a grief observed II…

Posted on Sunday 9 February 2014

I thought I could describe a state; make a map of sorrow. Sorrow, however, turns out to be not a state but a process…
A Grief Observed,C.S. Lewis, 1961

To their credit, Lisa Cosgrove of the Safra Center and her colleagues stayed on the case:
by Cosgrove L. · Krimsky S. · Wheeler E.E. · Kaitz J. · Greenspan S.B. · DiPentima N.L.a
Psychotherapy and Psychosomatics. 2014 83:106-113.

Background: The revision process for and recent publication of the DSM-5 initiated debates about the widening of diagnostic boundaries. The pharmaceutical industry had a major financial stake in the outcome of these debates. This study examines the three-part relationship among DSM panel members, principal investigators [PIs] of clinical trials for new DSM-5 diagnoses, and drug companies.
Methods: Financial conflicts of interest [FCOI] of DSM panel members responsible for some new diagnoses in the DSM-5 and PIs of clinical trials for related drug treatments were identified. Trials were found by searching ClinicalTrials.gov. Patent and revenue information about these drugs was found using the US Food and Drug Administration’s Orange Book and manufacturer Annual Reports.
Results: Thirteen trials met inclusion criteria [testing drugs for some new DSM disorders]. Sixty-one percent of the DSM Task Force members and 27% of Work Group members reported FCOI to the trial drug manufacturers. In 5 of the 13 trials [38%], PIs reported ties other than research funding to the drug manufacturer. In 3 of the trials [23%], a PI had financial ties to the drug manufacturer and was also a DSM panel member who had decision-making authority over the revision process.
Conclusions: These findings suggest that increased transparency [e.g., registration on ClinicalTrials.gov] and mandatory disclosure policies [e.g., the American Psychiatric Association’s disclosure policy for DSM-5 panel members] alone may not be robust enough strategies to prevent the appearance of bias in both the DSM revision process as well as clinical decisions about appropriate interventions for DSM disorders.
I try not to say this too often, but this is one of those articles that bears reading in full. The details of these particular Conflicts of Interest are worth looking at the specifics and what they mean in the title when they say …High Stakes Patent Extensions. And now to the Newsweek article that puts all of this into lay terms:
Newsweek
By John Ericson
February 6, 2014

… When the APA released the fifth edition of its manual in May 2013, it was instantly criticized by several researchers and clinicians, who claimed that some of the revisions and modifications reflected the agenda of an editorial panel that did not have the public’s best interest in mind. For example, many therapists and parents denounced the decision to define Asperger’s syndrome as a part of the autism spectrum rather than a stand-alone diagnosis. Some said it would skew statistics. Others said it would mess with identities…

… That, however, wasn’t the biggest concern. Other experts, including Sheldon Krimsky, professor of Urban & Environmental Policy & Planning at Tufts University, have pointed out that changes to the DSM can also be big business, with lots of downstream profit for everyone involved. If, for example, the DSM-5 finds a new "indication" for a particular drug, the developer can renew its patent and keep generic competitors off the market for another three years. For most industries, this would have a pretty modest impact on revenue. But in the business of curing ills, in which price tags can be very high and demand is often buoyed by nature, those three years can make a huge difference.
What? I didn’t know that. Back to the Cosgrove et al paper for a moment, they found 13 trials on clinicaltrials.gov that were testing drugs for the new DSM-5 diagnoses:
    Thirteen clinical trials met inclusion criteria. These clinical trials were designed to investigate 10 patented drugs and one investigational new drug. Nine of these trials were testing ‘blockbuster’ drugs with patents that had expired or would expire in the next 2 years. Table 1 [see full text] provides a summary of trial drugs, their patent status, and their 2012 revenue [obtained from the drug manufacturers’ 2012 annual reports]. The trial drug manufacturer was one of the sponsors or collaborators for 8 of the 13 trials [62%].
moving back to Newsweek:
… Take, for example, the drug Cymbalta – one of a group of drugs referred to by the industry as "blockbusters" – drugs that rake in at least $1 billion in annual revenue. Cymbalta, which is prescribed for major depressive disorder and generalized anxiety disorder, earned its blockbuster title almost five times over in 2012, bringing in nearly $5 billion to developer Eli Lilly. Lilly’s patent on Cymbalta expired in December 2013, and the developer should soon begin to lose revenue to generics… But thanks to the changes made by the APA to the DSM, the money will likely keep rolling in.

