Former NIH Director Spins Through Revolving Door, Ends Up at Sanofi-Aventis

A bit of news that got little attention this month was a new job for the former head of the US National Institutes of Health (NIH).  Dr Elias Zerhouni had left the NIH in October, 2008.  Here is the Reuters version of the story of his hew career:

French drugmaker Sanofi-Aventis (SASY.PA) replaced its head of research and development with a leading academic and former top U.S. health official on Tuesday to raise its game in medical innovations.

The company said Elias Zerhouni would lead R&D of drugs and bring R&D for vaccines under his control too as Sanofi reshapes its portfolio and looks to vaccines as one area for growth to offset sales losses from mounting generic competition.

The appointment of Zerhouni, a professor of radiology and biomedical engineering, comes as Sanofi battles to buy U.S. rare disease specialist Genzyme.

Chief executive Chris Viehbacher brought in Zerhouni in February 2009 as his scientific adviser, shortly after taking charge of the group which he has been transforming to include the development of drugs based on biotechnology.

Zerhouni's Embrace of Corporate Health Care

Although Zerhouni ostensibly left the NIH to return to academia at Johns Hopkins University, note that by February, 2009, four months after his resignation was announced, Zerhouni was already advising the Sanofi CEO. 

Soon after he joined the corporate health care world in earnest.  In April, 2009, he was proposed for membership on the board of directors of Actelion Ltd, a Swiss biotechnology company.  On December 8, 2009, he was elected to the board of Danaher Corp, a diversified technology corporation which makes medical devices.  At some time he had become President of the Zerhouni Group, which advertised itself as a resource to "pharmaceutical and biotechnology companies, trade organizations, sovereign wealth funds, government agencies, and research entities around the globe."

Zerhouni at the NIH: His Response to the Conflict of Interest Scandal

There is more than a little irony inspired by Zerhouni's quick circuit through the revolving door.

Zerhouni became director of the NIH in 2002, and announced his departure in October, 2008. In December, 2003, David Willman published his landmark article in the Los Angeles Times on severe conflicts of interest affecting NIH scientists and leaders.  It revealed that formerly stringent conflict of interest policies at the Institutes were rescinded by then director Dr Harold Varmus in 1995, during the Clinton administration, and increasingly since 1998, disclosure of NIH personnel's conflicts of interest had been reduced.  Thus, in 2002, Zerhouni had taken charge of an agency already deeply affected by conflicts of interest affecting many of its leaders, even though that was not yet public.  He initially did nothing about the situation. 

Willman published another series of articles revealing even more breathtaking conflicts of interest in December, 2004.  (See our post here.)   By then, a Los Angeles Times editorial said there was the "appearance of corruption" at the NIH, and called for Dr Zerhouni's resignation. 

Only after the second series of articles did Dr Zerhouni swing into action (see post here).  In February, 2005, he announced that he would now hold the NIH to a "higher standard."  Yet new conflict of interest stories kept surfacing and their handling kept provoking concern (e.g., see this post from 2007, and this post from 2008), and concerns about how NIH deals with conflicts of interest affecting the extramural researchers it funds persist to this day (e.g., see this post). 

By the late 1990s, the NIH, like many other government agencies, seemed to have become extremely cozy with the world of big corporations.  Dr Zerhouni did nothing to obvious to reduce the local version of this coziness until it had become a public scandal.  His actions let questions about the relationships of the NIH, once a pristine example of a government run biomedical research agency, with big health care business persist to this day. 

So it should perhaps be no surprise that he so quickly transitioned from the government that is supposed to be"of the people, by the people, for the people" to top leadership positions in corporate health care.

Other US Government Health Care Agency Leaders Transit the Revolving Door

Meanwhile, the previous commissioner of the US Food and Drug Administration, Dr Andrew von Eschenbach, is Senior Director for Strategic Initiatives at the Center for Health Transformation, a group whose membership includes some of the biggest health care organizations, many of which have had their own moments in the sun on Health Care Renewal.  For example, see Charter Members, AstraZeneca, Sutter Health, and Wellpoint; and Platinum Members, GlaxoSmithKline and Merck.  Dr Eschenbach is also on the board of directors of Histosonics Inc. 

