We posted a number of times about questionable practices Eli Lilly used to market its atypical anti-psychotic drug Zyprexa (olanzapine). A post from 2007, with links backward, is here, and our most recent post is here. The company remains entangled in litigation over its marketing of this drug. That litigation has lead to the release of numerous internal documents that provide quite a view of Lilly's marketing practices. Bloomberg continued its reporting on these documents, with its latest effort here via the Boston Globe, describing yet another surprising way this drug was sold:

A unit of CVS Caremark Corp. used its access to doctors to market Eli Lilly & Co.'s Zyprexa antipsychotic while it was under contract to bargain with the drug maker on behalf of health insurers, internal Lilly files disclosed in a multibillion-dollar lawsuit by insurers show.

The subsidiary of CVS, the largest US drugstore chain, touted Zyprexa starting in 2003, according to e-mails made public by lawyers suing Lilly for overpayment. CVS's AdvancePCS, a pharmacy benefit manager, or PBM, offered to send 120,000 letters to doctors promoting the drug, Lilly's top-seller with $4.7 billion in sales last year, according to a confidential 2004 proposal. The CVS unit said it would charge $5 per letter.

AdvancePCS, acquired by Woonsocket, R.I.-based CVS in 2007, said in the documents that the direct-mail campaign was 'designed to influence key prescribers' as part of a 'tactical plan for Zyprexa.'

Furthermore,

In AdvancePCS's 2004 pitch to Lilly offering to send out letters promoting Zyprexa, Kevin Aholt, the company's assistant vice president in charge of strategic alliances, said he could target physicians based 'on the most recent AdvancePCS claims data,' according to the unsealed documents.

Aholt also said that one of the 'key issues' in the market for antipsychotic drugs was finding ways to 'accelerate the growth of new patient starts,' according to the proposal.

Also,

Steven Fuchs, an official at the PBM, asked Lilly officials in an April 2004 e-mail whether he should include information about Zyprexa's ability to calm agitated patients in the next round of letters to doctors.

'Would a discussion of that be something you would want to include?' Fuchs asked, according to the document.

Lilly marketing executive Scott Dell responded in an e-mail that officials at the drug maker had discussed asking AdvancePCS to include material highlighting 'the new bipolar maintenance indication for Zyprexa.'

AdvancePCS was not the only pharmacy benefits manager (PBM) that offered to help sell Zyprexa.

CVS rival Express Scripts Inc. also sent out Zyprexa marketing letters, according to the unsealed documents and also isn't named as a defendant in the suits.

So here we have at least two pharmacy benefit managers (PBMs) offering to help market a particular drug, for money, of course. What is the problem here?

CVS's contracts with insurers and pensions meanwhile place it in an adversarial posture with Lilly, requiring it to use its buying power as leverage in drug-price negotiations.

'The problem is that PBMs are negotiating these hidden deals while at the same time telling employers that they represent them at the negotiating table,' said Gerry Purcell, a former PBM executive who advises companies on their drug plans. 'These documents will add fuel to the perception that the companies and the PBMs are in cahoots with each other.'

Also,

While PBMs negotiate on behalf of insurers, most states don't designate them as agents of the benefit plans, said Robert Garis, a pharmacy professor at Creighton University in Omaha who studies the industry. As a result, they aren't legally required to act only in the best interest of their clients, he said. Maine is one of a few states that have specified PBMs as fiduciaries, or agents, he noted.

'The companies have gotten around that by adding language to their contracts that exclude them from having to meet those fiduciary duties,' Garis said.

Apparently, in this case, one PBM said it disclosed its relationship to the drug company to physicians, but it is not clear whether it was disclosed to the health care insurers and managed care organizations which paid the PBM to reduce the costs of drugs:

CVS, which isn't a defendant in the Lilly suit, said that it tells doctors when it has 'financial relationships' with drug makers and that they are free to opt out of mailings.

'To engage in a point/counterpoint in a media outlet rather than in court would not be productive,' said Lilly spokeswoman Marni Lemons.

Lemons declined to answer specific queries about the CVS or Express Scripts letters, whether Lilly paid for the practice, or other questions raised by the unsealed documents....

CVS said in its e-mailed statement that it has 'no active educational programs' related to Zyprexa.

'CVS Caremark discloses to its PBM clients that it may have financial relationships with pharmaceutical manufacturers in connection with these educational programs,' said Christine Cramer, a spokeswoman for the chain. 'CVS Caremark's PBM clients are aware of these programs and have the opportunity to opt out.'

Maria Palumbo, a spokeswoman for Express Scripts, didn't respond to eight telephone and e-mail requests seeking comment.

CVS covers 82 million people, with a market share of 12 percent, and is the largest pharmacy benefit manager, according to Atlantic Information Services. Express Scripts, which covers 55 million people, is the fifth largest. PBMs process about 75 percent of the retail prescriptions written annually in the United States, according to the insurance plans.

The insurance plans sued the drug maker in 2005, contending it used researchers, pharmacy benefit managers, advocacy groups, and public agencies to promote Zyprexa.

