FDA Response to Utah Court Must Be Truthful Re:
Mon, 29 Aug 2005
FDA Amicus Curiae–Kallas–claims FDA infallibility pre-empts state safety laws (warning: large 1.6 MB file)
A federal judge in Utah has asked the FDA to explain its position as it relates to the association between antidepressants and suicidality in children and adolescents. The case involves a 15 year old girl, Shyra Kallas, who was prescribed Zoloft (sertraline) by her primary care doctor for warts. While taking Zoloft, she shot and killed herself – she died in her father’s arms. (Kallas v Pfizer, Case No. 2:04-CV-00998 PGC)
“Specifically, the court is interested in the government’s positions as to whether the FDA had considered the issue of whether there was an association between Zoloft (or similar SSRIs) and an increased risk of suicide prior to November 2002. This is in contrast to the issue of whether Zoloft (or similar drugs) can and does cause suicide (causation rather than association).”
The Court has also asked the FDA whether an amicus brief filed by FDA’s (then) Chief Counsel, Daniel Troy, in September 2002, would have applied to the Kallas case:
“In addition to the causation versus association issue, the court invites the government to better educate the court on any other issue it views as important to the preemption issue before it, including whether the position taken in the amicus brief (previously filed in 2002) is applicable in this case.”
In the 2002 brief cited by the court, Daniel Troy claimed that FDA’s authority preempts state drug safety requirements. (The case, Motus v. Pfizer, involved a California businessman in his 50’s who shot and killed himself after a 2-week course of Zoloft). In his brief, Troy argued that, even though Pfizer never sought to strengthen Zoloft’s warning label, any warning, no matter how worded, that suggested a link between Zoloft and suicidality would have been false and misleading, would have “misbranded” the drug, and the FDA would have rejected any effort by Pfizer to use such a warning.
Pfizer has used Daniel Troy’s brief for the past 3 years to fend off lawsuits involving Zoloft suicides by arguing that the FDA’s authority preempted state requirements to warn the public about drug hazards.
However, across the country, courts have rejected Pfizer’s arguments to dismiss wrongful death lawsuits arising from its failure to warn physicians and the public about evidence of a “reasonable association” between Zoloft and suicide. “With little exception, courts that have considered this exact issue have concluded that state failure-to-warn claims are not preempted by the FDCA and its attendant regulations.”  [FDCA: Food Drug and Cosmetics Act]
In a number of recent court rulings, judges have not only rejected Pfizer’s arguments, but have rejected the FDA brief itself:
- One state court judge in California, ordered the FDA brief stricken from the record, calling it “hearsay and irrelevant.”
- In another case in Illinois, the judge pointed out that the brief “contains nothing more than legal argument by [FDA] counsel.”
- In a case pending in Minnesota, the judge rejected Pfizer’s arguments, stating that it “declines to treat statements from a single FDA legal brief as declarations afforded the preemptive force of law.” The judge also called Pfizer’s arguments “perverse” and a “public policy argument gone awry.”
- A federal judge in Texas said “[I]t would be inconceivable to argue that an additional warning regarding suicidality would be false or misleading.” The judge pointed out that the law “allows, even encourages, manufacturers to be proactive when learning of new safety information related to their drug” and that “[drug] manufacturers, not the FDA, are tasked with the responsibility of taking proactive steps once a manufacturer learns of "reasonable evidence of an association of a serious hazard with a drug.”
The ultimate question the FDA will be answering in its court submission, due September 1, 2005, is: had Pfizer sought to add a warning to its Zoloft label before November 2002, when the drug was prescribed for Shyra Kallas, would the FDA have prevented Pfizer from do so?
The current Black Box warnings highlighting the increased risk of suicidal behavior in children and adolescents taking antidepressants came months after UK regulators banned the use of antidepressants for children and adolescents, citing evidence of the suicide risk, coupled with lack of efficacy evidence. The US warnings were issued after several in-depth analyses of the evidence from company controlled pediatric clinical trials dating back to 1983. The scientific evidence – which had been concealed from physicians and the public, until 2004, when it was finally analyzed by a senior FDA medical officer, Dr. Andrew Mosholder (a child psychiatrist) – was then corroborated by FDA’s Dr. Tarek Hammad, and later confirmed by a panel of experts contracted by Columbia University at FDA’s request. [See documents at: www.ahrp.org]
The compelling evidence linking antidepressants to an increased risk of suicidality led one of the FDA advisory panel members (Dr. Thomas B. Newman), to point out that “such a dramatic result would be expected to occur by chance only 1 time in 20,000.” Dr. Newman also noted that: “The fact that an association emerged from the meta-analysis . . . for an outcome that the sponsors of the trials were not looking for, and presumably did not wish to find, was quite convincing.”
