Turn That Door Around - A Physician Substantially Tied to the
Pharmaceutical Industry Nominated to Run the FDA
September 27, 2015
Roy M. Poses, MD
Thursday, September 24, 2015
Health Care Renewal
It seems to be the season of the revolving door [1] in health care. The latest version got some media attention, because
it involves one of the most important health care leadership positions in the
US government, the Director of the Food and Drug Administration (FDA).
However, the case actually seems much more serious than what the media has
recently reported.
The Basics
President Barack Obama plans to nominate the prominent cardiologist and
medical researcher Robert Califf as the next commissioner of the Food and Drug
Administration, the White House said Tuesday.
Dr. Califf had been named the FDA’s deputy commissioner for medical
products and tobacco—effectively the No. 2 post—in February. He joined the FDA
from Duke University, where he had served as a professor of medicine, a leading
pharmaceutical researcher and the vice chancellor for clinical and
translational research.
The new nomination got some rave reviews. For example, from the WSJ
article,
Francis Collins, director of the National Institutes of Health and a
scientist who has worked with Dr. Califf for years, called this 'a fantastic
nomination.'
'He’s never forgotten that at his core he’s a doctor, and he cares
deeply about providing evidence to help people take better care of
patients,' said Dr. Robert Harrington, professor and chairman of the department
of medicine at the Stanford University School of Medicine, who worked with Dr.
Califf at Duke.
'He has a very good understanding of industry and academia, and
think that will serve him well,' Caleb Alexander, MD, co-director of the Johns
Hopkins Center for Drug Safety and Effectiveness in Baltimore, told MedPage
Today....
Also, this from Dr Harlan Krumholz,
He's a broad thinker and a very creative and visionary individual.
He will be an outstanding choice.
And this from Dr Sanjay Kaul,
I can't think of a more qualified person than Dr. Califf to lead the FDA at
the present time. He is an accomplished leader in cardiovascular disease
research whose work has resulted in therapies that save lives and improve the
quality of life for millions of patients.
Is it time to break out the confetti yet?
Conflicts of Interest a Fly in the Ointment?
The only fly in the ointment was the matter of Dr Califf's ties to
industry. The WSJ article included,
Diana Zuckerman, president of the National Center for Health Research, a
Washington-based group focusing on medical-product safety, questioned his ties
to the drug industry.
'Dr. Califf’s expertise and his close ties to the pharmaceutical
industry are both well-known,' she said. 'His ties to industry have been a source
of great concern to public-health experts when he was previously considered
for FDA commissioner, and those ties raise important questions about this
nomination.'
The MedPage Today article noted that Public Citizen's Health Research Group
stated,
'During his tenure at Duke University, Califf racked up a long history of extensive
financial ties to multiple drug and device companies, including Amgen,
Astra-Zeneca, Eli Lilly, Johnson & Johnson, Merck Sharpe & Dohme and
Sanofi-Aventis, to name a few,' Michael Carome, MD, the group's director,
said in a statement. 'Strikingly, no FDA commissioner has had such close
financial relationships with industries regulated by the agency prior to being
appointed.'
The MedPage Today article, however, then went on to undermine those
concerns, implying that only fringe people like those at Public Citizen were
really worried.
Most experts contacted by MedPage Today seemed to think Califf
would not have a problem getting Senate confirmation. 'I expect him to be
confirmed," said [Dr. Steven] Nissen. 'He is very well liked by
people ... in both parties, and I would expect the nomination to go well.'
'All signals suggest that Dr. Califf is well-respected on both sides
of the political aisle,' Jay Wolfson, DrPH, JD, senior associate dean at the
University of South Florida's Morsani College of Medicine, in Tampa, said in an
email.
'There are some who believe his relationship with [the drug industry] may
be a problem, but most see it as a value-added factor in building a
functional, more streamlined relationship with the industry in order to improve
the speed with which truly effective and quality drugs and devices are made
available, mitigate the excessive costs associated with pharmaceuticals,
and influence policies and practices intended to improve health status.'
