Was Topol Fired for Investigating Conflicts of Interest at the Cleveland Clinic?

The story of the firing of Dr Eric Topol from his leadership positions at the Cleveland Clinic Lerner College of Medicine has just gotten murkier.

The Wall Street Journal published an investigative report on the Cleveland Clinic's complex financial dealings, involving the Clinic's own venture capital fund, and a company called AtriCure. It suggests the possibility of multiple conflicts of interest affecting the top leadership of the Clinic, which were under internal investigation by a conflict of interest committee which included Dr Topol, that is, until he was fired.

In summary,

• Searching for "new ways to make money," the Cleveland Clinic sent up its own venture capital fund, Foundation Medical Partners (FMP).
• The Clinic became the biggest single investor, or limited partner, in FMP, putting in $25 million, which entitles the clinic to 38% of FMP's profits.
• Dr Delos (Toby) Cosgrove was one of the original general partners who managed the fund, and he invested in it personally. At the time, Dr Cosgrove was Chairman of the Department of Thoracic and Cardiovascular Surgery at the Clinic. "The fund's general partners were entitled to share an annual management fee of 2.75% of the money raised from investors that totals about $1.7 million a year. There were three general partners." Furthermore, "the fund's profits are known as 'the carry.'" "Dr Cosgrove was 'compensated with carry,' but didn't receive any of the management fees.."
• "Dr Cosgrove said he was required to invest in the fund by virtue of his role as general partner." Dr Cosgrove invested about $200,000 in the fund. "The fund lent ... the money to invest."
• In 2002, FMP invested $3 million in AtriCure, a private start-up company making medical devices. AtriCure makes a device that it advertises as allowing "you to make linear, transmural lesions that you can trust every time in a matter of seconds." Furthermore, "Using discreet field bi-polar radiofrequency, the AtriCure ASU delivers targeted ablative energy while simultaneously measuring the change in conductive properties of the lesion as it is created." The AtriCure web-site is very vague about what one might use such a device to do.
• Dr Cosgrove became a member of AtriCure's board of directors.
• "Dr Cosgrove also has developed a device for AtriCure ... which the company says it plans to begin marketing in the second half of next year. Dr Cosgrove would receive royalties for the device, known as the Cosgrove Clip."
• "Dr Cosgrove confirmed he also has a financial interest in companies doing research at the Clinic through his personal investment in Canaan partners," another venture fund run by Harry Rein, a friend of Cosgrove's who helped set up FMP.
• Physicians at the Cleveland Clinic have actually used to AtriCure device to treat atrial fibrillation (an irregular heart rhythm that predisposes patients to strokes) by ablating (destroying) electrically conductive heart fibers. For example, a group of Clinic physicians, including Dr. Cosgrove, published an article describing the results of this procedure on 513 patients. (Gillinov AM, McCarthy PM, Blackstone EH et al. Surgical ablation of atrial fibrillation with bipolar radiofrequency as the primary modality. J Thorac Cardiovasc Surg 2005; 129: 1321-8.) Cleveland Clinic physicians, specifically including Dr. Cosgrove, have promoted this procedure, using the AtriCure device, at national meetings.
• These physicians, again specifically including Dr Cosgrove, have not revealed their direct or indirect financial ties to AtriCure to the patients on whom they use this device, in their talks, and in their publications. For example, the article above lists Dr Gillinov and Dr McCarthy as consultants to AtriCure, but did not mention any ties that Dr Cosgrove had to the company. The article also did not mention that at the time it was written, Dr Gillinov and McCarthy had both been offered options to buy 25,000 shares of AtriCure stock.
• The US Food and Drug Administration (FDA) "has three times rejected AtriCure's application to have the system approved for cardiac use...." "Four patients are know to have died shortly after having the AtriCure procedure, at hospitals other than the Cleveland Clinic. AtriCure didn't notify the FDA...."
• "FMP has also invested in two other companies conducting trials at the Clinic: Immunicon Corp. and CardioMems Inc." The amounts it invested were $5 million and $3 million respectively. The Clinic also directly invested $2.75 million in Immunicon.
• "Last winter the Cleveland Clinic's conflict-of-interest committe learned that the FMP venture fund was an investor in companies doing research at the Clinic...." One of the members of the committee was Dr Eric Topol. "Some committee members worried that the Clinic's ties to AtriCure could color what patients were told when weighing treatment options. They also worried that their CEO's roles at AtriCure and the venture fund that invested in the company created a conflict...." "The Institutional Review Board in February directed Clinic researchers conducting clinical trials of the three companies' products to put a 'voluntary' hold on their work...." "The hold was lifted in May after the Clinic reworded consent forms."
• "The conflicts committee began to look into the role of Dr Cosgrove at FMP and AtriCure.... Not long afterward, Dr Cosgrove stepped down from AtriCure's board and said he would give up his position as a general partner at FMP."
• "Dr Cosgrove last week told Dr Topol he was losing his top post at the Clinic's medical school, a change that will take Dr Topol off the conflict-of-interests committee and the Clinic's board of governors."

The Cleveland Plain Dealer reported today that the Cleveland Clinic's board of directors has confirmed the removal of Dr Eric Topol as chief academic officer and provost of the Lerner Medical School. This action also definitively removed Dr Topol from the conflict of interest committee that had been investigating the ties among Dr Delos Cosgrove, Cleveland Clinic CEO, other Clinic physicians, FMP, AtriCure, and other companies doing research at the Clinic. Dr Cosgrove reiterated that this was part of a "streamlining move, nothing more." He said, "there are a lot of people trying to put a lot of spin on what the facts are." However, "students at the medical college sent a letter to the Clinic's board of trustees in support of Topol...." The Plain Dealer article suggested "the exposure also opens the door to questions from the Senate Finance Committee Chairman Charles Grassley, who has launched an investigation into the practices of nonprofit hospitals.
So was Dr Topol fired from his academic leadership positions to streamline the administration? This explanation seems unlikely, given Topol's prominence, and his role in creating the very medical school from whose leadership he was fired.
Was Dr Topol fired because he criticized Merck's Vioxx drug and its marketing, and revealed how Merck executives tried to intimidate him? Or was it because he helped investigate some conflicts of interest and other strange financial goings on involving top Clinic physicians and leaders, including its current CEO?
It seems more credible to suggest that Topol was punished by his own institution for blowing a whistle, regardless of which whistle proved most offensive.
Again, if such a prominent physician and academic leader can be published for whistle blowing, who in health care is safe? And if no physician or medical academic can feel safe speaking truths that offend the powerful, should any patient or student feel safe?
[Update: the MedPundit take on this story is here, the Schwitzer Health Care News take is here. Retired Doc is a bit ambivalent. Medical Rants doesn't agree, though.]

"One Horrible Debacle," Indeed: Topol Fired

Dr Eric Topol, an internationally known cardiologist at the Cleveland Clinic, a member of the Institute of Medicine, has been an important skeptic about Vioxx (rofecoxib), a drug recently withdrawn from the market by Merck amidst questions about its cardiac adverse effects. We recently posted about how Merck executives tried to discredit Topol, as revealed by Topol's trial testimony last week (see our posts here, here and here.)

After the New England Journal of Medicine published an editorial suggesting that Merck had suppressed data about the adverse effects of Vioxx in a landmark 2000 article, Topol said, "This is one horrible debacle in American medical history. I've never seen the likes of this."

Only a few days later, Topol was fired from the positions of Chief Academic Officer of the Cleveland Clinic and Provost of the Cleveland Clinic Lerner College of Medicine, of Case Western Reserve University, according to the Cleveland Plain Dealer. Although Topol "deserves a lot of credit" for the founding of the medical school, the newspaper reported that there had been recent "tension" between Topol and Cleveland Clinic CEO Dr. Delos "Toby" Cosgrove.

The New York Times talked to Topol, however, who suggested that the real reason he was fired was his testimony against Merck. Topol said,

The hardest thing in the world is just trying to tell the truth, to do the right thing for patients, and you get vilified. No wonder nobody stands up to the industry.

A Clinic spokesperson countered that Topol's firing was just part of an administrative reorganization, "the organization made the decision that position was no longer needed." There was no word of who, if anyone, would now be in charge of the medical school.

(Note: Via the blog GoozNews, the Wall Street Journal just reported serious allegations about Dr. Cosgrove's conflicts of interest related to a company named AtriCure, in which the Cleveland Clinic has a minority interest.)

Thus in the last week we have heard about two major cases involving retaliation against health care whistle blowers. We just posted about the plight of Dr. Aubrey Blumsohn, who was suspended from Sheffield University for telling the press how he had to fight a pharmaceutical company for the integrity of his clinical research (most recently here.)

The plight of whistle blowers is becoming increasingly dire. If Eric Topol can be fired for critical comments about a drug, who will be able to say anything that displeases the powers that be in health care?

Medicine cannot function if physicians cannot speak their minds. Medical research cannot function if scientists cannot freely express their opinions.

The process is even closer to "collapsing into rubble" than Dr. Curfman thought last week.

