Tossing the Legionella Samples: A Case from the Homer Simpson School of Health Care Management

Sometimes you just cannot make this stuff up. Here are extracts of a story in the Pittsburgh Tribune-Review:

U.S. House members on Tuesday admonished Veterans Affairs officials from Pittsburgh for ordering the destruction of thousands of Legionella samples even as a researcher was attempting to save the 'irreplaceable' collection.

The destroyed samples represented nearly 30 years of medical research by Dr. Victor Yu, former chief of the VA's Infectious Disease Section, and Dr. Janet Stout, former director of the Special Pathogens Laboratory in Oakland and one of the nation's leading researchers in Legionnaires' disease.

During a congressional hearing held in Washington and carried live on the Internet, VA officials said they destroyed the samples because Yu and Stout did not provide a catalog of their research material after they were abruptly fired in July 2006.
The officials said they tossed the vials six months later, unaware of their research and diagnostic value.

Rep. Brad Miller, D-N.C., chairman of the House Science and Technology subcommittee on investigations and oversight, was not convinced.

E-mail records show Dr. Mona Melhem, the associate chief of staff for clinical services at the VA's Pittsburgh Health Service, ordered the destruction of the samples shortly after learning that Stout would arrive at the lab the next day to pick them up.

'The most troubling part of this story is that the destruction of this one-of-a-kind collection occurred less than an hour after Dr. Melhem learned that formal steps were being taken, on the following day, to transfer the collection,' Miller said.

'All of us may pay a price for this conduct, veterans most of all,' he added.

Rep. Dana Rohrabacher, R-Calif., accused the VA panel of tossing the samples out of jealousy and spite.

'Have any of you had that kind of accomplishment?' he said, raising his voice. 'Have you reached that plateau yet in your career? Or is it that you're just looking through the refrigerators of people who are involved in that kind of activity? ... We've got a bureaucratic attitude problem here.'

Melhem testified she had no personal problem with Yu or Stout.

She said she shuttered the Oakland laboratory where Stout and Yu worked because it 'was not productive and was a drain on clinical resources.'

Melhem insisted repeatedly that she did not know the thousands of vials -- each marked with letters and numbers and placed in racks -- were being used for research when she ordered staff to toss them. Melhem said she and staff found "a freezer filled with unidentifiable specimens," some of them stored in 'broken or unidentifiable tubes.'

Michael Moreland, who headed the VA Pittsburgh Healthcare System at the time, said he was unaware of the collection's significance.

Here are some health care managers who seem to have come from the Homer Simpson School of Health Care Management.

Whether or not closing the laboratory was justified, throwing out what appears to have been a scientifically collection of samples because it was too much trouble to figure out what they were reaches a new low in management dumbness.

This is what Enthoven's call to break the medical guild and turn over health care to professional managers has wrought. D'oh.

Commercial Funding of CME, and Distinguishing Babies from Bathwater

There has been quite a bit of discussion lately about how industry funding influences continuing medical education. One of our industrious scouts pointed out one of the most recent entries in this discussion, an article on this subject by the Editor-in-Chief of the Journal of the American College of Cardiology, Dr Anthony N DeMaria [DeMaria AN. Continuing education, industry, and physicians. J Am Coll Cardiol 2008; 52: 1035-1036. Link here.]

Dr DeMaria confessed to "very mixed feelings" about the move to end commercial support of CME. He felt that such commercial support did some good.

This support has been estimated to amount to nearly $1 billion per year and has enabled us to have the breadth and depth of learning opportunities we currently enjoy.

Although he acknowledged that commercial support "sometimes appeared to primarily serve the interests of the supporters," he felt that full disclosure would allow physicians to be properly skeptical of that support.

I have a further, even more basic, reservation about the proposal to end commercial support for CME. Inherent in such an action is the idea that physicians are like sheep: easily led and without the ability to recognize biased or slanted information. I find this demeaning to the profession. In my experience, physicians are more skeptical than naïve; by nature they are not anxious to accept, but rather are waiting to be convinced. Given the competitive demands entailed in becoming a physician, we are likely intelligent enough to recognize bias when it is present.

Thus, he also felt that terminating commercial support would be bad.

I worry that termination of all commercial support is a major overreaction.

I view the proposal to eliminate all industrial support of medical education as throwing the baby out with the bath water. I agree that certified CME should be objective and free of all bias, and I am not naïve enough to think that this has been fully achieved. However, I think there are other ways to accomplish this goal, and that we have the structure in place to be successful in the ACCME, medical societies, and academic institutions. Tightening existing guidelines and greater diligence to adherence should be adequate. Equally important, I think physicians are intelligent, savvy, and independent enough to know bias when they see it, and to resist recommendations that are not based on firm data. Physicians may not be perfect, but in pursuing continuing education, we have set an example for other professions to follow. Industrial support has helped to make this possible; let's think long and hard before we upset the cart.

First, note that this is yet another argument that physicians ought to be offended by the notion that they can be influenced by commercial relationships. I agree that maybe few physicians consciously alter their decisions and judgments according to their financial relationships with companies that have vested interests in selling health care products or services. But, common sense and experimental psychology suggests that such relationships can influence judgments and decisions even without conscious awareness of their effects.

Second, note that Dr DeMaria makes yet another argument that full disclosure can resolve conflicts of interest. However, there is also evidence from experimental psychology that disclosing conflicts may give people a license to further exaggerate their communication and actions in favor of their personal financial interests, and that recipients of disclosure may not know how to adjust for it adequately (see post here.)

I disagree with Dr DeMaria. I do not think the current approach, based on full disclosure as an adequate way to manage the conflicts caused by industry funded CME, and to manage conflicts of individual continuing medical educators, is adequate.

Finally, it appears that Dr DeMaria did not disclose his own financial relationships with commercial suppliers of health care goods and services. A bit of searching revealed that he serves or has served on medical advisory boards for CardioNet, Cardiodynamics International, and ResMed, on the scientific advisory board of BSP, and on the board of directors of Biosite. A disclosure for the American College of Cardiology ACCEL program also stated he has gotten modest (<$10,000) consulting fees or honoraria from "all echocardiography and ultrasound companies." He did not disclose these relationships in association with the article cited above, nor did he disclose them in conjunction with his role as editor-in-chief of the journal. A disclosure for a 2006 CME program included "Stock Options: Resmed, Biosite, Targe GW. Consulting Fees: Resmed, Targe GW, Vasomedical. Research Grants: Resmed, Acoufiant. Speaker: Acoufiant. Employment: Resmed. Ownership/Partnership: Resmed. Officer/Trustee: Resmed, Biosite. Receipt of Royalties: Resmed."

Although Dr DeMaria asserted that physicians are smart enough to recognize bias when they see it, it is not clear they could recognize the effect of financial relationships which are not disclosed to them at all. Dr DeMaria did not give his physician readers an opportunity to judge whether his defense of commercially sponsored CME might have been influenced by his own relationships with industry, nor did he give his readers an opportunity to judge whether his actions and writing as the editor in chief of a major medical journal were otherwise influenced by these relationships.

In my humble opinion, as I have said before, those who advocate particular health policy positions have the same obligation to disclose relevant conflicts of interest as do those who advocate particular approaches to clinical problems. Policy positions ought to be skeptically evaluated taking into account whether those expressing them stand to gain personally from what they advocate. Failure to adequately disclose conflicts of interest ought to inspire even more skepticism.

I fear much that today much of the health policy debate amounts to stealth health policy advocacy.

Furthermore, in my humble opinion, those who exercise editorial control over health care and medical journals have the same obligation to disclose relevant conflicts of interest as do authors of clinical research articles.

Finally, based on the experimental psychology study to which I alluded above, I doubt that even full disclosure of all conflicts in detail will allow adequate management of the conflicts of interest that now pervade medicine and health care.

BLOGSCAN - On the APAs "Long Traditions and Established Practices"

On Alison Bass' blog, this post discussed the ongoing US Senate probe of, among other things, the American Psychiatric Association's relationships with pharmaceutical companies. In a memo to its members, APA President Nada Stotland, seemed more concerned about the questioning of "long traditions and established practices" than about whether the questions were valid. In a final twist, although the APA publicized the existence of the memo, its content is not available to the general public.

