Another Hired Gun Repents, This Time a Cardiologist

When it comes to conflicts of interest, cardiology is the new psychiatry.

Psychiatry is cleaning up its act through a combination of external forces and the profession’s own commitment to ethical rehab. But cardiology, a field awash in drug company cash, is only now taking baby steps in the right direction. The pace of change is about quicken, in part because of a remarkable cardiologist named James Stein, who was profiled yesterday in this article by John Fauber in the Milwaukee Journal Sentinel. Also, watch this video of his talk at a recent ethics conference.

James Stein is not your everyday cardiologist. He a full professor at the University of Wisconsin, and is one of the top researchers in the country, having invented techniques to use echocardiograms to take more precise measurements of atherosclerosis. He was named one of the top 20 cardiologists in the country by Men’s Magazine.

Dr. Stein, like me, used to be a hired gun for the pharmaceutical industry. Unlike me, he was in the game at the highest levels, having been on speakers' bureaus, advisory boards, and research steering committees for many different companies. It all started when he was a 29 year old cardiology fellow. His academic mentor could not make it for a scheduled promotional talk and invited Stein to pinch hit for him. Stein gave the talk, and was handed a sealed envelope containing a $500 check. According to the Journal Sentinel article:

"I got a pat on the back and he said, 'There's more where that came from, son.' I had no idea what that meant, but I went home and paid off part of my student loans," Stein said in a presentation at UW this month.

One thing led to another. From the article:

Over the years, many of the big names in the drug industry would hire Stein to give speeches or serve as a consultant, eventually leading to fees of $2,000 to $3,000 per talk....For instance, in 2005 Stein did work for six drug makers, according to a disclosure form filed with UW. That year, Pfizer paid him between $10,000 and $20,000 for four days of work as a speaker and advisory board member. LipoScience, a firm that markets a cholesterol test, paid him $10,000 to $20,000 for four days of similar work. Another firm, Schering-Plough, paid him about $12,000 for two days as a lecturer.

Like all hired guns who hop onto gravy train with the best of intentions, Stein thought he was providing added value for everyone concerned. In his videotaped talk at UW, Stein characterized this as an apparent “win-win-win-win situation” in which he benefitted financially and professionally, patients benefitted from the education he provided to their doctors, his university reaped benefits in prestige and the drug companies sold more of their products.

When journalists started publishing the amounts of money he and other opinion leaders made from their talks, he went on the offensive, arguing that such relationships were fine:

“I defended my relationships with industry by saying that conflicts were inevitable for successful researchers, that my relationships with industry helped build bridges, that my talks always were educational, that this was part of the UW mission, and that at the end of the day I saved lives by educating people about the medications and diseases states I spoke about.” (This and most of the quotes that follow are from my transcription of his recent talk).

Inside, however, he said he felt embarrassed about the public disclosures of his income and noted that many of his patients made a pittance in comparison, and sometimes could not even afford their medications. He decided to make some changes. He pushed for better disclosure policies at the university, he sent letters to his patients disclosing his industry relationships, and he decided to donate all his promotional money to charity.

Even with all his growing misgivings, he continued to give the talks because, as he put it:
“I was sure I could avoid bias because I controlled the content and I had these strong personal convictions.” But then, things changed: “Well, unfortunately, over the past several months, I’ve learned that I was wrong. I’ve learned that I could not stay unbiased, that I could not control all the content of my talks, and that my personal convictions were not good enough.”

In fact, he said he realized that everybody is a little biased, even physicians, and not because they are evil, but because they are human. He noted that bias is inevitable in research, and that no one is insulted when they are told that certain research designs are off limits because they would lead to bias.

“So I ask myself, why are physicians so insulted when similar influences might be influencing us in our patient care?”

He realized that he was wrong in supposing that simply disclosing his relationships with industry was enough:

“I really felt that if I stood up in front of a crowd and said that these are my disclosures, look how honest I am, that I was really managing conflict of interest. But actually the medical literature and the social science literature tells me that it is actually the opposite effect. Although it is laudable to disclose your relationships, actually thinking that disclosure manages relationships is harmful. It has the perverse effect that when you disclose your relationship, the recipient of your information becomes more trusting, and the social scientists also have shown us that professionals who disclose actually become more biased…. I would argue … that the solution is not disclosure, because if you are doing something that is wrong or unethical, don’t disclose, just don’t do it!”

He also realized that every drug company he had worked with over the past 15 years had been fined or convicted for ethical or legal violations involving activities like off-label marketing or suppression of data.