If we do not speak out for Blumsohn and Topol now, will anyone speak out later when they come for us?

[Update: MedRants doesn't agree.]

The New England Journal Charges Merck Suppressed Vioxx Research Results: "One Horrible Debacle in American Medical History"

Late last week, the New England Journal of Medicine published an unusual Editorial "Expression of Concern." (Curfman GD, Morrisey S, Drazen JM. Expression of concern: Bombardier et al., "comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis," N Engl J Med 2000; 343: 1520-8. N Engl J Med 2005; 353: 26.)

The editorial stated that an article in journal which reported on VIGOR trial, which compared Merck's drug rofecoxib (Vioxx) with naproxen, omitted mention of cardiac adverse events that were known to the study's authors before the final version of the manuscript was submitted to the journal. Specifically, the editorial states that at least two of the authors knew that three patients who had received rofecoxib in the trial had suffered myocardial infarctions (heart attacks), but did not include these patients in their calculations of adverse events. Furthermore, some of the authors were apparently aware of "other data on cardiovascular adverse events that we believe would have been relevant to the article," but did not include this data in the article.

Subsequent interviews with Dr. Curfman revealed that the two authors who knew about the extra adverse events were both Merck employees (Toronto Star, Dec. 8). The only two Merck employees now known to be authors were Dr. Alise Reicin, Vice President for Clinical Research, and biostatistician Dr. Deborah Shapiro. When Curfman was giving a deposition for a case brought against Merck, he was shown a Merck internal memo dated July 5, 2000, two weeks before the VIGOR authors submitted a revised but not final version of the manuscript to the journal. The memo suggested that three patients had suffered heart attacks, yet that data was not included in the revised (or final) version of the paper. Curfman also said,

We hope by issuing the statement of concern that it will be a stark reminder to the science community, to the scholarly community, that if we don't his this principle of trust, that the whole scholarly process is just going to collapse into rubble.

Merck's response was a statement, "These additional events were disclosed to the FDA in 2000, presented publicly at the FDA's advisory committee in February, 2001, and included in numerous press releases subsequently issued by Merck. We also note that these additional events did not materially change any of the conclusions of the article."

Forbes reported that "a pre-submission version of the study from which data, including the number of heart attacks and deaths, were deleted by a Merck editor two days before submission." Forbes also quoted Dr. Eric Topol,

This is one horrible debacle in American medical history. I've never seen the likes of this.

Curfman talked more to the Boston Globe (Dec. 10, 2005), admitting that he should have been more skeptical about the VIGOR trial article. In particular, the authors of the study suggested that any apparent differences between adverse cardiac events for patients receiving rofoecoxib versus naproxen were due to a protective effect of naproxen. Curfman said, "I should have been more diligent in questioning the hypothesis at the time."
The Globe also reported that some of the plaintiffs' attorneys involved in Vioxx litigation are questioning whether Merck Vice President Reicin may have commited perjury. Attorney Mark Lanier said that he plans "on using it [the New England Journal editorial] to show that she's been less than honest with other juries." Furthermore, "What a jury is going to get is A, Merck fudged on the details, B, the fudge was in their favor, C, it was on purpose, D, Merck lied about fudging, or at least covered it up. And E, the most prestigious medical journal in the United States of America has called their hand and said this is unethical and wrong."

The evidence that Merck was reluctant about disclosing research data unfavorable to Vioxx just gets stronger and more extensive. We can only hope that this increasingly sad case will force pharmaceutical companies, and other large health care organizations, to be more open, transparent, accountable, and honest.

It would help if health care professionals united to demand these changes. Bravo, at least to Dr. Curfman and the other editors of the New England Journal, and Dr. Eric Topol, for speaking up.

[Update as of Dec 19, 2005: Merck's full statement in response to the New England Journal of Medicine editorial statement, and its news coverage, is on the Merck web-site. To quote the statement in more detail than provided above,

The article in the NEJM was based on cardiovascular data reported as of a prespecified cutoff date established by the Company. The reason for specifying a cutoff date in advance were to ensure that the data analysis could be completed in a prompt manner and to avoid any later allegation that the data were manipulated.
All potential CV serious adverse experiences eligible for adjudication that had been reported to Merck by the cutoff date, February 10, 2000, were referred for adjudication and the confirmed events formed the basis of Merck's communication on the primary study data.... The NEJM thus received the data that was part of the primary analysis.
Any additional CV events eligible for adjudication but reported to Merck after the February 10 cutoff date were subsequently adjudicated.
Merck used other means to disclose the additional information.
The statement of concern by the NEJM editors may have left the mistaken impression that the updated data, including the 3 additional MIs on rofecoxib, were in the original draft version of the manuscript submitted to the NEJM but deleted before submission. That is incorrect. The basis for this misimpression was a document submitted electronically to the NEJM that simply showed the deletion of a header and footers for a table discussion cardiovascular events in the study. There was no data in the table.

As some other bloggers might say, "read the whole thing," and see what you think.]

No Protection for Whistle-Blowers: The Blumsohn - Procter & Gamble - Sheffield University Case

The (UK) Guardian reported the latest developments in the case of Dr. Aubrey Blumsohn at Sheffield University. We had posted earlier (here and here) how Dr. Blumsohn had attempted, in vain, to get access to the data from a research project that he was ostensibly leading, and to control the writing of research abstracts that was done supposedly in his name. His attempts were opposed by Procter & Gamble, the company that made the drug he was studying, and paid for the research. Sheffield University failed to support his efforts, and after he talked to the media about his problems, suspended him
from his duties.
It turns out that Dr. Blumsohn "warned the Journal of Bone and Mineral Research more than a year ago that he had grave doubts about some of the research it had published in his name." At that time, Blumsohn wrote, "I am the first author on both abstracts and have serious concerns about the analysis which has been presented in my name, as first author. Is there a mechanism for comment or dissociation?" At first, no investigation was done. Now, "the Journal has confirmed that it will hold an inquiry into Blumsohn's concerns."
The Guardian also reported, "Ghostwriting and a lack of data for independent researchers are just two issues that worry academics. For years, scientists have argued that Britain needs a statutory body to investigate such problems, as well as to detect the most serious cases of academic fraud. Professor Ian Kennedy, chairman of the Healthcare Commission, has said there must be proper protection for whistleblowers. He said they were often ignored, victimised, or labelled as pathological."
This case, like those of Dr. David Kern and of Dr. Nancy Olivieri in the 1990's, (described here) illustrates how academics may be "victimised," to use Dr. Kennedy's term, when they try to secure the integrity of research in ways that offend vested interests. This case also illustrates how academic institutions seem to be willing to cooperate in this victimization, even when such actions undermine their mission to provide for free enquiry and free expression. Finally, it illustrates that at present, in neither the UK, Canada, nor the US are there organized means or protection for such victimized academics. Up to now, no health board, accrediting agency, or physicians' organization has gone to bat for them.
Maybe the unfortunate case of Dr. Blumsohn will finally spur physicians and researchers to unite to defend their own core values. Until we make it safe for researchers to produce data that displeases the powers that be, why should we trust what data the powers that be allow us to see?

NHS may not treat smokers, drinkers or obese

Ah, the wonders of socialized medicine ... and a really, really, really slippery slope here.

NHS may not treat smokers, drinkers or obese
By Celia Hall, Medical Editor
The Telegraph
(Filed: 09/12/2005)

People who are grossly overweight, who smoke heavily or drink excessively could be denied surgery or drugs following a decision by a Government agency yesterday.

The National Institute for Health and Clinical Excellence (Nice) which advises on the clinical and cost effectiveness of treatments for the NHS, said that in some cases the "self-inflicted" nature of an illness should be taken into account.

But the report bars any discrimination against patients on grounds of age alone.

Nice stressed that people should not be discriminated against by doctors simply because they smoked or were overweight. Its ruling should apply only if the treatment was likely to be less effective, or not work because of an unhealthy habit.

The agency also insisted that its decision was not an edict for the whole NHS but guidance for its own appraisal committees when reaching judgments on new drugs or procedures.

But the effect is likely to be the same.

Nice is a powerful body and the cause of much controversy. It is seen by some as a new way of rationing NHS treatment.

Across the country primary care trusts regularly wait for many months for a Nice decision before agreeing to fund a new treatment.

One group of primary care trusts is ahead of Nice. Last month three PCTs in east Suffolk decided that obese people would not be entitled to have hip or knee replacements unless they lost weight.

The group said the risks of operating on them were greater, the surgery may be less successful and the joints would wear out sooner.

It was acknowledged that the decision would also save money.

I'll bet it will.

-- SS

Cafepharma censorship?

At this link, it can be seen that Cafepharma.com (a bbs for pharma sales and marketing people) seems to censor the name of the website Pharmagossip , a site that looks "beyond the spin of Big Pharma PR."

Typing the pharmagossip URL into a message gets replaced with ********* .

I'm not sure what this means, but it is certainly unusual.

-- SS

Bad Health Informatics Can Kill

Bad Health Informatics Can Kill. I've emphasized this issue in a number of posts.