An "Unfashionable" Pitch for More Academic-Industry Collaboration

The Wall Street Journal Health Blog reported

Marc Feldmann and Ravinder Maini, scientists from the Kennedy Institute of Rheumatology at Imperial College London ... [were] feted by Johnson & Johnson for work that paved the way for drugs called TNF inhibitors, used to treat rheumatoid arthritis and other inflammatory diseases.

The scientists won the second Dr. Paul Janssen Award for Biomedical Research, which carries a $100,000 prize and honors a legendary drug researcher at J&J.

Feldmann took the opportunity to opine on health science policy, making a pitch for even more cooperation between biomedical science and pharmaceutical and biotechnology companies.

From the podium at the New York Academy of Sciences, Feldmann made the case for closer collaboration between the drug industry and academia, not exactly the fashionable thing to say these days. Science, he said, is meant to be original and novel, while medicine is conservative and needs to be safe. The melding of the two is necessary for medical progress, but the process for doing so is 'ill-defined' and 'difficult.'

More efficient academic-industry interactions, he argued, would help increase the success rate for translating lab work into real-life medicine. The hurdles in the development of a drug that eventually became Remicade spoke to this notion. He and his colleague Maini approached several companies with their research on TNF before Centocor, bought by J&J in 1999, took them seriously.

Feldman said scientists understand the course of disease and how to make the most of innovative clinical trial methods, while companies understand products, regulatory requirements and marketing. The knowledge and skills are complementary, he said, and can 'augment success' for development of new therapies.

It was not clear from the article whether Prof Feldmann was only talking about collaboration on bench research, but the examples above suggest he was also talking about clinical research. In that case, he did not address the downsides of too much entanglement between companies who want to sell products and academics who are supposed to pursue the truth. These downsides, frequently discussed on this blog, include manipulation and suppression of clinical research by firms seeking results favorable to their marketing goals.

Feldmann's advocacy of policies to increase academic-industry collaboration ought to be viewed in light of his own relationships with industry. A quick Google search revealed that he is on the scientific advisory boards of multiple biotechnology companies, including Nuon Therapeutics, Receptor BioLogix Inc (note that only a cached version of their relevant web-site is available at the moment), and Trillium Therapeutics. He is a consultant to the research programme of Genesis Research and Development Corporation (see page 10 of this annual report.) He was also on the Roche Bioscience Advisory Board.

In my humble opinion, those who advocate particular health policy positions have the same obligation to disclose relevant conflicts of interest as do those who advocate particular approaches to clinical problems. Policy positions ought to be skeptically evaluated taking into account whether those expressing them stand to gain personally from what they advocate. Failure to adequately disclose conflicts of interest ought to inspire even more skepticism.

I fear much that too much the health policy debate amounts to stealth health policy advocacy.

BLOGSCAN - "Thyroid Storm" Revisited

On the Scientific Misconduct Blog, Dr Aubrey Blumsohn revisited one of the classic cases of research suppression from the 1990s, the attempted suppression of the study by Dr Betty Dong showing that a brand-name version of L-thyroxine was not superior to a generic version, also known as "thyroid storm."

"I'm Not a Hospital Guy Anymore"

Some of the issues most important to us at Health Care Renewal are how bad leadership and governance of health care organizations threaten physicians' core values, and thus help fuel our continuous health care crisis of rising costs, decreasing access, stagnant quality, and demoralized health care professionals. These issues are not often discussed in the "main stream medical media," but have been creeping in more often lately.

An important cri de coeur just appeared in the Cleveland Clinic Journal of Medicine, by Thomas F Lansdale III MD [Lansdale TF. A medical center is not a hospital. Cleveland Clinic J Med 2008; 75: 618-619. Link here.] Dr Lansdale dealt mainly with poor leadership of teaching hospitals that threatened the core clinical and academic mission.

The leadership was poor in that it was ill-informed about health care and its values, and perhaps incompetent:

Now the medical center, riddled with 'centers of excellence' instead of departments, answered only to administrators who cared nothing about medical education, except for the Medicare dollars they would lose if they cut the training programs. They spent enormous amounts of money marketing the centers of excellence, and they cut everything else to manipulate the bottom line.

Poor hospital leadership was abetted by poor leadership of accrediting agencies and insurance companies.

We struggled to keep up with the unending deluge of arcane demands from the accreditation organizations watchdogging our teaching efforts.

we capitulate to the for-profit insurance industry that informs us they won’t pay for day 4 of Mr. Jones’ hospitalization because he has failed to meet some arbitrary criteria in their manual.

The effects of the poor leadership were mediated through a stifling bureaucracy that ignored the health care and educational mission.

Nurses now cared for their patients by managing their own support staff, and spent much of their time entering useless information in the computer.

I couldn’t stand the management retreats in which we obsessed about 'customer service' while the waiting time in the emergency department ballooned to 12 hours because there were 'no beds.' There were plenty of beds, but no nurses to staff them.

Furthermore, as we have seen time and time again, managers were quick to suppress any criticism of their power.

I was marginalized when I protested the budget cycles bleeding out support of medical education in favor of the annual purchase of new scanners and surgical gizmos.

The results were:

Medical education slowly slipped from being a calling to folks like me, finally succumbing to bureaucratic lunacy. The pace of teaching and caring for acutely ill patients became intolerable.

The biggest casualty, of course, was the nursing staff. Underpaid, depleted of leadership and morale, they simply disappeared. They were replaced by agency nurses who worked their shifts and didn’t know the doctors or the patients.

We lurch toward physician computer order entry, clinging to the false belief that software programs will prevent adverse drug reactions and delivery of the wrong dangerous drug to the wrong patient. We understaff our pharmacies so that they can’t get the medications to the patients on time or alert us to our own prescribing errors. We burn out our nurses despite years of loyal service

So finally,

My real job is to do everything in my power to keep my patients out of the medical center. I walk the halls now and don’t recognize the institution I grew up in and came to love. Everywhere I look, I see not magic and promise, but dirt and danger.

I'm not a hospital guy anymore.

Read the whole thing, and weep.

So I get to say again: health care is reeling under poor leadership of increasingly large and dominant health care organizations, enabled by poor governance structures. We need to make health care governance more representative of its constituencies, accountable, transparent, and subject to ethical standards. We need health care leaders who are informed about health care and understand its values, are committed to the mission ahead of personal gain, and are unfailingly ethical and honest. Meanwhile, demoralized doctors and nurses succumb to foolish bureaucracy piled up by self-interested managers, and it is the patients finally who suffer the most.

StandUp4Pharma?

Many people in the US watched a telethon carried on all three major television networks meant to raise money for cancer research. The telethon was sponsored by StandUp2Cancer.org, a not-for-profit organization apparently run by a number of Hollywood celebrities, whose mission is to sponsor cancer research.

On the Schwitzer Health News blog, this post raised some questions about the purpose of the organization, and in particular noted that its "heroes" included GlaxoSmithKline and Amgen.

On perusal of the organization's poorly organized and not very functional web-site, I found a listing of the membership of its Scientific Advisory Committee, who will determine who gets research money from the organization. The committee included many notable scientists, but I also noted that it included four people who worked full-time for pharmaceutical or biotechnology companies:

• Julian Adams, Chief Scientific Officer, Infinity Pharmaceuticals Inc
• Richard B Gaynor, Vice President, Cancer Research and Clinical Investigation, Eli Lilly and Company
• Cecil B Pickett, President, Research and Development, Biogen Idec
• Laura K Shawver, Chief Executive Officer, Phenomix Corp

In addition, the board member biographies disclosed other members with financial ties to other such corporations:

• Philip A Sharp, Institute Professor, David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology also "co-founded Biogen (now Biogen Idec), Alnylam Pharmaceuticals, an early-stage therapeutics company and Magen Biosciences Inc., a biotechnology company developing agents to promote the health of human skin."
• Vicki L Sato, Professor of Management Practice, Harvard Business School, also is the retired President of Vertex Pharmaceuticals, and a current business advisor to Atlas Ventures "and other enterprises in the biotechnology and pharmaceutical industry." She is also a current member of the boards of directors of Bristol Myers Squibb, PerkinElmer Corporation, Infinity Pharmaceuticals, and Alnylam Pharmaceuticals.

