One focus in HOOKED is the need to appreciate the history of the pharmaceutical industry in the 20th century, to trace today's developments to their origins. In a similar historical vein, I've called attention in this blog to the belief system I like to call "economism":
http://brodyhooked.blogspot.com/2011/11/shameless-commerce-division-new-book.html
--though I am increasingly outnumbered by historians and social scientists who prefer the label neoliberalism.
Economism/neoliberalism (E/N) is an ideology generally characterized as faith in the unregulated free market along with demands for tax cuts and corporate-friendly government policies. However, as economist Philip Mirowski (Never Let a Serious Crisis Go to Waste: How Neoliberalism Survived the Financial Meltdown, Verso, 2013) insists, such a description misses one of the key elements of E/N. Originating with Austrian economist Friedrich Hayek, a founder of E/N during the 1940s, is the idea that the market serves not merely as a medium for the exchange of goods and services, but as a perfect information processing system. The price of a commodity in the truly "free" market reflects at any given time the sum of millions of exchanges across the world, and reflects what any commodity is "worth" much more accurately than any alternative way of approaching the problem--such as scientific research, for example. In short, the market is omniscient; in short, the market is God. The fact that no real-life market ever did or ever could function in this manner does not seem to bother any committed believer in E/N--tending to confirm my claim, in The Golden Calf, that E/N pretends to be hard-headed economic science but actually functions logically like a quasi-religion.
By now you are wondering (if you're still awake) what any of this has to do with Pharma. I was moved to address this topic by a recent article (subscription required) by economist Edward Nik-Khah on how a major E/N enterprise, the Chicago School of Economics, played a critical role in the creation of a new E/N think tank, the Center for the Study of Drug Development, initially located at the University of Rochester and later moved to Tufts University. A key figure described by Nik-Khan in this process was the famous clinical pharmacologist, Louis Lasagna (1923-2003).
In his early career Lasagna was a widely respected academic, often credited with originating the field of clinical pharmacology. Like most of his academic fellows he strongly supported the efforts of the FDA to rein in drug-industry advertising and replace misleading marketing with solid science. He was initially a supporter of the Kefauver-Harris amendments of 1962 that strengthened the FDA's regulatory powers. But through the 1970s something changed. Lasagna cast the sole vote on a review committee of the National Academy of Science in favor of Upjohn and its drug Panalba, that the FDA was trying to take off the market as ineffective. Lasagna took his losing case to the public through an editorial in the Wall Street Journal. Eventually he became the co-founder of the CSDD at his home university, Rochester. The CSDD became a supposedly independent unit to study the science and economics of drug development, but was in actuality captive to the drug industry that funded it. Its most notorious product was the estimate of "the $800 Million Pill," the widely-criticized (but also widely believed) figure of how much the industry must spend in research to create a single successful new drug (discussed at length in HOOKED).
Nik-Khah never documents precisely how Lasagna was "turned" from a position in keeping with academic clinical pharmacology to a stance at odds with virtually all his fellow academics. But he does show that Lasagna attended a conference sponsored by the Chicago School of Economics in 1972, organized and attended by such E/N figures as Milton Friedman and George Stigler, which became a one-sided mouthpiece for promulgating E/N doctrine in opposition to government regulation of the drug industry. (One of the key Chicago staffers later argued that weakening drug regulation would still be worth it economically even if it produced several thalidomide tragedies, because of the greater benefits of allowing more wonderful new drugs to reach the market quicker.)
Following Lasagna's attendance at the Chicago conference and his WSJ piece, the chancellor at Rochester, Allen Wallis, who traveled in the highest E/N circles of that day, took Lasagna under his wing and suggested the creation of the CSDD, personally interceding with drug companies and pro-business foundations to fund it. (Following good free market principles, Tufts eventually stole the CSDD away from Rochester by offering more money, in an effort to build its own drug-industry-funding portfolio.)
Nik-Khah illustrated how Lasagna had signed on to the E/N agenda by quoting extensively from some of his later writing on deregulation of the drug industry. Lasagna eventually turned against academic science almost totally. He argued instead that the minimal amount of clinical trial research should be required to get a drug onto the market, and thereafter the company should be responsible for monitoring how the drug performed as to safety. He viewed the ideal state of affairs as the physician and patient being bombarded with information from numerous sources, including industry marketing, and then making up their own minds as to using the drug. The clash of multiple, conflicting information sources would work much better than any scientific study as a way to find out the truth about the drug. If patients complained that they were ill-equipped to sort through such detailed, technical data, Lasagna replied--tough, this is the real world, live with it. In short, Lasagna spoke like a true convert to E/N, believing that the "free market" of ideas was far superior to, and much more reliable than, scientific research.
