical research, combined with clinical judgment, knowledge of biology, and patients' values and preferences. (See also: "Evidence-Based Medicine: What It Is and What It Isn't" from the 1996 British Medical Journal for a better explanation.) Although most EBM advocates regard evidence from clinical trials, all things being equal, as more trustworthy than evidence from observational research studies, it is a relatively common misperception that EBM disregards evidence from other kinds of studies. I have never heard of EBM placing any special emphasis on cost-benefit studies.

EBM Ignores Biology and Patient Preferences? -

Healy wrote,

EBM sees itself as a major shift away from traditional medicine that emphasizes the expertise of the medical profession. That includes knowledge of the underlying nature of disease, mechanisms of therapy, basic and clinical research, and physician experience.

As noted above, most EBM advocates see EBM as incorporating clinical expertise, knowledge of biology, and patients' values and concerns. This has been expressed in many of the seminal articles on EBM.

EBM is an Attack on Physicians? -

Healy wrote,

The autonomy and authority of the doctor, and the subsequent variability in care, are the problems that EBM wants to cure.

She also wrote,

According to Marc Rodwin, professor of law at Suffolk University Law School in Boston, EBM puts experts trained in social science, public health, epidemiology, and economic analysis on par with physicians and 'breaks the lock hold' the profession has over how medicine is practiced and compensated.

Most of the early EBM advocates were physicians. Most of us physicians who support EBM see it as a way to empower individual physicians (and other health professionals, and patients) to independently make judgments about the best way to manage particular medical problems based on best evidence and logic, rather than edicts from above. There are certainly some epidemiologists involved in the EBM movement, which makes sense. I have never seen a large number of sociologists, non-physician public health specialists, or economists involved in the movement, and have never been aware they were trying to deprofessionalize physicians.

EBM is Cook-Book Medicine? -

Healy wrote,

patients are forced into a one-size-fits-all straitjacket

EBM advocates have taken pains to show that EBM involves using the best available evidence to make decisions for individual patients, based on each patient's unique circumstances, clinical context, values and preferences.

EBM is Meant to Support a "Microfascist" Ideological Agenda? -

Healy first wrote,

EBM carries its own ideological and political agenda separate from its clinical purpose.

Later she seemingly approvingly wrote about

a scathing commentary on the EBM movement in the International Journal of Evidence-Based Healthcare by Dave Holmes, a professor of nursing at the University of Ottawa. He and his colleagues argue that EBM is 'outrageously exclusionary' and even 'microfascism' in the way it sifts knowledge. Though harsh, he makes a point....

I wrote an extensive post on the article by Holmes et al (here). I wonder if Healy has any idea that she was agreeing with an argument that based on the authority of post-modernists like Deleuze, Guttari, and Foucault (and based on little else). I also wonder if Healy had any idea that she was agreeing with an attack on the biomedical research basis of health care. (Holmes et al wrote, for example, "The philosophical work of Deleuze and Guattari proves to be useful in showing how health sciences are colonised (territorialised) by an all-encompassing scientific research paradigm – that of post-positivism – but also and foremost in showing the process by which a dominant ideology comes to exclude alternative forms of knowledge, therefore acting as a fascist structure.")

Innuendo and Illogic

By writing that EBM emphasizes the "'best' evidence," with the word best in quotes, Healy implies that EBM uses an arbitary method to assess evidence. Later she wrote that EBM was "anointing only a small sliver of research as best evidence and discarding or devaluing physician judgment and more than 90 percent of the medical literature." She seems to have no idea about how much effort EBM advocates have put into developing clear, objective, logical methods to assess clinical research. For an example, see the 600+ pages of Guyatt G, Rennie D. Users' Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice.

Although Healy clearly acknowledges that an important element of EBM is addressing clinical research, she wrote that EBM is a "major shift" away from medical expertise, and included within the scope of that expertise, "clinical research." That's illogical.

Healy attempted to illustrate her concerns with two examples, the controversies over screening mammography and using PSA to screen for prostate cancer. Both examples had to acknowledge that some of the EBM based concerns about these screening tests were based on knowledge of the biology of the relevant diseases, contradicting her earlier assertion that EBM ignores biology. And neither controversy was resolved in a way that suggested some fault with EBM concepts. Note that Healy wrote that the mammogram controversy was resolved by political power, not necessarily by clear consideration of what was actually best for patients.

Summary

In summary, it is too bad that Dr Healy used her bully pulpit for such a cheap set of shots at EBM. As a former NIH director, she should know better.

EBM is actually a way to use logic and evidence to figure out the best way to help patients. It is the antidote to all the vested interests, ideological as well as economic, that seek to influence health care.

In that vein, could Healy's writing have been affected by her fiduciary duties to protect the interests of Invacare, obligated by her membership on its board of directors? (Invacare makes durable medical devices.) Could her writings have been affected by Dr Floyd Loop, her husband's fiduciary duties to protect the interests of Tenet Healthcare, obligated by his membership on its board of directors? I would suggest that she should have disclosed such financial interests when writing her column.

Massachusetts Hospital CEOs Cash In

In Time to Heal, Kenneth Ludmerer traced the evolution, if that is the right word, of the academic medical center from a relatively "flat" organization dedicated to service and academics to a large, complex quasi-corporation. Ludmerer wrote:

The new hospital administrators assumed business titles (president or chief executive officer rather than superintendent or director), demanded and received corporate levels of compensation, and retained hordes of management consultants.... A corporate approach began to dominate the institutional culture of the academic medical center.... It became increasingly difficult to distinguish some academic medical centers from the for-profit hospital chains and HMOs they so often criticized.

Christopher Rowland, reporting in the Boston Globe last week, documented the latest step in this process. It seems that nearly every CEO of a Boston "not-for-profit" hospital got at least $1 million in total yearly compensation in fiscal 2005. The article reported the following amounts of total compensation:

• James J Mongan, CEO of Partners HealthCare received $2.1 million in total compensation, up 10.5% from $1.9 million the previous year;
• Peter Slavin, Massachusetts General Hospital, $1 million, up 13.1% from $0.884 million;
• Gary Gottlieb, Brigham and Women's Hospital, $1 million, up 6.9% from $0.935 million;
• Elaine Ullian, Boston Medical Center, $1.37 million, up 54% from $0.886 million;
• John O'Brien, UMass Memorial Medical Center, $1.27 million, up 37% from $0.922 million;
• David M Barrett, Lahey Clinic, $1.25 million, up 32% from $0.945 million;
• Mark R Tolosky, Baystate Health, $1.24 million, from $1.03 million;
• James Mandell, Children's Hospital Boston, $1.07 million, up 9.9% from $0.979 million;
• Ellen Zane, Tufts-New England Medical Center, $1.05 million, who stared part-way through the previous year;
• Paul Levy, Beth Israrel Deaconess Medical center, $1 million, up 4.5% from $0.957 million.