This link contains summaries of a number of reported incidents in healthcare where IT was the cause or a significant factor. It comes from the Working Group for Assessment of Health Information Systems of the European Federation for Medical Informatics (EFMI).

Any clinician involved in health IT projects, even as users, should be well-versed in these issues.
-- SS

Power Speaking to Truth

A number of stories that have appeared on Health Care Renewal recently share an unfortunate theme.

In chronologic order, first there was the story of a scientist, Dr. Victoria Hampshire, at the US Food and Drug Administration (FDA) who raised concerns about a veterinary drug, ProHeart 6, an anti-heartworm drug made by Wyeth. Since then, reports in the New York Times and the Newark Star-Ledger documented how Wyeth attempted to discredit and intimdate Dr. Hampshire. Wyeth's CEO, Robert A Essner, complained about Hampshire directly to the then FDA commissioner, Lester M. Crawford. Wyeth hired a private investigator to "dig up dirt" on Hampshire. After the investigator found that Hampshire had received fees (all of $196 over four years) from a veterinary pharmacy related to her small part-time veterinary practice, the FDA launched a criminal investigation of her. (Thanks to Pharma Watch for the tip.) (See our previous post here.)

Then there was the story of Aubrey Blumsohn, who was suspended from his faculty position at Sheffield University for talking to the press about his unsuccesful attempts to get and analyze the raw data produced by a research study Blumsohn supposedly lead from the study's "sponsor," Procter & Gamble. The Times (UK) Higher Education Supplement reported that Blumsohn was suspended, and was in danger of being fired "for 'conduct incompatible with the duties of office'. This includes charges of raising serious complaints outside agreed university procedures, of 'briefing journalists' and of 'distributing information, including a Times Higher article, to third parties with apparent intent to cause embarrassment'." Blumsohn apparently had a bad experience when he previously reported allegations of misconduct to university officials. (Thanks to an anonymous commentator on this blog reminding me of this.) (See our previous post on this story here and here.)


And then there was the story of Dr. Eric Topol, the prominent Cleveland Clinic cardiologist. After Topol had written an article critical of Merck's cox-2 inhibitor drug Vioxx, now withdrawn from the Market, the CEO of Merck, Raymond Gilmartin, called the chair of the Cleveland Clinic's board to complain about Topol. (See our previous posts here and here.)

So the theme is intimidation, coercion, and/or threatened punishment of health care professionals who dare to speak out about dangers of drugs or potential reseach misconduct of pharmaceutical companies. Particularly distressing was that in two cases (but presumably not that of Dr. Topol, to the credit of the Cleveland Clinic), pressure by a commercial entity apparently resulted in adverse action by the the professional's employer, even though the employers in these cases, a UK university, and a US federal agency, ought by their very natures and stated missions to protect the rights of their professional employees to honestly communicate about scientific and medical matters.

Thus these cases are disturbingly similar to some infamous cases of the last century, in which physician-researchers who blew the whistle about potential hazards to patients were punished by their hospitals and universities apparently under pressure from commercial interests (not always pharmaceutical companies) threatened by revelations of these hazards.

In our last discussion of these cases (see post here), I argued that "clinical research should be open, transparent, not confidential or secret (except for the identities of the research subjects, and perhaps in some special cases involving national security)." Clinical research will not be open and transparent as long as those who do or evaluate research are at risk of investigations, law-suits, or loss of their jobs should they say or write anything negative about some commercial (or political) vested interest in the course of their work. And patients (and of course, doctors) will suffer as long as research is not open and transparent.

We need some leaders of universities and government agencies who are willing to stand up a protect their researchers' rights to speak truth to power. But right now, it is more often power that speaks to truth.

New AAMC Principles for Protecting Research Integrity: A Small Step For Medical Research

In last month's American Association of Medical Colleges (AAMC) Reporter was a notice of the new AAMC Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials (The full document is here.)

The Principles contain some good bits. For example, they insist that a multi-site randomized controlled trial should have a publication and analysis committee which should have a right to access "any data generated druing the study that the committee deems necessary to ensure the integrity and validity of the study and any presentations based on it." The Principles also declare "ghost or guest authorship is unacceptable."

Had these Principles been in force in the UK (although, admittedly, they were written for the US), they might have averted the messy case at Sheffield University that we just addressed here and here.

However, the Principles are also notable for what they do not say.

In a previous post on Health Care Renewal, we discussed the study bv Mello et al of contracts between commercial sponsors and academic research institutions. The study identified a number of contract provisions that could let sponsors manipulate the design, execution, analysis, dissemination, and discussion of research.

Most of these contract provisions were not addressed by the new Principles.

To illustrate, I will list the provisions mentioned in this previous post (in italics), with comments on how the new Principles do or do not address them. (The percentages after each provision refer to the proportion of medical school contracting officials who would permit that provision in a contract with a research sponsor.)

• The sponsor will own the data produced by the research - 80%
  The principles implicitly allow the sponsors to own the data, but they say that a publication and analysis (P&A) committee should have access to any part of the data it "deems necessary to ensure the integrity and validity of the study...." This committee, in turn, should have a majority of academic members, but can include sponsors' representatives. How the committee should function is not specified.
• The sponsor will store the data and release portions to the investigator - 35%
  Again, the Principles implicitly allow this practice, as noted above.
• The investigators (whether at your site or any other site) are not permitted to alter the study design after the agreement is executed - 68%
  The Principles do not address who designs studies, nor who may alter them. They only state that "any deviations to the pre-specified plan should be identified and discussed."
• The sponsor is permitted to alter the study design after the agreement is executed - 62%
  Again, since alterations of the study are allowed, but who may alter them is not discussed, this is not directly addressed.
• The sponsor may prohibit individual site investigators from publishing manuscripts independently of the sponsor or group - 15%
  The Principles state "individual site investigators in a multisite trial should be free to analyze and publish data from the individual site, consistent with sound principles of analysis, but only after publication of the study as a whole and after review and comment (but not approval) by the P&A committee, or, in the absence of acceptance of the full publication, within 18 months from the specified end points or earlier termination of the study." So the Principles seem to prohibit this provision.
• The sponsor may include its own statistical analysis in manuscripts - 24%
  The Principles include a statement that "the P&A committee of multisite clinical trials (or the principle investigator of a single site study) should require that the sponsor of the study perform its analysis of trial data in a defined period of time." Thus, the Principles implicitly allow the sponsor to do the primary analyses of study data, and hence do not directly contradict this provision.
• The sponsor will write up the results for publication and the investigators may review the manuscript and suggest revisions - 50%
  Although the Principles state that all people who have a role in authoring manuscripts accurately disclose these roles, they do not specify who should be primarily responsible for manuscripts. They also explicitly say "it is acceptable for an employee of the sponsor to participate in drafting and publication activity, if fully disclosed." Thus the Principles do not contradict this provision.
• While the trial is going on, the investigators may not discuss research results (including presentations at scientific meetings) with people not involved in the trial - 66%
  The Principles do not address this provision at all.
• After the trial is over, the investigators may not discuss research results (including presentations at scientific meetings) until the sponsor consents to dissemination - 21%
  The Principles state that "the P&A committee or PI should make a good faith effort to disseminate results of the study through peer reviewed mechanisms," and that "researchers and their institutions have an ethical obligation when conducting human research to seek to make the results available publicly," and that "all trials meeting the ICMJE requirements for registration should make their results publicly available ... within 18 months of submission of a manuscript for publication." However, nothing in the document prevents the sponsor from otherwise exerting control over dissemination.
• The terms of the clinical-trial agreement are confidential - 62%
  The Principles do not address this provision.
• After the trial is over, the industry sponsor may prohibit investigators from sharing raw research data with third parties - 41%
  The Principles state "the sponsor, the investigators, and their institutions should a adopt a model for data sharing, post publication, similar to that of NIH." They do not further specify the NIH model.

Although these new AAMC Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials are a step forward, they are but one small step. Unfortunately, these principles fail to address many of the egregious contract provisions that commercial firms that sponsor research insert in contracts made between them and medical schools or academic medical centers in the US. Until more is done, commercially sponsored clinical research done in the US remains potentially under the control of the sponsors, rather than the academic "principle investigators."
I wonder how many patients would sign up as research subjects if they knew that the research was controlled by the company who made the drug or device being studied, rather than by the white-coated academic researchers?

How the legal profession disciplines it members, and other screwups related to medical malpractice

A sad personal tale of medical malpractice that ironically might have been prevented with an EMR, the legal malpractice that followed, as well as a comment on how the legal profession disciplines it members:

In this document from the National Association of Personal Injury Lawyers are the specifics of the events that led my father to miss being at the 2000 malpractice suit he initiated in 1995 for a two-year failure to diagnose bilateral renal cell adenocarcinoma and medical abandonment.

A dozen retrograde pyelograms in the O.R., performed from 1992-1994 didn't show his problem, as they wouldn't. They did not visualize the renal parenchyma, and despite repeated bouts of severe renal colic and GU bleeding with suspicious CT/MRI's, nothing else was done besides prescribing percocet.

