DOES AMERICAN PSYCHIATRY MATTER?

DOES AMERICAN PSYCHIATRY MATTER?

The blogmeister of 1boringoldman.com has done it again. A semi-retired psychiatrist in rural Georgia, he has done more than anyone to document the follies and the ethical challenges of contemporary American psychiatry. His site is required reading for all who care about behavioral health issues.

In his latest posting he compared the domain of American psychiatry to Yugoslavia. Cast Melvin Sabshin as Marshal Tito. Sabshin was the medical director of the American Psychiatric Association in the late 1970s, the period leading up to DSM-III. Tito and Sabshin each strong-armed a confederation of sorts but failed to deal with the conflicts beneath the surface. Both leaders were faced with the prospect of their domains disintegrating – Tito’s at the hands of Moscow and Sabshin’s at the hands of insurance companies. Both persuaded wary stakeholders to sign on to a compromise, for want of anything better and fearing a worse outcome.

The domain of psychiatry hasn’t yet reached the stage of ethnic cleansing and genocide that we saw in Yugoslavia after Tito’s death, but it is well on the way. One only has to look at the vicious response of the American Psychiatric Association leaders to Allen Frances and other critics of DSM-5. The APA president in 2009, Alan Schatzberg from Stanford, went out of his way to smear Dr. Frances and Robert Spitzer, the architects of DSM-IV and DSM-III because he had no credible scientific response to their criticisms of the directions DSM-5 is taking. He was joined in this low act by David Kupfer and Darrel Regier, who are directing the DSM-5 effort. Where is the comity, Comrades? Where are the shared values? Why is the APA holed up in a bunker?

Then we have the unsavory sight of the APA lawyers threatening a blogfrauchen in the U.K. with a SLAPP lawsuit for alleged infringement on the APA’s intellectual property – as though the APA owns psychiatric classification! Talk about chutzpah. So now the confederation Sabshin cobbled together is breaking up and the stakeholders are starting to go their separate ways – psychologists, counselors, social workers, patient advocacy groups, even many psychiatrists. Christopher Lane in Psychology Today has said American psychiatry is facing “Civil War” over its diagnostic manual. Even an international psychiatric journal like British Journal of Psychiatry is distancing itself from DSM-5 and there is talk of abandoning DSM-5 for the next ICD classification.

Why is American psychiatry self destructing? Because the grand bargain forged in 1980 with DSM-III was a sham from the get-go and the promised benefits of diagnostic reliability have not materialized. They knew all along that reliability was a poor substitute for validity, but they settled for half a loaf. That compromise led us into the epistemologic quagmire of today, where there is no solid ground for clinical decisions or clinical research progress or drug development. A stunning absence from the DSMs to date is any statement about treatment. That compromise also led us to diagnostic inflation, which Pharma embraced. Pharma quickly filled the vacuum with experimercials that pretended to be real clinical science, and in the process diverted precious clinical research infrastructure away from genuinely important questions. Just look at the clinical trials er, experimercials, mill operating out of Massachusetts General Hospital at Harvard University.

What lies ahead? Stakeholders are going to vote with their feet. DSM-5 is likely to be a footnote in the history of psychiatric classification. The APA will become even less relevant than it is today, much like the American Medical Association, which now commands the loyalty of maybe 30% of U.S. physicians. Mel Sabshin will turn in his grave, the APA will lose revenue, ICD-11 will become the dominant classification of psychiatric disorders, and the quagmire will continue until a new synthesis arises from the ashes. If Yugoslavia is any kind of model, don’t hold your breath.

12:38 AM

STOSSEL and ACRE: WHERE'S the BEEF?

STOSSEL and ACRE – WHERE’S the BEEF?

Thomas Stossel from Harvard is at it again. As Daniel Carlat has humorously described, Stossel is planning the inaugural meeting next week of a group to counter those he calls pharmascolds. The group is named ACRE – Association of Clinical Researchers and Educators. Here is its website: http://www.acreonline.org/ For months, Stossel has been warning of the dire negative consequences that will result from tightened conflict of interest policies, but he has not presented any persuasive examples of damage to “productive relationships between industry and physicians involved in clinical research and educational outreach.” At the same time, Dr. Stossel has conveniently overlooked the shenanigans of the bad actors whom Senator Grassley exposed. Dr. Stossel is a blowhard, as I have described here before.

