Middlemen and a Health Care System Dominated by Bureaucrats and Managers

The Wall Street Journal today wrapped up its series on "middlemen" in health care. The summary article has some telling quotes, and some very important data. To start with the quotes,

A lot of the money goes more toward fattening middlemen's bottom lines than toward improving the quality or efficiency of American health care. 'At the end of the day, the only reasonable conclusion is that we waste a huge amount of money on the most nuttily cumbersome administrative system in the world,' says Henry Aaron, a Brookings Institution economist.

While the middleman business booms, health-care costs keep rising, the ranks of the uninsured grow, and paperwork expands as each party in the system tries to enlarge its slice of the pie. 'There's more money to be made by monitoring cash flow than monitoring patients,' says David Cutler, a prominent Harvard University health economist.

And here are the statistics. According to the article, the majority of people who work in doctors' offices, 1.8 million out of 3.3 million, do so in non clinical jobs. Nearly a majority of people who work in hospitals, 2.3 out of 5.5 million, do so in non clinical jobs. So currently almost 50% of people who work in what appear to be the most clinical settings are not doing clinical work.

Health care has been taken over by clerks, bureaucrats, and managers.

This appears to be the fruit of the movement began in the 1980's to break the medical "guild," which some economists held responsible for the high cost of health care (see post here).

The results has been even more rapidly increasing health care costs, decreasing access, stagnant quality, and of course, dispirted professionals tired of contending with myriad clerks, bureaucrats, and managers, most of whom do not seem to understand health care or believe in its values.

And this horrendously complex, bureaucratic non-system is a fertile breeding ground for the conflicts of interest and outright criminality we discuss so often on Health Care Renewal.

Some happy new year to us from the WSJ.

Medical Meeting Spikes Session on Conflicts of Interest

There seems to be a run of stories about academic fora rejecting discussions of conflict of interest (see most recent post here about how the New England Journal of Medicine seemingly rejected a commentary on conflicts of interest by one of its own "national correspondents.") Now the Boston Globe has published an article by Christopher Rowland about the cancellation of a session on conflicts of interest at the American Society of Hypertension (ASH) 2007 meeting. We previously discussed a controversy at the Society over industry involvement in guidelines it sponsored that featured a broadened definition of "pre-hypertension," one that seemingly would include many more patients as candidates for drug treatment. According to the Globe,

The title of the proposed panel discussion cut straight to the point: "Conflicts of Interest." But attendees at the American Society of Hypertension's spring meeting in Chicago won't get to hear what panelists have to say about financial ties between the drug industry and medical societies and physicians. The society has rejected the session, saying it was 'one-sided' and did not meet 'standards for fair balance and scientific rigor.'

Now, the cancellation itself is causing a conflict, prompting three prominent drug industry critics from Boston who had been invited to participate to accuse the society of stifling debate.

'The society is hiding under a rock,' said Dr. Jerome Kassirer, a former editor of the New England Journal of Medicine, who would have been a panelist.

The panel about conflicts of interest [would have been lead] by Jean E. Sealey, a researcher and former president-elect of the American Society of Hypertension. Sealey has said the drug industry wields too much influence over the society's activities through its financial contributions to the group and by paying for honoraria, speakers fees, grants, and research contracts with individual doctors.

But the society's leadership alleged that Sealey had her own conflicts of interest: While she served on the society's board, her husband, Dr. John Laragh , edited one of the society's academic journals.

Sealey agreed to give up her chance to be president, but was allowed to organize a half-day session for next May's annual meeting.

The group said in a statement that it sent Sealey's panel proposal to its continuing medical education review committee, which determined Sealey's plan to limit the panel to three prominent drug industry critics lacked balance. It suggested adding a Food and Drug Administration official to the roster, but Sealey refused.

In response to questions from the Globe, the society initially said in an e-mail that fair balance is required under national standards for continuing medical education programs, and that its internal continuing medical education committee was compelled to reject the panel on those grounds. In a subsequent e-mail, after Kassirer said there is no such requirement in the national rules, the society said the expectation of fair balance is 'inherent.'
Sealey said the purpose of her proposed panel was to provide a counterpoint to the many industry sponsorships and payments to physicians who are scheduled to present medical information at the meeting. At last year's meeting, she said, 100 of the 165 presenters disclosed financial ties to pharmaceutical companies.

Obviously, the American Society of Hypertension has the legal right to determine what presentations will occur at its national meeting. However, in my humble opinion, the Society's stated reason for rejecting this single panel presentation on conflict of interest was bizarre. As noted above, there is no known requirement that each individual presentation at a medical meeting must in some way be "balanced."

Furthermore, the ASH meeting seems to be one of the many medical meetings in which there is a large amount of industry participation. ASH itself has 12 corporate members, all pharmaceutical companies. At the annual meeting, high-powered pharmaceutical advertising is quite evident, and the meeting web-site includes a pamphlet to promote even more. It suggests that over 70 commercial exhibitors will participate, indicates a vast variety of advertising and promotional opportunities, and claims, "the enthusiastic response to our exhibit area from both participants and visitors affirms our belief that this is one of the most productive exhibit showcases available."

So it seems that one panel on conflicts of interest featuring critics of the pharmaceutical industry would likely be completely over-balanced by the tremendous amount of industry participation elswhere at the meeting.

This case seems to be yet another in our catalog of examples of the anechoic effect. Criticisms of the role of commercial vested interests in medical science are considered impolite in certain venues, particularly venues that unquestioningly feature a large amount of industry support. Such impoliteness is unwelcome, as it might trouble those who are otherwise happy to let the good times roll.

Medical societies, however, ought to think of what they may have sold to finance their continued rolling.

"Medical Journal Spikes Article On Industry Ties"

From the Wall Street Journal, an article that will pretty much speak for itself, with a little re-ordering and editing by yours truly. First, there was the spiked commentary,

The New England Journal of Medicine last month published studies warning that aggressive efforts to treat anemia in kidney-disease patients with the drug erythropoietin, or EPO, as recommended by the National Kidney Foundation, appear to increase the risk of heart failure and the need for dialysis. [See related posts here and here.] But the medical journal spiked an opinion piece commissioned from one of its senior writers that was critical of the foundation's reliance on multimillion-dollar donations from the companies that make such drugs.
Meanwhile, the author of the spiked editorial, Dr. Robert Steinbrook, submitted it to one of the journal's chief rivals, the British medical journal Lancet, which ran a version on its Web site on Nov. 17, a day after the New England Journal published its reports on the matter. [Steinbrook R. Haemoglobin concentrations in chronic kidney disease. Lancet 2006; 368: 2191-3.]

Dr. Steinbrook's article said that the foundation's guidelines have been questioned because of the group's close relationship with the drug industry. The article also noted that in fiscal 2005, the foundation received more than half of its support from 'corporate and organizational partners,' and, in the calendar-year 2005, it received $4.1 million from Amgen Inc. and $3.6 million from Johnson and Johnson's Ortho Biotech, the current marketers of EPO in the U.S.

The kidney foundation, which issued its recommendations earlier this year, credits Amgen as the 'founding and principal sponsor' of the guidelines. Such sponsorship is unusual -- the American Diabetes Association, for instance, says it doesn't 'receive or allow for any corporate contributions for our clinical practice recommendations.'

Ellie Schlam, a foundation spokeswoman, says Amgen's sponsorship money paid for guideline-development staffers, a $3,000 grant to each member for travel to meetings and other expenses, plus phone, faxing, copying and other administrative expenses. A disclosure on the foundation's Web site noted that most members of the guideline group have a financial relationship with either Amgen or dialysis providers, who resell EPO and stand to profit from its increased use. Still, the foundation says sponsors aren't informed or involved in any aspect of guideline development.

A spokesman for Amgen said the company is 'not involved in the creation and design of the guidelines we sponsor.'

The New England Journal declined to discuss Dr. Steinbrook's article, saying 'we discuss only content that we have published.' Dr. Steinbrook, a former deputy editor of the New England Journal, has been a national correspondent since 2002. According to a person familiar with the matter, he was told his manuscript lacked balance because it suggested that the commercial support of the guidelines influenced the medical recommendations made by that group. New England Journal editors also criticized the piece for failing to credit the guideline writers for striving to find the right balance when it comes to anemia guidelines.
Meanwhile, Richard Horton, editor of the Lancet, said 'I was surprised Robert came to us because I have admired his work for the New England Journal of Medicine.' Dr. Horton said of the article: 'We thought it extremely important -- because of the significant clinical implications and because of the questions it raised about the propriety of the arrangements over funding and guideline development.'

