Friday, December 31, 2010

In Defense of Paranoia: Suspecting Deliberate Obfuscation in Medtronic's Payments to Spine Surgeons

For background you need to look at an earlier post:

--plus two more recent news items:

To develop further a brief comment made in my previous post, what we have here is roughly the following:
  • A number of spine surgeons, some academic types, some practitioners, are getting paid royalties and/or consulting fees by Medtronic to the tune of $500K-$1M or more per year.
  • The practicing surgeons are affiliated with hospitals where a very high volume of procedures are done using expensive devices manufactured by Medtronic. (A single surgery can result in using $20K worth of Medtronic stuff.)
  • The academic orthopedists have conducted research or published papers praising the Medtronic devices and the surgeries that use them--despite views among non-conflicted experts that many of these articles are simply infomercials and leave out all the minor things like complications, failures, etc.
  • Medtronic insists that it is getting very high value out of these guys, but is notably sketchy on providing any details as to just what is the intellectual property, consulting advice, etc. it has received in exchange for these vast sums
  • There is a strange disconnect between the Medtronic products that these surgeons routinely use and/or do research or write about, and the product for which they are paid the royalties or other fees
  • This disconnect allows both the surgeon and Medtronic to deny that there's any quid pro quo at work, since presumably, the surgeon is using vast quantities of, or shilling for, Device A, but is getting paid royalties or other fees related to Device B--hence, no conflict of interest exists
As I said in the previous post, this amounts to a mystery--why is Medtronic paying these guys huge sums in exchange for "intellectual property" related to devices that the surgeons do not routinely use or have not conducted research about? Just what sort of "intellectual property" fills the bill here? (Ouija board messages? Pieces of paper inside fortune cookies?)

There is a possible solution to this mystery, but offering it would open me up to charges of having gone off the deep end, becoming frankly paranoid, and no doubt being a candidate for at least one expensive brand-name antidepressant drug plus one expensive brand name atypical antipsychotic. The possible solution is: Medtronic anticipated the need to start posting all its payments to physicians on a publicly available website. Therefore it entered into tacit agreements with its most valuable KOLs, both the guys responsible for the highest volume of use of its devices, plus the academics who provided the best cover for their widespreead use. The agreement was--we'll label the payments we send you as being for some other device, not the one you use (or write about). We'll both know that if you want to keep getting such goodies in the future, you'll have to keep using the same device that you actually do use, at the same high volumes. But both of us now have deniability of any snoops ask why you're raking in so much dough. ("What? Reward docs with huge payments based simply on the volume of devices used? Perish the thought. They're getting paid for different devices entirely.")

If this suspicion holds any water, it shows that an important line has been crossed. As I was at pains to show in HOOKED, drug industry marketing to physicians has traditionally followed a certain pattern, especially well described by the former-drug-rep-turned-anthropologist, Michael Oldani. According to these practices, docs did what the company wanted them to, and in exchange, the company showered them with gifts--in the old days, sports event tickets, trips to resorts, etc.; in more recent times, fancy dinners, and consulting and speakers fees (after the most obvious luxury items were supposedly banned). But neither side admitted what was really happening. The company and the doc both pretended that the doc was a scientist of stalwart integrity who could never be bribed, and that these gifts were all legitimate forms of "education," not marketing.

If by chance I should be right about what Medtronic and these surgeons are up to, then an implicit arrangement papered over with rationalizations was probably not sufficient. It seems that an explicit arrangement of some sort would have had to be arrived at. If this is so, then these surgeons have shown us a new low within medicine. They have simply allowed unalloyed greed to take over, and don't care any more to try to disguise that fact either from themselves or from their Medtronic handlers. They can't any longer even blame self-deception for their blatant and unprofessional conflicts of interest.

OK, suppose that I'm way off base here and paranoia has truly set in. What would be required to show the world how silly are my fears and fantasies? The solution is simple. Medtronic and these surgeons simply have to demonstrate for us exactly what these surgeons did for Medtronic that was worth all that money for "intellectual property," other than old-fashioned payola. What has allowed all my suspicions to build up to this level is their failure to have provided us with any such information.

What if Medtronic cannot come up with such information (or won't)? Then, I am afraid, the implications for the "sunshine" approach to conflict of interest are serious. Up till now, we have imagined that if we could just shed a bright light on these activities, we would know what was going on and then be able to take appropriate corrective action. Medtronic seems intent upon showing us that we can demand all the daylight we want, and they can still create enough nooks and crannies to allow all the cockroaches to scurry about under the protection of darkness. In short, that we don't merely have lack of transparency; we have deliberate and sustained efforts to mislead and confuse us.

Tuesday, December 21, 2010

Highest Rolling Spine Surgeons: Digging Out the Truth

John Carreyrou and Tom McGinty on the Health Industry page:

--illustrate for us just how hard it is to get the goods on the medical device industry and the bribes and kickbacks that are paid to their top guns to promote the use of lucrative implants and other devices.

Carryrou and McGinty delve into Medtronic and its royalty and consulting payments to spine surgeons. Medtronic is the prime manufacturer of the equipment used for spinal fusion surgery (binding two adjacent vertebrae together using hardware). A single surgery can use up to $20,000 worth of devices, with a single screw to hold the hardware to a vertebra costing $1000-2000. Medicare now pays the surgeon a much higher fee to do the more-hardware-intensive form of surgery, giving both the surgeon and the device maker (but not the hospital, incidentally) a strong financial incentive to do more of these procedures than is strictly necessary.

There are several back problems where all experts agree that implants are the best answer. The problem lies with the very common problem of degenerative disc disease. It's been shown many times now that if you lined up a lot of patients complaining of chronic lower back pain, and gave them all MRI scans, a bunch of them would have degenerative disc disease. If you also lined up a lot of people of the same age complaining of no back pain at all, and did the same scans, a bunch of them would have degenerative disc disease. There is no reliable correlation between any anatomic abnormality of the spine and most cases of chronic low back pain; and patients who have surgery very commonly end up having about as much pain afterwards as they did before. The only difference is that those who have surgery, besides often having just as much pain in the long haul, also suffer from the many possible complications of the surgical procedure itself. Still, both doctors and patients get desperate after struggling for months or years with chronic pain, so if you add extra financial incentives, the field is ripe for unnecessary surgery.