Another telling quote from Lasagna's writing during this time is what he called the supposed censorship imposed on industry by overweening FDA regulations, according to his view--he deemed it "Lysenkoism," comparing the FDA with the Stalinist suppression of Mendelian genetics in the USSR. Daniel Stedman Jones's political history of E/N (Masters of the Universe: Hayek, Friedman, and the Birth of Neoliberal Politics, Princeton, 2012) points out that the major founders of E/N, Hayek and Friedman, shared a conviction that all "collectivism" was cut from the same cloth, whether it be Hitler's Germany, Stalin's Russia, the New Deal, Britain's welfare state, or even a labor union. A doctrinaire anti-communism all during the Cold War characterized their public utterances. By invoking a Stalinist bogeyman, Lasagna indicated that he was singing straight out of the E/N hymnal.
Nik-Khah's work seems a useful historical exploration of how many of the pro-Pharma policies and politics that emerged in the US in the later decades of the 20th century can be traced directly to the influence of the E/N ideology, and how the echo chamber of E/N institutions helped to spread the word. (Hat tip to my colleague Daniel Goldberg for recommending this article.)
Nik-Khah E. Neoliberal pharmaceutical science and the Chicago School of Economics. Social Studies of Science, 2014, e-published ahead of print
Addendum 4/13/14: By coincidence, I have recently finished reading Dominique Tobbell's book, Pills, Power, and Policy: The Struggle for Drug Reform in Cold War America and Its Consequences (University of California Press/Millbank Books, 2011). Historian Tobbell paints quite a different picture of how Louis Lasagna did a 180 on the FDA. According to her account, Lasagna's conversion was much more gradual, was based at least in part on a reasoned assessment of how the FDA appeared to be overreaching in its responses to the 1962 post-thalidomide Congressional amendments, and was already largely completed by the time he was first exposed to a strong dose of E/N. So before one buys into Nik-Khah's account, it's only fair to mention this alternative assessment.
Monday, March 3, 2014
Sunday, February 23, 2014
Pradaxa: More Evidence of Drug Firms Manipulating Science
Thanks to Dr. Roy Poses at Health Care Renewal:
--for calling attention to two articles in the New York Times by Katie Thomas:
Let me give some medical background and then review the
contents of Thomas’s articles, relay Dr. Poses’ take on the matter, and then
end with a reflection of my own.
For many years, the most commonly used oral anti-clotting
drug (commonly referred to mistakenly and misleadingly as “blood thinners”) has
been warfarin. Warfarin has a number of disadvantages. First, it has a very
narrow safety range—let blood levels get too low and the person is at risk for
forming potentially fatal clots; let them get too high and the person is at
risk for a potentially fatal bleeding episode. That leads to the second
disadvantage—that patients taking warfarin have to report regularly for blood
tests to measure the levels and to adjust the dose if needed. So if anyone
succeeds in developing a new-generation replacement for warfarin, but without
these problems, then it would qualify as a better mousetrap par excellence.
Recently, several firms have proclaimed the advent of the
better mousetrap; one version is Pradaxa (dabigatran) made by the German firm
Boehringer Ingelheim. Pradaxa has been marketed for preventing clots in one of
the most common conditions for which such drugs are prescribed, the irregular
heartbeat known as atrial fibrillation, and the company claims it is at least
as good as warfarin without requiring any inconvenient blood testing. Warfarin
works by blocking the step in the clotting process that’s controlled by Vitamin
K, so that if a patient taking warfarin starts bleeding dangerously, an
intravenous dose of Vitamin K will immediately reverse the drug’s effects.
Pradaxa and the other new drugs work at a different point in the clotting cycle
and there’s no available antidote if a patient bleeds—leading some experts to
advise that the drug is too dangerous to use for that reason alone. The FDA has
received reports of 1000 deaths attributed to Pradaxa (out of some 850,000
patients prescribed the drug, netting Boehringer the hefty revenues of $2B).
It’s patients suing the drug firm over Pradaxa-related harm
that led to the articles in the Times.