Then there was the more innocuous in-house editorial,

The journal did run a less-critical editorial on the studies co-authored by Julie Ingelfinger, a nephrologist and deputy editor at the journal who is the immediate past president of the Massachusetts-based chapter of the National Kidney Foundation and a member of the state group's medical advisory board. The editorial that ran made no mention of the foundation's industry funding, and Dr. Ingelfinger's relationship with the foundation wasn't disclosed.
Asked why Dr. Ingelfinger's roles at the Massachusetts Kidney Foundation weren't listed along with the article she co-authored, a spokeswoman for the New England Journal said, 'We publish financial associations that are relevant to the content of the article. We tend to be inclusive, rather than exclusive.'

Frank Davidoff, the editor emeritus of the Annals of Internal Medicine, says Dr. Ingelfinger's association with the kidney foundation should have been made known to readers. 'She should have disclosed that, even if she is the best person to write the editorial,' he said. Dr. Davidoff said medical journals historically have paid less attention to the potential conflicts of editorial writers than they have to researchers publishing original studies.

And the somewhat under-stated conclusion,

The handling of the two articles has reignited debate about the journal's standards and whether it is tough enough on issues involving industry funding of research and treatment guidelines.

Again, as we have stated before, people with conflicts of interest may not be consciously aware of the binds in which they find themselves. However, common sense, economics, and cognitive psychhology suggest people respond to incentives, including financial incentives (see post here). If a person or organization is paid by company x, how likely is he, she, or it to criticize company x's products? How likely is he, she, or it to give company x the benefit of the doubt?

Thus, at a minimum, we urge that all potential conflicts of interest affecting health care decision makers, and those who seek to influence them, ought to be fully and thoroughly disclosed. And we need to consider whether some such conflicts ought to be banned outright.

But people with conflicts, who are now prevalent in academic medicine, and various other health care organizations, are likely to find such discussions very uncomfortable. But that is just why we need to have them.

UMDNJ as a Political Sand-Box

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

Now the Star-Ledger has come up with a story of some mind boggling decisions made by the former UMDNJ leadership that seemingly wasted millions on expensive building projects that now stand vacant. The article then concluded with another insightful analysis of what went wrong in the leadership culture of the university, an analysis that may generalize to other health care organizations.

First, let's summarize the blundering building projects. The first was a highly secure site to develop vaccines against biologic terror agents, which is years behind schedule because a UMDNJ leader wanted to relocate it to a piece of land owned by his neighbor. Per the Star-Ledger,

It was known as a Regional Biocontainment Lab.

It was announced in September 2003 by then-Health and Human Services Secretary Tommy Thomp son, who hailed it as 'a major step' toward providing effective vaccines and diagnostics for diseases caused by agents of bioterror as well as in fections such as SARS (Severe Acute Respiratory Syndrome) and West Nile virus.

The federal grant stipulated the project be built in Newark's University Heights, adjacent to an existing bioresearch lab operated by UMDNJ.

Memos and e-mails show that within four months, Robert A. Saporito -- then UMDNJ's senior vice president for academic af fairs -- was looking for another site, as university officials grew concerned they would be unable to find matching funds required to build the project.

The search for alternate sites was never disclosed to the public, to the political leaders who secured the money, or to the federal agency that awarded it.

Saporito was forced to resign in March after he was accused of abusing his expense account. In an interview before he left, he said changes in the original design, mandated by security concerns, led to discussions about relocating the lab. He said he explored moving the lab to Picatinny after receiving a call from William Marcellino, a developer who lived a few doors down from him in Brick Township.

When the National Institutes of Health learned about the Picatinny plan last year, the agency was clear: 'We explained to UMDNJ that alternate sites were not an option,' said John J. McGowan, an administrator at NIH.

In an August 2005 letter to the university, NIH officials complained that they had seen little progress on the project and warned 'if you are unable to show the project can be completed, we will need to begin to negotiate the return of funds.'

The next was a cancer center that sits mostly vacant.

The newest building on UMDNJ's Newark campus is a nine-story structure emblazoned with distinctive red signs identify ing it as the New Jersey Medical School/University Hospital Cancer Center.

It includes vast expanses of glass, state-of-the-art research labs, underground vaults for linear accelerators used in cancer treatment, and an outdoor garden for patients.

But no cancer treatment is going on. There are no doctors, no clinical services and no patients. While some researchers have moved in, more than half the building remains empty.

Christopher Paladino, a former university trustee, said there was never a real plan for the cancer center. He said millions were spent without benefit of any economic feasibility studies, or any examination of whether the center would actually bring in patients.

Paladino, named a trustee after the project began, concluded the center had been the product of jealousy between the school's Newark and New Brunswick campuses. In Newark, he said, there was a feeling that because the university has a cancer institute 'in New Brunswick, we should have it here.'

The article documented other expensive buildings that sit partially vacant in lieu of any realistic plans to use the space they provided. In particular,

Adjacent to the cancer center in Newark is a new, six-story building for ambulatory outpatient services completed this year. Walk through this structure, past the cool pastel walls, and there are few people. One level is vacant, as are large parts of the rest of the building.

Since before construction began in April 2003, UMDNJ officials knew they would have trouble down the road because the center was built with tax-free government bonds and money raised that way cannot be used for profit-making operations such as doctors' offices.

'The total confusion on that subject has been the major obstacle,' [Interim UMDNJ President] Vladeck said. 'We're starting to untie that knot.'

Vladeck said the complex was planned and built by people who put off the financial issues, figuring it would be constructed and 'by then, they would have to fix the problem.'

Finally, the Star-Ledger discussed a fascinating analysis of what has gone wrong with the leadership of UMDNJ.

Interviews with past and current officials indicate many projects were a product of a school that increasingly was divided into two worlds the past few years.
In one, nurses and doctors battled to provide health care in a poor, urban environment. But at the top were administrators who got their jobs through political patronage and whose basic job experience was not teaching or medicine, but state government and politics.

Paladino, who was an assistant counsel to Gov. Jim Florio, said political jobs seemed to be part of the lifeblood of the university.

'It's a Sharpe guy. It's a Rice guy. It's a McGreevey guy, or a DiFrancesco guy, he remarked, referring to former Newark Mayor Sharpe James, state Sen. Ronald Rice, and two former governors, James E. McGreevey and Donald DiFrancesco. Everyone has a guy. They don't hide from it.'

It wasn't always evil, he said, but it became a slippery slope as politicians sought comfortable jobs for their political supporters.

U.S. Attorney Christopher Christie, who is overseeing a criminal investigation into the university that was launched after a series of stories in The Star-Ledger last year, saw it all as less than innocuous.

"There were people in political life who were in charge of the budget process who made sure UMDNJ got taken care of, because they knew folks could go there and be employed,' said the U.S. Attorney. 'There was a very symbiotic relationship there between the political world and the university.'

He added that his parents once told him character was what you do when you think nobody's watching.

'UMDNJ,' Christie said, 'was the way politicians acted when they thought nobody was looking, and it's a pretty ugly picture.'

So there you have it. One fundamental problem with UMDNJ was that the University was run by people with no background or fundamental interest in health care, who did not share, even at an intellectual level, the values of health care. The leaders treated the country's largest health care university as there own political sand-box, completely disregarding its core mission, and thus completely disrespecting the patients and learners it was supposed to serve, and the health care professionals who tried to serve them.

After the revolution that turned health care over to business people, bureaucrats, and politicans, how many other health care organizations are run for the benefit of their leaders, rather than the missions they were supposed to support?

Another Electronic Medical Record Horror Story

The Wall Street Journal today published a story on a patient, Patricia Galvin, who was screwed by insurers after medical information she thought was confidential (about her psychotherapy) was divulged to an insurance company. The story is "Spread of Records Stirs Patient Fears of Privacy Erosion", Theo Francis, Dec. 26, 2006 (subscription needed; I will post a public link if it becomes available).

Here is a brief summary from this link:

Medical Dilemma: Spread of Records Stirs Patient Fears Of Privacy Erosion

Dec 26, 2006 By Theo Francis, WSJ.com

After her fiancé died suddenly, Patricia Galvin left New York for San Francisco in 1996 and took a job as a tax lawyer for a large law firm. A few years later, she began confiding to a psychologist at Stanford Hospital & Clinics about her relationships with family, friends and co-workers.

Then, in 2001, she was rear-ended at a red light. When she later sought disability benefits for chronic back pain, her insurer turned her down, citing information contained in her psychologist's notes. The notes, her insurer maintained, showed she wasn't too injured to work.

Ms. Galvin, 51 years old, was appalled. It wasn't just that she believed her insurer misinterpreted the notes. Her therapist, she says, had assured her the records from her sessions would remain confidential.

As the health-care industry embraces electronic record-keeping, millions of pages of old documents are being scanned into computers across the country. The goal is to make patient records more complete and readily available for diagnosis, treatment and claims-payment purposes. But the move has kindled patient concern about who might gain access to sensitive medical files -- data that now can be transmitted with the click of a computer mouse.

The U.S. Department of Health and Human Services implemented standards in 2003 for guarding patient privacy, supplementing a patchwork of state laws. The federal standards, which grew out of the 1996 Health Insurance Portability and Accountability Act, single out psychotherapy notes for extra protection.