The national average is that 17% of spinal fusion surgery is done for patients who have degenerative disc disease (and as I say, that's probably far too many anyway). The reporters went out looking for hospitals and docs whose average was considerably above the national numbers. They struck pay dirt at (among other places) Norton Hospital in Louisville, where the docs on staff report doing 24% of their fusions for degenerative disc disease.

The reporters then hit a brick wall with confidentiality requirements (based on a 30-year-old court ruling). They were able to identify a number of surgeons whose personal statistics suggested a major overuse of this procedure, but they were prohibited from publishing their names. They could only publish the statistics for a hospital.

But they were able to name five surgeons who all worked at Norton and who, in the first 9 months of 2010, received a combined $7 million in royalty and consulting payments from Medtronic.

The surgeons and the hospital all countered that nothing was amiss. The surgeons said that some of the billing codes are nonspecific so the data on their surgeries was probably not fully accurate. They also include in the consent forms signed by their patients a notice that they have a financial relation with Medtronic. Finally, the hospital and the company both protest that there's a firewall because the surgeons receive royalty and consulting fees only for products that they personally do not use in their surgeries, eliminating any possibility that the payments are pure payola based on volume.

Over against this account is, first, a statement from two unidentified former Medtronic employees whom initiated whistleblower lawsuits, that "the royalty agreements are intended to disguise the fact that the payments the company makes to surgeons are really kickbacks for using Medtronic devices."

Second, there is the interesting statement in defense of the current payment arrangements, that the firewall works because the surgeons are not paid for consulting on the devices that they actually use every day in their own procedures, but some other devices instead. Really? These docs, though they may be excellent docs, are after all practicing surgeons. They are not academic investigators. What is the great and wonderful knowledge that these guys bring to the company, that's worth a cool $1.4M (per doc average) in only 9 months, about some device that they do not use? "Oh, that device. I've heard of it"? It would seem that if these folks have anything useful to teach the company about how to improve their product, it would be with regard to a device for which they have daily practical familiarity.

Let's for a minute, on the other hand, give vent to cynicism, and imagine that these payments are nothing but payola in exchange for high volume of use of Medtronic products. If that were the case, then it would be just as easy for Medtronic to agree to pay these dudes consulting fees for some product they never use, as for the fees to be paid for the spinal implant devices they do use.

Perhaps giving support to the cynical take on the issue, Carryrou and McGinty appeared unable to find anyone at Medtronic to explain exactly what were the great intellectual insights that were provided by these surgeons in exchange for their lavish fees.

Bottom line: some of my surgeon colleagues who actually care about professionalism and ethics believe that these "royalty and consulting" payments are a huge cesspool. It's that much harder to get to the bottom of it because the device companies have been smart about how to cover their tracks. (If anything, they're doing better than the pharmaceutical companies so far.)

More from ProPublica: Pharma Speakers/Shills on Shorter Leash

In writing yesterday about the most recent investigative reporting from ProPublica, I missed a sidebar story:

This story describes the steps drug companies are taking to restrict what physicians who are part of their paid speakers' bureaus say during their talks. According to the companies, these speakers ("shills" is the term that seems more to get to the heart of the matter) are now told not only that they must use exactly and nothing but the slides that the company provides, but that they must even show the slides in the same order as specified by the company. With the company pulling all the strings, one wonders why they even need the physicians to give the talk at all; any robot apparently could do it.

The ProPublica reporters (Charles Ornstein and Tracy Weber) note that this puts the company policies on a collision course with the typical conflict of interest policies enacted by academic medical centers. While some of these policies simply ban speakers' bureau participation, others try to find a middle ground by saying that speaking is OK so long as the speaker retains some control of the content of the lecture--exactly what it seems the company wants to avoid.

There's no mystery as to why all this concern--of the huge settlements recently paid out by Pharma firms in federal cases, the biggest single category has been off-label marketing. Any hint from a paid physician-speaker that a drug might be used for something that is not on the officially approved label, and the company could be looking at a huge federal legal liability.

The degree to which companies are now exercising this control seems to put a lie to most of the rationalizations that my academic colleagues trot forth when asked about their accepting speakers' fees. "The slides may say one thing, but I can say whatever I want to" and "They send me the slides, but I always throw in a few of my own slides" are common responses I've heard in the past.

On the other hand, just who can be believed? A key comment in the ProPublica story is from Julie Gottlieb, an associate dean at Johns Hopkins: “Many companies may overstate the extent of their involvement in such activities to avoid the potential of running afoul of FDA regulations.” After all, it is not exactly as if the industry has set the highest bar in the world for believability... So maybe the docs who claim to exert control over their own presentations are not spinning us a tale. That, on the other hand, hardly justifies their taking drug company cash and shilling for them. It also suggests that those medical centers that have a policy of "it's OK to be a paid speaker so long as you retain some control of the content" might best consider scrapping that part of the policy, realizing that it's simply an unrealistic fig leaf in light of company goals.

Monday, December 20, 2010

From ProPublica: Do Med Centers Follow Up on Their Own Guidelines?

From those pesky investigative reporters over at ProPublica:

If any of you wanted to become investigative reporters, here's how you do it.
  1. Find out which prestigious medical centers have new conflict of interest guidelines that prohibit their faculty from being a part of drug companies' speakers' bureaus.
  2. Look on the new ProPublica database that combines the data released by all companies that have done so, on which physicians are paid by them as speakers.
  3. Count the number of docs from each of those prestigious centers, and how much they raked in as paid shills.
  4. Stir and serve immediately.
The bottom line is that each medical center seems to have expected that this would all be on the honor system--that once they enacted their new guidelines, they'd be self-enforcing because all their faculty would immediately obey the new rules. Some deans seemed quite surprised and disappointed that it does not seem to work that way. And most seemed willing to admit that if the ProPublica guys could find out this information on a freely accessible website, then maybe the medical centers could too.

The ProPublica database, by the way, is at

Thursday, December 16, 2010

From the Recent Literature: Further Insights on Major Themes

The medical literature keeps piling up in ways that reinforce the fundamental messages I have been ragging on about in this blog. For a couple of examples, join me as I visit the November, 2010 issue of "Primary Care Medical Abstracts" put out by my good friends Drs. Richard Bukata and Jerry Hoffman. This, for those who came in late, is a series of audio recordings of comments on 30 representative journal articles each month of interest to primary care docs. I had to go three deep into their list of 30 abstracts to come up with two prize examples.