The judge ordered release of some documents related to the case that include
internal company e-mails about a research study coordinated by a company
scientist, Paul A. Reilly. Reilly’s study showed that a part of the safety
problem with Pradaxa was that some patients had too high a blood level and some
patients too low (sound familiar?). He concluded that a blood test that
measured drug levels could be helpful for at least some patients in avoiding
dangerous reactions. (Such a blood test is available now in Europe but not the
U.S.)
A draft of Reilly’s paper that included these findings
unleashed a storm of e-mails from other company scientists and officials. They
argued that publishing a paper with these conclusions would undermine the
company’s primary marketing point in favor of Pradaxa, the result of a
fine-tuned marketing effort going back a decade. Moreover, some feared that if
the paper were published, it would be that much harder to get the government
regulators to hold off demanding blood tests. The end result was that the paper
was published recently but with many of the offending details removed.
Boehringer Ingelheim insists that this was a simple matter
of scientific review and refinement. A draft was circulated, others chimed in
with appropriate criticisms, and in the end the final paper was suitably
modified to better present the actual facts. Nobody here but us scientists,
boss.
Other experts aren’t buying that, and Dr. Poses
appropriately asks how often such censoring of scientific findings in the name
of marketing occurs with no friendly judge to force the release of the secret
company documents.
One of the common complaints from pharmapologists is that
pharmascolds quite unfairly would have physicians distrust a scientific paper
merely because it’s sponsored by a drug company, when ideally, they should read
the paper carefully, review the methods, and believe the paper or not based
solely on its merits. Dr. Poses comes out with a powerful contrary statement: “I
strongly advocate that those who author authoritative systematic reviews,
meta-analyses, and clinical practice guidelines… assume the likelihood that all
commercially sponsored published clinical research has been manipulated…”
Now for my own comment—this sounds very much like a replay
of the case of the so-called atypical antipsychotics that we previously
discussed:
Recall there that a new class of drugs was introduced with
great fanfare and said to be far superior to the original class of drugs, and
only after years of use did it become clear in hindsight that the supposedly
new drugs were in fact hardly different at all from the old ones, except in the
eyes of the company marketers, who managed to bamboozle the entire medical
profession very neatly, much to the harm of patients.
Reilly PA, Lehr T, Haertter S, et al. The effect
of dabigatran plasma concentrations and patient characteristics on the
frequency of ischemic stroke and major bleeding in atrial fibrillation
patients: The REL-Y Trial (Randomized Evaluation of Long-term Anticoagulation
Therapy). Journal of the American College
of Cardiology 63:321-328, 2014.
Saturday, February 15, 2014
"You're Another" Should Be an Admission of Guilt
Charles Ornstein, investigative reporter at ProPublica, recently commented on a flap involving (to put it bluntly) university docs shilling for a device company:
http://www.propublica.org/article/when-a-university-hospital-backs-a-surgical-robot-controversy-ensues
He cited a blog by Paul Levy, a former CEO of New England Deaconess Medical Center in Boston. Levy noted an ad for the da Vinci surgical robot that featured a group photo of surgeons from the University of Illinois (Chicago) Hospital. Mr. Levy did a little digging around and discovered that such an appearance in an ad seemed to violate U-Ill. official policy. So he sounded off in several blog posts and the University eventually took note and said they'd look into the matter, while insisting that these surgeons did all this out of the kindness of their hearts and were not paid for appearing in the ad.
You might wonder why the flap over a surgical robot. These devices can cost a cool $2M or more each, and of course when introduced were touted as the greatest new medical breakthrough. Sadly, to the extent that evidence is becoming available (and I admit I have not followed this debate as closely as one might), the bulk of data seem to question whether robotic surgery produces outcomes that are superior to the old garden variety surgery, and indeed in some cases there may be worse complications--leading for instance the American College of Obstetrics and Gynecology (ACOG) to state (as Ornstein noted) that robotic hysterectomy has not even been shown to be as good as, much less better than, the old-fashioned and vastly cheaper procedure.
This has left a lot of hospitals, who rushed to obtain "the latest" out of fear that both their surgeons and their patients would desert them for the "better" hospital up the street, with expensive robots that now threaten to become white elephants. So you can see why the maker of the robot would want to run ads reassuring everyone that these devices are indeed worth their weight in gold.
What I wanted to comment on regarding this incident are two things.