Furthermore, a bit of searching the web revealed other financial ties of the scientific advisory board:

• Philip A Sharp is also, according to his CV, a Member of the Scientific Advisory Board of Sirtris Pharmaceuticals, 2003- ; Member of the Scientific Advisory Board of Fidelity Biosciences Group, 2004- ; Member of the Board of Advisers, Polaris Venture Partners, 2002- ; Chairman of the Scientific Board (to 2002) and member of the
  Board of Directors of Biogen Idec; Chairman of the Scientific Board and member of the Board of Directors of Alnylam Pharmaceuticals; and member of the Scientific Board and member of the Board of Directors of Magen Biosciences.
• Arnold J Levine, Professor, Institute of Advanced Study and Cancer Institute of New Jersey is also a member of boards of directors of Theravance, Applera Corporation and Infinity Pharmaceuticals, Inc, according to the Theravance web-site.
• Brian J Druker, Professor of Medicine, Oregon Health Sciences University Cancer Institute, is also on the scientific advisory board and clinical advisory board of Avalon Pharmaceuticals, per the company web-site; on the clinical oncology advisory board of Ambit Biosciences, according to this news item; and in 2003, disclosed consulting for and receiving honoraria from Novartis, in this article.
• Richard N DuBois, Provost and Executive Vice President, UT MD Anderson Cancer Center, also has been a consultant to Pfizer, and received honoraria from Axcan Pharmaceuticals, disclosed in this article; and disclosed consulting for Abbott, Novartis, and Salix in this article.
• Waun Ki Hong, Head, Division of Cancer Medicine, UT MD Anderson Cancer Center, is a member of the medical oncology advisory panel for Omnitura, according to the company web-site; a member of the medical oncology advisory panel for Genyous, according to the company web-site; on the scientific advisory board of GenVault, according to this news item; and on the scientific advisory board of Agennix, according to this news item.
• William G Kaelin, Professor, Dana-Farber Cancer Institute, is also a founder of Imigen Systems, according to this article; a member of the scientific advisory board of Nextech Ventures, according to the company web-site; and a member of the scientific advisory board of Arqule, according to the company web-site.
• Ronald Levy, Chief, Division of Oncology, Stanford University, is also a member of the
  scientific advisory boards of XTL Therapeutics, Therion Incorporated, Coley Pharmaceutical Group Inc., Xcyte Therapeutics, Agensys, Pointilliste, Cell Genesis, and Five Prime, according to his CV; and is also on the scientific advisory board of InNexus Biotechnology, according to this news article.
• Tak W Mak, Chief Scientific Officer, Princess Margaret Hospital, Campbell Family Institute for Breast Cancer Research is also a founder of Agios Pharmaceuticals, according to the company web-site, and on the scientific advisory board of Entremed, according to the company web-site.

The explanation by StandUp4Cancer.org of where the money it raises goes, and why, includes,

SU2C believes that it can benefit the most patients by accelerating the course of cancer research through raising philanthropic dollars and developing unique mechanisms to utilize these funds.

SU2C is committed to transparency and high-quality science in its funding activities and believes that this can be accomplished within the framework of a truly innovative approach to support SU2C-funded research.

However, of 19 people on the board that will control how this research money is spent, 4 were disclosed to work full-time for pharmaceutical or biotechnology companies, and two others were disclosed to have ties to such companies. Seven other board members had multiple, undisclosed ties to pharmaceutical or biotechnology companies. Thus, 13 of 19, a clear majority, including the board chair and vice-chair, had multiple and significant financial ties to pharmaceutical and device companies. Most of those ties were not disclosed on the organization's web-site. I did not watch all of the organization's telethon, but did not see anything approaching such disclosure in the part I did watch.

Where is the transparency there?

A major new effort to raise money to do research on the extremely important topic of cancer, supposedly devoted to transparency, should at least make clear what financial ties the people in charge of the effort have to companies that have commercial interests in selling cancer tests and treatments, and stand to benefit from particular research directions. This is even more important when appeals for funding are widely broadcast to an audience which may not be very sophisticated about biomedical and clinical research, and not in an easy position to determine who may be benefited from research that goes in particular directions.

A Wide Web of Healthcare Data: He Who Controls The Data, Controls the Playing Field

In posts such as here and here, it's become apparent that "Evidence Based Medicine" (EBM), while perhaps reasonable in theory, is probably unreasonable in practice with the ethics of healthcare in 2008.

One cannot have evidence based rules for anything, let alone healthcare, if the evidence is tainted.

Think clinical research and the drivers of "publish or perish" are the only domains where this evidentiary taint can occur?

Think again.

From a medical colleague, a talented ER physician:

Did anyone see that Wolters Kluwer (a leading multidomestic multimedia company with corporate office in Amsterdam) plans to buy electronic medical platform Up-To-Date?

Correct me if I am off track on the issue of the "full-circle web" of information exchange - an exchange that starts with the sanctity of the private physician patient relationship.

OK, I have a private relationship with my patient, but the perverse laws say that our relationship and the information ‘collected’ is no longer sacred. It may be used without consent under the guise of 'Treatment, Payment or Healthcare Operations' (TPO).

From the Miller School of Medicine Privacy & Data Protection project glossary:

HIPAA bundles a large number of functions into the term "health care operations." This expansive list is important for many reasons, most notably because HIPAA requires no permission from patients for uses and disclosures of protected health information (PHI) for "treatment, payment or health care operations (TPO)."

Covered entities may obtain a consent for TPO-related uses and disclosures, but the practice is optional under HIPAA. (It may nonetheless be required by state law.)

Additionally, the prescription information ‘exception’ from that sensitive relationship is fair game for the data-miners to sell to Pharmacy Benefit Managers (PBMs) and the like.

The so-called ‘Publishing’ company, Wolters Kluwer, who by the way unashamedly writes friend of the court briefs supporting the data merchants and miners (e.g., Amicus Briefs supporting the plaintiffs; IMS and Verispan), is now buying one of the most widely used point of care "Evidence based medicine" tools, Up-to-date.  This is a software application for physicians to practice ‘evidence’ base medicine.

Verispan is a subdiary of one of the largest EHR vendors, McKesson. Without sounding like a nut-case full of crazy conspiracies ...

Is not this bizarre web not only destroying the trust between the patient and the physician, but additionally eroding the trust of what actually is ‘evidence’ based medicine?

I thought the rigor of science was supposed to be the driver and best influence of my decision making process for my patients, not the pull of ‘Pharma and Friends’ puppet stings.

I guess as a physician I am just marginalized to an assembly-line worker for big Pharma.

As an aside:

1. the direct to patient(consumer) marketing expenditures of Pharma – est. $30 billion / year.
2. the entire NIH budget $28 bil/yr.

So, it seems, evidence based medicine is not only threatened by commercial taint of clinical trials and research, it's also potentially threatened by the drivers and behaviors of the Data Merchant component of the healthcare IT ecosystem.

Who polices them, I ask?

-- SS

Health Care Leaders at 30,000 Feet

The Times of Trenton (New Jersey, USA) reported this insight about the leadership of large health care organizations:

Bristol-Myers Squibb [BMS] is preparing to shut down its aviation operation at Trenton-Mercer Airport, sell four aircraft and dismiss about 32 employees as the drugmaker and leading Mercer County employer seeks to cut costs, according to sources familiar with the company's plans.

The company will sell its two Gulfstream V jets and two Sikorsky S-76C helicopters, terminate pilots, mechanics and other personnel, and move out of its hangar at the airport in Ewing.

Other corporations with aviation operations at the airport include Unisys and drugmakers Pfizer, Johnson & Johnson and Merck, Hughes said.

Bristol-Myers' two jets could sell for approximately $40 million each depending on their age....

The helicopters could fetch $6 million each, according to GlobalPlaneSearch.com and other sources.

