BLOGSCAN - Stanford's CME Money Goes Into a Pool

On the Carlat Psychiatry Blog, Dr Daniel Carlat analyzed the new Stanford policy that would direct all commercial funds supporting continuing medical education (CME) into a single pool. As Dr Carlat pointed out, the devil may be in the details of this policy, which still allows connection of funding to some (admittedly broad) particular clinical categories. Furthermore, although the policy would apparently sever direct connections between funding from particular companies and particular CME courses, I do not see how it could prevent informal communications between commercial sponsors and academics that could shape the subject matter and content of these courses. Such communication is now easy since so many medical faculty already have financial relationships with specific drug, device, biotechnology or other health care corporations.

Post Title → BLOGSCAN - Stanford's CME Money Goes Into a Pool

MANAGING CONFLICTS of INTEREST at STANFORD

MANAGING CONFLICTS OF INTEREST AT STANFORD

The case of Stanford University and Dr. Alan Schatzberg, chairman of Stanford’s department of psychiatry, continues to raise questions. You can see previous discussions here. The questions concern transparency at the academic-corporate boundary, reporting conflicts of interest to NIH, and Stanford’s “management” of a faculty member known to have a significant conflict. The conflict involves a company Dr. Schatzberg founded (Corcept Therapeutics), a drug called mifepristone that Corcept has in clinical trials for depression, and NIH-supported studies of the same drug at Stanford.

Stanford’s position is that Dr. Schatzberg “has not been involved in managing or conducting any human subjects research involving Mifepristone …” Dr. Schatzberg’s 2006 published disclaimer stated “…Dr Schatzberg played no direct role in the recruitment, assessment, or follow-up of subjects enrolled in this study. Dr Schatzberg was not directly involved in the analysis of data stemming from this research.” Stanford represented that this disclaimer applies also to earlier publications with Dr. Schatzberg as co-author.

This disclaimer is hardly credible, considering the responsibilities of NIH-funded Principal Investigators. I pointed out many of the inconsistencies before. Now there is new evidence that Dr. Schatzberg failed to maintain an arm’s-length relationship to the projects at Stanford.

In a 2008 review article, Dr. Schatzberg discussed the Stanford projects in ways that contradict the claim of an arm’s-length relationship. This article acknowledged Dr. Schatzberg’s NIH grant support at Stanford. Corcept Therapeutics was not acknowledged as a source of funding. The first concern is that, if Dr. Schatzberg’s relationship to the Stanford studies is as Stanford claimed, then he has no business publishing a NIH-supported review article that portrays his drug’s prospects in a favorable light. Hello! Is there a conflict of interest here? Review articles that assess a field and synthesize data form a crucial part of science that has to be off-limits to Dr. Schatzberg just as much as assessing patients in one of his clinical trials would be. His many favorable, even exaggerated, articles, reviews and commentaries since he founded Corcept should have come under this proscription. So much for Stanford’s “management” of the conflict. Dr. Schatzberg certainly had a role in managing the research supported by NIH at Stanford – he managed the climate of scientific opinion for his drug and he managed the tone of the NIH-supported publications from Stanford.

Second, Dr. Schatzberg made a claim of efficacy for his drug that differed from what was originally reported in an NIH-supported Stanford study. He claimed a 31% decrease of symptom ratings with a scale called the BPRS. The original report does not confirm that claim. From the published data tabulated in the report, the reduction of symptom severity was 20%. Readers can easily check that for themselves. So, in a current scientific review article Dr. Schatzberg deviated from the published record. He also inflated by half the efficacy estimate for his drug. Hello! Is there a conflict of interest here?

Third, this false claim indicates that Dr. Schatzberg performed and published his own reanalysis of the primary data from an NIH-funded Stanford study. He didn’t get the number 31% from the published article. Yet Stanford says he had no part in managing or conducting the research or in analyzing any data. So here we have an NIH-funded Principal Investigator, with a clear conflict of interest, who supposedly remains at arm’s length from the project, accessing the primary data files, running a new analysis himself, and publishing an exaggerated new efficacy result for his drug that does not match what he published previously as a co-author. That is inconsistent with Stanford’s defense of Dr. Schatzberg. Hello! Is there a conflict of interest here?

