PATTESON et al v. ASTRAZENECA, LP et al

Filing 92

Memorandum Opinion re 91 Order on Motions to Preclude Testimony Regarding Seroquel-Induced Tardive Dyskinesia. Signed by Judge James E. Boasberg on 09/16/2013. (lcjeb4)

UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF COLUMBIA

KAY PATTESON and GARY
PATTESON,
Plaintiffs,
v.

Civil Action No. 10-1760 (JEB)

JOHN R. MALONEY, M.D.,
Defendant.

MEMORANDUM OPINION
In 2008, Plaintiff Kay Patteson’s doctor diagnosed her with tardive dyskinesia, a
movement disorder characterized by repetitive, involuntary movements and uncontrollable
muscular tics. Patteson then brought this suit against her former psychiatrist, Defendant John
Maloney, M.D., who had prescribed Seroquel – an antipsychotic drug – to treat Patteson’s
insomnia in 2006. She claims that the Seroquel caused her tardive dyskinesia. To establish that
causal link, Patteson relies on expert testimony both from medical researchers and from her own
treating physicians.
Maloney now moves to exclude all testimony linking Seroquel to tardive dyskinesia. He
argues that Patteson’s expert testimony is unreliable under Federal Rule of Evidence 702 and the
testimony should thus be excluded. In essence, Maloney contends that his expert’s study –
which shows no link between Seroquel and tardive dyskinesia – is scientifically more rigorous
than that of Patteson’s experts. The Court, however, finds that the science linking Seroquel to
tardive dyskinesia is sufficiently reliable under Rule 702 to be admitted – and that Maloney’s

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argument goes to the weight of the testimony, not to its admissibility. The Court therefore denies
the Motion.
I.

Background
Patteson first sought treatment from Maloney on or about May 30, 2006. See Patteson v.

AstraZeneca, LP (Patteson I), 876 F. Supp. 2d 27, 30 (D.D.C. 2012). At the time, she complained of
“depression, anxiousness, chronic insomnia, and serious alcohol abuse/dependence.” Id. Maloney
eventually prescribed Seroquel to address Patteson’s insomnia. See id.
Seroquel is a second-generation antipsychotic. Antipsychotics are typically used to treat
psychoses; for example, Seroquel itself is approved for the treatment of schizophrenia and bipolar
mania, as well as bipolar depression, bipolar maintenance, and major depressive disorder. See id. 3031. Seroquel, however, is not currently approved for the treatment of insomnia, although such offlabel prescription does not necessarily constitute negligence. See id. at 31; see generally Ortho
Pharm. Corp. v. Cosprophar, Inc., 32 F.3d 690, 692 (2d Cir. 1994) (“FDA permits doctors to
prescribe drugs for ‘off-label’ uses.”); James M. Beck & Elizabeth D. Azari, FDA, Off-Label Use,
and Informed Consent: Debunking Myths and Misconceptions, 53 Food & Drug L.J. 71, 76-77
(1998) (“Courts have repeatedly recognized the propriety of off-label use, and several states
statutorily recognize off-label use in various contexts.”) (footnote omitted).
“Second-generation” antipsychotics were engineered to treat psychoses with a lower risk of
certain side effects, such as the risk of movement disorders like tardive dyskinesia. See Mot., Exh. 2
(Deposition of Dr. Thor W. Rak) at 15:23-16:10. Whether second-generation antipsychotics actually
carry a lower (or no) risk of those side effects is a matter of research and debate among the medical
community. Compare Opp., Exh. A (Affidavit of Dr. Robert Rosenheck) at 8 (side effects of secondgeneration antipsychotics are more or less the same as first-generation antipsychotics) with Rak Dep.
at 123:23-124:15 (Seroquel cannot be shown to cause tardive dyskinesia). Nevertheless, Seroquel’s

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FDA-approved label includes warnings for many of those side effects, including a warning
concerning the risk of tardive dyskinesia, a “syndrome of potentially irreversible, involuntary
dyskinetic movements.” See Rak Dep. at 11:6-9.
In April 2007, around 10 months after she began taking Seroquel, Patteson began
experiencing difficulty walking. See Patteson I, 876 F. Supp. 2d at 31. In January and February of

