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Posted on Thursday 7 July 2016

^{Being deposed in a legal case is one of the more odious experiences of adult life. The lawyer asking the questions has pored over whatever you’re there to talk about looking for ways to discredit you, then hammers away trying to get you to admit your sins [whether you’ve committed them or not]. No one looks very good in a deposition transcript. But in this post, I’m only going to talk about snippets from a deposition where Karen Dineen Wagner is not being brow-beaten and simply answers in a matter-of-fact manner. While there are plenty of contentious segments in this deposition, they are for another time.}

Karen Dineen Wagner is something of an enigma to me. She is a listed author on four heavily contested ghost-written Clinical Trial Reports and was investigated by the US Senate for unreported income from pharmaceutical companies. And yet she’s the head of Child and Adolescent Psychiatry at UTMB; was the longstanding Deputy Chairman of Psychiatry there until recently when she was promoted to full Chairman; and she is the President Elect of the American Academy of Child and Adolescent Psychiatry.

^{From 2001 to 2004, Karen Dineen Wagner was a listed author on a series of Clinical Trial articles investigating Paxil®, Prozac®, Zoloft®, and Celexa® respectively in depressed adolescents – each reporting a favorable efficacy and safety profile.

2001: Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A Randomized, Controlled Trial. "Paroxetine is generally well tolerated and effective for major depression in adolescents."

2002: Fluoxetine for Acute Treatment of Depression in Children and Adolescents: A Placebo-Controlled, Randomized Clinical Trial. "Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent outpatients with severe, persistent depression."

2003: Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials. "…sertraline is an effective and well-tolerated short-term treatment for children and adolescents with MDD."

2004: A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents. "…treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated."

Since 2004 when the FDA finally issued a black box warning about the possible suicidality in adolescents taking SSRIs, there has been a multifocal attempt to debunk it lead by, among others, Dr. Karen Dineen Wagner, who even served on the ACNP team tasked to do an independent analysis:

2006: ACNP Task Force Report on SSRIs and Suicidal Behavior in Youth.

2008: Statement of Senator Charles E. Grassley Before the United States Senate.

She is the Child and Adolescent columnist for the Psychiatric Times: Articles promoting antidepressants in MDD, stimulants in ADHD, antipsychotics in childhood Bipolar Disorder, and opposing the FDA Black Box Warning: articles.}

A lot of the information in the recent paper by Jon Jureidini, Jay Amsterdam, and Leemon McHenry about the 2004 Celexa Clinical Trial came from the discovery process in a court case [Celexa and Lexapro Marketing and Sales Practices Litigation: Master Docket 09-MD-2067-(NMG)].

The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance

In addition to the internal documents from the case mentioned in their article, there was also a deposition of Dr. Wagner. Here are a couple of snippets from that deposition posted on the Drug Industry Document Archive [DIDA]. First, what she had to say when asked about her authorship on the 2001 Paxil Study 329 article:

^{DEPOSITION OF KAREN DINEEN WAGNER, M.D., Ph.D. by Michael Baum, Esq., of Baum, Hedlund, Aristei & Goldman on Tuesday, July 16, 2013, page 61 [pdf page 16]}
^{QUESTION Do you recognize this document we’ve marked as Exhibit 2c?}
	^{ANSWER Yes.}
^{QUESTION And you were a contributing author to this article?}
	^{ANSWER I was an add-on site to this study. I was not involved in the writing of the manuscript.}
^{QUESTION Did you review the manuscript before it was submitted for publication?}
	^{ANSWER I don’t remember reviewing it. I assume — I don’t remember reviewing it. I would guess all of the authors saw a copy before it went out. I just don’t remember.}
^{QUESTION At the time it was issued, did you believe it to be an accurate and truthful statement of the results of the 329 study?}
	^{ANSWER Yes.}

^{QUESTION … just based on your recollection now, do you recall that there’s some data that’s come out or some indication since the publication of what’s now marked as 2c in July of 2001 that indicated that Study 329 was actually a negative result?}
	^{ANSWER There has been some controversy with that. It depends what outcome measure you look at. And again, I was an add-on site to this study.}
^{QUESTION You didn’t have anything to do with the publication of inaccurate information about Study 329, correct?}
	^{ANSWER I didn’t have anything to do with the design of the study, the analyses of the study. I provided subjects, some subjects, for the study. I think on — you can count what my authorship — one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, 17, 18 — I’m the 19th author in this multicenter publication.}
^{QUESTION You were low on the totem pole?}
	^{ANSWER I wasn’t involved in the design or the — this study was designed well before I was involved. The primary outcome measures were chosen before I was involved. All of it was done and they needed some more sites for enrollment.}
^{QUESTION Why is your name on the paper, then?}
	^{ANSWER Because I provided subjects for the study.}
^{QUESTION Okay. Do you know whether or not this paper is listed on your CV?}
	^{ANSWER It would be listed on my CV because my name is on it.}

She is being truthful in saying that she was brought into the Paxil Study 329 Clinical Trial late after they realized that recruitment was flagging and they needed to add more sites [Sites 007-012 added one year into the study]:

^{Table 7 Number of Patients Who Were Randomized (R) to Each Treatment Group} ^{and Who Completed (C) Acute Phase of Treatment at Each Center}
^Center	^Investigator	^Site	^Paroxetine		^Imipramine		^Placebo
			^R	^C	^R	^C	^R	^C

⁰⁰¹	^Geller	^{St. Louis, MO}	⁷	³	⁵	¹	⁶	⁴
⁰⁰²	^Keller	^{Providence, RI}	⁹	⁶	¹¹	⁶	¹⁰	¹⁰
⁰⁰³	^Klein	^{New York, NY}	¹⁰	⁸	¹⁴	⁹	¹¹	¹⁰
⁰⁰⁴	^{Papatheodorou}	^Toronto	⁵	³	⁴	¹	⁴	²
⁰⁰⁵	^Ryan	^{Pittsburgh, PA}	¹⁶	¹⁴	¹⁵	¹⁰	¹⁴	¹³
⁰⁰⁶	^Strober	^{Los Angeles, CA}	⁴	³	²	¹	³	²

⁰⁰⁷	^Wagner	^{Galveston, TX}	⁹	⁵	⁷	¹	⁵	⁴
⁰⁰⁸	^Clarke	^{Portland, OR}	⁵	⁵	⁶	⁵	³	³
⁰⁰⁹	^Emslie	^{Dallas, TX}	¹⁷	¹³	¹⁸	¹³	¹⁸	⁹
⁰¹⁰	^Weller	^{Columbus, OH}	³	²	²	²	⁴	³
⁰¹¹	^Carlson	^{Stony Brook, NY}	²	¹	⁵	⁴	⁴	³
⁰¹²	^{Kusumakar/Kutcher}	^{Halifax, Nova Scotia}	⁶	⁴	⁶	⁴	⁵	³

		^Total	⁹³	⁶⁷	⁹⁵	⁵⁷	⁸⁷	⁶⁶

But the rest of her claims of passivity and non-involvement are beyond suspect. In 1999, she was the main speaker at a SmithKline Beecham sales roll-out meeting based on this study [if you haven’t seen this report, it’s worth a look]. And by the time of this deposition, the literature was full of Paxil Study 329 references, GSK had settled the suit brought by New York Attorney General Elliot Spitzer, the Black Box Warning was on every antidepressant package insert, Paxil Study 329 was a major part of a $3.3B GSK settlement, and Wagner had herself been deposed twice about Paxil Study 329:

^{DEPOSITION OF KAREN DINEEN WAGNER, M.D., Ph.D. by Michael Baum, Esq., of Baum, Hedlund, Aristei & Goldman on Tuesday, July 16, 2013, page 12 [pdf page 4]}
^{QUESTION Have you had your deposition taken before?}
	^{ANSWER Yes.}
^{QUESTION Do you know how many times?}
	^{ANSWER I think I’ve been deposed three times.}
^{QUESTION Okay. One was in the Paxil litigation? Does that ring a bell?}
	^{ANSWER Yes.}
^{QUESTION And once in the Celexa/Lexapro securities litigation? Does that sound right?}
	^{ANSWER I don’t know what it was called, but there was a Celexa deposition.}
^{QUESTION Okay. And do you know what the third one was?}
	^{ANSWER I think that there were — I think with Paxil there may have been two, but I’m not certain. It was a long time ago.}

So it’s hard to buy that her feigned innocence and unfamiliarity were authentic. But beyond that, she’s stating outright that she didn’t review the data and may have not even read the paper before it was submitted with her name on the BY-LINE – that the only reason she was included was that she was a site director. That is a damning interpretation of the meaning of the word "author." And it goes downhill from there. This next snippet comes from the questioning about the 2004 Citalopram Clinical Trial:

^{DEPOSITION OF KAREN DINEEN WAGNER, M.D., Ph.D. by Michael Baum, Esq., of Baum, Hedlund, Aristei & Goldman on Tuesday, July 16, 2013, page 28 [pdf page 8]}
^{QUESTION Okay. So do you recall whether you had access to patient level data when you were working on this publication?}
	^{ANSWER No. We have access — well, as an individual investigator, you have access to your patients. But the individual patient data from other sites, usually when the data is presented, it’s put together. So I don’t — I just don’t recall if I saw individual — individual data.}
^{QUESTION When you say "put together," does that refer to the pharmaceutical company compiling information and providing it to you?}
	^{ANSWER The data is the property of the pharmaceutical company.}
^{QUESTION And so they collect it and provide some form of summary of it to you?}
	^{ANSWER Correct.}
^{QUESTION And except for the patient level data that you had from your own particular site, you relied upon the information conveyed to you by the pharmaceutical company regarding the other sites. Is that correct?}
	^{ANSWER In multicenter studies, each individual investigator has their own data and then it depends who sponsors the study. This was a Forest-initiated and Forest-sponsored study, so all of the data from the sites go to Forest.}
^{QUESTION Then they compiled it and then did statistical evaluations of it?}
	^{ANSWER Yes.}
^{QUESTION Did you do any of the statistical evaluations yourself?}
	^{ANSWER No.}
^{QUESTION It was essentially provided to you by Forest statisticians?}
	^{ANSWER Correct. I’m not a statistician.}