It is understandable that BMS, having some rough financial times, and operating under a corporate integrity agreement (see post here), wanted to cut costs. This post is not about criticizing the company's plans to shut down its aviation operation.

What is striking is how this short news article opens a window into the lives of the top leaders of at least some of the largest health care organizations. (Note the reference to the aviation operations of Pfizer, Johnson & Johnson, and Merck in the article.) Although the article did not explain why BMS operated two Gulfstream V jets, and two Sikorsky helicopters, it is hard to see how they might be used other than to transport top corporate leaders in the style and with the convenience to which they have become accustomed.

Thus, this aviation operation symbolizes how top health care organizations have come to serve their leadership more than any other constituency. It may reflect the belief, heavily promulgated in the last two decades, mainly by these top leaders and their advocates, that CEOs and other top leaders are not like you and me. Their work is so important, their insights so brilliant, and their time so valuable that they do ought have to deal with the more mundane tasks of life, like waiting in an airport departure lounge for a delayed connection.

The notion that corporate CEOs and other leaders are inherently so brilliant and their time is so valuable can be argued.

More important, in my humble opinion, may be the effects on these particular organizational employees' values and beliefs of how they are buffered from real life. Remember that what used to be called "ethical pharmaceuticals" are meant to relieve symptoms, mitigate disability, and even sometimes cure the diseases of individual patients. Understanding how well they do so requires some understanding of the lives of the ordinary people who take them. Yet the leaders of pharmaceutical companies have now been increasingly protected from experiencing the vicissitudes of life that their patients or clients, or employees for that matter, experience.

In fact, the leaders of smaller, and even not-for-profit health care organizations may also be protected from such vicissitudes, although perhaps not quite so much as the CEOs of large corporations. For example, many presidents of the universities that house medical schools, while they do not have access to corporate jets, do live in fully staffed houses and are transported by university supplied cars driven by university supplied drivers.

I would argue that thus the leaders of these organizations come to identify more with their fellow members of the power elite than they do with patients, clients, students, employees, and health care professionals. Hence, their ability to understand at a gut level what health care is all about is diluted, especially as they sit in the back of their chauffeured automobiles, or especially in the luxurious cabin of a Gulfstream V at 30,000 feet watching the world go by below.

(For some idea of this experience, see the Gulfstream web-site here.)

Hence, I suggest that to improve the leadership of health care organizations, we must make sure that they have a better understanding of the real life in which their products and services are used.

Hat tip to Ed Silverman on the PharmaLot blog.

(For discussion of Pfizer's fleet of aircraft, see posts here and here by Dr Peter Rost, and this post on PharmaLot.)

"Docs Ditched After Undesirable Diagnosis"

From the Johannesburg, South Africa Star, this story, entitled "Docs Ditched after Undesirable Diagnosis," has some eerie echoes of the past:

When medical specialists diagnosed at least 10 cases of manganese-specific illnesses at a factory in Cato Ridge, KwaZulu Natal, the Assmang manganese company dumped them 'like hot potatoes'.

They replaced them with a new team of doctors that revised the diagnoses to suggest the sick workers might be alcoholics, drug abusers or victims of Aids.

All 10 workers had also been certified previously by the Compensation Commissioner as being permanently disabled as a result of manganism, an occupational disease caused by exposure to excessive levels of toxic manganese.

Another 27 workers, also earmarked by doctors as possibly suffering from manganism, were also 'cleared' by the new team of medical doctors and some were put back to work.

This emerged on Wednesday during the testimony of Dr Susan Tager to the Department of Manpower inquiry into worker sickness and toxic dust exposure at the factory.

Tager, a senior Johannesburg neurologist who heads the movement disorders clinic at Wits University, expressed surprise that Dr Murray Coombs, a new member of the Assmang expert panel, had rubbished her diagnoses - even though Coombs had not seen or physically examined any of the 10 workers and based his opinion on a review of their medical files. Coombs, from Elixir Corporate Health Solutions, is employed by Assmang as an occupational health consultant.

We have often discussed how health care organizations may try to shut up doctors who might say something that goes against their vested interests. In particular, we have frequently discussed how corporations that sponsor clinical research on their own products have suppressed research unfavorable to these products (see relevant posts here). But it seems like all sorts of organizations now feel free to try to shut up physicians who say things counter to their interests, whatever these may be.

We have also often discussed how health care organizations cultivate physicians who might help them market their products. Again, we have most often discussed how biotechnology, device, and pharmaceutical corporations may cultivate "key opinion leaders," who seem happy to to promote the organization's line, at least while wined, dined and paid well. But it seems like all sorts of organizations now feel free to recruit compliant physicians happy to say what the organizations want.

The eerie echo is of the case of Dr David Kern, fired from his academic position after he tried to present an abstract on a new occupational disease, now called flock workers' lung,(1) in a way that offended leaders of the company whose workers acquired the disease (see summary on the Scientific Misconduct Blog here).(2) That company also recruited a new physician to investigate the disease outbreak,(3) but as far as I can tell, he never put anything on the public record about the results of his investigation, and what happened to the patients with flock workers' lung is unknown.

Thus, both these cases illustrate how directly patients may be affected by companies eager to shut up physicians, especially physicians warning of occupational disease.

References

1. David G. Kern, Robert S. Crausman, Kate T.H. Durand, Ali Nayer, Charles Kuhn III. Flock Worker's Lung: Chronic Interstitial Lung Disease in the Nylon Flocking Industry. Annals of Internal Medicine 1998; 129: 261-272 (Link here.)

2. Shuchman M. Secrecy in science: the flock workers' lung investigation. Ann Intern Med 1998; 129: 341-344. (Link here.)

3. Fulks JR. Intimidation of researchers by special interest groups. N Engl J Med 1997; 337:1314-1319. (Link here.)

BLOGSCAN - More on the JAMA Commentaries on Physicians' Relationships with Industry

We recently blogged about Dr Marcia Angell's commentary about how the increasing influence of those with vested interests in selling products or services has "broken" the clinical research system. In the same issue of JAMA were two other commentaries. For further discussion of Dr Arnold Relman's call to end industry influence on continuing medical education, see this post by Dr Daniel Carlat in the Carlat Psychiatry Blog. For further discussion of all three JAMA commentaries, see this post by Merrill Goozner on the GoozNews blog.

BLOGSCAN - "Academic" Contract Research Organizations - What Will They Think Of Next?

On the Hooked: Ethics, Medicine and Pharma blog, Dr Howard Brody discussed an article in the British Medical Journal by Jeanne Lenzer about the increasing role that contract research organizations (CROs) are taking in clinical research. Particularly enlightening were the discussions of academic CROs, a species not previously much in the limelight. It seems that medical schools, academic medical centers, and even schools of public health, stung by the loss of industry sponsored research to for-profit CROs, have spawned their own line of extra industry friendly affiliates. It seems not-for-profit academic medicine is getting less and less distinguishable from their for-profit benefactors.

Dr Marcia Angell on Reforming a "Broken System" of Clinical Research

This week's Journal of the American Medical Association (3 September, the paper version of which seems to arrive early at my house) is notable for having three commentaries on relationships among physicians, academic medicine, and industry. One, by David Rothman and Susan Chimonas, seemed rather optimistic, while two, by Dr Arnold Relman and by Dr Marcia Angell, were quite dark.

The latter [Angell M. Industry-sponsored clinical research: a broken system. JAMA 2008; 300: 1069-1071. Link here when available] should be required reading for anyone who worries about the issues we raise on Health Care Renewal. Dr Angell provided an excellent summary of how commercial "sponsors" have come to dominate clinical research, and thus ensure that the resulting studies favor their vested interests. My only criticism of her summary of the data was that it may actually have been too optimistic. For example, Dr Angell focused almost exclusively on pharmaceutical companies' influence on research, while the problem is even larger. Biotechnology companies, device manufacturers, and multiple miscellaneous commercial suppliers of health care goods and services also may influence research. Dr Angell's admittedly extensive list of the kinds of relationships among researchers and industry (grant support, paid consulting, service on speakers' bureaus and advisory panels, and stock ownership) was incomplete, leaving out, for example, the even more acute conflicts of interest generated by service on companies' boards of directors and service as companies' officers.

