Spinal Fusion Devices: What's the FDA Hiding?

Thanks to Marilyn Mann, I was directed to this article by John Fauber on MedPage Today Orthopedics:
http://www.medpagetoday.com/Surgery/Orthopedics/21908

(Regular readers will recall that we've seen Fauber's excellent investigative reporting previously with the Milwaukee Journal-Sentinel.)

The story is a complicated one and I refer interested readers to the full report. A couple of medical device companies have manufactured some stuff that makes the body grow new bone wherever it lands. The idea is to put it in a little cage sort of thing to contain it, slip the cage in between two vertebrae of a person who otherwise would undergo a spinal fusion to lock the two bones together (using a bone graft, with a bit of bone taken from the hip), and you have a fusion done without the need to harvest the bone from another site.

Two problems. First, the above story assumes there's some advantage to spinal fusion surgery in the first place. In the vast majority of cases this is highly questionable. However, since surgeons make a lot of money off fusions, and since patients with chronic back pain are among the most desperate and unhappy patients known to medicine, it seems spinal fusion will be among us for some time to come, evidence be damned.

Second problem--the magic stuff that makes new bone wherever it lands really indeed has a Midas touch. Numerous complications have been reported where new bone grows where you don't want it. This is especially bad in the neck where there can be swelling that compromises breathing.

This whole business made some folks wonder about the original FDA hearing at which this magic stuff was first approved. It turns out that most of the favorable data was generated by docs who had financial conflicts of interest with the manufacturer. The stuff was approved with a label that said don't use it on the neck, use it in the lower back only, but even at the time people warned that off-label use would be highly predictable and a huge problem. Guess what? Since 2002 off-label use has been a huge problem.

So these folks went to the FDA and asked for a simple piece of information--tell us the list of investigators, whose data were reviewed by your advisory board in 2002, that indicate which of them had financial conflicts of interest with the manufacturer.

Seems simple. But the FDA has said that this data cannot be released. More interesting, the FDA has provided, on three occasions, three totally different reasons why the information cannot be released. The company, of course, has it, but refuses to release it.

Now, a couple of observations. First: we come back regularly to the issue of how devices are different from drugs. This seems to be a case in point. Whether the stuff will leak out and cause bone to grow where you don't want bone might very well have something to do with the technical skill of the guy doing the surgery. One of the most conflicted surgeons in terms of total money brought home, is conflicted because he's credited with inventing the device. It would not be surprising to learn that the surgeon who invented a particular operation has better outcomes than your average surgeon off the street, even if for no other reason than he's had more time to do more surgeries. So you can't draw quite the same conclusions as you might if this were a drug being studied and not a device.

Second: This is related to the first. Given all that, you can see how a company might behave if research integrity and public trust were actually Job One in their value system. They would realize that having the bulk of their research carried out by folks with serious conflicts of interest was not a good thing. So as early in the game as possible, they'd ask some hard questions about the research strategy. They'd specifically look for ways to launch a clinical trial under conditions that as much as possible eliminated financial conflict of interest as a variable. They'd insist on several layers of disinterested third-party monitoring as a minimum condition. And so on.

So far as I can tell, none of those steps were taken; the company simply figured it could go about its usual business, using its own hired guns, and then push around the FDA approval process to get what it wanted (in this case, an approval that opened the doors wide to off label use and hence increased sales, and that asked no embarrassing questions about who needs spinal fusions anyway). The company was correct in its assessment of what it took to get what it wanted.

What Drug Companies Promote PSA Testing?

I've been very concerned for many years about the overuse of PSA screening for men, so I'm surprised that I was not aware of this op-ed in the New York Times back on March 10:
http://www.nytimes.com/2010/03/10/opinion/10Ablin.html?scp=2&sq=ablin+great+prostate+mistake&st=nyt

Richard Ablin, research professor of immunology and pathology at the University of Arizona, hammered away at what he calls the "great prostate mistake," routine screening for prostate cancer that costs $3B annually in the US and that ends up leaving 47 men "who can no longer function sexually or stay out of the bathroom for long" for each 1 man who might (under the most optimistic study yet published) have been saved from death by having had the test. (Another equally good study says that no men are saved from dying as a result of being tested.)

You might wonder what gives Prof. Ablin a right to sound off about the PSA test. Simple--he is credited as the discoverer of PSA back in 1970.

Ablin notes that despite recent major studies showing the lack of benefit from PSA screening, medical sopcieties and patient advocacy groups have been slow to change their advice on having the test. "So why is it still used? Because drug companies continue peddling the tests.... I never dreamed that my discovery of four decades ago would lead to such a profit-driven public health disaster."

So now it appears that I am doubly uninformed--I not only missed Ablin's op-ed, I also did not happen to notice that drug companies are pushing PSA testing. I don't know whether drug companies actually sell PSA test kits to labs or (more likely in my view) drug companies know that they'll sell a lot of prostate cancer drugs so long as men are stampeded into having themselves screened. (As I posted about earlier in describing how drug companies who want to sell osteoporosis drugs find it to their benefit to push bone mineral density tests: http://brodyhooked.blogspot.com/2009/12/npr-how-osteopenia-became-treatable.html.) Perhaps some of the kind people who put comments on this blog know the answers and can advise us.

A Wry Commentary on Medical Organizations' Corporate Links

I received an e-mail from Dr. Matthew R. Anderson, of the Department of Family and Social Medicine at Montefiore in New York, and editor of the journal Social Medicine. He wanted to call my attention to some recent articles in his journal that readers of this blog might find of interest.

First, the journal published a set of 3 papers commenting on the long history of medical society journals accepting cigarette ads:
http://www.socialmedicine.info/index.php/socialmedicine/article/view/459/902
http://www.socialmedicine.info/index.php/socialmedicine/article/view/460/910
http://www.socialmedicine.info/index.php/socialmedicine/article/view/461/911

As a cute illustration of this issue, the journal's website contains a 1947 ad that features, shilling for Camels, none other than the father of cellular pathology himself, Rudolf Virchow:
www.socialmedicine.info

If all this seems a bit far afield for us, Dr. Anderson's own editorial brings it back home. He addresses three more recent examples of corporate engagement by medical organizations, that he compares to the old practice of rationalizing taking tobacco company money by printing their journal ads. The examples are, first, the American Academy of Pediatrics and its links to manufacturers of baby formula; second, the American Academy of Family Physicians and its recent tie to Coca-Cola; and third, the AMA's role in selling its physician database to permit drug companies to keep detailed profiles of physician prescribing:
http://www.socialmedicine.info/index.php/socialmedicine/article/view/448/880

Some pertinent comments from Dr. Anderson's editorial: "We presume that these actions do not reflect the values of [the three medical organizations'] membership. It is legitimate to ask, therefore, if we have really progressed from the time when cigarettes were advertised in medical journals under the slogan 'more doctors smoke Camels.' ...Pulling our lens back, we see that these associations have become the captives of corporations which serve their profession. Rather than working for their patients or their members, they are promoting the ends of corporations."

Consumers Union Poll: Public Cares about Pharma Influence

Pharmapologists have long complained that pharmascolds like me fantasize that the U.S. public might lose trust in physicians if they knew all about the shenanigans that go on with Pharma influence, when in actual fact they don't give a darn or else are thrilled that their docs are big industry fans. I've addressed the data on this in a previous post:
http://brodyhooked.blogspot.com/2010/04/what-do-patients-think-of-docs.html

Now Consumer Reports weighs in with a new poll conducted back in May and just released:
http://blogs.consumerreports.org/health/2010/08/consumers-say-big-pharma-influence-on-docs-is-concerning-consumer-reports-survey.html

Basic findings:

• 69% of Americans think drug makers have too much influence on physicians' prescribing decisions
• Half say docs are too eager to whip out the drug prescription pad when a non-drug treatment option works just as well or better
• 47% say gifts from the drug industry influence physicians to prescribe certain drugs
• 41% worry that docs tend to prescribe newer and more expensive drugs
• 51% grumble that docs don't consider a patient's ability to pay when prescribing

Policing Unsafe Drugs--A Toothless System

Two brief news items about how hard it is to get the drug industry to behave, and keep unsafe substances off our shelves.

First, among many useful and informative recent items on our fellow blog, Health Care Renewal, is a post:
http://hcrenewal.blogspot.com/2010/08/proprietary-information-confidentiality.html
--which in turn is based on a Wall Street Journal article by Alicia Mundy (see post for link). At issue is the 2007-8 deaths of 81 patients due to contaminated heparin imported from China, and sold in the US by Baxter and Scientific Protein Laboratories LLC. Previous accounts have suggested that we don't know where the contaminants in the heparin came from and who is responsible because the Chinese government investigation sort of petered out, and the FDA lacked the wherewithal to go in themselves and get to the bottom of it. In sum, we treated the deaths of 81 people as if it was a sort of natural disaster, with no one to blame. But Mundy's story tells a rather different tale-- that a Federal judge has ruled in favor of a motion by Baxter and SPL to declare various company documents proprietary and hence protected from publication. Other parties to the suit (admittedly who have their own financial dogs in the fight) objected to this motion on the grounds that the documents, if revealed, would be of great public health importance in identifying the likely sources of the contamination.

So what we seem to have is a Federal court that is willing to help private companies keep documents secret, that could actually have answered at least some of the outstanding questions about a drug safety problem that caused 81 deaths. Suddenly the disaster is not seeming so natural any more.

Next, we can turn to an article in the New York Times by Gardiner Harris (see comment below):
http://www.nytimes.com/2010/08/20/health/policy/20fda.html?scp=2&sq=gardiner%20harris%20glaxo%20memo%20avandia&st=cse
This article shows that one ancient element of FDA lore has not changed over many decades. The FDA ordered GlaxoSmithKline to send out a "dear doctor" letter in July, summarizing the conclusions of an expert panel on the risks of the diabetes drug Avandia (see my previous post about the panel, http://brodyhooked.blogspot.com/2010/07/follow-up-on-fda-avandia-hearings.html). Now, critics are charging that the letter is misleading and amounts to a whitewash of Avandia.

In HOOKED, I described an interesting incident in FDA history about the antibiotic chloramphenicol. It was found to cause a rare but deadly adverse reaction, but neither could the FDA withdraw it from the market because it was the only available treatment for a couple of rare but deadly infections. The end result was a peculiar dance, in which at every point the FDA was outmaneuvered by the manufacturer, Parke, Davis. The FDA would order Parke-Davis to write a "dear doctor" letter telling physicians about the risks of side effects with chloramphenicol, and not to use it for colds and sore throats but to keep it in reserve for really serious infections. Parke, Davis kept sending out letters which said that chloramphenicol had been found to be safe by the FDA--after all, they had not taken it off the market--and so doctors should keep using it with confidence.

Bottom line--if you want the letter to say what you want it to, write it yourself. The fact that the FDA keeps going hat in hand to beg the drug company to say what needs to be said is just one more sign of the system's inability to protect the public health.

My promised comment: I used to regard Gardiner Harris as one of the heroes of investigative journalism for his role in regularly exposing Pharma misdeeds. Now I need sadly to take anything he writes with a grain of salt, after his role earlier this year in trashing the Dartmouth Atlas research group without any discoverable basis in fact.

More Tidbits from White Coat, Black Hat

I recently announced Carl Elliott's new book, White Coat, Black Hat:
http://brodyhooked.blogspot.com/2010/08/new-book-of-interest-from-carl-elliott.html

What follows here is a set of brief quotes gleaned from my now having read the complete volume, and then I will end with some summary comments.

• On ghostwriters who work for medical communications companies: Carl quotes a biology PhD who went to work for a medical communications company and quit after a year, on being asked when exactly he decided "there was something ethically dubious going on at the agency": "The first day I was there."
• Objecting to the idea that what's wrong with ghostwriting articles is that the putative author, who did hardly any work, gets credit for having written the paper, and quoting the same former ghostwriter: "The moral crime that I was being asked to commit was to do with truthfulness." That is, the problem is the "spin" that the article contained, not whose name is on the paper. Notice that this is a mirror image of the defense of the practice of ghostwriting offered by pharmapologists, who say that so long as the paper is accurate, who cares whose name is on it?
• Carl's interview with psychiatrist David Healy of the University of Cardiff, on the latter's extensive insider's view of the psychology of physician "KOLs" or opinion leaders shilling for industry: Healy argues that most of these so-called "leaders" are distinctly second-rate intellects. They and the industry need each other. These guys realize after getting to a certain point in their early careers "that they're not going to get the chair at Harvard or Yale, but [they] enjoy the lifestyle of being courted by industry, and having [their] articles written for [them], of having articles in JAMA or NEJM, which [they] wouldn't otherwise have". They realize that the only way they are going to advance in the field commensurate with their ambition is to jump in bed with industry. Industry in turn needs people with this psychological weakness in order to have a gang of bought physicians who will reliably do what the industry wants.
• How a person who had worked all his life in pharmaceutical marketing came to have his career-changing moment of epiphany: "I was in the exam room waiting for my doctor...[Seeing the room filled with industry knickknacks and brochures, he immediately thought:] I hope he's getting his information from the medical literature and not from people like me....That's when I realized that I was part of a big scam..."
• Quoting from the same former marketer, Joel Roselin: "When Joel worked in medical advertising, he used to schmooze with one of his bosses over coffee. The two of them got along well, and Joel felt comfortable joking around with him. One day Joel asked, 'If someone asked you to promote a product you thought was dangerous, would you do it?' His boss paused and thought about the question for a while. Eventually he came up with an answer: 'I'd like to think we wouldn't.'" (Talk about a clarion call for ethical behavior!)
• Carl, reflecting on his visit to Western IRB in Olympia, Washington, the most successful and prominent for-profit research ethics review board: Carl was invited by the founder of WIRB to visit, so that he'd see that his criticisms of for-profit IRBs were misplaced. Just before his arrival he was sent a detailed confidentiality agreement to sign, basically gagging him from telling anyone, ever, a single thing he saw during his visit. He arrived at WIRB and told the staff person who met him that he would not sign the form, nor any modification of it. This caused considerable consternation, but eventually the leadership decided that Carl could stay and visit, so long as he did not actually sit in on any ethics reviews of any actual research protocols. All through his visit, Carl heard a steady refrain: if only he could have actually seen the way WIRB reviews protocols, he would finally see why it had such a good reputation and why for-profit IRBs could function in a highly exemplary way. "As I drove away from the WIRB campus, it struck me that this obsession with secrecy was the hidden perversity of putting research oversight into the marketplace. Once such competitive pressures are instituted, there is no reason for any commercial IRB to share techniques to improve oversight. In fact, there is every reason not to share, because each commercial IRB has a competitive interest in the failure of other IRBs. ... Even if the members of any given commercial IRB sincerely want to protect the research subjects they oversee, they do not have any financial reason to want other IRBs to protect them, because every IRB that fails represents a potential business opportunity for the ones left standing." This contrasts markedly with university-based IRBs that routinely share their technques for improving their reviews of protocols--assuming that they ever develop any such techniques, which critics of IRBs commonly wonder about.

Summary comments: I have offered these tidbits from Carl's book because the majority of his content is already well known to regular followers of this blog. What, then, is the advantage of his book? One advantage is the nice way he was organized the material, running down the list of actors in the drama, and not sparing our own fellow bioethicists. The other, as illustrated here, is the great set of interviews that he has done and his lively presentation of what he learned.

How Many New Drugs Are Lemons? Ask Donald Light

This is a very important post because it refutes more conclusively than anything previously posted here the general position taken by the group we have come to call the "pharmapologists." These folks, as demonstrated in numerous earlier posts, argue that the pharmaceutical industry produces life-saving drugs and fantastic innovations in health, and when physicians get paid handsomely for working closely with Pharma, the result is more innovation and more lives saved. So it is against the public interest to derail the Pharma-medicine gravy train by imposing strict conflict-of-interest policies, etc. To the pharmapologists, the huge social benefits created by today's pharmaceutical industry are obvious; but the burden of proof is on us pharmascolds to document that any harm at all is caused by these wonderful drugs and the industry's marketing of them. Pharmapologist-in-chief Dr. Thomas Stossel of Harvard enjoys repeating that the pharmascold position lacks an evidence base because we cannot prove that there is anything about the marketing of drugs that causes bad patient outcomes.

What we offer in response to this confident pro-industry advocacy is often pretty mealy-mouthed. We fear being dismissed as Luddites and cranks if we deny that new drugs are largely useful. So we say, "New drugs are largely useful, but..." and then try to get on to our main point.

Well, there is nothing at all mealy-mouthed about my esteemed colleague Dr. Donald Light, medical sociologist and health policy expert based at University of Medicine and Dentistry of New Jersey and visiting professor at just about every place he can buy a plane ticket to. I will soon post about Dr. Light's new book (to which I conributed a chapter); but the text for today's sermon is a paper that Dr. Light delivered recently at the American Sociological Association annual meeting in Atlanta, August 17 (session 487), entitled, "Pharmaceuticals: A Two-Tiered Market for Producing 'Lemons' and Serious Harm." The paper is thoroughly documented and supported and I would like to see a Pharmapologists' factual rejoinder.

The entire paper is worth reading and I hope Don will get it into print soon. By way of trying to summarize, Dr. Light builds the paper around an economist's idea, Akerlof's theory of "a market for lemons." The idea is that when there is an imbalance in the information available to buyer and seller, sellers can take advantage by pushing inferior products off on buyers. This leads to a general distrust, with buyers being unwilling to pay top dollar because they fear getting a lemon. If you have a good product but know you can't get top dollar for it, then you will take your product elsewhere to be sold. Eventually, predicted Akerlof, the market will simply fall apart. Dr. Light shows why pharmaceuticals don't exactly follow the Akerlof prediction, and how it can work that a more or less permanent market for lemons characterizes the U.S. pharmaceutical business.

In the market that Akerlof originally looked at, used cars, we don't see any car company trying to produce lemons. Says Light: "[T]he pharmaceutical market for 'lemons,' differs from other markets for lemons in that companies develop and produce the lemons. Evidence in this paper indicates that the production of lemon-drugs with hidden dangers is widespread and results from the systematic exploitation of monopoly rights and the production of partial, biased information about the efficacy and safety of new drugs. The institutional practices differ profoundly from car manufacturers working tirelessly to produce safe cars but inadvertently discovering a serious problem, like Toyota discovering its sticking accelerator problem in 2009. The massive reaction, Congressional investigations, and recalls [in the Toyota case] involved less than 1/10,000 as many deaths as are attributed to prescription drugs every year." Light adds that the information asymmetry also characterizes the relationship between the drug companies and the government regulators, who now rely havily on industry user fees to fund their own operations, assuring that the FDA has little power to impede the "market for lemons" and instead becomes a sort of enabler, providing additional cover for the companies because they can always point to FDA approval in their own defense.

If one dispassionately surveys this institutional landscape, says Light, then it is easy to predict the outcome: "Companies will design and run their clinical trials to minimize evidence that their drugs cause adverse reactions and maximize evidence that they are not inferior to or [are] better than a placebo for the target indication. And companies will also learn from the regulatory body how to game accelerated approvals and condition[al] approvals with post-market studies by cutting corners and submitting partial evidence in order to get drugs on the market faster and put the regulator under pressure to approve and not to later rescind." Light might have added here that any company in today's highly competitive market that does not get good at playing these games will quickly lose market share and be put out of business, or gobbled up in a merger.

What, then, is the evidence that this account of Pharma's institutional environment is correct?

• It has been documented numerous times that of all the so-called "new drugs" put onto the market annually, only a few are actually novel chemical structures, and of those, only a handful are real advances over existing drugs. An estimate of 10-15 percent actually being significant advances in one way or another would be highly generous.
• With 85-90 percent of new drug discoveries not counting as real advances, it is herefore clear, as Light notes, that "company R&D goes largely to a marketing strategy that does not meet societal needs or the needs of patients."
• Drug companies constantly whine that they spend so much on R&D, taking huge risks of wasting money on drugs that don't work, that their profitability is always in jeopardy. Garbage, replies Light. R&D in the US drug industry rose during the decade between 1998 and 2008 from $18.9B to $47.4B. Societally speaking, this was a huge waste as so few real drug innovations resulted as noted above. But drug industry profitability did not suffer at all during this period (even though, as I reported in HOOKED, it looked a bit grim for a while in the early years of the 2000s).
• Extrapolating from the best available figures, the US suffers about 111,000 deaths annually from adverse drug reactions (that is, drugs prescribed and administered correctly, and leaving aside deaths from medical errors), or more than twice as many fatalities as from auto accidents. This puts adverse drug reactions as the 4th leading cause of death, and besides, adverse reactions lead to about 1.5M hospitalizations per year (the total damage toll being underestimated because we lack good data for nonhospital settings).
• If the industry produced drugs, many of which offer no real advantage over existing drugs, and then urged the maximum possible caution in their use, we could perhaps avoid some of this swath of death and destruction. But such, of course, would hardly suit the company bottom line; so instead we have what Light calls the "risk proliferation syndrome." Company-sponsored research talks up the efficacy and the safety of the drug. Marketing then tries to get physicians to prescribe the drug to as many patients as possible, including those (such as the elderly) inherently at higher risk for adverse reactions, and those who have less and less chance of actually benefiting (because their disease is mild, or for whom nondrug therapy would work better, etc.) The industry does everything possible to speed up FDA approvals of new drugs and to slow down any threatened FDA action to remove an unsafe drug from the market or to restrict its use. The end result is that as many patients as possible are put at risk, while revenues go steadily up. (More on this particular phenomenon later on when I have the chance to blog about a paper that Dr. Light and I co-authored, which is currently awaiting publication.)
• The financial power of the drug industry allows it to "colonize" medicine in the same way that it has effectively taken over the FDA. This means that more and more of medicine turns into a commercial enterprise placed at the service of industry profits. New diseases are "discovered" that require drugs to treat them. The medical literature becomes indistinguishable from the industry marketing juggernaut. And so on, as this blog has documented ad nauseam.

I lack the time and space here to reproduce Dr. Light's extensive list of citations, but while awaiting the end of the embargo imposed by the ASA before I was permitted to quote from the paper, I reviewed 6-8 of the key papers he cites and was impressed with the depth of the data that support his conclusions.

Bottom line: Let's put the burden of proof where it belongs. When anyone says that the drug industry, in its present form, is a benefit to society, we ought to reply, "prove it." Or, to put the matter in another (and perhaps kinder and more moderate) way, we must not mistake the level at which the bad stuff happens. When new drugs end up killing people instead of healing them, it is not something that just happens around the edges. The reasons for those bad outcomes are much deeper into the structure of the industry today than most of us (even pharmascolds) want to admit.

Continuing Our All-Carl-Elliott Issue: More on the Dan Markingson Case

Back in April I blogged about the tragic case of Dan Markingson and the so-far-futile efforts of his mother, Mary Weiss, to get justice from the University of Minnesota:
http://brodyhooked.blogspot.com/2010/04/u-minnesota-evading-responsibility-for.html

Carl Elliott's book (mentioned in the last post) contains a brief synopsis of this case; but he goes into more detail in an article in the current Mother Jones, "Making a Killing." (To access, go to the Mother Jones current issue website, http://motherjones.com/toc/2010/09, and look for the title "Making a Killing." Click on that and you'll get a screen that will allow you to register for free access.)

In "Making a Killing," Carl not only describes the sad case but also puts it in the context of the pressure placed on universities today to compete for grant dollars with commercial research entities, all funded by a drug industry that is looking for marketing, not science. As Carl summarizes:

"If these experts [who have reviewed the study in which Dan Markingson was enrolled, and have declared it to be scientifically next to worthless] are right, then then the study in which Dan Markingson committed suicide was not simply a matter of inadequate informed consent, or financial conflicts of interest, or even failure to monitor a subject's care. The ethical breach was built into the study from the start. It is one thing to ask people to take risks for science, or the common good, or to help other people. It is another thing entirely to ask them to risk their lives for the marketing goal of [the sponsoring drug copmpany] AstraZeneca."

Carl throws a couple of other scary passages at us. When Ms. Weiss attempted to sue the University and its psychiatrists (a suit that was dismissed based more or less on a variant of sovereign immunity), her attorneys deposed the director of the U's Institutional Review Board (IRB) or research subjects ethical review committee, Moira Keane. The attorney asked what she thought was a routine question--didn't the IRB have the responsibility to protect human research subjects?--before proceeding to the issues under dispute. But Ms. Keane refused to admit that the IRB had any such responsibility. The attorney thought she had misunderstood (after all, the U-MN website says the purpose of the IRB is to "protect the rights and welfare of human research subjects") but Ms. Keane stood firm. In the end, all she would admit was that it was the role of the IRB to make sure that research investigators at the U had a plan to protect human research subjects. As Dr. Elliott then notes, this is as good as saying that the IRB at U-MN doesn't do a thing--since it was precisely to protect human subjects from the dangers of an overzealous investigator that IRBs were first created.

The next scary quote relates to how you can end up with a study like CAFE (the study in which Markingson was enrolled), which is basically jiggered from the start not to answer any legitimate scientific question, but to provide the drug company with marketing spin to sell their drug, and which can more or less be guaranteed to produce the answers that the company wants. In HOOKED and previously on this blog, I have described in detail some of the tricks used by study designers to rig outcomes. But the march of progress continues, and as journal editors, however belatedly, start to catch on to these little games, the goal posts move. Summarizing a 2006 study of research on atypical antipsychotics, Carl notes, "Much of this manipulation came from biased statistical analyses and rigged trial designs of such complexity that outside reviewers were unable to spot them."

The CAFE study, for those interested, appeared as: McEvoy JP, Lieberman JA, Perkins DO, et al. Efficacy and tolerability of olanzapine, quetiapine, and risperidone in the treatment of early psychosis: a randomized, double-blind 52-week comparison. American Journal of Psychiatry 164:1050-60, 2007.

New Book of Interest from Carl Elliott

I have been privileged to receive an advance copy of Carl Elliott's White Coat, Black Hat: Adventures on the Dark Side of Medicine (Boston: Beacon Press, 2010, ISBN 978-0-8070-6142-8; $24.95 hardcover, 211 pp.). I have only just dipped into it, and may post more after I have read it all, but wanted to waste no time in getting the word out.

Carl, who has been mentioned in these parts previously, is an MD who then went on and got a PhD in philosophy and has taught bioethics at a number of world universities, currently at University of Minnesota. He's published his essays in such places as The New Yorker and The Atlantic Monthly, and I feared at first that this book would be merely a collection of those essays, but I see he's reworked the material for this book specifically.

Carl is concerned about the cast of characters that populates the "dark side of medicine" where business and market values seem to have taken over from any sort of professional commitment to the care and well-being of patients, with a special focus on Pharma. His chapters deal, respectively, with professional guinea pigs who volunteer for one research study after another;
the "ghosts" who actually write ghost-written articles; drug reps; medical "key opinion leaders"; marketers; and finally, a group that Carl has practically made a career of irritating, bioethicists like Carl and me who (unlike Carl and me) get seduced into signing on with corporate boards and taking corporate cash, assuming that the corporations actually want us to tell them what's ethical, and might listen if we tell them (while meanwhile we get to fly to their meetings first class and stay in five-star hotels).

The book is nicely illustrated with anecdotes and interviews, such as this nice quote from former drug rep Jordan Katz, about how the code of ethics introduced by PhRMA in 2002 actually made things worse: "The companies that tried to follow the guidelines lost a ton of market share, and the ones who didn't gained it. The bottom line is that if you don't pay off the doctors, you will not succeed in pharmaceuticals. Period."

I think it's a safe bet that readers who find this blog interesting will like this book.

British NHS Backtracks on Diabetes Guideline--What Are Pharma Implications?

My thanks to Marilyn Mann and Jerry Hoffman for the contents of this post.

Marilyn sent me a very nice blog posting:
http://www.straightstatistics.org/article/how-overtreatment-diabetics-may-have-cost-lives
--in which is described the backtracking of the British NHS after one year from a practice guideline that called for GPs to try to control their diabetic patients' blood sugar so tightly that the hemoglobin A1C level (a measure of long term control of sugar) would be below 7.0%, down from a previous target of 7.5%. These guidelines are used to determine financial bonuses for GP practices for "quality" care and failing to meet this guideline could cost a GP practice 3000 pounds annually.

At the time this guideline was announced, there were already studies published in the literature making it clear that tighter control of blood sugar in Type 2 diabetes was not helpful in improving patient outcomes and was instead associated with greater risk of harm (as I've covered in several previous posts). So there were loud critics when the guideline first went into effect; and those same critics, while glad that the NHS guideline people have backed off (returning to the 7.5% target) point out that almost certainly, patients died during this past year due to the application of this inappropiate guideline.

What does any of this have to do with ethics and Pharma? Here we come to a comment Jerry Hoffman made to me some time back that is pertinent--that the whole idea of "pay for performance," which the NHS has embraced eagerly and which bandwagon US insurers including Medicare are now eager to jump onto, has obvious advantages but some downside risks that are often hidden. Specifically, in the olden days, if drug companies wanted to sell drugs, they had to figure out a way to influence 800,000 free range US physicians. They figured this out, of course, quite well, but it cost them a ton to hire the 100,000 detail people (at the peak of their population) thought to be needed to do the job. If pay-or-performance comes to be, we have made Pharma's job much easier. They will simply have to figure out a way to influence 1000 or so physicians--the ones who write the guidelines on which the P4P targets are based. As I've pointed out before, there is a huge accumulation of evidence that the name of the game in treating Type 2 diabetes ought not be blood sugar control; yet we keep hearing of new drugs designed to provide better blood sugar control, and guidelines keep being written (usually by authors with financial conflicts of interest) advocating better blood sugar control. If that all seems like a way to sell drugs rather than to treat patients properly, we might wonder how that could have come to pass.

Are Electronic Health Records Medical Devices? Who Is Monitoring Their Safety?

I see it's been more than a year since I posted about Electronic Health Records (EHRs):
http://brodyhooked.blogspot.com/2009/05/briefly-back-to-emr-another-market.html

--so maybe it's time for an update. Those of you unsure what EHRs have to do with ethics and the pharmaceutical industry, please hang on for a second, and all shall be revealed.

This week's New England Journal of Medicine offers two perspectives on the EHR. David Blumenthal, the Obama administration's lead EHR advocate, and Marilyn Tavenner talk about "meaningful use" regulations for EHRs, while Surgeon General Regina Benjamin tells how she became an EHR believer after her rural clinic was first washed away by a hurricane and then burned down. Do these cheerleading articles tell us the full story about the EHR? I wish.

First you can consult a recent post on our friends, the Health Care Renewal blog:
http://hcrenewal.blogspot.com/2010/07/open-question-on-moral-authority-and.html

"MedInformaticsMD" provides us with some telling clinical insights about what happens when a hospital or clinic buys EHR software off the shelf and then tries to go live with it with minimal time and effort devoted to staff preparation and training. He happened to be in the hospital with a sick relative when the prescription order-entry system "went live," and he observed at first hand the ensuing pandemonium, making careful note of the impact this could easily have had on the safety of the patients then hospitalized. None of them, he noted, gave their informed consent to be experimented on in this way; is that ethical, he asks?

MedInformaticsMD knew whereof he spoke because he had described in detail how his mother had suffered from a similar mishap-- but let him talk:

A newly-admitted patient who needed urgent heparinization did not receive the medication promptly. The patient's physician could not order it, as nursing had not yet "admitted" the patient and entered data such as weight. Physicians found no way to override, despite calls to the help desk, attempts by on site IT people and users from the parent hospital, etc. In the end, the pharmacist simply provided the med using a weight estimate despite no "official" order having been entered into CPOE.
This story sticks in my mind as it was due to disappearance of an anti-arrhythmic med on my mother's ED admission med list at the parent hospital, without any alerts that a medicine she'd been on for years was somehow removed as an 'active medication', that led to her needing heparin acutely. The iatrogenic need for heparinization then led to an iatrogenic cerebral hemorrhage and emergency craniotomy, followed by many complications.

So here is an anecdotal example of one patient (the author's mother) having a stroke caused by a screw-up in an EHR, and another patient being put at risk of a serious event, including a possible stroke, due to a screw-up in an EHR. Are these rare events? No, says the Huffington Post:
http://www.vuvox.com/collage/detail/02b26ea6c3

This little slide show illustrates how, despite an increased number of warnings from sensible and authoritative people about safety issues in EHRs, the political juggernaut to adopt EHRs universally presses forward, aided and abetted by a corporate lobby that is trying to ward off any significant government safety oversight.

What does this have to do with Pharma and ethics? Regular readers of this blog may be surprised that I'd be holding the pharmaceutical industry up as a paragon of virtue; but at least Pharma recognizes that at some level, it has a moral corporate responsibility to submit to appropriate oversight to make sure its products don't kill people. This level of understanding that human health is at stake here appears thus far to have escaped the software firms that now make up the EHR Industrial Complex.

Reply to My Article on COI-Coke-AAFP

The "Policy and Medicine" blog has recently posted a lengthy rebuttal by Thomas Sullivan--
http://www.policymed.com/2010/08/aafp-childhood-obesity-patient-education-program.html

--to my own article on conflict of interest in the AAFP-Coca-Cola matter:
http://www.annfammed.org/cgi/content/full/8/4/354

The rebuttal is carefully done, but you can get a sense of it from the last summary paragraph:

We need to build a culture of trust. To begin that culture, we need to trust that the leadership at the AAFP is motivated to conduct this program to help children and families. Trust the physicians participating in the program who are almost desperate for tools to help these children and families. In the end we are all trying to do what is best for patients; working with industry resources to accomplish this goal is good for everyone.
In the end, our efforts and energy should not be concerned “about the development of a corporate culture within a medical professional society,” because doctors and physicians are trained to avoid such motivations. For the overwhelming majority of doctors, especially those in family medicine, the only role corporate culture plays is helping physicians conduct the research, training and education needed to make families healthier. As such, we should be encouraging the funding from and collaboration with industry to help physicians carry out their moral duty to their patients, which includes working with industry to find new ways that can help treat diseases like obesity.

OK, let me see if I get it. We are supposed to trust the AAFP leaders, because we believe that they are trying to do what's best for patients and for the general public. What about the evidence that getting into bed with a for-profit company that has a financial interest in selling beverages that add to the risk of obesity might be contrary to those goals, and motivated less by what helps patients and more by AAFP's own financial bottom line? Well, don't believe that evidence. ("Who are you going to believe--me, or your lying eyes?") Why not believe it? Well, it cannot be true. Why? Because "doctors are trained to avoid such motivations." Even when they seem to have given into those motivations? Well, just trust us.

"For the overwhelming majority of doctors, especially those in family medicine, the only role corporate culture plays is helping physicians conduct the research, training and education needed to make families healthier." Oh, really? The only reason for-profit companies fork over those bucks is because they want to make families healthier? There is nothing in it about making more money by selling more drugs or other products? There is no evidence that drug company-sponsored research is tilted away from the true scientific questions about human disease, and toward whatever will give the company's marketing a leg up? There is no evidence that any company ever tried to hide important scientific data that might interfere with sales?

I was tempted to end this post with, "Just what world do these people live in, anyway? Because maybe I'd like to buy a condo there." But that would be a churlish response to a commentary which is, after all, written in a completely polite fashion. So in an attempt to offer an equally polite reply, I will say that it makes excellent sense, in assessing the ethics of medicine's relationship with industry, to weigh the pros against the cons. But in order to do so, one has to be willing to admit that there are both pros and cons. A group of defenders of the recent status quo, on the other hand, appear to be unwilling to admit that there are any cons at all. On their view, there is nothing but good that can come from a close financial relationship between medicine and industry. But that does not strike me as a rational way to conduct an ethical analysis.

Getting our $100 Worth: Special Correspondent Reports from AAFP Meeting

Talk about getting your money's worth... I donated $100 to Oregon medical student Richard Bruno so that he could buy stickers to distribute at an AAFP students' and residents' meeting, to protest AAFP's "deal" with Coca-Cola:
http://brodyhooked.blogspot.com/2010/07/aafp-and-coca-cola-continued-how-i-just.html

For that sum I not only allowed the purchase of some materials (as you'll see below) but also secured Richard's services as this blog's Special Correspondent at the meeting. Herewith the Special Correspondent's report:

***
Wow, what an incredible experience. We fought hard, but our "end the coca cola alliance" resolution lost by one vote! I'll give you a rundown of what happened, but considering no one has ever done anything like this at the conference, I think we made quite an impact.

Last Tuesday I spent a few hours getting quotes for stickers and postcards. I placed an order for 250 "no coke" stickers for $75 to be delivered to the Kansas City Marriott on Friday. Looking back I think it would have been better to pay the extra $25 to have overnight shipping and have had them there on Thursday so we could have gotten them out to more people. But I was also placing an order for 500 postcards ($75). As soon as I placed it, however, I received a call from Dr Amy McGaha, asst director of medical education for the AAFP. She informed me that someone had forwarded her [our] blog post on our campaign efforts and let me know that we would not be able to hand out any materials at the convention center, parking lot, or hotel, without reserving an exposition booth.

In what was likely a hasty move, I cancelled the postcards, not knowing how we would manage to get them signed by attendees if we were going to have eyes on us all weekend. Just to be sure, I emailed the Oregon Health and Science University family medicine residency director asking if he would allow us to distribute materials from the residency program booth. He assured me that he believed in our cause, was equally outraged at the partnership, and that we could have materials on their table.

Our resolution was coming along nicely, and was a collaborative effort from 4 OHSU students and 4 students at other medical schools (with input by a resident Lenny Lesser). It was submitted on Thursday before I arrived. I gave testimony to the Reference Committee hearing on Friday, and there were 4 AAFP board of directors there to hear it. Afterwards, Dr Ted Epperly (Idaho), former President of AAFP and current board member, came up to me afterwards. I had met him in the fall when he came to speak at OHSU and gave him a stack of scientific papers implicating sugar-sweetened beverages as the number one cause of obesity. He vowed to take them back to the board of directors and later told me that he was the lone voice of dissent on the board. After the hearing, he told me that he had spent a lot of time considering the board's position, and that he has finally seen it their way, as a necessary step for financial stability. I was definitely disappointed he had changed his position, but vowed that I would never trade my values for what is status quo, or even what is "politically feasible."

I had also submitted a resolution to "establish a single payer task force," which I thought would be a small but important step toward the AAFP endorsing universal healthcare. Dr David Ellington, another board member approached me after the hearing and told me that he was actually a single payer supporter, but that we would have to agree to disagree on the coke partnership. He also cautioned me not to confuse ethics with justice. I had apparently miffed him when I brought up the question of ethics during my testimony, though I relied more on the conflict of interest strategy as outlined by your AFM article.

After the hearing I picked up the stickers which had arrived at the hotel, and started getting them out to everyone from OHSU. There were a number of parties being thrown by various residency programs in hotel ballrooms and meeting rooms across the city, and we made our way to many of them, proudly displaying our "no coke" stickers. It was amazing to see what kind of reaction it got from folks. I did not carry enough with me--they went very quickly. I told people to come Saturday morning to vote on the resolution (because even if the reference committee did not adopt the resolution, which I assumed they wouldn't, I would extract it for debate and open it up for a vote among the entire congress of delegates).

Saturday morning came, and before the general session, I stood on the street corner and handed out stickers for half an hour. More folks took them than didn't and I felt pleasant about bringing awareness to those who didn't know anything about it. During the congress of delegates meeting, I extracted the resolution (along with my other resolution on single payer) and it went through some lively testimony from me and many other students. About half of the AAFP board of directors was there--I know they were very interested to see how things would shake out. After about half an hour of debate, the vote came down and we lost by one.

I'm confident that our voice was heard, and that the board will put a little more thought into the student viewpoint when engaging in decisions like this. I still believe the partnership compromises the integrity of the organization, and will continue to fight it. I'm pleased to know that the Oregon and Washington Academies both have similar resolutions that were passed and will be brought before the national congress of delegates in September.

I am really grateful to your support which lent momentum to our efforts. I would like to return the $25 we did not use.

***
Richard, please keep the $25, your long message was worth it to keep our readers updated! (Even those readers who are keeping an eye on this blog to tip off AAFP leaders to upcoming demonstrations!) Also, perhaps one of the intellectual lights on the AAFP board of directors could explain to me exactly what is meant by "not confusing ethics and justice."