But wait! ACRE has found something! A News item in the July 2009 issue of Nature Medicine (“Conflict of interest rules seen by some as too stringent”) quoted one of the participants in the upcoming ACRE conference. Avi Markowitz, chief of oncology at UT Medical Branch, Galveston, came up with this example: Patients taking a Sanofi Aventis chemotherapy product may experience peripheral neuropathy, which can cause unpleasant sensations in the hands and feet. ‘Sanofi Aventis had been providing Markowitz and his UTMB colleagues with free blankets and gloves for those patients. Last fall, however, the university adopted stricter rules banning industry freebies. Now, Markowitz can’t even accept the unbranded blankets and gloves that Sanofi Aventis has offered to provide.’ Reading between the lines, it is a good bet that these items originally were branded.

Whatever. And never mind that the patients receiving chemotherapy at UTMB are doubtless billed a hefty facility fee that must include comfort items like blankets and gloves. Since when does a chief of oncology need to beg for these basic patient care provisions from drug companies?

Is this all that ACRE can come up with? The ACRE homepage warned sternly of “restrictive conflict of interest policies that often sever productive relationships between industry and physicians involved in clinical research and educational outreach.” Does Thomas Stossel’s whining and catastrophizing through ACRE come down to piffling items like blankets and gloves for chemotherapy patients? That’s it? Where’s the beef?

At least ACRE has the good sense not to include on its program the smooth operators whom Senator Grassley outed – like Nemeroff at Emory, Schatzberg at Stanford, Kuklo at Walter Reed, Keller at Brown, Biederman at Harvard. Not even Stossel has been brazen enough to try to defend them.

The Nature Medicine News item does close on a helpful note: 'Stossel would like to see abuses involving financial conflicts of interest treated more like cases of scientific misconduct. Rather than forcing everyone to abide by prohibitive rules, he says administrators should focus on weeding out those who misbehave.' I say Amen to that, even if it is a day late and a dollar short.

We have arrived at our present state of discomfiture because the leaders of academic institutions and professional societies looked the other way for too long. They failed to do their job of reining in the ethical outliers. Grassley had to do it for them. As a result, the rest of us will be burdened with new regulations for years to come. Those who did speak up years ago were ignored or demonized. As the saying goes, every group gets the leadership it deserves. Those in academic medicine had better not count on Stossel and ACRE to lead them out of the wilderness.

Bernard Carroll.

2:30 PM

INSTITUTE of MEDICINE REPORT on CONFLICT of INTEREST

INSTITUTE of MEDICINE REPORT on CONFLICT of INTEREST

Today we saw a new marker laid down in the arena called Conflict of Interest (COI). The Institute of Medicine of the National Academy of Sciences issued a report of its Committee on Conflict of Interest in Medical Research, Education and Practice. The report is comprehensive, even exhaustive, running to 353 pages. Gardner Harris in the New York Times today calls it “scolding,” “stinging,” and “damning.” The recommendations go well beyond any proposed in the recent past by medical schools or by other professional organizations. The NYT quoted David Rothman, president of the Institute on Medicine as a Profession at Columbia University: “With the I.O.M.’s endorsement, issues that were once controversial now are indisputable. Conflicts of interest in medicine are no longer acceptable.”

It will take some time for the field to digest the scope of the IOM recommendations. It will take even longer for the new standards to be implemented. For now, I offer just a few observations.

First, if the IOM hopes for maximum credibility then it might ought want to do some housecleaning. A few years ago I fired a shot across the bow of the IOM concerning COI. [Can the Institute of Medicine Review the FDA? Nature Medicine 11, 369 (1 April 2005) doi:10.1038/nm0405-369] Nothing much changed, and in the following years, national scandals erupted involving several of the issues I had highlighted. Prominent IOM members, who were well known to be poster boys for COI, were exposed by Senator Charles Grassley (R-Iowa). Their embarrassing behaviors included incomplete financial disclosures and noncompliance with NIH policy on financial conflict of interest. The exposés included Emory’s Charles Nemeroff and Stanford’s Alan Schatzberg. In both cases, administrative rearrangements have now been implemented. The case of Dr. Nemeroff has been referred by Senator Grassley to the Inspector General of the Department of Health and Human Services. It is perhaps no accident that Dean Claudia Adkison of Emory and Dean Philip Pizzo of Stanford were included as external reviewers of the draft IOM report. Their insights would have been invaluable.