Whether or not the PBMs disclosed their relationships to the pharmaceutical company to everyone who might be interested, it does seem that having PBMs who are supposed to help insurers and managed care organizations control drug costs be paid by pharmaceutical companies to market drugs is yet another new species of institutional conflict of interest. Like the many other conflicts of interest, individual and institutional, we have discussed, this one appears to be mutually advantageous to the parties involved. However, it could have adverse consequences for physicians, patients, and the health care system. If the organizations that are supposed to be controlling drug costs are also promoting expensive drugs, the likely result would be excess prescription of expensive drugs to patients who may not derive benefits from the drugs outweighing their harms.

This is another reminder how much we need more sunshine shone on the multitudinous conflicts of interest affecting just about every type of actor within the current US health care system.

Here is another case to raise questions about the true goal of some medical societies.  As reported by Alicia Mundy in the Wall Street Journal in late June,

A medical researcher and two medical groups with financial ties to Sanofi-Aventis SA have asked federal regulators to hold off on approving generic forms of a Sanofi blood-thinner....

Citing potential patient safety issues, the head of the Society of Hospital Medicine and a medical researcher at Duke University last month sent letters to the Food and Drug Administration contending that Lovenox is too complex for any generic maker to copy fully.

Earlier this year, another Sanofi-sponsored medical group, the North American Thrombosis Forum, sent two letters in favor of Sanofi's position opposing generic Lovenox. None of the letters mentions the signer's financial support from Sanofi.

Two small drug companies, Amphastar Pharmaceuticals Inc. and Momenta Pharmaceuticals Inc., filed applications to the FDA in 2003 and 2005 respectively seeking to sell generic Lovenox, called enoxaparin.

Of course, the two medical societies involved denied that there was any relationship between their support from Sanofi-Aventis and their concerns about the safety of biogeneric medications that might compete with a Sanofi-Aventis product (which, as the WSJ article noted, "had global sales of $4.57 billion in 2009").

Laurence Wellikson, chief executive of The Society of Hospital Medicine, which represents doctors who coordinate patient care, said his letter to the agency 'was based entirely on the best evidence-based medicine available and the collective experience of SHM's senior hospitalists.'

Also

Ilene Sussman, executive director of the North American Thrombosis Forum, said the group's doctors are concerned about generic Lovenox, and its letter was independent of Sanofi.

The CEO of the SHM denied even a responsibility to disclose the Society's support from Sanofi-Aventis:

Dr. Wellikson said it wasn't necessary to disclose that the group receives financial support from Sanofi because its letter 'focused on providing the best, most effective care to the hospitalized patient.'

In fact, the SHM web-site includes a "disclosure of organizational support" page which suggests Sanofi-Aventis provided somewhere between $200,000 to $800,000 for three projects of the Society's projects, "pharmacoeconomics," "improving glycemic control," and "preventing VTE." The latter presumably could have something to do with anti-coagulants such as Lovenox. (The numbers are vague because the statement only discloses the amount of support provided in broad ranges.) Thus, support by Sanofi-Aventis could provide as little as 2.7% or as much as 11.1% of the Society's total income, which was noted to be $7,203,596 in its 2009 Form 990 filed with the IRS, and publicly available via Guidestar.

Given the broad mission of the SHM

SHM is dedicated to promoting the highest quality care for all hospitalized patients. SHM is committed to promoting excellence in the practice of hospital medicine through education, advocacy and research.

one wonders why it would want to get officially entangled in the approval process for specific biogeneric drugs.  If the leadership of the Society is so concerned about the safety of anti-coagulants, one wonders why they did not speak up about the case of the lethal contaminated heparin, about which we have blogged extensively, most recently here.  (I can find nothing on the web to suggest the Society, or Dr Wellikson, ever noted any concerns about this issue.)  Of course, that case involved heparin sold by Baxter International, whose production was out-sourced to a questionable supply chain.  SHM also receives support, amounting to something between 0 and $100,000, according to its "disclosure of organizational support" page, from Baxter International. 

Thus it appears that the leadership of SHM was very concerned about the safety of an anti-coagulant manufactured by a competitor of Sanofi-Aventis which could threaten that company's revenues from the drug, while Sanofi-Aventis is one of the Society's major financial supporters.  On the other hand, the leadership seemed unconcerned about the safety of an anti-coagulant sold under the Baxter International label, while Baxter-International is also one of the Society's major financial supporters.  So it is hard to tell whether the leadership is more concerned about the safety of anti-coagulants, or the financial interests of the drug companies that support it. 

The problem with the funding of health care professional societies by health care corporations that sell products or services that doctors can prescribe or order is that it raises the suspicion that such societies may use their considerable influence to serve the corporations', not patients' interests, and so undermine the professional values of the societies' members.  For this reason, Rothman et al suggested that such societies sever most of their financial ties to such corporations.(1)  (See our blog post here.)  As long as the SHM chooses to accept support from drug and device companies, questions will be asked about the effects of such support on how the Society uses its influence.  Furthermore, assertions that such support is so irrelevant that the Society need not even disclose it will only fuel more suspicion.

If ostensibly mission-driven not-for-profit health care organizations, like health care professional societies, but also including medical schools, academic medical centers, and patient advocacy groups, want the public and health care professionals to believe that they really are mission-driven, they need to spurn funding from organizations with vested interests whose service might distort these missions.