But those are quibbles. Most striking was Dr Angell's summary:

Looking at this picture altogether, it would be naive to conclude that bias is only a matter of a few isolated instances. It permeates the entire system. Physicians can no longer rely on the medical literature for valid and reliable information. This is the conclusion I reluctantly reached toward the end of my 2 decades as an editor of the New England Journal of Medicine, and it has been reinforced in subsequent years. Clinicians just do not know anymore how safe and effective prescription drugs really are, but these products are probably nowhere near as good as the published literature indicates.

I am afraid I must concur, and also concur with her summary of the effects of the substitution for valid clinical research of pseudo-evidence favoring the vested interests of "research" sponsors:

Physicians learn to practice a very drug-intensive style of medicine.

Physicians are also led to believe that the newest, most expensive brand-name drugs are superior to older drugs or generics, even though there is seldom any evidence to the effect because sponsors do not usually compare their drugs with old drugs at equivalent doses.

Physicians learn to use drugs for off-label uses without good evidence of effectiveness.

Keep in mind that the same considerations apply to devices, so that physicians also learn to practice a test- and procedure-intensive style of medicine; are led to believe that the newest tests, devices, and procedures are superior to older ones without any evidence comparing the new to the old; and physicians learn to extend the use of tests, devices, and procedures far beyond what the evidence would support.

In addition, I agree with Dr Angell's advocacy of an independent body that would administer all clinical trials of drugs. Dr Angell suggested it be an Institute within the NIH. I think it might be possible to form a not-for-profit body that would be independent of government that would do the same thing. Furthermore, that body, or another in parallel should also administer all clinical trials of diagnostic tests, devices and procedures, for analogous reasons.

Finally, Dr Angell urged academic investigators and their institutions to "be at the forefront of efforts to reform the system of clinical research and not leave it to the government and legal profession." However, as Dr Angell previously noted, a majority of medical school faculty have financial ties to drug, device, biotechnology and other health care companies, as do a majority of department chairs. As we have noted, some top leaders of academic medicine serve also as top leaders of for-profit health care corporations (see this post), and other corporations whose products have profound effects on health, even tobacco companies (see this post). Many academic leaders make a small fortune working on the side for such companies. It may be too much to expect that such leaders would be at all interested in reforming a system that has so effectively lined their pockets. For better or worse, we may need a wholesale change in the leadership of academic organizations before we can expect any real cooperation from them in transforming clinical research from being mainly a marketing exercise to once more being real clinical science.

ADDENDUM (5 September, 2008) - See also comments by Dr Howard Brody on the Hooked: Ethics, Medicine and Pharma blog.

Response from author of "The ADVANTAGE Seeding Trial"

In response to my earlier post "Merck scientific debate hits bottom" I received the following from one of the authors of the VIOXX seeding trial paper The ADVANTAGE Seeding Trial: A Review Of Internal Documents, Ann Intern Med 2008", Dr. David Egilman, MD, MPH.

I posted Dr. Egilman's opinions below at his request. My own thoughts follow.

Dr. Egilman also posted numerous documents to and from Merck's lawyer at this link. (The tone of some of those documents towards Dr. Egilman is particularly disturbing, such as the one here.)

------------------------------------------------------

From: David Egilman, MD, MPH
To: Healthcare Renewal

I am one of the authors of the "Seeding" paper.

Merck executive Dr. Jonathan M. Edelman, Executive director, Global Center for Scientific Affairs wrote:

There's no doubt that the ADVANTAGE clinical trial had a legitimate scientific purpose. That purpose was to assess the gastrointestinal tolerability of VIOXX compared to naproxen – a commonly used arthritis medicine with known tolerability problems – in the treatment of patients with osteoarthritis in a primary care setting, and for the first time allowed patients taking concomitant aspirin to participate.

Dr. Edelman's claim that ADVANTAGE was the first trial that permitted aspirin use with Vioxx is incorrect. Study 058, which was part of Merck's application for new drug approval submitted in November 1998, permitted the use of up to 325 mg of aspirin per day. ADVANTAGE only permitted up to 100 mg per day. Study 058 was a 30 week trial. ADVANTAGE was only a 12 week trial. Study 058 involved patients older than 80, comparing Vioxx to namebutone (another NSAID) and was completed in April 1998, about 10 months before ADVANTAGE enrolled a single patient. Study 078, the ghost-written Alzheimer’s trial also permitted aspirin, began in April 1998 and was scheduled to be completed by April 2000 before the end of the ADVANTAGE trial. More patients took low dose aspirin in the Vigor trial than the Advantage trial.

Further, ADVANTAGE was not designed to test the effect of aspirin on anything. Although aspirin was permitted, the examination of aspirin effects was not included as part of the study objective which Merck described: "[t]o assess the tolerability of rofecoxib (VIOXX) compared with naproxen for treatment of osteoarthritis." On the other hand, Merck Study 136 was designed to test the effects of concomitant aspirin and NSAID use. This study revealed that Vioxx offered no GI protection to low dose aspirin users who constituted the majority of potential Vioxx users.

By November 1998, when Merck sought FDA approval for an OA indication and three months before the ADVANTAGE trial enrolled any patients, Merck had already informed the FDA it had sufficient studies to prove Vioxx was efficacious for osteoarthritis patients. Merck's osteoarthritis trials (that it used to get FDA approval for use of VIOXX in osteoarthritis patients) had compared Vioxx to 3 other NSAIDS. The VIGOR trial, which tested Vioxx and naproxen in rheumatoid arthritis patients, started at the same time as ADAVANTAGE and used twice the dose of Vioxx than was used in ADVANTAGE. VIGOR was, therefore, a more valid scientific trial to determine relative safety of the two drugs.

This request for and subsequent approval meant that Merck could claim VIOXX was as effective for pain as naproxen. Beginning long before the Advantage trial Merck claimed Vioxx was safer than all NSIADS including naproxen.

While ADVANTAGE was the first study that compared Vioxx to naproxen in OA patients, Merck had completed trials comparing the two drugs in other pain patients.

It is for these reasons that the President of Merck Research Laboratories (MRL) Dr. Scolnick characterized ADVANTAGE as "intellectually redundant."

Merck wrote:

ADVANTAGE was a double-blind, randomized, controlled clinical trial with a legitimate scientific purpose designed to answer previously unanswered questions about the use of VIOXX in osteoarthritis in a primary care setting. It was not a seeding study.

Merck’s personnel called it a seeding trial internally but in an apparent effort to hide its true purpose wrote:

“I eliminated the reference to seeding. It may be a seeding study, but let’s not call it that in our internal documents.”

Merck apparently tried to make it look like a typical science-based clinical trial to mislead IRBs and journals. All seeding trials make some claim to some usually trivial scientific purpose. For example the question of whether or not Vioxx works better on people as a function of height is a scientific question. It is of course a trivial question. In this case Merck had studies that compared Vioxx to naproxen for pain control before the Advantage trial had started. Merck also had a larger trial that tested GI toxicity.

Merck wrote:

ADVANTAGE was important because although the earlier VIOXX clinical trial program provided extensive data on efficacy and safety, it did not include naproxen as a comparison Medication.

This is not correct. Merck had a study that compared Vioxx to naproxen for pain control before the Advantage trial started. This was presented to the FDA in the original New Drug Application and was published in October 1999.

Merck wrote:

The ADVANTAGE clinical trial was designed, conducted, analyzed, interpreted and published by the scientific department of Merck's U.S. Human Health (USHH) organization, Clinical Development (CDP), in conjunction with participating investigators. CDP was part of the Medical and Scientific Affairs department of USHH and was separate from the marketing department within USHH.

A more complete picture is:

USHH was the marketing division of Merck. It included sub-divisions including sales, marketing and a medical/scientific group called CDP. CDP performed “medical” studies that could be used by marketing to increase product sales. These studies were only conducted if favorable results could increase sales. They were not done to obtain new indications for drug use and Merck did not publish or provide the FDA with some of these studies (example 106).