Note that the experts were not all named, or their expertise described, the
first two paragraphs were really about Dr Califf's political support, and the
third paragraph clearly reflected the views of someone who thought that the FDA
needs to have a lighter regulatory touch.
There was additional reporting about Dr Califf's conflicts of interest, but
again with the effect of minimizing their importance. The Wall Street
Journal published a second article on September 18, 2015 [5] which first reported,
From 2009 through early 2015, Dr. Califf received consulting fees of
roughly $205,000 from companies including Johnson & Johnson, Merck &
Co., GlaxoSmithKline PLC and one medical-device maker, records show. The
payments are documented by the federal Open Payments database, and PharmaShine,
a database of pharmaceutical disclosures operated by Obsidian Healthcare
Disclosure Services LLC. Drug makers spent an additional $21,000 on travel,
meals and other expenses for Dr. Califf, data show.
But the article provided this counterpoint,
Kevin Griffis, a spokesman for the Department of Health and Human Services,
said Dr. Califf had ceased all work with drug makers once he was hired by the
FDA and that he has gone through a rigorous screening process for potential
conflicts of interest. Mr. Griffis said Dr. Califf had donated all the
consulting fees he has received since the mid-2000s to nonprofit groups.
'Dr. Robert Califf’s professional career has been dedicated to advancing
biomedical research, including the rigorous evaluation of the safety,
efficacy and appropriate use of both new medical products and those already on
the market,' said Mr. Griffis, assistant secretary for public affairs at HHS.
Note that Dr Califf already is at the FDA, in a position that I do not
believe required Senate confirmation. It is striking, however, how the
agency's own public relations people have jumped to his defense now as a
nominee who has to be confirmed by the Senate.
However, I suppose that
had Dr Califf donated all this fees to a local soup kitchen, they could not be
called much of a conflict of interest. But Mr Griffis said
"nonprofit groups," without specification, not "soup
kitchens." And continue reading to find out more.
He has written scientific papers with pharmaceutical company researchers,
and his financial disclosure form last year listed seven drug companies and
a device maker that paid him for consulting and six others that partly
supported his university salary, including Merck, Novartis and Eli Lilly. A
conflict-of-interest section at the end of an article he wrote in the European
Heart Journal last year declared financial support from more than 20
companies.
However the NYT article also quoted Mr Griffis about the donations to
"nonprofits," and added,
A résumé studded with industry funding is not unusual in academic
medicine, Dr. Califf’s supporters note. Doctors are paid consulting fees
all the time, and universities routinely conduct clinical trials on
behalf of companies. Those contracts help support university
researchers’ salaries, a standard practice. Many emphasize that it does not
imply an inherent conflict.
His supporters contend that Dr. Califf’s vast experience in the clinical
science world could be a major asset in his new post.
Furthermore,
Supporters and former colleagues say Dr. Califf’s background makes him
perfectly suited to the job of commissioner. He has spent years
improving the way clinical trials are conducted, coming up with
groundbreaking trial designs for medicines against blood clots.
'His integrity in scientific matters is impeccable, and his
innovation in clinical trial design is legendary,' said Dr. Steven Nissen, a
cardiologist at the Cleveland Clinic, who has been an outspoken critic of both
the F.D.A. and drug companies.
Even better,
Dr. Califf is often in the gym on the StairMaster before 6 a.m., said a
former colleague at Duke, Dr. Adrian Hernandez. He often invites younger
doctors to join him in golf and has a passion for Duke basketball that he
expresses by wearing the team colors on game days.
How could anyone criticize a man who is at the gym at 6 AM?
