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.

Senate CME Hearing: Impressions, More Links

There's no question that the recent Senate hearing on CME was stacked against industry funding of CME, but that's because from the standpoint of the American public and Congress, the practice is slimy and wrong.

Senator Mel Martinez, a republican from Florida, summed up the mood best with his perplexed question (I'm paraphrasing here): "Wouldn't it just be better if doctors paid for their own continuing medical education?" As a lawyer, he said, he always paid for his own CLE (continuing legal education) and he was never paid to give CLE lectures.

To those of us who have lived and breathed this issue for years, his question came across as innocent, but in fact it hit the obvious point, and surely summarized the view of most Americans.

Tom Stossel, to his credit, came out swinging in a ring where he was badly outnumbered, but as he often does, he conflated two issues: the remarkable advances in medicine over the past few decades and industry funding of CME. The two are not related. We've had advances in medicine because of great science and appropriate interactions between doctors and industry--bona fide relationships based on developing products and conducting clinical trials. None of these relationships would be threatened in any way by the Physician Payments Sunshine Act or by the IOM's proposal to greatly scale back industry funding of CME.

My favorite moment of the hearing was when Senator Al Franken directly confronted Stossel, saying (again, I'm paraphrasing): "You seem to draw a lot of conclusions from anecdotes of people who have benefited from modern medicine. Medicine is a lot better now than when we were kids, but that doesn't mean that industry should fund CME."

Dr. Kopelow's comments were disappointing in the extreme. He repeated a single refrain, saying, in essence: "There is no problem with bias in CME. We are doing our job well. ACCME is the firewall between promotion and education." C'mon Murray! You know what's going on. You've seen the many, many letters of complaint reporting biased programs. In fact, you reprimanded one company for bias within the last few months--I know, because the reprimand was based on my letter. It only took you about two years to issue your decision. I won't mention the specifics in this blog because I promised you I wouldn't.

I liked Lew Morris's comments. He's the General Counsel, U.S. Department of Health and Human Services, Office of the Inspector General, and so he's pretty influential. He wants to set up "independent CME grant organizations" that would pool industry funds and divvy them out in ways that don't promote specific treatments or lucrative disease categories. Good luck to him. He admits that drug companies have shown zero interest in parking any of their so-called "unrestricted educational grants" in such organizations. He alluded to one that was set up by a surgical association. Its current budget: $0.00. Clearly, companies will only fund CME if they see a promotional advantage.

LINKS:

The Senate Aging Committee website has now posted links to all the written testimony, including my testimony (I am erroneously identified as being from the Cleveland Clinic--apparently they mixed me up with Steve Nissen and I am flattered!), as well as testimony from Pharmed Out (Dr. Adrian Fugh-Berman), and from a series of organizations that have vested interests in keeping things as they are, including the University of Wisconsin, PhRMA, AdvaMed, and Merck.

Senate Hearing on CME: Links to Testimony

Industry-supported CME received a merciless drubbing today at the Senate Hearing. I'll report some of my observations tomorrow, but for now I wanted to post some of the written testimony, since it may not be available from the Senate for another week or so.

--Steve Nissen's Testimony

--Eric Campbell's Testimony

--ACCME (Murray Kopelow) Testimony

--Thomas Stossel's Testimony

I'll post others as I receive them.

Live Blogging the Senate Hearing on Industry-Funded CME

2 pm: Let the games begin!

2:15-- Senator Al Franken: Proud that his state of Minnesota was the first to pass a disclosure law in 1993. However, transparency is not enough, because between 2002-2004 many millions were paid to physicians for marketing activities.

2:25-- Lew Morris, General Counsel, U.S. Department of Health and Human Services, Office of the Inspector General: We need more effective safeguards. The current environment allows drug companies to choose topics related to their products. We suggest independent CME grant organizations. They would serve as firewalls between donors and the education. It's not clear that companies will go along with this.

2:30-- Dr. Steven Nissen, Chair, Cleveland Clinic Department of Cardiovascular Medicine:
CME has become an insidious vehicle for the promotion of medical products. This is undermining the independence of medical societies. Current ACCME oversight is ineffective. Few if any communication companies have lost their accreditation for biased CME. He has written letters of complaint about some activities to ACCME but he received no response.

2:35-- Dr. Eric Campbell, Associate Professor and Director of Research, Institute of Health Policy, Massachusetts General Hospital, Harvard Medical School:
The members of the Institute of Medicine Committee generally agreed that CME has become far too reliant on industry funding. The current system of funding is unacceptable. More transparency is necessary.

2:40-- Jack Rusley, Chair, Culture of Medicine Action Committee, American Medical Student Association; Student, Brown University Alpert School of Medicine:
AMSA has been a leader in the movement to clean up conflicts of interest. Students are able to be passionate advocates for patient care, since they are not already tangled up in payments from industry. He talked about the Harvard Medical student's rally to improve its COI policy. Harvard had received an "F" on AMSA scorecard in past but due to recent changes now earns a "B".

3:00-- Dr. Thomas Stossel, Director, Translational Medicine Division and Senior Physician, Hematology Division, Brigham & Women’s Hospital; Leadership, Association of Clinical Researchers and Educators (ACRE):
Medicine is much better now than when he started training. Death rates from cancer and heart disease are lower. We have a great system of innovation and education. There has been a lot of moral bullying, but not a lot of evidence. Do patients benefit from physician industry collaboration? Definitely.

3:05-- Dr. James Scully, Medical Director and CEO, American Psychiatric Association (APA):
We do need to support continuing innovation in medicine. But patients need to be able to rely on the objectivity of their physicians. The APA has decided to phase out all industry-supported medical education symposia. We are the first medical society to do this. This will cost us a million and a half dollars this year. But we feel it is well worth the cost.

3:10-- Dr. Murray Kopelow, President, Accreditation Council for Continuing Medical Education:
ACCME is the firewall between promotion and education. 15% of providers receive 80% of commercial support. He recounted many proposals to limit promotional influence, but said that none of them have been implemented yet. We are improving our surveillance of CME activities. We are increasing our staff.