Tuesday, February 23, 2010

Internal Medicine Residencies and Pharma Money: We Don't Like It but We Take It

Duff Wilson in the New York Times:

--offered a handy synopsis of a paper by Dr. Laura L. Loertscher and colleagues (subscription required to access). The Association of Program Directors in Internal Medicine (residency program directors) conducted a survey of their members. A little more than half, 55.9% reported receiving some form of money from the pharmaceutical industry; the most common item funded was food for lunch conferences (90%). A wide majority (72.0%) of the directors disapproved of taking these funds, but were swayed especially by the popularity of these benes among the residents (40%), as well as by a general sense of the lack of alternative funding sources. The authors remarked that overall this represents an improvement over a 1990 survey that showed 88.6% of residencies taking money.

The surveyers next tried to correlate one measure of a residency's quality, the percentage of residents who pass the Board exam, with taking Pharma money, and found a direct inverse correlation--the worse the residency, the more likely it was to accept Pharma money. (One has to wonder whether if this word gets around, "drug lunches" will still be such a popular item among the residents.)

Wilson's article in the Times noted that the Accreditation Council for Graduate Medical Education has the authority to end this practice instantly by fiat. The authors, like good internists, did not make such a suggestion, but rather called for more research.

Loertscher LL, Halvorsen AJ, Beasley BW, et al. Pharmaceutical industry support and residency education: a survey of internal medicine program directors. Archives of Internal Medicine 170:356-62, Feb. 22, 2010.

NPR: More Details on the Obama-PhRMA Back Room Deal

A while back we noted the possible connection between Billy Tauzin's departure as president of PhRMA and the deal the lobbying organization made with the Obama White House over health reform legislation:

Anyone wanting more details about this deal should check out the NPR Fresh Air story:

(Note: The NPR link has additional links to source materials)

Paul Blumenthal, a writer for a nonprofit open-government group, documented a series of meetings between Tauzin and major drug company CEOs, on one side, and Obama chief of staff Rahm Emanuel and his deputy Jim Messina on the other. They cut a deal with the following features:
  • PhRMA would pay for $150 million in ads favoring health reform (the ads appeared as sponsored by a coalition of organizations and PhRMA funding was not clearly labeled).
  • PhRMA would agree to back Obama's efforts overall, and also to forgo $80B in potential profits over the next decade to support reform.
  • Obama would eliminate from any final bill the cost-cutting measures PhRMA most feared-- allowing reimportations of cheaper drugs from canada, and using government mass purchasing power to negituiate lower prices.
  • The deal would be made around the draft bill being prepared by Max Baucus's Senate Finance Committee; the House committees and other Senate committees working on reform legislation were cut out.

The deal became public knowledge in the late summer when Tauzin started to fear that Obama might be pulling back, and leaked the deal to the press. That led the White House to admit the deal two days later. Blumenthal reconstructed who came to the meetings from the White House visitors log which the Obama administration, for the first time, has made public.

Blumenthal offered as his take on Tauzin's resignation that PhRMA was upset because it spent the $150M on ads and has no bill to show for it. He added that at present, PhRMA stands to make out like bandits if some type of health reform similar to the Senate bill becomes law. Millions more Americans will be insured and able to afford to buy their products, and to pay top dollar for the privilege. As we noted in a previous post, the drug firms have already jacked up their prices of brand-name drugs to the tune of a $100B increase over the next decade, effectively cancelling out the promised $80B price savings.

Bottom line-- if you're a political cynic and expect health reform to be done according to the age-old Washington formula, you're not surprised to see this particular brand of sausage being made. You can defend your cynicism by noting that at this point, health reform has come closer to passage under Obama's watch than it has in the past century, so he must be doing something right. If you were hoping that Obama would, as promised, change the way Washington does business, you have to be somewhat disappointed.

The Secret Avandia Tapes: Comedy or Smoking Gun?

Gardiner Harris broke this story yesterday in the New York Times:

My own opinion is that this is more of a bit of Pharmagossip than anything really substantive that moves forward our understanding of the ethical issues at the medicine/Pharma interface; but who can withstand the attraction of a really juicy bit of gossip?