Mr. David Anstice, a marketing executive with no apparent scientific training or background was the President of Merck's USHH division. In contrast Dr. Edward Scolnick, a physician/scientist of international renown, was the President of Merck’s research division which was called Merck Research Laboratories. Mr. Anstice the person ultimately responsible for the Advantage trial testified:

Q. I understand that. All I'm saying is, this is the study [Advantage trial] that was initiated and conducted by marketing, right?
A. Yes, by doctors in marketing.

A picture being worth a 1000 words I provide the Merck graphic for the organization of the Advantage trial:



Here is the power point description of marketing’s role in the Advantage trial:



While the marketing division of USHH set the study “objectives” CDP was in charge of the technical aspects of study implementation.

Further proof that ADVANTAGE served little scientific purpose is the fact that Merck had already claimed that Vioxx was safer than and as effective as all NSAIDS including naproxen prior to the initiation of the ADVANTAGE.

Merck did not rely on any ADVANTAGE results to make any claim about Vioxx efficacy or safety to the FDA. The lack of scientific purpose behind ADVANTAGE is demonstrated by the fact that Merck had withheld the ADVANTAGE results from its application to the FDA that requested a label change that would allow them to claim Vioxx was safer than naproxen. Merck only produced the results after the FDA made numerous oral and written requests for the safety data discovered during the trial.

Merck claims Advantage produced important scientific information:

In the end, ADVANTAGE showed a different gastrointestinal profile between VIOXX and naproxen that was unaffected by concomitant use of aspirin. This was an important medical result for physicians. In addition to measuring the GI tolerability of VIOXX, investigators also monitored patients for adverse events, which were required to be submitted to the FDA. Therefore, in ADVANTAGE, Merck was further evaluating any potential risks of VIOXX.

In fact the trial that Merck performed to test the effect of concomitant aspirin and Vioxx use (136) showed that aspirin use thwarted Vioxx’s GI advantage. (Gastroenterology. 2004 Aug;127(2):395-402.) The conclusion Merck reached based on the Advantage result was wrong precisely because Advantage was not designed to test this question. This conclusion was based on data mining.

Merck wrote:

We also want to underscore that the scientific purpose of ADVANTAGE was properly disclosed to physicians-investigators, participants, and institutional review boards, and Merck's business interests were clearly understood.

Merck never disclosed the marketing purpose of the trial which included the fact that Marketing “set objectives.”

Merck accuses the authors of "bias.”

In this open letter to the editors of The Annals of Internal Medicine, Merck would like to put in perspective the latest article by four authors who served as paid consultants to plaintiffs' lawyers in the VIOXX litigation against Merck. We are troubled by the biased article, which contains numerous inaccuracies, and wonder about the motivation behind this attack on Merck's scientific excellence and integrity.

Merck writes that the authors were “plaintiff witnesses” and “cherry picked” documents. As far as I know, all litigation ended about a year ago. None of the authors were paid on a contingency basis, the authors received no compensation from plaintiffs to work on the papers we have written and none of the authors are working on any Vioxx litigation at this time.

If money motivation equates to bias then it is Merck and its representatives who suffer from this problem. The same cannot be said of Merck or its representatives because while the authors have nothing to gain Merck’s future earnings depend, in some measure, on its reputation for honesty.

Merck does not explain how any theoretical bias impacted on the paper. They have not come forward with contradictory documents or testimony.

The authors agree that all the documents should be made public so readers can decide for themselves if we “cherry picked.” Merck, and Merck alone, continues to block the release of the documents.

Merck would not allow us to cite documents that showed that Advantage investigators were accused of fraud and at least one was convicted. Some of this data was deleted from the published paper but readers and editors were never informed of these problems.

It should be noted that eight Vioxx patients had heart attacks during the ADVANTAGE trial compared to one patient on naproxen. Merck never informed any of these patient volunteers of the cardiovascular risks of Vioxx before or after the trial although the informed consent stated that Merck would pay for treatment of drug related side effects. Unfortunately for some, this would have been funeral costs.

Merck wrote:

It is unfortunate that the authors and journal editors chose not to contact Merck before finalizing these publications. Had any of these individuals contacted Merck, factual errors could have been avoided.

I contacted Merck's main trial lawyer Ted Mayer and provided Merck an opportunity to comment on another paper related to the Advantage trial before it was submitted for publication. I did not send a pre-publication copy to plaintiff lawyers. Mr. Mayer provided comments and i included his comments in the final version.

Merck then complained about my contact to Mr. Mayer to Judge Higbee and requested that she sanction me for contacting their lawyer and then insisted that I make no further contact with them.

-- David Egilman

-----------------------------------------

My own thoughts on all of this are as follows:

The lessons of the Annals article are clear. The scientific community and the public are simply fed up with cavalier practices in the biomedical industry. While the article may affect remaining VIOXX litigation as pointed out here, it also should have an necessary "cleansing effect" on drug R&D.

It was not clinicians and scientists outside the industry who earned it the public's animosity. It was, and continues to be, the industry itself. As Roy Poses observed, there cannot be evidence based medicine if the evidence is distorted by commercial zealotry. I think the public recognizes this.

Further, marketing personnel have no place in pre-approval, pre-marketing scientific studies such as clinical trials. If they have a scientific role, it is perhaps in post-marketing studies, especially post-marketing surveillance for adverse effects. The latter is a function the pharma industry performs poorly.

Even in that latter domain, there must be honesty and transparency, characteristics with which the biases of marketing and its leaders (e.g., towards maximizing sales) may interfere.

Merck's responses to this new Annals article seem the antithesis of science. Instead, the responses appear to be right out of the political and legal warfare playbook (where logical argument prevails - except when presenting logical fallacy is to the advantage of the protagonists) ...

The response has been this:

• ignore the arguments and evidence [in this case, emails and documents from Merck itself],
  
• issue an ad hominem attack,
  
• issue slogans ("litigation in the name of science"),
  
• present a Red Herring as a distraction,
  
• issue accusations of bias,
  
• issue accusations of cherry picking,
  
• issue accusations of the authors taking evidence "out of context", etc.

and finally:

• produce no context or new evidence of your own, hoping the above tactics will make that unnecessary.
  

All that's seemingly missing are ... puppets.

Merck seems to expect the "courtesy" of being allowed to be a participant in any issues written about its conduct, as if the authors of this paper are its employees who under employment policies must permit any pubs they produce to be reviewed internally for approval. I believe the company's executives forget that their authority ends at the front gate.

It is also an odd and even arrogant request, especially considering the way the authors' evidence (Merck's own emails and documents) was essentially ignored in the responses, and the insinuations promulgated against the authors as serving plaintiff's lawyers -- which also implies that scientific integrity and the interest of patients is not their motivation.

As I mentioned in my earlier post, this is classic ad hominem and is insulting to authors in my opinion, as well as insulting to any clinician or scientist. Why would anyone want to provide a company that acts in this manner the courtesy of pre-publication involvement in investigative journalism?

Another issue I find interesting is noted in the limitations section of the paper where it is stated that:

... we did not identify, despite an exhaustive and systematic search strategy, documents detailing discussions between the marketing and research divisions, nor could we identify documents describing contracts between Merck and collaborating companies.

As well as the Annals editor's obervations that:

... despite the large body of documents searched by the authors, they discovered few details about exactly how Merck's marketing division carried out ADVANTAGE.

This is surprising. From an information science standpoint, it would not be unreasonable to believe there might be more related to this trial of a major drug in emails or powerpoints or other documents. This document sparsity could mean that the documents did not exist, but it also raises a speculative question about the document corpus produced in Discovery.

Could "inconvenient documents" have selectively been eliminated from the corpus of documents before it was released, and therefore not be present in the corpus of documents the authors searched? Could the documents the authors did find represent ones that were "missed" by some weeding out effort?

Finally, I believe the entire tenor of Merck's responses - ignoring evidence, stating the trial was "published in a peer reviewed journal" as a Red Herring and a justification of its legitimacy while ignoring Sox & Rennie's (the Annals editors) accompanying commentary Seeding Trials: Just Say "No" , belitting the authors, etc. - is very disturbing.