Fourth, in this review article Dr. Schatzberg presented the first data on mifepristone blood levels in a peer reviewed journal, along with an elaborate scientific argument for the importance of the blood level as a moderator of response. These blood level data came from Corcept’s clinical trials, but the target blood level stated by Dr. Schatzberg did not correspond to SEC filings and press releases from Corcept. The administrative issue here is how Stanford justifies the presentation and discussion of original scientific data by a Principal Investigator who is supposedly insulated from the scientific work of the project in order to avoid bias. Dr. Schatzberg’s discussion of the new data and his scientific arguments about blood levels form a crucial part of the scientific platform for his drug’s current prospects, and as such must be off limits, just as assessing patients in one of his clinical trials would be off limits under Stanford’s policy. Hello! Is there a conflict of interest here?

This current example undercuts the assertions by Stanford and Dr. Schatzberg that his conflicts of interest have been “managed” by the University. Dr. Schatzberg may not have assessed any patients in Stanford’s trials of mifepristone, but he has had the lead role in responding to scientific critiques, where he clearly was the manager. He also has had the lead role in selling the mifepristone story to the scientific community and in shaping the tone of the NIH-supported Stanford publications that Corcept relied on to raise capital. Hello! Is there a conflict of interest here? How does Stanford justify these academic-commercial boundary violations, and why does NIH not act on the known conflicts of interest? That was Senator Grassley’s question to Dr. Zerhouni today.

Post Title → MANAGING CONFLICTS of INTEREST at STANFORD

Widespread Conflicts of Interest at Stanford: the Dean Responds

In an a commentary fo the San Jose Mercury News, Dr Philip A Pizzo, the Dean of the Stanford University School of Medicine responded to the series of articles in that newspaper documenting widespread conflicts of interest at the Medical School, which we posted about here and here. Some key quotes:

What would be the cost to the health of the American public if such ties between academia and industry were severed?

It should be noted that the federal government has explicitly promoted these ties since 1980, when Congress enacted the Bayh-Dole act, which authorized and encouraged universities to hold ownership of inventions made under federal funding. In fact this law mandates universities and private industry to work together to bring the fruits of university research to the public. This process has resulted in many medical innovations and advances that have improved the lives of millions of Americans.

There are now some 1,000 therapies and technologies that are based on university-licensed discoveries.

Of course, collaboration between university researchers and private companies carries with it the potential for conflicts of interest. The July 9 article describes one way Stanford addresses this: by requiring faculty members to disclose potential conflicts, regardless of the dollar amount of the financial interest.

But disclosure is far from the only strategy that the Stanford School of Medicine uses to protect the public's interest. When we identify a significant conflict, we take steps to eliminate, mitigate or manage it. These steps include modifying the research plan, disclosing the conflict to the public, disqualifying a faculty member from participating in all or a portion of a research project and in some cases requiring the faculty member to sever a relationship with industry.

As for the July 10 article, it is important to point out that Dr. Alan F. Schatzberg's research over the past 25 years has been consistently subject to rigorous peer review by scientific leaders at the National Institutes of Health and throughout the nation. His research findings have been published in highly respected peer-reviewed medical and scientific journals.

It is misleading to air criticism of his pilot studies for lack of statistical significance when, in fact, the studies were exploratory and not designed to show statistical significance in the first place. More important, and above all, through his research and care of patients, Dr. Schatzberg is a man devoted to alleviating the pain and suffering of those who face the challenge of the most severe and chronic forms of depression.

Dr Pizzo's response did not seem to address the points made in our previous posts about the conflicts at Stanford. (Of course, he probably has not read our posts.)