Finally, he was particularly disturbed to realize that accredited CME had been adopted as a marketing technique by drug companies.

“I trusted continuing medical education but what I found was that many times it was a sanitized way of presenting a marketing message….My personal conclusion is that the medical device and pharmaceutical industries are no longer trustworthy partners in medical education.”

As of Dec 31 of 2008, Dr. Stein ended all of his industry interactions that were not related to bona fide research activities.

Congratulations, Dr. Stein. Welcome to the small but growing “I’ve Had It” club of former hired guns!

Historic IOM Report: A Knock-Out Blow to Greed in Medicine

The long awaited report on conflict of interest from the Institute of Medicine has been released, and it is a landmark document in the history of medicine.

Before reviewing the report, what is the Institute of Medicine, and why is everybody making such a fuss about what it has to say? The IOM was created in 1970 by the federal government as part of the National Academy of Sciences. According to its website, “The nation turns to the Institute of Medicine (IOM) of the National Academies for science-based advice on matters of biomedical science, medicine, and health.”

You can think of the IOM as the most important advisor to Congress and the White House on medical issues. It is not formally a part of the government, and therefore none of its recommendations have the force of law. However, when the IOM speaks, everybody who is anybody listens very closely.

This 300 page report, formally titled “Conflict of Interest in Medical Research, Education and Practice,” can be accessed here.

Pared down to the essentials, its recommendations are:

1. Drug companies must disclose any payments they make to doctors, hospitals, and many other institutions. This is similar to the proposed Physician Payments Sunshine Act, but goes further because it recommends that these financial disclosures extend to consumer groups (such as the National Alliance for the Mentally Ill), medical societies (i.e., the American College of Cardiology, which is the new poster child for industry money-lust), and medical education companies. Basically, IOM is saying, “no more hiding any money that you may be using to surreptitiously influence medical care.” This is an extremely powerful and sweeping recommendation, and will complete the process of bringing integrity back to medicine.

2. Doctors should no longer accept any free meals, gifts or other items from companies. Various academic medical centers have already announced such rules but they vary in the details. For instance, Johns Hopkins says "no gifts" except expensive medical textbooks and educational charts, and "no free meals" except for a long list of examples where free meals are okay. IOM endorses a very simple policy—no meals or gifts of any kind.

3. Doctors must not participate in speaker’s bureaus for drug companies.

4. Doctors must not do clinical research if they have a financial interest in the outcome of the research. As Dr. Carroll points out in Health Care Renewal, this rule would have prevented the unfortunate series of events involving Dr. Alan Schatzberg, Stanford University and the NIH.

5. Revamp the system of continuing medical education (CME) so that there is no more industry influence in the content.

The actual verbatim recommendation regarding CME is:

"RECOMMENDATION 5.3: A new system of funding accredited continuing medical education should be developed that is free of industry influence, enhances public trust in the integrity of the system, and provides high-quality education. A consensus development process that includes representatives of the member organizations that created the accrediting body for continuing medical education, members of the public, and representatives of organizations such as certification boards that rely on continuing medical education should be convened to propose within 24 months of the publication of this report a funding system that will meet these goals."

Industry funding of CME was the most controversial issue faced by the IOM, and you’ll notice that the above recommendation is rather artfully crafted to avoid explicitly calling for a ban on industry funding. In the subsequent discussion, the IOM explains that some committee members were worried about “unintended consequences” of an immediate funding ban, such as fewer courses. But guess what? There are far too many redundant industry-funded courses anyway, on the same topics over and over again—treatment of carefully hand-picked conditions with drugs made by the sponsor.

Nonetheless, later in their report, the IOM makes quite a strong statement anyway. Some industry funding might be acceptable, they say, but only if funneled into pooled sources of money over which the companies have no control. Crucially, direct funding—which constitutes essentially all of industry-funded CME as currently practiced--would be forbidden under the new system:

“Both direct company funding to institutions for specific continuing medical education programs and direct company provision of unrestricted grants to institutions offer clear opportunities for undue influence, particularly for continuing medical education providers that also receive the great majority of their funding from companies. A plan for a system free from industry influence would exclude such funding as well as funding from company-controlled foundations.” (section 5, page 32).

The bottom line is that this report will serve as the authoritative guide for medical centers and policy makers for the next several years as they clean up conflicts of interest in medicine. Change is coming, big time.

ACCME's Existential Crisis

ACCME (the Accreditation Council for Continuing Medical Education) knows what it needs to do, but it is having a very hard time bringing itself to do it.

