no longer a given…

Posted on Monday 27 January 2014

Well, I was on the road for the weekend and came back to find three posts about the Kupfer Affaire, each looking at a different piece of the puzzle:
Sandra lands on what I think is the central issue in this story:

But in the end, I decided that I had an obligation to use whatever platform I have to bring more attention to this issue. For me, one of the biggest problems we have in psychiatry is unacknowledged COI. Given the sensitive nature of the work we do, the power we can wield over people’s lives, the history of our improper relationships with Pharma – even if it turns out all rules were followed – that is not good enough. We should be above reproach.

At the level of Chairman of the DSM-5 Task Force, even the appearance of a Conflict of Interest is already a deal-breaker. To have an unacknowledged Conflict of Interest of this magnitude is simply too far over the line to be tolerated. The memo from the speaker of the Assembly is written as a report to the Board of Trustees of the American Psychiatric Association. It reached three conclusions:

[1] Dr. Kupfer should have disclosed to APA his interest in PAI in 2012. [2] Dr. Kupfer’s interest in PAI, which came after the decision had been made to include dimensional measures in DSM-5, did not influence DSM-5’s inclusion of dimensional measures for further study in Section 3. Interest in inclusion of these measures in DSM-5 began with conferences starting in 2003. [3] If and when PAI develops a commercial product with CAT, it will not have any greater advantage than the dozens of dimensional measures currently being marketed by others.
Conclusion [1] is correct. Conclusion [2] is indefensible. Dr. Kupfer pushed for inclusion of dimensional  measures as part of the main diagnostic system throughput the process of the revision. The inclusion in Section 3 was a wise decision by the trustees and a disappointment for Dr. Kupfer, but that’s an aside. The question of whether his unacknowledged Conflict of Interest had an impact on the product is important, but not the central point. Conclusion [3] is clearly unfounded, counter-intuitive, and deserves little comment. So that memo is little help to the Board of Trustees. The central issues are professional standards and trust, and the memo doesn’t address either.

There’s no way for the Trustees to avoid this revelation. Silence would be the worst choice because it speaks complicity or indifference. Defensiveness or minimization are the second worse choices. Of course there’s little that can be done to change the past, but they can certainly take action on what has happened and make policy that directly addresses future occurrences [and oversight in general]. This statement in the Memo needs to be proved, "The Board of Trustees and APA leadership take conflict-of-interest principles and guidelines very seriously." It is no longer a given…
Mickey @ 8:25 AM

testing 1 2 3…

Posted on Friday 24 January 2014

This isn’t really a post, it’s a test to see if a Nexus tablet with a Blue Tooth keyboard will actually work on the road. So far, so good. If you can see it, it means it made it to my server. 
UPDATE: Well thanks for the feedback.  It does work. I couldn’t resist looking up "bluetooth." from Wikipedia:
"The word ‘Bluetooth’ is an anglicized version of the Scandinavian Blåtand/Blåtann, (Old Norse blát?nn) the epithet of the tenth-century king Harald Bluetooth who united dissonant Danish tribes into a single kingdom, according to legend, introducing Christianity as well. The idea of this name was proposed in 1997 by Jim Kardach who developed a system that would allow mobile phones to communicate with computers. At the time of this proposal he was reading Frans Gunnar Bengtsson’s historical novel The Long Ships about Vikings and king Harald Bluetooth. The implication is that Bluetooth does the same with communications protocols, uniting them into one universal standard."
Mickey @ 7:10 AM

risky business…

Posted on Thursday 23 January 2014


Antidepressants and Suicide Attempts in Children
by William O. Cooper, S. Todd Callahan, Ayumi Shintani, D. Catherine Fuchs, Richard C. Shelton, Judith A. Dudley, Amy J. Graves, and Wayne A. Ray.
Pediatrics 2014 133:1–7.

OBJECTIVES: Recent data showing possible increased risk for suicidal behavior among children and adolescents treated with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) antidepressants have created significant concern among patients, families, and providers, including concerns about the risk of individual antidepressants. This study was designed to compare the risk for medically treated suicide attempts among new users of sertraline, paroxetine, citalopram, escitalopram, and venlafaxine to risk for new users of fluoxetine.
METHODS: A retrospective cohort study included 36842 children aged 6 to 18 years enrolled in Tennessee Medicaid between 1995 and 2006 who were new users of 1 of the antidepressant medications of interest (defined as filling no prescriptions for antidepressants in the preceding 365 days). Medically treated suicide attempts were identified from Medicaid files and vital records and confirmed with medical record review.
RESULTS: Four hundred nineteen cohort members had a medically treated suicide attempt with explicit or inferred attempt to die confirmed through medical record review, including 4 who completed suicide. The rate of confirmed suicide attempts for the study drugs ranged from 24.0 per 1000 person-years to 29.1 per 1000 person-years. The adjusted rate of suicide attempts did not differ significantly among current users of SSRI and SNRI antidepressants compared with current users of fluoxetine. Users of multiple antidepressants concomitantly had increased risk for suicide attempt.
CONCLUSIONS: In this population-based study of children recently initiating an antidepressant, there was no evidence that risk of suicide attempts differed for commonly prescribed SSRI and SNRI antidepressants.
In 2002, Prozac was approved by the FDA for use in children and adolescents. In 2004, the FDA held hearings about suicidality in adolescents on SSRIs and issued the black box warning we’re all familiar with:
And while everyone was trying to jump on the bandwagon in those days, Prozac made it through the FDA process before the warning was added:
They tried their dead level best to get Prozac exempted from the black box warning, but the FDA said nothing doing. So for all intents and purposes, the fact that Prozac is approved for use in adolescents is an artifact of timing.  Here, for comparison, is the FDA meta-analysis [FDA Hammonds Review, published full text on-line] and Kaizar’s extension [Do antidepressants cause suicidality in children? A Bayesian meta-analysis.]. This is from the latter listing all the clinical trials in youths used in the 2004 decision highlighted by yours truly [available on-line]:
The attempts to resolve the issue of an idiosyncratic syndrome in which some kids react to SSRIs with a dramatic syndrome that leads to violence by using statistical evaluations goes on and on. It has a life of its own and is never definitive. Does it happen? Yes. I’ve seen two cases and I believe my eyes. It apparently doesn’t happen frequently enough to make it into the record books. I rarely see a reaction to penicillin either, but it’s in my mind with every prescription. That’s all I know to say about that.

This study is at some level totally absurd, but it points up a glaring piece of craziness in the system we live with. It compares all of the SSRIs to Prozac and finds no difference. Any thought that there would be a difference is a testimony to leftover Eli Lilly advertisement trying to make something out of that artifact of timing. In spite of the FDA’s being unwilling to go along with Lilly, I’ve heard "Prozac is the only SSRI approved for use with adolescents" repeatedly – implying something the FDA never intended. FDA approval is never a treatment recommendation. The efficacy standards for the FDA are low as its primary mission is safety. But the drug companies have used FDA approval as a seal of approval beyond its intent – like some holy writ handed down from the Vatican.