Critics claim that loopholes in the rules have left patient privacy under threat. Ms. Galvin, for example, discovered that when psychotherapy notes are mixed in with general medical records, the federal rules afford them no special protection. That is precisely what happened with her records at Stanford, she says.

The article points out that complaints to HHS about breaches of medical privacy have exceeded 23,000 and that HHS presently receives about 700 new complaints monthy, while enforcement of "guarantees" such as in the HIPAA act are basically non-existent. I'd bet a large proportion of these breaches were facilitated by electronic legerdemain.

Here is my Letter to the Editor in response. I do not know if it will be published:

(Update: An edited version of the letter below was indeed published as a Letter to the Editor in the Wall Street Journal, Saturday, 12/30/06, print edition. Edited out for brevity were mention of the UK's difficulties, explicit mention of psychology information as inappropriate in an EMR, and unfortunately, mention of the HCRENEWAL blog. However, the letter was otherwise intact.)

To: wsj.ltrs@wsj.com
cc: theo@theowire.com
Date: Tuesday, December 26, 2006
Subject: Re: Spread of Records Stirs Patient Fears of Privacy Erosion

Dear Wall Street Journal,

Ms. Galvin’s fears that her most private thoughts and secrets are “mere data of a transaction, like a grocery receipt” are well-founded and truly give life to an observation I made several years ago while leading electronic medical records (EMR) implementation at a large hospital. I observed that clinical computing and business computing are entirely different specialties of computing. I felt that the dominance of EMR efforts by information systems personnel would lead to devaluation of doctor-patient confidentiality and of the doctor-patient relationship itself.

As Drucker wrote in 1999, information systems personnel have taken a somewhat peculiar view of the world, namely that the entire world operates on the principles of 19th century accounting theorem, and computerized it in a form where events are deconstructed to “transactions.” Unfortunately, as Ms. Galvin discovered to her horror, good things do not come from treating twenty-first century medical “transactions” as nineteenth century accounting data.

We’re not alone in the United States. In the UK, the ambitious Connecting for Health (CfH) national EMR project and plans for a central clinical database have been met with stiff resistance from patient advocacy groups. Plans to upload medical records onto the central clinical database will put patient confidentiality at risk, the UK program has been told by its own consultants [1]. Professor Ross Anderson, Professor of Security Engineering at Cambridge University and one of the founder members of privacy advocacy group http://TheBigOptOut.org made the telling point that people should opt out of inclusion in the national database, if only to wait and see if their government delivers the ‘protections’ that it is promising - and if it does, to see if they are sufficient and effective [2]. HIPAA must have been on Prof. Anderson’s mind.

A similar advocacy movement is needed in the U.S., for there has been an idealistic and almost reckless push in the US to put any and all healthcare information into EMR’s and other electronic databases, even when the financial and clinical benefits are unproven.

A critical issue in the Journal story that needs consideration is why detailed notes of psychotherapy sessions, of all things, were available in electronic form. This makes little sense and is entirely unnecessary. For instance, data on Ms. Galvin’s feelings and private affairs would not be needed – or even useful – to other doctors in a medical emergency. Indeed, even if Ms. Galvin switched doctors, her history would best be redone by a new psychologist in building an effective doctor-patient relationship.

In a decade when conflict of interest and mismanagement in healthcare is common [3], break-ins to supposedly secure databases appear in the news almost weekly, and dominant computer operating systems are barely able to keep ahead of hackers’ attempts to circumvent security, the dream of patient confidentiality is increasingly utopian. The reality is that the HIPAA act lacks teeth, enforcement initiatives non-existent (as the Journal reports), and stated exceptions to the HIPAA rules are prone to misuse by the powerful and those with financial incentives. These factors make it likely that the HIPAA “guarantees” are not worth the weight of the paper they’re written on.

In reality, if you want to keep information secure, don’t put it on a computer; and if you have to put it on a computer, and the computer is to be put on a network, then the information by definition is no longer secure.

These harsh realities call for a critical rethinking of the types of clinical data that should be put into electronic databases, and on governance of privacy, security and confidentiality. In the U.S. there is an office with a mandate to consider such issues, the Office of the National Coordinator for Health IT (ONCHIT) in the Department of Health and Human Services [4]. I call on ONCHIT to lead this needed rethinking in our national strategy for electronic healthcare information.

Notes:

[1] “CfH report confirms confidentiality risk,” The Register, Nov. 27, 2006, http://www.theregister.co.uk/2006/11/27/care_record_conf/

[2] http://www.nhsconfidentiality.org/?p=37

[3] Foundation for Integrity and Responsibility in Medicine, http://hcrenewal.blogspot.com

[4] Office of the National Coordinator for Health IT (ONCHIT), Department of Health and Human Services (HHS), http://www.hhs.gov/healthit/rfi.html

-- SS

More on Questionable Marketing of Atypical Anti-Psychotic Drugs

Yet more information is emerging about questionable practices used by pharmaceutical companies to market psychiatric medications.

The New York Times has continued its series about how Eli Lilly and Co. marketed its best-selling anti-psychotic drug, Zyprexa (olanzapine). Yesterday it published an article suggesting that Lilly suppressed data that suggested a relatively high rate of adverse effects from the drug, while releasing data that made the drug appear safer:

For at least a year, Eli Lilly provided information to doctors about the blood-sugar risks of its drug Zyprexa that did not match data that the company circulated internally when it first reviewed its clinical trial results, according to company documents.

The original results showed that patients on Zyprexa, Lilly’s pill for schizophrenia, were 3.5 times as likely to experience high blood sugar levels as those taking a placebo, according to a February 2000 memo sent to top Lilly scientists.

The 2000 memo indicates that it was prepared as Lilly considered changing Zyprexa’s prescription label to provide doctors with more information about the drug’s potential to raise blood-sugar levels.

According to the memo, Lilly scientists initially wanted to propose a relatively straightforward statement on the label that high blood sugar had been observed in patients taking Zyprexa in clinical trials. That change was never made.

According to the memo, Lilly had reviewed data from its clinical trials and found that 'the incidence of treatment-emergent hyperglycemia in olanzapine group (3.6%) was higher than that in the placebo group (1.05%).' Olanzapine is the generic name for Zyprexa.

But when Lilly subsequently discussed the clinical trial results with doctors, it used a different comparison. Lilly told doctors that Zyprexa had caused 3.1 percent of patients — not 3.6 percent — to have high-blood sugar. And it said that 2.5 percent of patients on the placebo — not 1.05 percent — had high-blood sugar. As a result, the rates of high blood sugar in the two groups seemed almost identical in the revised data.
Another Lilly report, from November 1999, shows that Lilly found after examining 70 clinical trials that 16 percent of patients taking Zyprexa for a year gained more than 66 pounds.

The company did not publicly disclose that figure, instead focusing on data from a smaller group of clinical trials that showed about 30 percent of patients gained 22 pounds.

A few days earlier, the Times had published an editorial on Lilly's marketing of Zyprexa.

It was bad enough when studies showed that the newest and most heavily promoted drugs for treating schizophrenia weren’t worth their high cost. Now the disturbing tale of their excessive use has taken a tawdry turn with revelations that Eli Lilly, a pharmaceutical giant, has consistently played down the risks of its best-selling antipsychotic drug, Zyprexa, and has promoted it for unapproved uses.

Although Lilly says the documents present an inaccurate picture, they offer persuasive evidence that the company engaged in questionable behavior to prop up its best-selling drug, which creates almost 30 percent of Lilly’s revenue.

Meanwhile, it was widely reported that Bristol-Myers-Squibb had agreed to settle charges having to do with problems with its sales and marketing practices, particularly of its big-selling atypical anti-psychotic drug, Abilify (ariprazole). Again, from the New York Times report:

Bristol-Myers Squibb has reached a tentative agreement to pay $499 million to settle a federal investigation into illegal sales and marketing activities from the late 1990s through 2005, the company said yesterday.

That settlement, and separate special charges the company also announced yesterday, would wipe out Bristol-Myers fourth-quarter profit.

Bristol-Myers, based in New York, declined to disclose which years, which drugs and which practices the tentative agreement covers. But Jeff Macdonald, a company spokesman, confirmed previous reports that one product involved was the antipsychotic drug Abilify, one of the company’s best sellers.

Bristol-Myers said it also expected to sign a corporate integrity agreement with regulators in the Health and Human Services Department who monitor industry compliance with federal insurance programs.

The antipsychotic drug Abilify covered in the settlement has become the company’s best-selling product outside of its flagship cardiovascular group....