This was despite a history of prior successful treatement with nitrogen mustard and other carcinogens two decades prior for mycosis fungoides, a lymphoma. The diagnosis was always "a kinked ureter" and a stent was placed, which the doctor accused my father of "knocking loose" by picking up heavy packages, etc.

In late 1994 when I became aware of a GU bleed so severe that it dropped my father's hematocrit several points, I demanded a renal arteriogram. At first the medical team refused, but then gave in when I basically threatened legal action (I was faculty at Yale School of Medicine at the time). According to my father, the radiologists said during the arteriogram: "ooops." The result: bilateral golfball-sized renal carcinomas. A "special file" was opened by the hospital.

We were then told the problem was inoperable; but the doctor did not order medical or oncology consults despite my asking him to do so directly. My direct requests to the Department of Medicine to intervene were refused on the basis of "can't get involved in this mess." I then transferred my father to the hospital where I did my residency just as he became septic from obstruction, and after some time in the ICU to clear up his septic shock his cancers, perfectly operable via partial nephrectomies, were removed. There were fortunately no metastases.

The urologic surgeon who did the surgery informed us there were no ureteral "kinks."

He lived without pain, and without bleeding, and without dialysis until 2000. In July 2000, he died of septic shock as a complication of dialysis for the renal failure that set in earlier that year. His battered kidneys, that had been subjected to repeated obstructions and hydronephrosis while the tumors were growing over a several-year period, finally gave out. My intervention in his case had given him six extra good years.

He filed suit for medical malpractice and abandonment in early 1995.

My father was not at the trial that did not take place until late 2000 (CHARGE VIII, Item 131: The Silverstein Matter) because the trial had been cancelled, and he died before the trial could be reinstated (itself a near precedent in Pennsylvania law). My father's case along with multiple other major injury/malpractice cases had been dropped by the court due to malpractice attorney Thomas W. Smith's secret problems.

My father did, however, attend the trial posthumously in the form of a videotape made under court-acceptable conditions, at my demand, since I felt my father might die before the case reinstatement matter was resolved.

My father won the case, posthumously.

At the trial, the defense had an "expert witness" (a urologic surgeon from another hospital) try to make the case that in elderly people (my father was 68 at the time the problems began) , renal cancers should be "left alone." Of course, this did not take into account the repeated bouts of renal colic, obstruction, bleeding and pain and was, I thought, an odd defense.

Presented as evidence in this regard was an article from the American Journal of Urology that had non-operation of renal cancers in the 'elderly' as its thesis.

Unfortunately for the defendants, the article's conclusion stated that such a course was experimental and that the standard of care was indeed surgery. When this 'expert witness' was asked by my parents' attorney to read the article's conclusion to the jury, he realized his error, and stammered and came out with such literal nonsense and 'spin' to try to explain away this little discrepancy, that I thought I was in an alternate universe. Everything I'd learned about medicine - the need to be cautious and honorable, the value of expertise, the respect for the patient - seemed to be just meaningless window dressing. (I paid for a transcript of that testimony just because I wanted to make sure I was not hallucinating at the time.)

Rubbing salt into the wounds, Medicare then put a lien on a portion of the winnings, to recover for the expense of "unnecessary procedures", including the dozen retrograde renal studies. An amount of money was put in an escrow account. It did not matter that the patient is not the person responsible for the tests being ordered, and in Pennsylvania the jury was not permitted to be informed that Medicare could recoup some of the expense of unnecessary medical procedures. Talk about screwed up. I fought this on the basis of it being unfair, based on a technicality in the language of the act that allows such recovery, and just a few weeks ago, in 2005, Medicare released the escrow and the amounts were given to my mother. I think this was done more due to the voluminous length of my father's records and the shortage of Medicare resources and personnel time to adjudicate my complaint, more than anything else.

My father and mother, as well as nearly a dozen other plaintiffs in numerous severe malpractice cases, suffered twice. Once, as a result of medical malpractice and then again, as a result of the legal malpractice that the National Association of Personal Injury Lawyers report linked above described as "both serious and grave in nature," with "eleven separate instances of major case neglect and multiple instances of misrepresentations [i.e., lies] about the status of the cases on seven separate dates."

The penalty, imposed in 2003?

Suspension from the practice of law for a period of four years, retroactive to December 13, 1998.

As to the physician involved, that's another matter. He received a promotion to Chief of Staff. I don't think he's practicing law.

Did I mention the physician was attending law school at the same time he was treating my father, while also running several urologic surgery practices? We found this out only several years ago.

Dad, it's a screwed-up world. Rest in peace.

-- SS

Report: Life Science Manufacturers Adapt to Industry Transitions

Of potential interest to the medical community, the Gartner Group's recent report " Predicts 2006: Life Science Manufacturers Adapt to Industry Transitions " (unfortunately only available to Gartner clients) agreed with a number of my assessments about improving postmarketing drug surveillance via clinical IT ("Reflections on the future of drug safety surveillance from the Medical Informatics perspective"), as well as observing the lack of Medical Informatics specialists involved in such activities in pharma . I had been interviewed in the report's preparation after a Gartner principal had seen my essay on the Web.

Some quotes in the report echoed my essay linked above. In the section " Underutilization of analytical tools to review clinical study data will obscure the risks of approved drugs " the report states:

- The swift and severe judgment in favor of the plaintiff in the first Merck Vioxx trial sent a shock wave through the biopharma industry. It shows that biopharma manufacturers must do more to ensure that healthcare providers and the public have an accurate, ongoing assessment of medication risks. Biopharmas must also ensure that information on these risks is communicated promptly in an open, understandible manner. Posting clinical trial information on a web site is one step towards greater transparency, but does not provide information in a way that enables ... comparions of benefits and risks.

- ... It is still well recognized that all the possible side effects of a medication cannot be uncovered using a randomized sample of study subjects. The true test of safety and efficacy can only be determined when trial data is combined with other sources of information such as clinical encounters, adverse events (MedWatch) or observational studies (National Registry of Myocardial Infarction).

- In the furure, it is hoped that the EMR system will capture point-of-care information in a standardized format that can be used for drug surveillance. Today, biopharmas must be content with these other available, if imperfect, information stores.

- Biopharmas that ignore the opportunity to use analytical tools to proactively review contradictory sources of study information (for example, pre- and post-approval clinical data sets, as well as registries) will miss essential signals regarding product safety. Yet today, only a small percentage of biopharmas routinely utilize personnel with medical informatics backgrounds to search for adverse events in approved drugs.

- Biopharmas ... should look at risk from multiple perspectives ... they must also get actively involved in defining the electronic health and medical record so that it will contain the type of information required to make better safety assessments in the future.

The recognition of a gap in formally-trained medical informatics-trained personnel in the pharmaceutical industry is welcome. For example, from my own experience:

I recall an interview I had last year with the head of an adverse events department at Merck in a rehire situation. I came highly recommended by an Executive Director in the department, to whom I had shown my prior work. This included well-accepted, novel human-computer interaction designs I'd developed for use by busy biomedical researchers for a large clinical study in the Middle East , as well as my work modeling invasive cardiology and leading the development and implementation of a comprehensive information system to detect new device and treatment modality risks in a regional center performing more than 6,000 procedures/year. In addition, I'd worked with the wife of the Executive Director in years prior, when she ran the E.R. of the hospital where I was director of occupational medicine.

Despite all this in my favor, the Executive Director's boss, himself a former FDA adverse events official, dismissed me in five minutes as I was showing him the cardiology project, saying flatly "we don't need a medical informatics person here." I had driven 80 miles to Rahway for this interview to save the executive a trip to Pennsylvania, where I was originally scheduled to come for the interview, since the executive's father was ill in the hospital. In an instance of profound social ineptness, my effort was not even acknowledged. Perhaps he was in a bad frame of mind, but the dismissal under the circumstances was all the more disappointing.

Seeng this issue raised by Gartner, a world's leading provider of research and analysis about the global information technology industry, was undoubtedly a positive development.

-- SS

Freedom of the (clinical) press?

Amplifying Roy Poses' post on the Cleveland Clinic and Dr. Topol's writings:

Company officials even complained about Topol's research to a member of the Cleveland Clinic's board, the cardiologist said in his deposition ... Former Merck Chairman and Chief Executive Officer Raymond Gilmartin called Malachi Mixon, head of the hospital's board, in October 2004 to question why Topol was targeting Vioxx, the cardiologist testified in his deposition. Gilmartin questioned, ``What has Merck ever done to the Cleveland Clinic to warrant this?''

My response is that Merck never 'did anything' to Cleveland Clinic to merit 'this.' They are a pharmaceutical R&D organization subject to critique by experts in the field as part of the normal flow of biomedical science. 'This' [insinuating a supposedly ill-intentioned attack], I would remind, was an expression of scientific concern and doubt based on a clinician expert's interpretation of data, in the interests of patients and patient care.