The pharmaceutical industry funds over half of all the education U.S. doctors receive, which is an embarrassment to our medical establishment and a danger to patients. Whenever I tell my patients that drug companies are in charge of most medical education, they react the same way--they shake their heads in an "are you serious?" expression of disbelief.

ACCME knows this system is inherently wrong but it also know that most of its income is dependent on the system.

Its latest effort to distance itself from the corrupted system over which it presides is to create a new category of "Commercial Support Free (TM)" CME. It's a strange proposal. It implies, of course, that CSF-CME (as I'll abbreviate it) is an essentially different kind of medical education from industry-supported CME. After all, if it were not different, then there would be no point in creating a separate category.

And how is CSF-CME different? It is presumably better in some way, because it is not tainted with the biasing influence of industry. As the industry-friendly journal Medical Marketing and Media has put it, the new designation is an official "Good Housekeeping Seal" for CME.

But herein lies the rub. The entire mission of the ACCME is to accredit only the cream of the crop of medical education. If it is now proposing to create a platinum category of truly unbiased CME, then what does this mean for industry CME? That it isn't very good. And now ACCME has boxed itself into a difficult position. If it is creating a second class citizen category of "not-as-good" medical education, why accredit it at all?

Perhaps this is a way for the organization to gradually transition toward a ban on commercial funding, a ban which the Board of Directors has announced is not in the cards any time soon. Thus, CSF-CME may be part of a 5 year plan to gradually wean CME off of industry funding. Here's how it would work. You create a category of the "best" CME, and, under the theory that "if you build it, they will come," you hope that doctors will naturally gravitate away from the phony tin courses and toward the platinum courses. This would hasten the shift of drug company money away from CME, and would make the eventual ban on industry funding a little less painful.

But, like gradually peeling off a bandaid, it won't really make it less painful for the MECCs--it will just make it more protracted, and more like slow torture. It's much better to simply rip the bandaid off in one fell swoop. The pain is harsh but brief, and we can all move on.

Partners COI Policy: Better than Hopkins, But Not Great

Partners has anounced that it will implement a new conflict of interest policy. You can read the press release and summary of the policy here. I also recommend reading the excellent Boston Globe coverage here.

The good:

--A sweeping ban of all gifts, including meals and textbooks. This makes it a true gift ban, unlike John's Hopkins half hearted gift ban which I panned here.
--While industry funds for CME will still be accepted, they will have to be pooled into a hospital-wide President's Fund, or they will have to be approved by a newly established "Educational Review Board." Any program that passes muster with this new ERB must be jointly funded by at least two companies, lessening the potential for product-specific promotional bias.
--Faculty will no longer be allowed to be hired guns for drug companies.

The bad:

Let's get real. Industry funds education in order to promote their products. Thus, any CME program that holds itself out as "independent" of industry influence, is inherently a deception. It's rather embarrassing that the Harvard hospitals, with their incredible endowments, brainpower, and prestige, can't simply get it together to do the right thing, which is to say: WE WON'T TAKE ANY DRUG COMPANY MONEY FOR PHYSICIAN EDUCATION.

Seroquel gets the Abilify FDA Treatment

The FDA's Psychopharmacological Advisory Committee voted last week to recommend that Seroquel be approved as an adjunctive treatment for depression, but it rejected AstraZeneca's request that the drug be approved as monotherapy treatment for depression or generalized anxiety disorder.

According to this article in The Philadelphia Inquirer, "Panel members, including scientists from outside the FDA and consumer advocates, said Seroquel's risks in depression and anxiety outweighed its benefits."

One of the panel members, Richard Malone, explained that "the risks are fairly well-documented, and I don't think they are acceptable for this use."

While I agree with the committee's rejection of two indications, I'm concerned that they were inappropriately impressed by the Seroquel augmentation data. As far as I know, the augmentation studies have not been published, but a summary can be found on page 27 of AZ's briefing document. It looks like they used the same research design as BMS did in their Abilify augmentation studies, and that the Seroquel results were equally unimpressive (see this article at Clin Psych for a slam of the Abilify data). Seroquel reduced the MADRS depression score by about 15 points, while placebo decreased it by about 12 points. This 3 point advantage is tiny, considering that the MADRS is a 60 point scale. Personally, I don't think that this 5% advantage (3 divided by 60 possible points) is worth Seroquel's side effects.

Particularly since this recently published randomized trial showed that when Seroquel was added to Prozac, it yielded no advantages over placebo, aside from helping patients sleep better over the first few weeks. This was not a study of treatment-resistant patients (unlike the FDA data) but it nonetheless shakes my confidence in the potency of the medication.