First: Intuitive, the company that makes the robot in the ad, responded to the discussion by saying: "In the past year, there has been much misinformation about robotic-assisted surgery, spread largely by plaintiffs’ lawyers as well as segments of the health-care community threatened by our groundbreaking technology. ... The University of Illinois, which uses our technology, and the people featured in the advertisement agreed to appear without compensation. Those who use our technology see first-hand the outcomes resulting from its use. Their unpaid testimonials of da Vinci surgery are credible and sincere."
So, first, only evil folks with an axe to grind say anything bad about robotic surgery (take that, ACOG); and second, no one paid these nice Illinois surgeons a dime to be in the ad. Now that latter may be true; I can't disprove it. But knowing what we know about both the largesse of device makers toward docile docs who tout their wares, and the extent the makers sometimes go to to launder the money as it changes hands, I'd frankly be quite surprised if there's no quid pro quo someplace.
Second: Ornstein spoke with Thomas Hardy, executive director of university relations at U-Ill. Chicago. Mr. Hardy wanted to be sure that Ornstein knew all about a shady event in blogger Levy's past, which if you want to read the dirt, is detailed here:
http://www.boston.com/bostonglobe/editorial_opinion/oped/articles/2010/05/09/how_not_to_run_a_hospital/
So Ornstein asked Mr. Hardy exactly how this previous, and admitted lapse of Mr. Levy was relevant to the discussion of the ad with the U-Ill. surgeons that appears to violate U-Ill. official policy. Hardy's reply was: “I believe if you’re attributing claims and accusations to the blogster, your readers deserve to know his reported background so they can make an informed decision about his credibility…Wanted to make sure you have the pertinent information.”
Right. So know we know what sort of person we're dealing with.
I have a proposal for a new rule: If a person accuses you of conflict of interest or a similar lapse of professional responsibility, and the best defense you can come up with is an ad hominem attack against the person regarding something that's irrelevant to the present controversy, then your ad-hominem attack ought to be viewed as in itself an admission of wrongdoing.
http://www.propublica.org/article/when-a-university-hospital-backs-a-surgical-robot-controversy-ensues
He cited a blog by Paul Levy, a former CEO of New England Deaconess Medical Center in Boston. Levy noted an ad for the da Vinci surgical robot that featured a group photo of surgeons from the University of Illinois (Chicago) Hospital. Mr. Levy did a little digging around and discovered that such an appearance in an ad seemed to violate U-Ill. official policy. So he sounded off in several blog posts and the University eventually took note and said they'd look into the matter, while insisting that these surgeons did all this out of the kindness of their hearts and were not paid for appearing in the ad.
You might wonder why the flap over a surgical robot. These devices can cost a cool $2M or more each, and of course when introduced were touted as the greatest new medical breakthrough. Sadly, to the extent that evidence is becoming available (and I admit I have not followed this debate as closely as one might), the bulk of data seem to question whether robotic surgery produces outcomes that are superior to the old garden variety surgery, and indeed in some cases there may be worse complications--leading for instance the American College of Obstetrics and Gynecology (ACOG) to state (as Ornstein noted) that robotic hysterectomy has not even been shown to be as good as, much less better than, the old-fashioned and vastly cheaper procedure.
This has left a lot of hospitals, who rushed to obtain "the latest" out of fear that both their surgeons and their patients would desert them for the "better" hospital up the street, with expensive robots that now threaten to become white elephants. So you can see why the maker of the robot would want to run ads reassuring everyone that these devices are indeed worth their weight in gold.
What I wanted to comment on regarding this incident are two things.
First: Intuitive, the company that makes the robot in the ad, responded to the discussion by saying: "In the past year, there has been much misinformation about robotic-assisted surgery, spread largely by plaintiffs’ lawyers as well as segments of the health-care community threatened by our groundbreaking technology. ... The University of Illinois, which uses our technology, and the people featured in the advertisement agreed to appear without compensation. Those who use our technology see first-hand the outcomes resulting from its use. Their unpaid testimonials of da Vinci surgery are credible and sincere."
So, first, only evil folks with an axe to grind say anything bad about robotic surgery (take that, ACOG); and second, no one paid these nice Illinois surgeons a dime to be in the ad. Now that latter may be true; I can't disprove it. But knowing what we know about both the largesse of device makers toward docile docs who tout their wares, and the extent the makers sometimes go to to launder the money as it changes hands, I'd frankly be quite surprised if there's no quid pro quo someplace.