The first study, from Denmark, looked at bleeding complications in about 40,000 patients who had been placed on an anti-clot drug following a heart attack. It has been generally agreed that in this very-high-risk group, such treatment is beneficial. But the number of complications the Danes discovered is sobering. They counted it as a serious complication if the bleeding was so bad that you either died, or had to be admitted to the hospital. (As Rick noted, a nick while shaving did not qualify.) Here are the risks (per person-year) of having such a major bleed depending on the drug you were taking:
  • Aspirin: 1 out of 40
  • Coumadin/warfarin or similar: 1 out of 23
  • Clopidogrel (Plavix): 1 out of 22
  • Aspirin plus Plavix: 1 out of 27
  • Plavix plus Coumadin: 1 out of 8
In the previous post I reminded you of the statitics that suggest that appoximately 111,000 Americans die every year as a result of prescription medicines properly taken. You might well wonder how properly prescribed drugs could be so harmful. Well, here's one example. It is generally agreed that these drugs are needed in the setting of recent heart attack. Yet when you figure out how many people are likely to have serious bleeding, given the odds quoted above, you start to add up to large numbers of folks.

Next study: A team based at Cambridge, UK did a meta-analysis of 11 studies of statin drugs used to lower cholesterol in patients who are at high risk for coronary artery disease, but so far have not had a heart attack or other vascular event (primary prevention studies). We have noted in previous posts that statins definitely seem useful in secondary prevention (once you've had a heart attack or vascular event); that they appear to be questionably useful, if at all, in primary prevention generally; and as you get into higher and higher risk populations, you start to get more potential benefit in primary prevention, even if the number needed to treat remains high.

These investigators decided to look at an important study endpoint, all-cause mortality. Many statin trials produce paradoxical results. They show decreased mortality from heart disease, but no reduction in all-cause mortality, meaning more patients must die of something other than heart disease to make up the difference. These investigators decided to use all-cause mortality as their endpoint, reasoning that if you die, you are probably not a happy camper, regardless of exactly what you die of.

They found that there was no statistically significant likelihood that statins decreased all cause mortality across the 11 trials, though there was a trend in that direction. Conclusion: either statins do not reduce your overall risk of dying, or else the evidence for such an outcome is quite modest--even if you start out at quite high risk for a heart attack. If you decide that the right answer is "modest evidence" rather than "none," their data translate into a number needed to treat of 1428 for 1 year. That is, 1428 people would have to take statins for a year in order for one of them not to keel over dead. Rick and Jerry add that the total subject population in these 11 trials was 65,000. If you cannot find a statistically signifiant benefit from statins from studying that many people, it is quite unlikely that statins have any benefit to write home about, again as a primary prevention drug specifically.

Also driving home another point I've made before, in the 65,000 folks in these studies, their LDL ("bad") cholesterol dropped from 138 to 94, which by most estimates is a substantial drop. Despite this there were no, or only a very small number, fewer deaths. So it seems increasingly likely that whatever good statins might do for some people in some circumstances, it is probably not a result of their cholesterol lowering properties but for some other reason.

Take home message: Once again we see that the modern medical mantra, that everyone with high cholesterol should be tested and placed on a statin for prevention, is based on company marketing much more than science--even though all the supposedly "evidence-based" guidelines say that this is what you should do.

Sorensen R, Hansen ML, Abildstrom SZ, et al. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data. Lancet 374:1967-74, December 12, 2009.

Ray KK, Seshashi SR, Ergou S, et al. Statins and all-cause mortality in high risk primary prevention. Archives of Internal Medicine 170:1024-31, June 28, 2010.

Outsourcing Pharma Research to "Rescue Countries"

One of the closest things we've seen recently to a "must read" article for followers of this blog is in Vanity Fair by Donald Bartlett and James Steele:

Please check out the link if for no other reason than to view the highly effective and chilling illustration.

The basic gist of the article is to say that US drugs are becoming less safe as companies increasingly resort to nations in Eastern Europe, Africa and Asia to get their clinical trials done, for reasons that have nothing to do with good science and everything to do with profits. Some highlights:
  • The concept that is new to me, but reportedly well known to Pharma insiders, of "rescue countries." These are supposedly the counties that if you are having trouble finding evidence to persuade FDA to approve your company's drug, outsource your clinical trial to that country, and you can count on getting positive results that you can submit and gain approval. Examples: When the FDA approved the antibiotic Ketek, later shown to have huge safety problems, the decision was based heavily on trial results from Hungary, Morocco, Tunisia, and Turkey. This was shortly after a US trial physician from Alabama was sentenced to prison for falsifying 90 percent of her data.
  • Some of the worst examples of outsourcing causing harm to local populations occurs due to the pediatric exclusivity law, which had the good intention of creating incentives for drug companies to do more research on children to identify the best dose, etc. rather than simply trying to extrapolate adult data to kiddies. The problem has been that the reward for doing these pediatric trials--6 months' extra patent life--can be so lucrative that the companies do pediatric trials on drugs that never conceivably could have a pediatric use, just to get the extra 6 months of brand-name sales. At the All India Institute of Medical Sciences in New Delhi, 49 babies died over a 30-month period while being administered drugs in clinical trials for conditions like hypertension, which virtually never occurs in infants. The head of pediatrics at the Institute insisted that none of the deaths was due to a study medication--but if the practice there was similar to other trial sites, that guy was pocketing about $350 for every child enrolled in the trials.
  • Studies in foreign countries often take place with inadequate or absent consent and purely pro forma ethics committee review. Patients often believe that they are getting routine medical care, not participating in experiments. These ethical laxities (as well as the much lower personnel costs of running experiments in resource-poor nations) are partly what attract the for-profit contract research organizations overseas.