According to the timeline provided by Cleveland Clinic cardiologist Dr. Steve Nissen in the last post, it's now May 10, 2007. On May 1, Nissen and his colleagues submitted a manuscript of a meta-analysis showing excess cardiac risks with the diabetes drug Avandia (rosiglitazone) to the New England Journal of Medicine. On May 17, highlighting the public health importance of the findings, NEJM will publish the paper on line. I gather from the story that Nissen knew by May 10 that NEJM was about to accept the paper if they had not already formally accepted. What Nissen did not know on May 10 was that an NEJM reviewer, Dr. Steven M. Haffner of the University of Texas-San Antonio medical center, had faxed a copy of the manuscript to GlaxoSmithKline, with whom he had a financial relationship (in violation of all the rules of journal publishing and academic peer review--see previous post).

On May 10, four executives from GlaxoSmithKline, the manufacturers of Avandia, met with Nissen in his office. Presumably Nissen knew that they knew that a paper had been submitted to NEJM. Nissen did not know that they knew the paper's exact contents. Nissen knew that they would not like the conclusions of the paper. Nissen did not know that GSK had internally crunched the numbers and that their own statisticians agreed that Nissen et al. had got the numbers right.

Now, add to the who-didn't-know-what that Nissen decided to tape the meeting without telling the GSK execs--which is legal in Ohio, we are told. Harris says that Nissen "fear[ed] he would face pressure and criticism from executives" and therefore decided to record the meeting. I don't know if Nissen had read John Le Carre's novel, The Constant Gardener, or had seen the movie, but if so, he might have feared further that if GSK had its way, he'd soon be sleeping with the fishes. For whatever reason he decided on the recording gambit.

GSK told the Times they were "disturbed" to learn that the meeting had been recorded without their knowledge. GSK did not indicate that they were disturbed that their lackey had violated all the rules of journal peer review by sending them a fax of Nissen's paper.

So, with all this high drama, what do we now know from the tape? Well, not all that much, but a few nuggets.

First, GSK tried to buy off Nissen from publishing his paper by promising that important new data would be available very soon, and hinting that Nissen might look stupid if he published his own, incomplete data before awaiting the new, definitive study. (Again, no hint that they had already internally confirmed the correctness of Nissen's numbers.) Specifically, on June 6, 2007, GSK published an interim analysis of another trial called RECORD. GSK's chief medical officer, Dr. Ronald L. Krall, is captured on the tape playing a "what if" game with Nissen. Nissen's group had calculated that the hazard ratio for excess heart disease due to Avandia was 1.64. "Let's suppose," said Krall, "RECORD was done tomorrow and the hazard ratio was 1.12."

The lesson here is that when RECORD was later published, the hazard ratio was 1.11. Krall would not have known this fact on May 10 if the study protocol had been followed correctly; as of that date the study would still have been blinded. So the tape suggests that GSK was playing fast and loose with the study methodology, looking for ways to cover its rear end with the disclosure of Avandia's risks imminent.

Krall's next "what if" move was--"Suppose we did [a] patient-level analysis and it looked very different from what you have?" Nissen shot back that he agreed that a patient-level analysis, returning to the actual raw data, would be superior in reliability to his meta-analysis that relied only on grouped study data. But he also had enough confidence in his meta-analysis numbers to claim that it was not mathematically possible that the patient-level data could deviate from his calculations by a significant degree--certainly not enough to remove evidence of a serious risk. In any event, if GSK ever actually ran the patient-level data and were not simply bluffing, those data have never been made public.

Sunday, February 21, 2010

The Avandia Story: Failures of Regulation and Professionalism

Rosiglitazone (Avandia) is back in the news. First I opened my newspaper this morning to read the following article:


Next, faithful reader Marilyn Mann kindly alerted me to a new editorial on rosiglitazone by Steve Nissen of the Cleveland Clinic, author of the meta-analysis that revealed the serious cardiovascular risks associated with the drug (citation below). Finally, through that article's citations, I was alerted to a New York Times article I had originally missed:


Let's do a quick recap of the story Nissen tells. Early on there were reasons to be concerned that rosiglitazone's blood-sugar-lowering effects might come at the cost of cardiovascular risk, especially increased risk of congestive heart failure. This was important news because there are many other drugs available for management of diabetes, and one of the main reasons doctors want to control Type 2 diabetes is to reduce, not increase, heart risks. (More on that at the end.)

