Timothy Boehm v. Eli Lilly & Company ( 2014 )

United States Court of Appeals
For the Eighth Circuit
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No. 13-1350
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Timothy Boehm
lllllllllllllllllllll Plaintiff - Appellant
v.
Eli Lilly & Company
lllllllllllllllllllll Defendant - Appellee
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Appeal from United States District Court
for the Eastern District of Arkansas - Little Rock
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Submitted: September 26, 2013
Filed: March 10, 2014
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Before LOKEN, COLLOTON, and BENTON, Circuit Judges.
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LOKEN, Circuit Judge.
Zyprexa (active ingredient olanzapine) is an “atypical” or “second generation”
antipsychotic drug manufactured and sold by Eli Lilly & Company (“Lilly”).
Timothy Boehm’s doctors prescribed Zyprexa to treat his bipolar disorder from
January 2003 until March 2007, when he developed symptoms later diagnosed as
tardive dyskinesia (“TD”) -- an involuntary movement disorder long recognized as
a side effect of antipsychotic drugs. Boehm brought this action, later removed by
Lilly, asserting personal injury and product liability claims. The district court1
granted summary judgment dismissing the failure-to-warn claim, applying the
Arkansas learned intermediary doctrine2 and concluding that Lilly adequately warned
Boehm’s treating and prescribing physicians of the risk of developing movement
disorders like TD. After Boehm dismissed his remaining claims,3 the district court
entered final judgment dismissing the complaint. Boehm appeals the summary
judgment order, including the district court’s decision to exclude expert testimony
that fifteen percent of Zyprexa users will develop TD after three years of use.
Reviewing the exclusion of expert evidence for abuse of discretion and the grant of
summary judgment de novo, we affirm.
I.
The testimony and medical records of two physicians who prescribed Zyprexa
to treat Boehm’s bipolar disorder are relevant to the summary judgment issues on
appeal. Dr. Forrest Miller, a general practitioner, first prescribed Zyprexa in January
2003, when Boehm complained of sleep problems, overwhelming anxiety, a racing
mind, and depression. Dr. Miller’s notes record that Boehm had been taking lithium,
but it was not effectively controlling these symptoms and was relatively unsafe for
1
The Honorable D.P. Marshall, Jr., United States District Judge for the Eastern
District of Arkansas.
2
“This doctrine provides that a drug manufacturer may rely on the prescribing
physician to warn the ultimate consumer of the risks of a prescription drug. The
physician acts as the ‘learned intermediary’ between the manufacturer and the
ultimate consumer.” West v. Searle & Co., 806 S.W.2d 608, 613 (Ark. 1991).
3
The district court dismissed two claims without prejudice. At oral argument,
Boehm agreed to accept dismissal of those claims with prejudice to ensure that we
have a final order to review.
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a patient like Boehm who was not monitored regularly. Dr. Miller prescribed
Zyprexa and an antidepressant. In the following months, Dr. Miller noted that Boehm
gained weight (a common Zyprexa side effect). But Boehm liked Zyprexa much
better than lithium, and his bipolar disorder was doing “extremely well.” Dr. Miller
testified that he planned to continue prescribing Zyprexa to Boehm “until it quits
working.” Though Boehm saw Dr. Miller only sporadically, pharmacy and clinic
records show that Dr. Miller refilled Zyprexa prescriptions and provided Boehm
Zyprexa samples through June 30, 2006.
In August 2006, Dr. Gregory Kaczenski, a psychiatrist, began treating Boehm
when he was hospitalized for increased depression and irritability. After Boehm’s
discharge, Dr. Kaczenski continued prescribing Zyprexa until late August, when he
prescribed a different second-generation antipsychotic, Geodon, because Boehm
wasn’t sleeping well and his appetite had increased. Dr. Kaczenski again prescribed
Zyprexa in October when Boehm reported that he preferred Zyprexa to Geodon. In
March 2007, Dr. Kaczenski noted that Boehm had “some difficulty with articulation”
and “a repetitive movement of his neck, pulling his head towards the left shoulder.”
Suspecting either dystonia or TD, Dr. Kaczenski stopped prescribing Zyprexa
because it was the most likely cause of these involuntary movements. Another
physician subsequently diagnosed Boehm as suffering from TD caused by
antipsychotic drug use. Boehm also claims to have torticollis, a type of dystonia.4
Dr. Miller and Dr. Kaczenski testified that they were well aware of the risks
and benefits of antipsychotics. Dr. Miller became familiar with the side effects of
older, “first-generation” antipsychotics, including movement disorders, when he
attended medical school across the street from a state hospital and observed patients
4
TD involves repetitive involuntary muscle movements. Dystonia involves
involuntary sustained muscle contractions. Torticollis is a type of dystonia that
involves twisting of the neck muscles. Boehm alleges that painful involuntary neck-
twisting motions make him unable to work and cause mental anguish.
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who suffered from these side effects. Dr. Kaczenski’s experience with the side
effects of first-generation antipsychotics began with his residency at a state hospital,
where it was “very, very common” to see patients suffering from movement disorders.