Robert Haddad, Caritas Christi Health Care, just missed the million mark. He only got $0.933 million. Haddad, of course, was forced to resign his position at Caritas Christi after allegations of sexual harassment surfaced (see post here).

Note that both Zane and Ullian split their allegiances to their hospitals with their fiduciary duties on boards of directors of public for-profit health care corporations whose interests may conflict with those of their hospitals. Zane was recently appointed to the board of Parexel, the contract research organization that administered the disastrous TGN 1412 trial (see most recent post here). Ullian is on the boards of ThermoElectron, Valeant Pharmaceuticals, and Vertex Pharmaceuticals.

The rationale for the amounts received by the CEOs and the often considerable increases from the previous year were what one would expect. The Chairman of Partners (and of the board's compensation committee) reportedly asserted "Partners HealthCare and its member hospitals want to pay Mongan and other chief executives enough to keep them from being lured away by competitors and private industry." Furthermore, "Just because the hospitals are nonprofit doesn't mean they can afford second-class leadership. I really feel we're doing the right thing by paying these guys top dollar in the field." The Chair of the Boston Medical Center board said in a similar vein, "We wouldn't want someone to swoop in here from Cleveland and offer her [Elaine Ullian] three times the salary." A spokesperson for UMass Memorial "said O'Brien's compensation package is comparable to what top executives at other hospitals receive."

How quaintly old-fashioned seems the notion that leading a non-profit hospital is a sort of calling or community service that might inspire loyalty independent of a top-drawer corporate salary.

It seems that the boards of trustees of nearly every non-profit hospital in Boston believe they have absolutely superb CEOs who must be paid handsomely lest they be tempted to bolt out the door. Like the children of Lake Woebegone, all the hospital CEOs in Boston are considered (greatly) above average. Whether all the CEOs performed so brilliantly as to deserve their increased compensation was not further addressed in the Globe article.

The ever-increasing largesse afforded to hospital CEOs stands sharply contrasts how primary care physicians and other health professionals are paid. The average compensation given to primary care physicians fell about 10% adjusting for inflation from 1995 to 2003 (see post here.) A spokesperson for the Massachusetts Nurses Association responded thus to the compensation given the CEO of UMass Memorial, "it's obscene for him to take all that money when he's asking nurses who provide the bulk of care at that hospital to accept concessions."

A final contrast is with the extremely heavy work-load of physician trainees at these same hospitals. In JAMA this week is an article which documents how teaching hospitals have failed to reduce interns' work-loads in response to recent regulations. 15 of 16 teaching hospitals in Massachusetts, and hence nearly all of the hospitals listed above, were reported to have violated regulations restricting work shifts to no more than 30 hours, and work weeks to 80 hours, and mandating at least one day off a week during the first year the regulations were in force. (Landrigan CP, Barger LK, Cade BE et al. Interns' compliance with Accreditation Council for Graduate Medical Education work-hour limits. JAMA 2006; 296: 1063-1070.)

But since the CEOs are paid for their scintillating leadership abilities, maybe they can get around to fixing these problems this year.

Should Physicians Prescribe High-Dose Lipitor to Prevent Strokes?

The Boston Globe just reported about how Pfizer Inc, the world's biggest drug company, is "using the results of a study it sponsored to persuade doctors to switch patients to pricier doses of its blockbuster drug, Lipitor."

Pfizer has a simple strategy for maintaining market share: The company has sent thousands of sales representatives to doctors' offices to convince them that higher doses of Lipitor are more effective than generic statins in protecting patients' hearts. In particular, the sales reps point to a Pfizer-sponsored study that said Lipitor in high doses reduces the chance that stroke survivors will be stricken again.
'It's been part of our strategy that we ought to be encouraging physicians to move their patients to the higher doses,' Peter Brandt , Pfizer's newly promoted leader of US pharmaceuticals, told analysts in a recent call.

Pfizer also makes more money from higher doses of Lipitor. A 10 milligram Lipitor pill costs $2.44 . The 40 milligram and 80 milligram doses cost $3.33 apiece.

The Globe also noted that:

The Pfizer-sponsored study on Lipitor's impact on stroke was written by 11 authors who were either company employees or reported financial ties to it. The New England Journal of Medicine article linked daily , 80 milligram Lipitor doses with a 16 percent reduction in the risk of a repeat stroke.

An editorial, also published last month in the journal, could provide another driver for Lipitor revenue growth. The study adds to 'gathering momentum' that could convince insurers to count statin use as a measure of 'quality' after-stroke care, according to the editorial. Dr. David M. Kent , the editorial's author, reported receiving grant support from Pfizer.

But what does the study actually tell us? [The article was: The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006; 355: 549-559.] In the spirit of evidence-based medicine, let us examine how the study was done and what its actual results were.

In summary, this was a randomized controlled trial (RCT) which compared high-dose atorvastatin (80 mg/day) with placebo. Eligible patients were over 18, and had a stroke or transient ischemic attack (TIA) within one to six months. Patients with hemmorhagic stroke were "included if they were deemed by the investigator to be at risk for ischemic stroke or coronary heart disease." Patients had to be ambulatory, with at least somewhat preserved functional status (Rank score less than four), and had to have an LDL cholesterol between 100 md/dl and 190. Patients were excluded for a variety of reasons, including atrial fibrillation and sub-arachnoid hemmorhage, most of which were not specifically listed (and only found in a 2003 article which I could not find on-line).

Note that this study was not designed to determine whether lower dose atorvastatin, atorvastatin with dose-adjustment to achieve a particular cholesterol value, or treatment with another cholesterol lowering drug would affect the risk of stroke. Thus, one cannot tell whether any benefits conferred by atorvastatin at a fixed high dose could have been achieved with a lower dose, an adjusted dose, or another cholesterol lowering drug. Also note that the study's results may not apply to patients with conditions which would have excluded them from this study, but it is not immediately obvious who those patients might be.