A while back I reported the statistic from Donald Light's book on the risks of prescription drugs ( that approximately 111,000 deaths annually in the US are caused by prescription drugs taken properly and as directed. Bartlett and Steele propose that the number of deaths due to unsafe prescription drugs is as high as 200,000 annually--their figures may differ due to Light's concern to restrict his statistic to drugs that are actually taken as prescribed rather than to medication errors, etc. Regardless of which figure you use, more people die of prescription drug use in the US than of many major diseases. It is high time that we frankly recognize that the financial incentives that currently control the drug industry research/marketing machine are making drugs less safe and less effective in a seriously widespread fashion. (That's the topic of a paper that Don Light and I have forthcoming in the American Journal of Public Health, which I hope to be able to blog about soon.)

Wednesday, December 15, 2010

Oh, Give Me a Home Where the Sales Reps Roam

Sales reps (detail reps, drug reps) have been sort of off our radar for a little while. Some think with new rules of conduct from PhRMA, limiting the gifts/bribes they can give out to docs, even doing away with the infamous pens and coffee mugs, they are no longer much of a threat to the scientific integrity of medical practice. Not so fast, a couple of sources would say.

First, the Baltimore Sun--,0,3445835.story
--in ongoing coverage of the case of Dr. Mark Midei and his allegedly excessive use of cardiac stents, due to extensive wooing from Abbott, the manufacturer of one of his favorite devices. We need to take what's said in this case with some grains of salt due to the fingerpointing now going on, with the hospital and Dr. Midei each claiming that the other is mainly at fault and trying to dodge blame by accusing the other. However, in testimony before the administrative judge who's ruling on his licensure action, Dr. Midei, while insisting he took no payola from Abbott, claimed that Abbott reps wandered freely in and out of the cath lab at St. Joseph Hospital, in violation of the hospital's rules. The Sun cites a recent study that demonstrated that when sales reps were allowed free access to a cath lab, the use of their own company's devices went way up while they were around.

I have admitted that device reps are a bit different from drug reps in that no rep has to be on site to tell the patient how to swallow a pill, but sometimes a trained engineer-type rep is needed to help the staff adjust or fine-tune a complicated device. The device companies seem to use this exception to create a huge loophole, justifying the presence of their sales reps everywhere and all the time. I doubt that once a cardiologist has been trained on how to insert a stent, there is any serious need for a company rep actually to be in the cath lab while the stent is being placed--let alone show up on a regular basis and have a tight relationship with the staff, as is alleged in the Baltimore case.

More evidence on the ubiquity of drug reps is provided by our good friends at the Pew Prescription Project (, as summarized by Kate Petersen on their Postscript e-mail blog. Kate looks at the latest AMSA report card for med schools ( and notes that in many areas, great improvement is being shown--many med schools that used to get Ds and Cs are now getting As and Bs for tighter policies controlling relationships with the drug industry. But one area that seems to be a general exception to the trend of improvement is the refusal of academic medical centers to adopt strict rules banning drug reps from the campus. Many have policies limiting access of reps to specific areas, e.g. eliminating any patient care areas, but very few have taken the step of completely driving the moneychangers out of the temple. Kate offers some cogent thoughts on why this is strange, especially given the cuts in the numbers of drug reps as companies have retrenched in more difficult economic times. My own guess would be that the academic leaders get too much pushback from rank and file physicians when they suggest a no-reps-on-campus policy.

The bottom line: Don't think that the days when drug reps exerted considerable influence over medical practice are over just yet.

Van H, Yamen E, Blanchard J, et al. Does the presence of a corporate representative affect choice of coronary stent? [poster abstract] American Journal of Cardiology 106:204D, Sept. 21-25, 2009.

Tuesday, December 14, 2010

A Nice Honor: Science Students Should Read Us

It was nice to be notified that this blog was selected as one of the Top 50 ethics blogs students in the sciences should read:

Frankly, it was nice to read that science students are being advised to read blogs about ethics, period.

Hamburg's FDA Getting Tough?

A website called FDAzilla, designed to assist industry in "working smarter with the FDA," says that the FDA is getting tougher under Commissioner Margaret Hamburg:

  • A commitment to go personally after Pharma execs who violate the law around marketing off label drugs, rather than just slap the company with a fine. A former Glaxo lawyer has been indicted for lying to the FDA in such a case.
  • Doing away with the Bush administration practice of demanding that warning letters sent to companies first have to go through a review by the Legal department--which turned out to massively slow down the process of issuing such letters.
  • Increasing foreign inspections in the wake of scandals regarding unsafe imported chemicals, and making moves to hold US companies responsible for shoddy imported ingredients.
Says their blogger, "A lot of people talk about how the FDA has hired a ton (hundreds?) of new inspectors and that the FDA FY11 budget is almost 2x that of FY08. I think a lot of that just comes with an increasingly complex world (both with science and with globalization). But make no mistake about it, the FDA under Hamburg will only get more aggressive. While she has already instituted a lot of changes, changing an organization the size and complexity of the FDA takes time. So, expect a lot more in the next few years."

Some say it's about time.

Friday, December 10, 2010

WikiLeaks, Trovan, Nigeria, and Pfizer

For some reason, neither in this blog nor in HOOKED did I discuss the infamous Trovan case. Briefly, Pfizer was studying a new antibiotic, Trovan, when a meningitis outbreak struck Kano, Nigeria, in 1996. Pfizer physicians quickly started a randomized trial comparing Trovan to a standard antibiotic. It was later charged that parents were inadequately informed and thought their children were getting standard treatment and not being enrolled in a trial. (Doctors Without Borders was treating children with standard therapy in the same hospital, making it easy for parents to become confused.) Pfizer recently paid a $75M settlement to the Nigerian state government to settle charges. Trovan, in the end, was withdrawn from the market due to liver toxicity.

I was not expecting the WikiLeaks scandal to have any bearing on this blog, until a long-time correspondent sent me this link:

According to The Guardian, American diplomatic cables from Nigeria detailed the allegations that Pfizer hired investigators to dig up dirt on the state attorney general who was leading the prosecution against Pfizer. After finding some dirt and releasing some to the media to show they meant business, Pfizer then threatened to reveal even more damaging evidence of corruption unless the AG agreed to go easy on them. The end result was the $75M settlement, reduced(according to the cables) from an initial figure of $150M.

The Guardian added that Pfizer denies all these allegations.

Comment: If any of these allegations turn out to be true, perhaps John Le Carre will favor us with a sequel to The Constant Gardener...