Second: Ornstein spoke with Thomas Hardy, executive director of university relations at U-Ill. Chicago. Mr. Hardy wanted to be sure that Ornstein knew all about a shady event in blogger Levy's past, which if you want to read the dirt, is detailed here:
http://www.boston.com/bostonglobe/editorial_opinion/oped/articles/2010/05/09/how_not_to_run_a_hospital/
So Ornstein asked Mr. Hardy exactly how this previous, and admitted lapse of Mr. Levy was relevant to the discussion of the ad with the U-Ill. surgeons that appears to violate U-Ill. official policy. Hardy's reply was: “I believe if you’re attributing claims and accusations to the blogster, your readers deserve to know his reported background so they can make an informed decision about his credibility…Wanted to make sure you have the pertinent information.”
Right. So know we know what sort of person we're dealing with.
I have a proposal for a new rule: If a person accuses you of conflict of interest or a similar lapse of professional responsibility, and the best defense you can come up with is an ad hominem attack against the person regarding something that's irrelevant to the present controversy, then your ad-hominem attack ought to be viewed as in itself an admission of wrongdoing.
Wednesday, February 12, 2014
Update: Detailing in India and Pakistan
The very nice people at the Centre for Biomedical Ethics and Culture, Sindh Institute of Urology and Transplantation, Karachi, Pakistan, publish a newsletter. I was attracted by the cover story, "The Drug Industry and Doctors: An Unholy Alliance," by Sandhya Srinivasan, a journalist and researcher from India:
http://www.siut.org/bioethics/Sandhya%20Srinivasan.pdf
In many ways the issues in that part of the world are the same as here, but a few highlights of interest:
It may be hard to imagine a part of the world where freeing medicine from the grip of industry influence is even more of an uphill struggle than here, but that seems to be the case in South Asia.
http://www.siut.org/bioethics/Sandhya%20Srinivasan.pdf
In many ways the issues in that part of the world are the same as here, but a few highlights of interest:
- Presumably due to the general lower income enjoyed by physicians in poorer nations, it's become more acceptable and commonplace for drug reps to bribe physicians with less subtle "gifts" such as air conditioners, washing machines, microwaves, TVs, etc., compared to the pretense kept up in richer countries that the "gifts" relate solely to one's professional role.
- While efforts have been made in both India and Pakistan to declare such bribes unethical, in India, especially, enforcement has been marred by numerous roadblocks--both the influence exerted over government by drug company interests; and also the dubious position of some of the folks issuing the "ethics" guidelines, for example: "The [Medical Council of India, who promulgated one Code of Ethics on the subject] is not viewed as a guardian of medical ethics. Less than a year after the amendment, its president was arrested on charges of corruption."
- A study in Pakistan likewise found widespread acceptance of drug reps and their largesse, with doctors meeting with an average of seven reps daily.
It may be hard to imagine a part of the world where freeing medicine from the grip of industry influence is even more of an uphill struggle than here, but that seems to be the case in South Asia.
The NIH Accelerating Medicines Partnership—Francis Collins Sings a Few Bars
I had wanted to respond to a news release some days ago
about the Accelerating Medicines Partnership announced by the NIH and 10 drug
companies, but before I got around to it, I caught a tiny bit of this interview
on The Diane Rehm Show on my car
radio:
http://thedianerehmshow.org/shows/2014-02-10/conversation-dr-francis-collins-director-nih
--in which not only did Dr. Francis Collins, head of the NIH, talk about the AMP, but also sang about it self-accompanied on his guitar (which, he explained, suitable for the former head of the Human Genome Project, has a double helix inlaid in mother-of-pearl on its fretboard).
http://thedianerehmshow.org/shows/2014-02-10/conversation-dr-francis-collins-director-nih
--in which not only did Dr. Francis Collins, head of the NIH, talk about the AMP, but also sang about it self-accompanied on his guitar (which, he explained, suitable for the former head of the Human Genome Project, has a double helix inlaid in mother-of-pearl on its fretboard).
I’ll let you enjoy the music if you wish on the audio and
turn straight to the written transcript.
Here’s how Dr. Collins explains the AMP:
So more than 1,000 new drug targets have emerged in the last five years from
that kind of study, but it's very hard to sift through them and pick out which
ones are going to be the real home runs that we're all looking for…. this is
full 50/50 skin-in-the-game kind of collaboration, $230 million committed to
this over five years, half of that coming from NIH, half of that coming from
the 10 companies that are participating. The scientists from both sectors will
sit around the same table and work together to make this happen in a fully open
access atmosphere…. We already have detailed research plans
for these disease areas that have been worked out over the past year with very
clear milestones that have to be met. This is not one of those where everybody
goes off and plays in the lab. We are really serious here about making real progress.