The study's main results were as follows. The key result emphasized by Pfizer was that the rate of strokes in the patients treated with atorvastatin (265/2365, 11.2%) was lower than that in patients on placebo (311/2366, 13.1%) over an average of 4.9 years of observation. However, although the rate of ischemic strokes (those due to reduced blood flow) was lower in patients treated with atorvastatin compared with placebo (0.78 hazard ratio), the rate of hemmorhagic strokes (those due to bleeding) was higher in patients treated with atorvastatin (1.66 ratio). Importantly, the death rate of patients treated with atorvastatin (216/2365, 9.1%) during the study was higher than the death rate of patients given placebo (211, 8.9%), although the difference did not reach statistical significance, i.e., they could have been due to chance alone. Numerically more patients who received atorvastatin died from cancer, infection accidental or violent death, and "other causes" and "unclassified reasons" than did those who received placebo, although these differences also were too small to be statistically significant.

The article's discussion section noted the increased risk of hemmorhagic stroke, and suggested "the potential risk of recurrent hemmorghage should be considered when one is deciding to administer a statin to patients who have had a hemmorhagic stroke." I could not find data in the article, however, that indicated the risk of a hemmorhagic stroke after atorvastatin administration was only found in patients who had already had such a stroke. The discussion did not address the increase in total death rate in patients who received atorvastatin.

The accompanying editorial noted above [Kent DM. Stroke - an equal opportunity for the initiation of statin therapy. N Engl J Med 2006/ 355: 613-615] also attributed the increase in hemmorhagic strokes to the enrollment of patients with previous hemmorhagic strokes, and failed to mention the increase in total death rate in patients given atorvastatin.

These results are, in my humble opinion, troubling. The use of atorvastatin is being promoted as a means to reduce stroke, and other serious cardiovascular events. Such events can be fatal. If the only effect of the drug is to reduce these events, the death rate in patients treated with atorvastatin should be numerically lower, or at least no higher than that in those treated with placebo. Although it is possible that the increased death rate actually found was due to chance alone, it may be hinting at some adverse effect of the drug in this setting that may be offsetting its beneficial effects. Based on this single study, one cannot conclude that the overall benefits of high-dose atorvastatin for patients with previous strokes unequivocally outweigh the possible harms of the drug in this situation.

What are the lessons here? Per the Boston Globe, Dr John Abramson, author of "Overdosed America," suggested, "because this is a drug company-sponsored study, what we're seeing is just tunnel vision of the effect of high-dose Lipitor on stroke." I would agree that physicians ought to be very cautious about using this single study as a reason to prescribe high-dose Lipitor to prevent recurrent stroke.

This case, and numerous others discussed on Health Care Renewal suggest that

• studies sponsored by organizations with vested interests in the results coming out in a particular way ought to be interpreted with caution.
• physicians ought to be very skeptical about enthusiastic opinions about drugs expressed by authors who have financial arrangments with the drug's manufacturer
• physicians ought to be very skeptical about how those with products or services to sell interpret their own sponsored clinical research when marketing their wares

Another Case of Attempted Research Suppression: the Famvir vs Valtrex Study

Another story of apparent suppression of clinical research has surfaced, spotted first by Pharma Watch. The details come from an article just published reporting the results of two trials of famciclovir versus valacyclovir for recurrent genital herpes simplex (HSV) infections,(1) plus an accompanying editorial.(2)

Famciclovir (Famvir) was originally made by SmithKline Beecham, and valcyclovir (Valtrex) was made by Glaxo Wellcome. In 1997, SmithKline Beecham supported two clinical trials of Famvir versus Valtrex, under the assumption that Famvir would prove superior. It did not publish the results of these trials. When the firms merged in 2000 to form GlaxoSmithKline (GSK), US regulators forced them to sell Famvir to Novartis. This year, six years after the merger, and nine after the trials were conducted, their results were finally published.(1)

Briefly, the results of the first trial were that Famvir and Valtrex had similar effects on the rates of clinical recurrence, and on the time to clinical recurrence. Patients on Famvir manifested recurrence by laboratory test earlier than those on Valtrex. The result of the second trial was that patients on Famvir were somewhat more likely to shed virus than those on Valtrex. Thus, the clinical effects of the drugs were indistinguishable, while the laboratory data somewhat favored Valtrex, but the clinical significance of these results is debatable.
At the end of the trial report,(1) the authors noted:

We acknowledge that the process of analyzing data for publication beyond a study report and preparing a manuscript is labor intensive, and companies are understandably wary of devoting resources to a report that is not in favor of their product. We appreciate that Novartis Corporation made these data available after their own in-house review. Although we received data tables and listings for this study, we were not able to obtain data tapes to verify the analyses and to conduct what we consider the most clinically relevant analyses for these types of data, such as the monthly frequency of recurrent episodes or the frequency of days with lesions during the observation period.

The accompanying editorial observed:

These studies took over 7 years to publish and some of the analyses are limited. The role of the study sponsor in this report should be considered. The studies were originally funded by SmithKline Beecham when it owned the rights to famciclovir. A condition imposed by U.S. regulatory agencies permitting the merger of SmithKline Beecham and Glaxo Wellcome that created GlaxoSmithKline was that famciclovir (including these study data) be sold. Novartis was the eventual buyer of famciclovir. As stated by the authors, Novartis provided the authors with the study report and the data listings, but not the primary data itself. Was the delay in the release and publication of the study data a result of the corporate shuffling and movement of responsibility for the study data created by the sale of famciclovir? Alternatively, was it an effort to suppress potentially unfavorable data? Should the full dataset have been provided so that the authors could confirm the analysis and perform additional analyses? Is Novartis to be criticized for delaying and limiting the release of the study report? Alternatively, should Novartis be praised for permitting potentially unfavorable results to be published? The answers to these questions may depend on one's view of the pharmaceutical industry.

All authors of the trial report(1) acknowledged receiving research fjunding from SmithKline Beecham. One is currently a consultant to Novartis. The author of the editorial(2) received research funding from GlaxoSmithKline and Novartis, and is a consultant to GSK.

In summary, these studies' results failed to favor the product made by the company who originally sponsored them. That company delayed publication of the results for the following three years. When it transferred the product and the study data to another company, that company delayed publication for another six years. Eventually, the company transferred pre-analyzed data to the ostensible academic investigators of the study, who were not allowed access to the original study data.