Nature Takes Strong Anti-Ghost Stand

Nature's editorial yesterday on the ghostwriting flap involving the American Psychiatric Association:

--seems significant to me for a couple of reasons. One: Nature's editorial page, in the early days of the debate over conflicts of interest between medicine and Pharma, was one of the least sympathetic venues. It's nice to have them on board. Two: The specific proposal the editors offer, in response to NIH Director Francis Collins's "shocked" comment: "A good start would be for the NIH to require all institutions that take its funds to articulate, publicize and vigorously enforce a clear ban on ghostwriting. Other funders should follow suit. Without such a clear signal, and the willingness to give a ban teeth, this troubling ghost will linger at the feast." The "vigorously enforce" part would be both overdue, and a neat trick if they could pull it off.

How To Encourage Drug Development for Resource-Poor Populations? A Quandary

An ongoing debate at the medicine-Pharma interface is what to do about the huge disparity in drug R&D that focuses almost exclusively on chronic and lifestyle conditions in the rich countries and ignores most of the diseases that now kill millions in the poorer nations--where it is not profitable for the big companies to sell their brand-name drugs. A debate over one creative plan to fix this problem exposes one of the lingering issues in developing regulations or incentives for the pharmaceutical industry.

Aidan Hollis and Thomas Pogge have proposed a Health Impact Fund ( to be paid for by the rich nations, and to attempt to use the current patent process by providing monetary incentives. Briefly, a company marketing a new drug could apply for funding to the HIF. The HIF would pay a fee based on the total, global health impact of the drug. In return the company would agree to sell it basically at cost for 10 years, then to make it available by open licensing agreements (while retaining all its basic patent rights throughout). Ideally companies would now be incentivized to develop drugs that cured or prevented the most cases of diseases, globally, and also to help fix the broken health systems in resource-poor countries that now prevent those suffering from getting needed medicines even when they are affordable. Hollis and Pogge estimate that about a $6B nest egg would get the HIF off and running.

In a recent volume on global public health and patent law, Kathleen Liddell of Cambridge offers a number of criticisms of HIF, stressing that she believes that HIF is a very important proposal and that her criticisms should be viewed as trying to improve rather than sideline it. In the process she makes an important statement: "[T]here is an unsettling feeling that the proposal plays right into the hands of the pharmaceutical industry. It fuels their search for profits, offering them yet another optional method to increase their existing profit margins at the expense of the public purse, when they are already among the very wealthiest industries." In short, Hollis and Pogge feel that one of the strengths of their HIF proposal is that it is almost all carrot and hardly any stick, whereas Liddell would like to see a bit of stick brought out--or at least pressure placed on the industry to better live up to its social obligations.

Let me explain why I found this passage from Liddell especially scary, first by delving into a bit of ancient history. The 1980s marked one of the first experiments at the Federal level in containing medical costs. The focus was on hospital costs which were skyrocketing due to the ease with which hosptials, and the doctors who worked there, could simply keep patients longer and do more stuff, and both Medicare and the private insurance of the day would simply pass the costs through to the payers. The response was the DRG (diagnosis related group) system: "Tell us what, in the end, you figured out was wrong with the patient that caused the hospitalization. We will then consult a table of averages for the cost of taking care of a patient with that condition. We'll pay you the average figure, regardless of what the stay actually cost you." In other words, incentivize hospitals to provide care more efficiently, not at higher cost.

Now, the Feds figured that the DRG system would work in a certain way, based on its pedigree. DRGs had been invented by a group of health service researchers at Yale, because to do their research, they needed to have a way of calculating how sick and with what diseases were the patients being admitted to different hospitals. When they initially used their DRGs for research purposes only, no one got paid more or less because of it.

But as soon as actual payments hinged on DRGs, a lot of things changed--most of which were not anticipated by the Feds. To take just one example, in about 1.3 seconds, software firms developed complex packages to tell hospitals, if a patient with certain symptoms and diagnoses could potentially be classified under 2-3 different DRGs (as often occurred), which classification would net the hospital the most bucks. The result was "DRG creep." If in 1984, hospital discharge diagnoses were more or less evenly distributed over the whole DRG spectrum, by 1986 or 1988, the distribution had changed dramatically, so that a majority of hospitalizations just by coincidence fell under the DRGs that reimbursed the most. In short, once real money was at stake, it took the hospitals an eyeblink to figure out how to game the system.

Now fast forward to today, when we are all too keenly aware of how easy it is for the drug industry to manipulate research findings for its profitable drugs--which as we have seen mostly affect a few million people in the rich nations of the world. If, for example, Merck lies to us about how risky Vioxx is, then the people getting the heart attacks are people in the wealthy part of the world, and relatively few of them on a global scale. Now imagine that we made it worth a half billion or a billion dollars to a drug company if only they could show, scientifically, that a new drug for malaria or TB was saving lives across Africa and Asia. Could we seriously doubt that some of the same gamesmanship that we see evidenced today in industry research would not reappear, in spades, in the global health context--even though now the lives and health of hundreds of millions are at stake? No matter what the other advantages of something like the HIF, is this really something we want to try to wrestle with?

Liddell K. The Health Impact Fund: a critique. In: Pogge T, Rimmer M, Rubenstein K, eds. Incentives for global public health: patent law and access to essential medicines. New York: Cambridge University Press, 2010.

Thursday, December 9, 2010

APA: Earlier NY Times Article Incorrect

The following comment was added to an earlier post ( As it involves a correction in the original source that was used as the basis of that post, I thought in fairness it should be highlighted also as a new post. I append it without further comment:

I'm with the communications office at the American Psychiatric Association. Please not[e] this correction from The New York Times:Correct, December 8, 2010:A headline on Nov. 30 with an article about SmithKline Beecham’s role in the publication of a book about treating psychiatric disorders overstated SmithKline’s actions. While documents show that SmithKline (now known as GlaxoSmithKline) hired a writing company for the book, they do not indicate that the company wrote the book for the authors, Dr. Charles B. Nemeroff and Dr. Alan F. Schatzberg. The article also described incorrectly, in some editions, events outlined in a letter from the writing company to Dr. Nemeroff. The correspondence proposed a timeline for the writing company to furnish the doctors and SmithKline with draft text and final page proofs for approval; the letter did not say that the company had already provided those materials for final approval. And the article misstated the context under which Dr. David A. Kessler, the former commissioner of the Food and Drug Administration, commented about the book’s production. The letter and other documents were described to him; he did not personally review the documents. [no name signed]

Pharma: Angels or Demons? What Does It Matter?