References

1. Rothman DJ, McDonald WJ, Berkowitz CD et al. Professional medical associations and their relationships with industry. JAMA 2009; 301: 1367-1372.

The vast amounts spent in the US on health care have not translated into access for many patients, consistently excellent quality of care, and signiticantly improved outcomes. While we spend all this money, the primary care and generalist practitioners on the front lines are increasingly embattled and disgruntled, and their numbers are rapidly thinning. One problem may be the pattern of fees paid to physicians. Fees paid to physicians not only influence costs directly, but provide incentives for physician decision making about what tests and treatments patients receive. We have posted several times, most recently in February, 2009, here, about how the US Medicare system sets fees paid to physicians.

Since health care reform is now a hot topic in the US, there has been increasing discussion of the plight of primary care and generalist practitioners, but little consideration of how it arose. What we wrote in February was (with updated links):

As we have discussed, the US Medicare system determines what it pays physicians using the Resource Based Relative Value System (RBRVS). This system determines the pay for every kind of medical encounter according to a complex formula that is supposed to account for physicians' time and effort, physicians' practice expense, and the cost of malpractice insurance. The components of physicians' effort assessed are, in turn, technical skill and physical effort; the required mental effort and judgment; and stress due to the potential risk to the patient.

To keep the system, which was started in 1990, current, requires addition of new kinds of encounters, which means encounters involving new kinds of procedures, and updating of the estimates of various components, including physicians' time and effort. To do so, the Center for Medicare and Medicaid Services (CMS) relies almost exclusively on the advice of the RBRVS Update Committee (RUC). The RUC is a private committee of the AMA, touted as an "expert panel" that takes advantage of the organization's First Amendment rights to petition the government. Membership on the RUC is allotted to represent specialty societies, so that the vast majority of the members represent specialties that do procedures and focus on expensive, high-technology tests and treatments. However, the identities of RUC members are secret, as are the proceedings of the group.

This opaque and unaccountable process has resulted in increases outstripping inflation in fees paid for procedures, while fees paid for "cognitive" medicine, i.e., for primary care, and for services that involve diagnosis, management of acute and chronic disease, counseling, coordination of care, etc, but not procedures, have lagged inflation. The effects of the RUC have been amplified by the unexplained tendency of commercial managed care and health insurance to track the RBRVS system when making their own payments to physicians.

For further details about the RUC, see these posts on Health Care Renewal  and important articles by Bodenheimer et al,(1) and Goodson.(2) By the way, why the US Center for Medicare and Medicaid Services (CMS) relies de facto exclusively on the RUC to control the RBRVS system, and why the AMA made the RUC into a secret organization apparently beholden only to the organization's proceduralist members are unanswered questions.

The next month, Dr William L Rich III, and Dr Barbary Levy, the Chair and Chair-Elect of the RUC, wrote me a letter to "point out several blatant inaccuracies within your blog entry that severely misrepresent the nature and work of the AMA / Specialty Society RVS Update Committee (RUC)." They then asked me to "retract or correct the inaccurate statements within the aforementioned blog immediately." However, the letter did not specify the supposedly inaccurate statements within the blog post. So, my email response noted that "the letter contains no detail about the alleged 'inaccurate statements.' If you define them, we will certainly consider your views." I never got a reply to this message, therefore thinking the matter to be closed, and I saw at that time no reason to make the exchange public.

Apparently, the matter was not closed. A few days ago, two anonymous comments were appended to the post. They stated that my letter had appeared on the AMA web-site, here. So it is now public. The comments did not say, and I have so far not been able to find out when the letter was posted, and what its context is within the AMA web-site, including any indication that I had already replied to it in private.

Despite these irregularities, however, given that the AMA apparently has chosen to make the letter public, I believe I ought to respond publicly.

"Blatant Inaccuracies?"

Dr Rich and Dr Levy wrote:

We would like to take this opportunity to point out several blatant inaccuracies within your blog entry that severely misrepresent the nature and work of the AMA / Specialty Society RBRVS Update Committee (RUC). We request you retract or correct the inaccurate statements within the aforementioned blog immediately.

First, as I noted above, the letter never specified which of my statements the letter writers considered "blatant inaccuracies." If there are any specific statements of fact in the post above (or any other post I write) that can be shown to be inaccurate, I will correct or retract them. However, I do not believe the letter by Dr Rich and Dr Levy demonstrated any particular statements of mine to be blatantly inaccurate.

The Obscurity of the RUC Membership

The letter stated:

The RUC does not operate in the shadows.

One of my major criticisms of the RUC was that it is opaque. Before I wrote my first post on the RUC, I tried to determine its membership by searching the AMA web-site, easily available AMA publications, and the web. I could find lists of past members, but no current list. In addition, I asked RUC staff by email whether they could provide me the list, or an easy way to access it. They would or could not do so, and the highest ranking staffer I contacted wrote, "we do not give out the RUC members' contact information. We attempt to shield the RUC from lobbying by industry or others." Only after these inquiries did I dub the RUC membership "secret."

