in the sunlight…

Posted on Sunday 5 January 2014

A recent post on Behaviorism and Mental Health, Psychiatry’s Over Reliance On Pharma, took a meta-look at Dr. Lieberman’s The NIMH-CATIE Schizophrenia Study: What Did We Learn? Dr. Hickey pointed to Dr. Lieberman’s blaming pharma for their distorted messages, rather than holding psychiatrists responsible for listening to those messages, and continuing to listen even now after all the scandal. Fair point, well made. But there was a discussion in the comments about clinical trials that brought back some old memories. They have to do with calling clinical trials of drugs research. I don’t think of clinical drug trials as research. I think of them as product testing.

In my case, the DSM-III revolution arrived in the form of a person, a new chairman, and he spoke of nothing except research. At first, I thought he was interested in building the department into a more academic place, and maybe that was right. But as I listened, what he primarily meant was clinical drug research. For that and a thousand other reasons, I began to look for other work. That’s a long story that’s not pertinent here. What  is pertinent is that I had left a research tract in an earlier time of life, not in psychiatry, and I had a fairly solid idea what research was. Drug trials were an aside, something reasonably important, but not research. At some point, part of this department building thing was to institute a monthly Grand Rounds with outside speakers. The first one was a presentation by someone who gave a drug talk about Mellaril, paid for by Sandoz [that speaker was later the first author on the primo Seroquel clinical trial and even later spent ten years in prison for fraud]. I was gone into private practice not too long after that Grand Rounds.

By any right-thinking that I know, a clinical drug trial is essentially composed of two parts: the design, which specifies all the details in a protocol about how it is to be conducted and analyzed; and the trial itself, which is carried out according to that protocol including the result analysis at the end [predefined]. The whole point of the pre·definition is to curb the temptation to play with the data once it is in hand. I would see that not as a research endeavor, but as administrative enterprise – something important to do well, but more in the range of robotic than creative. I hate to use the term assembly line because it has negative connotations and I don’t mean that, but I can’t think of something else – so "good assembly line" is the point here. And one needs to be paid well to do it, because it’s a pain in the ass to do. Part of the drill is to treat all subjects the same, and that’s hard to do in clinical medicine with sick people.

Everything about a clinical drug trial design is an attempt to eliminate bias, human and otherwise: randomization, blinding, standardized instruments, placebo control, active comparators, an a priori protocol, etc. Creativity, following hunches, making outside observations, anything that branches from the straight line is verboten – antithetical to the point of the trial. If something interesting happens along the way, apply for another grant because it doesn’t belong in this one. Research is something else. Research has branches. A hypothesis or a question is where it starts, but it’s refined, or redirected, or even abandoned along the way. It’s more about immersion in a question that’s unanswered and looking all around for a way out, like a spot of mold on the petri dish. In a clinical trial, that’s a contaminated sample, missing data. In research, it’s the discovery of penicillin.

At least in psychiatry, those invested in the outcome of a clinical trial have found a number of ways to lean the results. Sometimes it’s in the design e.g. an active comparator given in the wrong dose. But usually it’s by adding a third part – playing with the results to see if they lend themselves to presentation enhancement techniques; or re·framing adverse effects; or putting the whole thing in a file drawer to grow old alone. A lot of the KOLs who sign these things really don’t involve themselves in that process it turns out. They’re just tickets into an academic journal or window dressing for the author’s byline. Five or six years ago, I didn’t actually know that. They’re called researchers, but they aren’t, and many aren’t even trialists. They’re more like trophy·wives or front·men. They know a lot and present well, but they’re something other than researchers or trialists.

So back to Phil’s point. Why have psychiatrists continued to listen? Why psychiatry’s over·reliance on pharma? Part of the real answer is that they didn’t know it was just pharma. Another part is that there was no other place to listen. Another part is that their patients watch too much television. Another part is that’s what they get paid to do. Another part is that’s what they get referred patients for – "med consults." Another part is it’s easy. And the worst part is that they don’t put the time and effort into swimming upstream and figuring things out for themselves. I actually liked the CATIE study even if I’m not so taken with Dr. Lieberman. Maybe the overly-positive messages about the Atypical Antipsychotics did ultimately come from pharma, but they came out of the mouths of academic psychiatrists and flowed into algorithms and guidelines certified by same that were everywhere.

Back to the beginning and my memories. I have been reassured by many who were there to know that I trust that the pharmaceutical invasion of academic/practicing psychiatry came after the DSM-III revolution and did not have a finger in causing it. I have to take that on faith, because in my microcosm, they came at the same time. And there were a number of young psychiatrists who came to Atlanta [from Saint Louis] who opened clinical research centers in that same time frame [that are still going strong]. For that matter, John Feighner, the Saint Louis psychiatry resident whose criteria formed the nucleous of the DSM-III went on to have a successful and lucrative career running a clinical research center. So, at the least, the synergy between a segment of psychiatry and pharmaceutical industry funded clinical drug trials came early on in the days of the DSM-III, certainly in my neck of the woods.