Dr. Michael Kirsch, a private-practice gastroenterologist in Highland Heights, Ohio, who manages and occasionally favors us with comments, kindly sent me a copy of his recent paper:

Basically, Dr. Kirsch is upset with the media for vilifying the pharmaceutical industry. He attempts to set the record straight by listing some of the recent sins of industry but also the many things they do right, and the many sorts of social good for which they are responsible.

On the one hand I am happy to see this paper for two reasons. First, I try to stay abreast of what’s being written about the medicine-Pharma interface. Second, for those readers who think this blog is too one-sided in condemning industry behavior, here’s a chance to read something more to your liking. (If you don’t feel better after reading it, take two aspirin, lie down, and call me in the morning.)

On the other hand, I am also tempted to point out that this paper, however lovely and accurate it may be, is utterly irrelevant to this blog. Dr. Kirsch titles his piece: “The Pharmaceutical Industry: Angels or Demons?” My overriding attempt in this blog is to argue that I don’t know which they are and I don’t care. I care about exactly one thing—are the interests of the pharmaceutical industry reliably and consistently aligned with the goals and ethical duties of medical science and medical practice? I suggest that the answer is “no,” and once we know that, we know what we need to know. Calling them names is quite unnecessary, whether the names are nice or nasty.

Wednesday, December 8, 2010

Trust in a Social Role: Key Concept

I apologize if at times this blog seems to turn into Health Care Renewal Blog West, where I just refer you over to something that just appeared from our friends at HCR. A nice post by Dr. Bernard Carroll, however--

--requires brief comment here because it makes an important point so well.

Dr. Carroll uses the impeachment hearings of a Louisiana Federal judge as his starting point. It would be understandable, but wrong, to see these impeachment hearings as aimed at humiliating or punishing Judge X. Impeachment, Dr. Carroll notes, is actually a quite different concept. It aims to protect the institution, not attack the individual. If an individual is acting in a way to bring disgrace onto the institution (in the case the judiciary), then that person must be removed--and the standards of evidence required to justify the removal are less than what would be required to prove guilt in a court of law.

Dr. Carroll goes on to list a number of instances from his own field of academic psychiatry, where the medical-school equivalent of impeachment would have been warranted. But for us the issue is not giving more examples, but seeing how this insight from the impeachment analogy focuses us on the critical background notion behind "conflict of interest." As I explained in HOOKED, and drawing on the analysis by philosopher Ed Erde, you don't "get" conflict of interest until you see that the underlying idea is trust in a social role. The goal in talking about conflict of interest is not to play "gotcha!" with the doc who has his hand in the cookie jar at the present moment; it is to try to preserve public trust in medicine against the damage done by the general impression that such behavior creates.

Tuesday, December 7, 2010

Is Commercially Sponsored CME Biased?

I've addressed commentary by Thomas Sullivan, CEO of Rockpointe, a medical education and communications company with strong ties to the drug industry, in previous posts:

I gave him high marks for care and thoroughness in arguing the opposing point of view. I'm not sure I can be so generous with regard to his latest:

Mr. Sullivan is upset because commercial support for CME programs has been on the wane in recent years, in part because of what he believes is unwarranted suspicion about commercial bias, a charge he considers baseless. He details all the safeguards built into the CME system which, if they worked as they are supposed to, would indeed guarantee very little if any bias based on who pays the piper. (I listed reasons both in this blog and in HOOKED to doubt that the system works so well much of the time.)

Here, for brevity, I'll just make two points.

Mr. Sullivan writes, "Despite these safeguards, critics point out that because many other professionals pay for their own continuing education, doctors should begin doing the same. These critics believe that industry funded CME 'is not education, but subtle marketing,' despite overwhelming evidence from three studies this year that showed almost no bias in commercially funded CME programs..." Now, just what is this overwhelming evidence? He proceeds to cite (and provide links to) three research studies. What did the studies show? When physicians attend CME programs, they have to check off boxes on an evaluation sheet, stating whether they do or don't think that the presentation they just listened to showed inappropriate or excessive commercial bias. What all three studies showed is that the vast majority of docs, most all the time, check the NO box. To me that suggests that either the docs are lazy about what boxes they check, or else that they may be unable to detect bias when it might actually exist. To suggest that a study that consists of these data show positively that no bias exists in CME programs seems a far stretch. (There might in fact be no commercial bias in CME programs, but you'd need far better methods than in these three studies to know that.)

In a more minor point, Mr. Sullivan goes on at length listing the conflicts of interest of Dr. Martin Samuels, a Harvard neurologist who's just announced that he's starting up a no-commercial-sponsorship CME program to address the supposed problem of bias. (Some similar firms have been running non-commercially sponsored CME programs for decades and have a great track record, but as they don't come from Harvard, apparently they're chopped liver.) It's interesting that Mr. Sullivan forgot to mention that as a MECC exec he might have a few conflicts of interest of his own.

Monday, December 6, 2010

Embarrassing Light on Unnecessary Procedures

It's instructive to compare two items of news coverage for this story:,0,2116790.story

First, the basic story outline: Dr. Mark Midei trained at John s Hopkins to become an interventional cardiologist. He co-founded MidAtlantic Cardiovascular Associates, a practice with dozens of cardiologists that handled much of the cardiac business in the private hospitals in Baltimore. Dr. Midei became such a big shot that when MidAtlantic planned a $25M merger with Union Hospital in 2007, his continued membership in the practice was crucial to the deal. That led St. Joseph Hospital in Towson, just outside Baltimore, to worry about losing too much of its own lucrative cardiology business. St. Joseph offered Dr. Midei a $1.2M salary to ditch MidAtlantic and come on board with them exclusively. Dr. Midei took the offer, the merger deal collapsed, MidAtlantic sued, and the former CEO of MidAtlantic was recorded as saying he'd "spend the rest of [his] life trying to destroy [Dr. Midei] both personally and professionally."

All that soap opera is merely prelude to what is really important. As to destroying his career, Dr. Midei took care of that himself, with a little help from St. Joseph and Abbott Laboratories, maker of one of the cardiac stents that he used.