Dr Rich and Dr Levy suggested that it is not quite secret. It stated that "a list of the individual members of the RUC is published in the AMA publication, Medicare RBRVS 2009: The Physicians Guide." This publication is available from the AMA here for a mere $71.95. However, the book is not on the web, or in my local or university library, and I have no other way to easily access it.

Additionally, although the letter stated, "any individual may solicit AMA staff directly or a specialty society to learn the names of the members of the RUC," the letter was not accompanied by any communication from AMA staff containing this information.

Thus, to date, I still do not know who the members of the RUC are. If the letter authors had wanted to show that the membership of the RUC was not meant to be obscure, they could easily have sent me the list with their letter, appended a copy of the pages of the book which contained the list, or asked their staff to provide this information. They chose not to do so. So, while the RUC membership may not be exactly secret, it remains obscure, only barely public, and relatively inaccessible.

The Secrecy of RUC Proceedings

Furthermore, to support its contention that "the RUC does not operate in the shadows," the letter stated that

any individual may attend a RUC meeting upon: (1) the invitation of and notification by a relevant specialty society; (2) an express invitation by the chair of the RUC; or (3) the approval of a written request to attend; and a review of conflicts and potential conflicts of interest.

This does not mean that RUC meetings are open, or that their proceedings are public. Instead, as Goodson(2) noted, RUC "meetings are closed to outside observers except by invitation of the chair." Furthermore, he stated, "proceedings are proprietary and therefore not publicly available for review."

The letter also personally invited me to attend "the next meeting of the RUC, which will take place April 23-26, 2009 in Chicago." In retrospect, this invitation did not appear serious, since it was never repeated or expanded after my email reply to the March letter.

Nor did the invitation include any assurance that I could make anything about this meeting public. I had learned from a previous RUC attendee who will remain anonymous that attendees are obligated to sign non-disclosure agreements. Signing such an agreement might jeopardize my further ability to write anything of substance about the RUC. Furthermore, making all meeting attendees sign non-disclosure agreements effectively makes the meeting secret.

The RUC and Primary Care

Dr Rich and Dr Levy asserted that:

Your publication irrationally and unreasonably paints the RUC as the perpetrator of all physician payment policies that have negatively affected primary care.

Furthermore, they argued that the RUC has been good for primary care and cognitive practice:

The RUC has made several recommendations that positively benefit cognitive and non-procedural physician specialties.

My opinions about the RUC's influence on payments to physicians, and the decline of primary care and generalist and cognitive practice are hardly original. My previous posts were clearly based on evidence and discussion from references 1-4. Let me summarize these arguments, using direct quotes from these references, which perusal of the original articles would reveal are not taken out of context.

Primary and generalist practice is threatened by the current payment system.

From Bodenheimer et al(1):

Incomes of primary care physicians are well below those of many specialists, and the primary care–specialty income gap is widening.

... the lower income of primary care physicians is a major factor leading U.S. medical students to reject primary care careers.

Primary care practice is not viable without a substantial increase in the resources available to primary care physicians.

From Goodson(2):

Medicine's generalist base is disappearing as a consequence of the reimbursement system crafted to save it—the resource-based relative value scale.

Current reimbursement incentives substantially favor procedures and technical interventions and offer financial advantages for expensive care, thereby encouraging specialty services.

The continued and sustained incentives for medical graduates to choose higher-paying specialty careers and for those physicians in specialty careers to increase income through highly compensated professional activities have been associated with the dwindling of the generalist workforce. The lack of incentives for medical graduates to choose generalist careers in internal medicine, family medicine, and pediatrics has had a profound effect on the workforce mix and, ultimately, US health care expenditures.

The RUC has been the major influence on the physician payment system leading to these problems.

From Bodenheimer et al(1):

In summary, the RUC process favors increases in procedural and imaging reimbursement for 3 reasons: specialty society influence in proposing RVU increases, the specialist-heavy RUC membership, and the desire of RUC specialists to avoid increases in evaluation and management RVUs. With their ability to create new codes and influence RVU updates, many procedural specialists can influence fees in a way that observers find to substantially overvalue procedural and imaging services. Moreover, high fees may encourage physicians to increase the volume of profitable services, leading to even higher income gains and greater spending growth.

From Goodson(2):

The RUC has powerfully influenced CMS decision making and, as a result, is a powerful force in the US medical economy. Furthermore, by creating and maintaining incentives for more and more specialty care and by failing to accurately and continuously assess the practice expense RVUs, the decisions of CMS have fueled health care inflation. Doing so has affected the competitiveness of US corporations in the global market by contributing to years of double-digit health care inflation that have consistently increased the costs of manufacturing and business in the United States over the last decades.

The current mechanism fails to provide sufficient checks and balances and is skewed and dysfunctional.

The resource-based relative value scale system originally developed to achieve full value for cognitive services currently threatens the sustainability of the generalist base. As a result, a large portion of the population will lose access to the continuous and personalized care provided by generalist physicians whose repertoire of clinical skills and interventions coupled with access to specialty and diagnostic services are essential for ensuring efficient and effective health care delivery.