There is increasing reason to fear that the basis of much current thinking about the management of major psychiatric disorders, particularly schizophrenia, is on very shaky ground. More and more of the information that pharmaceutical companies have provided to physicians appears to be dubious. And very recently, allegations surfaced that pharmaceutical companies got far too cozy with state mental health departments to develop treatment algorithms for major psychiatric disease that emphasized the use of the newest, most expensive drugs, even though it is no longer clear that these drugs are so much better than older and cheaper treatments (see post here). Note that these Texas Implementation of Medication Algorithms (TIMA) pushed five new atypical anti-psychotic drugs for schizophrenia, including Abilify and Zyprexa.

To take the best possible care of each patient, physicians (and patients) need maximally accurate and unbiased information about the performance of drugs, devices, and diagnostic tests. It may be in the financial interests of companies that make such products to gimmick the data in their favor, but such manipulation can hurt patients, and surely is an unheralded reason for the continuing rapid rise in health care costs.

It is high time to get pharmaceutical, biotechnology, and device companies out of the business of the clinical testing of their own (or competitors') products. Let these companies sponsor the basic biology research needed to develop innovative new products. Clinical research on patients to evaluate these products should be done by organizations and researchers with no horse in the race.

Guidelines in Whose Interest? - Pharmaceutical Companies and the Texas Medication Algorithm Project (TMAP)

Out of Texas comes a story with allegations of pharmaceutical industry involvement in the crafting of state mandates for the treatment of psychiatric illness. Per the Dallas Fort Worth Star Telegram (edited, and re-ordered):

A recently unsealed lawsuit accuses Johnson & Johnson and related companies, including Janssen Pharmaceutical, of conning the state of Texas into spending millions of dollars on costly psychiatric drugs.

The suit targets a controversial state program that instructs doctors at state-funded healthcare facilities about which medicines to prescribe for a variety of mental illnesses.

The suit was filed in 2004 in Travis County by Allen Jones, a former employee of the Pennsylvania Office of Inspector General who investigated drug companies' ties to his state's officials. In the process, he learned of allegations related to Texas. The Texas attorney general's office has joined the lawsuit.

While the suit does not name a "state mental health program decision-maker" who it alleges received payments and other benefits, a spokeswoman for the Texas Health and Human Services Commission confirmed that the lawsuit refers to Dr. Steven Shon, who managed the program. Shon took more than 80 trips throughout the country and abroad to promote it, with his expenses often underwritten by drug companies.
Shon, who left the Department of State Health Services this fall while the investigation was ongoing, said he has not received money from drug companies in connection with his work for the state. Money paid for his travel expenses or to reimburse taxpayers for his time away from the office, he said.

'These assertions are really ridiculous, he said.

However, Shon said he received a few thousand dollars from Janssen several years ago for consulting work unrelated to his state job. He said he got approval from the department's legal staff, but commission spokeswoman Stephanie Goodman said the agency was unaware of payments and would not have approved them.

The lawsuit alleges that Johnson & Johnson and its subsidiaries misled state officials about the benefits of the antipsychotic drug Risperdal, including promoting it for treating children when the drug had not been federally approved for such use. The company's influence led the state to purchase the expensive brand-name drug instead of cheaper generic alternatives, according to the lawsuit. The result, it alleges, was that the state paid excessive amounts in claims for Medicaid, which covers medical costs for low-income people.

A major portion of the lawsuit focuses on the Texas Medication Algorithm Project, which Shon coordinated. That program offers a series of treatment plans, or algorithms, for various mental illnesses, including which drugs to use. In many cases, the plans recommend the newest drugs, which are the most expensive and are not available in generic form.

Such drugs generate much income for pharmaceutical companies. In a recent three-year period, more than $190 million was paid in Texas for outpatient Medicaid claims for Risperdal alone, according to the state Health and Human Services Commission. During those same years -- 2002 to 2005 -- almost $700 million was spent on all antipsychotic medications combined. That does not include care for those who are in state institutions.

Drug companies, including Janssen, gave the state more than $1 million to help promote the plan. And the Robert Wood Johnson Foundation, established by the founder of Janssen parent company Johnson & Johnson, gave $2 million. A company spokesman previously said the foundation is independent of the company.

The exact amount donated by the companies remains unclear. Shon has acknowledged that his agency did not always seek required approval from the department's governing board before accepting donations.

Shon left his job with the state in October.

Shon said he was given the option of resigning or being terminated, and he chose to leave.

In addition, per a reporter for an Austin television station,

Shon spent a great deal of his time traveling around the country promoting the TMAP treatment guidelines.

Shon made at least 84 trips. Many of the trips were courtesy of the drug companies whose drugs are specified in TMAP and have a financial interest in getting other states to adopt the program.

'So when ever you were going on trips to speak on behalf of this and the money was coming from the pharmaceutical companies were you ever aware that it might look like a conflict of interest,' CBS 42’s Nanci Wilson asked.

'I think that it possible could, but I thought that given the fact that this is how conferences and education works, I didn't think that this was really any different then what was going on anywhere else,' Shon said.

But Shon's trips to Pennsylvania weren't business as usual.

'The check originated as an unrestricted educational grant from Janssen to the Harrisburg State Hospital here in Pennsylvania,' Allen Jones said. 'However, the check was deposited to an off the books account and a separate check written out to Shon in the exact amount of the unrestricted educational grant. And while they called it an unrestricted grant, the supporting documentation clearly, clearly established that the purpose of the monies was to bring Shon to Pennsylvania to sell the TMAP program to Pennsylvanian officials.'

Before commenting, I need to acknowledge that the story above is based only on allegations, so far. The law-suit has not gone to trial, and there may be more than one side to this story.

Nonetheless, the allegations are striking. We have previously posted on allegations of attempts to influence guidelines by those trying to sell drugs, devices, or services that such guidelines may support. However, in the current case the allegations were of attempts to influence state mandated treatment algorithms (the Texas Implementation of Medication Algorithms, or TIMA), not mere guidelines. (As best as I can tell from the TMAP web-site, particularly its FAQ section, these algorithms are mandatory for all state mental health outpatient facilities.)

If nothing else, this reinforces the need for physicians, health care professionals, and patients to be extremely skeptical about how guidelines are written, and who has influenced their writing.

Parenthetically, note that this skepticism should extend to guidelines labelled as "evidence-based." The TMAP algorithms are described as evidence based, but I can find nothing on the TMAP web-site that explains how the process used to develop them fit this definition.

ADDENDUM (12/20/2006): See also these posts (here and here) on Clinical Psychology and Psychiatry.

Conflicts of Interest: All in the Family

In the last week two stories surfaced about conflicts of interest within health care organizations that involved family ties.

The St Jude Sales Representative and the Jackson Memorial Chief Cardiologist

The first one was in the Miami Herald. The basic elements were as follows. Monica Rodriguez was a representative first for Medtronic, specializing in implantable cardiac devices. She had been a patient of Dr Alberto Interian Jr, who was interim chief of cardiology at Jackson Memorial Hospital, a major teaching hospital for the University of Miami. Rodriguez had listed Interian "as a recommendation on her application to Medtronic." Rodriguez quit Medtronic in May, 2004. " That summer, Interian and Rodriguez say, they began seeing each other socially." Interian first urged Medtronic to re-hire Rodriguez, then urged Guidant to hire her. Finally, she took a job with St. Jude Medical. Then, suddenly, sales of St. Jude devices to Jackson Memorial increased. "In the final four months of 2004, Jackson paid $499,145 to Medtronic, $405,750 to Guidant and $166,000 to St. Jude. That changed. Starting in February 2005, St. Jude sales led the other two for the next six months. In 2005, investigators say, St. Jude's sales at Jackson increased about $2 million. Medtronic's fell about $2 million at Jackson and about $1.8 million at the VA hospital. Guidant didn't offer figures but said sales fell."

Soon, Rodriguez and Interian's ongoing relationship was revealed. A Medtronic manager "received a call from a sales rep who handled Medtronics accounts at Jackson: 'She was incensed. She . . . said they were dating. She said, `We are going to lose our shirt.' . . . She started losing business right away.'' Then, "In June 2005, anonymous letters faxed to UM President Donna Shalala and Jackson chief executive Marvin O'Quinn revealed the romance and the shift of sales to St. Jude."

Then, "On Aug. 16, UM's internal audit department decided there was ''at the very least, a possible perception of conflict of interest.' The UM report indicated Interian said 'it's a coincidence that he's come to view [St. Jude] as better since he started dating her.'" Apparently, Interian and Rodriguez decided she should stop working at Jackson Memorial. However, her departure was delayed. "On Nov. 17, Interian's boss, Laurence B. Gardner, fired off a heated e-mail to Interian: 'Al, the board of trustees has told me your 'friend' still has Jackson. I would remind you that is exactly the opposite [of what] you told me.''' Then Interian was fired as interim chief of cardiology. "Eventually, Rodriguez left Jackson but kept working at Mercy Hospital, where Interian operates under a contract as medical director of the Arrythmia/Syncope Center. In April, ethics investigators Karl Ross and Kennedy Rosario submitted a report noting that taxpayer dollars had been spent at Jackson and that the county code states no person 'shall use or attempt to use his official position to secure special privileges or exemptions for himself or others.' The report concluded that the 'primary beneficiary' of St. Jude's rise in sales was Rodriguez, who earned more than $100,000 from sales to Interian's department at Jackson alone, along with tens of thousands at other hospitals where he worked."