From "Seeding Trials: Just Say No":

No one told Annals the true purpose of ADVANTAGE. We learned about it when we received a letter to the editor from Dr. David Egilman, who was a consultant to the plaintiffs' attorneys in the civil suits against Merck. He had access to publicly accessible trial documents, which included Merck employees' e-mail messages that disclosed the true intent of the ADVANTAGE trial ... The article provides clear evidence that the intent of ADVANTAGE was to increase prescriptions of Vioxx (the study outcome of greatest interest to Merck seems to have been Vioxx prescribing rates) ... The documents do tell us that deception is the key to a successful seeding trial.

When I review NIH grant applications, if I suspect deception I will mention it to the study section leaders, and I can assure that if deception is verified higher up the chain, that application will not get funded (at the very least). I can also assure that legitimate medical journals do not willingly publish studies involving deception.

Merck's responses to the Annals article seem to represent a belief that the public (laypeople and physicians) are stupid and gullible.

This is not science, and is not a path to a return to the corporate greatness and respect that Merck once enjoyed and had earned.

Finally, a Red Herring of my own:



-- SS

Merger Mania Redux: the Case of the Carilion Health Care System

The Wall Street Journal published an article on how one not-for-profit hospital system came to dominate its market, and the effects of that domination on local health care.

How the System Became Dominant

The WSJ article documented how a hospital merger created a vertically-integrated health care system. Note that in the old days of "merger mania," there was a lot of buzz in the health care research and policy circles about how creating such integrated systems to benefit quality and access, and lower costs. This rationale appears below.

In 1989, the U.S. Department of Justice tried but failed to prevent a merger between nonprofit Carilion Health System and this former railroad town's other hospital. The merger, it warned in an unsuccessful antitrust lawsuit, would create a monopoly over medical care in the area.

After the 1989 merger, Carilion continued to operate Roanoke's two hospitals separately. It later consolidated the hospital boards and in 2006, transferred most of Roanoke Community Hospital's staff and services to a renovated and enlarged Roanoke Memorial Hospital.

The moves eliminated any hospital competition in Roanoke proper....

[Carilion CEO Dr Murphy] was convinced that the cost and quality of care in Roanoke could be improved if doctors worked in a more centralized system. In June 2006, he announced a seven-year, $100 million plan to transform Carilion into a multispecialty clinic, like the Mayo Clinic.

Carilion began approaching private physician groups, offering to buy their practices and pay their salaries.

We shall see what effects CEO Dr Murphy's advocacy of more centralization had.

Effects on Costs

The domination by a single vertically integrated health care system apparently lead to rising costs.

Nearly two decades later, the cost of health care in the Roanoke Valley -- a region in southwestern Virginia with a population of 300,000 -- is soaring. Health-insurance rates in Roanoke have gone from being the lowest in the state to the highest.

That's partly a reflection of Carilion's prices. Carilion charges $4,727 for a colonoscopy, four to 10 times what a local endoscopy center charges for the procedure. Carilion bills $1,606 for a neck CT scan, compared with the $675 charged by a local imaging center.

Alan Bayse, founder of a local benefits-consulting firm who has sold health insurance in the area for 30 years, says health-insurance rates in the Roanoke Valley used to be 20% lower than in Richmond, Virginia's capital, and the lowest in the state. Today, he says, they are the highest in the state and 25% higher than in Richmond, citing rate information from insurer Cigna Corp. Anthem, another health insurer, says its rates are 6% higher in Roanoke than in Richmond.

Mr. Lionberger, whose construction company has about 100 employees, says his health-care costs have risen 50% over the past three years, hampering his ability to compete with contractors from other parts of the state.

While the increasing domination by the system been associated with increased health care insurance rates, its leadership has aggressively pursued patients who failed to pay their share of its exaggerated bills.

The Roanoke City General District Court devotes one morning a week to cases filed by Carilion. In its fiscal year ended Sept. 30, Carilion says it sued 9,888 patients, garnished the wages of 5,478 people and placed liens on 3,920 homes. Carilion says the people it takes to court have the means to pay their bills.

When some patients don't pay their bills, Carilion places liens on their homes. Carilion says it doesn't track how many liens it has outstanding, but the close to 4,000 it filed in 2007 'is representative of a typical year,' Mr. Earnhart says. Carilion doesn't foreclose on homes and only collects when properties are sold, he says.

Dr. Murphy says Carilion only sues patients and places liens on their homes if it believes they have the ability to pay. 'If you're asking me if it's right in a right-and-wrong sense, it's not,' he says. But Carilion can't be blamed for the country's 'broken' health-care system, he says.

Ah, yes, the "broken" health care system made me do it, says CEO Dr Murphy.

Decreasing Access

One effect of the merger seems to be a squeeze on physicians who are not part of the integrated system, which presumably will decrease, not improve access to health care.

Some doctors who chose to remain independent say the number of patients referred to them by Carilion physicians plummeted. Carilion controls a large proportion of Roanoke's referrals because it employs a majority of doctors who make them, such as family practitioners, pediatricians and emergency physicians.

Joseph Alhadeff, an orthopedic surgeon who is a member of a private practice called Roanoke Orthopedic Center, says the number of joint replacements he performed dropped off sharply after he stopped getting such referrals from Carilion doctors, prompting him to plan to relocate to Pennsylvania. 'I spent seven years building up a practice and watched it evaporate in six months,' he says.

In fact, it appears that the integrated system was out to decrease the business of physicians not in the system.

Geoffrey Harter, an ear, nose and throat doctor at another Roanoke private practice, Jefferson Surgical Clinic, says Carilion-employed colleagues told him the hospital system asked them not to refer patients to doctors it didn't employ, calling such referrals 'leakage.' Keeping referrals within Carilion is lucrative for the hospital system because it ensures tests and procedures performed on patients take place at Carilion facilities.

Dr. Murphy says Carilion uses the term 'leakage' in internal marketing discussions and that he would rather see its doctors refer patients to other Carilion doctors to optimize their care. But he says Carilion doesn't require its doctors to keep referrals in-house even though it would be legal to do so.

Meanwhile, as the integrated system grew more powerful, its leadership appeared to use other tactics that have become all too familiar to readers of Health Care Renewal

Silencing Criticism

As tension between Carilion and Roanoke's independent doctors grew in 2006, a group of 200 doctors formed an organization called the Coalition for Responsible Healthcare to protest the Carilion Clinic plan. The group posted a petition on its Web site and put up billboards around Roanoke that read: 'Carilion Clinic. Big Dream. Big Questions.' The local newspaper, the Roanoke Times, covered the controversy in a series of articles written by its health-care reporter, Jeff Sturgeon.

A few months later, in March 2007, the Roanoke Times moved Mr. Sturgeon off the health-care beat after Carilion complained repeatedly about his coverage. Carilion says it communicated its displeasure to the paper's editors, but never asked that Mr. Sturgeon be reassigned. Carilion withdrew most of its advertising from the paper, but says it did that as part of a reallocation of its ad budget.

Follow the Money

As the system became more dominant, and more profitable, more money accrued to its top leaders, particularly, of course, its current and former CEOs.

In 2001, Dr. Murphy took the nonprofit hospital system's helm. Dr. Murphy, ... has a medical degree from Harvard but doesn't practice medicine....

Fueled by large, untaxed investment gains, Carilion's profits have risen over the past five years, reaching $107 million last year. Over the same period, the total annual compensation of its chief executive, Dr. Murphy, nearly tripled to $2.07 million. His predecessor, Thomas Robertson, received a lump-sum pension from Carilion of $7.4 million in 2003, on top of more than $2 million in previous pension payouts.

Carilion says Dr. Murphy's compensation is in line with comparable health-care organizations and notes he doesn't receive car allowances, a spousal allowance or club memberships. It says Mr. Robertson's pension accrued over a 32-year career at Carilion.

Members of Carilion's board of directors also seemingly profited from their relationship with the hospital system. The WSJ documented some major financial relationships among the hospital and companies in which board members had an interest.