Well, in this phase of trying to identify the next generation of drug
targets, everybody agrees that this is precompetitive, and that is that all the
information has to be openly shared both within this consortium and for anybody
else who's watching. The competitiveness, Diane, kicks in once you've
identified, oh wow, that particular molecule is a really promising target for
the next generation of Alzheimer's therapy…. Then every company will run off and do what they do really well… And we
want them to do that. That's good competition. That means that things move
quickly and there's lots of ways that you can get to yes.
Let me see if I can make sense of this from the standpoint
of the view of current pharmaceutical science that I proposed in HOOKED. I
suggested then that the current drug pipelines were so dry because there are
only a limited number of molecules that do useful things in the human body
without killing us. Not that there would never again be a “golden age” of major
advances in drug therapy; but the new golden age would not come from drug
companies doing cranked-out research on their assembly line—it would require
breakthroughs in our basic understanding of disease, discoveries that the NIH
and academic centers are better able to make than industrial labs. So Take Home
Message #1, I hear Dr. Collins saying that we’re poised to enter another age of
advancement, that basic science research has now identified a bunch of exciting
new possibilities—locks that we now need to discover the keys to.
Take Home Message #2 seems to be that the “translational
science” model, which NIH has embraced in the last decade, tells them that
we’re now ready for a more accelerated and focused phase of discovery, when NIH
scientists and Pharma scientists can both participate in a program that will quickly move (as the translational
mantra has it) from (lab) bench to bedside. At this point, as a complete
non-expert, I would enter a note of caution. I generally support the
translational science model (full disclosure: a small portion of my salary is
currently funded under a translational science grant, to address the ethical
issues). However, there are times in the life cycle of a discovery when you can
safely go on the fast track and other times when you’d be better off “playing
in the lab” just a little bit longer. I hope the NIH gurus are right that their
particular list of diseases—Alzheimers, diabetes, and autoimmune disease—is
truly ready for this hurry-up approach.
OK, so that’s the science part; what about the
potential-conflict-of-interest part, the rocks on which so many previous
scientific ships have broken up and sank? Says Dr. Collins:
With regard to the drug companies, I know that people are concerned about
what their motives are. Again, they make pills. NIH doesn't. … We believe, by
working together, we can speed up the process of getting the right answers. … You know, five years ago, I don't think
this [collaboration] would have been possible. I think it's a combination of
scientific opportunity that is so exciting but so overwhelming that no company
can tackle it on their own, plus their own anxieties about the failures that
are all too common, even now, in drug trials where you've spent hundreds of
millions of dollars and you get to the end of that Phase III trial and it
didn't work. They've had enough of that, and they're anxious to try something
different.
So two things here—first, with a demand for open access, NIH
figures they have a safeguard against one of the main dangers of industry
collaborations of the past; and second, they believe that the drug industry
today is in a different place and more willing to play nicely in the sandbox.
Interestingly, Dr. Collins made a comment similar to one I have made previously
in this blog—
http://brodyhooked.blogspot.com/2011/08/in-praise-of-good-corporate-behavior.html:
[Rehm] I'm interested that Johnson & Johnson hired Yale University to oversee
the sharing of clinical trial data. What can you tell us about that? [Collins]
I think that's
fascinating. So the person at Yale University, Mr. Harlan Krumholz, who's a
cardiologist, who is a wonderful leader in this whole idea about getting
information out there where everybody can see it -- and he has a lot of
credibility so people will believe that if Harlan is involved that what Johnson
& Johnson proposes to do is the real deal and not just some window
dressing. I think it's great.
Final conclusion I’d offer: NIH seems to be
going into the AMP with decent reasons and with eyes open, but so far, Pharma
has an excellent track record of managing to have such folks for lunch
nonetheless. I hope Dr. Collins is right and this time it will be different,
and if so, we may have yet another good model of positive collaboration to work
with. Stay tuned.