… In past editions of the DSM, a so-called bereavement exclusion from major depressive disorder recommended that actively grieving individuals not be diagnosed with depression. In the DSM-5, this recommendation has been erased, giving rise to "bereavement-related depression" – a subset of major depressive disorder that is treatable by all the standard methods [and drugs] that ease depression. But if you didn’t need to treat the loss of a loved one with medication in 2000, is it really necessary in 2014?

… Companies like Lilly certainly want it to be – and they may just get their way. Public records regarding clinical investigations show that Lilly’s expired patent on Cymbalta will in all likelihood be renewed, as it is currently the focus of a new trial for the pharmacological treatment of bereavement-related depression. In other words, it’s going to end up being the drug of choice for treating what was merely called "grief" at the time of Lilly’s original patent filing.

… The APA’s disclosures regarding the DSM-5 include several instances that appear to support the contention that the public’s best interest has fallen in the shadow of financial gains. Take, for example, the Cymbalta trial: Of the 43 APA panel members involved in the implementation of this new diagnosis, 20 had disclosed financial conflicts of interest with drug manufacturer Lilly. These disclosures, which range from stock holdings and consultancies to honoraria and research funding, suggest that more diagnoses ultimately means more money for everyone involved…
hat tip to Altostrata
Maybe everyone else knows about extending patents for three years if a new indication comes along. I didn’t – but then, here at 1boringoldman.com, I don’t have a bevy of patent lawyers poring over the laws looking for loopholes. Maybe everyone else knew to look for clinical trials aimed at exploiting such a loophole to rationalize giving medications to grieving people. I didn’t, being in the C.S. Lewis camp that sees grief as an important life process that may need some fellow travelers, but not something to shut it up. But Cosgrove, Krimsky, and their colleagues knew enough to chase down the implications of their previous COI article [see a grief observed I…] and we owe them a debt of gratitude for their perseverance. I had breathed a mistaken sigh of relief that the patent medicines for depression had mercifully expired just in time.

Was there a direct connection between the influence exerted by the pharmaceutical companies and their affiliated psychiatrists in high places that opened up this possibility of patent extensions? Given the track record of the industry/academic psychiatry alliance for decades, only a fool would say "No." And whether that could be proved in court doesn’t even matter. That’s the kind of thing David Kupfer, Derral Regier, James Scully, and the APA Presidents/Trustees are there to protect us from having to even think about. Instead of handing out defensive homilies and damage control press releases, we could’ve used a lot more evidence that they were doing their jobs. And this is also why even the appearance of Conflict of Interest has been the traditional standard in medical ethics until the recent era.