Ensconced at St. Joseph, Dr. Midei soon became the darling of his new employer and also of Abbott due to the steady high volume of stents that he inserted (the procedure takes half an hour or less and nets a cool $10-12,000). He reached his height in August, 2008, when he implanted 30 stents in one day. Top execs at Abbott sent him special congratulations at this accomplishment. Abbott also paid for plush cookouts and barbecues (including one whole, slow-smoked pig) at his 7000-square-foot house on 30 acres of rolling hillside. They also showered him with research money and VIP trips.

Apparently neither St. Joseph nor Abbott was worried about the obvious difficulty of finding as many patients that truly needed cardiac stents as fast as Dr. Midei seemed to be lining them up. St. Joseph had a system of quality review of its procedures, whereby the head of a department would select which cases were to be reviewed. Dr. Midei was head of cardiology. For some odd reason he did not select any of his own cases as requiring review.

Eventually there were complaints to the state medical board and a Federal investigation. Finally St. Joseph felt enough pressure to start its own investigation. When that study showed that over the previous two years, nearly one-third of the stent implantations were judged unnecessary, St. Joseph removed him from his duties and eventually revoked his hospital privileges. That led many former patients to sue both the doc and the hospital, and Dr. Midei to sue St. Joseph claiming they were trying to make him the fall guy to evade their own responsibility.

Abbott's response to that little kerfuffle? They decided to hire Dr. Midei on as a consultant--"It's the right thing to do because he helped us so many times over the years," wrote one exec in an e-mail (one of about 10K documents obtained by Sen. Max Baucus's Finance Committee). In early 2010, when a Baltimore Sun columnist wrote about the case and allegations of widespread unnecessary stenting, Abbott's vice president of global marketing, sent an internal message: "Don't you have connections in Baltimore????? Someone needs to take this writer outside and kick his ass! Do I need to send the Philly mob?"

Despite such touching concern, Abbott soon decided that the publicity around Dr. Midei made him too hot to handle. They cut short his VIP trip to Japan (for which they paid him $30,000), where he was extolling the wonders of Abbott's Xience V stent. Now, the best Abbott can say about the guy is, "Dr. Midei has been a highly regarded physician in his field, with whom Abbott had consulted in the past. Our affiliation with Dr. Midei ended early this year."

OK, so why did I suggest you compare the two articles? The Baltimore Sun, as appropriate for a home town boy, focuses on the saga of Dr. Midei, but leaves the unwary reader with the impression that he might well be a relatively isolated case. The New York Times, with veteran medical/business writer Gardiner Harris, does a much better job of showing the big picture--that this sort of abusive overuse of well-reimbursed procedures is widespread in cardiology particularly. Harris for instance quotes Dr. Steve Nissen of Cleveland Clinic: "What was going on in Baltimore is going on right now in every city in America....We're spending a fortune as a country on procedures that people don't need." And in it up to their respective eyeballs are the unholy trinity of greedy docs, greedy hospitals, and drug and device makers willing to pay huge kickbacks for sales volume.

The political implications of which version you buy into are huge. If you see things the way the Times puts it, you realize that measures like the "doc fix," either allowing Medicare fees paid across the board to physicians to be cut by 23%, or saving docs from that hit, is clearly the wrong way to go about seeking health care cost savings. We will somehow have to garner the political will to identify the stent type procedures--the unnecessary, nonbeneficial procedures that place patients at serious risk for harm, and that cost a ton, without making anyone live any longer or better. Whichever specialty that procedure is a big cash cow for will scream bloody murder about "the government getting between you and your doctor." So the best possible solution (as I wrote in the New England Journal of Medicine last January, would be for us docs to assume real leadership and identify those wasted procedures ourselves and quit doing them before waiting for the Feds to come and get us.

Then we just might be worthy of being called a "profession" once more.

U-Minn Bioethicists Call for Independent Investigation

As very well summarized (with multiple embedded links) in the MinnPost:

--eight of my colleagues in bioethics at the U of Minnesota have signed a letter calling on the Board of Regents to launch an independent investigation into the case of Dan Markingson:

The letter acknowledges that an FDA investigation in 2005 cleared the University and the drug firm sponsoring the research study that led to Markingson's death by suicide, AstraZeneca, of any blame. Still, say the bioethicists, there are many unresolved issues that demand further inquiry, which they proceed to list:
  • "recruiting a mentally ill, possibly incompetent subject into a research study while he was under an involuntary commitment order;
  • large financial conflicts of interest on the part of the university researchers conducting the study;
  • a payment structure for the study which included financial incentives to recruit and retain subjects rather than provide them with standard therapy;
  • an allegedly biased study design aimed at generating positive results for AstraZeneca rather than investigating a genuine scientific question;
  • the failure of university researchers to address the legitimate concerns of Mr. Markingson’s mother, Mary Weiss, who warned that her son was suicidal and who attempted for months to have him removed from the study as his mental condition deteriorated;
  • the apparent development of a specialized unit in Fairview Hospital designed to identify severely mentally ill subjects for recruitment into research studies;
  • and finally, a failure of the institutional oversight system for protecting human subjects of research.”

Perhaps the most egregious, from an ethical standpoint, is the last. Carl Elliott of U-Minn, in the Mother Jones article profiled in my most recent post on this topic (link above), quoted the erstwhile chair of the University's IRB as denying that the institutional review board had a responsibility to protect human subjects of research, when most of us assumed that that was precisely the mission of an IRB.

I would like to be able to say that it's standard procedure for those of us in bioethics to be the first to protest loudly and publicly when our own institutions cross the line into questionable behavior. Sadly, it's often not the case; few see the bioethics program as a base of true power within an academic medical center, and most of us, consciously or not, end up adopting a don't-rock-the-boat mentality. Nevertheless, one of the signatories to the Minnesota letter has been there and done that. Mary Faith Marshall, PhD was once the bioethicist for the Medical University of South Carolina, and lost her job there as a result of critizing the institution's policies of secretly screening and then arresting newly delivered mothers for cocaine use (policies that were later found unconstitutional in a major U.S. Supreme Court decision).