The FDA Manager and the Platinum Solutions Advisory Board Member

The second story comes from the Los Angeles Times. Margaret "Margo" Burnette was a senior manager at the US Food and Drug Administration (FDA). She was in charge of developing a new data system to handle industry applications for medical products. She was working with a contractor called ProObject Inc. to develop the system. In April, 2004, Burnette married Mark A Boster. "That same month Burnette was promoted to information-technology director. A top FDA official praised her as a 'very successful leader.' Boster, who was working full-time with another technology contractor, joined Platinum Solutions [Inc.] ' advisory board about then. He was paid a retainer and fees for attending meetings, he said." At about the same time, "Burnette was making no secret within the FDA of her displeasure with ProObject." The agency did not obtain a satisfactory replacement through the competitive bidding process. "At that point Burnette conferred with her husband and steered her deputy, James Shugars, to contact Platinum Solutions." Then, "Once Platinum Solutions was aboard, Burnette said, she assigned Shugars to handle 'contract issues' directly with the company. Shugars briefed her regularly, she said. [Burnette's supervisor James J] Rinaldi said that Shugars voiced concerns to him and was 'very, very nervous' about managing the data project while reporting to Burnette. I think he was concerned about just the overall conflict of interest,' said Rinaldi, now chief information officer at the federal Jet Propulsion Laboratory in La Cañada Flintridge. 'Obviously that was because of the spouse.' Rinaldi confirmed that the FDA awarded the initial contract to Platinum Solutions without competition, a move that hinged on the company's special status as a disadvantaged business."

"In June 2005, Burnette said she relinquished any role with the data project because about two months earlier her husband had become a full-time executive with Platinum Solutions. In addition to salary, Boster's new position placed him in line for extra pay when the company's revenue increased, he said. 'Since he was actually working there as the chief operating officer, the perception would have been just too bad,' Burnette said. 'It would have appeared that I would have had some influence.' This year, the FDA sought competitive proposals for the completion of its data system. On Nov. 27, Platinum Solutions said that it won the contract. Although Burnette said she no longer oversees the project, she helps shape technology priorities from the FDA commissioner's office. Her husband said that he was in charge of Platinum Solutions' performance on all ongoing contracts, including with the FDA."

There is no report yet of any official response by the FDA to all this.

Comments

It seems that if we search, we may find every possible species of conflict of interest affecting large health care organizations. It also appears that organizations that have issues with any one type of conflict are likely to have issues with other types. For example, we previously posted about apparently major conflicts of interest affecting the President of the University of Miami, Jackson Memorial's parent university. And we very recently posted about conflicts of interest affecting members of FDA scientific advisory panels.

One wonders how practicing physicians and other health professionals in the trenches, much less the public at large would react if all such conflicts were fully disclosed.

The pervasive web of conflicts that spans many of the large organizations that now dominate health care suggest that much of the health care system may operate more for the private benefit of its insiders than to actually improve the health of the public.

Lilly's Dubious Marketing of Zyprexa

The New York Times published articles yesterday and today about how Eli Lilly and Co. marketed its best-selling anti-psychotic drug, Zyprexa (olanzapine). The articles revealed several issues.

Lilly's Marketers Minimized the Risks of Obesity and Diabetes

In particular, (quotes from yesterday's article somewhat re-ordered):

Lilly’s own published data, which it told its sales representatives to play down in conversations with doctors, has shown that 30 percent of patients taking Zyprexa gain 22 pounds or more after a year on the drug, and some patients have reported gaining 100 pounds or more. But Lilly was concerned that Zyprexa’s sales would be hurt if the company was more forthright about the fact that the drug might cause unmanageable weight gain or diabetes, according to the documents [supplied to the Times], which cover the period 1995 to 2004.

Critics, including the American Diabetes Association, have argued that Zyprexa, introduced in 1996, is more likely to cause diabetes than other widely used schizophrenia drugs. Lilly has consistently denied such a link, and did so again on Friday in a written response to questions about the documents. The company defended Zyprexa’s safety, and said the documents had been taken out of context.

The documents show that Lilly encouraged its sales representatives to play down those effects when talking to doctors. In one 1998 presentation, for example, Lilly said its salespeople should be told, 'Don’t introduce the issue!!!'

To reassure doctors, Lilly also publicly said that when it followed up with patients who had taken Zyprexa in a clinical trial for three years, it found that weight gain appeared to plateau after about nine months. But the company did not discuss a far less reassuring finding in early 1999, disclosed in the documents, that blood sugar levels in the patients increased steadily for three years.

But as early as 1999, the documents show that Lilly worried that side effects from Zyprexa, whose chemical name is olanzapine, would hurt sales.

'Olanzapine-associated weight gain and possible hyperglycemia is a major threat to the long-term success of this critically important molecule, Dr. Alan Breier wrote in a November 1999 e-mail message to two-dozen Lilly employees that announced the formation of an 'executive steering committee for olanzapine-associated weight changes and hyperglycemia.'

At the time Dr. Breier, who is now Lilly’s chief medical officer, was the chief scientist on the Zyprexa program.

In 2000, a group of diabetes doctors that Lilly had retained to consider potential links between Zyprexa and diabetes warned the company that 'unless we come clean on this, it could get much more serious than we might anticipate,' according to an e-mail message from one Lilly manager to another.

Lilly did expand its marketing to primary care physicians, who its internal studies showed were less aware of Zyprexa’s side effects. Lilly sales material encouraged representatives to promote Zyprexa as a “safe, gentle psychotropic” suitable for people with mild mental illness.

Not surprisingly, Lilly spokespeople did not agree with the Times' assertions.

On Friday, in its written response, Lilly said that it believed that Zyprexa remained an important treatment for patients with schizophrenia and bipolar disorder. The company said it had given the Food and Drug Administration all its data from clinical trials and reports of adverse events, as it is legally required to do. Lilly also said it shared data from literature reviews and large studies of Zyprexa’s real-world use.

Lilly's Marketers Promoted Zyprexa for Unapproved Uses, Particularly Dementia
According to the second article,

Lilly encouraged primary care physicians to use Zyprexa, a powerful drug for schizophrenia and bipolar disorder, in patients who did not have either condition, according to internal Lilly marketing materials.

In the [promotional] campaign, called Viva Zyprexa, Lilly told its sales representatives to suggest that doctors prescribe Zyprexa to older patients with symptoms of dementia.

Zyprexa is not approved to treat dementia or dementia-related psychosis, and in fact carries a prominent warning from the F.D.A. that it increases the risk of death in older patients with dementia-related psychosis.

Yet in 1999 and 2000 Lilly considered ways to convince primary care doctors that they should use Zyprexa on their patients. In one document, an unnamed Lilly marketing executive wrote that these doctors 'do treat dementia' but 'do not treat bipolar; schizophrenia is handled by psychiatrists.'

As a result, 'dementia should be first message,' of a campaign to primary doctors, according to the document, which appears to be part of a larger marketing presentation but is not marked more specifically.

Later, the same document says that some primary care doctors 'might prescribe outside of label.'

As part of the 'Viva Zyprexa' campaign, in packets for its sales representatives, Eli Lilly created the profiles of patients whom it said would be suitable candidates for Zyprexa.

The third patient was 'Martha,' a widow with adult children 'who lives independently and has been your patient for some time.' Martha was described as being agitated and having disturbed sleep, but without the symptoms of paranoia or mania that typically marked a person with schizophrenia or bipolar disorder.

[Lilly spokeswoman] Ms. Nobles said that Lilly had actually intended Martha’s profile to represent a patient with schizophrenia. But psychiatrists outside the company said this claim defied credibility, especially given Martha’s age. Instead, she appeared to have mild dementia, they said.

This appears to be yet another sad tale of how marketing enthusiasm has been given free rein in the pharmaceutical industry, unopposed by any sense of the evidence of particular drugs' benefits and risks.

This is another reminder about how skeptically physicians ought to view the marketing of health care goods and services.

Note that several other health care bloggers have commented on this story (See Medrants, Retired Doctor's Thoughts, and Clinical Psychology and Psychiatry). But given the size of the company involved, and the popularity of the drug, it seems worthy of all this attention.

Johns Hopkins President (and Medtronic Director) Claims Right to Punish Speech He Deems "Not Substantive and Serious"

Manifestation of concentration and abuse of power that we discuss frequently on Health Care Renewal are attempts to suppress free expression. These attempts are usually directed at expression that those in power find offensive. Two recent examples include: attempted suppression of clinical research that suggested an increased incidence of adverse effects due to the drug aprotonin (most recent post here), and the prolonged silencing of a whistle-blower who questioned the financial conduct of a hospital CEO (see most recent post here). (The CEO was later convicted of fraud.)