In the Newsweek article, Dr. Allen Frances who has tirelessly lead the critique of the DSM-5 was also asked to respond:
Frances believes that while pharmaceutical companies may indeed pounce at every opportunity to drive revenue and retain exclusivity, the panel members themselves have also been blinded by their desire to help "the missed patient" – the individual in pain who, for one reason or another, disappears through cracks in the system. "The experts on the DSM-5 were given a tremendous amount of freedom, and what this resulted in was a kind of dream list of new diagnoses that turned the everyday problems of life into mental disorders," he tells Newsweek. "They are naive about how something that may work in their hands will be misused in the average practice." adding "The biggest risk is not financial conflict of interest, but intellectual conflict of interest," he says. "The pressure of experts is always to expand their area."
Dr. Frances knows these APA people, and I don’t doubt that this more benign interpretation may be true for some, maybe many. Who knows? We’re not likely to be privy to that information. But I personally see no distinction between an intellectual Conflict of Interest and a financial Conflict of Interest. Experts with any Conflict of Interest are intrinsically dangerous – not experts at all. Likewise, among Cosgrove, Krimsky, et al’s recommentations, they include:
    Finally, as a policy objective, it is critical that the APA recognize that transparency alone is an insufficient response for mitigating implicit bias in diagnostic and treatment decision-making. Specifically, and in keeping with the Institute of Medicine’s most recent standards, we recommend that DSM panel members be free of FCOI. In the future, DSM panel members should also be prohibited from serving as PIs of trials for any disorder being considered for inclusion in the DSM.
Given the behavior of DSM-5 Chair, Dr. Kupfer himself, [open letter to the APA…, no longer a given…] and the behavior of the workgroup members documented here, I would instead recommend that the clock has run out on the APA even being involved in future DSM efforts. I see this as the end of the line…

UPDATE: Speaking of "defensive homilies and damage control press releases," the current APA President is keeping the tradition alive in a new medium:
  1.  
    February 9, 2014 | 7:05 PM
     
  2.  
    Peter Parry
    February 9, 2014 | 8:54 PM
     

    I googled for patent extension on Cymbalta. It doesn’t seem to have happened. Yet, anyway. Eli-Lilly have taken a financial hit with the patent expiration in December 2013 and the FDA has approved Duloxetine generics. So has the horse-bolted for the company? Can they still get a patent extension now for bereavement-related depression – presumably they can – but won’t people just be able to prescribe and take generic Duloxetine that’s coming onto the market?

  3.  
    February 9, 2014 | 11:34 PM
     

    (sorry for posting on this thread too, but hey, increased attempts should get your attention, although i think one time is enough hehehe)

    Hi,
    I just wanted to mention that the APA did a “neuroimaging markers” report in 2012 where they tried to essentially throw a bunch of math at fMRI in order to generate a method that can reveal psychiatric illness.
    of course, this is a very challenging problem (it was rumored to be pursued by the great Sir Isaac Newton as an application for his laws) and they failed miserably. see here: http://www.psych.org/File%20Library/Learn/Archives/rd2012_Neuroimaging.pdf
    they have, since, tried to hold me down. i have had experiences with a few doctors at NYU langone who have been nothing short of amazing (dr michael milham especially, and a few of his colleagues).
    in short, if you look at my thesis on my webpage in the future work, i allude to the underpinnings of the method that produces 80% on 3 different disorders using a consistent experimental design inspired by the greats from the 1960s (David Ingvar, Goran Franzen and Niels Lassen). If you google their study (ingvar franzen 1974) you’ll see essentially the approach that this mathematical method allows (it’s very powerful).
    you can contact me at the listed email for any other questions.
    i’m delighted i found your blog. again, check the future work section of my thesis, ingvar & franzen’s 1974 study, and the neuromarker report from the APA given above.
    put 2 and 2 together. i am being held down by these very same beaurocrats. there is a very promising medical tool on the horizon that is being short shrift because it’s my intellectual property (and thus the drug companies are at the mercy of the scientific community, as the research must demonstrate causation between brain regions and the disorder).

  4.  
    Steve Lucas
    February 10, 2014 | 7:47 AM
     

    Once again, in my opinion psychiatry is the business model pharma would like to put in place all across medicine. They become the arbiter of disease, and its solutions, and nothing, nothing will stand in the way of them maximizing profits realized from this endeavor.

    Remember, while the first pill may cost a billion dollars, a number in dispute, the marginal cost of every pill after is almost 0.