From my perspective, the entire point of the Data Transparency movement is to eliminate that third part I mentioned above – playing with the results. The trials themselves are well regulated, but as we’ve seen, the end of the trial is often the beginning of the manipulation phase. If the raw data is there, there are plenty of people poised to analyze it correctly. It’s a profession in its own right – vetting these studies. If psychiatrists, physicians, other mental health types, and patients have access to the truth, it’s a different game. The fate of psychiatry as defined by its critics, or the majority of practitioners, or by yours truly isn’t really any of my business. That’s for a future clinical trial played out in the sunlight…
  1.  
    Steve Lucas
    January 5, 2014 | 10:11 AM
     

    “Facts are the enemy of truth.”

    Steve Lucas

  2.  
    January 5, 2014 | 10:55 AM
     

    “The road to hell is paved with good intentions” does not absolve one from not paying attention that the intentions did not have good outcomes. But, those immature defenses by those with dysfunctional personality disorders really come in handy in doing just that, defending the indefensible. And so many who are just followers have no interest to hold people accountable for poor choice, poor intent, poor foresight.

    Hence why the antisocial seems to prevail more consistently and pervasively these days. Apathy and indifference prevails, but, why the hell in people who really know better?! Well, back to your screens for the day.

  3.  
    January 5, 2014 | 11:46 AM
     

    The modern iteration of the DSM is related to drug studies because it gave a foundation to the notion that the things we treat are easily quantifiable and measurable. It is when we begin to question that premise, we are seen as the true renegades of our profession.
    Have you discussed ADHD? I apologize if I missed your posts on this but I think this is a growth industry in our field. Many of the drugs are still on patent and the potential market is huge. Psychiatrists who have come to question the growing Bipolar franchise, see hope for patients with this diagnosis.
    In my opinion, there are clinicians who think it is better to do something than nothing when there is inadequate data and there are others who remain more reluctant to act. Of course, as with everything, this is a gross simplification.
    In any event, stimulants are more like benzodiazepines in that the effects are noticed by patient and physician almost immediately and that reinforces the notion that the are “working”. I believe there is grossly inadequate data on long term outcome. Clinical work does not inform us on long term outcome (it is so easy to attribute poor outcomes to other factors and it is just hard to track as a clinician). We have learned how problematic that is.
    An interesting article:
    http://www.nytimes.com/2013/12/15/health/the-selling-of-attention-deficit-disorder.html?_r=0

  4.  
    January 5, 2014 | 12:19 PM
     

    Dr Steingard:

    Might want to check out my blog and search “ADD & stimulants” there, it may be illuminating, although just my opinion on the issue. I even talk about the article you link above.

    I believe the medications that act “the quickest” are usually the ones that get abused, misused, and confused the most. I don’t think that is a message we want to sell or impart to patients, do you?

    And while I would cautiously agree doing nothing is not good, rushing to start medication is not a better alternative just on the face of it. Besides, how many patients come to us already having been quickly put on a medication, or more likely, medicationS by other providers first, and are expecting us to find the quick fix?

    Just curious, to anyone out there who still belongs to the APA, at the May conference in the past 5 years, have there been any seminars/conferences of real substance that not only talked primarily about therapy, but encouraged it as an intervention by psychiatrists?

    My expectation to replies is simply this: people won’t admit to being a member, or, can’t remember seeing a seminar on such topic, much less attend one. Yes, cynical, pessimistic, and jaded.

    But, beats being recklessly naive, cluelessly optimistic, and fatally determined to stick to a single dogma. Hey, there is a sales pitch for encouraging membership for the APA this year!

    “Who needs skills when people need pills, and we are the best to treat the rest!” Wow, I could actually see something like that used!

  5.  
    January 5, 2014 | 1:34 PM
     

    Sandy/Joel,

    I haven’t talked ADD/ADHD and you are astute to notice. I’ve avoided it for the same reason I avoid Thomas Szasz. But I’ll have a go at it soon.

  6.  
    January 5, 2014 | 2:36 PM
     

    Clinicians maintain their fantasies about safety and tolerability of psychiatric drugs by ignoring what their patients have to say about how they’re feeling (and such signs as weight gain, tremors, etc.). Such practitioners should not even be called doctors, they’re an arm of pharmaceutical distribution.

    Are they responsible for what they do? Heck, yes.