More seriously, note that while the recent reporting may bring up questions
about Dr Califf's conflicts of interest in terms of financial relationships
with drug, device and biotechnology companies when he was on the Duke faculty,
all the reporting also included passages minimizing the importance of these
conflicts. To minimize the issue of conflicts of interest, articles cited
unnamed experts, suggesting the logical fallacy of an appeal to authority [7]; noted that the financial ties that were criticized are standard practice
in academic health care, suggesting the logical fallacy of an appeal to common practice [8]. The articles also cited Dr Califf's positive attributes which may
have been relevant to his work at the FDA, like knowledge of research, but were
not related to the question of conflicts of interest. This suggests another
appeal to authority, or something of a reverse ad hominem [9] (pro hominem?) fallacy. It seems odd that what appear to be
straightforward journalistic reports of a presidential nomination included such
attempts to defend the candidate. Note further that many of these logical
fallacies appeared not in quotes from Dr Califf's supporters, but in text
apparently written by journalists (e.g., "industry funding is not
unusual," "in the gym on the Stairmaster," etc.)
Nonetheless, this is the state of play as of this moment. The thrust
of the media coverage suggested that Dr Califf is a brilliant physician and
researcher, and while he as some ties to industry, they do not amount to much
of a problem, except in the eyes of the likes of Public Citizen.
If one digs deeper, however, there is more. When Dr Califf was appointed to
his current FDA position in February, 2015, and years earlier when his name was
first mentioned as a possible candidate to run the FDA, evidence appeared that
his ties to pharmaceutical, biotechnology and device companies were much more
serious than what the recent accounts suggested.
Where Does the Money from Industry Sponsored Research Grants Go?
Califf says his salary is contractually underwritten in part by several
large pharmaceutical companies, including Merck, Bristol-Myers Squibb, Eli
Lilly and Novartis.
Note that apologists for physician and academician interaction with
industry often claim that industry funding of research grants that does not go
directly to individuals does not cause important conflicts of interest. In one
sentence, however, this article underlined how these grants support academic
salaries, and hence lead to the dependency that is at the heart of conflicted relationships.
As we posted [11] in 2007, academic medical institutions now depend on "external,"
including corporate research funding to support their research faculty's
salaries, and via "overhead," their overall budgets. Dr Lee
Goldman, then Dean and Executive Vice President at Columbia University, called
faculty who bring in a lot of grant money "tax payers," who earn
gratitude, and likely bonuses and perks. Thus Dr Califf's multiple large
corporate research grants cannot be completely dismissed as conflicts of
interest.
A More Extensive List of Industry Relationships
Furthermore, a relatively obscure February, 2015, report from MDDIOnline [12] noted that Dr Califf had more industry relationships than were reported
this month,
Conflict of interest disclosures dating back to 2007 made public by the DCRI
show that Califf has been paid for consulting or other services provided to
a number of medical device pharmaceutical, and biotech companies, including
Medtronic, Acumed, Bayer Healthcare, Merck, Novartis, Roche, GlaxoSmithKline,
Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly & Co. Califf
also disclosed that he held equity in two pharmaceutical
companies—Boulder-based N30 Pharmaceuticals and South San Francisco, CA-based
Portola Pharmaceuticals—as recently as 2014. Califf retired from
Portola’s board of directors January 26, according to a press release from
the company.
A somewhat more obscure commentary by Martha Rosenberg in OpEdNews [13] provided even more extensive listings of Dr Califf's
industry relationships. And it suggested having a look at the disclosures he
has made in the past in medical journal articles. A statement in a 2013 JAMA commentary [14] was particularly telling,
Dr Califf receives research grants that partially support his
salary from Amylin, Johnson & Johnson, Scios, Merck/Schering-Plough,
Schering-Plough Research Institute, Novartis Pharma, Bristol-Myers Squibb
Foundation, Aterovax, Bayer, Roche, and Lilly; all grants are paid to Duke
University. Dr Califf also consults for TheHeart.org, Johnson & Johnson,
Scios, Kowa Research Institute, Nile, Parkview, Orexigen Therapeutics, Pozen,
WebMD, Bristol-Myers Squibb Foundation, AstraZeneca, Bayer/Ortho-McNeil,
Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Gilead,
GlaxoSmithKline, Li Ka Shing Knowledge Institute, Medtronic, Merck, Novartis,
sanofi-aventis, XOMA, University of Florida, Pfizer, Roche, Servier
International, DSI-Lilly, Janssen R&D, CV Sight, Regeneron, and Gambro;
all income from these consultancies is donated to nonprofit organizations,
with most going to the clinical research fellowship fund of the Duke Clinical
Research Institute. Dr Califf holds equity in Nitrox LLC, N30 Pharma,
and Portola.