The research sponsors' actions in this case resemble those of another sponsor of another study. That study's academic principal investigator was Dr Aubrey Blumsohn (see post here, and the links to earlier posts it contains, and Dr Blumsohn's Scientific Misconduct Blog). Unlike the investigators of the current study, Dr Blumsohn insisted on getting the raw data from his own study. His persistent efforts to do so got him fired by Sheffield University.

As we have said before, unreasonably delaying or attempting to suppress publication of results of clinical research betrays the trust of the research subjects. Research subjects usually volunteer with the understanding that results of research done on them would be published. Such results could only have been obtained because of their willingness to participate.

Furthermore, failure to let ostensibly academic investigators see and analyze the raw data from their own research undercuts academic freedom, and damages trust in the study's results.

Increasing numbers of research suppression by commercial research sponsors, usually pharmaceutical companies, unfortunately should make physicians very skeptical of all commercially sponsored research.

ADDENDUM (6 September, 2006) - See also related comments on the Scientific Misconduct Blog.

References
1. Wald A, Selke S, Warren T et al. Comparative efficacy of famciclovir and valacyclovir for suppression of recurrent genital herpes and viral shedding. Sex Transmitted Dis 2006; 33: 529-533.
2. Fife KH. Are the antiherpes nucleosides really all the same? Sex Transmitted Dis 2006; 33: 534-535

Case-Study: "The Rise and Fall of Natrecor"

Health Affairs recently published an article from the Division of Pharmacoepidemiology and Pharmacoeconomics at Harvard about the "rise and fall" or Natrecor [nesiritide], manufactured by Scios, as an example of what is currently wrong with how drugs are researched, marketed, and used. [Kesselheim AS, Fischer MA, Avorn J. The rise and fall of Natrecor for congestive heart failure: implications for drug policy. Health Affairs 2006; 24: 1095-1102.] Note that Scios was merged into Johnson & Johnson in 2003. We posted last year about problems with how Natrecor.

Kesselheim et al suggested:

Pre-Marketing Clinical Trials Are Not Designed to Provide Enough Data to Make Informed Clinical Decisions - Particular problems with the Natrecor trials were that they:

• Emphasized assessment of "intermediate measures," like laboratory test results, which may not predict the clinical effects of drugs. Trials of Natrecor were designed to measure pulmonary capillary wedge pressure (PCWP), a measurement of how well the heart is pumping, but not outcomes more meaningful to patients, like recurrent hospitalization or death.
• Excluded many of the patients who might be candidates for the drug in usual practice. In particular, trials excluded patients with diseases that commonly co-exist with heart failure, or patients taking drugs commonly used to treat heart failure.
• Were too small to have statistical power to assess clinically important outcomes, especially adverse effects. The less common an outcome, the more patients must be enrolled in a trial to determine whether differences in outcome rates across groups receiving different medications were due to the medications, or to chance alone. Some trials of Natrecor found more kidney problems or a higher death rate in patients who received that drug, but the authors dismissed these as "not statistically different," i.e., due to chance alone.
• Failed to report about possible adverse effects of drugs in an organized way. For example, published papers about Natrecor sometimes omitted mention of kidney problems that might have been due to the drug.

Marketing Encouraged Uses of the Drug Not Supported by Clinical Research - Particular instances cited by Kesselheim et al were:

• Print advertising in medical journals used graphics that suggested that Natrecor was a general treatment for CHF, "the heart's response to CHF is now recombinant therapy," rather than one that had only been tested in narrow circumstance.
• Journal articles advocated Natrecor for uses not supported by trial evidence. Kesselheim et al cited articles, "many underwritten by the manufacturer," that suggested using Natrecor as first-line therapy for CHF, as a chronic therapy for stable patients with CHF, and as first-line therapy for acute CHF in the Emergency Department. No trials had been done on the drug in these applications.
• The manufacturer of Natrecor, Scios, provided materials to physicians explaining how they could more easily bill for Natrecor given as an intravenous infusion to outpatients.
• The manufacturer supported continuing medical education (CME) activities that promoted Natrecor as a first-line therapy.

Without Organized Post-Marketing Surveillance, Adverse Effects May Not Be Quickly Appreciated - Kesselheim et al asserted "after a drug is approved, there is no organized post-marketing surveillance system in place." Perhaps the lack of such a system accounted for the four year time span from the approval of Natrecor to the appreciation of its hazards.
Natrecor sales were running $400 million in the year before its short-comings became clearer. This case-study illustrates how the current imbalance between the pharmaceutical industry and its regulators leads to the use of expensive treatments whose benefits may not out-weigh their harms.
This week, the New England Journal of Medicine published two articles about how primary care is imploding, particularly because of excess demands that far exceed reimbursement. (Commentary from Medical Rants here and here, and the articles are here and here.)
Maybe if pharmaceuticals (and devices, and many other health care goods and services) were priced more in proportion to their net benefit to patients, we could afford to pay doctors to take enough time to actually take care of all their patients' medical problems. Better evidence about the benefits and harms of goods and services to patients, more honest marketing, and more stringent regulation would help.
WHAT CAN BE DONE?
Kesselheim et al advocated a number of possible solutions at the policy level. There are some things physicians can do meanwhile:

• Learn enough about evidence-based medicine to understand the need for skepticism when applying the results of clinical studies to real patients.
• Become more skeptical of academic review and opinion articles financed by those with vested interests in the products or services advocated.
• Of course, do not forget that the point of marketing is to get physicians to prescribe or use particular products, not to provide a disinterested review of the evidence.

Pay for Malfeasance?

"Pay for Performance" (P4P) is the current fashion in health care management. It is claimed that P4P will improve quality and reduce costs. The burden of most P4P efforts falls squarely on physicians, especially primary care and other "cognitive" physicians, groups who are already faltering under considerable external stress. We most recently posted about P4P here, here and here.

Yet although "pay for performance" is an attractive concept, all things being equal, it hardly reflects how things work in the rest of the global >$2 trillion health care system.

Take, for example, the recent case of Schering-Plough (see our post here). The drug company just settled civil and criminal charges for about $435 million. Yesterday, the Wall Street Journal provided some additional coverage (here, but requires subscription).

