Karen Barth Menzies testified before the FDA Advisory Committee on February 2, 2004 regarding antidepressants and reports of suicidal risks for children
"Good morning, my name is Karen Barth Menzies. I am an attorney for Baum Hedlund. We represent several thousand SSRI victims and we’ve been doing this for 12 years.
US Code of Federal Regulations 201.57 mandates that you require the drug companies
to warn when there is reasonable evidence; not causation; reasonable evidence
of an association of a serious risk. The clinical researchers who did these
trials on kids and the drug companies themselves, confirmed that there are multiple
events of suicidality caused by the drug. The methodology that you are going
to be using is designed to explain away those events. Even Dr. Laughren admits,
in the memo he gave you for this hearing today, that there is evidence in these
trials of an increased risk of suicidality. Reasonable evidence is there. If
there’s reasonable evidence you must make them warn.
Serious Risk? We certainly have that. Akathisia, psychosis,
mania. When you’re looking at this data you’re not just looking at the suicide,
also look for signs of akathisia and psychosis and mania. These aren’t as easily
explained away by the drug companies by blaming the disease; by blaming the
victims.
Paul Leber predicted this day when he said that the FDA would come under attack because they weren’t as demanding as they ought to have been when they were looking at the efficacy of the antidepressant products.
Put me out of business for the right reasons. Warn about these drugs."
February 1, 2004
FOR IMMEDIATE RELEASE
Concern
Over Legitimacy of FDA’s Review of Antidepressants and Suicide in Children,
Attorneys
Claim FDA’s Methodology Scientifically Illegitimate
Los Angeles, February 1, 2004—An FDA Advisory Committee meeting is scheduled to take place on February 2, 2004 to review the risk of suicide in children and adolescents taking the antidepressants Paxil, Zoloft, Prozac, Luvox, Celexa, Effexor, Wellbutrin, Serzone, and Remeron. The FDA intends to "determine whether those given antidepressants may have been, in aggregate, at greater risk of committing suicide than those given inert pills.” (New York Times.) In response, attorney for thousands of SSRI victims, Karen Barth Menzies of Baum Hedlund, stated that "it would appear the FDA is looking for ways to explain away the higher rates of suicide, not to legitimately examine the issue.” Attorney Karen Barth Menzies will be speaking at the public hearing Monday at the Holiday Inn in Bethesda, MD.
The FDA’s announcement
that it would be holding an advisory committee meeting followed the UK government’s
December 10, 2003 announcement that all SSRI antidepressants (except Prozac 
) would be contra-indicated
for use in children and adolescents under 18 in the UK due to their lack of
efficacy and their association with suicidal thoughts and actions.
Baum Hedlund, a Los Angeles based law firm that represents thousands of victims adversely effected by the SSRI antidepressants (including more than 20 families whose children either committed suicide or attempted suicide while on an SSRI) is skeptical about the February 2, 2004 FDA Advisory Committee Meeting.
First, an October 28, 2003 New York Times article stated that the FDA "plans to re-examine many of the clinical conclusions made during studies of the drugs." In essence, the FDA proposes to second-guess the clinical judgment of the researchers who had first-hand contact with these patients and who, at the time, determined that the patients experienced a suicidal event during the trial. In some instances, the researchers and the sponsoring pharmaceutical company concluded that the suicidal event was caused by the SSRI. Barth Menzies argues: "What the FDA proposes is scientifically illegitimate and predestined to reach a favorable conclusion for the drug companies."
According to an overview memorandum issued by the FDA on January 2nd, the FDA has enlisted the help of a group from Columbia University that, according to the FDA, has a “well-recognized expertise in adolescent suicidality.” The FDA memo states that the group has “developed an approach to classifying events possibly representative of suicidality that precisely fit [FDA’s] needs.” (Memo, page 14.) However, according to David Healy, a world renowned psychopharmacologist from the University of Wales College of Medicine and an expert witness for plaintiffs: "The principles of clinical trial randomization mean you cannot post hoc analyze to look for confounding factors."