It also seems important to note that criticizing conflicts of interests does not mean criticizing the general concept of industry-academic collaboration. However, there are many ways in which universities and corporations can interact that minimize such conflicts. For example, for-profits can sponsor research at universities, but need not control the design and implementation of studies, and the analysis and dissemination of their results.

However, the examples described in the San Jose Mercury News were not simply of academic researchers collaborating with industry. They included researchers and academic leaders who owned substantial numbers of company stock options, who had corporate administrative titles, or who sat on corporate boards while doing research on the companies' products, or as full-time academics expressing opinions on topics relevant to the companies' products. It is not clear why university researchers need to get stock options, administrative positions, or board memberships from corporations in order to work collaboratively with them.

Furthermore, how can an academic be "full-time" while working for industry in an administrative position, or getting the sort of incentives that corporations usually only give to top management and key employees? At a minimum, a person in such a situation should acknowledge being only a part-time academic.

Finally, an academic who also works for industry ought to make completely transparent what masters he or she serves when expressing opinions about topics relevant to the company's product or service. Such opinions may be regarded differently than those from true full-time academics. But that's life.

However, what sort of trust is inspired when an author of scientific articles about a drug turns out to be not just a full-time university professor with some "financial interest" in the company that makes the drug, but the Chairman of the Board of the company?

Post Title → Widespread Conflicts of Interest at Stanford: the Dean Responds

Widespread Conflicts of Interest at Stanford: Affecting the Board of Trustees

We recently posted about reports of widespread conflicts of interest at Stanford University School of Medicine found in an investigative series in the San Jose Mercury News (see links here and here).

Just before that series was published, the San Francisco Chronicle was looking into conflicts of interest affecting the Stanford University Board of Trustees.

The most glaring example was of Trustee Mary Cranston, who runs a law firm entitled Pillsbury Winthrop Shaw Pittman. But, "according to its 990 tax form, Stanford paid $2.18 million in legal fees during fiscal 2003-04 to Pillsbury Winthrop Shaw Pittman." Also, "Pillsbury Winthrop has consistently ranked among the five highest paid independent contractors the university used between 2001 and 2004. The firm earned between $937,000 and $2.7 million annually during that period."

Although "Stanford has done business with Pillsbury Winthrop since 1993, and Cranston began serving as trustee in 2000. Only in the most recent tax form filed with the IRS that has been made public -- for the year ending Aug. 31, 2004 -- did Stanford make clear it did significant business with one of its trustees' companies and give details."

The Chronicle interviewed governance experts who found the relationship between Stanford University, Ms Cranston, and her law firm "troubling." "Such relationships, they said, while not illegal, can be inherently problematic because they can make it difficult to avoid conflicts of interest or, at least, the appearance of conflicts of interest. As a trustee, she is a watchdog for the university at the same time her law firm is paid millions of dollars for legal advice and litigation services. 'It affects the perception of her ability to be independent,' said Charles Elson, chairman of the John L. Weinberg Center for Corporate Governance at the University of Delaware. 'If she voices opposition to the administration, the fear is the law firm loses legal fees -- that's the public perception.'

The Chronicle found that "Cranston declined to discuss the matter. In January, she announced plans to step down as chairwoman of Pillsbury Winthrop at year's end to become a senior partner. A spokesman for Stanford, which as a private institution does not open its business records to the public, said the university stands by the relationship. Jeff Wachtel, senior assistant to [University President John] Hennessy, said Cranston would recuse herself from any legal decisions. 'We're confident this is an appropriate relationship,' he added. Burton McMurtry, chairman of the Stanford board, agreed, saying people like Cranston are too valuable to exclude simply because there's a potential conflict of interest -- a conflict that can be managed. 'You would cut off your nose to spite your face if you eliminate all people who could have a potential conflict,' he said.

In my humble opinion, it is hard to believe that among the immense pool of talented Stanford alumni and donors one could not find capable potential board members whose firms do not do major business with the University.