2008, Patteson’s doctors determined that tardive dyskinesia was most likely responsible for her
symptoms and that Seroquel could be the cause. See id. at 31-32. Patteson subsequently sued
Maloney in D.C. Superior Court in 2010. See id. at 32. She alleged that he had improperly
managed her course of treatment and that her tardive dyskinesia was a side effect of the
Seroquel. See Amended Compl., ¶¶ 46-48. The case was removed to federal court, and trial is
currently scheduled for October 2013.
Patteson plans to call three experts to prove that Seroquel caused her tardive dyskinesia:
Dr. Robert Rosenheck, a medical professor and researcher from Yale University School of
Medicine, will testify generally that the link exists; and Drs. Steven Lo and Sudeshna Bose, who
have been Patteson’s treating physicians, will testify both that Seroquel can cause tardive
dyskinesia generally and that the drug did, in fact, cause Patteson’s condition. See Joint Pretrial
Statement (JPS) at 12. Rosenheck will base his testimony on a study of second-generation
antipsychotics that he co-authored and that was published in the New England Journal of
Medicine, as well as on other published medical studies. See Rosenheck Aff. at 4. Lo and Bose
will rely on their differential diagnoses of Patteson as well as medical literature to establish
causation. See Opp., Exh. B (Affidavit of Dr. Steven Lo), ¶¶ 14, 15, 21; Exh. D (Deposition of
Dr. Sudeshna Bose) at 14:7-15:16; JPS at 12. “Differential diagnosis” is the medical term for a
diagnosis made by determining the potential causes of an ailment and then eliminating causes to
reveal the most likely culprit. See Lo Aff., ¶ 15.
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Maloney now moves in limine to exclude all testimony relating to causation. He
contends that, under Federal Rule of Evidence 702, Patteson’s expert testimony is unreliable and
should not be admitted. Maloney argues, at bottom, that Patteson’s expert studies are
inadmissible because his own expert studies are better – that is, Maloney’s studies are based on
sounder scientific methodology. Defendant also maintains that, because Patteson’s experts have
not diagnosed other patients with Seroquel-induced tardive dyskinesia, such a diagnosis must not
be accepted within the medical community and is inherently unreliable. At a minimum, Maloney
asserts that the Court should hold a pretrial hearing to determine the admissibility of the
causation testimony.
Because Patteson must prove causation to prevail on her medical-malpractice claim,
excluding evidence of causation would, practically speaking, end her case.
II.

Legal Standard
A district court has “‘broad discretion in determining whether to admit or exclude expert

testimony.’” United States ex rel. Miller v. Bill Harbert Int’l Constr., Inc., 608 F.3d 871, 895
(D.C. Cir. 2010) (quoting United States v. Gatling, 96 F.3d 1511, 1523 (D.C. Cir. 1996)).
Federal Rule of Evidence 702, which governs the admissibility of such testimony, provides:
A witness who is qualified as an expert by knowledge, skill,
experience, training, or education may testify in the form of an
opinion or otherwise if:
(a) the expert’s scientific, technical, or other specialized
knowledge will help the trier of fact to understand the
evidence or to determine a fact in issue;
(b) the testimony is based on sufficient facts or data;
(c) the testimony is the product of reliable principles and
methods; and
(d) the expert has reliably applied the principles and
methods to the facts of the case.
Under Rule 702, trial courts act as gatekeepers who may admit expert testimony only if it is both
relevant and reliable. See Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579, 589 (1993).
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Here, Defendant concedes, for purposes of his Motion, that Plaintiff’s experts are qualified and
that the testimony is relevant. The only issue, then, is whether the testimony is reliable.
The trial judge has “considerable leeway in deciding in a particular case how to go about
determining whether particular expert testimony is reliable.” Kumho Tire Co. v. Carmichael,
526 U.S. 137, 152 (1999); see also Daubert, 509 U.S. at 588 (noting “the liberal thrust of the
Federal Rules and their general approach of relaxing the traditional barriers to ‘opinion’
testimony” in context of expert testimony) (internal quotation marks omitted).
In Daubert, the Supreme Court outlined four useful factors for evaluating the reliability of
scientific testimony under Rule 702: “(1) whether the theory or technique can be and has been
tested; (2) whether the theory or technique has been subjected to peer review and publication; (3)
the method’s known or potential rate of error; and (4) whether the theory or technique finds
general acceptance in the relevant scientific community.” Ambrosini v. Labarraque, 101 F.3d
129, 134 (D.C. Cir. 1996) (citing Daubert, 509 U.S. at 593-94). This “test of reliability is
‘flexible,’ and Daubert’s list of specific factors neither necessarily nor exclusively applies to all
experts or in every case.” Kumho, 526 U.S. at 141. Rather, the gatekeeping inquiry is tied to the
facts of each case. See Daubert, 509 U.S. at 591.
At the end of the day, the basic question posed by both Daubert and Rule 702 is this: Is
the proposed expert testimony “ground[ed] in the methods and procedures of science” and likely
to aid the jury, or is it mere “subjective belief or unsupported speculation,” liable to waylay the
finder of fact? Id. at 590.
III.