So my alternative title for this article is simply Risky Business…
Mickey @ 8:31 PM

not a problem…

Posted on Thursday 23 January 2014

The trajectory of the DSM-5 revision was set in the book, A Research Agenda for the DSM-5, published in 2002 – a time of high hopes for a biomedical basis for psychiatric disorders. The plan was to include biomarkers in the manual and to add dimensional parameters that cut across disorders, getting around the imprecision of the categorical diagnostic entities. While the DSM-III and earlier revisions were widely used by clinicians, researchers were frustrated that neither the research tools nor the psychopharmacologic agents mapped to the defined criteria. In short, they were looking not to just revise the existing manual. They wanted to change it. The book was followed by an elaborate series of conferences, meetings, and presentations to shape the DSM-5 to fit that vision:
By the time They got underway and began the revision process, they were in a different place from where they started. The world had changed. There was an increasing awareness of the extent to which the pharmaceutical industry had invaded psychiatry and that edifice was crumbling. The fabled "pipeline" was headed for extinction. The dreams of a psychopharmacologic and neuroscientific future were met with the reality of scandal, adverse effects, limited efficacy, disappointing discovery, and a pharma bail-out.

The criticism seemed to come from an unusual direction, but in retrospect, it makes perfect sense that the people who had invested themselves in the DSMs and biological research were the ones who were looking. The watchdogs like Drs. Bernard Carroll and Bob Rubin began to look at some of the misbehavior in the publications filling our journals. Whistle-blowers like Allen Jones with TMAP and prosecuters like Elliot Spitzer in New York began to look at false claims and corruption. Civil suits for damages against the pharmaceutical industry became common. And then in 2007, Robert Spitzer who had shepherded the DSM-III and -IIIR focused attention on the DSM-5 process and its secrecy [confidentiality agreements]:
A MOMENT OF CRISIS IN THE HISTORY OF AMERICAN PSYCHIATRY
h-madness
by H.S. Decker
04/27/2010

The scenario started simply and privately in April 2007, five years before the revised manual was scheduled for publication.  Robert Spitzer, the psychiatrist who had headed the  APA’s Task Force that revised the association’s third diagnostic manual in 1980 [ DSM-III], dropped a two-line request to a colleague, Darrel Regier, Vice Chair of the Task Force that is currently updating the Association’s fifth manual [DSM-5].  Would it be possible for Regier to forward to him a copy of the minutes of the Task Force’s first two meetings? Regier answered Spitzer quickly, saying summary minutes would be available to individuals like him for private use, but asking him to wait until the APA Board of Trustees formally approved the membership of the Task Force.  After an interval, having received no minutes, Spitzer renewed his request.  But nine months passed before Regier gave Spitzer a definitive answer in February 2008: Due to “unprecedented” circumstances, including “confidentiality in the development process,” David Kupfer, Chair of the Task Force, and Regier had decided the minutes would be available only to the Board of Trustees and the Task Force itself…

In a letter to the editor, June 11, 2008, Spitzer began: “The June 6th issue of Psychiatric News brought the good news that the DSM-V process will be ‘complex but open.’”  And, he added, just a few weeks before, the outgoing president of the APA had stated that in the development of DSM-V the APA is committed to “transparency.” Then Spitzer expostulated:  “I found out how transparent and open the DSM-V process was when [Regier] informed me that he would not send me a copy of the minutes of DSM-V task force meetings … because the Board of Trustees believed it was important to ‘maintain DSM-V confidentially.’”  Spitzer then made available in his letter a paragraph from the Acceptance Form that all Task Force and Work Group members had signed stating that during their term of appointment and after, they would not “make accessible to anyone or use in any way any Confidential Information”…

Spitzer continued: “I didn’t know whether to laugh or cry.  Laugh – because there is no way Task Force and Work Group members can be made to refrain from discussing the developing DSM-V with their colleagues.  Cry – because” to revise a diagnostic manual in secrecy destroys the scientific process, “the very exchange of information that is prohibited by the confidentiality agreement”… Once galvanized into action, he began an unrelenting campaign against the “secrecy” of the fifth DSM revision process and urging “transparency,” soon forcing the APA to defend itself…
The APA did defend itself – but that was all it did. The Task Force remained a closed shop. Dr. Allen Frances, Chair of the DSM-IV Revision, had declined to join Spitzer’s earlier challenge. But in 2009, he too complained about the DSM-5 [A Warning Sign on the Road to DSM-V: Beware of Its Unintended Consequences]. This time the APA came out swinging with a condescending response that ended with an accusation that Frances was motivated by a COI [Setting the Record Straight: A Response to Frances Commentary on DSM-V]. And so it went for several years as others joined Dr. Frances challenges to both the process and content of the revision. The responses from the APA and the Task Force were often silence, defensive denial, or attacks. They hired a PR person who called Spitzer and Frances dangerous men. They set up a website DSMFacts that published regular refutations to criticisms or negative press. They were more polite to critics from outside psychiatry, but the shop doors remained closed, and they didn’t ever really engage their critics, just reiterated their given position.

Throughout the remaining revision process, the APA and DSM-5 Task Force maintained a "circled wagon" posture and continued along the path set out in 2002 – by this time an anachronism perhaps embraced inside their compound, but few other places. There were crises – having to abandon the planned biomedical additions, a remarkably bad showing in the field trials, widely publicized revolts by the other mental health professions. One such problem was the increasing focus on Conflicts of Interest in psychiatry – particularly at the upper levels. Senator Grassley’s investigations in 2008 brought Conflicts of Interest into more focus, and several chairmen of psychiatry were unseated. The president of the American Psychiatric Association at the time was on that list. What was more disturbing was that Grassley’s charges were of personal entrepreneurialism, failing to report personal outside income to their universities.

In a less publicized critique, Lisa Cosgrove and Harold J. Bursztajn followed Senator Grassley’s revelations with a challenge to the DSM-5 Task Force about COI among its members [see Toward Credible Conflict of Interest Policies in Clinical Psychiatry] and the response from the APA and DSM-5 Task Force was by this time predictable – not a problem. In 2012, Cosgrove and Krimsky published A Comparison of DSM-IV and DSM-5 Panel Members’ Financial Associations with Industry: A Pernicious Problem Persists documenting the DSM-5 Task Force members’ COI profiles. It was refuted by an article on DSMFacts [APA Refutes Secondary Analysis of DSM-5 Disclosures] – not a problem. That article says:
In assembling the DSM-5’s Task Force and Work Groups, the APA’s Board of Trustees developed an extensive process of written disclosure of potential conflicts of interest. These disclosures are required of all professionals who participate in the development of DSM-5. An independent APA committee reviews these disclosure documents, which are updated annually or whenever a member’s financial interests change.  Individuals are only permitted to serve on a work group or the Task Force if they are judged to have no significant financial interests.
Now the DSM-5 is in print, and we learn that Dr. Kupfer and other colleagues on the DSM-5 Task Force had an entrepreneurial Conflict of Interest of major import that was unreported throughout the period when they kept saying not a problem – admitted only after being exposed. So far, the APA has responded only with a memo from the Assembly Speaker that minimizes the impact and doesn’t address the real meaning of this revelation. As I said, it "reads more like a defense attorney’s closing argument than an impartial investigation." It’s another version of not a problem. The details are catalogued elsewhere [why?…, when?…, why? again…], but the facts are pretty damning – particularly since they are focused on one of our most vocal spokespersons for psychiatry at large. So I presumptuously wrote the Open Letter to the Board of Trustees and the Assembly of the American Psychiatric Association posted below.