Institutional conflict of interest was a problem at U-Minn even before the Markingson case arose. It's understandable, but ultimately indefensible, that precisely at the time in an institution's history when a thorough airing out of the problem followed by serious reform is the right thing to do, the natural instinct is instead to hunker down and circle the wagons.

Saturday, December 4, 2010

AAFP and Coca-Cola-- an Update

I have in the past blogged a bit about American Academy of Family Physicians taking big bucks from Coca-Cola to fund a consumer education website on nutrition and obesity prevention, for example:

I add for recent readers that while this blog is supposed to focus on pharmaceutical issues, the AAFP-Coke matter seemed pertinent as an example of how supposedly "professional" medical organizations are seduced by corporate money.

I made a strategic decision when I started blogging on this topic. I wanted to stress my ethical position (contrary to a rebuttal offered by AAFP leaders) that it did not matter what ended up on the consumer website in question. The conflict of interest existed as soon as AAFP took the money for that purpose. Even if the website contained material critical of sugary soft drinks (actually, I guess, high-fructose-corn-syrupy drinks, as the companies are too stingy to put actual sugar in them any more), there was still a COI that could not be rationalized away. For that reason I actually avoided putting in my posts any comments on the actual AAFP web content.

I was reminded of my omission by an excellent older post by Dr. Josh Freeman, family medicine chair at the U. of Kansas: Dr. Freeman in turn cites:

This is a blog by Michele Simon, a public health lawyer and author of Appetite for Profit, a study of the financial influence of the Big Food industry analogous to what we've been reading about Big Pharma. She does go to the AAFP website and reports on its supposedly unbiased content. Some of her main findings:
  • Messsages favorable to Coke--including how good caffeinated and artificially sweetened beverages are for you--appear throughout the AAFP website.
  • No surprise--while the credit given to Coke is for general program support only, the same sorts of messages appear almost verbatim on Coke's own website. Seems like Coke had more control over content than AAFP was letting on.
  • Just for extra fun, Simon lists the recent misdeeds of the Coca-Cola company on numerous fronts, asking whether a professional medical society really wants to be seen in such company.

The AAFP website is: When I logged on just now, a "Live Positively" logo appeared prominently at the top of the web page. When you click on that logo, it goes to the "Consumer Alliance Partnerships" page (AAFP manages to assume that somehow a "corporate alliance" is a "consumer alliance" as if Coca-Cola was some sort of non-profit charity) on which the full logo, "Live Positively--Coca-Cola" is shown. Why the key words "Coca-Cola" do not appear on the main page is an interesting, but very minor question.

Yet More on Ghostwriting: NIH, Wake Up

While we're on a ghostwriting tear, I appreciate a colleague calling my attention to this letter from POGO, the Project on Government Oversight:

The letter begins by noting that NIH Director Francis Collins told C-SPAN last year that he "was shocked by that revelation—that people would allow their names to be used on articles they did not write, that were written for them, particularly by companies that have something to gain by the way the data is presented….If we want to have the integrity of science preserved, that’s not the way to do it."

Well, Francis ol' boy, say POGO, while you were busy being shocked, your agency was throwing millions of dollars in grants at the very people whose association with ghostwriting has been most thoroughly documented--so if you are so big on Integrity of Science, how about not further lining the pockets of these (alleged) slimeballs? (Bearing in mind of course that we are talking still about allegations, and not proof of guilt in any legal sense.) Or at least taking some serious action to check out what they did or didn't do? The letter goes on to name names and to list how many million bucks each high-roller has obtained in NIH grants since the allegations were made public.

Another note here that the POGO list consists of academic psychiatrists, and not to imagine that somehow the specialty of psychiatry has less ethics and integrity per cubic meter than any other medical field. It's just that lately there's been more legal action around psychotropic drugs; and with legal action comes the discovery of secret industry memos, without which we'd never know any details about ghostwriting. Still, if you believe sources such as Robert Whitaker's Anatomy of an Epidemic, profiled here a while back-- has in fact been relatively more in bed with Big Pharma than many other specialty groups.

Thursday, December 2, 2010

More on Recent Ghostwriting Allegations: A Crazy Theory

I have a somewhat off the wall theory to offer regarding the recent ghostwriting revelations/allegations from the New York Times:

Okay, in this crazy world of the medicine/Pharma interface, can anything really be off the wall?

Let's go back to the revelations from the recent round of ProPublica investigations of drug payments to docs:

One of the things this drove home, though we had much evidence of it before, is that speakers' bureaus are basically bribe machines to reward high-prescribing physicians; the ability to speak coherently is much less of a qualification.

So what are we to make of the fact that (according to documents obtained by the Times) SmithKline Beecham paid muchos bucks to a medical communications company to ghostwrite a textbook that KOLs Drs. Charles nemeroff and Alan Schatzberg could sign on as authors, and the textbook was supposed to educate family docs about how to treat psychiatric illnesses, but only 10,000 copies were sold (vs. a family doc population in the US of about ten times that much)?

Let's ask-- supposing that that book contained information that SmithKline really wanted family docs to know, and that they judged the textbook a useful format by which to convey that information, what would they have done?

Answer--that's easy. The sales for the textbook would have been 100,000 not 10,000. All copies would have been bought by SmithKline. A SmithKline rep would have personally delivered a copy to each family doc in the US, as a gift from the company. The cost would have been chump change for a big drug firm.

So how do we account for the fact that only 10,000 were sold? How about the notion that SmithKline chose to handle KOLs Nemeroff and Schatzberg just like Dr. Big Prescriber up the road, but on a grander scale, given their presumably huge value to the industry as Shills Extraordinaire? Everyone knows that having a medical textbook to list on your CV as an author is a plum perk for an academic physician. So SmithKline ultimately didn't care if no one bought the book and if no family doc ever read a page of it--just like they really don't care who or how many attend the drug talk given by the paid speaker, so long as the speaker gets his bribe to put in his pocket and know's there's more where that came from if he keeps that prescription mill going. (The Times did not reveal specifically what Drs. Nemeroff and Schatzberg were paid, personally, for their role in putting their names on the cover of this book; but past behavior would cause us to doubt that they would have participated without being offered a nice honorarium--in addition to the honorific of having a major publication to list on their CVs.)

Like I say, maybe I've finally gone off the deep end. This business will do that to you.