Analysis
In this case, Patteson must offer two types of causation evidence, both of which are

required to satisfy Rule 702 and Daubert: First, she must prove general causation – that is, that

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Seroquel, in fact, can cause tardive dyskinesia. Second, she must prove specific causation – that
is, that Seroquel caused her tardive dyskinesia. The Court will consider each separately.
A. General Causation
Maloney argues – despite Seroquel’s FDA-approved label warning that it can cause
tardive dyskinesia and a New England Journal of Medicine article to the same effect – that “[n]o
scientific methodology has attributed Seroquel to causing tardive dyskinesia.” Mot. at 4. He
further maintains that the study he will proffer – a clinical trial conducted by AstraZeneca, which
manufactures and sells Seroquel – uses a more rigorous methodology and hence is more reliable
than the studies Patteson will offer. See Supp. to Mot. to Preclude at 8-10. While a jury may
ultimately agree with this second argument, the sole question for the Court is whether Patteson’s
studies are sufficiently reliable under Rule 702 and Daubert to be admissible – not whether
Patteson’s studies trump Maloney’s. In so determining, the Court will examine each Daubert
factor in turn.
1. Ability To Be Tested
Patteson satisfies the first Daubert factor – i.e., whether her theory can be and has been
tested. The link between Seroquel and tardive dyskinesia has been tested by studying
populations of patients taking the drug and the relative frequency of tardive dyskinesia in those
populations compared to populations taking other medications. One such study, the Clinical
Antipsychotic Trials for Intervention Effectiveness – or CATIE study – was conducted in part by
one of Patteson’s expert witnesses, Yale University School of Medicine Professor Dr.
Rosenheck. See Rosenheck Aff. at 4. That study involved almost 2,000 patients in at least 57
sites across the United States. See id. at 5-8. The study compared both the effectiveness and the
side effects of multiple antipsychotic drugs, including first- and second-generation

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antipsychotics. See id. The data, according to Rosenheck, “to a reasonable degree of medical
and scientific probability establish a causal connection between quetiapine [the active ingredient
in Seroquel] and the development of TD [tardive dyskinesia].” Id. at 11. In other words, the link
between Seroquel and tardive dyskinesia has been tested, and at least one reliable study shows
that it exists.
2. Subjected to Peer Review and Publication
The CATIE study also satisfies the second factor, which asks if the theory was subjected
to peer review and publication. That study was peer reviewed and published in the New England
Journal of Medicine, one of the top-ranked medical journals in the United States, as well as in
Archives of General Psychiatry, the American Journal of Psychiatry, and Health Affairs. See id.
at 4. A similar study, published in the British Journal of Psychiatry, also found a link between
Seroquel and tardive dyskinesia. See id. at 10. The rigors of peer review and publication, then,
suggest that evidence linking Seroquel to tardive dyskinesia is reliable.
3. Known or Potential Rate of Error
As Maloney concedes, the third Daubert factor – whether the theory has a known or
potential rate of error – is not useful in this case, which involves a general (and generally
accepted) medical phenomenon rather than a testing methodology like fingerprinting or DNA
testing.
4. General Acceptance Within the Scientific Community
The final factor looks at whether the theory enjoys general acceptance within the
scientific community. Here, although Defendant’s primary expert Dr. Thor Rak’s contrary
position shows that the medical community is not unanimous in agreeing on a causal link, there is
sufficient acceptance for admissibility. To begin with, Seroquel’s own FDA-approved label

warns of tardive dyskinesia as a potential side effect. See Rak Dep. at 11:6-12:15, 13:7-15. In
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addition, copious medical literature points to the fact that both Seroquel and other first- and
second-generation antipsychotics can cause tardive dyskinesia. See Lo Aff., ¶ 21 (collecting
studies). Perhaps the most potent evidence that the medical community generally understands

that Seroquel can cause tardive dyskinesia is the fact that some of Maloney’s own experts – as
well as Maloney himself in his deposition – admit the link exists. See Maloney Dep. at 176:17177:9; Opp., Exh. E (Dr. Brent G. Petty Report) at 1; Exh. F (Dr. Jeffrey Lieberman Report) at 5.
The Court, accordingly, finds that the causal link between Seroquel and tardive dyskinesia is
sufficiently accepted by the medical community to be reliable.
***
Having considered the factors, the Court concludes that the relevant theory has been
tested, peer reviewed, and sufficiently accepted by the medical community. As the Court noted
in Daubert, the Federal Rules have a “liberal thrust” and take the “general approach of relaxing
the traditional barriers to ‘opinion’ testimony.” Daubert, 509 U.S. at 588 (internal quotation
marks omitted). Instead, “[v]igorous cross-examination” and “presentation of contrary
evidence” are the “appropriate means of attacking shaky but admissible evidence.” Id. at 596.
So it is here. Patteson’s proposed testimony is reliable, and the jury may decide for itself whose
scientific evidence is more persuasive.
B. Specific Causation
Although Maloney challenges the reliability of the testimony of Drs. Lo and Bose,
Patteson’s experts on specific causation, he never actually contests the reliability of their method
for determining specific causation: that is, the doctors’ process of reaching a differential
diagnosis. Instead, Maloney points to the facts that Lo and Bose have not diagnosed any other
patients with Seroquel-induced tardive dyskinesia and that neither could identify a study linking

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Seroquel to tardive dyskinesia where Seroquel was the only medication administered to patients.
Although those arguments may be useful on cross-examination, they are not enough to bar
testimony on specific causation under Rule 702 and Daubert.
All that Rule 702 and Daubert require is that the method used to arrive at a scientific
conclusion be reliable and reliably applied. See Daubert, 509 U.S. at 595. “Pertinent evidence
based on scientifically valid principles” will generally satisfy that demand. Id. at 597.
Here, the method used to determine that Seroquel caused Patteson’s tardive dyskinesia
was differential diagnosis. According to Lo, differential diagnosis involves “the creation of a list
of possible and/or most likely causes for a patient’s signs and symptoms, based on his/her
medical history, examination findings, and ancillary testing.” Lo Aff., ¶ 15. The doctor then
eliminates options from the list until the most likely cause is found. Picture a whiteboard filled
with possible medical culprits for a patient’s symptoms – familiar to fans of the medical
television drama House – and then watch each being methodically crossed off the list through
testing and deduction until a single diagnosis remains.
“Most circuits have held that a reliable differential diagnosis satisfies Daubert and
provides a valid foundation for admitting an expert opinion. The circuits reason that a
differential diagnosis is a tested methodology, has been subjected to peer review/publication,
does not frequently lead to incorrect results, and is generally accepted in the medical
community.” Turner v. Iowa Fire Equip. Co., 229 F.3d 1202, 1208 (8th Cir. 2000) (citing
Westberry v. Gislaved Gummi AB, 178 F.3d 257, 262-63 (4th Cir. 1999)).
Given the prevalence and reliability of differential diagnoses, the Court will allow
testimony from Patteson’s treating physicians indicating that, in their opinion and according to
their differential diagnoses, Seroquel caused Patteson’s tardive dyskinesia.

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C. Pretrial Hearing
Finally, because the Court believes that Plaintiffs’ expert testimony easily clears the
admissibility bar on causation, there is no reason to hold a pretrial Daubert hearing.
IV.

Conclusion
For the aforementioned reasons, the Court will deny Defendant’s Motion to Preclude

Testimony Regarding Seroquel-Induced Tardive Dyskinesia. A separate Order consistent with
this Opinion will be issued this day.
/s/ James E. Boasberg
JAMES E. BOASBERG
United States District Judge
Date: September 16, 2013

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