While the Board of Trustees and the Assembly may look at the letter as detritus from the great unknown, I hope they take it seriously. The issue is much bigger than just the one on the table, and the reason for that is of their own making. We’ve literally had years of the APA minimizing, refuting, or ignoring what is now common knowledge – Conflicts of Interest have been an epidemic problem in psychiatry for years – at the top. This is no time for a terse internal blow off – another not a problem. It  is well beyond high time for the Trustees to take a stand that Conflicts of Interest will be taken as seriously as they should have been taken for years. And that the ethical standards for our leadership are the highest possible – not even the appearance of Conflicts of Interest. Our reputation has been indelibly tarnished already. It’s time for the Trustees to shed the damage control mentality of the past and turn this particular case over to an independent investigation, followed by an ethical renaissance that repositions us for the future. Dr. Lieberman began his presidency saying seize the moment. This is the moment that is crying out to be seized…
Mickey @ 1:07 PM

open letter to the APA…

Posted on Tuesday 21 January 2014


Open Letter to the Board of Trustees and the Assembly of the
American Psychiatric Association

January 21, 2014

It has been a dark time for psychiatry. Since the investigations of Senator Grassley exposed significant corruption and unseated three chairs of Psychiatry in 2008, there has been a series of disturbing exposures involving widespread ghost writing, guest authoring, and questionable clinical trial reporting; escalating widely publicized settlements by pharmaceutical companies involving psychoactive drugs and implicating prominent psychiatrists; charges of overmedication and entrepreneurialism; the drying up of the pharmaceutical pipeline; recurrent charges of ubiquitous Conflicts of Interest in high places; and an ongoing and divisive process that spanned the DSM-5 Revision process. Besides the gravity and frequency of the problems, their handling by the administrative levels in our specialty have played poorly in the eyes of the public and our currency is at an all time low.

The recent revelations of multiple unreported Conflicts of Interest by the Chair and other members of the DSM-5 Task Force threaten to throw gasoline on an already uncontrolled fire. The public memorandum from the Speaker of the Assembly, Dr. Mindy Young, reads more like a defense attorney’s closing argument than an impartial investigation, and is being viewed as a "whitewash" – threatening to add to our reputation of sweeping things under the rug rather than thoroughly exploring and dealing with charges of impropriety. It focuses on the concrete impact of their actions, but doesn’t address the more cogent issue of conduct unbecoming persons of high responsibility – people we entrust to make important decisions. Our specialty is in a steady decline, much of it our own making, and we don’t need to help it along by ignoring this obvious issue of integrity.

I have prepared below a Timeline of the major events in these revelations, with links to the salient documents involving Dr. Kupfer and his business associates. I have also provided a link to commentary by a respected weblog professional, Neuroskeptic. I ask you to read these materials carefully and appoint an outside panel that can review them independently. The Trustees approaching this issue with integrity, open-mindedness, and thoroughness will go a long way towards restoring our reputation as the ethical medical specialty that we need to be, and set a new precedent that Conflicts of Interest will be thoroughly pursued.

TIMELINE:

  Date Public   Submitted Accepted Published Disclosure
1 07/01/1993 Exactly what does the Hamilton Depression Rating Scale measure?
by Gibbons RD, Clark DC, and Kupfer DJ.
Journal of Psychiatric Research. 1993 27(3):259-273.
"… the HDRS total score is a weak index of depressive syndrome severity. The findings provide a benchmark by which the adequacy of future results may be judged, because the multidimensional IRT model does not suffer from the statistical limitations that arise when applying traditional factor analytic methods to discrete symptom ratings…"
2 2002-2010 COMPUTERIZED ADAPTIVE TESTING – DEPRESSION INVENTORY
NIMH Project MH066302
NIH RePORTER
"Total project funding amount for 9 projects is $4,958,346"
3 2002 A Research Agenda for DSM-V
edited by David J. Kupfer, Michael B. First, and Darrel A. Regier,
"DSM-IV and ICD-10 are both categorical classifications or typologies, and so were all their predecessors. In principle, though, variation in the symptomatology of mental disorder could be represented by a set of dimensions rather than by multiple categories…"
4 11/01/2005 Dimensional Models for Research and Diagnosis: A Current Dilemma
in Toward a Dimensionally Based Taxonomy of Psychopathology
by Kupfer, David
Journal of Abnormal Psychology. 2005 114[4]:557-559.
"Ultimately, new methodological strategies need to be incorporated that address both categorical and dimensional aspects of the overall diagnostic framework. These refinements will be vital in determining the extent and reality of co-occurrence of disorder and the determination of boundaries across specific disorders."
5 04/01/2006 Kupfer appointed chair DSM-5 Task Force
6 04/01/2008 Using Computerized Adaptive Testing to Reduce the Burden of Mental Health Assessment
by Robert D. Gibbons, David J. Weiss, David J. Kupfer, Ellen Frank, et al
Psychiatric Services 2008 59:361–368.
"Instead of using small fixed-length tests, clinicians can create item banks with a large item pool, and a small set of the items most relevant for a given individual can be administered with no loss of information, yielding a dramatic reduction in administration time and patient and clinician burden."
7 03/27/2009 Dr. Jane Costello resigns from the DSM-5 Child and Adolescent Disorders workgroup. In her letter of resignation, she said:
"…The tipping point for me was the memo from David and Darrell on February 18, 2009, stating “Thus, we have decided that one if not the major difference between DSM-IV and DSM-V will be the more prominent use of dimensional measures inDSM-V”, and going on to introduce an Instrument Assessment Study Group that will advise workgroups on the choice of old scale measures or the creation of new ones."
8  unk Drs. Robert Gibbons and Paul Pilkonis appointed as Expert Advisors to the Instrument Assessment Study Group
9 11/29/2011 Psychiatric Assessments Inc. incorporated in Delaware [enter File #5072041].
10 01/23/2012 Psychiatric Assessments Inc. incorporated in Illinois [enter File #68256313].
11 08/31/2012 Yehuda Cohen, a professional management executive, registers Adaptive Testing Technologies website. Mr. Cohen is featured as a principal on the corporate website. .
12 10/23/2012 Privacy Policy posted on the website.
13 11/01/2012 Development of a computerized adaptive test for depression.
by Gibbons, Weiss, Pilkonis, Frank, Moore, Kim, and Kupfer.
Archives of General Psychiatry. 2012 69[11]:1104-12.
"Traditional measurement fixes the number of items administered and allows measurement uncertainty to vary. In contrast, a CAT fixes measurement uncertainty and allows the number of items to vary. The result is a significant reduction in the number of items needed to measure depression and increased precision of measurement."
    Publication [CAT-DI] 08/19/2011 01/04/2012 11/01/2012 no
14 12/01/2012 DSM-5 approved by the APA Trustees.
"Cross-Cutting Dimensions" moved to Section III [Emerging Measures and Models].
15 02/25/2013 The Future Arrived
by David J. Kupfer; Emily A. Kuhl; Darrel A. Regier.
JAMA. 2013 309[16]:1691-1692.
"The next revision of psychiatry’s Diagnostic and Statistical Manual of Mental Disorders [DSM-5] will be published in May 2013 and is the first revision of this psychiatric nomenclature in almost 2 decades…"
    Publication [DSM-5]     02/25/2013 no
16 03/02/2013 Dr. Kupfer’s lecture to ACP Virginia
by David J. Kupfer
Dr. Kupfer’s lecture to ACP Virginia promoting the Dimensional Measures in DSM-5 [see slides 8, 17, 32, 34, & 36]. No disclosure of PAI/ATT.
    Presentation [slides]     03/02/2013 no
17 05/18/2013 DSM-5 Published.
18 07/01/2013 Computerized Adaptive Test–Depression Inventory Not Ready for Prime Time
by Bernard Carroll
JAMA Psychiatry. 2013 70[7]:763.
"The goal of commercial development seems premature; patients risk being “assayed” against a non–gold standard. Though CAT-DI may have been an interesting statistical challenge, it lacks a solid clinimetric grounding. It is not ready for clinical use…"
    Publication [letter] 11/19/2012 11/26/2012 07/01/2013 yes
19 07/01/2013 Computerized Adaptive Test–Depression Inventory Not Ready for Prime Time: In Reply
by Gibbons, Weiss, Pilkonis, Frank, Moore, Kim, and Kupfer
JAMA Psychiatry. 2013 70[7]:763-765
"In this case, it is Carroll who has the overwhelming conflict of interest.As developer,owner,and marketer of the Carroll Depression Scale–Revised, a traditional fixed-length test, it is not surprising that the paradigm shift described in our article would be of serious concern to him."
    Publication [reply]     07/01/2013 no
20 07/01/2013 The Computerized Adaptive Diagnostic Test for Major Depressive Disorder [CAD-MDD]: A Screening Tool for Depression
by Gibbons, Hooker, Finkelman, Weiss, Pilkonis, Frank, Moore, and Kupfer.
Journal of Clinical Psychiatry. 2013 74[7]:669–674.
"Inexpensive [relative to clinical assessment], efficient, and accurate screening of depression in the settings of primary care, psychiatric epidemiology, molecular genetics, and global health are all direct applications of the current system."
    Publication [CAD-MDD] 12/20/2012 04/05/2013 07/01/2013 yes
21 08/09/2013 Development of the CAT-ANX: A Computerized Adaptive Test for Anxiety
by Gibbons, Weiss, Pilkonis, Frank, Moore, Kim, and Kupfer.
American Journal of Psychiatry. published on-line Aug 9, 2013
"Potential applications for inexpensive, efficient, and accurate screening of anxiety in primary care settings, clinical trials, psychiatric epidemiology, molecular genetics, children, and other cultures are discussed."
    Publication [CAT-ANX] 02/08/2013 05/06/2013 08/09/2013 yes
22 08/20/2013 Dr. Carroll’s letter to JAMA Psychiatry
This letter was provided by Dr. Carroll at my request – 1boringoldman
    [letter] 08/20/2013 rejected unpublished yes
23 10/09/2013 The Future of Mental Health Diagnostic Screening [click on page 4]
PsychsTalk Blog: CME Institute
by Robert Gibbons, Ellen Frank, and David Kupfer.
"… The CAD-MDD and related CAT-DI and CAT-ANX share goals similar to those of the new version of DSM: they seek to improve screening and assessment of mental health disorders in a number of ways for patients, clinicians, and caregivers, including decreasing clinician and patient burden. The third section of DSM-5 is aimed at providing tools for cross-cutting and dimensional assessment, often involving patient-reported outcomes. The electronic version of the DSM-5 will allow for the development and application of many more scales and certainly better possibilities for tracking change and the effectiveness of treatment. Another objective of DSM-5 is to improve the interface with the rest of medicine, especially primary care…"
    Publication [CME]     10/09/2013 yes
24 11/20/2013 Failure to Report Financial Disclosure Information
by Gibbons, Weiss, Pilkonis, Frank, and Kupfer.
JAMA Psychiatry. 2013 71[1]:95.
"To the Editor We apologize to the editors and readers of JAMA Psychiatry for our failure to fully disclose our financial interests in an article that reported a diagnostic tool, the Computerized Adaptive Test for Depression [CAT-DI]… Lead author Robert D. Gibbons, PhD, is the president and founder of PAI, which was incorporated in Delaware in late 2011, then registered to do business in Illinois in January 2012. Dr Gibbons awarded “founder’s shares in PAI” to us, yet all 5 of us failed to report our financial interests in connection with our article and again in a Reply to Letters to the Editor regarding the article… Our submitted disclosure lacked transparency, and we regret our omission."
25 11/21/2013 When is Disclosure Not Disclosure?
Healthcare Renewal
by Bernard Carroll
"Here is a case study in conflict of interest [COI]. A remarkable confession has just appeared by a group of 5 prominent academics, writing in the journal JAMA Psychiatry. Having been outed to the Editors, they now admit to concealing pertinent financial information. One of the five is David J. Kupfer, MD, chairman of the DSM-5 Task Force and past chairman of the department of psychiatry at The University of Pittsburgh…"
26 12/23/2013 DSM-5 – Dimensional Diagnoses – More Conflicts of Interest?
Behaviorism and Mental Health
by Phil Hickey
"… why hasn’t Dr. Kupfer issued some kind of explanation for the lack of transparency? The JAMA Psychiatry letter of apology was just a stark statement of fact, which leaves a huge cloud of doubt not only over Dr. Kupfer, but also over DSM-5 and psychiatry generally…"
27 01/14/2014 Mindy Young, MD, Speaker
Memo to APA Assembly members
APA Newsroom
"Dr. Kupfer should have disclosed to APA his interest in PAI in 2012. Dr. Kupfer’s interest in PAI, which came after the decision had been made to include dimensional measures in DSM-5, did not influence DSM-5’s inclusion of dimensional measures for further study in Section 3. Interest in inclusion of these measures in DSM-5 began with conferences starting in 2003. If and when PAI develops a commercial product with CAT, it will not have any greater advantage than the dozens of dimensional measures currently being marketed by others."
Mickey @ 3:35 PM