Another ongoing embarrassment for the IOM is Lester Crawford. He was the FDA Commissioner who resigned abruptly in 2005 and later pleaded guilty to criminal conflict of interest. He had been charged with falsely reporting information about his stock holdings in companies he was in charge of regulating. He received a sentence of three years of supervised probation and a fine of about $90,000. He is now senior counsel with a health care lobbying firm in Washington, DC. The Institute of Medicine does not help its image by continuing the membership of such a compromised individual.

As the Emory-Nemeroff and Stanford-Schatzberg cases unfolded it appeared that the respective institutions had themselves contributed to the problems, either through inaction or through studiously nontransparent procedures on disclosure. Stanford, for instance, apparently did not require faculty members to report the proceeds of stock sales, and when challenged the university invoked on-line financial reporting services and SEC filings as a sufficient substitute. Not surprisingly, because Stanford didn’t know about Dr. Schatzberg’s realized gain of some $109,000 from sale of founder’s stock in his biotech start-up company, Corcept Therapeutics, this information was not reported to NIH.

Recommendation 4.1 One of the IOM’s recommendations applies particularly to the Stanford-Schatzberg case. Recommendation 4.1 addresses the boundary between academia and commerce in the case of research involving human subjects. Here is the specific language:

“Academic medical centers and other research institutions should establish a policy that individuals generally may not conduct research with human participants if they have a significant financial interest in an existing or potential product or a company that could be affected by the outcome of the research. Exceptions to the policy should be made public and should be permitted only if the conflict of interest committee (a) determines that an individual’s participation is essential for the conduct of the research and (b) establishes an effective mechanism for managing the conflict and protecting the integrity of the research…” (page S-14).

Last year I posted several times about this issue in the Stanford-Schatzberg case. It is gratifying now to see the IOM affirm the importance of the boundary. The activities declared off-limits by the IOM include not only “recruiting subjects; obtaining informed consent; assessing the clinical end points;” but also “analyzing data; or writing the results, conclusions, and abstracts for publications reporting the findings of the study.” (page 4-17). In Stanford’s earlier plan for managing the conflict and protecting the integrity of the research, Dr. Schatzberg was free to engage in the latter group of activities. Indeed, his hands were all over the project when it came to responding to scientific critiques, managing the climate of professional opinion, attacking and threatening critics, promoting his company’s interest through review articles and press releases, slipping unpublished and non-peer-reviewed commercial data into academic reviews, and generally conducting commercially slanted public relations through academic outlets.

When Stanford adopts the IOM recommendations, such activities will be blocked. As I stated last year, “Review articles that assess a field and synthesize data form a crucial part of science that has to be off-limits to Dr. Schatzberg just as much as assessing patients in one of his clinical trials would be.”

We should congratulate the IOM committee members for their work, and we hope to see the field embrace their recommendations.

Bernard Carroll.

UPDATE 04-30-2009: The link provided earlier for the IOM report document is no longer operative. Here is where to go now for a copy of the report. This time it will cost you.

http://www.nap.edu/catalog.php?record_id=12598

5:40 PM

In Defense of Psychiatric Diagnoses and Treatments

In Defense of Psychiatric Diagnoses and Treatments

The Boston Globe is out today with a story about conflicts of interest involving American Psychiatric Association guidelines for treating depression, mania, and schizophrenia – disorders for which the market in medications is said to be $25 billion annually. Conflicts abound, it seems, and the consequent implication is that industry influence has led to guidelines that “focus heavily on medications and give relatively little attention to nondrug treatments.”