Dr Rich and Dr Levy are entitled to their opinions, but I would argue that there is considerable evidence and opinion suggesting that the current dysfunctional physician payment system is a major cause of the decline of primary care and cognitive practice, and simultaneous rise in health care costs and decline in health care access in the US. Furthermore, there is also considerable evidence and opinion suggesting that the RUC has singular responsbility for the dysfunctionality of the payment system and how it is skewed in favor of procedures as opposed to cognitive services and primary care.

Summarizing: the Opacity of the RUC, and its Negative Effects on Primary Care and Cognitive Services

So, I stand by my statement that the RUC process is opaque. Instead of saying "the identities of RUC members are secret, as are the proceedings of the group," I would be willing to now say, "the identities of the RUC members are obscure and difficult to ascertain, and the proceedings of the group are secret." That is not much of an improvement.

If the RUC leadership wants to make its membership transparent, all it needs to do is post it on the web. If it wishes to make its proceedings transparent, all it needs to do is publish them as well. If it makes such changes, I would happily and publicly applaud them.

If the RUC leadership wants to show that their members are not influenced by individual conflicts of interest, transparency about the committee's membership would inspire more trust than making the information as obscure as possible.

Furthermore, there may be more reason to be concerned about the effects of institutional rather than individual conflicts of interest on the RUC. Most RUC members appear to represent specialty societies. Rothman et al claimed that industry funding of professional medical societies is "pervasive."(5) If the RUC leadership wants to show that their committee as a whole is not affected by institutional conflicts of interest of its specialty societies, it ought at least to disclose the relationships of those societies and their leaders with companies that stand to profit from increasing utilization of the specific services whose use is influenced by the incentives which the RUC largely determines.

Finally, if there is a "wedge between cognitive and procedural specialties" it was driven a long time ago, particularly by a payment system that progressively favored the latter over the former, and by a bureaucratic burden that fell disproportionately on the former. But blaming the messenger is a time-honored, if not necessarily honorable tactic.

References

1. Bodenheimer T, Berenson RA, Rudolf P. The primary care-specialty income gap: why it matters. Ann Intern Med 2007; 146: 301-306. Link here.
2. Goodson JD. Unintended consequences of Resource-Based Relative Value Scale reimbursement. JAMA 2007; 298(19):2308-2310. Link here.
3. Ginsburg PB, Berenson RA. Revising Medicare's physician fee schedule - much activity, little change. N Engl J Med 2007; 356: 1201-1203.
4. Newhouse JP. Medicare spending on physicians - no easy fix in sight. N Engl J Med 2007; 356: 1883-1884.
5. Rothman DJ, McDonald WJ, Berkowitz CD et al. Professional medical associations and their relationships with industry: a proposal for controlling conflict of interest. JAMA 2009; 301: 1367-1372. Link here.

Earlier this year, a remarkable commentary in JAMA suggested major reconsideration of the relationships among professional medical associations (PMAs) and health care corporations.(1) Because of the influence of PMAs on clinical care, education, research, and policy, Rothman et al suggested that these organizations sever most of their financial ties to corporations such as pharmaceutical, device, and biotechnology companies. The authors suggested that the only acceptable payments to PMAs from these companies are those for advertising in publications that is clearly labeled as such, and advertising exhibits in meetings, again that is clearly labeled. Furthermore, the authors suggested that people with current or recent (within the last two years) relationships with such corporations ought not to serve as officers or trustees of PMAs, and ought not to serve on program or practice guideline committees. Rothman et al thus suggested that professional medical associations return to their roots, to be advocates for their physician members, and those members’ core values, not marketers of drugs and devices, and promoters of the interests of health care corporations.

The Journal of the American College of Cardiology (JACC) just published the first rebuttal of Rothman et al to appear in a peer-reviewed journal, written by Dr Alfred A Bove, President of the American College of Cardiology (ACC), one of the more influential PMAs.(2) Dr Bove contended that there is nothing wrong with the current relationships among corporations and PMAs, and PMAs should be free to relate to health care corporations any way they want. Dr Bove also asserted that “the assumptions that lead to ... [Rothman and colleagues’] conclusions can be challenged on many fronts.” However, in my humble opinion, Dr Bove supported these contentions with logical fallacies, rather than evidence and logic.

Appeals to Authority, Fear, and Pity

Early on, Dr Bove used a striking set of appeals to authority. (Note that his relevant quotes below appear in italics.)

“There is no comment about trust or virtue as a characteristic of the medical profession.”

“We are not to be bribed by a cheap pen or a free lunch.”

“The authors' assumptions imply that physicians as a group are not responsible people, yet physicians are among the most responsible professionals.”

These appear to be appeals to the traditional authority of the medical profession. Dr Bove simply asserts that physicians are inherently virtuous and deserving of trust, and thus no one could question the virtue of the profession.

He then compounded these appeals to authority with a veiled appeal to fear.

“The authors' assumption that the worst behavior is the average behavior of all physicians insults the profession.”

As noted below, Rothman et al did not make this assumption, so the appeal in turn rests on a straw man argument. This appears to be an appeal to fear in that an “insulted” profession might be expected to take action, legal or otherwise, to avenge the insult. It also could be a form of an appeal to pity, in that the reader might be inclined to pity the poor “insulted” physicians.