Dr. Poses raises the issue of such an accusation reflecting a misunderstanding of the scientific process, especially in the field of patient care, by someone with no experience in the latter. While I agree with that assessment as per my many writings on clinical IT mismanagement by healthcare-naive IT leadership, I think a much more fundamental issues needs to be addressed.

A core value in the United States of America is freedom of the press. The answer to speech or writings which a person or corporation considers objectionable is more writing, not suppression of others' speech or writings.

I think it is up to a powerful CEO who calls the Chair of the Board of an organization where a staff person has written something the CEO finds objectionable to prove that the purpose of the call was not to do damage to the author, up to and including causing that person a loss of livelihood. Calling a Chair of the Board, as opposed to the author himself or the author's manager, certainly raises at the very least the appearance of bullying (a form of impropriety). The 'acid test' of a decision or an action, Merck employees are told, is whether it would look bad in the press.

I find these developments especially disappointing considering the stated corporate values:

Corporate conduct is inseparable from the conduct of individual employees in the performance of their work. Every Merck employee is responsible for adhering to business practices that are in accordance with the letter and spirit of the applicable laws and with ethical principles that reflect the highest standards of corporate and individual behavior ... Our ethical business practices motivate our people and help to inspire confidence and trust among doctors who prescribe our medicines, regulators who approve them, health officials who decide whether or not to pay for them, and legislators and policy makers who can influence the cost and timeliness of their discovery."(R.V. Gilmartin)

Calling Chairs of the Board to complain, rather than writing sound scientific rebuttals, does not "motivate and inspire confidence" in my mind.
This is especially relevant in the situation where the company had to withdraw the drug in question.
-- SS

More on the Blumsohn - Procter & Gamble - Sheffield University Case

We had previously posted on the case of Sheffield University (UK) faculty member Aubrey Blumsohn. The original reports of the case in the Times Higher Education Supplement were not accessible on the web without a subscription. Now the Guardian has also published about it. (See its two articles here and here.)
The Guardian reports much the same story as we had narrated earlier. In short, Blumsohn was the lead scientist (principle investigator) for a clinical study of a Procter & Gamble (P&G) drug, Actonel (risedronate). After Blumsohn lead data collection efforts for this randomized controlled trial, P&G refused to give him the raw data from the trial, or to allow an independent analysis of this data. P&G arranged for three abstracts to be written about study results, which designated Blumsohn first author, even though he did not draft the abstracts, nor, again, have access to the data to which they alluded. Blumsohn eventually made his concerns known about his inability to access the data to several officials at his university. Because, however, the University charged that he did not go through proper channels, and eventually talked to the news media, it has suspended him.
The Guardian reports add something to those by the Times. Particularly revealing was a conversation Blumsohn had with Professor Richard Eastell, head of the university's bone and metabolism unit, about his attempts to get the data from P&G. Eastell said,

The only thing that we have to watch all the time is our relationship with P&G. Because we are... we have the big Sheffield Centre Grant which is a good source of income, we have got to really watch it. So, the reason why I worry is the network within P&G is like lightning. So if Ian [Barton] is unhappy it goes to Arkadi [Chines, global medical director of P&G Pharmaceuticals] and before we know it, there is an issue, there is a problem.

The Guardian also reported that the case may be investigated by the UK Medicines and Healthcare Regulatory Authority. It may also come up in a House of Commons debate this week.
Finally, the Guardian quoted Stephen Evans, Professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, "If a research partnership is a genuine one then there has to be complete openness."

Worse, as we have said before, allowing commercial sponsors to keep data from clinical research done in academic settings secret may

• cause patients to suffer
• violate promises made by subjects who volunteered to participate in the research, and
• conflict with the core mission of the university.

Unfortunately, we have heard of too many university leaders who seem to be more concerned about their industrial funding streams than the interests of their patients, students, and faculty.

When More Equals Less in the British NHS

The Times (UK) and other UK papers have reported on continuing deficits afflicting the UK National Health Service (NHS). For example, this Times report noted how London hospitals are delaying elective services for as much time as is allowed by national targets (e.g., outpatient appointments, 13 weeks, elective surgery, 6 months). Furthermore, "other NHS trusts are saving money by removing patients from waiting lists, a policy condemned yesterday by doctors." "Dr Paul Miller, chairman of the British Medical Association's consultants committee, said this practice was 'outrageous.'"

A Times editorial wondered why these deficits were happening, given that "NHS spending has increased by 20 billion [pounds sterling] since 2000, a 40 per cent rise." Particularly,

Money that voters expected to go to the sharp end has instead been spent on administration. Since 1998, the number of NHS managers in England has risen three times as fast as the number of clinical staff, doctors and nurses. At the same time, despite the injection of billions, NHS productivity has fallen 1 per cent a year since 1997, which itself is an indictment of those managers.

The rising numbers and costs of health care managers, accompanied by rising costs of health care, but not necessarily better access or quality, seems to be a frequent, if not global pheonomenon. (See our previous post about the rapidly rising numbers of US managers here.)

Again, part of the problem is that work in a bureaucracy tends to grow to occupy all the bureaucrats. A bigger part of the problem, as we just noted, is that many of these managers don't seem to understand the health care context, or share the values of health care professionals.

More Allegations That Merck Executives Intimidated Researchers About Vioxx

According to Business Week, and Bloomberg News, testimony by Dr. Eric Topol of the Cleveland Clinic alleged that Merck executives attempted to intimidate him as he was preparing an article about the cardiovascular risks of Vioxx. In Business Week,

In 2001, as Topol was preparing to have published an article he had written highlighting cardiovascular risk from Vioxx, he received a visit from Dr. Alise Reicin, vice president of clinical research at Merck Research Labs.
According to Topol, Reicin told him he would be "embarrassed" if he published the article because he didn't have all the data.
After the article was published, he said, Merck sent letters to doctors all over the country saying his analysis was wrong. He was said Merck also attempted to "trash" others who criticized Vioxx.

Bloomberg reported that after the article was published,

Company officials even complained about Topol's research to a member of the Cleveland Clinic's board, the cardiologist said in his deposition. The facility has been ranked by U.S. News & World Report magazine as one of the U.S.'s four best hospitals.
Former Merck Chairman and Chief Executive Officer Raymond Gilmartin called Malachi Mixon, head of the hospital's board, in October 2004 to question why Topol was targeting Vioxx, the cardiologist testified in his deposition. Gilmartin questioned, ``What has Merck ever done to the Cleveland Clinic to warrant this?''

We had previously posted about other alleged attempts by Merck executives to stifle criticism of Vioxx.

As I said then, if physicians and researchers cannot openly discuss scientific findings, science will not advance. If they cannot openly discuss possible harms to patients, patients may be harmed.

What this anecdote adds may be some insight into the cognition of some health care executives. Gilmartin seemed to take the whole thing personally, or at least politically. He allegedly spoke as if Topol was attacking Vioxx, rather than simply noting evidence supporting the possibility of its cardiac adverse effects. This indicates potentially a fundamental misunderstanding of how scientists and clinicians think, and of how science and clinical medicine works.

Again, health care would be better served if its leaders had some understanding of the clinical and scientific context.

Pfizer Fires Outspoken Executive

Some interesting issues are raised by this story. Whistleblowers in the pharmaceutical industry, beware, may be one of them.

Drug maker Pfizer Inc. fired outspoken executive Peter Rost Thursday, citing the government's decision not to participate in a whistleblower suit he brought against the company.

Rost, vice president of marketing, charged in a 2003 complaint that Pharmacia, a Pfizer subsidiary, marketed the human growth hormone Genotropin for unapproved, or "off-label" uses, and improperly sought reimbursement from federal health plans.

"Peter Rost's employment at Pfizer had been maintained over the past two and half years to avoid any complications in light of the government's review of the claims that he raised," Pfizer spokesman Paul Fitzhenry said.

Rost's position has been in a kind of limbo since he came to Pfizer in that company's 2003 acquisition of Pharmacia. Pfizer says it didn't have the position Rost requested; he claims he didn't rule out accepting another position. He has essentially been working for Pfizer without any executive responsibilities.

"My understanding is that I've been terminated," Rost said Thursday. "I need to check what this all means with my lawyers," before making any decisions, he added.

The government is currently investigating the Genotropin allegations in a separate criminal case. Fitzhenry said the company continues to cooperate with this probe.

On Nov. 10, the U.S. Attorney for Massachusetts declined to intervene in the lawsuit and a federal judge later ordered the complaint unsealed. Pfizer filed a motion Thursday to dismiss Rost's complaint altogether.

Rost said Pfizer's motion to dismiss was premature because he hasn't decided on whether to continue with the suit.

In its motion, Pfizer alleges that Rost's complaint was filed after the company had already disclosed Pharmacia's marketing practices for Genotropin. The company said Rost failed to identify any false or fraudulent claims made to a federal health care program involving Genotropin as required under the False Claims Act.

Rost countered that he filed his suit before he received notice from Pfizer that it had reported the matter to the government.