The FDA, meanwhile, was mostly focused on the first drug in that class to be aproved for diabetes, troglitazone (which I discuss at length in HOOKED). That drug (Rezulin) was causing big concern because of recently revealed risks of liver damage, in some cases so bad as to require liver transplant. The FDA wanted to get troglitazone off the market but feared reaction of the diabetes treatment community if it removed the only drug in this promising new class. Problem solved-- in 1999 the FDA quickly approved rosiglitazone plus another cousin, pioglitazone, both known to be relatively free of the liver problem; then later took troglitazone off the market. Trouble was the FDA was in such a rush that the heart risks of rosiglitazone (not shared, it seems, by pio-, thank goodness) got short shrift.

One prominent endocrinologist, Dr. John Buse, started to talk about the increased heart risks associated with the new drug. A delegation from the manufacturer paid him a visit. The upshot was that he ended up signing a contract essentially gagging him from commenting unfavorably on rosiglitazone. (Earlier post on the ins and outs of the Buse case at: http://brodyhooked.blogspot.com/2007/11/intimidation-of-dr-john-buse-some.html)

By October, 2006, GlaxoSmithKline had pretty good evidence from a large trial that there was a significant increased heart-failure risk with its drug, then selling in excess of $3B annually. The company shared the evidence with the FDA. Neither notified the medical profession or the general public. (Hence, the recent report from the US Senate reported by the AP, of how long the company knew the risks before revealing them.)

Nissen and his team conducted their independent meta-analysis and submitted it for publication in May 2007. As soon as he received a copy of the manuscript from the New England Journal of Medicine for his confidential review, Dr. Steven M. Haffner of the University of Texas-San Antonio medical center faxed a copy of it to GlaxoSmithKline, with whom he had a financial relationship, in violation of all the rules of journal publishing and academic peer review. However, GSK had already (as noted) been alerted to the risks of Avandia and merely noted that the figures calculated in Nissen's meta-analysis matched closely its own internal figures. The advance leak of the NEJM paper did however give GSK time to rush the publication of another study as a partial response to the unfavorable publicity. Eventually Avandia sales plummeted. (The Times reported in 2008 that UT-San Antonio was dealing internally with the Haffner accusations, as was NEJM. If any action was taken against him, a quick Google search reveals no sign of same.)

Nissen in his editorial provides a handy time line of all these events and lists the various failures of both government regulation and professionalism. I would add to his list the continued miseducation of both the physicians and the general public that the "answer" to Type 2 diabetes is better glucose control. (If you don't think this is the general impression, watch all the ads on daytime TV for glucose monitors, paid for by Medicare despite repeated evidence that home monitoring of Type 2 diabetes not treated with insulin does nothing to improve patient outcomes.) Starting with the massive UKPDS trial many years ago, several large studies have shown that unfortunately, tighter control of blood glucose does nothing to prevent the major complications of Type 2 diabetes, which are heart attack, stroke, and vascular conditions such as those leading to amputation of limbs. By contrast, aggressive attention to other cardiovascular risk factors, such as controlling blood pressure, and at least one drug, an old generic, metformin, can reduce the cardiovascular risk significantly.

So, if the scientific evidence says forget about close monitoring and tight control of blood sugar in Type 2 diabetes, why are both physicians and patients still so fixated on blood sugar? Well, if GSK is busy marketing a drug that lowers blood sugar, but that just so happens actually to increase cardiovascular risk, you'd expect a marketing campaign that says a lot about the importance of lowering blood sugar and keeps mum about real strategies for reducing cardiovascular risk. The fact that rosiglitazone once sold $3.3B worth of drug is good evidence of the resulting miscommunication--the glitazone drugs were never supposed to be first-line drugs for diabetes even under the best of circumstances, and if that much was sold, it could only be because what truly works for diabetes was completely distorted in the minds of most physicians.
I don't mean to say that it's solely on GSK's head that docs are bonkers about what really works for Type 2 diabetes. Clearly we all want to believe that diabetes = sugar--isn't that what all of us learned on our mother's knees?--and we don't want to believe evidence to the contrary no matter how high it piles up. However, it's one thing when this bias works all by itself, and quite another when millions of marketing dollars are spent to further convince us that what is untrue is true, thereby reinforcing the bias in spades. Even if we aggressively started today we will be years reversing this massive misinformation campaign.