Ironically, the drug companies themselves have argued, one for one, against this position in litigation. For instance, GlaxoSmithKline’s vice president of clinical development testified that “[a]t every single [clinical trial] visit [by a clinical trial patient], it’s one of the questions that is asked [questions related to suicidality] . . ., so we are prospectively looking at suicide in relation to our treatment every single time we study the drug.” If that is the case, how is it appropriate, then, to post hoc reassess events that clinical researchers identified as suicide events?
Another cause for skepticism is the Columbia University connection to the advisory committee. Dr. John Mann (of Columbia) has significant financial ties to the companies whose drugs are under scrutiny. Mann has also been a defense expert witness for Pfizer and GlaxoSmithKline in litigation related to SSRIs on this very issue. He is consistently relied upon by the companies as a spokesperson to counter the claims that SSRIs cause suicide. Moreover, Mann was the co-chair on a review conducted by the American College of Neuropsychopharmacology (ACNP) which concluded (while admitting it did not possess all the data) that the SSRIs are effective in treating children and do not pose a risk of increased suicidality. (Nine out of ten of the ACNP “task force” members have financial ties to the pharmaceutical companies in question.) Moreover, some of the task force members are defending their own studies that found the drugs safe and effective in children. For instance, Dr. Karen Dineen Wagner, in August 2003, and shortly following the UK’s ban of Paxil for use in children, published a study which, according to the author, demonstrated that Zoloft is effective and safe in children and adolescents. In fact, Dr. Wagner conducted four Paxil studies, apparently never published, which formed the basis, in part, of the UK's ban. Dr. Wagner recently conceded, however, that this issue "requires further investigation and looking at the entire database of these medications." (The Guardian.)
Notwithstanding, the Wagner study received a massive amount of positive press coverage, touting Zoloft as a drug found safe and effective for children and adolescents, no doubt orchestrated by Pfizer. However, unbeknownst to those lacking a subscription to the Journal of the American Medical Association (JAMA), the study has been seriously criticized by a number of scientists through letters sent to the editor of JAMA, published in the January 7, 2004 edition of the journal. One letter states: “The relative benefit increase of sertraline over placebo . . . suggests that there might in fact be no benefit from sertraline for these patients.”
Another doctor stated: “[Zoloft] barely achieved a statistically significant improvement over placebo . . . I would appreciate more information about the degree of influence the sponsor [Pfizer] had over the presentation of the data and interpretation of the results. . . . Given the safety and efficacy precautions recently raised about [Paxil], another selective serotonin reuptake inhibitor with a similar mechanism of action (at least in adults), I believe that more convincing data are needed before [Zoloft] can be recommended as first-line treatment for major depression in children and adolescents.”
Another letter complained that Dr. Wagner’s claims about the study “reach[] well beyond the trial’s results” and concluded “this trial suggests that [Zoloft] shows little to no perceptible benefit compared with placebo in the treatment of depressed youths.”
Baum Hedlund has now learned that Dr. John Mann will be a member of the FDA panel, according to a January 21, 2004 WebMD article. In response, Barth Menzies stated: “It’s just a gross conflict of interest. It is beyond me that the FDA would even consider having him on the panel or a participant in reviewing the issue for the FDA. It’s as if they have no concern whatsoever about appearing unbiased.”
The timing of the ACNP’s statement was no accident, less than two weeks before the FDA advisory committee meeting, particularly given that the report is ‘preliminary’ and ACNP admitted it ‘did not have access to all the data held by regulatory agencies and pharmaceutical companies.’ So why was it compelled to issue this preliminary and incomplete report at this time? The report isn’t even consistent with the FDA’s own findings. At the same time, it’s hard to believe that the FDA was unaware of the task force or that it would be releasing its preliminary findings when it did.”
Adding fuel to the already raging fire is the fact that two other members of the ACNP task force will be members of the FDA advisory committee on February 2 (Andrew C. Leon and Neil D. Ryan). If members of this “task force” can rush to make such bold conclusions knowing full well they do not have access to all the data, how can they be expected to keep an open mind? “It’s just unbelievable. How can the FDA allow these people to participate under the circumstances -- the whole process is becoming a farce,” stated Karen Barth Menzies. “Between Laughren’s memo, the ACNP report and the overlapping members on the advisory committee and ACNP, it seems clear that FDA has no intention of following in the UK government’s footsteps if doing so can be avoided,” said Barth Menzies.