The lead author of a forthcoming analysis, Lisa Cosgrove from the University of Massachusetts is quoted in the Globe as saying “…the lack of biological tests for mental disorders renders psychiatry especially vulnerable to industry influence." Maybe so, but it’s not just psychiatry. And this new study should not be taken to invalidate psychiatric diagnoses or to undermine the efficacy of psychiatric treatments.

The existence of disease is not predicated on having a biological test. It’s nice when we do have one, but there are many disorders throughout medicine, not just in psychiatry, for which there is no conclusively defining biological test. Think migraine. Think multiple sclerosis. Think chronic pain.

There is a distinguished tradition of clinical research, going back to the late 1950s, wherein disorders like depression, mania, and schizophrenia were studied for their genetic profiles, their clinically meaningful subtypes, their biological correlates, and their responses to treatments. This bottom-up approach yielded useful theories, which in turn led to better theories and to new treatments for depression, mania, and schizophrenia. Like any other branch of science, clinical science has a self-correcting function that distinguishes it from pseudo-science and propaganda. So, we welcome new theories even though most will not survive, and we welcome new diagnostic proposals and we welcome potential new treatments. All are subject to the test of independent confirmation, and nobody is surprised when many fall away.

Since around 1990 that tradition has been corrupted by Pharma and Pharma’s money. There is no shortage of examples regularly in the news. Academic key opinion leaders lost their ethical compass and, with or without a figleaf, devolved into spokespersons for industry. One is reminded of Julien Benda’s term la trahison des clercs. Instead of moving on from undistinguished and problematic new drugs, key opinion leaders work with the marketing departments of Pharma to promote and defend the brand. Remember the PsychNetters? Of course, psychiatry is not the only medical specialty corrupted in this way. Stents, anybody? Orthopedic devices, anybody?

Lost in the marketeering and propaganda since around 1990 is the discipline of clinical therapeutics. As one commentator put it, if there is no way to confirm biologically the existence of disease, then “…we cannot confirm with much confidence that this or that treatment treats mental disease.” It actually is possible to identify effective treatments for mental disease. We did it with lithium. We did it with the early antidepressant drugs. And we did it with the early antipsychotic drugs. There was room for improvement in all of these, but make no mistake – they were dramatic positive developments. Most of the work in the past 20 years, however, put marketing first and clinical therapeutics second. Humbug aside, the goal was not to improve the management of depression or mania or schizophrenia but to jump whatever bar the FDA was setting in order to get a product on the market. Indeed, the really hard clinical research issues were studiously avoided. Along the way, the clinical research enterprise became dominated by academic and for-profit contract research organizations in which, to put it gently, standards of recruitment of patients apparently suffered, so that response rates in placebo-treated patients skyrocketed. As a result, proving that a drug does work became harder, and the overall drug advantage over placebo in treating depression came into serious question. In effect, the corruption of clinical research standards has brought us to an epistemologic quagmire about the efficacy of today’s most popular antidepressant drugs.

As for the charge that psychiatrists and primary care physicians just throw drugs at mental health problems, that is nothing new. It is a reflection of the professional pragmatism that permeates medical practice. Think back to the 1950s when the new wonder drugs called antibiotics were handed out like Pez, mostly for people who did not really need them and who would not benefit from them. The working principle was misguided simplicity and pragmatism, which minimized and discounted the risks. Even today the over-use of antibiotics remains a public health concern. Just as in the 1950s patients with nonspecific upper respiratory symptoms were “given the benefit of the doubt” and were prescribed an antibiotic on the reasoning that it might help them while probably not hurting them, so today patients with nondescript depressive or anxiety symptoms are prescribed an SSRI drug on the same reasoning. The cost of this approach in wasted money, in unnecessary side effects, and in unproductive clinical management is non-trivial.

So, the issues are more nuanced than today’s Boston Globe story would suggest. For good and for ill, psychiatry is not so very different from the rest of medicine. Corruption and compromise respect no subspecialty boundaries. We can have reliable and valid knowledge of disease without a biological test. We can show efficacy of treatments for disorders that lack a biological test. But when simplistic pragmatism and cutting corners dominate in therapeutics and in clinical trials, then we are in trouble.

4:41 PM