Sunday, February 9, 2014
AAUP Chimes In on COI
The American Association of University Professors has now published its 356-page report, Recommended Principles to Guide Academy-Industry Relationships:
http://www.aaup.org/article/report-academy-industry-relationships-published-book-form#.Uvf0_5CYY5s
What the AAUP essentially appears to have done is to review reports issued previously by such organizations as AAMC and IOM, and select the provisions their committee most approved of. In general, the AAUP has taken a strong stand in favor of what they consider to be academic values and academic freedom, and opposing any intrusion of financial conflicts of interest. For example, among the 56 guiding principles that they offer, Principle 3 demands the right for faculty to publish their research with at most a minimal delay (30-60 days) to protect patent and other so-called "intellectual property" interests. Principle 4 condemns any and all instances of ghostwriting. The report states clearly that disclosing COI is usually not enough and that avoiding COI is by far preferable.
While subsets of principles relate directly to academic medicine and biomedical research, the AAUP here attempts to address the broadest set of academic-industry relationships, and not to restrict their purview solely to medicine and the life sciences. They acknowledge, however, that the medical area has been especially problematic (no surprise to any readers of this blog).
One area that draws special attention in the report is what they call Strategic Corporate Alliances, major multi-year commitments between a university and a corporate sponsor to cover all faculty working in a specific field. The original poster child for such an alliance, discussed at some length in HOOKED, was the 1998 agreement between UC-Berkeley and Novartis for rights to all research conducted in its Plant Biology department. Since then, says the AAUP, such agreements have only grown and expanded. The principles they propose to govern such agreements strongly tips the balance in favor of an academic-governance model and away from giving too much control to the corporate sponsor--so much so that one wonders what corporations would agree to major alliances under the conditions specified.
I suppose in the name of full disclosure I should mention that among the 770 endnotes, at least one cites HOOKED-- I cannot state that I have read all 770 of them, however.
http://www.aaup.org/article/report-academy-industry-relationships-published-book-form#.Uvf0_5CYY5s
What the AAUP essentially appears to have done is to review reports issued previously by such organizations as AAMC and IOM, and select the provisions their committee most approved of. In general, the AAUP has taken a strong stand in favor of what they consider to be academic values and academic freedom, and opposing any intrusion of financial conflicts of interest. For example, among the 56 guiding principles that they offer, Principle 3 demands the right for faculty to publish their research with at most a minimal delay (30-60 days) to protect patent and other so-called "intellectual property" interests. Principle 4 condemns any and all instances of ghostwriting. The report states clearly that disclosing COI is usually not enough and that avoiding COI is by far preferable.
While subsets of principles relate directly to academic medicine and biomedical research, the AAUP here attempts to address the broadest set of academic-industry relationships, and not to restrict their purview solely to medicine and the life sciences. They acknowledge, however, that the medical area has been especially problematic (no surprise to any readers of this blog).
One area that draws special attention in the report is what they call Strategic Corporate Alliances, major multi-year commitments between a university and a corporate sponsor to cover all faculty working in a specific field. The original poster child for such an alliance, discussed at some length in HOOKED, was the 1998 agreement between UC-Berkeley and Novartis for rights to all research conducted in its Plant Biology department. Since then, says the AAUP, such agreements have only grown and expanded. The principles they propose to govern such agreements strongly tips the balance in favor of an academic-governance model and away from giving too much control to the corporate sponsor--so much so that one wonders what corporations would agree to major alliances under the conditions specified.
I suppose in the name of full disclosure I should mention that among the 770 endnotes, at least one cites HOOKED-- I cannot state that I have read all 770 of them, however.
Sunday, February 2, 2014
Reps on Safety Issues, or, the Sounds of Silence
When writing in HOOKED about drug reps, I asserted that they seem to soft-pedal safety concerns, seldom mentioning any adverse reactions to their drugs. Unfortunately, the data at the time were restricted to one major study in France, so one could claim that we actually knew very little about what reps did or did not say to physicians on this subject.
We can therefore welcome the more recent study of Dr. Barbara Mintzes and her colleagues (subscription required), who studied drug rep-physician interactions in four cities in three countries, Montreal, Vancouver, Sacramento, and Toulouse. A major weakness immediately arises as they relied on physician recall of the visit rather than directly observing the visit. However, it's nearly impossible to imagine drug reps agreeing to have these visits observed, or acting "normal" if they knew the visit was being recorded, so I gather this is the best evidence that is ever likely to be available. The folks ended up with 255 physicians reporting on 1692 detail visits.