If the full FDA decides to go along with the committee's recommendation, AZ will mount the kind of mega direct-to-consumer marketing campaign that we have seen with Abilify (for background, see two excellent LA Times pieces here and here), and consequently there will be a little epidemic of obesity among depressed patients. Now that's what I call depressing!

Johns Hopkins: Read My Lips--No More Gifts!

To a surprising amount of fanfare and press, Johns Hopkins has voted to ban free samples and to restrict some gifts from drug companies. But it is hardly a “ban” on gifts, though you wouldn’t know it from the news reports.

Here’s what has been reported, followed by what the new guidelines actually do.

1. NO MORE FREE DRUG SAMPLES. This is true. Here is the relevant excerpt:

The practice of accepting free pharmaceutical samples risks interference with one’s prescribing practices since industry representatives often provide the newest and most costly drugs. Therefore, free pharmaceutical samples and vouchers for free pharmaceutical samples may not be accepted.

2. NO MORE FREE GIFTS…er, at least no pens, mugs, and notepads, a redundant rule because these were already banned months ago under PhRMA’s updated Code on Interactions with Health Professionals, eg., the “no tchotchkes rule.” But expensive textbooks, anatomical models, and informational posters are okay. Therefore, while a company cannot simply hand a Hopkins doctor a new i-pod nano, it can save the doctor the $100 he or she would have otherwise spent on a new textbook. Said doctor can then use these savings to buy a fourth generation i-pod nano online for $99.99.

3. NO MORE FREE FOOD…er, except at industry-supported CME events, where you can enjoy a nice meal free of charge as long as you are also getting free CME credit as well. Otherwise, NO FREE MEALS...umm, well, you can have meal if it’s part of an industry sponsored consultation gig…and, let’s see, if it is offered at a professional society meeting… and, oh yeah, if it’s part of a “research meeting”…and if the drug company gave an “unrestricted grant” to the department which decided to use that money for free food, that’s okay, as long as the company HAD NO INPUT INTO WHICH ENTRÉE WAS OFFERED. But if a drug rep invites you out to dinner in order to try to convince you to prescribe more of his drug, you must refuse the invitation…wait a minute…you CAN go out to dinner with him, but you have to pay for your own meal! (He can share an appetizer with you though) (Okay, and you can have a sip of his martini).

4. NO MORE CASH GIFTS. Johns Hopkins will no longer allow drug reps to hand doctors thick wads of money in unmarked envelopes! HOWEVER, (quoting directly from the new policy) “Gifts from industry may be used by the department to support faculty and staff education, research, and/or patient education. Distribution of the funds will be at the discretion of the department director, who will disseminate the criteria for requesting funds to all faculty members in the department.”

Okay, so let me get this straight. Companies are still allowed to give unlimited amounts of cash to academic departments, and the departments can do anything they want with the cash. Now that’s the kind of gift ban any key opinion leader on the gravy train can support!

Oh, and here’s a nice bonus. Drug companies can still give individual doctors thick wads of cash, as long as it is called a “prize” for “scientific or medical achievements.” To quote again from the policy: “For purposes of this policy, prizes and awards are not considered gifts.”

The bottom line is that Johns Hopkins has crafted a policy to generate good PR for the university, but which continues to allow a free flow of money, food, and educational gifts from the pharmaceutical industry to doctors. Let’s hope that our other academic medical centers can do better.

Seroquel XR and Marcia Angell's Blueprint for the FDA

There's a nice editorial by Marcia Angell (former editor of New England Journal of Medicine and author of the classic book The Truth About Drug Companies) in today's Boston Globe.

Dr. Angell lays out seven specific recommendations for changes in FDA policy, all of which are sensible and will encourage better drug pipelines and safer medications.

Before presenting them, I want to highlight her recommendation number 5, which is that the FDA should be able to require drug companies to compare new drugs with existing drugs of the same type. This is especially relevant in the context of an upcoming meeting of the FDA's Psychopharmacological Advisory Committee. Tomorrow it will begin a two day meeting to discuss, among other things, AstraZeneca's application to approve Seroquel XR for generalized anxiety disorder (GAD) and major depression (you can learn the particulars here).

Seroquel XR is, indeed, more effective than placebo for both depression and GAD. Nonetheless, the application should be soundly rejected, unless AZ can show that Seroquel XR works better than the dozens of other drugs that are already available for these conditions. Why approve an antidepressant that causes weight gain, diabetes, and cardiac death, when there are equally effective alternatives that cause none of these side effects?