These lists of corporations from which Dr Califf got salary support and
consulting fees are much longer than previous lists. He acknowledged 13
commercial research sponsors, and consulted for 32 organizations, most of which
were pharmaceutical companies. Again, given that the salary support and
overhead likely supplied by corporate research grants do suggest conflicts of
interest, Dr Califf may have had many more of these sorts of conflicts than
current reports implied
A Seat on a Pharmaceutical Company Board of Directors
Note that the MDDIOnline article mentioned that Dr Califf was a member of
the board of directors of Portola Pharmaceuticals. That was a significant
source of income. According to the Portola Pharmaceuticals 2015 proxy statement [15], Dr Califf received $259,623 in cash and stock options
from the company in 2014. I cannot find anything to suggest that this
payment did not go directly to him. This position, and the money it paid
were not mentioned in the recent coverage. That payment alone seems to
represent a major conflict of interest.
However, being on the board of directors of a health care corporation
presents a deeper conflict than that produced by a simple payment of money or
stock options, no matter how large. In 2006, we discussed [16] corporate directorships as a new and important species of conflict of
interest for medical academics. As we have previously posted [17], corporate directors have fiduciary responsibilities to the company and
its shareholders to support its financial success. They are supposed to
"demonstrate unyielding loyalty to the company's shareholders" [Per
Monks RAG, Minow N. Corporate Governance [18], 3rd edition. Malden, MA: Blackwell Publishing, 2004. P.200.]
Thus corporate directors have a much more significant commitment to the
corporation than do corporate consultants, or researchers supported by
corporate grants.
Where Did Those Donated Consulting Payments Go?
Also note that the disclosure statement in the JAMA article mentioned that
most of the consulting payments Dr Califf received went to the clinical
research fellowship of the Duke Clinical Research Institute (DCRI). Dr
Califf was the first director of DCRI,
So, while Dr Califf apparently did donate the consulting fees to a
non-profit organization, that organization actually was part of Duke, and an
organization that Dr Califf once led. It appears likely that Dr Califf
benefited at least indirectly in terms of institutional gratitude and
reputation from these consulting fees that he donated to his own
institution. So it appears that Dr Califf's donations of his consulting
fees did not reduce the conflicts of interest generated by these fees to the extent
suggested by the current FDA spokesperson and current media reports.
Payments for "Educational Activities"
Finally, perusal of disclosures [19] of Dr Califf's commercial relationships made by the Duke Clinical Research
Institute for the years 2010-2015 showed that he received payments for
"educational activities" in 2011 from Amylin. Information about
earlier years is not available on this site, but in 2009, Dr Daniel Carlat
wrote this about Dr Califf's then rumored candidacy for leadership of the FDA in the Carlat Psychiatry Blog [20],
look at these industry disclosures [21]. He took money—lots of money--from 18
different pharmaceutical or device firms. Most of this was not for research,
but for consulting and speaking, including CME [22]. If Dr. Califf believes that it is ethical
for physicians to help drug companies market their products, that’s his own
business. But to elevate him to a position in which he is the country’s chief
watchdog over unsafe medications and foods seems a dangerous move. With money
from 18 drug companies padding his bank account, he will presumably spend most
of his FDA career recusing himself from crucial decisions. Not a good idea.