The FDA advisory panel voted, 25 to 1, that the data presented demonstrated a causal relationship between the antidepressants and increased suicidality.
Even though the FDA did not conduct its review of pediatric clinical trials by the time of Shyra Kallas’ death in 2002, there was more than sufficient evidence at that time of an association between Zoloft and suicide. The legal standard requiring drug companies to issue a warning is “reasonable evidence of an association” of a serious hazard to a drug. Indeed, FDA documents show that as far back as 1990, key FDA safety officers had knowledge of the associated risk between Prozac and suicidality. [Prozac was the first SSRI antidepressant to gain FDA approval.]
In a memorandum to FDA’s Director of Neuropharmacology, Dr. David Graham, FDA Section Chief of Epidemiology Branch, noted “largescale underreporting” of fatal and potentially fatal adverse effects. Dr. Graham noted that fewer than 10% to 20% of fatal effects were reported. Nevertheless, the data showed a “higher percentage of suicidality among patients on fluoxetine [Prozac] than among tricyclic or placebo patients.” 
However, FDA safety officers’ admonitions were largely ignored by FDA top brass – just as their admonitions about cardiac arrest linked to the painkiller Vioxx were ignored. Moreover, FDA documents show that the FDA was aware of an apparent 7-times greater rate of suicidal behavior in children taking Zoloft since 1996, yet the agency did nothing about it.
While certain “self-interest” groups (backed by the pharmaceutical industry) have criticized the FDA for issuing the Black Box warning, arguing that antidepressant prescriptions for children and adolescents have decreased and children are not getting “the treatment they need,” the fact remains that these drugs have failed to demonstrate a benefit for adolescents but have been shown to pose serious life-threatening risks. One must wonder about the financial conflict of interest that may likely have motivated the American Psychiatric Association (APA), the American Academy of Child and Adolescent Psychiatry (AACAP), and the American Medical Association (AMA) to express alarm at physicians’ greater caution about prescribing antidepressants for children.
The antidepressant controversy has also highlighted deep-seeded problems within the FDA. The professional assessments and recommendations by FDA’s Medical Officers – whose task it is to uncover safety hazards – have been overruled by FDA bureaucrats who have repeatedly disregarded safety concerns. Those undisclosed concerns led to preventable loss of life. Serious conflicts of interest were uncovered by congressional investigations, by a lawsuit filed by the New York State Attorney General, and by investigative reports by the media.
The evidence suggests that FDA administrators disregarded the scientific evidence and allowed drugs with lethal side effects to remain on the market without adequate warnings. For example, Daniel Troy who filed the 2002 FDA brief (Motus) that Pfizer used to its advantage, counted Pfizer as one of his clients in the year before he took public office.
The public will be watchful to see how the FDA responds to the Utah court – and whether the FDA has been chastened by its lethal mistakes and whether FDA officials recognize that FDA’s true “customers” are the American public, not the pharmaceutical industry.
The question that should be asked by the court is: what did Pfizer know, when did it know about the increased suicide risk, and why did it fail to include that information in its Zoloft label? The scientific evidence is clear to all except those with a financial stake in the drug business.
The evidence of a suicidal link is unassailable: at the September 14, 2004 joint meeting of the FDA Advisory Psychopharmacology Committee and the Pediatric Committee, FDA’s Director of Medical Policy, Dr. Robert Temple, acknowledged: “we could say that causality for this risk has been established in pediatric patients.” The FDA label change request of Oct 15, 2004, stated:
“A causal role for antidepressants in inducing suicidality has been established in pediatric patients.” 