Nissen SE. The rise and fall of rosiglitazone [editorial]. European Heart Journal, published online Feb. 12, 2010; doi 10.1093/eurheartj/ehq016.

NOTE ADDED 3/1/10: The original version of this post contained a typo that distorted the meaning; that typo has now been corrected. Sorry!

Friday, February 19, 2010

Saturday, February 13, 2010

Departure of the Two Million Dollar Man--A Blow to Reform?

On a speaking trip to LA, I belatedly opened yesterday's edition of the Los Angeles Times to encounter Tom Hamburger's detailed reporting on Billy Tauzin's announced resignation as head of PhRMA (Sorry, my recalcitrant laptop refuses to copy/paste the URL for the story--go to www.latimes.com and search on "Tauzin").

Billy Tauzin, former congressman from Louisiana, is best known to us pharmascolds for his appearance in Michael Moore's Sicko, shamelessly mugging for the camera while holding the outsized cardboard check for $2 million as he celebrated being hired by PhRMA as their CEO, immediately after he had successfully pushed Medicare Part D through Congress with multiple provisions handcrafted to suit the desires of the drug industry. With that background, it seems odd to read Hamburger's account of how Tauzin's departure may present a serious problem for advancement of health reform.

Here's how Hamburger totes the balance sheet on Tauzin's negotations to date with the Obama White House. Tauzin gave up: a promise of a total of $80B in the next decade in drug industry profits, and a promise to launch a series of ads supporting health reform. Tauzin got: promises that the White House would oppose legislation to use government mass purchasing power to negotiate down drug prices, and legislation allowing the reimportation of cheaper drugs from Canada and elsewhere. Add to that the information presented in the most recent previous post, that in the runup to this year, the drug industry actually managed to raise its prices by an amount that promises a $100B increase over the next decade, and you see that the promised $80B savings has already been wiped out. The negotiating score seems to be Tauzin and PhRMA 100, White House 0. (No wonder that Hamburger reports that the PhRMA board was in favor of retaining Tauzin and that his resignation was for purely personal reasons.)

Yet there is no joy in Mudville, apparently. Other business interests, notably the US Chamber of Commerce, want to continue to oppose health reform tooth and nail and were livid when PhRMA broke ranks with a uniform business front. The GOP, which used to count on getting almost all of PhRMA's campaign contributions until PhRMAS responded to recent Democratic gains by splitting their lobbying largesse more or less 50-50, has threatened retaliation if they win big this fall as they hope to.

Lessons for us folks who make less than $2M annually? I offer two. First: If we want health reform we are going to have to really pitch in, work hard, and take off the gloves. The simple matter is that health care is becoming completely unaffordable in the US because of money that flows into the pockets of many corporate interests. They have shown us that they are not going to go quietly--they will fight with everything they have to keep that gravy train. Good sense, rational arguments, and evidence count as nothing against that entrenched lobbying power.

Second: Those corporate interests would like nothing more than to be joined by yet another corporate interest--physicians. Many US physicians are falling into line, refusing to look at any cost saving that would cut into their already bloated incomes, and lobbying hard to make the government leave their pet profit lines alone. This is an abject failure of medical professionalism and medical leadership. The remaining medical specialties must loudly denounce that behavior. The days of doctors always being polite to other doctors in public, and never pointing fingers no matter how egregious the behavior, must end.

Wednesday, February 10, 2010

Big Pharma's Sacrifice for Health Reform--Not

Today's Houston Chronicle features a hard-hitting editorial--

--detailing a number of important facts about recent increases in drug prices. (While the cost of drugs, and the doings of the drug industry that do not directly affect relationships with the medical profession, are generally beyond the purview of this blog--to be brief, industry-bashing is not what I try to be about--there are times when the issues overlap and when we need an update about general industry behavior.)

Specifically, the Chronicle states that if there ever was any perception that the drug industry was stepping up by agreeing to support health reform and to agree to moderate future price increases as its contribution to the need to cut medical costs, that posture has been revealed as an empty facade. The figues are: proposed future savings of $8B annually; recent runups in drug prices in advance of any future savings due to possible health reform, $10B annually; net result, $2B annual extra profits for Pharma rather than any real reductions in the price of drugs.