Fitzhenry said that Rost will be offered a severance package similar to those offered to other employees of Pharmacia after its acquisition by Pfizer.

Rost is best known for an appearance on the television news program "60 Minutes" in June, when he criticized the industry's efforts to block drug reimportation into the United States from Canada, where drugs are much cheaper, and called arguments that reimportation is unsafe a scare tactic designed to protect profits.

-- SS

Another Challenge to the Integrity of Clinical Research: The Blumsohn - Procter & Gamble - Sheffield University Case

The Times (UK) Higher Education Supplement (THES) reported an important case involving the integrity of clinical research. Unfortunately, it is not available online without a subscription, so I will quote where needed. The citations are at the bottom of this post. The case involves research carried out at Sheffield University on the drug risedronate (Actonel, made by Procter & Gamble Pharmaceuticals [P&G]).

In 2002, Professor Richard Eastell, of the Bone Metabolism Research Group at Sheffield University, was quizzed by a colleague after presenting a paper on a clinical trial of risedronate to the International Osteoporosis Foundation. Eastell then wrote to P&G statistician Ian Barton, "I think that to avoid criticism in the future it would be good if we could say that we had done the analyses independently." However, Mike Manhart, director of clinical development at P&G, did not agree, saying that letting the academics do an independent analysis would mean that "industry loses the opportunity to demonstrate its ability to be a true partner in scientific endeavors." Furthermore, he said the company had invested "hundreds of millions of dollars" in its drug trials data, so that giving out the data was not "something to be taken lightly."

Yet, when results of the trial were reported (Eastell R, Barton I, Hannon RA et al. Relationship of Early Changes in Bone Resorption to the Reduction in Fracture Risk With Risedronate. J Bone Mineral Research 2003; 18(6):1051-6.), the THES reported that the journal stated, "all authors had full access to the data and the analyses." Another author, Rosemary Hannon, however, denied that she saw all the data, but also noted "neither did I request access to all the data."

In 2002, the research unit signed another contract with P&G to do a another trial (the HIP trial) of risedronate. Aubrey Blumsohn, a Senior Lecturer, was the principal investigator. Eastell again asked Barton, "Could I suggest that Aubrey works with you to see how you did the analyis for the [previous] VERT trial, and then, when we have the HIP data, we could have the analyses run by you and by Aubrey so that we can say that we got the same result with independent analyses?" But Barton again replied, "we ... don't need to ask an independent person to analyse the data just to make a few people happy." Blumsohn later also tried to get access to the data, but by 2003 was not succesful.

However, in 2003, Blumsohn discovered that P&G had written three research abstracts and had submitted two to the American Society for Bone and Joint Metabolism and one to the American College of Rheumatology. In all cases, P&G had listed Blumsohn as first author, but Blumsohn had not written the abstracts. Blumsohn presented the latter abstract, but then said, "In retrospect I might have refused to present this work."

Furthermore, P&G started pushing Blumsohn to write a manuscript reporting trial results. Blumsohn again requested access to the data. But Barton once more replied that this would be a "distraction" from getting the manuscript "written and submitted before ... our competitors pip us to the post."

Blumsohn and P&G started to argue about the interpretation of what analyses were done. In 2004, Blumsohn formally complained to Eastell, "no self-respecting scientist could ever be expected to publish findings based on data to which they do not have free and full access." No paper has been published to date.

Eastell later said that Blumsohn should have taken his concerns "through the appropriate university channels." The university did not launch a formal investigation of Blumsohn's complaints. Instead, "Dr. Blumsohn is suspended from duties, facing disciplinary action for disussing concerns with the Times Higher."

In summary, this case illustrates

• a commercial clinical research sponsor which would not share raw data with or allow analyses by the academics who were ostensibly the principal investigators for the studies it sponsored;
• a commercial research sponsor which ghost-wrote research abstracts;
• a university which seems to have punished one of its faculty for complaining about the sponsor's excess control of clinical research.

Letters subsequently published in the Times Higher Education Supplement made valid points about all this.

When universities become dependent on drug company money they risk losing their fundamental commitment to the truth - Arthur Schafer, University of Manitoba

More than half a century ago, sociologist Robert Merton observed that the normative structure of science should be based on free and open exchange of knowledge. The situation of Aubrey Blumsohn and the acknowledgement that limiting academics' access to data is 'standard industry practice', illustrates the extent to which Merton's ideals have been eroded - Nancy Olivieri, University of Toronto

It is extremely troubling then that a university hides behind procedure and refuses to take a strong and principled stance in support of a researcher who demands full access to research data - Trudo Lemmons, University of Toronto

Stories about ghostwritten journal articles, hidden research data, a bullied academic and a university kowtowing to its industry funders have become depressingly familiar - Carl Elliott, University of Minnesota

Enough said.
References
Baty P. Data row sparks research debate. Times Higher Education Supplement, November 25, 2005.
Baty P. When access to data is a real bone of contention. Times Higher Education Supplement, November 25, 2005.
Letters & Opinion: Ensure integrity in industry links. Times Higher Education Supplement, December 2, 2005.

Pulp Phiction

The story of how the Pharmaceutical Research Manufacturers of America (PhRMA) paid for the writing of a thriller about terrorists poisoning drugs imported from Canada seems to have legs.
We previously posted about it here and here.
Now the story has been recounted in Slate, in an article by Shannon Brownlee and Jeanne Lenzer. This version clearly summarizes the story so far, and then adds a few bits that weren't in our earlier posts. One bit was about Mark Barondess, consultant to PhRMA. When he tried to cancel the project, he offered $100,000 to the authors of the book manuscript, but on the condition that they would sign a formal nondisparagement agreement, promising not to disparage "Barondess, the pharmaceutical industry, or PhRMA" in any "public, private, or promotional statements or writing." Another bit is that the current version of the book features a pharmaceutical company as a villain: the plot reportedly has the company poisoning Canadian drugs, then trying to blame it on terrorists.
In one sense, this story is so ridiculous that it's hard not to laugh out loud - LOL as my teen-ager would text message - at it.
But in another sense, it's deadly serious. Medicine is a serious undertaking. Physicians prescribe drugs in an effort to help prevent or alleviate pain and suffering, or prevent or cure disease. Patients and physicians depend on having accurate, unbiased, complete evidence about these drugs to help decide which drugs should be taken, when and how much, based on clear information about the drugs' benefits and harms.
Stories like this bring into question all the information we get from the pharmaceutical industry. Although I'm sure that much of what the industry says and does is honest, it's no longer clear how to separate the good stuff from the ridiculous stuff.
The many honest, hard-working, smart and capable people in pharma need to stand up and put an end to this nonsense, before the nonsense puts an end to what used to be some great and highly-respected companies that made products that did a lot of good things for patients.

Pharmaceutical company executive luxury

While I cannot vouch for the accuracy of this Cafe Pharma post (a site for pharmaceutical sales and marketing professionals) regarding the luxuries afforded to Pharmaceutical Company executives, I can vouch for having to watch the Merck helicopter take off and land periodically, since the commuter train station I now use to commute to my university faculty position is literally 100 yards from the helipad. The chopper is used by executives to commute between sites in West Point, PA, Rahway, NJ and Whitehouse Station, NJ, distances I frequently drove on a regular basis.

The choppers, which resemble this but in white, are very familiar to those who reside in the vicinity of Merck sites and observe them in flight. Hardly a day passes when I, in walking in the nearby park or shopping in the vincinity, fail to see the familiar Merck chopper in the sky.

With today's technologies in videoconferencing and teleconferencing, one could question whether the considerable expense of helicopters (vs. limos with conferencing facilities) has a justifiable ROI.

I also am aware of former Pharma executives at other companies who lived cross-country from where they worked and who 'commuted' to work on jets the way line employees commute to work on the subway.

In my opinion, if you want to work at a company, Pharma or otherwise, then move yourself to the area where the worksite is located, instead of wasting operational dollars as if you were royalty.

-- SS

Washington Hospital wasting advertising dollars?

Speaking of healthcare marketing and advertising and the waste it represents:

This past weekend I received a glossy multi-page brochure from the Washington Hospital Center promoting their excellent cardiac surgery outcomes statistics. This mailing had a machine-generated mailing label, presumably sent to a list of physicians in my home town and likely other geographic areas outside Washington, D.C. This is not the first time I've received such glossy mailings from this organization.

I offer genuine compliments on their excellence in cardiac surgery. Their excellence in invasive cardiology is known to me from clinical IT-related site visits there a number of years ago. However...

Being that I'm living in the northern suburbs of Philadelphia, appx. 150 miles from D.C. and surrounded by nearby, excellent cardiac surgery centers (University of Pennsylvania, Jefferson, Temple University, Drexel University/Hahnemann, Christiana Care, to name just a few locals), and that patients are unlikely to travel to Washington, D.C., far from family and friends for heart surgery, I find this marketing brochure wasteful.

Also considering that I have not practiced medicine for a number of years after completing a postdoctoral fellowship in Medical Informatics and holding management positions in that field, this makes the mailing even more questionable. It's not as if such information is unavailable as to who might be likely to refer patients, and who might not.