Straw Man Arguments

The bulk of the editorial consisted of a string of straw man arguments. A straw man argument propounds a distorted, exaggerated, or misrepresented version of his opponent’s argument, and then attacks it, rather than his opponent’s actual argument.

“The sole source for support of PMAs could only come from government or foundation grants....”

Actually, Rothman et al included membership dues, and by implication, meeting registration fees, journal subscription fees etc as acceptable sources of support.

“The article implies that all physicians who receive support from industry will forever be biased to support the products of the related pharmaceutical or device company.”

Actually, Rothman et al seemed to assume that conflicts of interest might affect someone for up to two years, but not forever. Thus, they suggested that board members should be “conflict free for a 2-year period before assuming the position.”

[The Rothman article] “also implies that industry does not work for the best interests of patients or the better [sic] public good, but only for profit.”

Actually, Rothman et al stated “the pharmaceutical and medical device industries make important contributions to medical progress. Their role in the development and testing of new compounds and instruments is essential for the diagnosis and treatment of disease and disability.”

“First, to assume that physicians would not be responsible for providing the best care for their patients after being associated with an industry study or consultation is inappropriate. The authors cited isolated examples of errant physicians who received large sums of money from industry and then promoted their products. They presume that all physicians are represented by these few—that we all have a price.”

Actually, Rothman et al did not discuss any particular cases of “errant physicians.” What Rothman suggested was that gifts, even of “modest value,” can bias decision making, and that the receipt itself of the gift may itself be influential. However, if even modest gifts have some influence, it is logical that large financial transactions might have major influence.

“Society understands that reward drives innovation, so expecting a financial gain from a commercial medical enterprise is not wrong. In fact, it is the only way that new ideas will move from the laboratory to the public good. Using public funds for manufacture and distribution would add an enormous burden to government costs and, based on past experience, would be unproductive.”

Rothman et al were not remotely suggesting nationalizing the drug and device industries.

“If one of us has an idea for a new device and needs industry to help refine its design, fund its development and manufacture, and establish its value by animal and clinical studies, this process should be honored, not condemned. Will the government fund the development of the next new drug? Would the government have funded the development and manufacture of an implantable pacemaker?”

At the most, Rothman et al recommended not allowing physicians who are paid by companies in conjunction with their development work to serve as top leaders, and on certain committees of PMAs. They never broadly “condemned” physicians who work with industry to develop devices.

“Governments have not shown an interest in funding the development of new drugs and devices. Industry raises the funds, takes the risks, and should reap the rewards for its role in creating a better life for our patients.”

Actually, governments have helped development considerably by funding much of the underlying basic science research. Again, Rothman et were not remotely suggesting nationalization of drug development.

Summarizing the Arguments

So Dr Bove ended up by warning that the suggestions Rothman et al made about reducing institutional conflicts of interest affecting professional medical societies, and individual conflicts of interest affecting their leaders would “destroy the best of what we have in our science and industry,” that is, destroy biomedical and clinical science, and lead to nationalization of important forms of medical production. None of that was suggested or implied by Rothman et al. After positing this dire future, Dr Bove then asserted that professional societies ought to be entitled to money from industry limited only by their “professionalism.” Thus, “industry should be able to support unbiased programs aimed at educating physicians and other health care providers about the therapies available for the care of their patients. Professional societies should be able to receive unconditional educational grants to provide up-to-date information to their members on medical therapies.” Furthermore, “the proper relationships should allow us to work with industry and allow our professional societies to receive undesignated funds from industry to foster better patient care.” So, Dr Bove wound up where he started, asserting that doctors and professional societies are inherently virtuous, and thus should be trusted to do whatever they think is right, without any external scrutiny or accountability. Yet he never demonstrated the virtue of the ACC under his leadership, or of PMAs in general, or showed why they should be trusted.

Why did the president of one of the nation’s most important medical associations publicly make such poor arguments to support his organization's current financial relationships with health care corporations? I can only speculate, but there may be some clues found by looking at what is publicly known about the current relationships of the ACC and its leaders to health care corporations.

Publicly Disclosed Relationships Among the ACC and Its Leaders and Health Care Corporations

My sources for these clues were a report on the ACC web-site on its relationships with health care corporations (through 2007), and the form 990s that the ACC is and the highly related ACC Foundation are required to file with the US Internal Revenue Service. (The form 990s are publicly available from GuideStar with a free membership. The ACC form is here, the ACCF, here.)

Perhaps unsurprisingly, it turns out that the ACC gets a large proportion of its income from industry. In 2007, it acknowledged receiving $35,882,095.15 from industry. The largest categories of industry support were "promotional/quality program support," $12,664,650; "charitable contributions," $7,603,639; and "exhibits" at meetings, $7,318,807; and "educational grants," $5,084,600. The total revenues of the ACC (which include the ACC Foundation), were $94,560,000, so that industry support accounted for 38% of total revenue. These figures should be compared to the revenue the society received from membership dues (found on its 990 form), $11,995,056, and the income it claimed from its annual scientific session, $8,400,632. So to put it another way, the ACC got about three times as much money from industry as it got from its members' dues, and almost twice as much money from industry as it got from dues and its annual meeting combined.