Some insight into the thinking of those who attempt to suppress free expression in health care may come from a recent case at Johns Hopkins University, parent university for one of the world's most renowned medical schools and academic medical centers. The recent controversy started when a JHU undergraduate student posted an invitation on the web to a campus party which included crude language. Some found the language offensive, if not racist. It was not surpising that the student received fierce condemnation. However, the university then charged him with “failing to respect the rights of others and to refrain from behavior that impairs the university’s purpose or its reputation in the community,” violating the “university’s anti-harassment policy,” “failure to comply with the directions of a university administrator,” “conduct or a pattern of conduct that harasses a person or a group,” and “intimidation.” His punishment was a year's suspension, and that he complete 300 hours of community service; read 12 books and write a reflection paper on each; and attend a workshop on diversity and race relations.

The University's actions were condemned by the FIRE (Foundation for Individual Rights in Education), which has stood up forcefully for free speech and academic freedom in US institutions of higher education. A FIRE spokesperson stated, “Hopkins’ unconscionable treatment of [the student] ... should shock anyone who values free speech,” Furthermore, “Johns Hopkins must not be allowed to promise free speech to its students and then deliver heavy-handed repression.”

However, JHU President Dr William R Brody attempted to justify the university's actions in an article in the Johns Hopkins Gazette. Although he condemned past attempts by the university to suppress speech "of a substantive and serious nature," he then argued:

But I think we all know that it stretches our credulity to assert that two crude and tasteless invitations to a fraternity party posted on an Internet Web site rise to this standard of seriousness of purpose or intent. What I see here is not a courageous trespass of taboo speech but rather a fundamental breach of civility of the sort that is so commonly displayed in disparagement, mockery or epithets drawn along racial or ethnic lines. It is, simply put, common name-calling. This is what I believe we should agree is unacceptable in our community of free and open discourse. Let us not forget that true civility is not a program of fair treatment for this or that constituency but rather an underlying and fundamental commitment to showing respect for everybody.

So Brody asserted that only "substantive and serious" speech is protected. And Brody reserved to himself the right to determine what speech is "substantive and serious." Brody's "community of free and open discourse" would not protect discourse which its leader deemed to be only "common name-calling," or a "fundamental breech of civility." Yet, claims that free speech is protected ring hollow when the only speech protected is that which the powers that be find acceptable.

The Torch, the blog sponsored by FIRE, provided this telling quote from FIRE's Guide to Free Speech on Campus:

[John Stuart] Mill addressed one of the major rationales for imposing constraints on free speech on campuses today, namely that speech should be 'temperate' and fair.' Mill observed that while people may claim they are not trying to ban others’ opinions but merely trying to banish 'intemperate discussion…invective, sarcasm, personality, and the like,' they never seek to punish this kind of speech unless it is used against 'the prevailing opinion.' Therefore, no one notices or objects when the advocates of the dominant opinion are rude or uncivil or cruel in their denunciations of their detractors. Why shouldn’t their opponents be equally free to show their disdain for the dominant opinion in the same way? Further, Mill warned, it always will be the ruling orthodoxy that gets to decide what is civil and what is not, and it will decide that to its own advantage.

Although the particulars of the current case at Johns Hopkins University seem far afield from the issues of concern to Health Care Renewal, Dr Brody did not limit the application of his argument to party invitations posted by undergraduates to the internet. His ability to punish any speech not deemed to be sufficiently "substantive and serious" should thus give pause to anyone at JHU who might publish clinical research that could offend vested interests, blow the whistle on health care quality issues, or question hospital or university administrators. Dr Brody's ability to punish such speech also seems to contradict the University's mission statement, which aims to "foster independent and original research, and to bring the benefits of discovery to the world."

Finally, I should note that Dr Brody's writings may also give insight into how little leaders of commercial health care organizations respect free speech, free expression, and academic freedom. Note that Dr Brody leads not only Johns Hopkins University, but also, as a Director, Medtronic Inc, "the global leader in medical technology." According to Medtronic's 2006 proxy filing, Dr Brody's yearly compensation as Director is $80,000 in cash, and $70,000 in stock options. Dr Brody currently owns more than 72,000 shares or the equivalent in the company's stock (worth more than $3,900,000 at the stock price of $54.28 /share today). Yet, I wonder if he would regard any questions about whether this part-time job, entailing fiduciary responsibility to a company which has "research and/or business relationships" with JHU, and which "periodically makes donations and/or grants" to JHU, constituted an important conflict of interest as not "substantive and serious," but mere "common name-calling?" I doubt anyone at JHU will try to find that out.

Medical CME and Conflicts of Interest: GSK Funds Talks About Screening Pregnant Women for Herpes

The Wall Street Journal just published an article by David Armstrong about how continuing medical education (CME) often seems to serve the interests of its commercial sponsors. The focus of the article was on how GlaxoSmithKline funds speakers who seem to favor clinical policies that just might end up increasing the use of the GSK drug valacyclovir (Valtrex) for genital herpes infections. (See our recent post about the attempted suppression of a study comparing Valtrex to Famvir here.)

The article focused on talks given by Dr Zane A Brown of the University of Washington. To quote from the article,

Addressing doctors, medical residents and students at Ohio State University Medical Center in September, Zane Brown advocated a big change in prenatal care: testing all pregnant women for genital herpes.

Widespread testing would reduce herpes infection in newborns, said Dr. Brown, an obstetrician at the University of Washington medical school.

It also would probably lead to a rise in the use of herpes drugs by pregnant women. That would be a boost to GlaxoSmithKline PLC, which sells the top-selling herpes drug -- and which paid for Dr. Brown's lecture.

Glaxo says it doesn't market its herpes drug, called Valtrex, in any way for pregnant women.

Doctors, however, aren't restricted in how they use an approved drug, nor in what they can say about it in talks to other medical professionals. And currently, about 10 doctors are fanning out across the U.S. making the case for universal genital-herpes screening of pregnant women. Glaxo funds these talks by giving grants to hospitals and other institutions that host them.

The lectures are called continuing medical education, or CME. Doctors who attend earn credits needed to maintain their medical licenses. Drug makers increasingly use lectures and articles by outside doctors to get their message across, at a time when hospitals often restrict salespeople's access. The funding reflects a broader trend of drug companies trying to influence medical practice, not always with full disclosure of their role. However, Dr. Brown, speaking to doctors in Ohio in September, mentioned Glaxo's funding of the talk.

Dr. Brown says he gives two to three lectures a week advocating universal herpes testing for pregnant women, earning $1,000 to $2,500 per talk. He says his motive isn't money but a desire to reduce the number of babies born with herpes. Because his own university lacks the funds to pay for his lectures, he says, he has a relationship with Glaxo born of necessity. 'I am using them and they are using me,' he said recently as he waited to board a flight to Tennessee for a series of lectures at hospitals there.

A Glaxo spokeswoman said the company has no 'control over the selection of speakers or the material presented' at CME lectures it funds. In the case of the Ohio State lecture, a professor who organized it, Wayne Trout, said, 'We approached [Glaxo] and said we want to bring Dr. Brown in -- can you give us some funding?' Glaxo declines to comment on specific programs.

Dr Brown is not the only one getting into this particular act.

The message doctors get in continuing-medical-education lectures and Web sites clearly favors testing and treatment of pregnant women. An example is an online CME lecture provided by Medscape LLC last March. Medscape says it picked the herpes speakers -- Dr. Brown and another pro-screening doctor, Serdar Ural of the University of Pennsylvania -- from a list provided to it by Glaxo, which funded the event. Glaxo said there's nothing wrong with providing names of potential speakers and added that CME sponsors have ultimate control over who speaks.

In the lecture, Dr. Ural advocated giving antiviral medication to all pregnant women who test positive for herpes even if they show no symptoms. He acknowledged there wasn't a lot of evidence such a strategy works but said, 'What is the downside? If she takes medication for a couple of weeks, side effects compared to placebo are about the same.' Dr. Ural said he has given 11 Glaxo-funded talks this year, declining to say how much he has been paid.

David A. Baker, a professor of maternal-fetal medicine at the medical school at the State University of New York in Stony Brook, lectures on herpes for Medscape and also for a firm called Omnia Education. Omnia receives funding both from Glaxo and from Quest Diagnostics Inc., maker of a herpes test. Dr. Baker typically discloses he is a consultant to Glaxo. In a filing with the New York State Ethics Commission, he also reported owning Glaxo stock. Asked about his stockholdings, he declined to comment, through a spokesman.

The American Journal of Obstetrics & Gynecology published a study in March that promoted the use of Valtrex in pregnant women over a generic alternative or no treatment at all. Not mentioned was that co-author Richard Whitley, a pediatrician at the University of Alabama at Birmingham medical school, is a member of the Valtrex maker's speakers bureau.