According to the Journal, penalties in the recent settlement were divided. "Schering-Plough, of Kenilworth, N.J., will pay $255 million to settle related civil accusations. Its Schering Sales unit will pay a $180 million criminal fine." In addition, "Schering Sales agreed to plead guilty to one count of criminal conspiracy for making false statements regarding its price for Claritin as negotiated with a health plan and for lying to the Food and Drug Administration about its promotion of Temodar and Intron A. Except for that plea, Schering-Plough neither admitted or denied other wrongdoing alleged in the settlement." So, "'With this agreement, we are putting issues from the past behind us,' Brent Saunders, senior vice president of global compliance and business practices, said in a statement." The Journal noted, "A company's criminal conviction or guilty plea can often be fatal. But in its health-care cases, the government has repeatedly reached settlements that exact a guilty plea while avoiding the direst consequences. The guilty plea from Schering Sales means it can no longer sell drugs to the government, but its marketing functions have been taken over by other parts of the company, which are permitted to continue doing business with Medicaid and Medicare. Schering Sales 'is an entity whose sole purpose is to plead guilty in these matters,' said Mr. Saunders. 'Schering-Plough takes responsibility for the actions of the past while not putting patients in a position where they can't get important medications,' he said.

I certainly understand the public's interest in continuing the production of beneficial pharmaceuticals. But what is striking about this case is that no individual at Schering-Plough took responsibility for the company's admittedly criminal conduct.

A search revealed that the former CEO of the company, Richard Jay Kogan, did retire early in 2002 after a variety of allegations about the company's conduct surfaced. But as far as I can tell, he paid no other penalty, presumably getting to keep all his retirement benefits, stock options, etc. After Kogan left, the new CEO, Fred Hassan, made many management changes, so presumably other top managers retired early, or were even fired. However, I could find no record of anyone paying a clear penalty for the company's admitted criminal behavior, or for the losses that it incurred due to that behavior. Of course, it's possible that relevant law-suits are pending.

Some commentators have said that executive pay has gotten so ridiculous, and has so little relationship to any measure of performance, that it should be called "pay for pulse." (For example, see this commentary on the "5 lousy CEOs who got fabulous pay," including one famous pharmaceutical company CEO.)

So what would you call the failure of companies to apply negative incentives to executives who have presided over criminal behavior: "pay for perpetration?" "Pay for malfeasance?" I'll take some suggestions.

I am aghast at the hypocrisy that touts pay for performance for primary care doctors as a solution to all our problems, while silence reigns about pay for malfeasance by health care executives.

WHAT YOU CAN DO? - If you own stock in a public for-profit health care company that has recently admitted to misconduct or has had to make a huge financial settlement in response to civil litigation (see the Health Care Renewal archives for examples), demand changes in your company's governance such that negative incentives apply to the leaders responsible for these problems.

If you are a physician, demand that P4P must apply to the whole health care system if it is to apply to physicians.

And maybe everyone should write their congresspeople demanding better regulation of the leaders of health care organizations, at least sufficient to hold people responsible for their worst decisions.

"Money-Driven Medicine"

I don't get to do a lot of book reviews, possibly because I don't have a lot of time to read whole books. However, I have just finished one book that may be of particular interest to people interested about threats to physicians' core values, especially from concentration and abuse of power.

Money-Driven Medicine by Maggie Mahar (New York: HarperCollins, 2006) takes a broad look at what has gone wrong in US health care. Especially good are its sections on:

• The History from the Beginning of Medicare Through the 1990s - Mahar briskly starts with the background of Medicare, providing some important insights along the way. Of particular interest was how the AMA was originally equally opposed to "socialized medicine," and "corporate medicine." The organization, however, used up most of its political capital fighting the former, and hence was unable to resist the latter. Another fascinating tale was how commercial managed care arose (or was perverted?) from the original not-for-profit model, perhaps inadvertantly fueled by the demise of federal money that only went to not-for-profit HMOs.
• For-Profit Hospitals: the National Medical Enterprises Case - Mahar gives a detailed history of the case of National Medical Enterprises, a large, for-profit hospital chain that specialized in psychiatric hospitals and substance abuse facilities in the 1990s. NME was charged not only with run of the mill offenses like over-billing, but more exotic ones like kidnapping patients. NME eventually settled with federal authorities in 1994 for $379 million, and plead guilty to a variety of charges. Of course, no one went to jail, and the CEO walked away with a golden parachute. Thus, this case looked like the perfect precursor to newer cases discussed on Health Care Renewal. More striking, and what I hadn't realized, was that NME did not disappear. It didn't either go out of business or get swallowed up by some larger company. It simply changed its name - to Tenet Health, a company which has not been featured positively on this blog, and which seemed to repeat, in a broad sense, all the mistakes it had made before under a different name.
• Medical Devices: the Johnson & Johnson Charite Spinal Disc Case - Mahar again demonstrated that those ignorant of history are doomed to repeat it by narrating the more recent case of J&Js Charite spinal disc prosthesis.

Other chapters deal with the cost of competition, the hazards of over- and under-treatment, and the issues of quality, all worth reading.
In my opinion, the book's biggest weakness is its failure to dig into the causes of what it repeatedly identified as a fundamental problem, the irrational reimbursement system. However, given all that the book does address, that is a quibble.
In summary, Money-Driven Medicine provides vital background, clearly narrated, and should provoke a lot of thought about how we got ourselves into this mess, and maybe about how to get out of it.

After Revelations of Undisclosed Conflicts of Interest, a Journal Editor Steps Down

In July, we briefly posted about several cases in which articles published in prominent journals were discovered to have been written by authors who had relevant, but undisclosed conflicts of interest. One of those cases we summarized thus:

• An article was published in Neuropyschopharmacology in July about vagus nerve stimulation as a treatment for depression [Nemeroff CB, Mayberg HS, Krahl SE. VNS therapy in treatment-resistant depression: clinical evidence and neurobiological mechanisms. Neuropsychopharmacology 2006; 31, 1345–1355.] The Wall Street Journal discovered that eight of the article's nine authors had financial ties to Cyberonics Inc, the manufacturer of the device. The ninth author is an employee of the company, which was disclosed." (See previous post on Cyberonics here.)

In August, Bernard Carroll posted in more detail. He noted that the case involved more than the failure to disclose possible conflicts of interest, but also that one of the authors of the first draft the article was a hired writer, whose role was not fully disclosed; that "the review carefully followed the corporation's marketing message and branding language"; and that Cyberonics produced a press release touting VNS therapy featuring Nemeroff, but without revealing his financial relationships with the company.