Also, the previous director of the Centers for Disease Control, Dr Julie Geberding, became President of Merck Vaccines in late 2009. 

Conclusions

So the revolving door just keeps spinning, its revolutions suggesting how closely tied together big government and big corporations have become in what is now the health care business.  Whatever the motivations of Doctors Zerhouni, von Eschenbach, and Geberding were, the message to every person in a leadership position in health care in the US government has to still be: you too can earn big corporate compensation soon after you leave here.  Who knows how much that siren song will lead current government leaders to avoid antagonizing the leaders of big health care corporations during their government "service."  That is, of course, not what we want them to be thinking about if government agencies ae to serve the people, not the CEOs of big corporations. 

I am sure that the career transitions of Doctors Zerhouni, von Eschenbach, and Geberding were perfectly legal.  If we want government health care agencies to put the peoples' interests ahead of those of the CEOs of big health care corporations, should not, however, the law be changed to at least slow down the revolving door?

Sanofi-Funded Society of Hospital Medicine Stands Up for Lovenox

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

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

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

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

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

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

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

Also

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

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

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

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

Given the broad mission of the SHM

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

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

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

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

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

Hat tip to Steve Lucas for his comment here.

References

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

Deja Vu All Over Again - Sheffield Researcher Under Threat for Trying to Present Data that Offends Research Sponsor

It's deja vu all over again.  A case reported (so far only) in the UK Times Higher Education Supplement of a biomedical researcher apparently threatened because she tried to present data that did favor a particular commercial health care product. Here is the summary:

An academic has risked the wrath of her university by submitting results to a forthcoming conference without permission.

The University of Sheffield has claimed that the submission has been made in breach of a contract it has with a pharmaceutical company, which funds work in the scholar's field.

Guirong Jiang, a research radiologist who has worked at Sheffield for 13 years, is due to face a disciplinary hearing over her actions this week.

Her findings - submitted to a symposium of the European Calcified Tissue Society (ECTS), to be held in Glasgow in June - add to the debate over what some have claimed is a distortion in the field of osteoporosis caused by the over-diagnosis of vertebral fractures.

Here are more particulars:

Sheffield has censured her for making the submission without the consent of her supervisor, Richard Eastell, head of Sheffield's Academic Unit of Bone Metabolism.

It said her actions breached the terms of a 2007 contract the unit has with pharmaceutical manufacturer Sanofi-Aventis to conduct studies relating to the osteoporosis treatment risedronate, which is sold as the drug Actonel.

It also said Dr Jiang failed to follow 'reasonable requests' to withdraw the submission.

Dr Jiang said she believed her results should be published as they had not been reflected in the unit's previous output.

She added that last December she was informed that her contract would not be renewed when it came to an end this March, which she said had prompted her to throw caution to the wind and publish without permission.

She has queried whether her work is bound by Sheffield's Sanofi-Aventis contract, which stipulates that the company must be allowed to review manuscripts and abstracts prior to publication.

She pointed out that the work was carried out in 2002 when the unit's risedronate work was funded by Procter & Gamble in partnership with Aventis. Dr Jiang added that she had not seen or signed the full Sanofi-Aventis contract.

Dr Jiang is still under threat:

The disciplinary hearing, scheduled to take place on 18 February, will consider the allegation that Dr Jiang 'acted inappropriately in making a direct submission of an abstract to a journal outside unit protocol and in contravention of the terms of the research contract'.

It will also consider the charge that she 'failed to follow a request by her head of unit and head of department to rectify her actions', which 'aggravated a situation which otherwise could have been quickly resolved'.

A long time ago, in a galaxy far, far away, academics had the expectation that they could publish or present their research without first acquiring the express approval of their academic superiors (at least as long as their work was original, the research project was under their control, and that they had properly protected the rights of any human subjects). Furthermore, in at least the US, academics are citizens who expect to have free speech.

But as academic institutions became more enamored of and dependent on "external funding," faculty were increasingly pressured to do only sponsored research. The growing dependence on sponsored research allowed the sponsors to try to get more control over how research was done.