Ironically, the FDA memo does admit that when FDA “re-reviewed” the data submitted by the drug companies for pediatric approval, “there were signals of increased risk of suicidality for patients assigned to [the] drug[s].” In addition, based on FDA’s review of summary data later submitted to it by drug manufacturers at FDA’s request: “A signal of increased risk on drug is apparent for at least 4 of the 7 programs, i.e., paroxetine [Paxil], sertraline [Zoloft], venlafaxine [Effexor], citalopram [Celexa], with perhaps a weak signal for nefazodone [Serzone].” The memo also states: “While fluoxetine [Prozac] is generally without a signal, in the suicide attempts analysis for study X065 there is actually a signal for drug.”
It should also be noted that a pivotal part of the British government's determination concerned the drugs' lack of efficacy. The question of whether these drugs are generally efficacious (even in the adult population) has been a public issue for many years. In fact, according to an internal memorandum written by a former FDA official, Dr. Paul Leber, there was some concern within the FDA that the approval of Zoloft (for adults) may "come under attack" because the FDA is not "as demanding as it ought to be in regard to its standards for establishing the efficacy of antidepressant drug products."
Dr. Leber went on to state: "I have considered the fact that the evidence marshaled to support [Zoloft's] efficacy as an antidepressant is not as consistent or robust as one might prefer it to be."
According to Leber, there were a number of studies (in adults) that "found no difference between placebo and [Zoloft] treated subjects." However, Laughren in his memo defends the lack of efficacy found in the pediatric studies, arguing that such failure can be expected. This is despite the overall failure rate of 80%.
Another cause for skepticism
is that the FDA, in the past year and a half, has joined forces with drug manufacturers
and against consumers in SSRI litigation. For instance, the FDA intervened in
favor of Pfizer, the maker of Zoloft, in a Zoloft suicide case (Motus v. Pfizer)
being litigated by Baum Hedlund. The FDA took such action after its newly appointed
Chief Counsel, Daniel Troy, received a personal telephone call from Pfizer's
national counsel, Malcolm Wheeler, asking for help.
Alarmingly, Baum Hedlund
learned that Troy worked for Pfizer during the pendency of that very case. The
FDA argued in the Zoloft suicide case that it would not allow Pfizer to warn
of a suicide risk even if it sought a warning. But the FDA states in
its January 2, 2004 memo that
“it has been part of medical lore for many decades that antidepressants
may have an early activating effect that perhaps gives depressed patients the
energy to follow through on suicidal impulses before the mood improvement associated
with antidepressant treatment takes effect.” (Memo, page 2.) The same
memo states that “this particular mechanism proposed to explain a possible
increase in suicidality early in antidepressant treatment is so well known that
it is referred to as the ‘roll back’ phenomenon” and “if
this view that initial antidepressant treatment may be associated with an actual
increase in risk of suicidality is in fact empirically established, this would,
in a sense, confirm a view that is already widely prevalent in clinical lore,
whatever the proposed mechanism.”
In response, Barth Menzies stated: “This is just incredible. Drug manufacturers do not warn of this risk and thus, doctors -- primarily general practitioners -- are unaware that such a risk exists. In fact, there isn’t a single reference in the collection of scientific literature known as Medline that refers to ‘roll back’ in relation to suicidality. Furthermore, how on earth can the FDA say on the one hand that it won’t allow a drug company to warn of a risk while on the other arguing that everyone already knows of the risk. It’s just internally inconsistent and absurd.”
According to Barth Menzies: "FDA has been violating its own mandate to act in the interests of the American consuming public by taking sides with the pharmaceutical companies it is supposed to police. The problem is not only the cover-up by the pharmaceutical industry, it is the FDA's lack of objectivity, which facilitates that cover-up. The consequences of this complicity has, in far too many instances, led to tragedy and death."