  7.  
    jamzo
    January 5, 2014 | 4:32 PM
     

    re: Clinical Trial as research….see david healy April 2013

    the fifth is the Lasagna series of posts that began with Not So Bad Pharma, April Fool, Tragedy of Lou Lasagna, Empire of Humbug: Bad Pharma and will continue through to Brand Fascism and Witty A: Report to the President.

    http://davidhealy.org/the-empire-of-humbug-not-so-bad-pharma/

    re: Clinical Trial as research Gerald Klerman

    From 1977 to 1980, he was the head of the Alcohol, Drug Abuse and Mental Health Administration, appointed by President Jimmy Carter.

    began multi-site studies to define both treatment efficacy and disorders

    Arch Gen Psychiatry. 1979 Jul;36(7):765-71.
    NIMH clinical research branch collaborative program on the psychobiology of depression.
    Katz MM, Secunda SK, Hirschfeld RM, Koslow SH.
    Abstract

    This is a report on the history and implications of the collaborative effort that evolved from the 1969 National Institute of Mental Health conference on the psychobiology of depression. The major issues identified at that time were the need to (1) assess relative validities of current systems of nosology and (2) retest critical biological hypotheses concerning the etiology and nature of the depressive disorders. Research was required that would be multidisciplinary and involve clinical settings treating diverse types of depression. The objectives and the nature of the biological and clinical collaborative programs that were designed to address these problems are described. These unique programs, initiated in the early 1970s, currently span research on nosology, genetics, neurochemistry, neuroendocrinology, and psychosocial factors. Although these studies are still in the early stages, they have resulted in significant methodologic developments in diagnosis, descriptive psychopathology, and biological measurements.

    Genet Epidemiol. 1989;6(1):179-82.
    NIMH Collaborative Program on the Psychobiology of Depression: clinical.
    Rice J, Andreasen NC, Coryell W, Endicott J, Fawcett J, Hirschfeld RM, Keller MB, Klerman GL, Lavori P, Reich T, et al.
    Author information

    Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri.

    Abstract

    As part of the National Institute of Mental Health Collaborative Program of Depression study, data were collected on 2,225 first-degree relatives of 612 probands. A subset consisting of 187 families of bipolar patients was made available to participants of Genetic Analysis Workshop 5 (GAW5). A description of these data, including sample sizes, diagnoses, and a summary of published analyses, is given.

  8.  
    jamzo
    January 5, 2014 | 4:38 PM
     

    Alcohol, Drug Abuse, and Mental Health Administration Nomination of Gerald L. Klerman To Be Administrator.
    October 12, 1977
    Public Papers of the Presidents
    Jimmy Carter1977: Book II
    Jimmy Carter
    1977: Book II
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    The American Presidency Project

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    The President today announced that he will nominate Gerald L. Klerman, of Chestnut Hill, Mass., to be Administrator of the Alcohol, Drug Abuse, and Mental Health Administration. He would replace James Isbister, resigned.

    Klerman was born December 29, 1928. He received an A.B. from Cornell University in 1950 and an M.D. from New York University College of Medicine in 1954.

    From 1954 to 1956, Klerman was an intern and resident in medicine at Bellevue Hospital in New York. From 1956 to 1959, he was a resident in psychiatry at the Massachusetts Mental Health Center.

    Klerman was a research associate at the National Institute of Mental Health from 1959 to 1961. From 1961 to 1965, he was at the Massachusetts Mental Health Center as a psychiatrist, then assistant director of psychiatry. He was at the Connecticut Mental Health Center from 1965 to 1969, serving as director of clinical services, then general director.

    From 1970 to 1976, Klerman was superintendent at the Erich Lindemann Mental Health Center in Boston. Since 1976 he has been professor of psychiatry at Harvard Medical School and director of the Stanley Cobb Laboratories in Research Psychiatry at Massachusetts General Hospital.

    Klerman is a consultant to the American Medical Association Council on Drugs, the National Institute of Mental Health Clinical Research Branch, the Medical Letter, Drug and Therapeutic Information, and the Veterans Administration Cooperative Studies Evaluation Committee. He has been a principal investigator on a number of research studies.
    Citation: Jimmy Carter: “Alcohol, Drug Abuse, and Mental Health Administration Nomination of Gerald L. Klerman To Be Administrator.,” October 12, 1977. Online by Gerhard Pete

  9.  
    Mike Howard
    January 6, 2014 | 8:24 AM
     

    Chiming in strictly as a lay person with absolutely no medical background but with some achieved knowledge of clinical trials, especially the CAFÉ’ study, which was also under the leadership of Lieberman, I can recall vividly the “headlines” regarding the CATIE study. Such as,
    The CATIE study marks a true milestone in the treatment of people with schizophrenia. The results from this trial will likely have a huge impact in how people with schizophrenia are treated in the U.S and around the world, potentially transforming the way patients are treated..Etc
    Supposedly the problems that the CATIE studies were designed to address are, in part, that the FDA’s clinical trials don’t answer some of the key questions that doctors say that they really need. The FDA clinical trials only tell if a new drug is “safe”, and if it at least meets some minimum threshold of effectiveness. What the trials don’t do is compare one drug with another. So, the problem, therefore, is that psychiatrists don’t have any in-depth studies to help guide them on whether one drug works better than another, or has fewer side effects than another.