In the 1990s, there were several important cases in North America in which academic researchers tried to present or publish results that clashed with their research sponsors' vested interests. Doing so resulted in lesser or greater threats to the faculty. Two of the classic cases of research suppression in the 1990's demonstrated this issue.


* In the "David Kern case," a textile manufacturer, Microfibres Inc., tried to prevent Dr. David Kern, a general internist and occupational medicine physicians at Memorial Hospital of Rhode Island and faculty member at Brown University, from presenting an abstract that described a case-series of a new pulmonary disease, flock-workers lung, that affected workers at Microfibres Inc. factories. Kern did present the abstract, but under a threat, never carried out, of law-suit, Memorial Hospital of Rhode Island removed Kern as head of the Occupational Medicine program, and refused to renew his contract, even though he was an Associate Professor. Brown University was unable to reverse these moves by the hospital, and Brown officials blamed Kern for signing an agreement to protect trade secrets, even though the agreement was unrelated to the research Kern did on the disease, and his research did not obviously reveal any trade secrets. [1-4]

* In the "Nancy Olivieri case," Apotex, a pharmaceutical company, acted against Dr. Nancy Olivieri for revealing preliminary data from a trial of deferiprone, a chelating agent for the treatment of iron overload in thalassemia, suggesting that the drug was often ineffective in treating iron overload, and appeared to be associated with hepatic fibrosis. Ultimately, a report by the Canadian Association of University Teachers also held that her academic freedom was abridged, in the context of a negotiation between the University of Toronto and Apotex over a large donation, and that the hospital harassed Dr. Olivieri during her dispute with Apotex (link here for report)
 
In the early 21st century, there was a case in the UK with spooky similarites to the present case: at the same university involved in the present case, and with at least one participant in common with that case.  About a year after we started Health Care Renewal, in late 2005, we wrote multiple posts about the complex and unfortunate case of Dr Aubrey Blumsohn's attempts to keep a research project honest. Our most recent summary of the case was here. Dr Blumsohn was also doing clinical research on the drug Actonel, again at the University of Sheffield.  He was denied access to the very data he had collected, and to analyses of the data by Procter and Gamble, the then manufacturer of the drug and sponsor of the research.  Dr Blumsohn found that Procter and Gamble seemed to be arranging for ghost-writers to author abstracts about the research based on these hidden analyses.  After he complained to numerous officials at Sheffield, including Dr Richard Eastell, to no avail, he spoke to the press, and thereafter lost his academic position.  The case was just recapped in an interview of Dr Blumsohn published in the British Medical Journal(5).
 
So we seem to have made little progress.  Most clinical research at academic medical institutions is sponsored by firms that make drugs and devices.  The firms try to secure contracts that give them control over most aspects of the research.  Thus, they can determine how the research is designed, implemented, ana analyzed.  If the resulting manipulation still does not yield results that make the firms' products look good, the sponsors can then just suppress them.  Academics who naively think it is their duty to find and disseminate the truth are in jeopardy when they attempt to present or publish results that challenge their research sponsors' vested interests.
 
Suppression of clinical research, however, is bad for patients and honest health care professionals, since it misleads about the benefits and harms of tests and treatments.  Suppression of clinical research dishonors research subjects who volunteer for studies, often at risk to themselves, thinking they may help to advance science and clinical care.  Suppression of clinical research undermines the fundamental mission of academia: to seek out and disseminate the truth.
 
Those who truly want better health care, here in the US and globally, should advocate for clinical research done without the influence of those with vested interests in how the research comes out. 
 
Thanks to an anonymous Health Care Renewal scout who located the Times article. 
 