The editorial continues by noting that Congress is increasingly exasperated with this game and is now proposing to add legislation that will limit "pay-for-delay," the industry practice by which the brand-name company pays off the generic company to postpone the arrival of a lower-cost generic on the scene once a drug patent expires. (Ending this practice, says the FTC, could save consumers $35B over the next decade.) In response, the industry is now threatening to withdraw completely from its support for health reform. Sounds like they want the entire $10B a year, rather than having to pay back the $8B they promised.

Tuesday, February 9, 2010

What Would It Take to Prove Harm from Detailing?

I hope to do a few posts about a recent exchange in the American Journal of Bioethics centering on a paper by Dr. Thomas S. Huddle, a general internist at Universityof Alabama-Birmingham. Dr. Huddle objects to the recent report by the AAMC, "Industry Funding of Medical Education" (see http://brodyhooked.blogspot.com/2008/04/aamc-has-spoken-more-or-less-pharm-free.html). AJOB ran 10 peer commentaries in response to Dr. Huddle's paper, one by yours truly, to which Huddle then replied.

In this post I want to focus on only one point Huddle raised. He takes issue with the AAMC for trying to turn the presence of drug detailing on an academic medical campus into an ethical issue. So far as he is concerned, it ought to be treated strictly in prudential terms: does it cause more good vs. harm or vice versa? And in both of his commentaries he regards the record as straightforward--there is some substantial evidence that good results from drug detailing, and no reliable evidence whatever of harm having resulted, so prudential considerations require that detailing be allowed.

I am struck by this "on what planet do you live?" disagreement between those of us who take the perspective usually represented on this blog-where just about every post is about some harm that presumably has resulted from today's system of drug marketing--and those people we have labeled as pharmapologists, and who have now formed the organization ACRE (though I see no clear link between Dr. Huddle and that organization). The latter group has dismissed as merely anecdotal all the evidence that the former group believes to be overwhelming. By way of trying to tease out the presumptions underlying that radical difference in worldview, I will address here what would count as a truly definitive study of harms resulting from drug detailing.

We would have to select a cohort of entering medical students and randomly assign them to two groups. The first group would be encouraged to maximize their contact with, and acceptance of gifts from, the pharmaceutical indistry, while the second group would be absolutely prohibited from any such contacts or goodies. We would follow both groups through medical school and residency and into practice. After each group had been in practice for (let's say) five years, we would do an in-depth health assessment of all their patients. If we could demonstrate worse health outcomes among the patients of the maximum-contact group, compared to those of the no-contact group, then we would have proven that drug detailing is harmful. Absent that result, we'd have no reliable evidence on the matter.

I used to say that we'd have to examine the prescribing patterns of the two groups of docs and prove that according to some set of objective criteria for "rational" prescribing, there was more irrational prescribing among the maximum-contact group. But that would not do the trick, because the buzzword in evidence-based medicine today (to which I try my best to adhere) is patient-oriented outcomes. Even if drug detailing caused physicians to prescribe irrationally, it would mean nothing unless that irrational prescribing caused worse health among the patients.

It seems to me that folks like Dr. Huddle can say with a straight face that we have no evidence that docs' hanging out with drug reps leads to any harmful consequences for patients only so long as they adhere to this sort of standard for what would count as good evidence. I trust it's clear that no such study could or will ever be done, and so it is a foregone conclusion that there will never be evidence that meets the criteria set forth by the pharmapologists.

Do us pharmascolds then simply abandon the field? There are many areas of medicine where we can show that the ideal randomized controlled trial cannot practically be done, and evidence-based medicine requires then that we consult the best available evidence, not some ideal evidence that will never exist. I believe that websites such as Drug Promotion Database and Healthy Skepticism have done an excellent job of compiling the best available evidence. What is striking to me about that evidence is its univocal nature. We do not see some studies saying that detailing provides benefits and others that detailing causes harm. Virtually every study shows some sort of negative outcome as a result of drug marketing to physicians, and the sorts of harm shown in one study are usually replicated in similar studies. So I take the evidence (as I attempted to summarize in HOOKED, and which has only grown since that book was published in 2007) as quite clear in raising serious concerns about the consequences of drug marketing to physicians in the form of standard detailing practices.