Healthcare disparities being a professional interest, I also can imagine that there are disadvantaged children and adults with heart disease in the proximity of Washington Hospital Center. How many of these patients could have been served with the money spent for composing, printing and mailing these glossy brochures?

Finally, it's ironic that a senior executive at Washington Hospital Center is someone I worked with in the past at another large healthcare system. This person made a project I led, the development of an information system for cardiac outcomes in invasive cardiology and cardiac surgery, a nightmare.

In part due to the fact that he had been overseeing the I.S. department that had been struggling for several years to bring up a failed commercial system, and in part due to the fact that he did not play well with the Sr. VP for Medical Affairs (who happened to be the person who hired me to rectify the cardiology IT problems), the political dysfunction that resulted made the system's success far more difficult to achieve than it should have been.

Success was achieved anyway, despite the executive's politics, and recognition for IT excellence by national cardiology figures who came to inspect the facility was in fact obtained. The facility saved almost $1 million in the system's first year of operation as well, due to the improved operations and materials procurement the new computer system facilitated. However, I left this organization shortly afterward in large part due to these political dysfunction issues.

It's ironic that I now receive costly brochures touting excellent outcomes in cardiology from another institution with the same executive in a leadership role.

Being an optimist, the least I can say is that I'm glad this executive may have learned something about "the value of the data" from Medical Informatics, although apparently not much about thrift.

-- SS

Are You Ready for Some Football?

When I first heard about this one, I thought it was a joke, but...
The New York Times reported today that pharmaceutical companies seem to be going out of their way to hire former or current college or professional (US) football cheerleaders as pharmaceutical representatives.
It provided two examples. Ms. Cassie Napier, former cheerleader for the University of Kentucky, "now plies doctors' office selling the antacid [actually, the proton pump inhibitor] Prevacid [lansoprazole] for TAP Pharmaceutical Products." Ms. Onya [last name not printed by the Times] is currently is a cheer leader for the Washington Redskins, and "weekdays find her urging gynecologists to prescribe a treatment for vaginal yeast infections."
"Known for their athleticism, postage-stamp size skirts, and persuasive enthuisiams, cheerleaders have many qualities the drug industry looks for in a sales force." "T. Lynn Williamson, Ms. Napier's cheering adviser at Kentucky, says he regularly gets calls from recruiters looking for talent, mainly from pharmaceutical companies." "They don't ask what the major is," he said. "Exaggerated motions, exaggerated smiles, exaggerated enthuisaism - they learn those things, and they can get people to do what they want." There is now at least one employment firm, Spirited Sales Leaders, that specializes in recruiting cheer-leaders. The article reported that quite a few former University of Kentucky and some current Washington Redskin cheer-leaders are now pharma reps.
Lamberto Andreotti, MS, Executive Vice President, and President, Worldwide Pharmaceuticals for Bristol-Myers-Squibb rationalized the interest in cheer-leaders as pharma reps thus, "Obviously, people hired for the work have to be extroverts, a good conversationalist, a pleasant person to talk to; but this has nothing to do with looks, it's the personality. However, industry critic Dr. Thomas Carli of the University of Michigan charged that "seduction appeared to be a deliberate industry strategy."
You just can't make this stuff up.
Obviously, there is nothing wrong with hiring current or former cheer-leaders as pharmaceutical representatives per se. What is dismaying is the pharmaceutical companies' emphasis on hiring people, regardless of their academic background or knowledge of pharmacology or medicine, mainly because they are attractive, have "exaggerated" mannerisms, and perhaps even imply "seduction."
This emphasis on short-term, superficial marketing rather than serious science, integrity, and focus on the welfare of patients seems already to have gotten big segments of the pharmaceutical industry in trouble.
One explanation for the continuing unraveling of once highly-respected Merck (for example, see this article in the Washington Post on the latest budget cuts and layoffs there) is its shift in emphasis from science, integrity, and patient welfare to marketing glitz.
You would think the leadership of the pharmaceutical industry would put down their pom-poms and pay attention.
[See widely ranging blog-sphere coverage of this at Dr. Sanity, Health Business Blog, Medical Rants, and PharmaGossip.]

Did Wyeth attempt to discredit an FDA employee?

Did Wyeth attempt to discredit an FDA employee who came out against a Wyeth drug?

See letter below from Sen. Grassley, from http://www.medadnews.com/News/Index.cfm?articleid=292534 and a related post on Pharmawatch.blogspot.com .

Note the extensive "instructions" at the end of Grassley's letter. Great boilerplate for an inquiry or for legal discovery. This senator knows how to avoid the strategies of semantic gamesmanship, feigned confusion, stonewalling and obfuscation utilized by large organization legal departments.

-- SS


November 17, 2005
Mr. Robert Essner
Chairman, President, and CEO
North America and Global Business
Wyeth Pharmaceuticals
500 Arcola Road
Collegeville, PA 19426

Dear Mr. Essner:

As a senior member of the United States Senate and as Chairman of the Committee on Finance (Committee), it is my duty under the Constitution to conduct oversight into the actions of the government and companies that do business with the government. Over the past year, the Committee has reviewed various matters relating to the pharmaceutical industry and its relationship with the Food and Drug Administration (FDA). In previous letters to you, the Committee sought your assistance with inquiries into nominal pricing, educational grants, as well as employer sponsored education of the False Claims Act. I write today seeking your continued cooperation with a matter concerning Wyeth Pharmaceuticals (Wyeth) and FDA’s Center for Veterinary Medicine (CVM).

Recently, the Committee received allegations regarding Wyeth and events surrounding the recall of the heartworm medication ProHeart 6. Information and documents reviewed by the Committee appear to support allegations that Wyeth investigated an employee of the FDA involved in the safety review of ProHeart 6. It appears that the express purpose of the investigation was to discredit the employee and have the employee reassigned. Further, following the investigation conducted by Wyeth, the FDA initiated an internal criminal investigation into the same FDA employee. The Committee’s review of these allegations raises serious questions regarding, among other things, the appropriateness of the actions taken by both the FDA and Wyeth.

Wyeth manufactures and distributes a number of animal health care products through its division Fort Dodge Animal Health (FDAH), including at one time, the heartworm preventative drug called ProHeart 6. Originally approved in 2001 by the FDA, ProHeart 6 was a novel heartworm prevention drug for dogs. It was an injectable sustained-release drug that provided six months of coverage and was administered only by a veterinarian. As part of the FDA’s postmarket review of ProHeart 6, the FDA assigned Dr. Victoria Hampshire, V.M.D., as the Adverse Drug Event Coordinator, to monitor adverse events sent in by both consumers and veterinarians. From 2003 to 2005, Dr. Hampshire compiled the results of over 5500 adverse drug event reports (ADEs) related to ProHeart 6, including nearly 500 canine deaths. Responding to the numerous adverse drug reports, Dr. Hampshire urged the FDA to take action on ProHeart 6 in November of 2003. While this initial call to action garnered little attention within the FDA, a subsequent effort by distraught consumers in July 2004 caught the attention of Dr. Sundlof, the Director of CVM. Dr. Hampshire presented this information and subsequently brought the matter to the attention of former Commissioner Dr. Lester Crawford. Dr. Crawford, a veterinarian himself, agreed with the findings and on September 1, 2004, the FDA organized a meeting with Wyeth to review the adverse event data.

Following the presentation, CVM, the Acting Commissioner and FDA Legal Counsel agreed to recall ProHeart 6 from the market. After two days of negotiating with the FDA, Wyeth voluntarily recalled ProHeart 6 from the market on September 4, 2004.

Shortly after the recall of ProHeart 6, Wyeth sought a review of the recall decision through a meeting of the Veterinary Medicine Advisory Committee (VMAC). The FDA granted the request for a VMAC meeting and scheduled it for January 2005. It appears the timing of the VMAC would have allowed Wyeth a chance to reintroduce ProHeart 6 for the spring heartworm season if the VMAC voted to support its return to the market. In preparation for the VMAC meeting, Dr. Hampshire prepared a presentation regarding the thousands of ADEs received and worked to ensure that the advisory committee would have complete information regarding these events.

Documents obtained and reviewed by the Committee, coupled with interviews conducted by Committee staff, appear to support allegations that Wyeth investigated Dr. Hampshire and presented its findings to Dr. Crawford. Following Wyeth’s presentation, Dr. Hampshire was removed from the review of ProHeart 6 and subjected to a criminal investigation by the FDA. FDA Investigators advised Committee staff that the criminal investigation resulted in no action taken against Dr. Hampshire. Furthermore, the FDA recently gave Dr. Hampshire an award for her job performance related to ProHeart 6.

Information available to the Committee appears to support allegations that Wyeth’s efforts to discredit Dr. Hampshire were not limited to the FDA. More specifically, it appears that Wyeth’s efforts to reintroduce ProHeart 6 to the market included a Wyeth sales representative presenting information to the veterinary community in an apparent effort to discredit Dr. Hampshire. Attached is a two-page letter from a veterinarian and former commissioned officer in the United States Public Health Service. According to the letter, a Wyeth sales representative in Alabama stated that Dr. Victoria Hampshire was the sole reason for the recall of ProHeart 6.