References


1. DG Kern, RS Crausman, TH Durand et al. Flock worker's lung: chronic interstitial lung disease in the nylon flocking industry. Ann Intern Med 1998; 129: 261-272. (link here)
2. Shuchman M. Secrecy in science: the flock worker's lung investigation. Ann Intern Med 1998; 129: 341-344. (link here)
3. Marsh DJ. Intimidation of researchers by special interest groups. N Engl J Med 1997; 337: 1317-1318. (link here)
4. Shuchman M. Consequences of blowing the whistle in medical research. Ann Intern Med 2000; 132: 1013-1015. (link here)
5.  Cyer C. Aubrey Blumsohn: academic who took on industry. Brit Med J 2009; 339:b5293. (link here)

Sanofi-Aventis Settles

Here is another addition to the parade of multi-million dollar legal settlements by health care corporations. As reported by the AP:

Drugmaker Sanofi-Aventis has agreed to pay nearly $100 million to settle allegations it cheated Medicaid on the cost of nasal sprays.

The Justice Department said Aventis Pharmaceutical Inc., a wholly owned subsidiary of Sanofi-Aventis U.S. LLC, has agreed to pay the government $95.5 million to settle the charges.

The government charged that between 1995 and 2000, Aventis and its corporate predecessors did not offer Medicaid the best prices for the sprays Azmacort, Nasacort and Nasacort AQ.

In reaching the settlement, Sanofi-Aventis U.S. did not admit any wrongdoing. The company, based in Bridgewater, N.J., issued a statement saying it believed the old pricing system was legal.

Under the law, the company was required to tell Medicaid the lowest price that it charged companies for those products, and offer state Medicaid programs rebates based on those prices.

Prosecutors contend that in order to dodge that obligation, Aventis entered into a private deal with the HMO Kaiser Permanente that repackaged Aventis drugs under a new label, allowing them to overcharge Medicaid programs for the same product.

It seems that scarcely a week goes by without a settlement of charges of unethical behavior by some major health care organization. The ongoing parade of such cases ought to inspire some worry about the ethics of the leaders of such organization. Given the current very public discussion of how expensive health care has become, one would think that there would be some discussion of how much of this expense is due to various kinds of deceptive and unethical behavior by some of the biggest, richest, and most powerful health care organizations. But perhaps that would be too upsetting for those who make so much money running these organizations.

As we have said before, most recently here, while human beings authorized or committed the acts that got the organization in trouble, rarely do these people seem to suffer any negative consequences. At most, the organization may pay a fine. In this case, the fine was, in corporate terms, of modest size. However, even a large fine, may come out of dividends or the stock price, dispersing the cost to stock-holders, or out of salaries across the board, dispersing the cost to all employees. Thus, those who got the organization into trouble are unlikely to feel pain from it. Perhaps because of reverence for all organizations related to health care, and fear that the bankruptcy of any health care organization will leave patients in the lurch, prosecutors do not seem inclined to actually prosecute such organizations. The net effect, though, seems to be that dishonest executives of health care organizations can continue to act with impunity.Until bad leadership of health care organizations leads to negative consequences for those practicing it, health care leadership can be expected to continuously degrade.

ADDENDUM (2 June, 2009) - See these comments on the Effect Measure blog.

Fat Chance: Conflicts of Interest and Calorie Counting

Stephanie Saul in the New York Times, and Karl Stark in the Philadelphia Inquirer have covered the curious story of the downfall of the president-elect of the Obesity Society. Last month, Ms Saul set the stage,

New York City’s new rules for menu labels at chain restaurants have set off a food fight among the nation’s obesity experts.

Most support the theory of the city’s health commissioner that forcing chain restaurants to list the calories alongside menu items — flagging that a Double Whopper With Cheese has 990 calories, for example — will make patrons think twice about ordering one. The rules are set to take effect at the end of March.

There is a countertheory, however, set forth by Dr. David B. Allison, the incoming president of the Obesity Society, a leading organization of obesity doctors and scientists. An affidavit he recently submitted to the United States District Court for the Southern District of New York has ignited a controversy within his organization.

In the filing, Dr. Allison argues that the new rules could backfire — whether by adding to the forbidden-fruit allure of high-calorie foods or by sending patrons away hungry enough that they will later gorge themselves even more.

It might be only a scientific debate among nutrition experts, except for the fact that Dr. Allison was paid to write the document on behalf of the New York State Restaurant Association, which is suing to block the new rules.