Essentially, this study confirmed the earlier French study. They used as a primary outcome "minimally adequate safety information," which they defined as "mention of [at least] 1 approved indication, [at least one serious adverse event (SAE), [at least] 1 common non-serious adverse event (AE), [at least] 1 contraindication (CI) and no unapproved indications or unqualified safety claims". They thought they were setting the bar pretty low with these requirements, so it's impressive that this desired endpoint was reached overall in only 1.7% of all visits, ranging from 0.9% in Sacramento to 3.0% in Toulouse.
As an example of just how far off the mark was the information provided in most details, in terms of safety, the physicians recorded what they took to be the "key message" of the detail. For details for Avandia, taken off the market in Europe and restricted in Canada and the U.S. in 2010 due to concerns about excessive heart risks, key messages included, "'Avandia is safe even in patients with heart disease, as long as they don't have heart failure' (Montreal); 'Avandia is not as dangerous as the public makes it out to be' (Sacramento); 'New studies indicate safety' (Vancouver)."
Despite the near-total absence of valid information about the safety of drugs, these physicians (who of course have to be willing to see reps to be included in the study; a number of candidates were excluded because they never saw reps) rated 57% of the details as "good" or "excellent," and nearly two-thirds of the time stated they were "somewhat" or "very" likely to start prescribing the drug being detailed.
The authors noted that details that were conducted in the way that the vast majority of these apparently were are actually illegal according to the official criteria for the FDA and equivalent agencies in Canada and France, but of course there's virtually no enforcement at the level of the private conversation between rep and doc in the office.
If anyone still thinks that visits from reps to physicians are "not marketing but education," this study seems to put one more nail in that coffin. (Hat tip to Primary Care Medical Abstracts for clueing me in to this article.)
Mintzes B, Lexchin J, Sutherland JM, et al. "Pharmaceutical Sales Representatives and Patient Safety: A Comparative Prospective Study of Information Quality in Canada, France and the United States." Journal of General Internal Medicine 28:1368-75, 2013.
We can therefore welcome the more recent study of Dr. Barbara Mintzes and her colleagues (subscription required), who studied drug rep-physician interactions in four cities in three countries, Montreal, Vancouver, Sacramento, and Toulouse. A major weakness immediately arises as they relied on physician recall of the visit rather than directly observing the visit. However, it's nearly impossible to imagine drug reps agreeing to have these visits observed, or acting "normal" if they knew the visit was being recorded, so I gather this is the best evidence that is ever likely to be available. The folks ended up with 255 physicians reporting on 1692 detail visits.
Essentially, this study confirmed the earlier French study. They used as a primary outcome "minimally adequate safety information," which they defined as "mention of [at least] 1 approved indication, [at least one serious adverse event (SAE), [at least] 1 common non-serious adverse event (AE), [at least] 1 contraindication (CI) and no unapproved indications or unqualified safety claims". They thought they were setting the bar pretty low with these requirements, so it's impressive that this desired endpoint was reached overall in only 1.7% of all visits, ranging from 0.9% in Sacramento to 3.0% in Toulouse.
As an example of just how far off the mark was the information provided in most details, in terms of safety, the physicians recorded what they took to be the "key message" of the detail. For details for Avandia, taken off the market in Europe and restricted in Canada and the U.S. in 2010 due to concerns about excessive heart risks, key messages included, "'Avandia is safe even in patients with heart disease, as long as they don't have heart failure' (Montreal); 'Avandia is not as dangerous as the public makes it out to be' (Sacramento); 'New studies indicate safety' (Vancouver)."
Despite the near-total absence of valid information about the safety of drugs, these physicians (who of course have to be willing to see reps to be included in the study; a number of candidates were excluded because they never saw reps) rated 57% of the details as "good" or "excellent," and nearly two-thirds of the time stated they were "somewhat" or "very" likely to start prescribing the drug being detailed.
The authors noted that details that were conducted in the way that the vast majority of these apparently were are actually illegal according to the official criteria for the FDA and equivalent agencies in Canada and France, but of course there's virtually no enforcement at the level of the private conversation between rep and doc in the office.
If anyone still thinks that visits from reps to physicians are "not marketing but education," this study seems to put one more nail in that coffin. (Hat tip to Primary Care Medical Abstracts for clueing me in to this article.)
Mintzes B, Lexchin J, Sutherland JM, et al. "Pharmaceutical Sales Representatives and Patient Safety: A Comparative Prospective Study of Information Quality in Canada, France and the United States." Journal of General Internal Medicine 28:1368-75, 2013.
Subscribe to:
Posts (Atom)