In this Clinical Trial, Wagner was anything but an "add-on," she was the Principal Investigator [PI], and yet her answers are the same. She only saw the actual data from her own site and she didn’t do or check the statistical analysis, accepting the evaluation of Forest Laboratory’s statisticians. After all, "The data is the property of the pharmaceutical company." So she neither reviewed the data nor involved herself in the analysis. And, by the way, she wasn’t involved in drafting the paper either. The internal documents discussed in The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance simply confirm something discovered by the AJP editors after the original paper was published. It was ghost-written. And further, it omitted mentioning that a European Lundbeck Trial had been negative and reported significant harms [outlined in my collusion with fiction… and published in the American Journal of Psychiatry. 2009 166:942-943].

And so to return to my initial comment, "Karen Dineen Wagner is something of an enigma to me." She is known as an authority on psychopharmacology in children and adolescents – presenting CME courses at the APA and AACAP meetings and speaking and writing widely on the topic. These early articles seemed to have launched her career. Yet in these examples she is, at best, a signifier, in large measure a placeholder for the work of others – others with tainted motives at that. So the story raises some very big questions like "what is an author?" and "what constitutes authority?"

Neuroskeptic

July 7, 2016 | 4:06 PM

We see the same phenomenon whenever a paper gets retracted. As soon as the paper goes bad, no-one is willing to take responsibility for it, heaping blame on the first author or whichever author was found to have screwed up.

All of the other authors are willing to share the credit for the paper when times are good but they want no share of the blame when times are bad.
Bernard Carroll

July 7, 2016 | 5:27 PM

Good point, NS.

Wagner seems different from other notable KOLs like Nemeroff and Keller. They at least had a background in original science, basic or clinical, before their names started appearing on clinical trials reports as (ahem) authors. A review of Wagner’s publications reveals that clinical trials is pretty much all she has done, plus a few spinoffs where she was a minor co-author. So her self-description in the deposition as “I am not a statistician” is correct. She wouldn’t recognize statistical errors that are obvious to competent readers. Likewise, she seems to have had little input qua scientist into the design of the trials for which she recruited patients. This raises the question about such KOLs – are they authorities or cheerleaders?
James OBrien, M.D.

July 7, 2016 | 5:45 PM

The ultimate cheerleader since she is President Elect of AACAP.

Are stock analysts at investment banks authorities or cheerleaders? A bit of the former a lot of the latter. I think the same principle applies to KOLs.
Tom

July 7, 2016 | 9:08 PM

Now I finally see the way. I can pad my vita simply by providing subjects to a pharma run trial! Authorship without any thinking or writing on my part! Who knew it was this easy?
Joel hassman, md

July 7, 2016 | 10:36 PM

Are you trying to invite comparisons here to what happened earlier this week with the FBI and Hillary Clinton?!.

It just shows you this disgusting double standard that exists within organizations and political systems. There’s no sense of responsibility or accountability to the people who depend on these services and representation.

Corruption is beyond pandemic and endemic, it’s almost an acceptable part of the American way of life!
James OBrien, M.D.

July 8, 2016 | 12:17 PM

Maybe we’re just basically watching WWE wrestling and complaining that it’s fixed. It’s occurred to me that maybe I’m not skeptical enough.
Arnold Wilson

July 8, 2016 | 12:36 PM

From the American Psychological Association Code of Ethics:

8.12 Publication Credit
(a) Psychologists take responsibility and credit, including authorship credit, only for work they have actually performed or to which they have substantially contributed. (See also Standard 8.12b, Publication Credit.)

(b) Principal authorship and other publication credits accurately reflect the relative scientific or professional contributions of the individuals involved, regardless of their relative status. Mere possession of an institutional position, such as department chair, does not justify authorship credit. Minor contributions to the research or to the writing for publications are acknowledged appropriately, such as in footnotes or in an introductory statement.

(c) Except under exceptional circumstances, a student is listed as principal author on any multiple-authored article that is substantially based on the student’s doctoral dissertation. Faculty advisors discuss publication credit with students as early as feasible and throughout the research and publication process as appropriate. (See also Standard 8.12b, Publication Credit.)

Is there an argument to be made for unethical conduct?
1boringyoungman

July 9, 2016 | 9:00 PM

“what constitutes authority?”
This is an enormously important question. A major tie that binds the threads discussed on this blog.
James OBrien, M.D.

July 11, 2016 | 1:38 AM

I think most KOLs are part expert, part showman:

https://www.youtube.com/watch?v=ZOWeyumx7Cc
Joel hassman, md

July 12, 2016 | 10:24 PM

I guess my comment over the weekend about living in a personality disordered Society was too over-the-top for this thread?

Sorry, won’t change my opinion about Authority. When there’s an issue of obedience and control that plays a major dynamic in some types of authority, it brings out the worst in people.

I know this first-hand having dealt with colleagues who redefined the term Power Trip!

Oh well, have a nice summer

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