I doubt that AZ has done such comparative studies, because they were not forced to do so. From their stockholders' perspective, they would be foolish to conduct such studies, because there's a good chance that Seroquel would do no better than drugs like Zoloft or Celexa. Its disadvantageous side effect profile would be highlighted in a head-to-head trial. And as we know from recent court documents, AZ has done everything it can to bury the truth about Seroquel's side effects.

Marcia Angell's Seven Recommendations for a Better FDA:

1. Congress should repeal the Prescription Drug User Fee Act.

2. Consultants for drug companies should no longer be permitted to serve on FDA advisory panels.

3. The agency should see that the post-marketing studies it mandates are actually carried out.

4. The FDA should review generic drugs as fast as brand-name drugs.

5. Congress should give the FDA the authority to require drug companies to compare new drugs with existing drugs of the same type.

6. The FDA should stop approving me-too drugs on the basis of surrogate endpoints.

7. The FDA should prohibit direct-to-consumer advertising for three years after drugs are approved.

JAMA Recommendations for Medical Societies and Industry; or, Breaking Up Is Hard To Do

This week, JAMA published a major paper outlining recommendations for what kinds of money professional medical societies should and should not accept from the pharmaceutical industry.

The short version is that the authors believe that PMAs can continue to accept advertising and exhibit booth money, but that all other funding should eventually be eliminated. But they realize that many associations would probably cease to function if they had to divorce their patrons immediately, so they recommend a number of “interim” measures. Below are some of their key recommendations, followed by how the American Psychiatry Association deals with some of these issues.

·PMA leadership. All leaders, elected or non-elected, should have no financial relationships with industry.

APA: New rules now require that anybody involved in any level of governance, including committees, task forces, and councils, must declare their conflicts of interest at the beginning of meetings. While there are no restrictions on conflicts for leadership, most of the current officials (with the conspicuous exception of the president-elect, Dr. Schatzberg) have no relationships with industry. This should become a requirement of election.

·Practice guidelines committees. Typically, such committees are comprised mainly of academics with industry relationships. Furthermore, PMAs often accept industry grants to support the proceedings of such committees and to disseminate the resulting practice guideline materials. The paper recommends no industry involvement of any kind.
APA: Most of the members of APA practice guideline committees have industry relationships, although the organization does not accept industry grants to support the committees. In addition, most of the DSM-V committee members have industry relationships, although they are required to limit such income to no more than $10,000 per year while sitting on the committee. Should we exclude members with industry relationships from participating on any treatment guideline committees or on the DSM committee? The problem with this is that many of the most knowledgeable clinicians do industry-sponsored research and I wouldn’t want to exclude their expertise. Instead, I would propose that we allow a maximum quota of members with industry ties (perhaps no more than 25%), as long as these relationships do not include clear marketing activities, such as promotional speaking, participation in industry-funded CME events, or marketing consultation.

·Product endorsements. The group recommends that PMAs never solicit or accept deals from companies that allow them to offer their services to members.

APA: The APA currently has a number of such relationships, seen as important incentives for psychiatrists to become members of the organization. This includes, most egregiously, an official endorsement of PRMS, a malpractice insurance carrier that accepts money from Eli Lilly to put on pseudo-educational programs. I have written about this topic here. I agree that entering into deals with these companies is fraught with ethical pitfalls, as the PRMS fiasco shows. It’s just not worth it.

·Conference sponsorship. The group would allow industry support of meetings, as long as the money does not influence the content. However, they call for the elimination of industry-supported satellite symposia at meetings.

APA: The APA has just voted to phase out industry support of symposia, and once this is accomplished, there will be no industry support for the annual meeting, other than payments for exhibit booths. I disagree with the report’s willingness to allow even arms-length industry support of educational meetings, which I believe will inevitably lead to promotional activities in the guise of education. Theoretically, setting up “firewalls” between industry money and choice of content is a good idea, but the example of industry-funded CME shows that it is rarely effective in practice.

·Research and fellowships. The group is willing to allow industry grants for research and for fellowships, but they specify that research grants should not be pegged to specific research projects. Furthermore, fellowships should not be named after companies, and the fellows should not be told which company supports their fellowship.

APA: The APA currently accepts industry funding for a variety of research projects and for research or travel fellowships, often awarded to residents in support of travel to the annual meeting. I support the paper’s recommendations, but I think it is naïve to believe that any company would support a fellowship if nobody is allowed to know they supported it. Nor do I believe it would possible to keep such information secret.