Because of these side effects, Dr. Miller does not prescribe first-generation
antipsychotics, and Dr. Kaczenski avoids prescribing them. Both doctors instead
prescribe atypical second generation antipsychotics like Zyprexa. In their experience,
these newer drugs are effective in treating serious psychiatric diseases, such as
schizophrenia and bipolar disorder; while they can cause the same movement
disorders as the first generation drugs, they do so much less frequently. Both doctors
continue to prescribe Zyprexa.
Since Zyprexa first came on the market, Lilly’s FDA-approved package insert
has expressly warned about the risk of developing TD:
Tardive Dyskinesia -- A syndrome of potentially irreversible,
involuntary, dyskinetic movements may develop in patients treated with
antipsychotic drugs. . . . Whether antipsychotic drug products differ in
their potential to cause tardive dyskinesia is unknown.
The risk of developing tardive dyskinesia and the likelihood that it
will become irreversible are believed to increase as the duration of
treatment and the total cumulative dose of antipsychotic drugs
administered to the patient increase. . . .
There is no known treatment for established cases of tardive
dyskinesia, although the syndrome may remit, partially or completely,
if antipsychotic treatment is withdrawn. . . .
Given these considerations, olanzapine should be prescribed in a
manner that is most likely to minimize the occurrence of tardive
dyskinesia. . . . In patients who do require chronic treatment, the
smallest dose and the shortest duration of treatment producing a
satisfactory clinical response should be sought. The need for continued
treatment should be reassessed periodically.
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If signs and symptoms of tardive dyskinesia appear in a patient on
olanzapine, drug discontinuation should be considered. However, some
patients may require treatment with olanzapine despite the presence of
the syndrome.
(Emphasis added.) The package insert also notes: “There is no body of evidence
available from controlled trials to guide” maintenance treatment of bipolar disorder
with Zyprexa, meaning treatment for longer than a month.5
Dr. Miller testified that his practice is to read a drug’s package insert before
ever prescribing it, and to re-read the insert occasionally to refresh his memory. Dr.
Kaczenski consults the Physicians’ Desk Reference, which contains package insert
information, and re-reads package inserts when they are updated. Dr. Kaczenski
testified that Lilly’s package insert was adequate to warn him of the risk of TD with
Zyprexa use. Independent of the package insert, Dr. Miller and Dr. Kaczenski
learned about Zyprexa’s side effects from their own clinical experience and from
speaking with their colleagues. Both doctors testified that an alternative warning
about the risk of movement disorders would not have changed their decisions to
prescribe Zyprexa to treat Boehm’s bipolar disorder.
Based on the express TD warning it gave all physicians, and the testimony of
Boehm’s prescribing physicians that they read the warning and considered it adequate
in deciding to prescribe Zyprexa, Lilly moved for partial summary judgment on the
failure-to-warn claim, relying on the learned intermediary doctrine.
5
The package insert also reported that the incidence of dystonia (including
torticollis) in a Zyprexa clinical trial was not significantly higher than with a placebo.
On appeal, Boehm asserts that this was far short of an adequate warning. We agree
with the district court that “Boehm has not produced any reliable evidence to show
an increased risk of torticollis and dystonia associated with Zyprexa [and therefore]
has not demonstrated the need for a warning.”
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II.
In opposing summary judgment, Boehm argued that Lilly failed to adequately
warn physicians of the risk of developing TD after long-term use of Zyprexa. Boehm
focused on additional deposition testimony by Dr. Miller and Dr. Kaczenski. After
Dr. Kaczenski described weight gain and movement disorders as two side effects that
can occur with long-term Zyprexa use, he was asked:
[Boehm’s counsel]: I’m going to ask you about something that -- a
figure that I have seen here, that 15 percent -- and I will ask you if you
are aware of this. But 15 percent of those who have taken neuroleptics,
such as Zyprexa, for three years, develop tardive dyskinesia?
[Dr. Kaczenski]: Yes, that’s a number I have known for a long time.
Counsel used that answer in cross-examining Dr. Miller at his subsequent deposition:
[Boehm’s Counsel]: Did you receive any information that once a patient
is prescribed Zyprexa for three years, one in six patients will develop
tardive dyskinesia? Were you told that?
* * * * *
[Dr. Miller]: No.
Q: All right. If you had known that, and that is an established fact in
this case pursuant to Doctor Kaczenski’s deposition testimony * * * --
that the inciden[ce] of tardive dyskinesia increases to one in six patients
after three years of use, would you still have prescribed that to Tim
Boehm?
* * * * *
A: Not for that long.
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Q: All right. That’s just too long, isn’t it?
A: That’s too long.
To satisfy its duty to warn, the manufacturer of an “unavoidably unsafe” but
beneficial prescription drug must make “an adequate warning” to prescribing
physicians of the risks of adverse side effects. West, 806 S.W.2d at 613, applying
comment k to § 402A of the Restatement (Second) of Torts and the learned
intermediary doctrine. After initial briefing, the district court concluded “that this
testimony [by Dr. Miller], if supported, could create a triable issue” as to the
adequacy of Lilly’s TD warning. But the court noted that “Dr. Kaczenski did not
offer the 15% risk figure on his own; the percentage was part of a leading question.”