A large part of the clinic conversion's costs have involved the construction of a new medical campus around Roanoke Memorial Hospital that began several years earlier.

The lead contractor building the site is Swedish construction giant Skanska. But one of the project's biggest beneficiaries has been J.M. Turner & Co., which is owned by Carilion board member Jay Turner. Carilion says it paid J.M. Turner a total of $14.9 million in direct contracting work from 2004 to 2007.

Dr. Murphy says Carilion's board authorized 'arm's length work' with J.M. Turner, but adds that "a case could be made that we shouldn't award work to J.M. Turner to avoid the appearance of impropriety."

Mr. Turner isn't the only Carilion board member with a financial stake in the new medical campus. Another board member, Warner Dalhouse, has invested in a hotel being built on the campus to accommodate patients and their families. HomeTown Bank, a local bank Mr. Dalhouse founded and of which he was until recently chairman, is financing the hotel's construction. Dr. Murphy and Mr. Turner sit on HomeTown Bank's board.

Carilion and Mr. Dalhouse say he didn't make his $130,000 investment in the hotel until after Carilion sold the parcel to Texas developers in early 2006. 'I wasn't dealing with Carilion. I was dealing with the new owners of that land who had paid fair market value for it,' Mr. Dalhouse says.

Management versus Mission

The Carilion Health System's statement of mission and vision are as follows

Mission Statement

Carilion Health System exists to improve the health of the communities it serves.

Vision

- Assure accessible, affordable, high quality healthcare that meets the needs of the community
- Motivate and educate individuals to improve their health
- Champion community initiatives to reduce health risk

Yet, the investigative reporting by the WSJ has shown how the increasing domination of local health care by the Carilion Health System has made health care less accessible and less affordable, despite its leaders' proclamations to the contrary. It has "educated" the local newspaper to reduce its critical coverage of the system's activities. Thus, the bigger and more dominant the health care organization, the more mission-hostile its leadership is likely to be. Meanwhile, increasingly mission-hostile leadership tends to become increasingly lucrative for its practitioners.

I submit that if we really want better quality, more accessible, more reasonably priced health care, we need to bust the new health care "trusts." We need smaller health care organizations with ethical leadership truly devoted to the health care mission. We need organizations whose governance is representative of key constituencies; accountable to patients, health care professionals, and the public at large; open and transparent; and which upholds clear ethical principles.

BLOGSCAN - "Be the Power," Never Mind the Data

Available in 3 parts on the Clinical Psychology and Psychiatry Blog (here, here, and here), and in one part on PharmaLot, is a video apparently used for training Merck pharmaceutical sales representatives to sell Vioxx (rofecoxib) to doubtful physicians. The strategy seemed to be to use flash and bluster to avoid dealing with concerns that Vioxx was no more effective a pain reliever than generic non-steroidal anti-inflammatory medications (NSAIDs) like ibuprofen and that Vioxx caused adverse effects, including myocardial infarction. Although waving around graphically fancy sales brochures was advised, dealing with the shaky data for clinical research (some of which later turned out to be gimmicked in favor of Vioxx) was not. Tell me again that story that pharma sales reps serve an educational function.

No Denying the Haunting of the Medical Literature

There was a remarkable series of letters in the latest JAMA(1). They, in turn, were responses to an article by Ross et al about ghost and guest authorship of articles about rofecoxib [Vioxx, by Merck](2). (See our post about that article here.)

Two of the letters were notable because they came from the lead authors of articles that Ross et al described as ghost-written.

First was a letter by Hawkey, which said in part,

From my own publications, I was surprised to see references 79, 94, 96 and 108 as having been in a Merck publication status report since these were reviews independently invited by Lancet, Balliere, Gastroenterology Clinics of North America, and Gut respectively, and involved no contact with Merck beyond usual request for all relevant sources for information.

Second was a letter by Ferris, Galasko, and Kirby, which said in part, (referring to an article by Thal et al discussed by Ross et al)

The 3 alleged guests in fact played substantial roles: conceiving and designing the study (Thal), confirming accuracy of the primary study end point as a member of the end point adjudication committee (Ferris), and enrolling 109 patient (Kirby). The paper was initially drafted by Merck coauthors in August 2003, after discussion of the results had previously taken place with Dr Thal and Dr Ferris in June and July of 2003. Drs Thal, Ferris, and Kirby were formally approached about being coauthors on the paper and an associated abstract in September 2003. Each critically reviewed the complete statistical report and contributed to the revising the final manuscript.

Before I go further, let me say a little about how scholarly articles are customarily written when no guest and ghost authors are involved. For all the articles I have authored, the first author was the researcher who was in charge of the overall study, or at least was substantially in charge of the study component reported by the article. The first author always wrote the first draft of the manuscript, possibly getting help from other authors or medical writers, but always being overall in charge. The first author always took responsibility for the final draft and published version of the manuscript. The second and third authors were generally those most involved with the relevant project, and with rewriting the manuscript.

This process seems very different than that used to write the articles discussed above.

Note that neither Hawkey nor Ferris, Galasko and Kirby claimed to be the principal investigators of the relevant projects, to have written the first drafts of the manuscripts, or to be those with the final say on the final drafts or published versions of the manuscript. Furthermore, none denied that Merck authors wrote the first drafts of the relevant manuscripts or that Merck authors had substantial responsibility for the content of the published papers. Hawkey claimed to have had "little contact" with Merck, but that did not preclude Merck authors from writing the first draft, or taking substantial responsibility for the content of the manuscript. Ferris, Galasko and Kirby claimed to have had some roles within the research project, but did not individually or collectively claim to be the project's principal investigator or to be substantially iin charge of the project, and did not deny that Merck authors wrote the first draft and took substantial responsibility for the content of the manuscript.

Thus, these letter writers did not deny that they had failed to do the work and take the responsibilities normally entailed by first authorship of scholarly manuscripts. Nor did they provide any evidence that the claims made by Ross et al about the ghost authorship of their papers were incorrect.

On the other hand, Hawkey and Ferris, Galasko and Kirby did take the opportunity to fulminate about the original JAMA article. Hawkey criticized Ross et al for failing to "systematically evaluate" all the articles in their Table. Ferris, Galasko and Kirby decried "this unsubstantiated allegation of guest authorship" which raised "questions about the flawed methodology in the study by Ross et al."

It is ironic that the financial disclosures for the letters by Hawkey, and by Ferris, Galasko and Kirby used 24 lines of type. Dr Ferris alone disclosed being a former or current consultant to 32 pharmaceutical, biotechnology or similar corporations.

What is most troubling, in my humble opinion, about the letters discussed above is that their authors could not bring themselves to directly address the core issue raised by Ross et al: evidence that they used their good names and academic reputations to cloak articles generated for commercial purposes in the guise of scholarship.

The larger questions are: how much of the clinical research database and the body of scholarship on which physicians and patients base their decisions was commercially generated, but deceptively promoted as produced by academics only interested in the discovery and dissemination of the truth? Furthermore, how many respected academics have built their careers and reputations on the work of unnamed employees of commercial health care firms, and thus what should we make of their supposed scholarship? And finally, on a personal note, how many honest academics have been crowded out of the competition for the support and dissemination of their work by faux scholars who claimed as theirs work done by others for commercial purposes?

As was said on the PharmGossip blog, it may be time for a truth and reconciliation committee that will allow us to put these deceptive ways behind us. To better care for patients and better advance science, we need medical scientists who put allegiance to the truth ahead of allegiance to their personal financial gain.

ADDENDUM (27 August, 2008) - See also comments on Science-Based Medicine blog.

ADDENDUM (2 September, 2008) - See also comments by Dr Howard Brody on the Hooked: Ethics, Medicine and Pharma blog.

References

1. Guest authorship, mortality reporting, and integrity in rofecoxib studies. JAMA 2008; 300: 900-906. [Link here.]

2. Ross JS, Hill KP, Egilman DS, Krumholz HM. Ghost authorship and ghostwriting in publications related to rofecoxib: a case study of industry documents from rofecoxib litigation. JAMA 2008; 299: 1800-1812. [Link here.]