Dr. Whitley said in an interview he didn't disclose this because he hadn't yet begun his work as a Glaxo speaker. Yet his university disclosure forms indicate he has been a speaker for Glaxo since at least 2003. Asked about this, Dr. Whitley said through a spokesman that 'my omission of mentioning serving as a speaker for GlaxoSmithKline was an honest and simple oversight, made because my involvement in this role is quite minimal as a regional speaker.'

The article noted that there is no strong evidence supporting screening of pregnant women for herpes. In fact, the US Preventative Services Task Force, which usually follows the evidence-based medicine process pretty closely, suggests that screening not be done.

We just seem awash this week in conflict of interest stories. In this one, we have academic physicians whose talks, at $1000 - $2500 a pop, which suggest aggressive screening for herpes with little evidentiary justification, which presumably could lead to aggressive use of anti-viral agents for patients who test positive, just happened to be supported by a pharmaceutical company that makes those anti-viral agents.

Again, this suggests, at the least, the need for much more thorough disclosure of conflicts of interest by, in this case, all those who give CME presentations. One wonders if audience skepticism would have been increased if Dr Brown announced before each talk the amount he was paid to give it, and the total amount he received from GSK in the previous year, and made it clear that the strategies advocated in his talk would tend to increase the use of Valtrex, which just happened to be manufactured by GSK.

In lieu of such policies, doctors attending CME talks given by supposedly impartial experts (or those reading articles or guidelines written by other supposedly impartial experts) need to be very skeptical about for whom these experts actually work, and whose interests their talks, articles, and guidelines actually support.

FULL DISCLOSURE - I participate in a more or less monthly Roundtable discussion published by Medscape on the web.

Another Tale of Conflicts of Interest: Kyphon, Kyphoplasty, and the Surgeon with Stock Options

Here we go again. The Cleveland Plain Dealer published an investigative report about financial entanglements between an orthopedic surgeon who advocated for a particular procedure, kyphoplasty, for treating spinal fractures due to osteoporosis, and the company, Kyphon Inc, that made the equipment used in the procedure. To summarize, using quotes from the Plain Dealer:

Back braces, bed rest and medications had been the mainstays for treating the estimated 700,000 spinal fractures a year in this country alone caused by osteoporosis and other conditions. Then, in the mid-1980s, doctors in France began experimenting with the concept of vertebroplasty.

The first vertebroplasty in the United States was performed in 1993. An orthopedic surgeon, Dr. Mark Reiley, soon developed the idea of using a balloon to improve results, and he co-founded Kyphon. The company's focus the first few years was to raise money and develop the instruments used in kyphoplasty.

Next, Kyphon needed studies with influential practitioners and institutions to demonstrate that the treatment worked.

[Dr Isadore] Lieberman began offering advice to Kyphon in 1997, the [Cleveland] Clinic said, shortly after he came to Cleveland. In 1999, Kyphon provided equipment to a handful of major medical centers, including the Clinic. Lieberman, a specialist in the surgical treatment of spinal disorders, oversaw the hospital's inaugural kyphoplasty work. The findings of the Lieberman-led 30-patient trial were the first kyphoplasty results by a hospital detailed in a medical journal.

Well before the publication of that study in July 2001, Lieberman's work helped Kyphon generate buzz about its new technology.

On the SpineUniverse Web site, Lieberman, Kyphon co-founder Reiley and three other doctors published a four-paragraph synopsis of their initial experiences with kyphoplasty involving 26 patients. 'These results support further use of kyphoplasty,' the March 2000 summary concluded.

Also in 2000, Kyphon posted data from Lieberman's Clinic procedures in bar-graph form on its Web site to show kyphoplasty's favorable results.

Kyphon's use of Lieberman's data and other information without FDA permission prompted the agency in October 2000 to issue a warning letter to Kyphon.
Kyphon gave Lieberman a seat on its scientific and clinical advisory board. And during the period he was conducting his first kyphoplasty trial at the Clinic, he had an offer of stock options from the company.

When Kyphon officials took their company public in May 2002, they disclosed in a filing with the Securities and Exchange Commission that they had offered stock options to the eight members of their advisory board. All took them except Dr. Joseph Lane, a New York orthopedic surgeon who teaches at the medical school affiliated with Cornell University.

As of December 2001, the company had reserved 948,000 options for consultants and other non-employees at a cost of $1 or less - some as low as 3.5 cents, records show. The company is not required to divulge how many were held for individual members of the advisory board.

Medical journals show that Lieberman and most of the other consultants conducted kyphoplasty research around the time they were offered stock options. Their research was frequently cited by Kyphon in promotional material aimed at other doctors and medical insurance providers. Lieberman and other consultants also lobbied for insurance coverage of kyphoplasty treatments.
Kyphon was straightforward in describing its motivation for offering stock to consultants, saying it provided 'additional incentive' and was designed to 'promote the success of the company's business,' SEC records show.

The article went on to document how Lieberman had failed to disclose his financial relationships with Kyphon when speaking in favor of kyphoplasty and Kyphon's products:

In the spring of 2005, Lieberman testified to the benefits of kyphoplasty at a Centers for Medicare and Medicaid Services committee hearing. He and all other participants were asked to disclose all past and present financial involvement — including stock and stock options — with device makers.

But Lieberman did not reveal his past stock holdings, limiting his disclosure to working as a consultant for Kyphon and receiving grant and research support from the company.

Later in the hearing, the committee vice chairwoman reminded participants to disclose all holdings and specifically asked Lieberman and other doctors if they wanted to note anything else. Lieberman said nothing about his past holdings.

The Clinic said Lieberman had sold all of his Kyphon stock by that time and that he was not asked to go into detail about his financial interests. Yet minutes from the hearing show that he was asked to disclose past and current stock holdings, and there is no record he made such a disclosure.

Physicians are expected to disclose to medical journals financial relationships with companies that are the subjects of their research. That standard has been in place about six years, according to medical ethicists, following a well-publicized patient death in a University of Pennsylvania clinical trial.

But Lieberman did not divulge any relationship with Kyphon when results of his first two kyphoplasty studies were published in 2001 and 2002. In a 2003 article detailing other research, Lieberman noted only that he was a consultant to Kyphon, which is how he has usually described the relationship in articles about kyphoplasty or in presentations at conferences. The Clinic last week acknowledged that Lieberman held stock in 2003.

He failed to identify his stock interests in Kyphon for specialized medical and general audiences, according to a Plain Dealer review of medical journals, other publications and publicly available conference programs.

Also,

Lieberman's actions are noteworthy for another reason: He is a member of the Clinic's conflict-of-interest committee, charged with overseeing the relationships the hospital's physician-researchers have with private industry.

The Plain Dealer reporter asked for a response from Lieberman. In a written statement, he said, "I strive to be transparent in my disclosures and believe that I have disclosed my interests within the guidelines and policies of the Cleveland Clinic," but would not be interviewed.

The article included some opinions about Lieberman's conflicts of interests:

Medical-ethics experts say Lieberman's relationship with Kyphon Inc., the Sunnyvale, Calif., kyphoplasty equipment company, is troublesome because the more favorable Lieberman's research and the more exposure given to kyphoplasty, the more valuable his Kyphon stock would have become.

'This is a classic tale of why you wind up with a lot of technologies that are marginally better or turn out not to be better at all than what you already had - because you rely on reports from innovators who have economic dogs in the fight,' said Dr. Arthur Caplan, chairman of the department of medical ethics at the University of Pennsylvania.

Also,

Lieberman 'is out there pushing the procedure at the same time that he had an equity interest in the company that stands to gain from his pushing the procedure, said Dr. Jerome P. Kassirer, a former editor of the New England Journal of Medicine who has written extensively on the influence of business on medicine. 'He shouldn't be doing that.'

Indeed, not.

So here we go again, with another illustration of the pervasiveness of the web of conflicts of interest that now binds together commercial health care coroporations, academic medicine, hospitals, physicians, government agencies, not-for-profit organizations, etc., etc., etc. Furthermore, this case illustrates how people with considerable financial interests in particular companies and products may write and speak favorably about the companies and products as if they were only expressing their academic and/or professional opinions.

The frequent failure of physicians and scientists in government agencies, academic medicine, and other not-for-profit health care organizations to even minimally disclose their financial interests in companies that provide health care products or services ought to breed increasing skepticism about the sorts of biases that may afflict current health care discourse. Unfortunately, it may start to provoke outright cynicism.

WHAT CAN BE DONE?

At a minimum, we need clear policies requiring detailed public disclosure of conflicts of interest afffecting all health care professionals and decision makers, with strong negative incentives to those who fail to disclose.

I would go further and say we need to ban at least the most egregious conflicts.

Without such policies, it is becoming impossible to tell the difference between scholarly discussion, and professional opinion on one hand, and commercial marketing on the other.