why? again…

Posted on Sunday 19 January 2014

in this post, the footnotes [x] are keyed to the now numbered items in the earlier post when?… to cut down on the ground clutter…

The revelation of a closely held secret like Dr. Kupfer et al’s undeclared Conflict of Interest is like an embarrassing slip of the tongue – its meaning is immediately apparent. After a stammer, the usual first reaction is an attempt at damage control – like their published apology [24] without acknowledging that it was a response to being discovered [22, 25]. The next line of defense is to either deny that the impropriety in question did any harm, or say that it didn’t mean what it seems to mean. In this case, that came in the form of a memo from the Speaker of the Assembly of the APA, Dr. Mindy Young, to the APA Trustees [27]. Says Neuroskeptic [Psychiatrists From Another Dimension (Part 1)]:
Kupfer was actually put up before the APA’s version of a Congressional Committee, the Assembly of the APA, for this. And now, in a letter dated last week, the APA decided that he was wrong to fail to disclose a CoI:
    We believe that Drs. Kupfer, Frank and Gibbons should have disclosed their interest in PAI on APA’s conflict of interest form in 2012, and they did not do so. Dr. Kupfer did include his stock ownership in PAI on his April 2013 disclosure…
But the APA went on to say that the DSM-5′s dimensional turn was not influenced by commercial interests:
    Use of dimensional measures dates back to the 1960s… from 2003 there were entire conferences dedicated to exploring the use of dimensional measures in DSM-5. The dimensional measures used in field testing were selected by the end of 2010 – over a year before PAI was formed. Drs. Kupfer, Gibbons, and Frank did not advocate for inclusion of CAT in DSM-5.
Such is the APA’s retrospective. They then turn their hand to fortune-telling, and predict that
    PAI will not gain financially from DSM-5’s inclusion of dimensional measures in Section 3 or if CAT is included in future versions of DSM.
    If and when PAI develops a commercial product with CAT, it will not have any greater advantage because of DSM-5’s inclusion of dimensional measures in Section 3 than the dozens of dimensional measures currently being marketed by others.
I would be less forgiving here. There’s no grounding for either the fortune-telling or the predicting. Besides the obvious breach of ethics and integrity, this is the central problem with an undeclared Conflict of Interest. Its impact is impossible to evaluate when it’s revealed after the fact. Dr. Young has no basis for saying that their planned commercial enterprise had no impact on the DSM-5’s preoccupation with dimensional measures or that the NIMH funded, DSM-5 Chairman endorsed, CAT has no leg up on its competitors. In either case, these are her speculations. The APA she represents has a huge Conflict of Interest in that the now published DSM-5 is the cash cow extraordinaire in a time of famine as well as an important symbol. I would be in the same position if I said the opposite. Neither position can ever leave the realm of speculation. That’s why we insist on a priori declarations of Conflicts of Interest – a standard known and supported by Dr. Kupfer himself. He well knows the power of an accusation of Conflict of Interest, having exerted it himself in the initial response to Dr. Carroll’s criticism  [19] and in his response to Dr. Allen Frances in 2009 [Setting the Record Straight: A Response to Frances Commentary on DSM-V]. Speaking of setting the record straight, there are several points in Dr. Young’s letter [27] that deserve a response:

  • "The stock interest in PAI did not influence DSM-5’s move toward dimensional measures."
    That’s backwards for one thing. The allegation is that the company was capitalizing on the DSM-5’s move towards dimensional measures and may have, in turn, fueled some of that advocacy.
  • "Their work on CAT was well known to the DSM-5 Instrument Study Group because of the NIMH grant and their publications, but it was not considered viable for DSM-5 because of its complexity and immaturity."
    In the time frame she’s discussing, there were no publications about the CAT-anything. The first one came a month before the Trustee’s final approval [13]. If the CAT was not considered viable, that means that it was considered, ergo it had to have been brought up to the the DSM-5 Instrument Study Group for consideratio.
  • "… And, before the DSM-5 Task Force was formed, beginning in 2003, there were entire conferences dedicated to exploring the use of dimensional measures in DSM-5."
    … in response to Dr. Kupfer’s continuous strong advocacy of the dimensional measures [1, 3, 4].
  • "PAI will not gain financially from DSM-5’s inclusion of dimensional measures in Section 3 or if CAT is included in future versions of DSM."
    But by virtue of being developed by the NIMH, by being advertised in major peer-reviewed journals in academic articles, and by having the Chair of the DSM-5 Task Force behind it, it has an enormous competitive advantage.
  • "Drs. Gibbons, Frank and Kupfer disclosed their interest in PAI publicly in AJP before disclosing it in JAMA Psychiatry."
    The disclosure in a submitted but unpublished article prior to incorporation is a forced argument. They didn’t tell us about it. It’s an off-point legalistic argument.

Those are just a few of the arguments about parts of the letter, but they’re included only to say that the letter feels like the closing argument for a defense lawyer, not a thoughtful exploration of the obvious important issues engendered here. Surely this is not intended to be the APA’s final review of this affair. The Board of Trustees has both a need and an obligation to investigate with an unbiased panel. Their decision here will be a much needed precedent for future issues involving Conflicts of Interest in the APA. Likewise, the NIMH has a similar obligation to look into the use of NIMH Grant money to develop this commercial product. Is it even the author’s product to sell? And what about Dr. Gibbons’ current project? Is he doing it again [what!…]?

In medical school, we’re taught to begin every part of a physical exam with inspection. Look at the ear before poking in an otoscope. Look at the chest and breathing before listening with a stethoscope. And that’s good advice about looking at this timeline before getting lost in its details. Every article from the first one in 1993 to the most recent one reads like these tests are designed as commercial products [1, 6, 13, 20, 21]. They’re not better psychometrics. The question is still out on whether they’re as good as [I think Neuroskeptic plans to weigh in on that in his (Part 2)]. But they are quicker and easier. Dr. Kupfer’s enthusiasm for dimensional measurements pervades his commentaries [3, 4, 15, 16]. In Dr. Costello’s resignation, she quotes him as saying, "Thus, we have decided that one if not the major difference between DSM-IV and DSM-V will be the more prominent use of dimensional measures in DSM-V" [7]. He was still at it when the DSM-5 was released [Section III of New Manual Looks to Future]. And if there’s any question about the link between the CAT tests and dimensional measurement, read the PsycsTalk article [23 click page 4]. While there may have been a disclosure in a file drawer at the AJP and an April 2013 disclosure in some APA office, there was no public disclosure of a Conflict of Interest until after they knew of Dr, Carroll’s letter to JAMA Psychiatry [22], after the DSM-5 was in print. And there were several places where it could’ve should’ve been mentioned [15, 16, 19].

And of course the biggest question of all is why?…, why all the secrecy? It’s the one Dr. Young avoids. And it’s the one I started with, and I still think is the most important thing on the table…
Mickey @ 6:25 PM

what!…

Posted on Sunday 19 January 2014

Fool me once, shame on you.
Fool me twice, shame on me!

One subplot of the story detailed in when?… is the NIMH funding issue. In essence, the NIMH paid Dr. Gibbons around $5 M between 2002 and 2010 to develop his Computerized Adaptive Tests, some of which went for subcontracting with Dr. Kupfer’s Department of Psychiatry in Pittsburgh for the clinical testing.  And then they formed a company to market their test as a commercial product as soon as the grant ran out [Gibbons, Kupfer, Frank, and Pilkonis]. I can’t see any way to look at that other than the NIMH providing the start-up capital for their entrepreneurial enterprise. Plus there’s the value-added ticket to the academic journals as a way of advertising their product. I guess we could throw in having the Chair of the DSM-5 Task Force listed as one of Our People as more value-added:


[from the NIH RePORTER]

That doesn’t seem right to me. But, there’s more! He’s doing it again!
Project Number: 1R01MH100155-01
Contact PI / Project Leader: GIBBONS, ROBERT D
Awardee Organization: UNIVERSITY OF CHICAGO
Title: A NEW STATISTICAL PARADIGM FOR MEASURING PSYCHOPATHOLOGY DIMENSIONS IN YOUTH DESCRIPTION:
We propose to develop, test, and apply a new computerized adaptive testing approach to measuring severity of depression, anxiety, mania, disruptive behavior, and attention-deficit/hyperactivity disorders in children and adolescents (9-17 years). This proposal contributes both methodologically and scientifically to research on the assessment of pediatric psychopathology. The proposed work will advance mental health research and improve psychiatric screening and monitoring in primary care. The methodological work proposed in this application is driven by a fundamental scientific challenge that has limited progress in measuring psychopathology in pediatric populations. We need to understand how the measurement of psychopathology in youth changes from childhood through adolescence. Our proposed work includes new statistical methodology for a Computerized Adaptive Test (CAT) based on multidimensional Item Response Theory (IRT) that allows us to tailor the measurement process to each child’s developmental level (vertical scaling). The overarching aim of this application is to develop a CAT for children and adolescents that achieves the following goals…
hat tip to jamzo…   
It’s another NIMH Grant that looks to be for 5 years that started in May 2013. They’ve already collected almost a million dollars to develop CAT tests for childhood psychiatric conditions – things like "major depressive disorder (MDD), ADHD, oppositional defiant disorder (ODD), conduct disorder (CD), anxiety disorders (AD; generalized anxiety disorder, separation anxiety disorder, social phobia, specific phobia), and bipolar disorder (BD)." Little question in my mind that the NIMH is either wittingly or unwittingly funding yet another start-up for Dr. Gibbons and his associates to add to their commercial endeavor:
I wonder if PAI [Psychiatric Assessments Inc] or ATT [Adaptive Testing Technologies] were declared in the application for this NIMH grant? or if there were any discussions about what would come of these tests? Like the tests in the last post, it would seem to me like if the taxpayers are paying for their development, they ought to remain in the public domain rather than feeding the grant recipient’s private company…
Mickey @ 8:00 AM

when?…

Posted on Saturday 18 January 2014

Back in November 2012 when I read the first of these Computerized Adaptive Test papers, I noted that it ended with:
Funding/Support: This work was supported by grant R01-MH66302 from the National Institute of Mental Health…
Additional Information: The CAT-DI will ultimately be made available for routine administration, and its development as a commercial product is under consideration…

and registered a blip, but I didn’t have any idea the story would become so complex and convoluted. Here’s my blog log as I’ve tried to follow it:

11/09/2012    really?…
08/12/2013    a road to nowhere…
11/21/2013    careful watching…
12/29/2013    insider trading…
01/03/2014    DSM-5 retrospective I…
 		01/03/2014    DSM-5 retrospective II…
01/03/2014    DSM-5 retrospective III…
01/06/2014    royalty? …
01/11/2014    top down problem…
01/16/2014    why?…

My last post [why? …] was a transcript of an APA Memo in response to the revelation that the authors had not declared significant Conflicts of Interest while they were involved with the DSM-5 Task Force. I found that Memo way off point and started jotting down a timeline to organize my response, and that’s where yesterday went. So here’s my timeline for your perusal. I’ve thrown in a few short quotes from the selections, but the links connect to the real material. Rather than jump in with my thoughts, I’ve put it here for you read through yourself while I think about it too. It tells the story all by itself…

  Date Public   Submitted Accepted Published Disclosure
1 07/01/1993 Exactly what does the Hamilton Depression Rating Scale measure?
by Gibbons RD, Clark DC, and Kupfer DJ.
Journal of Psychiatric Research. 1993 27(3):259-273.
"… the HDRS total score is a weak index of depressive syndrome severity. The findings provide a benchmark by which the adequacy of future results may be judged, because the multidimensional IRT model does not suffer from the statistical limitations that arise when applying traditional factor analytic methods to discrete symptom ratings…"
2 2002-2010 COMPUTERIZED ADAPTIVE TESTING – DEPRESSION INVENTORY
NIMH Project MH066302
NIH RePORTER
"Total project funding amount for 9 projects is $4,958,346"
3 2002 A Research Agenda for DSM-V
edited by David J. Kupfer, Michael B. First, and Darrel A. Regier,
"DSM-IV and ICD-10 are both categorical classifications or typologies, and so were all their predecessors. In principle, though, variation in the symptomatology of mental disorder could be represented by a set of dimensions rather than by multiple categories…"
4 11/01/2005 Dimensional Models for Research and Diagnosis: A Current Dilemma
in Toward a Dimensionally Based Taxonomy of Psychopathology
by Kupfer, David
Journal of Abnormal Psychology. 2005 114[4]:557-559.
"Ultimately, new methodological strategies need to be incorporated that address both categorical and dimensional aspects of the overall diagnostic framework. These refinements will be vital in determining the extent and reality of co-occurrence of disorder and the determination of boundaries across specific disorders."
5 04/01/2006 Kupfer appointed chair DSM-5 Task Force
6 04/01/2008 Using Computerized Adaptive Testing to Reduce the Burden of Mental Health Assessment
by Robert D. Gibbons, David J. Weiss, David J. Kupfer, Ellen Frank, et al
Psychiatric Services 2008 59:361–368.
"Instead of using small fixed-length tests, clinicians can create item banks with a large item pool, and a small set of the items most relevant for a given individual can be administered with no loss of information, yielding a dramatic reduction in administration time and patient and clinician burden."
7 03/27/2009 Dr. Jane Costello resigns from the DSM-5 Child and Adolescent Disorders workgroup. In her letter of resignation, she said:
"…The tipping point for me was the memo from David and Darrell on February 18, 2009, stating “Thus, we have decided that one if not the major difference between DSM-IV and DSM-V will be the more prominent use of dimensional measures inDSM-V”, and going on to introduce an Instrument Assessment Study Group that will advise workgroups on the choice of old scale measures or the creation of new ones."
8  unk Drs. Robert Gibbons and Paul Pilkonis appointed as Expert Advisors to the Instrument Assessment Study Group
9 11/29/2011 Psychiatric Assessments Inc. incorporated in Delaware [enter File #5072041].
10 01/23/2012 Psychiatric Assessments Inc. incorporated in Illinois [enter File #68256313].
11 08/31/2012 Yehuda Cohen, a professional management executive, registers Adaptive Testing Technologies website. Mr. Cohen is featured as a principal on the corporate website. .
12 10/23/2012 Privacy Policy posted on the website.
13 11/01/2012 Development of a computerized adaptive test for depression.
by Gibbons, Weiss, Pilkonis, Frank, Moore, Kim, and Kupfer.
Archives of General Psychiatry. 2012 69[11]:1104-12.
"Traditional measurement fixes the number of items administered and allows measurement uncertainty to vary. In contrast, a CAT fixes measurement uncertainty and allows the number of items to vary. The result is a significant reduction in the number of items needed to measure depression and increased precision of measurement."
    Publication [CAT-DI] 08/19/2011 01/04/2012 11/01/2012 no
14 12/01/2012 DSM-5 approved by the APA Trustees.
"Cross-Cutting Dimensions" moved to Section III [Emerging Measures and Models].
15 02/25/2013 The Future Arrived
by David J. Kupfer; Emily A. Kuhl; Darrel A. Regier.
JAMA. 2013 309[16]:1691-1692.
"The next revision of psychiatry’s Diagnostic and Statistical Manual of Mental Disorders [DSM-5] will be published in May 2013 and is the first revision of this psychiatric nomenclature in almost 2 decades…"
    Publication [DSM-5]     02/25/2013 no
16 03/02/2013 Dr. Kupfer’s lecture to ACP Virginia
by David J. Kupfer
Dr. Kupfer’s lecture to ACP Virginia promoting the Dimensional Measures in DSM-5 [see slides 8, 17, 32, 34, & 36]. No disclosure of PAI/ATT.
    Presentation [slides]     03/02/2013 no
17 05/18/2013 DSM-5 Published.
18 07/01/2013 Computerized Adaptive Test–Depression Inventory Not Ready for Prime Time
by Bernard Carroll
JAMA Psychiatry. 2013 70[7]:763.
"The goal of commercial development seems premature; patients risk being “assayed” against a non–gold standard. Though CAT-DI may have been an interesting statistical challenge, it lacks a solid clinimetric grounding. It is not ready for clinical use…"
    Publication [letter] 11/19/2012 11/26/2012 07/01/2013 yes
19 07/01/2013 Computerized Adaptive Test–Depression Inventory Not Ready for Prime Time: In Reply
by Gibbons, Weiss, Pilkonis, Frank, Moore, Kim, and Kupfer
JAMA Psychiatry. 2013 70[7]:763-765
"In this case, it is Carroll who has theoverwhelming conflict of interest.As developer,owner,and marketer of the Carroll Depression Scale–Revised, a traditional fixed-length test, it is not surprising that the paradigm shift described in our article would be of serious concern to him."
    Publication [reply]     07/01/2013 no
20 07/01/2013 The Computerized Adaptive Diagnostic Test for Major Depressive Disorder [CAD-MDD]: A Screening Tool for Depression
by Gibbons, Hooker, Finkelman, Weiss, Pilkonis, Frank, Moore, and Kupfer.
Journal of Clinical Psychiatry. 2013 74[7]:669–674.
"Inexpensive [relative to clinical assessment], efficient, and accurate screening of depression in the settings of primary care, psychiatric epidemiology, molecular genetics, and global health are all direct applications of the current system."
    Publication [CAD-MDD] 12/20/2012 04/05/2013 07/01/2013 yes
21 08/09/2013 Development of the CAT-ANX: A Computerized Adaptive Test for Anxiety
by Gibbons, Weiss, Pilkonis, Frank, Moore, Kim, and Kupfer.
American Journal of Psychiatry. published on-line Aug 9, 2013
"Potential applications for inexpensive, efficient, and accurate screening of anxiety in primary care settings, clinical trials, psychiatric epidemiology, molecular genetics, children, and other cultures are discussed."
    Publication [CAT-ANX] 02/08/2013 05/06/2013 08/09/2013 yes
22 08/20/2013 Dr. Carroll’s letter to JAMA Psychiatry
This letter was provided by Dr. Carroll at my request – 1boringoldman
    [letter] 08/20/2013 rejected unpublished yes
23 10/09/2013 The Future of Mental Health Diagnostic Screening [click on page 4]
PsychsTalk Blog: CME Institute
by Robert Gibbons, Ellen Frank, and David Kupfer.
"… The CAD-MDD and related CAT-DI and CAT-ANX share goals similar to those of the new version of DSM: they seek to improve screening and assessment of mental health disorders in a number of ways for patients, clinicians, and caregivers, including decreasing clinician and patient burden. The third section of DSM-5 is aimed at providing tools for cross-cutting and dimensional assessment, often involving patient-reported outcomes. The electronic version of the DSM-5 will allow for the development and application of many more scales and certainly better possibilities for tracking change and the effectiveness of treatment. Another objective of DSM-5 is to improve the interface with the rest of medicine, especially primary care…"
    Publication [CME]     10/09/2013 yes
24 11/20/2013 Failure to Report Financial Disclosure Information
by Gibbons, Weiss, Pilkonis, Frank, and Kupfer.
JAMA Psychiatry. 2013 71[1]:95.
"To the Editor We apologize to the editors and readers of JAMA Psychiatry for our failure to fully disclose our financial interests in an article that reported a diagnostic tool, the Computerized Adaptive Test for Depression [CAT-DI]… Lead author Robert D. Gibbons, PhD, is the president and founder of PAI, which was incorporated in Delaware in late 2011, then registered to do business in Illinois in January 2012. Dr Gibbons awarded “founder’s shares in PAI” to us, yet all 5 of us failed to report our financial interests in connection with our article and again in a Reply to Letters to the Editor regarding the article… Our submitted disclosure lacked transparency, and we regret our omission."
25 11/21/2013 When is Disclosure Not Disclosure?
Healthcare Renewal
by Bernard Carroll
"Here is a case study in conflict of interest [COI]. A remarkable confession has just appeared by a group of 5 prominent academics, writing in the journal JAMA Psychiatry. Having been outed to the Editors, they now admit to concealing pertinent financial information. One of the five is David J. Kupfer, MD, chairman of the DSM-5 Task Force and past chairman of the department of psychiatry at The University of Pittsburgh…"
26 12/23/2013 DSM-5 – Dimensional Diagnoses – More Conflicts of Interest?
Behaviorism and Mental Health
by Phil Hickey
"… why hasn’t Dr. Kupfer issued some kind of explanation for the lack of transparency? The JAMA Psychiatry letter of apology was just a stark statement of fact, which leaves a huge cloud of doubt not only over Dr. Kupfer, but also over DSM-5 and psychiatry generally…"
27 01/14/2014 Mindy Young, MD, Speaker
Memo to APA Assembly members
APA Newsroom
"Dr. Kupfer should have disclosed to APA his interest in PAI in 2012. Dr. Kupfer’s interest in PAI, which came after the decision had been made to include dimensional measures in DSM-5, did not influence DSM-5’s inclusion of dimensional measures for further study in Section 3. Interest in inclusion of these measures in DSM-5 began with conferences starting in 2003. If and when PAI develops a commercial product with CAT, it will not have any greater advantage than the dozens of dimensional measures currently being marketed by others."
Mickey @ 8:00 AM