Now the Wall Street Journal, and The Scientist reported that Nemeroff, who not only wrote the article in question, but was the Editor of Neuropsychopharmacology, will be stepping down from that role in December, "in part, based on the recent adverse publicity to the journal and the ANCP [American College of Neuropsychopharmacology]."

The Scientist also noted that "This isn't the first time that Nemeroff has hit the headlines for undisclosed financial ties. In 2003, a review he coauthored in Nature Neuroscience neglected to mention significant financial interests in three therapies that were reviewed favorably (including owning the patent on one of the treatments), prompting the Nature Publishing Group to widen its disclosure policies."

The Scientist quoted Clare Stanford, past President of the British Association for Psychopharmacology, "I don't believe for a minute that the fact the paper was funded by a company would have influenced his conclusions. It is unfortunate that he has had to stand down over this incident which is largely a reflection of the scientific community's paranoia rather than any failing of his professional integrity."

Is this all paranoia? We should note that cognitive psychological research suggests that even small gifts affect peoples' cognition. Research to this effect was one motivation for a widely publicized call for physicians to reject even gifts like pens and coffee mugs (see post here). If such small gifts to practicing physicians are so worrisome, what about more substantial conflicts affecting clinical researchers, or medical journals? Of course, the effects of conflicts of interest on judgments and decisions are often unconscious, so that those with conflicts really do believe that these conflicts do not affect them, perhaps explaining some of the resistance to even disclose conflicts. (See a summary from the Wall Street Journal via the Pittsburgh Post-Gazette.)

However, research summarized by Carl Elliott in the Journal of General Internal Medicine (see post here) suggested that disclosure is not the answer, and may make things worse. More cognitive psychological research suggested that people discount the amount of bias caused by conflicts of interest, and that disclosure may cause those with conflicts to be even more biased. Thus Elliot wrote, "the solution to the bias created by conflict of interest is not simply to disclose the conflict, which makes bias even worse. Rather, the solution is to eliminate the financial conflicts."

Amen.

Sometimes There Are Consequences

A depressingly large number of the posts on Health Care Renewal deal with cases of mismanagement, conflicts of interest, and even corruption that infrequently seem to result in proportional consequences to those responsible.

There have been a few recent exceptions, to a degree.

UnitedHealth Foray Into Running British GP Practices Blocked

We had previously posted about attempts by UnitedHealth in the UK to take over practices formally run by local GPs. These attempts seemed to be facilitated by bureaucratic bidding requirements that emphasized being able to produce reams of business-speak more than ability to deliver good patient care.

The Times (UK) just reported that the High Court has now blocked one of these attempts, the same one used as an example in our post. The Court found that the Primary Care Trust (PCT) which put the contract out for bid "had a duty to consult [with the local community] and they did not properly perform it." The PCT now must again put the contract out for bid.

"Naturopathic Physician" To Go To Jail

We had previously posted (here and here) about a local "naturopathic physician," who claimed to be able to treat a variety of conditions, including ones as serious as metastatic cancer, with harmless and effective natural treatments. Curran purported to do "live blood analyses," which lead to diagnoses of such things as "parasites" in the blood.

The Providence Journal just reported that Curran will be going to jail for 12 1/2 years. The judge said that Curran was "not your run of the mill scam artist," but "the worst of the worst," who "scared the living daylights out of people." At the trial, it turned out that not one of approximately 300 people who had the "live blood analysis" was given a clean bill of health.

Scrushy Must Re-Pay His Bonuses

Although former HealthSouth CEO Richard Scrushy was acquitted of federal fraud charges, we previously posted about his conviction by a state court for bribery, conspiracy, and mail fraud. Now the Associated Press has reported that Scrushy must also re-pay $47.8 million in bonuses he received from the company during years when the company was actually losing more than $400 million. The judge said, "without annual net income, Scrushy could not have had the opportunity to earn the target bonuses."

Summary

In my humble opinion, we need to restructure the health care system so that there are negative incentives for bad behavior, and that these incentives are proportional to the badness of the behavior. Individual health care professionals are subject to strict licensing requirements and can be sanctioned by state boards in the US for behavior that is short of criminal. However, the leaders of the biggest health care organizations can often walk off with golden parachutes even after egregious behavior, save for those few who end up with criminal convictions. Somehow, we need to ensure that there are big negative incentives for health care leaders, like Scrushy, who put lining their own pockets ahead of fulfilling their organizations' missions.

Schering-Plough Settles, Again, Again

'Tis the season to settle, so it seems...

Multiple media sources just reported that Schering-Plough has settled civil and criminal charges. Representative coverage is by the Boston Globe, and AP via the Houton Chronicle. The essence, quoted from the AP, follows:

Schering-Plough Corp. on Tuesday agreed to pay $435 million and plead guilty to conspiracy to settle a federal investigation into marketing of its drugs for unapproved uses and overcharging Medicaid for certain drugs.

Kenilworth, N.J.-based Schering-Plough said it will pay $255 million to resolve civil aspects of the previously disclosed investigation. A subsidiary, Schering Sales Corp., will pay a criminal fine of $180 million and plead guilty to one count of conspiracy to make false statements to the government. The agreement is subject to court approval.

Schering-Plough said the settlement resolves an investigation by the U.S. Department of Justice and the U.S. Attorney's Office in Boston that began before a new management team took over at the company in April 2003.

'With this agreement, we are putting issues from the past behind us,' said Brent Saunders, senior vice president for compliance and business practices.

The agreement comes two years after Schering-Plough agreed to pay $346 million to settle charges that it paid a kickback to a big health insurer to protect the market for its allergy drug, Claritin.

U.S. Attorney Michael Sullivan, who announced Tuesday's settlement in a news conference in Boston, said health care corruption 'erodes public confidence, compromises the patient/physician relationship and adds costs to important government programs.'

Investigators found evidence that Schering-Plough marketed drugs for so-called 'off-label' uses.... One such drug was Temodar, which the Food & Drug Administration in 1999 approved to treat anaplastic astrocytoma, a type of brain tumor, in patients who hadn't responded to other drug regimens. Sullivan said Schering promoted the drug to treat several other types of brain cancers and cancer that spread to the brain from elsewhere, which the FDA had not approved.