One More Bites the Dust: Pediatrix Director Resigns After Stock Option Backdating Revealed

Yet another US publicly traded for-profit health care corporation had admitted a problem with backdated stock options, and consequently let go one of its top leaders. We had previously posted about the nationally known problems of this sort at UnitedHealth Group, which lead to the early retirement of the company's CEO. We had also posted about similar problems at Cyberonics, leading to the resignations of its Chairman and CEO, and chief financial officer.

Now it's Pediatrix's turn. Pediatrix describes itself as "the nation’s leading provider of maternal-fetal, newborn and pediatric physician services." Last week the Miami Herald reported:

Pediatrix Medical Group, South Florida's largest publicly traded healthcare company, said Wednesday its audit committee had found ''deficiencies'' in its granting of stock options to executives, including backdating, and the company may have to recognize an additional $28 million in compensation expense from 1995 through 2006.

The Sunrise-based company, which provides newborn and related physician services throughout the nation, also announced that Lawrence M. Mullen had resigned from the board.

In a prepared statement, the company said Mullen had served as chief financial officer, chief operating officer and vice president in charge of special projects from 1995 to his retirement in 2001. During that time, Mullen ``had a significant role in the administration of the company's stock option program and practices.''

Mullen had been a member of the audit committee but had recused himself from the option review.

So this is yet example of a health care organization whose leadership apparently put their personal financial gain ahead of the ethical management of the organization.

In the past, some people have dismissed cases of financial mismanagement like this as irrelevant to the current health care mess. I beg to differ. There are lots of ways this kind of leadership problem can make health care worse. Most obviously, it drains money that could have gone to actually providing health care. Next, managers who are spending their energy dreaming up schemes like this are not likely to be very good at managing actual health care issues. Then, the people who work for such managers are likely to sense what the managers' priorities are, and hence may be demoralized and unlikely to work as hard and as efficiently as they otherwise would.

Hence, we again call for transparent, accountable, ethical leadership of health care organizations. Such leadership would take us a long way to addressing the chronic problems of rising costs, declining access, stagnant quality, and dissatisfied professionals.

Sunderland Pleads Guilty to Criminal Conflict of Interest

We have posted frequently about allegations of conflicts of interest affecting top scientists and managers at the US National Institutes of Health (NIH). The most striking case has been that of Dr Pearson "Trey" Sunderland III, who formerly lead the Geriatric Psychiatry Branch of the National Institute of Mental Health (NIMH). Sunderland was just indicted for criminal conflict of interest, based on charges that the worked as a highly-paid consultant for Pfizer Inc while he did related research as a full-time NIMH employee. He also allegedly furnished Pfizer Inc with tissue samples he obtained during his NIHM work. (See most recent post here.)

Sunderland has just entered a guilty plea in this case. Per the Los Angeles Times, reported by David Willman:

A senior government scientist from the National Institutes of Health who took about $300,000 in unauthorized payments from a drug company pleaded guilty Friday to a federal charge that he committed a criminal conflict of interest.

The admission by Dr. P. Trey Sunderland III came after years of denials by his attorneys and six months after the scientist had asserted his constitutional right against self-incrimination to a congressional subcommittee.

The prosecution was the first of an NIH scientist under federal conflict-of-interest laws in 14 years.

Sunderland, 55, admitted that he failed to get required authorization for taking $285,000 in consulting fees and $15,000 in expense payments from the drug company Pfizer Inc. from 1998 to 2003. During the same period, he provided Pfizer with spinal-tap samples collected from hundreds of patients as part of a research collaboration approved by the NIH.

After the hearing Friday, U.S. Atty. Rod J. Rosenstein told reporters that Sunderland's actions were a breach of the public trust.

A plea agreement calls for Sunderland to pay the government the $300,000 he took from Pfizer, perform 400 hours of community service, and submit to two years of probation. [Judge] Motz set sentencing for Dec. 22.

Under the collaboration with Pfizer, Sunderland's staff provided Pfizer with spinal-tap samples they had collected from patients who had Alzheimer's disease or were at risk of developing it. Drug companies prize the material because it could contain genetic clues for finding a breakthrough treatment.

Sunderland at no point from 1998 to 2003 sought permission from his NIH bosses to take the personal payments from Pfizer, and he did not disclose the income on annual financial reports.

Also, as reported by The Scientist, the Geriatric Psychiatry Branch of the NIMH has been dismantled. But
despite Sunderland's plea, Pfizer Inc. denied any wrong-doing:

Sunderland 'received honoraria for consulting and educational activities that were reasonable and customary for an expert of his stature and expertise,' Pfizer spokesman Stephen F. Lederer told The Scientist in an email. 'We believe our actions complied with applicable laws and ethical standards. We are not aware of any allegation that we violated any law or regulation.'

In my humble opinion, the only way to start beating back the tide of conflicts of interest that has enveloped health care is to start assuring negative incentives that will outweigh the personal gain or business profits afforded by such conflicts. The conviction of Sunderland is a small, but important step in this regard.

On the other hand, it is unclear how Pfizer can maintain that its actions met "ethical standards" after a recipient of the payments the company made has been convicted of criminal conflict of interest for accepting these payments.

Conflicts of Interest on FDA Panel to Assess Drug-Eluting Stents

Bloomberg News reported (here via the Boston Globe) that a US Food and Drug Administration (FDA) panel which will re-assess the risks and benefits of drug-eluting stents (DES) for coronary artery disease will include six members with conflicts of interest. Per Bloomberg:

Six physicians with financial ties to Johnson & Johnson and other heart-device makers will be advising US regulators whether to restrict the use of some products because of potentially lethal side effects.

The panel members, listed on an FDA website Nov. 22, will include Robert Harrington, who runs a Duke University research institute funded by stent makers J&J and Boston Scientific Corp.

To allow the doctors to participate in the review, the FDA is waiving rules that bar panelists from serving in matters affecting companies in which the experts have stock ownership or consulting contracts.

Agency critics, including Republican Senator Charles Grassley of Iowa, say only advisers without financial conflicts should be chosen.

Some members of Congress, including Grassley, and consumer groups such as Public Citizen in Washington have criticized the FDA in past cases for selecting panelists with financial ties to companies whose drugs or devices are under review.

Here we go again. If some members of this panel work part-time for manufacturers of DES, how critical of DES do we really expect them to be during the proceedings of the panel? If some members of this panel work part-time for manufacturers of DES, do we really expect them to ignore the interests of their employers? Finally, why does the FDA persist in putting on supposedly impartial panels meant to protect the interests of the public employees, albeit part-time, of companies whose interests will be affected by the deliberations of these panels?

This is just another case that illustrates how pervasive conflicts of interest have become in government and other health care organizations.

In my humble opinion, government regulatory agencies that are supposed to protect the health and safety of the public ought to listen to representatives of drug, biotechnology, and device manufacturers, but should not give employees of such companies decision making power within the agencies.

Note that this is the third post this week about conflicts of interest in US government agencies that are supposed to be protecting the health and safety of the public at large (see here for post about the NIH, and here for post about the CDC). Something is going seriously wrong here.

ADDENDUM (12/7/2006) In the media today (Reuters here, HealthDay here via the Washington Post) are reports that the FDA panel discussed above did not seem all too worried about the risks of drug eluting stents. Per the latter, "While the panel of 21 experts broadly dismissed the more serious risks, they split on saying the clotting risk was real in comparison with older, bare-metal stents. They agreed only that more study of the drug-coated devices is needed...." Is this so unexpected, given that almost a quarter of the panel has conflicts of interest involving the companies that manufacture such stents?

Also, note that further detail about these conflicts of interest appear in the full story run by Bloomberg News that was excerpted above by the Boston Globe, and in a story by the Newark Star-Ledger. Here is a list of the conflicted panel members from the latter:

The waivers went to Richard Page of the University of Washington, who has unrelated consulting agreements with a maker of a drug-coated stent; George Vetrovec of Virginia Commonwealth University, who has a consulting deal with a manufacturer of drug-eluting stents; and Clyde Yancy of the University of Texas Southwestern Medical Center, who has a consulting agreement with a company that makes a drug being tested for use with drug-eluting stents.

Waivers also were granted to Judah Weinberger of Columbia University, who owns stock in companies that manufacture drug-eluting stents; JoAnn Lindenfeld of the University of Colorado Health Sciences Center, a consultant with a stent manufacturer and a firm with a competing technology; and Duke University researcher Robert A. Harrington, who has consulting arrangements with several drug manufacturers with a stake in continued use of drug-eluting stents.

The Newark Star-Ledger quoted these comments from Merrill Goozner:

There are literally thousands of experts all over this country who are well-schooled in the details of this field.

But instead of reaching out to that community to get a totally unbiased look at this question, the FDA appointed a committee on which a substantial fraction have conflicts of interest directly with manufacturers of products being evaluated. It's almost impossible to have confidence in the outcomes of this kind of deliberation.

Precisely.