I continue to believe that the best statement of the current evidence is the formula generally employed by our colleagues at Healthy Skepticism--we currently know of no way for physicians to receive either benefits or information from representatives of the pharmaceutical industry, in such a way that the exchange results in more good than harm for patients.

Huddle TS. The pitfalls of deducing ethics from economics: why the Association of American Medical Colleges is wrong about pharmaceutical detailing. Am J Bioethics 10(1):1-8, 2010.

Huddle TS. Response to open peer commentaries on "The pitfalls of deducing ethics from economics: why the Association of American Medical Colleges is wrong about pharmaceutical detailing." Am J Bioethics 10(1):W1-3, 2010.

Some Quick News Updates

During the last two weeks when I was away on vacation and blessedly mostly out of e-mail range, a number of news items occurred, some of which were even good news. For instance:

The New York Times business page warned that the FDA might be getting serious about slapping down cosmetic doctors who play fast and loose with unapproved indications for drugs in their marketing messages. Perhaps a sign that under the present administration, the FDA may have returned to its mission of regulating the drug industry, instead of just making nice?

An AP business interview with the new CEO of Glaxo, Andrew Witty, who has a couple of pretty radical ideas--first that his company has an obligation to address health concerns in the developing world even among populations that cannot afford to pay top dollar for brand-name drugs; and second, that maybe to properly discover useful new drugs, you actually needs teams of scientists with brains, rather than machines on autopilot that screen thousands of molecules per hour.

Another County Heard From: An ACRE Perspective on Conflict of Interest and 'Political Correctness'