Saunders said the company has agreed to plead guilty to making false statements in marketing Temodar, related to its sales people promoting the drug to doctors for uses other than the approved one.

Investigators said they also found evidence of unapproved promotion of Intron A for the treatment of cancer on the surface of the bladder.

Drug manufacturers are required to report their best price on drugs provided to commercial customers, including HMOs, to the Health Care Financing Administration and to pay rebates to the Medicaid program to make sure Medicaid obtains the benefit of that low price.

Prosecutors said that from April 1998 through 1999, Schering Sales reported a false best price to HCFA to avoid paying millions of dollars in additional rebates to Medicaid.

The investigation also found evidence of pricing manipulation involving K-Dur, used to treat stomach conditions.

Notet that this was the second biggest settlement by Schering-Plough in two years. According to the Globe, it was the third big settlement in five years. The total that the company will pay out from all will be "about $1.3 billion."

It all is becoming so familiar, almost wearisome, yet the questions remain. Why do the mainly monetary penalties seem mainly to come out of the hides of stock-holders and consumers, rather than the people who actually made the decisions that lead to the offenses? And after all the indictments, prosecutions, settlements, and convictions involving large health care organizations, when will academics, policy makers and politicians, much less company CEOs and other organizational leaders admit we have a systematic problem here?

St Barnabas Settles

The New York Times reported on how yet another hospital system has settled federal charges that it over-billed Medicare.

The system in question is the St Barnabas Health Care System in New Jersey. According to the Times, the background is:

The problems began a decade ago, when hospital administrators around the country —facing cuts in reimbursements from managed care companies — turned to a handful of accounting firms that promised to help them maximize their financing from Medicare, the nation’s health insurance program for the elderly.

By exploiting loopholes in the complex formula that Medicare uses to reimburse providers for their most expensive cases, known as outliers, many hospitals’ federal aid doubled, quadrupled or increased 10 times.

As recently as the early 1990’s, St. Barnabas — which was named after a martyr who sold his possessions to help the poor, but is not run by the Roman Catholic Church — operated with a low-key business approach usually found at institutions that are licensed as nonprofit.

Faced with pressure from managed care insurance plans and the prospect of federal health care reform, the system’s chief executive, Ronald J. Del Mauro, voiced determination to firm up St. Barnabas’s financial stability. He preached a strict devotion to the bottom line and engineered a bold set of mergers and acquisitions.

The Times then described the allegations about how the hospital system inflated its Medicare billing.

According to depositions by a St. Barnabas consultant and two former employees, which were filed in the settlement, the drive for profits soon affected the Medicare billing, and hospital administrators found a way to capitalize on a loophole in the formula Medicare used to determine reimbursements in outlier cases.

One part of the equation was based on a hospital’s retail charges: the amount paid by the small percentage of patients who do not have insurance. By rapidly increasing retail charges for procedures often covered by Medicare, St. Barnabas got a steep increase in federal aid. As a result, its Medicare payments for outlier cases jumped to $287 million in 2002 from $85 million in 1998.

A consultant hired to work with St. Barnabas said in a sworn deposition that the hospital’s top executives held meetings to plan a “corporate directive” to increase federal aid by raising the prices charged to Medicare patients. The consultant, James T. Monahan, said that St. Barnabas had routinely added hidden charges to the room-and-board fees of Medicare patients and tried to conceal the windfall profits it was receiving from Medicare, in part by overstating its debt.

Mr. Monahan, who later filed a whistle-blower complaint under which he stands to gain millions of dollars from the legal settlement, declined to be interviewed for this article.

In settling the government's charges, the St Barnabas system admitted no guilt. "Ellen Greene, a spokeswoman for St. Barnabas, described the situation as the result of a misinterpretation of Medicare’s complex rules." Although federal prosecutors originally contended that the system over-charged Medicare by "at least $630 million from 1995 to 2003," the settlement requires payments of only $265 million. The prosecutors did not demand more apparently because they feared "a harsher fine might run the St. Barnabas health system out of business."

Legal actions in this case are apparently not over.

Two people who had been questioned by Justice Department investigators said they had been asked for documentation on how Mr. Del Mauro and two other top administrators at St. Barnabas are paid.

Mr. Del Mauro gets no compensation from St. Barnabas Hospital Center, according to its public filings, but he and two other senior administrators are paid officers of SBC Management, a profit-making company that does business with the hospital center. That sort of arrangement is common in the hospital industry.

In 1998, Mr. Del Mauro received $613,000 from SBC, according to documents on file with the I.R.S. His compensation was $4.7 million in 2003, the last year St. Barnabas received the huge Medicare overpayments. In 2004, it was $4.2 million.

On one hand, this case is a reminder that the excessively complicated Medicare reimbursement rules make disputes over payments more likely, and make it easier for hospitals (and physicians) to find loop-holes.

On the other hand, it is a reminder about how previously staid, low-key not-for-profit hospitals began to look and act more like "go go" for-profits, partially because they faced seemingly formidable competition from go go for-profit hospital chains. And as the character of not-for-profits changed, the actions of their leaders changed, possibly in response to their suddenly enlarging incentives, such as the six-fold plus increase from 1998 to 2004 in the St Barnabas' CEO's salary.

Yet the effect of such changes in corporate culture on health care costs seem to be overlooked. And although everyone seems to wonder why health care costs seem to continually rise, no one seems to want to discuss the somewhat understandable resistance of highly-paid people to any decreases in their standard of living?

The Post-Modernist View: Evidence-Based Medicine as Fascism?

As many of you realize, I am an advocate of evidence-based medicine (EBM), roughly defined as medicine based on critical review of the best availalble evidence from clinical research, combined with clinical judgment, knowledge of biology, and patients' values and preferences. (See also: "Evidence-Based Medicine: What It Is and What It Isn't" from the 1996 British Medical Journal for a better explanation.)

Some of us who advocate EBM see it as an antidote to health care based on dogma, ideology, or commercial interest.

Unfortunately, although EBM has generated a lot of enthuisiasm among its advocates, it has been a hard sell in the larger health care world. I have always suspected one reason for this 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 any case, by 2002, only about one-third of US and Canadian internal medicine residencies included any time for EBM (Hatala R, Guyatt G. Evaluating the teaching of evidence-based medicine. JAMA 2002; 288: 1110-1111.) In 2004, "now most medical programmes in the United States attempt to teach EBM, although few succeed...." ( Del Mar C, Glasziou P, Mayer D. Teaching evidence based medicine: should be integrated into current clinical scenarios. Brit Med J 2004; 329: 989-990.)