Dr. Allison’s role in the debate has angered some members of the Obesity Society, setting off an e-mail fury since word of his court filing began to circulate. Some have pointed to Dr. Allison’s other industry ties, which have included advisory roles for Coca-Cola, Kraft Foods and Frito-Lay.

Many of the group’s 1,800 members are “completely mad that a president-elect of the Obesity Society, an organization that cares about obesity and cares about healthy eating, wants to hold back information from people that helps them make healthy choices,” said Dr. Barry M. Popkin, a member of the organization, who is director of the Interdisciplinary Obesity Center at the University of North Carolina, Chapel Hill.

Dr. Allison, a professor of biostatistics and nutrition at the University of Alabama, Birmingham, is scheduled to start a one-year term as president of the Obesity Society in October. He has defended his affidavit. In a telephone interview, he said he did not take a position for or against menu labeling in the document but merely presented the scientific evidence that the labeling might deter over-eating but might not and, in fact, might be harmful.

He also defended his work for the restaurant industry, but would not disclose how much he was paid for his efforts.

“I’m happy to be involved in the pursuit for truth,” Dr. Allison said. “Sometimes, when I’m involved in the pursuit for truth, I’m hired by the Federal Trade Commission. Sometimes I help them. Sometimes I help a group like the restaurant industry. I’m honored that people think my opinion is sufficiently valued and expert.”

The executive vice president for the restaurant association’s metropolitan New York chapters, E. Charles Hunt, said that Dr. Allison was retained by the association’s lawyers. “Obviously, a lot of it was in favor of our position,” Mr. Hunt said, “although he didn’t come right out and say that.”

So this sounds like yet another story about conflicts of interest, and their possible effects influencing the publicly expressed opinions of a prominent academic. As usual, the conflicted party angrily denied that his financial relationships could have affected his scientific judgment. As we have noted before, this is undoubtedly a sincere belief, but psychological evidence and common sense suggests that having financial ties to organization x may influence one to take positions in line with organization x's interests, even if these influences do not reach conscious thought.

The variant here seems to be that the academic had a financial relationship not with a drug, biotechnology or device company, the usual suspects, but with an association of restauranteurs.

But wait, Mr Stark added more in his story in the Philadelphia Inquirer,

The relationship between academic researchers and industry is a front-burner issue in many fields. Several congressional inquiries are looking at drug-firm support for the American College of Cardiology, the national cardiology group, and the American Heart Association.

Compared with those groups, the Obesity Society, based in Silver Spring, Md., would seem like a tiny outpost with its $2.1 million budget. But the group's 1,800 members include many influential researchers, physicians and dietitians.

The society relies heavily on industry money, raising about $1 million in the last year from various companies, said Morgan Downey, the group's executive vice president. The biggest corporate donors were drugmakers sanofi aventis, GlaxoSmithKline and Allergan as well as the health-care conglomerate Covidien, he said.

About $230,000 of the corporate money funded a conference in September for health advisers to presidential candidates, Downey said.

Fast forward to this week, when Ms Saul reported in the New York Times that Dr Allison is giving up his leadership position for the Obesity Society,

A dispute over food industry influence has resulted in the resignation of the incoming president of the Obesity Society.

Dr. David B. Allison, who was to take over the society, a national group of obesity doctors and researchers later this year, submitted his resignation from that position on Friday.

So what happened? Did the Obesity Society cast out a leader because he had conflicts of interest that interfered with his ability to advance science, education and clinical practice? Or did the Obesity Society cast out a leader because he was aligned with commercial interests opposed to the commercial interests that provide most of the society's support? That is, was he cast out not because he had conflicts of interest, but because he did not have the same conflicts of interest as the society?

Who can tell?

Once again, this case is an illustration of the pervasiveness of conflicts of interest affecting health care organizations. It also shows how the pervasiveness of such conflicts sometimes makes it impossible to discriminate debates about science and health policy from the claims of conflicting pitchmen.

Full disclosure of these conflicts beforehand would at least have given warning that the nature of the debate was ambiguous.

But to figure out the best answer in the current policy debate, that is, whether it really is a good idea to have legislation to put calorie counts on restaurant menus, would really require the input from people who are not paid by either restauranteurs, or those selling obesity treatments. Fat chance that will happen soon.