On a few occasions I have mentioned my colleague Dr. Avi Markowitz, chief of medical oncology at our medical center. Dr. Markowitz recently presented a Cancer Center Grand Rounds on “Academia and Industry.” As he’s a member of the Board of Directors of the Association of Clinical Researchers and Educators (ACRE), this talk promised to be a good summation of the position that I have opposed in this blog. I thought that a good way to present the ideas is to try to restrain myself and give Dr. Markowitz’s point of view as much as possible, perhaps then devoting a subsequent post to a rebuttal of specific points if need be. Where I was unable to stifle my responses, they appear below [in square brackets].
Suitable for a talk that vigorously defended, among other things, allowing industry to buy us lunch, there was free pizza and soda provided, courtesy of Fisher Scientific, a firm that primarily sells lab equipment; and the Fisher rep gave a short sales pitch before the grand rounds. This lunch was in line with the official UTMB policy, so far as I can gather, because the grant was prominently labeled as an “unrestricted educational” grant from the company to support the grand rounds.
Dr. Markowitz also started with his disclosure slide listing the 41 commercial firms he’s been associated with in his career, also accompanied by a statement of pride in all of those associations.
The subtitle of the talk (which I was not fast enough to write down in toto) prominently used the term “political correctness,” and in keeping with much ACRE material, AM returned regularly to this term. [As I do have a comment about the appropriateness of the ‘PC’ term, that will be the main issue I’ll take up briefly at the end.]
AM proceeded to a list of allegations that he finds offensive [suggesting thereby that these are the statements that his opponents actually make]—that physicians are for sale for a pen or a slice of pizza, that physicians would harm people for a fee, that physicians are too stupid to know if we are being biased, that if industry pays for it, it’s bad, that being a member of a company speakers bureau is bad, that being on an industry advisory board is bad, and that taking stuff from industry, including food, is bad. He alluded to data showing that delays in uptake of useful medicines by practitioners is a real problem, so therefore anything that interferes with industry marketing that might speed uptake potentially injures patients. He stated here that so long as a drug has gotten FDA approval, we can presume that it’s safe and effective, so there is then really no excuse not to promote its use. He added that in today’s world, if the industry did not pay top dollar, it could not get “real expertise” on pharmaceutical and scientific matters, so the amount paid for consultants, etc. should not be second-guessed.
In defense of providing food, AM mentioned the circumstances that arose here in Galveston following Hurricane Ike in September, 2008. The hospital was basically shut down, including the food services. Let me try to get the gist of his quote: “While a lot of staff were sitting at home collecting their paychecks, some of us, like me and my fellows, were here trying to get our clinic operations restarted. Some drug companies offered to send us food since we could not get anything to eat otherwise. I was told by a bureaucrat, one of the staff staying at home and collecting a paycheck, that this would be a violation of UTMB policy and so we had to refuse the food.”
That led to a long discussion of conflict of interest (COI). AM asserted that there is no generally accepted definition that measurably distinguishes benign from malignant forms of COI, so the term COI therefore becomes, with its negative connotation, a type of “insinuendo.” He reminded us that COI is ubiquitous in academics, where we all want to get raises and keep our jobs in addition to doing good science and patient care; hence “overlapping interests” and not COI would generally be the more accurate term. The legal principle should apply—innocent till proven guilty—whereas COI tends to label one as guilty until proven innocent.
AM then put up a slide that gave the definition of COI contained in the most recent IOM report on medicine and the pharmaceutical industry. He did not, however, discuss or analyze that definition. Instead, he noted that the IOM admitted that they could identify no data that showed that physicians and patients, themselves, view COI as a problem. This was a frank admission that the definition could not be data-based, and AM apparently felt that justified dismissing the definition out of hand for that reason. [AM asserted that there were data to show that patients, when asked if they were concerned about financial COI involving their physicians, denied any concern, and that the IOM ignored these data. On his side he denied that any data exist showing that patients are concerned about COI. I reviewed some of the data showing patient concern in HOOKED. I am aware of one study of cancer patients showing an apparent don’t-care attitude, but hardly believe that’s the totality of the data that exists.] “In science you are not allowed to reason without data,” AM said, [suggesting apparently that defining COI was a matter of science, and not, say, of ethics or policy.]
After some other comments AM turned to the Vioxx debate. While admitting that Vioxx was outside of his area of expertise, he cited several papers condemning the activities of Merck in that case, all written by physicians who admitted to having been paid by plaintiffs’ attorneys in anti-Merck lawsuits. AM then suggested that there was a double standard at play if some demand that those paid by Pharma disclose their conflicts, whereas there is no problem if others take more than $1M from plaintiffs’ lawyers. [The reasoning here seemed fallacious on several counts. By citing only those papers written by physicians with legal-fee conflicts, AM hinted that only people who were thus conflicted wrote papers critical of Merck. In fact there is a huge literature condemning what happened with Vioxx and the papers written by those physicians are only a small sampling. Second, there is a reason that these physicians wrote the few papers they did—as a result of the access to the legal documents, these physicians had evidence of ghostwriting and other things disclosed only as a result of access to internal company documents. The few papers that AM cited specifically dealt with company documents released as a result of legal discovery. Finally, there was no double standard. It is routine for journals to demand that authors list who pays them that could constitute a COI, but it is not usual to demand that the exact dollar amount be revealed. The plaintiffs’ lawyers’ advisors followed these same rules.]
AM mentioned that ACRE recently went toe to toe with the Council on Ethical and Judicial Affairs of the AMA and was pleased that they forced the draft on ethics and relationships with drug companies back to committee for the 3rd time. Who, we asked, is suited to determine our integrity for us? “Who is clean enough that they’re without sin?” [By this logic, no one could sit on a jury, because no one is so clean as to be without sin.] Among agencies that AM viewed as too conflicted themselves to be entrusted to tell the rest of us what integrity requires, he included the FDA, [apparently having forgotten that a few minutes previously, he had listed FDA approval of a drug as proof positive that the drug was both safe and effective.]
AM next asserted, “The real scandals in medicine have come not out of Pharma but out of academia.” He did not elaborate on this beyond an anecdote, of how he was involved once in a federally funded cooperative cancer trial, and a fellow mistakenly changed a drug dose in a way prohibited by protocol (due to a confusion as to what part of the protocol applied to the case). It took 8 months, AM reported, for the overseers of the trial to identify the protocol violation and notify him, by which time it was far too late to make any clinical changes (fortunately the patient was not harmed in any way by the minor dose change). By contrast, he stated from his experience commercially sponsored trials, had that been a company funded trial, the call would have come in 3 days.
AM next listed a set of truisms, including “the truth always comes out,” which he seemed to suggest meant that no company had any real incentive to conceal negative data. He proceeded to list advantages of partnering with industry: money, especially given limited federal research support; flexibility; scientific support; goal oriented; close monitoring; educational/CME support. “How do you develop a profitable drug? You invent something that works.”
In defense of industry’s making a profit, AM asserted that it’s the industry and not the government that develops new drugs—a point that he “proved” by listing how much money industry vs. government spends on clinical drug trials. [He did not address several studies claiming to show that a majority of drugs in important areas like cancer have their start in federally funded academic labs, not in industry.] He denied that drug companies make “excessive” profits by flashing a graph showing (I think) the net profit margins of a number of industries. Drug companies were near the top of the chart, but one of the handful of industries that were higher was brewers. AM then said that since the profit margin of the drug industry was slightly less than that of the beer industry, it could not be the case that drug companies earned excessive profits. He repeated the industry claims that if they did not charge the high prices they do today, they’d have no money to reinvest in R&D.
AM ended by listing Constitutional issues that he worries about due to the “moral bullying” in academia by the “politically correct” crowd, including violations of the First Amendment and of freedom of assembly (if people cannot gather for a company sponsored lunch). He used up all but 4 minutes of his hour giving the talk, and there were no audience questions in the brief time remaining.
[Had there been more time for questions, the one I would have asked AM would have been, “Please define ‘political correctness.’” I admit that there are some contexts where this term makes good sense. However, I think it is easy to misuse or overuse the term. In general, people use the term when they cannot think of a substantive ethical consideration to defeat their opponents’ case. Supposing that I support the rights of a minority group to do a certain thing. People who disagree with me, if they could think of a flaw in my ethical argument, would surely refute me by pointing out that flaw. So when the only thing they can say in opposition to my defense of minority rights is that I am being “politically correct,” it seems they are admitting that they have no substantive rebuttal. If that is so, then all “PC” can count as is an ad hominem argument—that is, being unable to attack my logic, they attack my motives instead. As AM objected to what he took to be the “insinuendo” aspect of COI, it was interesting that he saw nothing “insinuendo” about PC.]
I sent Dr. Markowitz a copy of the above text some time back and he did not reply to two offers to suggest amendments or initial reactive comments; so I have to assume that he will choose to comment on this post in the usual way if he wishes to.