The later omission of that statement from the label is a demonstration of drug manufacturers’ undue influence in shaping FDA warning labels. However, the evidence of a suicidal link to Zoloft (and the other SSRI class of antidepressants) is so compelling, the FDA issued another advisory to healthcare professionals in July, 2005, stating:
“FDA has concluded that suicidal thinking or behavior may increase in pediatric patients treated with any type of antidepressant, especially early in treatment. Increases in suicidal thinking or behavior due to drug can be expected in about 1 out of 50 treated pediatric patients. Note that, Zoloft is approved for treating pediatric patients only if they have obsessive-compulsive disorder.” http://www.fda.gov/cder/drug/InfoSheets/HCP/sertralineHCP.htm
Whatever the current FDA Chief Counsel’s office decides to do in the Kallas case, one thing is certain: the FDA would be unwise to pretend that the evidence does not warrant warnings. The American public will be watching and judging FDA’s commitment to drug safety by its actions and consistency in its public and private statements of policy. In the past 15-plus years, the FDA has sided with industry at the expense of consumer safety. However, public awareness about FDA’s failure to protect consumers from unsafe, hazardous drugs ensures that the FDA will not be able to shelve its submission to the court out of the public’s radar screen. FDA’s policy position should be open to public scrutiny: the public has the right to know what the FDA’s legal arm is communicating to the judiciary.
The question remains: will the FDA side with Big Pharma or with American consumers when it responds to the Utah court’s request for the agency’s position regarding antidepressants, suicidality and children/adolescents? The FDA is on notice to inform the Utah court truthfully about the existing evidence linking Zoloft to a suicidal risk. If FDA’s amicus brief raises doubt about the body of evidence supporting the black box warning, it will demonstrate that the agency has not changed its policy of accommodation, putting Pfizer’s corporate interests above public safety.
FDA’s Chief Counsel would be unwise to pretend – as senior agency officials recently did when they fed a New York Times reporter a bill of goods by insinuating that FDA’s recent warnings were not based on evidence, but rather the agency’s over cautiousness in response to criticism. Gardiner Harris was either duped or intentionally misled Times readers when he wrote: “over the last year, [the FDA] has demanded that pharmaceutical companies add tough warnings for drugs as diverse as the antidepressant Zoloft, because it might lead a small number of teenagers to become suicidal.”  In point of fact, Pfizer considered this Times article invaluable in its defense. So much so, Pfizer submitted it to the court as exhibit #1815 in Cartwright v Pfizer case. 
If the FDA’s brief to the Utah court does not validate the Black Box label warnings and FDA’s recent advisory warning about the risk for 1 in 50 adolescents prescribed an antidepressant such as Zoloft, it will demonstrate the agency’s bad faith. And will demonstrate the need for stringent legislative reforms to ensure that the American public is protected.
The ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP) is not alone in its commitment to ensure that the FDA puts patient safety above corporate profits. Court rulings have rejected Pfizer’s Preemption argument:
Minnesota Court Ruling: https://www.ahrp.org/SuitsDecisions/WitczakPreemption.pdf
Texas Federal Court Rulings: Cartwright v. Pfizer Inc., E.D. Texas, No. 04-292, 3/31/05 Dusek v. Pfizer Inc., S.D. Texas No. H-02-3559, 2/20/04; Needleman v. Pfizer Inc., N.D. No. 3:03-CV-3074-N, 8/6/04)
Louisiana: Miles v. Pfizer Inc., M.D. La., No. 03-691, 3/30/05
llinois Federal Court Ruling: Zikis v Pfizer Inc., No. Illinois No. 04C 8104
California State Court Ruling: http://www.baumhedlundlaw.com/media/ssri/Zoloft/Witczak/Szybinski-Preemption-Ruling.pdf
Kallas Court Order excerpt:
1. “Federal Labeling Law Does Not Preempt Claims That Drug Needed Suicide Warning” BNA: Product Safety & Liability Reporter, April 11, 2005Volume: 33 Number: 15. http://litigationcenter.bna.com/pic2/lit.nsf/id/BNAP-6B9NFS?OpenDocument&PrintVersion=Yes
2. See, memorandum from FDA’s Dr. David Graham, Section Chief Epidemilogy Branch, to Director, Division of Neuropharmacologic Drug Products, FDA, Re: Lilly’s submission on fluoxetine (Prozac), September 11, 1990
3. See, DHHS FDA CDER. Joint Meeting of CDER Psychopharmacology Advisory Committee and Pediatric Committee, September 14, 2004 at p. 25: http://www.fda.gov/ohrms/dockets/ac/04/transcripts/2004-4065T2.htm
4. Gardiner Harris, FDA Responds to Criticism With New Caution, The New York Times, August 6, 2005. Front Page.
5. See: Cartwright v Pfizer, US DC Texas, Defendant’s Amended Exhibit List, Case Number 6:004cv292.
Contact: Vera Hassner Sharav