The Chronicle also noted other potential conflicts of interest involving Stanford University's board:

-- University President John Hennessy, an ex officio member of Stanford's Board of Trustees, serves on the board of Google Inc. Stanford had $282 million invested in Google as of as of Aug. 31, 2004. According to the federal Security and Exchange Commission, Hennessy owns $2.5 million in Google stock and an additional 44,300 shares in stock options.

-- Former Stanford trustee William Landreth served as an advisory director for Goldman Sachs, an investment banking firm that underwrote $50 million in bonds for the university at the time Landreth was a board member.

-- Stanford trustee Jon Blum served as managing director for Morgan Stanley, an investment banking firm that underwrote $80 million in bonds.

I believe that the corporate culture of contemporary universities, which hardly operate as representative democracies, for better or worse is set at the top. Thus it should not be surprising that a university whose top leaders have conflicts of interest would also be susceptible to conflicts of interest affecting medical school leaders and faculty.

When leaders and faculty up and down the university and medical school hierarchy have financial arrangements with outside organizations whose interests may not always coincide with those of the university or the medical school, one wonders whom these leaders and faculty really speak for, what mission they really put first, and how well an academic institution with such leaders can fulfill its academic and clinical mission.

Post Title → Widespread Conflicts of Interest at Stanford: Affecting the Board of Trustees

Widespread Conflicts of Interest at Stanford: Defining Deviance Down?

The San Joses Mercury News just published a major series of investigative reports about conflicts of interest at the Stanford University School of Medicine, written by Paul Jacobs. In three articles published Sunday (How Profits, Research Mix at Stanford; Federal Rules Often Go Unenforced; and How We Did This Series), Jacobs describes the scope of conflicts of interest at the Medical School.

First, for an overview:

• The school's 700-plus faculty members last year disclosed 299 potential conflicts of interest related to their research, according to figures provided by Stanford.

• Potential conflicts occur throughout the school's ranks. More than a third of the school's administrators, department heads and other leaders -- at least 26 out of 67 reviewed by the Mercury News -- have reported outside financial interests related to their research within the last four years. These are scientists who are role models for junior faculty members and graduate students.
• Perhaps most important, seven of the 10 members of the school's conflicts of interest committee, which is responsible for enforcing the rules, have financial relationships with medical companies. Unlike a comparable committee at the University of California-San Francisco, Stanford's panel includes no outside volunteers.

And here are some telling anecdotes:

One researcher has founded six companies, most based on research that came out of his own lab. He is a managing partner of a venture capital firm focused on medical research and sits on the boards of several other companies. His role at the venture company was approved by the dean several years ago because he has no day-to-day management responsibilities. The researcher is a member of the school's conflict of interest committee.

One senior associate dean started a biotech company based on her federally sponsored lab work.

And the physician who until January chaired the department of gynecology and obstetrics is a longtime director of Wyeth, which manufactures controversial hormone replacement therapy for women -- therapy she defended in 2002 when potentially serious health risks were emerging.

Note that this information was not easy to obtain. Jacobs wrote:

To get information for this series, the Mercury News:

• Obtained correspondence between the university and the National Institutes of Health for the past five years under the federal Freedom of Information Act.

• Searched medical journals, most of which require authors to disclose any conflicts when they publish an article, and disclosures accompanying speeches given at medical conferences.

• Reviewed corporate news releases and other documents filed with the Securities and Exchange Commission, which frequently list information about faculty members who are company founders, directors or scientific advisers.

Stanford's main response to conflicts of interest is to require disclosure, and if necessary, management.

Stanford medical school has a 10-member conflict of interest committee, created in 2001 to oversee how substantial conflicts that exceed certain thresholds are handled. All faculty members are required to disclose their financial relationships at least once a year. Those reports go to the school's conflicts manager, who determines which cases must go to the committee.

The committee does its work in secret.