Further, the Wyeth representative stated that Wyeth investigated Dr. Hampshire and said that she pursued the withdrawal of ProHeart 6 for personal financial gain. Finally, the Wyeth representative added that once “[Dr. Hampshire] was taken care of” the number of adverse event reports being submitted for ProHeart 6 dropped significantly. As Chairman of the Committee, I request that Wyeth provide the following records and information to the Committee:

(1) State how Wyeth concluded that Dr. Hampshire had an “apparent conflict of interest.” In complying with this request, describe in detail the actions taken by Wyeth, including but not limited to whether or not Wyeth subsidized, either directly or indirectly, an investigation of Dr. Hampshire. Additionally, provide copies of all communications, documents, and records related to Wyeth’s conclusion that Dr. Hampshire had an “apparent conflict of interest,” including but not limited to, payments associated with one or more investigation(s) of Dr. Hampshire.

(2) Identify all individual(s) and/or agent(s) (including full name, title, and contact information) employed by and/or associated with Wyeth, either directly or indirectly, who were involved in any way with an investigation(s) of Dr. Hampshire. In the event that any individual(s) and/or agent(s) is/are no longer associated with Wyeth, identify that individual(s) and/or agent(s) as well.

(3) Identify all individual(s) and/or agent(s) (including full name, title, and contact information) employed by and/or associated with Wyeth, either directly or indirectly, who were involved in any way with the research supporting and the preparation of the Power Point presentation entitled, “ProHeart 6 Apparent Conflict of Interest,” dated November 19, 2004. In the event that any individual(s) and/or agent(s) is/are no longer associated with Wyeth, identify that individual(s) and/or agent(s) as well.

(4) Provide copies of all documents and records, including but not limited to communications and email, related to the Wyeth Power Point presentation entitled, “ProHeart 6 Apparent Conflict of Interest,” dated November 19, 2004.

(5) State whether or not Wyeth provided notice to the FDA that it was initiating or conducting a private investigation into an FDA employee? If so, provide the name(s) of any individual at the FDA who received notice prior to the initiation of the investigation. Provide copies of all records, including but not limited to communications and emails between Wyeth and the FDA related to the investigation of Dr. Hampshire.

(6) How many times has Wyeth investigated an FDA employee(s) and/or presented information to the FDA related to an FDA employee’s apparent conflict of interest? Additionally, describe in detail the facts associated with each investigation and/or presentation.

(7) Provide complete contact information for Mr. Clint “C.T.” Newsum, Vice President for Wyeth Pharmaceuticals. Additionally, please make Mr. Newsum available for an interview with my staff to take place no later than December 23, 2005.

(8) Provide complete contact information for Mr. Glen Kimmorely, a Senior Territory Manager for Fort Dodge Animal Health, a division of Wyeth Pharmaceuticals. Additionally, please make Mr. Kimmorely available for an interview with my staff to take place no later than December 23, 2005.

(9) Provide complete contact information for Mr. Tom O’Hare of Copiague, New York. Identify the relationship Mr. O’Hare has with Wyeth Pharmaceuticals, including but not limited to, any financial relationship. State whether or not Wyeth is able to make Mr. O’Hare available for an interview, and if so, please make Mr. O’Hare available for an interview with my staff to take place no later than December 23, 2005.

Thank you in advance for providing the name and contact information, including an email address, for a person who will act as the point of contact for Wyeth Pharmaceuticals during the Committee’s review by November 22, 2005, unless it is available sooner. All requests for communications, documents, records and written responses to questions should be received no later than December 16, 2005. In cooperating with the Committee’s review, no documents, records, data or information related to these matters shall be destroyed, modified, removed or otherwise made inaccessible to the Committee.

Sincerely,

Charles E. Grassley
United States Senator
Attachment

GENERAL INSTRUCTIONS

1. Please note that, for purposes of responding to this document request, the terms “document” and “record” should be interpreted in accordance with the general definitions attached to this letter.

2. In complying with this document request, produce all responsive documents that are in your possession, custody, or control, whether held by you or your past or present agents, employees, and representatives acting on your behalf. In addition, produce documents that you have a legal right to obtain, documents that you have a right to copy or have access to, and documents that you have placed in the temporary possession, custody, or control of any third party.

3. No documents, records, data or information requested by the Committee shall be destroyed, modified, removed or otherwise made inaccessible to the Committee.

4. If the document request cannot be complied with in full, it shall be complied with to the extent possible, which shall include an explanation of why full compliance is not possible.

5. In complying with this document request, respond to each enumerated request by repeating the enumerated request and identifying the responsive document(s).

6. Each document produced shall be produced in a form that renders the document susceptible of copying.

7. If any document responsive to this request was, but no longer is, in your possession, custody, or control, identify the document (stating its date, author, subject and recipients) and explain the circumstances by which the document ceased to be in your possession, or control.

8. This request is continuing in nature. Any document, record, compilation of data or information, not produced because it has not been located or discovered by the return date, shall be produced immediately upon location or discovery subsequent thereto.

GENERAL DEFINITIONS

1. The term “Wyeth” means Wyeth Pharmaceuticals, its corporation, its board of directors, or one or more of its divisions, subsidiaries or affiliates, or related entities, including, but not limited to, Fort Dodge Animal Health.

2. The term “document” means any written, recorded, or graphic matter of any nature whatsoever, regardless of how recorded, and whether original or copy, including, but not limited to the following: memoranda, reports, statistical or analytical reports, books, manuals, instructions, financial reports, working papers, records notes, letters, notices, confirmations, telegrams, receipts, appraisals, pamphlets, magazines, newspapers, prospectuses, interoffice and intra office communications, electronic mail (E-mail), contracts, cables, notations of any type of conversation, telephone call, meeting or other communication, bulletins, printed matter, computer printouts, teletypes, invoices, transcripts, diaries, analyses, returns, summaries, minutes, bills, accounts, estimates, projections, comparisons, messages, correspondence, press releases, circulars, financial statements, reviews, opinions, offers, studies and investigations, questionnaires and surveys, and work sheets (and all drafts, preliminary versions, alterations, modifications, revisions, changes, and amendments of any of the foregoing, as well as any attachments or appendices thereto), and graphic or oral records or representations of any kind (including without limitation, photographs, charts, graphs, microfiche, microfilm, videotape, recordings and motion pictures), and electronic, mechanical, and electric records or representations of any kind (including, without limitation, tapes, cassettes, discs, and recordings) and other written, printed, typed, or other graphic or recorded matter of any kind or nature, however produced or reproduced, and whether preserved in writing, film, tape, disc, or videotape. A document bearing any notation not a part of the original text is to be considered a separate document. A draft or non-identical copy is a separate document within the meaning of this term.

3. The term “records” is to be construed in the broadest sense and shall mean any written or graphic material, however produced or reproduced, of any kind or description, consisting of the original and any non-identical copy (whether different from the original because of notes made on or attached to such copy or otherwise) and drafts and both sides thereof, whether printed or recorded electronically or magnetically or stored in any type of data bank, including, but not limited to, the following: correspondence, memoranda, records, summaries of personal conversations or interviews, minutes or records of meetings or conferences, opinions or reports of consultants, projections, statistical statements, drafts, contracts, agreements, purchase orders, invoices, confirmations, telegraphs, telexes, agendas, books, notes, pamphlets, periodicals, reports, studies, evaluations, opinions, logs, diaries, desk calendars, appointment books, tape recordings, video recordings, e-mails, voice mails, computer tapes, or other computer stored matter, magnetic tapes, microfilm, microfiche, punch cards, all other records kept by electronic, photographic, or mechanical means, charts, photographs, notebooks, drawings, plans, inter-office communications, intra-office and intra-departmental communications, transcripts, checks and canceled checks, bank statements, ledgers, books, records or statements of accounts, and papers and things similar to any of the foregoing, however denominated.

4. The terms “relate,” “related,” “relating,” or “regarding” as to any given subject means anything that discusses, concerns, reflects, constitutes, contains, embodies, identifies, deals with, or is any manner whatsoever pertinent to that subject, including but not limited to documents concerning the preparation of other documents.

5. The terms “and” and “or” shall be construed broadly and either conjunctively or disjunctively to bring within the scope of this document request any information which might otherwise be construed to be outside its scope. The singular includes plural number, and vice versa to bring within the scope of this document request any information which might otherwise be construed to be outside its scope.

6. The term “communication” means each manner or means of disclosure or exchange of information, regardless of means utilized, whether oral, written, electronic, by document or otherwise, and whether face to face, in a meeting, by telephone, mail, telexes, discussions, releases, personal delivery, or otherwise. Documents that typically reflect a “communication” include handwritten notes, telephone memoranda slips, daily appointment books and diaries, bills, checks, correspondence and memoranda, and includes all drafts of such documents.