Ghostwriting: Academic Medical Centers Need to Step Up

In HOOKED I referred to ghostwriting of medical journal articles as "a particularly egregious ethical violation" but said little about what should be done about it. Our friends Jeffrey Lacasse and Jonathan Leo have made up the deficiency nicely:

Lacasse and Leo began by searching the on-line policies (and contacting staff at the medical school if policies were unavailable on line) for the 50 highest ranking medical schools in the US according to US News and World Report. They were able to identify policies explicitly banning ghostwriting, or else authorship policies that effectively banned ghostwriting without naming it, at only 13 of these schools. They then argued that even some of the schools that had policies seem to lack critical elements of an enforcement mechanism. They conclude their paper with their own suggested academic policy to prohibit ghostwriting and to bring real consequences upon the heads of academics who allow their names to be attached to ghostwritten articles.

A number of solid observations in this piece:
  • L&L note that academics in non-medical fields are (appropriately) shocked and outraged when they come to learn the degree to which ghostwriting has been implicitly tolerated in medicine. They list in their endnotes specific documentation of cases where ghostwriting has been proven and yet no action was taken against the putative academic authors.
  • L&L as a policy matter call for a period of amnesty--they would allow academics who have participated in ghostwriting to come forward, identify the offending articles for potential later journal retraction, and essentially apologize and promise never to do it again, without penalty. I recommended something similar on a more general basis in HOOKED. Basically we need to recognize that a generation of academic physicians have grown up in an era when certain practices were widely accepted as the norm, that today we are belatedly coming to criticize and condemn. While we can take strong issue with those of our colleagues who try to defend the old practices as ethically acceptable, we must have some mercy on well-meaning colleagues who simply went along with the crowd and now are willing to acknowledge their previous errors.
  • L&L reinforce the basic point that I also alluded to in HOOKED, that unless bad behavior has real consequences for the individual directly involved, we can expect it to continue, at least so long as it pays. I am still at a loss to provide any list of names of academic physicians who have been found allowing their names to be attached to ghostwritten articles, and who have suffered any ill effects to their careers as a result.

Sunday, February 7, 2010

HOOKED among Top 50 Public Health Blogs

I am posting this link to an article listing the Top 50 blogs on public health not just to brag about this blog making the list, but also since readers might be interested to know what other blogs are available on these important topics: