Thoughts on Orthogate

I haven't had much to say about orthogate, the ongoing scandal involving Medtronic, Dr. Tim (the forger) Kuklo, and Dr. David (the consultant) Polly.

It's pretty clear that Dr. Kuklo is a bad apple, assuming that it's true that he made up data regarding the Medtronic bone growth product Infuse, including forging the names of colleagues who later said they had no involvement in the study. (See Doug Bremner's particularly colorful review of these events here). Outright fraud can happen in any system, no matter how well regulated, so the Kuklo disaster is not necessarily grounds for calling for systemic reform.

The David Polly case is a tougher call. Obviously, Polly, a professor at the University of Minnesota and the former head of orthopedics at Walter Reed, made a barrel-full of money consulting for Medtronic on Infuse. In fact, between 2003 and 2007, Polly received more than $1.14 million in fees and expenses from Medtronic. According to the Wall St Journal, the main "bad" thing that Polly did was failing to disclose at a May 2006 senate hearing that Medtronic had funded his trip. Polly was at the hearing to drum up more government funds for research on treating wounded soldiers, and he and his colleagues in Minnesota evenutally won a $466,644 Department of Defense grant for a study on Infuse. Obviously, Polly should have told the Senate that he was speaking on behalf of Medtronic; instead, he claimed to be speaking on behalf of the American Academy of Orthopaedic Surgeons.

To his credit, Polly didn't run and hide behind a veil of "no comment." In fact, he went on the radio program All Things Considered and said that he was a "rookie" that day. He said it didn't appear there was a forum or venue to make such disclosures at the hearing. "If there had been, certainly I would have been delighted to disclose," he said. "And if I was asked to testify before Congress tomorrow or currently, I would probably do things differently to be a little more clear about who I have financial ties with."

Is this believable? Who knows? In my experience, people who rise to the rarified ranks of academia like Polly are extremely shrewd about regulations and paperwork. I'd be surprised if it didn't occur to Polly that the Senate would have wanted to know that Medtronic was paying him $6000 to testify, according to the New York Times account.

Subsequently, the WSJ and others had a field day going over Polly's detailed consulting and billing records:

His consulting log indicates that on one occasion he spent one minute to wake up a Medtronic executive, although he listed "no charge" for that service. He did bill Medtronic for the 30 minutes he spent in the car with that executive after waking him up.

The amounts of money seemed excessive, and while there's nothing wrong with a company paying an expert lots of money to help them develop products for patients care, even Medtronic shareholders were rattled by the scope of the payments. At the Medtronic annual meeting, shareholder John Burbidge was quoted in the Twin Cities Pioneer Press as saying that while he understood the need for input from physician consultants, he was "taken aback" by the sums of money involved.

"Is it really necessary to pay that kind of money to doctors in order to get good information?" he asked. "Can you rely on information that you pay that much money for?" added Burbidge, who said he is a longtime Medtronic shareholder. "Obviously, nobody is going to want to tell you anything you don't want to hear and jeopardize his relationship with the company."

Eventually, although Polly denied any malfeasance, the heat was too much for him and he resigned his post as a board member of the American Academy of Orthopedic Surgeons, saying that the issue had become a "distraction" for the organization.

What to make of orthogate? Kuklo, apparently, is just a unethical doctor/researcher who allowed his greed to influence his professional decisions. Polly, on the other hand, seems like a good guy who made a mistake in disclosure. In some ways, it's surprising to me that he even quit the orthopedics organization. I'm willing to bet that many of his colleagues on the board do the same kinds of lucrative consulting gigs. Are they all supposed to resign now?

Perhaps the lesson here is that when physicians decide to work with industry, and when the amounts of money become astronomical, they will inevitably teeter on the brink of greed. Once greed takes over, they may start to do bad things. That's why transparency of such payments will be helpful, so that we can closely monitor doctors who seem to be making just a teensy bit too much money from industry.

A MECC that BLISSfully keeps Promotion in Medical Education

Recently, medical writers from across the country have been forwarding me blatant examples of how medical education companies are currupting the basic tenets of continuing medical education. Although I've become jaded, this particular company astonished even me with their willingness to do away with the pretense that industry-funded medical education is anything other than advertising.

The company is called Brand(x) and they are based in the United Kingdom. They are mainly an advertising firm but they have a robust medical education department. Here is a screen shot from their website in which they explain their conception of "medical education."


If you can't quite make out the small print, you can reach this page by going to the home page, clicking "enter" then "services" then "med ed." Here is the definition of CME, Brand(x)-style:

In today's business environment clients increasingly recognize that to get the best results, medical education must be led by a clear understanding of what the brand stands for and be closely integrated with the promotional strategy. At Brand(x), we are uniquely placed to provide the exceptional skills, which will help shape your educational strategy and implementation so that your brand's business objectives are met.

The company has developed its own process for making sure CME promotes a drug company's brand. It's called "BLISS," an acronym for "Brand Led Integrated Support Service." Here's a screenshot showing how they make CME more BLISSful:

Recently, Dr. Murray Kopelow assured the Senate Special Committee on Aging that his organization, the ACCME, has everything under control. In fact, here is what ACCME's standards for commercial support has to say about the content of CME:

The content or format of a CME activity or its
related materials must promote improvements
or quality in healthcare and not a specific
proprietary business interest of a commercial
interest.

But here is what Brand (x) has to say about CME:

BLISS ensures that your medical education programmes and strategies are synergistic with your brand's promotional strategy and execution.

I guess ACCME will need to hire a few more compliance officers.

Industry-Funded Medical Writers vs. Health Care Reform

Recently, a former staff medical writer at a MECC (Medical Education Communication Company) anonymously alerted me to a particularly sleazy advertising tactic used by a medical writing company. This person had worked as a pharma-supported medical writer for several years, but recently quit because, “I really couldn't stomach the ethical problems associated with writing for the pharma industry." Recently, looking for medical writing jobs, this writer came across a company called "Emron--" no, not Enron, although the ethical standards of the sound-alike companies appear to be similar.

Here is how Emron advertises its writing services to the pharmaceutical industry:

When you’re looking to compete on quality, set your sights on Emron for top-flight healthcare marketing communications and brand management. We drive sales, access and reimbursement in competitive markets: our clients achieve sustained competitive advantage by creating product demand and reducing price-sensitivity.

Now, if Emron were simply an advertising company, I would have no problem with this. Ad copy writers specialize in the craft of helping companies gain market share. As a newsletter publisher, I appreciate the magic of good marketing copy when I am periodically forced to send out those annoying promotional mailers that most people toss into recycling.

But Emron does much more than advertising. It produces accredited CME programs in order to help their clients "achieve sustained competitive advantage." As the medical writer pointed out to me, the worst part of Emron's statement is the phrase "reducing price sensitivity." With healthcare costs being foremost in the nations' consciousness right now, this attitude is unconscionable. Emron is saying to pharmaceutical companies "To heck with healthcare costs! The pharmaceutical industry should not do anything to compromise their profit margins. And we will offer you our professional staff of writers (for a hefty fee) to write your CME so that doctors will prescribe more of the most expensive drugs."

One example of Emron's work is the The Contraception Report, a Wyeth-funded newsletter whose underlying purpose is to get doctors interested in Wyeth's latest birth control products. That newsletter has expanded into a website called Contraception Online, which is also entirely funded by Wyeth, and which also provides advertising dressed up as CME. This site is shamefully produced by Baylor College of Medicine; I don't know what part Emron still plays in it, as the website does a good job of making this opaque.

Recently, Murray Kopelow provided testimony in which he assured the Senate Special Committee on Aging that ACCME is the firewall between education and promotion. Emron's toll-free number is 800-367-6613. I suggest Dr. Kopelow give them a call to help them build a better firewall.

Ghostwriting Stays in the Spotlight

With Natasha Singer's article on ghostwriting appearing in the Health section of today's New York Times, this underhanded method of drug promotion is in the public spotlight as never before. Medical ghostwriting leaches out the confidence we have in the authenticity of medical research, because the articles are conceived and written by drug company marketers and their surrogates. But when they are published in the top journals, they look like serious reports of medical science, complete with the names of prestigious doctors who are dubbed "authors."

After you read the New York Times article, I suggest you read this very clever article by William Heisel, a two time Pulitzer finalist, who blogs on Reporting on Health, a project of the Annenberg School for Communication at USC. Heisel's focus is on the self-deluded ways doctors are rationalizing their partipation in medical ghostwriting. For example, Dr. Leon Speroff, a former professor of obstetrics and gynecology at Oregon Health Sciences University who allowed DesignWrite to put his name on a paper he didn't write, defended his bad behavior by saying that it was then "standard practice" to not disclose a drug company's involvement.

Comments Heisel:

Why is it when these researchers are caught with a drug company's hand playing them like a puppet, they pull the "standard practice" line? Standard for whom? Certainly not for the patients taking the pills and presumably not for the journal editors accepting the articles for publication. Perhaps this is something Sen. Charles Grassley, R-Iowa, should ask in a hearing. Speroff told the Journal Sentinel he had nothing to apologize for:

"There is nothing dishonest about it."

Speroff was quoted in this excellent investigative report on medical ghostwriting at University of Wisconsin written by--who else?--the incomparable John Fauber and Meg Kissinger of the Milwaukee Journal Sentinel, both of whom should be on the short list at the next awards meeting of the Pulitzer committee.

Eli Lilly Posts its Grand Deception

Eli Lilly has recently posted the Grand Deception which it is calling the "Lilly Faculty Registry." You can inspect it here. Why do I call it the "Grand Deception?" Because the doctors listed as "faculty" are not really faculty at all. They are salesmen and saleswomen, with MDs after their names.

The Wall Street Journal reported that over the first three months of 2009, Lilly pumped $22 million into doctors' pockets, and most of this was categorized as "Healthcare Professional Education." This is the same kind of education you'll get if you go to a Toyota dealership and ask the salesman to educate you about which hybrid to buy. You will get some education, most of it accurate, about the Toyota Prius. You'll hear about its gas mileage, its cubic footage and its GPS system. But you won't hear anything about Honda hybrids or Ford hybrids or Chrysler hybrids. You won't be getting "car-buying professional education." You'll be getting a marketing pitch.

Lilly's Healthcare Professional Education events are no different. Doctors who go to a Lilly-sponsored talk on depression, for example, will hear plenty of information about Lilly's blockbuster Cymbalta, most of it accurate. But they'll hear nothing about Zoloft, or Celexa, or Paxil, or Effexor, or Remeron, or Nardil, or any of the dozens of other antidepressants that are as effective as Cymbalta.

Here's how Lilly defines Healthcare Professional Education: "Speaker programs are intended to enhance a healthcare professional's knowledge and patient care expertise." Excuse my calling a spade a spade here, but that's simply a lie, and every speaker on the registry list (many of whom are friends and colleagues) knows it. The speakers are required to use Lilly's slides, and are required to say what Lilly wants them to say. And what Lilly wants them to say are things that will get the doctors in the audience to prescribe more Lilly drugs.

Aren't I insulting the intelligence of doctors? Don't the doctors who go to these talks understand that it is a hard sell? Of course they do. But this knowledge does not make them impervious to the effects of marketing. Everybody knows that the billboards for Bud Light are paid for by Anheuser Busch. But that doesn't make them any less effective.

The question is, do we want our doctors to get their medical education this way? To be plied with good food, plentiful wine, and a free ticket to a colleague's joke-filled presentation singing the praises of the company's drug? Of course not.

Most importantly, do these talks lead to patients being harmed? Almost certainly. Lilly's top-selling drug, Zyprexa, led to an average weight gain of 37 pounds in a year in one study (Strassnig M et al. Schizophr Res 2007 Jul; 93:90-8.). Now that's not a study you'll be hearing much about during Lilly's Healthcare Professional Education talks!

University of Wisconsin Whores itself to Solvay for Testosterone Money

The latest installment of John Fauber’s ongoing expose of University of Wisconsin’s shady CME practices was published in the Milwaukee Journal Sentinel this past Saturday: “UW tied to male hormone marketing: Testosterone prescriptions soar despite weak research, risks.”

Aided by UW’s lucrative alliance with Solvay Pharmaceuticals, AndroGel, a form of testosterone that you can slather over your body like sunscreen, has won 70% of the transdermal testosterone market share.

AndroGel is approved by the FDA for use in men with documented “low T” (as the company’s catchy ads call low testosterone levels). However, the actual science documenting benefits of testosterone replacement therapy (TRT) is weak. The largest and best designed study of TRT was published last year in the Journal of the American Medical Association. It did something that Solvay did not do in its FDA studies: it randomly assigned half of the 207 men to placebo. The Solvay AndroGel studies used another form of transdermal testosterone as its control.

According to the JAMA study, TRT (they used an injectable version of testosterone [correction--a reader pointed out that they used an oral form of testosterone rather than injectable]) mildly increased muscle mass and reduced fat, both by about 1%. But neither of these changes resulted in any subjective improvement. The TRT-treated patients felt no stronger and noted no improvement in the quality of their lives in comparison to those on placebo. On the other hand, the study hinted that TRT can cause heart disease: 47.8 % of the testosterone group vs. 35.5 % of the placebo group had the metabolic syndrome (a strong risk factor for cardiovascular disease and type 2 diabetes, a group of several metabolic components in one individual including obesity and dyslipidemia), though the difference was not statistically significant.

The authors concluded: “This study is, as far as we know, the largest study of testosterone supplementation with the most end points and a randomized, double-blind design. Adherence was high and the dropout rate was low,” the authors write. “The findings in this study do not support a net benefit on several indicators of health and functional and cognitive performance with 6 months of modest testosterone supplementation in healthy men with circulating testosterone levels in the lower range.”

To be fair, the UW promotional CME articles (you can read one here) were produced before the JAMA study, but that, really, is the point, isn’t it? UW allowed its reputation to be purchased by Solvay and medical education companies in order to create a buzz for AndroGel before good evidence was available. This is how the pharmaceutical industry often manipulates academic institutions and top scientists—not by inducing them to tell lies, but by paying them to say a whole lot about a topic in which the company has a commercial interest. This, in turn, generates wide interest in their product, more prescriptions, and greater profit.

How many more examples of this corrupt industry do we need before we see needed reforms?

New BBC Program: Rewriting the Psychiatrist's Bible

Several months ago, a BBC producer contacted me to ask if I'd like to be interviewed for a planned radio program examining the DSM and related topics, such as the relationship between the drug industry and the American Psychiatric Association. Being the shameless self-promoter that I am, I assented, and that program is now available on the BBC website.

Aside from listening to me ramble on about things that you've read about in this blog, you'll hear some very thought-provoking interviews of Michael First, the editor of DSM-IV, Lisa Cosgrove, the U Mass professor who published this influential article about the industry ties of members of DSM committees, Peter Tyrer, a professor at Imperial College in London who talks about the validity problems in DSM disorders, David Kupfer, chair of the DSM-V committee who makes a brief appearance, and others.

To listen to the program, click here.

Here is the BBC's description of the program:

Rewriting the Psychiatrist's Bible

Matthew Hill investigates the links between psychiatrists and the pharmaceutical industry. Should there be increased transparency over top psychiatrists' links to the industry? He looks at the influence of the Diagnostic and Statistical Manual of Mental Health Disorders (DSM), produced by the American Psychiatric Association (APA), which has been heavily criticised in the past for a lack of transparency between the panel members and pharmaceutical companies. Matthew also examines the 'Chinese menu' aspect of the DSM's diagnostic criteria and the sheer number of conditions it includes. Matthew investigates whether the APA's transparency policy goes far enough and if we are medicalising real conditions or just traits of human personality.

Broadcast on:
BBC Radio 4, 8:00pm Tuesday 4th August 2009
Duration:
40 minutes
Available until:
8:42pm Tuesday 11th August 2009

Ghostwriting for Premarin: Steroids on Steroids

Today's New York Times reveals the not particularly astonishing fact that Wyeth Pharmaceuticals engaged a medical writing company to produce 26 articles pushing Premarin as Hormone Replacement Therapy (HRT) in women from 1998-2005. The articles were outlined and written by writers employed by Design Write, and then were sent to top academics in the Ob/Gyn field, who reviewed them, rubber stamped them with occasionally minor edits, and submitted them to journals under their names. In no case was Wyeth's involvement in funding the articles disclosed.

We've heard this sordid tale before. Last year, an article in JAMA revealed that Merck commissioned ghostwriters to produce dozens of articles pushing Vioxx (see the NY Times coverage here--you'd need a subscription to JAMA to read the original paper by Joseph Ross); Eli Lilly paid ghostwriters to push Zyprexa; and Pfizer-funded ghostwriters generated the majority of articles about Zoloft in the late 1990s, according to the British Journal of Psychiatry.

What to make of all this? The best analysis I've heard yet was provided by Dr. Joseph Ross of Mt. Sinai Hospital in New York, who was quoted in today's paper:

“It’s almost like steroids and baseball,” said Dr. Joseph S. Ross, an assistant professor of geriatrics at Mount Sinai School of Medicine in New York, who has conducted research on ghostwriting. “You don’t know who was using and who wasn’t; you don’t know which articles are tainted and which aren’t.”

In this case, since Premarin is a steroid, Wyeth put its own steroids on steroids. As with baseball players on steroids, when companies pour marketing money into ghostwriting campaigns, they change the rules of the academic game. The playing field is no longer level; the drug company's version of the truth gains the upper hand. Sometimes, their truth really is the truth, but sometimes it's a carefully crafted lie. Sorting it out is difficult even for physicians who specialize in the area being written about. It's essentially impossible for the average generalist physician, to say nothing of patients who did not have the advantage of attending medical school.

As the New York Times article says, some journals now require that all authors detail precisely who wrote what and who was paid by whom before considering manuscripts. It is time for all journals to institute this policy. In addition, several academic medical centers now forbid their faculty from engaging in ghostwriting, a trend that will continue.
As I've said before, it would be nice if those who are caught with their hands in the cookie jar would have the courage to apologize. But nobody involved in this latest scandal is willing to so. Design Write, the company that did Wyeth's dirty work, said that:

[the company ] “has not, and will not, participate in the publication of any material in which it does not have complete confidence in the scientific validity of the content, based upon the best available data.”

Dr. Gloria Bachmann, a professor of Ob/Gyn who rubber stamped an article pushing Premarin for hot flashes and other symptoms, said:

“There was a need for a review article and I said ‘Yes, I will review the draft and make sure it is accurate,’ ” Dr. Bachmann said in an interview Tuesday. “This is my work, this is what I believe, this is reflective of my view.”

And Wyeth's spokesman said that "the articles on hormone therapy were scientifically sound and subjected to rigorous review by outside experts on behalf of the medical journals that published them."

Actually, the proper collective response from all of these participants should have been: "We sincerely apologize for having deceived the medical community by engaging in ghostwriting without disclosure. We have contributed to the erosion of the public's trust in medicine, and we regret it."

DSM-V Transparency: A Case Study

Last month, I wrote a few posts on the ongoing controversy about DSM-V, which is the next version of psychiatry's "bible," the Diagnostic and Statistical Manual. A quick recap: Dr. Allen Frances, the chair of the DSM-IV task force (who was shut out of the the DSM-V task force) wrote a scathing editorial for Psychiatric Times in which he questioned whether there has been sufficient progress in psychiatry to merit significant changes in the manual. The APA responded with a rebuttal, and so on.

Underlying these tiffs is something that must now be regarded by most APA leaders as a mistake: the early decision to require that DSM-V task force members sign a "confidentiality agreement." Drs. Regier and Kupfer maintain that this was merely a kind of "no-compete" clause to prevent task force members from writing and making money off their own versions of DSM. But Dr. Frances said the agreement was part of DSM-V’s “inexplicably closed and secretive process.”

Confidentiality agreement or not, as it turns out, there are glimpses of complete DSM-V transparency here and there. Take a look at this web page from the excellent Schizophrenia Research Forum website. Entitled "Live Discussion: Is the Risk Syndrome for Psychosis Risky Business?", this describes in detail the proposal for a new disorder called "Risk Syndrome for Psychosis." You can access the proposed criteria for the disorder, including the text discussing characteristics, associated features, differential diagnosis, etc.... So far, there are 23 comments posted, constituting a rigorous debate about the pros and cons of the proposal.

At this point, the diagnosis may or may not make it into DSM-V. It really depends on whether there is strong enough research indicating that treatment of early forms of psychosis can head off the later development of schizophrenia. My understanding is that the research is unconvincing, but I'm willing to defer to these specialists, who clearly know a lot more about psychosis than I do.

The point is not so much whether "Risk Syndrome for Psychosis" ends up winning a coveted spot in the DSM-V pantheon; rather, the point is that here is a case study of complete transparency, and it doesn't hurt one bit. In fact, it works exceedingly well, because it lets everyone in on the psychosis work group's thought process and it invites comments on a specific proposal. Where's the beef? It's here.

Unfortunately, if you go over to the DSM-V website and look at the official "Report of the DSM-V Psychotic Disorders Work Group," all you'll find is a very brief summary of some of the topics under discussion. The only mention of the Risk Syndrome for Psychosis is telegraphic: [One issue being considered is] "adding a risk syndrome section to DSM-V and including risk for conversion to psychosis as a category." There isn't even a link to Schizophrenia Research Forum website.

The same level of detail (ie., almost no detail) applies to the other work group reports as well. In their rebuttal to Frances, the APA leadership maintained that "the process for developing DSM-V has been the most open and inclusive ever.” Apparently they were referring to various presentations at conferences. If they want to be credible, I suggest they instruct the chairs of each work group at least to post links to all web pages containing specifics of proposed disorders. That would be true transparency, and it would make a lot of disgruntled psychiatrists happy.