There has been no mention of Dr Califf being a paid
speaker for pharmaceutical companies in any of the recent reporting. Dr
Carlat implied that Dr Califf was paid to speak to further marketing objectives
of pharmaceutical companies, that is, was giving "drug talks." Since the publication of "Dr Drug Rep" in the New York Times in
2007, authored by Dr Carlat, the public has learned that such talks mainly
include content provided by the pharmaceutical companies, and are meant by the
companies as marketing exercises. From that case we also learned that
physicians who deviate from the marketing message do not last long on speakers'
bureaus. (See posts here [23]
and here [24].)
Paid speakers may be regarded by pharmaceutical companies
as paid "key opinion leaders [25]," KOLs, who serve a marketing function
in the guise of academics. As noted here [26]
and here [27],
the companies buying their services may believe they have bought the services
of sales people. Evidence about key opinion leaders actually
performing like marketers has come from documents revealed during litigation
(e.g., see this recent example [28] of a huge monetary settlement made of charges that GlaxoSmithKline, a
major multinational drug company committed fraud among other things, and in the
course of its unethical activities used key opinion leaders as
marketers). Also, see the Neurontin marketing plan (see post here [29]),
and the Lexapro marketing plan (see post here [30])
for examples of how company keaders view key opinion leaders as marketers.
So the revelation that Dr Califf received corporate payments for
"education" suggests a bigger commitment to corporate marketing
objectives than has previously been revealed.
Summary
So, looking at not only current media reports, but media reports from
earlier this year, and also proxy statements, the fine print of journal
articles, and old blog posts, it appears that Dr Robert Califf really did have
very substantial financial interactions with the drug, device and biotechnology
industry. These interactions likely underwrote his salary and his
standing with the leaders of his former employer, Duke University. Dr
Califf seemed to be a paid speaker for drug companies on at least two
occasions, suggesting that the companies may have put him in a covert marketing
role, or viewed him as a paid key opinion leader. Finally, Dr
Califf served on the board of directors of one drug company, a much deeper
commitment than being a sponsored researcher or consultant.
Thus Dr Califf really appears to be one of the most, if not the most drug,
device and biotechnology industry connected individual ever nominated to lead
the agency that is the most important regulator of the US drug, device and biotechnology
industry. Some of his connections, particularly his previous membership
on a pharmaceutical company board, and his previous roles as a paid
pharmaceutical speaker, suggested not only financial relationships, but
commitments to companies' financial and marketing goals. These appear to
be major conflicts of interest vis a vis Dr Califf's current leadership
position at the FDA, and his nomination to be the ultimate leader of this
regulatory agency. This is the revolving door writ large.
As we have said very recently [31], the revolving door [1] can be veiwed as a species of conflict of interest [32]. Government officials who can look forward to extremely lucrative
employment in health care industry may be much more inclined to seem friendly
to the industry while in office. Government officials who just came from
industry are likely to maintain their industry mindset and be mindful of their
industry friends.
The literature makes clear that the revolving door process is a source of
valuable political connections for private firms. But it generates
corruption risks and has strong distortionary effects on the economy,
especially when this power is concentrated within a few firms.
Furthermore, the ongoing and increasing revolving door phenomenon clearly
suggests excess coziness between industry and government, now to the extent
that industry and government leaders of health care are becoming
interchangeable. This suggests that health care is increasingly run by
this cozy ingroup, who very likely put their own interests ahead of those of
patients and the public.
The continuing egregiousness of the revolving door in health care shows how
health care leadership can play mutually beneficial games, regardless of the
their effects on patients' and the public's health. Once again, true
health care reform would cut the ties between government and corporate leaders
and their cronies that have lead to government of, for and by corporate
executives rather than the people at large
Links:
"The master class
has always declared the wars; the subject class has always fought the battles.
The master class has had all to gain and nothing to lose, while the subject
class has had nothing to gain and everything to lose--especially their
lives." Eugene Victor Debs