So were the suggestions made by Rothman et al to be implemented by the ACC, it would stand to lose at least $28 million a year (given that in 2007, about $1 million of its industry revenue was from advertising , and about $ 7.3 million was from exhibits at meetings.)

The organization's lavish revenues have allowed it to pay its full-time managers very well. In 2007, its CEO received $534,452 in total compensation; its general counsel, about $394,000; and its CFO, about $336,000. It seems obvious that were the organization to foreswear industry revenue, the organization's top full-time managers would be unable to continue to live in the style to which they are now accustomed to.

In addition, the organization's form 990 reveals that it pays its supposedly voluntary officers and some of its trustees substantial amounts as well. In 2007, it paid its president $147,750; its president-elect, $80,000; its two immediate past presidents, $79,500 and $70,000; its vice president (at that time, Dr Bove), $63,751; its treasurer, $32,500; its secretary for the board of governors, $52,500; its board of governors chair-elect, $25,000; its immediate past board of governors chair, $25,000; and some trustees amounts from $1000 to $20,520.

To my knowledge, it is unusual for a professional society to pay salaries to its voluntary officers (as opposed to full-time, hired managers.) However, given that the ACC does, it seems that were the organization to foreswear industry revenue, its officers' personal income might be threatened to some extent.

Finally, Dr Bove has his own personal financial relationships with industry. Some were disclosed because of his role on ACCs Cardiosource editorial board, including "Consultant Fees/Honoraria: Insight Telehealth Inc,""Research/Research Grants: Astella Pharma, INC," and "Royalty Income: Elsevier." In addition, in a 2008 article(3), he disclosed receiving speakers fees from Medical Seminars, Inc, and serving as a consultant to Vasocom Inc. For a 2009 conference, he also disclosed "modest" equity interests in Cardiovascular Therapeutics, and Merck.

So, in summary, it seems that the ACC gets a very substantial portion of its revenue from health care corporations, and that were it to carry out the suggestions of Rothman et al, it would lose much of that revenue. Thus, it is not surprising that ACC leadership would take exception to Rothman and colleagues' point of view. This is not the first time that an ACC president has defeneded the organization's dependence on industry funding (see post here). However, as I said in that post,

My questions are how could a society which requires such a substantial proportion, 38% of funding from commercial sponsors ignore the preferences of the sponsors for particular topics and content areas? How could such a society dare to allow criticism of the sponsors, their products, or their activities? Knowing that the society is dependent on this level of support, could society leaders really hold industry representatives at arms' length? Knowing that industry supplies more than one-third of their salaries, would society staff really keep industry outside of some bureaucratic, but not concrete 'firewall?'

In addition, it now seems the ostensibly voluntary officers of the ACC may have a personal stake in the ACCs receipt of health care corporate funding, since it is the apparent policy of the organization to pay these officers five- and six-figure salaries. Dr Bove did not disclose this apparent conflict of interest, nor did he disclose his other personal financial relationships with industry. As we have noted before, people with conflicts of interest tend to have trouble making coherent, logical and evidence-based arguments for positions related to their conflicts. As Joe Collier wrote in the BMJ, "people who have conflicts of interest often find giving clear advice (or opinions) particularly difficult. "(4)

In any case, a previous ACC president wrote about the importance of "disclosure" and "transparency" in dealing with conflicts of interest. Whether disclosure of conflicts is sufficient to manage them, at least Dr Bove could have done the courtesy of disclosing that he is actually a salaried employee of the ACC, and disclosing his personal financial relationships with industry so that readers could try to evaluate how these financial entanglements might have affected what he wrote.

Summary

In conclusion, the first published rebuttal of Rothman and colleagues' suggestions for ensuring the independence of professional medical associations from outside vested interests was not based on evidence, but on logical fallacies rather than clear reasoning, and failed to disclose its authors' relevant financial relationships. We will see if anyone can make a better attempt.

ADDENDUM (17 July, 2009) - see additional comments by Dr Howard Brody on the Hooked: Ethics, Medicine and Pharma blog.

ADDENDUM (22 July, 2009) - see this post on the Cardiobrief blog, which alludes to the post above, but also discusses an interesting response by the CEO of the ACC to the Rothman paper, and adds original commentary on larger issues.


References

1. Rothman DJ, McDonald WJ, Berkowitz CD et al. Professional medical associations and their relationships with industry. JAMA 2009; 301: 1367-1372. (Link here.)
2. Bove AA. President's page: relations with industry: thoughts on claims of a broken system. J Am Coll Cardiol 2009; 54: 177-179. (Link here.)
3. Somers VK, White DP, Amin R et al. Sleep apnea and cardiovascular disease: an American Heart Association/ American College of Cardiology Foundation scientific statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. Circulation 2008; 118: 1080-1111. (Link here.)
4. Collier J. The price of independence. Br Med J 2006; 332: 1447-9. (Link here.)

We have posted multiple times about Avandia (rosiglitazone), GlaxoSmithKline's star-crossed glucose-lowering drug. While Avandia has received considerable media coverage, we focused on two questions: 1 - what are the benefits and harms of rosiglitazone as a treatment of type 2 diabetes, and therefore for which patients under what circumstances should this drug be used? 2 - what barriers have prevented physicians and patients from getting the best possible answer to the first question, and what can be done about them? (See recent post here.)