    Steve Lucas

  5.  
    February 10, 2014 | 11:45 AM
     

    hi sorry for the additional post, but if you remove the “www” from the link in my name, it should work (didn’t know adding the www would cause a problem).

    thx

  6.  
    February 10, 2014 | 6:47 PM
     

    Ron Pies, Jeffrey Lieberman, George Dawson http://real-psychiatry.blogspot.com/2014/02/an-obvious-response-to-psychiatry-gone.html and their ilk seem to think psychiatry gets pounded on unfairly, and by ignoramusses or nuts or people who have temporarily lost their senses, like Marsha Angell.

    That’s the reason there’s so much criticism of psychiatry. Otherwise, it’s just like any other medical discipline. Ignoring the bad research, the astronomical billions made in drug treatment, dubious premises for diagnosis, and lack of post-marketing data makes sense to these people.

  7.  
    Tom
    February 10, 2014 | 7:37 PM
     

    I just wish Lieberman and other KOL’s refrain from hyperbolic nonsense. For example, to use a term like “dangerous” to characterize the Newsweek article is plain dumb. If you feel the reporting was “shoddy” well so be it. Dangerous??? Really?

  8.  
    February 10, 2014 | 7:58 PM
     

    Dr. Lieberman and others are afraid criticism of psychiatry, particularly in the popular press, might scare people away from getting drug treatment. In their minds, there is a huge population of people who desperately need such treatment who are not getting it.

    The issues of overprescription and overmedication of tens of millions of people who do not have severe psychiatric disorders — they just shrug that off. Overshooting in the cause of stamping out psychiatric illness in every nook and cranny of civilization is justified, I guess.

    We’re all roadkill in their march towards their grand goal.

  9.  
    February 10, 2014 | 11:52 PM
     

    Nice rhetoric.

    You conveniently leave out the overprescription of antibiotics and the failed 20 year attempt by the CDC to reel that in. Currently the score is twice as many antibiotic prescriptions as antibiotic infections and several critics talking about us entering a “post antibiotic era”.

    Any idea what that means?

    The DSM-5 and all of the “scandals” in psychiatry will probably be irrelevant at that point.

  10.  
    AA
    February 11, 2014 | 4:17 AM
     

    Dr. Dawson, fair point about the antibiotics but I find it interesting that you and your colleagues will automatically change the subject and come across as defensive instead of acknowledging the concerns that are extremely valid by people who have been greatly harmed by psychiatry. I just fail to see how that contributes to the discussion.

    AA

  11.  
    Steve Lucas
    February 11, 2014 | 6:55 AM
     

    Having been around for awhile I find that when we enter the realm of straw man arguments, diversion, and dismissal we have entered the area of marketing. Many feel the need to defend the faith by shouting down those who are critical with ever increasing claims of danger.

    Comparing antibiotics to antipsychotics is truly an apples and oranges comparison.

    The APA has much to answer for in promoting a pharma based system that has harmed millions directly though the use of medications, and millions more through the stigma of taking medication. The profits received by those who have withheld their conflicts of interest need a very close review, and where appropriate, those people need to be removed from positions of authority.

    Steve Lucas

  12.  
    February 11, 2014 | 2:47 PM
     

    Saying psychiatry is as bad as any other medical discipline (although inaccurate) doesn’t say anything about psychiatry to be proud of.

    What about clinical practice improvement in psychiatry? Where is that going to come from? To have improvement, you must acknowledge and analyze shortcomings. This is entirely missing in psychiatry, unlike other medical disciplines.

    Defensive denial, however, is very much present in psychiatry, from the top at APA to the bottom.

  13.  
    Jonathon
    February 14, 2014 | 3:53 PM
     

    How soon before mood stabilizers and antipsychotics are approved for DMDD? Are the trials underway yet?
    Also–and this is a longshot—has anyone read literature suggesting that mood stabilizers are effective treatment for anger in the absence of mania or depression? what’s the evidence base for this practice (prescribing mood stabilizers to people with anger problems)?

Sorry, the comment form is closed at this time.