Stanford admininstrators defended the University's approach to conflicts of interest. For example,

'I'm not really sure where this wild West idea came from,' said Dr. Harry B. Greenberg, a senior associate dean for research. 'Very early on, Stanford has been associated with a lot of entrepreneurial activity and people may have equated the ability to carry out entrepreneurial activity with lack of oversight and regulation. I really don't think that has been the case.'

[However,] Greenberg holds stock options in and is a consultant to MedImmune, which makes an influenza vaccine he is studying under a federal grant.

Also,

However, despite rules requiring prompt reporting of substantial conflicts, Stanford failed to report six grants to NIH until after the Mercury News asked NIH and Stanford earlier this year for documentation of conflicts. Med school spokesman Costello said the failure was an administrative error and that all the scientists followed Stanford's disclosure rules.

One of those six grants involves Greenberg, a senior associate dean for research and chairman of the school's conflict of interest committee.

Greenberg is an expert on vaccines. In late 2000, he took a two-year leave from Stanford to become vice president of research at Aviron, now MedImmune Vaccines, where he helped develop the Mountain View company's nasal flu vaccine, FluMist. While there, he made the case for FDA approval of FluMist to the agency's vaccine advisory committee, which he had chaired just nine months before.

Today, Greenberg remains a paid member of MedImmune's scientific advisory board and holds stock options issued while he was employed by Aviron. He said the options are ``still underwater,'' meaning that exercising them would cost him more than the stock is currently worth. ``I had a great time at Aviron, but becoming filthy rich was not part of it, unfortunately,'' he said.

He is also one of three Stanford scientists now working on a federal grant to compare MedImmune's FluMist vaccine and Fluzone, a more traditional, injectable vaccine from Aventis Pasteur. Both vaccines have been approved by the FDA and are commercially available.

The principal investigator on the NIH-funded grant, which was worth $3.1 million last year, is Dr. Ann Arvin, the Stanford-wide associate dean for research -- a position with responsibility for faculty conflict of interest issues across the university.

For the past several years, she, like Greenberg, has been a paid member of MedImmune's scientific advisory board and holds stock options in the company.

The husband of a third researcher, Dr. Elizabeth Mellins, was vice president for clinical research at MedImmune Vaccines and helped bring FluMist to market. Mellins says she has no direct involvement in the clinical trial.

I will let the reader be the judge of how convincing Greenberg's defense of how Standford handles conflicts of interest is. Some are skeptical, though.

'There is a focus on procedural solutions and this magical belief that disclosure is the answer as opposed to dealing with the fact that many of these things should not be allowed,' said Barbara A. Koenig, a bioethics researcher at the Mayo Clinic and former executive director of Stanford's Center for Biomedical Ethics.

Tufts University Professor Sheldon Krimsky, author of 'Science in the Private Interest,' argues that fields such as law have stricter conflict policies than universities. A judge, for instance, isn't allowed to have any financial relationship with a party that might benefit from a ruling.

But is disclosure enough? Being on a corporate board of directors, for example, carries a legal responsibility that can clash with the interests of students and patients, said Dr. Roy Poses, who runs the non-profit Foundation for Integrity and Responsibility in Medicine. [That's you - ed. I know.]

'I am quite surprised that there seem to be many leaders in academic medicine, who also simultaneously have clear responsibilities to protect the interests of corporations and stockholders,' he said.

As the man said, read the whole thing.

My comments, in addition to the one above, are that this is yet another demonstration about how pervasive conflicts of interest have become in health care in general, and in academic medicine in particular. While conflicts have become so pervasive, individuals with conflicts may seem to blithely disregard any possible downside to such relationships. Thus, this seems to be an example of defining down deviance.

In my humble opinion, however, such pervasive conflicts threaten the core mission of academic medicine. If substantial numbers of faculty and administrators have major financial entanglements with outside organizations whose goals are to sell products or services (or to promote ideologies or belief systems, for that matter), how can one trust the medical school or academic medical center to provide unbiased, disinterested teaching, research, and patient care?

Post Title → Widespread Conflicts of Interest at Stanford: Defining Deviance Down?