why?…

Posted on Thursday 16 January 2014

What follows is a letter to the APA Assembly members that appeared on the APA website on Tuesday. I’ve posted it below for your perusal. It’s so far off the mark that it’s hard for me to respond to so I’ll defer that for the moment and stick to what it doesn’t do.

For the extent of his tenure as Chair of the DSM-5 Task Force, Dr. Kupfer, his wife Dr. Ellen Frank [a member of his Pittsburg faculty and the DSM-5 Mood Disorders Group], and another of his University of Pittsburg faculty, Dr. Paul Pilkonis [a consultant to the DSM-5 Instrument Assessment Study Group] have collaborated with Dr. Robert Gibbons [also a consultant to the DSM-5 Instrument Assessment Study Group] to develop Computerized Adaptive Tests that measure "dimensions" [anxiety and depression]. Both before and during the Revision process, Dr. Kupfer has strongly advocated for including "dimensions" in the DSM-5 classifications. The "dimensions" were only removed from the manual proper to Section 3 [further study] in the final approval meeting of the Board of Trustees in December 2012. The tests developed have been officially a commercial product since at least November 2011 [with Gibbons, Kupfer, Frank, and Pilkonis as stockholders]. None of the principles [Kupfer, Frank, Gibbons, or Pilkonis] declared this clear COI publicly until after the DSM-5 had gone to press in December 2012. And it wasn’t common knowledge until July 2013 when it was discovered after they accused a critic of a COI [which had, in fact, been declared].

The letter below plays around legalistically with the timeline and the details, but completely ignores the most obvious of points. Why was this multifaceted tangle of Conflicts of Interest kept secret until the DSM-5 process was ended? Why did Dr. Kupfer who repeatedly defended the DSM-5 Task Force’s transparency not declare this one? How could Dr. Kupfer in good conscience, participate in writing letters to Dr. Allen Frances and recently to Dr. Bernard Carroll accusing them of COI when he was sitting on this? I suppose there’s a further question. Is this letter the APA’s final investigation of this story? Is there no higher standard for someone with a position at this high level? While there a number of inaccuracies in this letter, the failure to even address the central issue here is beyond disturbing.

January 14, 2014


Dear Assembly Members,
I was recently made aware of a conflict of interest disclosure issue involving Dr. David Kupfer and his ownership interest in a company called Psychiatric Assessments, Inc. [PAI]. Upon receipt of this information, I took the matter to the Board of Trustees. The Board of Trustees and APA leadership take conflict-of-interest principles and guidelines very seriously. They instructed APA staff to review the matter and report back their findings. Below is a summary of the situation with APA’s findings.
Sincerely,   
Mindy Young, MD
Speaker of the Assembly
American Psychiatric Association
BACKGROUND

    Dr. Bernard Carroll and others in recent blog postings and listserv conversations questioned:
    1. whether Dr. Kupfer’s ownership interest in a company called Psychiatric Assessments, Inc. or PAI, was disclosed to APA;
    2. whether that PAI interest influenced the DSM-5’s decision to include dimensional measures in Section 3 for further study; and
    3. whether DSM-5’s inclusion of dimensional measures gives any product PAI may create a more favorable commercial advantage because of Dr. Kupfer’s role as chair of the DSM-5 Task Force. We also reviewed disclosures in the American Journal of Psychiatry [“AJP”] and JAMA Psychiatry.
    From 2002-2011, Dr. Kupfer, Dr. Frank, and Dr. Gibbons and several others, who were not involved in DSM-5, worked on an NIMH grant to create Computer Adaptive Tests [CAT] based on multidimensional response theory. Dr. Gibbons was the principal investigator and subcontracted with the University of Pittsburgh on the grant. Drs. Kupfer and Frank worked on the grant through the University of Pittsburgh. This grant resulted in several tests being developed. In November 2011, Dr. Gibbons formed a company, PAI and on January 3, 2012, Dr. Gibbons gave a 5% interest each to four people involved in the NIMH grant, including Drs. Kupfer and Frank, who are spouses. Dr. Ellen Frank was a Member of the Mood Disorders Work Group, and Robert Gibbons, PhD was an advisor to the Diagnostic Assessment Instruments Study Group for DSM-5. After reviewing the blog and listserv postings, interviewing people involved with instrument selection for DSM, reviewing the literature, internal documents relating to DSM-5’s recommendations on dimensional measures, and conflict of interest policies and disclosures, APA has drawn the following conclusions:

FINDINGS

  1. APA’s conflict of interest forms called for disclosure of any financial interest, including stock ownership, in any company related to the field of psychiatry.
      We believe that Drs. Kupfer, Frank and Gibbons should have disclosed their interest in PAI on APA’s conflict of interest form in 2012, and they did not do so. Dr. Kupfer did include his stock ownership in PAI on his April 2013 disclosure. Even though PAI has no product or revenue, and never has had a product or revenue, it is a company related to psychiatry and the stock interest should have been disclosed.
  2. The stock interest in PAI did not influence DSM-5’s move toward dimensional measures.
      Use of dimensional measures dates back to the 1960s and the Hamilton Depression Scale. The Patient Health Questionnaire-9 [PHQ-9] scale was developed for DSM-III’s diagnosis of major depressive disorder by Dr. Spitzer and his colleagues. DSM-IV, released in 1994, discussed the benefits of dimensional measures. And, before the DSM-5 Task Force was formed, beginning in 2003, there were entire conferences dedicated to exploring the use of dimensional measures in DSM-5. The dimensional measures used in field testing were selected by the end of 2010 – over a year before PAI was formed. Drs. Kupfer, Gibbons, and Frank did not advocate for inclusion of CAT in DSM-5. Their work on CAT was well known to the DSM-5 Instrument Study Group because of the NIMH grant and their publications, but it was not considered viable for DSM-5 because of its complexity and immaturity.
  3. PAI will not gain financially from DSM-5’s inclusion of dimensional measures in Section 3 or if CAT is included in future versions of DSM.
      If and when PAI develops a commercial product with CAT, it will not have any greater advantage because of DSM-5’s inclusion of dimensional measures in Section 3 than the dozens of dimensional measures currently being marketed by others. If CAT is developed commercially, PAI will not gain any special financial benefit if included in DSM because APA’s policy is to not include any measure in unless the owner agrees to provide it for free to clinicians and researchers.
  4. Drs. Gibbons, Frank and Kupfer disclosed their interest in PAI publicly in AJP before disclosing it in JAMA Psychiatry..
      Drs. Gibbons, Frank, Kupfer and others who worked on the NIMH grant published an article on CAT-Anxiety in August 2013 in the American Journal of Psychiatry, which included disclosure regarding their ownership interest in PAI. Thus, in APA’s journal, there is no disclosure issue. The non-disclosure issue arose in connection with a JAMA Psychiatry article. We understand the facts to be as follows. Drs. Gibbons, Kupfer, Frank and the other NIMH investigators submitted a paper on CAT for publication in JAMA Psychiatry in August 2011 – three months before PAI was formed. The article was published over a year later in November 2012 with the disclosure that “The CAT-DI will ultimately be made available for routine administration and its development as a commercial product is under consideration.” In November 2013 – three months after disclosure in AJP, the authors published a letter entitled “Failure to Report Financial Disclosure Information” in JAMA Psychiatry. The details of that disclosure and whether it satisfies JAMA Psychiatry’s standards are between the authors and JAMA Psychiatry.

CONCLUSION
    Dr. Kupfer should have disclosed to APA his interest in PAI in 2012. Dr. Kupfer’s interest in PAI, which came after the decision had been made to include dimensional measures in DSM-5, did not influence DSM-5’s inclusion of dimensional measures for further study in Section 3. Interest in inclusion of these measures in DSM-5 began with conferences starting in 2003. If and when PAI develops a commercial product with CAT, it will not have any greater advantage than the dozens of dimensional measures currently being marketed by others.
Mickey @ 2:36 PM

the end of an era…

Posted on Tuesday 14 January 2014

I was looking on the Psychiatric Times web site for an article, and the ads caught my eye. There were some for vitamin supplements, a few for ipad clones, and then the regular pharma ads – only they weren’t so regular. I guess it’s a testimonial to the dry pipeline. Pristiq® was there, a still in·patent Effexor® clone. Seroquel·XR® was in the house, this time as a stand·alone antidepressant in Bipolar Depression [Seroquel·XR® is in·patent until 2017 though Seroquel® is now generic]. There’s an ad for a christian psychology degree program at Jerry Falwell’s Liberty University. And then a couple of weird sisters. Serotune says it is an "all-natural supplement designed to increase your serotonin, dopamine and GABA levels, and is ideal for those who are looking for a safe, effective way to feel better."
“It doesn’t make me feel like I am taking something to help me feel happy, it just makes me feel like I am happy naturally.”
The safe alternative to ECT mentioned is a Fisher Wallace Stimulator® which is FDA cleared [whatever that means] for insomnia, anxiety, depression and chronic pain. You can order one on-line with a faxed authorization from your licensed healthcare practitioner [including a Psychologist, GP, Physician’s Assistant, Psychiatrist, OBGYN, Chiropractor, Acupuncturist, Nurse, etc.] or you can get phone authorization from their online Acupuncturist [$50]:

"Stop Depression in 2 Weeks or return your device for a refund. Use the Fisher Wallace Stimulator® for 20 minutes, twice a day, to reduce or eliminate depression, including bipolar depression and major depression."

The one that caught my eye was Nuedexta® for Pseudobulbar Affect problems.
Pseudobulbar affect [PBA], also known as emotional lability, labile affect, or emotional incontinence, refers to sudden outbursts of involuntary crying or laughing in patients with neurological disorders, even though there might not be any sad or humorous event to trigger those emotions.
There’s an article from a peer reviewed journal of Managed Care and Hospital Formulary Management [Nuedexta for the Treatment Of Pseudobulbar Affect] with a clinical trial graph to die for:
It’s obviously not a common condition, but if you see a case, this is the medicine to use. What is it? A mixture of Dextromethorphan [the cough suppressant in Robitussin DM] and Quinidine [an older antiarrhythmic drug]. The Quinidine keeps the Dextromethorphan bioavailable. Mechanism of action in PBA, unknown. But here was the part that was interesting:
And there were a few small ads for some of the late·comers: Latuda®, Fanapt®. Otherwise, that was about it. Obviously, this is hardly an in depth study of pharmaceutical advertising in 2014, but it’s an example that can be confirmed by looking at about any site around – the pharma ads we’re accustomed to are dwindling and there are many more that are reminiscent of the patent medicines from a century ago, the kind of ads that were actually the origins of the advertising industry:
And a change from what we’ve become used to:
While I’ve read the Psychiatric Times in the past, I’ve never kept up with the ads. I tend not to see ads [selective inattention?]. But overall, I have noticed that the journal ads are changing: cough medicine for PBA; scalp stimulator for depression; food supplements for enhancing neurotransmitters; etc. Obviously, ads for prescription medications are the ones still in·patent, and in psychiatry, that list is vanishing. And the drugs in·patent are the latter day saints – the so called "me too" drugs. There was a time when the new drugs were hailed as advances or innovations. Now they’re more in the range of "left-overs." Seroquel® has morphed from an antipsychotic, to a depression add-on, to a mania drug, to a stand·alone antidepressant – from Seroquel® to Seroquel·XR® [rivaling A Chorus Line and Cats for longevity]. Just another sign that we are at the end of an era…
Mickey @ 1:00 AM

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