    I think that’s the bare bones pre-determined outcome measure whatever….

    Well, here’s my problem. CATIE is/was no different than the “Landmark” CAFÉ’ study sponsored by AstraZeneca instead of the feds. All the hype is there, the fireworks went off before and after, all the industry’s KOL’s lined their pockets disseminating all the wonderful data, and supposedly the world is a better place now in the treatment of folks dealing with schizophrenia….except, that hasn’t happened.

    These drugs had already been on the market for years, and so are we to believe that up until they conducted the CATIE and CAFÉ’ studies clinician’s as well as the ill consumer had no clear direction on what was best for their chances of survival?

    Living in Minnesota we were privy to having pharma payments to physicians required by law to be made public. Well folks; psychiatrist’s topped the lists every year, and even a lay person could figure out from looking at the figures, that whatever drug was the newest on the market paid the highest return, and that “Speakers ,” and “Consultants,” and “Advisory Board members” all paid well. And then throw-in for good measure the pharma sponsored CME’s that are nothing more than paid propaganda disseminating the same old data from the same key KOL’s, that never had a damn thing to do with any of studies except to put their name on some pharma written paper.

    I bet if you walked into the office of Joe-Blow psychiatrist with symptoms of a “first episode psychosis” and said according to the outcome measures from the landmark CAFÉ’ study…how are you going to treat me? The psychiatrist would be ‘Googling’ Café…and finding a few recommended on some street in Paris. Same thing with CATIE.

    Lieberman, as well as many of the talking heads from the psychiatric community have only one true agenda, and it’s to keep the cash cow fed and stroke their ego’s.

  10.  
    wiley
    January 6, 2014 | 4:12 PM
     

    product testing

    Ya’ see, this is the kind of precise speech that gives clarity to the layperson.

    Truth.

  11.  
    Nick Stuart
    January 6, 2014 | 11:48 PM
     

    Mickey, why do you avoid ADHD discussions? Why do you avoid Szasz?

  12.  
    January 7, 2014 | 1:03 AM
     

    Nick,

    from: The six most essential questions in psychiatric diagnosis: a pluralogue part 1: conceptual and definitional issues in psychiatric diagnosis

    Thomas Szasz, M.D. SUNY Upstate Medical University.

    I thank Dr. James Phillips for inviting me to comment on this debate. I am pleased but hesitant to accept, lest by engaging in a discussion of the DSM (the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorder) I legitimize the conceptual validity of “mental disorders” as medical diseases, and of psychiatry as a medical specialty. Psychiatrists and others who engage in this and similar discussions accept psychiatry as a science and medical discipline, the American Psychiatric Association (APA) as a medical-scientific organization, and the DSM as a list of “disorders,” a weasel word for “diagnoses” and “diseases,” which are different phenomena, not merely different words for the same phenomenon…

    I’m not a member of the APA nor do I have any enthusiasm for the DSM-anything nor am I involved in involuntary treatment and confinement nor do I have any interest in whether psychiatry is or is not a medical specialty, and as he says above those are the only topics that are on the table. I’ve heard what he has to say about those things and have read some of his writings. I think he is monotonous, boring, and whenever I’ve been engaged in a discussion with any of his advocates have found myself the object of contempt and scorn. The only thing I know that he has to say about people with emotional pain is that they need to be protected from people like me [unless I “convert” to his way of thinking]. I’m now an old man and feel no need to discuss Thomas Szasz any more. I think I already said that to you several times. As he says above, he didn’t want to talk with me either [or at least the me he thought I was].

  13.  
    Nick Stuart
    January 16, 2014 | 1:00 PM
     

    You think he is monotonous, boring…

    The only thing I KNOW that he has to say….

    Well what does he say? That emotional states suffered by human beings are not a medical disease unless proven otherwise. Do you agree?
    That he practised ‘existential psychotherapy’ but refused to believe this was a medical speciality. i.e not a pathalogical condition. It was a person discussing life with another person. Not a scientific medical speciality. Do you disagree? Why?
    You may be an old man… and so am I. You may not feel the need to discuss Socrates either… but I encourage discussion amongst the young and old alike.

  14.  
    Nick Stuart
    January 18, 2014 | 3:02 AM
     

    But thank you for the link which I have not read before. It further confirms my belief that Szasz was a genius and ahead of his time. For anyone interested, Szasz says these things http://en.wikiquote.org/wiki/Thomas_Szasz

    including….

    ‘The passion to interpret as madness that with which we disagree seems to have infected the best of contemporary minds.’

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