Thus my jaw dropped when I saw an article entitled "Deconstructing the evidence-based discourse in health sciences: truth, power and fascism." (Full citation: 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.) This article has already created quite a bit of buzz among those who are skeptical about post-modernism, and those who advocate for EBM, i.e., people like me.

The paper is written in the usual turgid post-modernist style, with all the expected bowing and scraping to Foucault, Derrida, Lyotard, Deleuze, Guttari, etc, the tortured sentence structures, and the obscure ("interpellated"), and sometimes apparently made-up words ("hysterisation").

The paper includes some almost hilarious accusations. As noted above, providing effective teaching of EBM in medical schools and post-graduate medical education has been difficult. In medical schools that I have seen, EBM advocates are a minority, sometimes embattled. Yet Holmes et al accuse EBM of being so powerful that "in a number of faculties of health sciences ... the dominant paradigm of EBHS [evidence-based health science] has achieved hegemony." Moreover, according to Holmes et al,

Rather than risk being alienated from their colleagues, many scientists find themselves interpellated by hegemonic discourses and come to disregard all others. Unfortunately,privileging a single discourse (evidence-based medicine (EBM)) situated within a single scientific paradigm (postpositivism) confines the researcher to a yoke of exactly reproducing the established order. To a large degree, the dominant discourse represents the ladder of success in academic and research milieus where it establishes itself as a weapon used against those who praise the freedom of scientific inquiry and the free debate of ideas.

Say what? I'm sure all those who struggled to get a few hours of EBM instruction into about one-third of internal medicine residencies by 2002 will be gratified to know that they are supposed to be on "the ladder of success in academic and research mileius." The notion that someone thinks EBM has been used to suppress free speech is just plain mind-boggling, although post-modernism has certainly been used to justify the suppression of free speech. (See, for example, the title essay in There's No Such Thing as Free Speech, and It's a Good Thing, Too by Stanley Fish.)

If anyone knows of such an institution, please tell me about it so I can apply there for a job.

Holmes et al also asserted that EBM advocates get "institutional promotions and accolades, public recognition, and state contracts of all kinds." Huh? Boy, I sure have missed out, and so have many of my friends and colleagues. At least in the US, EBM has not exactly been high on the priority list for federal government funding. (To add further irony, the article by Holmes at al was funded by one of those "state contracts of all kinds." Their paper was funded by the Canadian government, through the Canadian Institutes of Health Research- Institute of Gender and Health.)

But the paper goes from hilarious to nasty (which is why I don't believe that it was a hoax or a parody). The paper literally accuses advocates of evidence based health of being fascists,

Drawing in part on the work of the late French philosophers Deleuze and Guattari, the objective of this paper is to demonstrate that the evidence-based movement in the
health sciences is outrageously exclusionary and dangerously normative with regards to scientific knowledge. As such, we assert that the evidence-based movement in health sciences constitutes a good example of microfascism at play in the contemporary scientific arena. The philosophical work of Deleuze and Guattari1 proves to be useful in showing how health sciences are colonised (territorialised) by an all-encompassing scientific research paradigm – that of post-positivism – but also and foremost in showing the process by which a dominant ideology comes to exclude alternative forms of knowledge, therefore acting as a fascist structure.

Them's close to fightin' words.

Holmes and colleagues then specifically accuse the Cochrane Collaboration of being a fascist organization,

The classification of scientific evidence as proposed by the Cochrane Group thus constitutes not only a powerful mechanism of exclusion for some types of knowledge, it also acts as an organising structure for knowledge and a mechanism of ideological reinforcement for the dominant scientific paradigm. In that sense, it obeys a fascist logic.

Furthermore,

Fascism is not too strong a word because the exclusion of knowledge ensembles relies on a process that is saturated by ideology and intolerance regarding other ways of knowing.

To get more of tthe flavor of Holmes and colleagues arguments,

A starting point for health sciences would be to promote the multiplicity of what Foucault describes as subjugated forms of knowledge (savoirs assujettis): these forms of knowledge are ways of understanding the world that are ‘disqualified as non-conceptual knowledges, as insufficiently elaborated knowledges: naïve knowledges, hierarchically inferior knowledges, [and] knowledges that are below the required level of erudition or scientificity’ These forms of knowledge arise from below, as it were, in contradistinction to the top-down approach that characterises the hegemonic thrust of EBHS. For Foucault, a subjugated knowledge is not the same thing as ‘common sense’. Instead, it is ‘a particular knowledge, a knowledge that is
local, regional, or differential’

In our view, this positive process begins with a critique of EBHS and its hegemonic norms. As we have argued, according to postmodern authors, these norms institute a hidden political agenda through the very language and technologies deployed in the name of ‘truth’. Again, Foucault sums up this position in his critique of modern medicine: ‘Medicine, as a general technique of health even more than as a service to the sick or an art of cures, assumes an increasingly important place in the administrative system and the machinery of power’ Here, in such an ‘administrative system’ and a ‘machinery of power’, we find a classic allusion to what Hannah Arendt defines as totalitarianism or fascism, as we defined it earlier.

That should make Hannah Arendt, a true foe of totalitarianism, spin in her grave.

Finally, Holmes et al compared the language of EBM with "Newspeak" in 1984. I invite readers to read the article by Holmes et al, compare it to some article that is reasonably typical of those that advocate for EBM (such as the one from the 1996 BMJ linked above) and decide which is more like Newspeak.

The pity is that post-modernism's word-play mumbo jumbo and its cults of personality seem to be a great way for academic institutions to distract themselves from what is really going wrong with health care, the real threats to our professional values of the sort we have documented on Health Care Renewal.

Recovering from the brain fever induced by reading about "colonised (territorialised) science," "regimes of knowledge," "interpellated academics," and the "hysterisation of the female body," one might speculate: Has post-modernism been deliberately encouraged by some academic leaders, possibly those with the most severe conflicts of interest, to distract us from concentration and abuse of power in health care, the pervasiveness of conflicts of interests in health care organizations, and unethical and even illegal behavior by health care leaders?

If so, it's working.

ADDENDUM (25 August, 2006). See also the commentary in the Guardian (UK) by Ben Goldacre.