BLOGSCAN - Sanofi-Aventis Teams with Mainstream Media to Promote Anatomy Education

On the PharmaGossip blog, there have been several recent posts about who now gets to be a pharmaceutical representative. This post is about a representative for an unnamed pharmaceutical company who is now appearing on the Big Brother television show. Her bio for the show features this self-description, "confident, agile and sexy." Two posts (here and here) are about "Playboy model" Cameron Haven, alleged to be a representative for Sanofi-Aventis. (Note: the links in these PharmaGossip posts are too explicit to open at work, or in the presence of children.)

Pharmaceutical marketers repeatedly argue that their main goal is physician education, so maybe they could argue that now they have teamed with mainstream media to increase the impact of anatomy education. Perhaps, though, if pharmaceutical companies really want to regain the reputation they once had, they ought to rethink sending Playboy models to "educate" physicians.

"A Catastrophic Failure" - More on the Ketek Trial Debacle

We previously posted (also here, here and here) about the ill-fated clinical trial, study 3014, of the antibiotic telithromycin (Ketek) made by Sanofi-Aventis, run by Pharmaceutical Product Development Inc. (PPD). Problems with the trial included fabrication of data at one clinical site, and allegations of manipulation of data at another. The physician in charge of the first site was convicted of mail fraud, and the physician in charge of the second had his license suspended. Although the results of this trial were never published, it still crept into the clinical literature: it was cited in a review article in the New England Journal of Medicine.

The case is now the subject of a US congressional investigation. As reported by the Associated Press (via the International Herald Tribune),

Democrats in the U.S. House of Representatives are threatening to hold a member of President George W. Bush's Cabinet in contempt for not turning over documents in a probe of a Sanofi-Aventis antibiotic.

Dingell, who chairs the House Energy and Commerce Committee, said he would support holding Health and Human Services Secretary Michael Leavitt in contempt for refusing to turn over FDA briefing documents subpoenaed by the committee.

The documents were used to prepare FDA Commissioner Andrew von Eschenbach for his appearance before lawmakers last year. Von Eschenbach testified the FDA did not use the flawed safety study to approve Ketek. Dingell and other Democrats say that statement may be untrue.

Robert West, an FDA agent who first investigated Ketek, said he tried to get permission in 2002 to look into whether Aventis was aware of fraudulent data when it submitted the study. West said his request was blocked by senior FDA officials, although he said he did not know which ones.

"A catastrophic failure" was how another FDA investigator, Douglas Loveland, described the company's handling of the study.

"The decision-making process Aventis used to investigate these problems was illogical and ineffective and it could have led them to come to the wrong conclusion," Loveland told House lawmakers.

The investigator stopped short of saying Aventis, Sanofi-Aventis' corporate predecessor, knew the results were false when they submitted them but said it "should have known." Loveland said the results contained all the hallmarks of sham data, including forged signatures and crossed out information.

Sanofi President for Research and Development Paul Chew testified that the company submitted the study in "good faith."

The company was not able to spot the fake patient results....

It seems clear that this case involved a very sloppy clinical trial sponsored and run by a pharmaceutical company. Such sloppy science breaks promises made to human subjects of clinical research that their participation would go to advance science and improve health care. Sloppy trials that produce dubious data will do neither. Furthermore, sloppy science that produces dubious results provides patients and doctors pseudoevidence rather than the best possible evidence relevant to decisions about health care interventions, and hence may also lead to bad decisions that harm patients.

It is bad enough that clinical trials sponsored by pharmaceutical, biotechnology, and device companies are often sloppy, and designed to show their products in the most favorable light, rather than provide valid and unbiased data testing hypotheses most important for patients' and physicians' decisions. This case now raises the more disturbing possibility that high government officials entrusted with protecting the public's health and safety may have hid the sloppiness and unreliability of the Ketek trial. Time and further investigation will tell if this possibility is more than speculation. But the latest events in the Ketek saga clearly show the need for more open and transparent clinical research on drugs and devices, and more open and transparent regulation of such companies by the government.