In particular, the Avandia case has illustrated how those with vested interests in the success of a health care product have done their best to obscure information that might threaten its success, even when doing so obscures the information that physicians and patients need to make the best possible decisions. At one point, (in 2007, no less) we called this the "Avandia spin cycle."

Avandia once again has been in the news after the US Food and Drug Administration's hearings on the safety of the drug. These hearings were so well covered in the media that a lengthy summary would be superfluous. However, their main points demonstrated the persistence of the Avandia spin cycle:
- An FDA reviewer felt that "the company's misreadings of the ... Record trial ... were so profound, he concluded, that they 'suggest serious flaws with trial conduct.'" (per Gardiner Harris writing in the New York Times)
-A former FDA reviewer "withheld from regulators a study showing its Avandia diabetes drug may cause heart attacks." (per Bloomberg News)
- GlaxoSmithKline's forerunner SmithKline Beecham "secretly began a study to find out if its diabetes medicine, Avandia, was safer for the heart than a competing pill, Actos, made by Takeda." However, "the study also provided clear signs that it [Avandia] was riskier to the heart. But instead of publishing the results, the company spent the next 11 years trying to cover them up." (per Gardiner Harris writing in the New York Times.
- "Government experts and a panel of medical advisers repeatedly voiced skepticism on Tuesday about the trustworthiness of GlaxoSmithKline, which makes the controversial diabetes drug Avandia." (per Gardiner Harris again writing in the New York Times.)

So the Avandia saga has brought to the front pages the concerns we have had with suppression and manipulation of clinical research, especially when pursued by health care organizations with vested interests in the results of specific research projects coming out a certain way, and how they have been enabled by those with conflicts of interest. Doctors thus should be worried whether those of us who try to practice evidence-based medicine have been fooled into practicing pseudo-evidence-based-medicine.

Those commenting on the story focused on the need for transparency when clinical research is funded and run by the corporations whose products are being evaluated.
- "GlaxoSmithKline, the maker of Avandia, can't be trusted to report adverse clinical results fairly. The company must be watched like a hawk as additional trials that it sponsors go forward." (NY Times editorial)
- "What America should demand in return for ... [generous patent] protection is that the FDA be able to make an honest evaluation of the efficacy of drugs. When drug companies make this impossible by suppressing test results, not only do they violate their fundamental obligation of honesty with the public, their customers and their regulator, but they also break the bargain they have struck in return for the protection of their intellectual capital." (Former NY Attorney General Eliot Spitzer in Slate.)

Instead, as I have written before, maybe we ought to consider whether those with vested interests in drugs or devices ought to be running clinical research meant to evaluate their own products.

Ironically, while this discussion of how the Avandia spin cycle first began to revolve were going on, others were still trying to add revolutions (per minute). In particular, a Reuters story noted:

Three influential groups of doctors who treat diabetes urged patients not to stop taking Avandia, saying on Thursday that while news about the controversial drug may be frightening, it would be worse to suddenly stop taking it.

That is odd, given that Avandia has never been shown to improve clinical outcomes for patients with diabetes, and that there are many other drugs that control blood sugar which appear to be safer. But wait, there is more,

The Endocrine Society, American Diabetes Association and the American Association of Clinical Endocrinologists worried that patients may be afraid to take Avandia.

'Patients should continue taking all currently prescribed medications unless instructed otherwise by their health care provider,' Dr. Robert Vigersky of the Endocrine Society said in a statement.

'Stopping diabetes medications can cause significant harm and result in higher levels of blood glucose that may cause severe short term health problems and could increase the risk of diabetes-related complications in the long term.'

Would not it make more sense to advise patients still on Avandia to consult with their doctors urgently about possible alternatives? Meanwhile, it does not seem irrational to be afraid of taking Avandia, given the increasing evidence about its harms, and increasing evidence that what we know about its harms may be an under-estimate.

So I wondered why these august medical societies seemed so unaffected about the doubts about Avandia's safety, and about the evidence offered to support its use that the latest news ought to generate. It turns out that all three of the medical societies get financial support from, -- wait for it --, GlaxoSmithKline.

The Endocrine Society lists GSK as one of its Corporate Liaison Board Members. The American Diabetes Association lists GSK as one of its Banting Circle Supporters, that is, those that give at least $1,000,000 a year. The American Association of Clinical Endocrinologists lists GSK as a member of its Corporate AACE Partnership. (I was not able to find out the total amount contributed by GSK to either the Endocrine Society or the AACE.)

So once again, the loudest voices in support of the product come from those used to, and perhaps dependent on financial support from its manufacturer. As a physician, I have been particularly disappointed that our medical societies, whose missions are ostensibly to support our professional values, seem to act more and more like marketers for the companies whose contributions, rather than members' dues increasingly support them.

The cycle keeps spinning.

For further thoughts on the latest in the Avandia case, see this post by Howard Brody on the Hooked: Ethics, Medicine and Pharma blog, and this by Alison Bass on the Alison Bass Blog.