Accordingly, the court “requested briefing on whether . . . the alleged 15% risk was
supported by [scientific] evidence that would be admissible under Daubert [v. Merrell
Dow Pharmaceuticals, Inc., 509 U.S. 579 (1993)].”
In response, Boehm relied on the opinion of his expert, psychiatrist Dr. Stefan
Kruszewski. Based on “clinical experience and review of relevant literature,” Dr.
Kruszewski opined that “Zyprexa is capable of a high rate of incident tardive
dyskinesia/dystonia after three years of use, affecting between 15-20% of those
prescribed the drug.” When Lilly challenged that opinion as lacking scientific
support, Dr. Kruszewski submitted two supplements to his report. The first
supplement cited two additional sources. First was an article by Dr. Patricia Deegan
published on the National Empowerment Center website claiming: “Different studies
quote different rates of tardive dyskinesia ranging from 15%-20% for people using
[antipsychotics] for more than three years.” The article stated that Zyprexa “has been
found to cause TD” but listed no sources for its information. The second new source
was a webpage where Dr. Peter Breggin advertises his work as an expert witness in
TD-related cases. Without citing a source, the webpage claims: “The rates for TD
are astronomical. In otherwise physically healthy adults, 5%-8% per year will
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develop the disorder, with cumulative rates in the range of at least 15%-20% for the
first three years.” Dr. Breggin claims it is “simply untrue” that “the newer or atypical
antipsychotic drugs cause TD at a very low rate.” Again, the only Zyprexa-specific
claim was that it can cause TD.6
Dr. Kruszewski again supplemented his report with a 2010 peer-reviewed study
comparing TD incidence rates for users of first-generation and second-generation
antipsychotic drugs.7 The study concluded: “[T]he incidence rate of TD with atypical
antipsychotics, while modestly reduced, remains substantial . . . . Despite the feeling
among some clinicians that TD is much less of a problem now in the atypical era,
such a conclusion may unfortunately be premature.” As Lilly pointed out, two
implications of the study data suggest that bipolar patients taking Zyprexa can expect
better results than other patients. First, the Woods study notes: “Little TD advantage
for atypicals was apparent in schizophrenia subjects, while a relatively strong
advantage was estimated in affective disorder subjects.” Second, based on available
data differentiating specific drugs, the study reported that “olanzapine [Zyprexa]
showed the lowest relative TD rate” in the second-generation group.
The district court concluded that Dr. Kruszewski’s first supplement -- a blog
post and website advertising -- “are a deficient foundation” to support Dr.
6
The cite for Dr. Deegan’s article is Tardive Dyskinesia and Tardive Dystonia:
where you can turn for help, National Empowerment Center, http://www.power2u.
org/articles/selfhelp/tardive.html (last visited Dec. 10, 2013). Dr. Breggin’s cite is
Selected Tardive Dyskinesia (TD) cases, Psychiatric Drug Facts with Dr. Peter
Breggin, http://breggin.com/index.php?option=com_content&task=view&id=184
(last visited Dec. 10, 2013). Copies of these internet materials are on file in the
Clerk’s Office.
7
Woods, S.W., et. al., Incidence of Tardive Dyskinesia with Atypical Versus
Conventional Antipsychotic Medications: A Prospective Cohort Study, J. Clin.
Psychiatry 71(4): 463-474 (2010) (the “Woods study”).
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Kruszewski’s 15% risk figure. Though the second supplement was a peer-reviewed
study in a well respected journal, the court reasoned, the Woods study “was not
designed to establish the risk of a particular drug, only the risk of a class of drugs to
which Zyprexa belongs.” The Woods study “does not even attempt to establish that
Zyprexa is a twin to conventional antipsychotics,” and it “indicates that Zyprexa
carries a lower risk of [TD] than other atypical antipsychotics.” Concluding there “is
too great an analytical gap to extract from the Woods study the 15% incidence rate
Dr. Miller said would have changed his prescribing decisions,” the court excluded all
evidence of that risk percentage under Daubert. The court then granted summary
judgment dismissing Boehm’s failure-to-warn claims because there was no genuine
issue of material fact as to the adequacy of Lilly’s TD warnings.
III.
On appeal, Boehm argues the district court erred in excluding Dr. Kruszewski’s
expert opinion that 15% of Zyprexa users will develop TD after three years of use.
Because the grant of summary judgment turned on this ruling, we will review it first.
Junk v. Terminix Int’l Co., 628 F.3d 439, 447 (8th Cir. 2010), cert. denied, 132 S. Ct.
94 and 95 (2011). “We reverse a trial court’s decision on the admissibility of expert
evidence only on the basis of a clear and prejudicial abuse of discretion.” Id.In determining whether to admit a qualified expert’s opinion testimony under
Rule 702 of the Federal Rule of Evidence, the district court acts as a gatekeeper to
“ensure that any and all scientific testimony or evidence admitted is not only relevant,
but reliable.” Daubert, 509 U.S. at 589. If “opinion evidence . . . is connected to
existing data only by the ipse dixit of the expert,” a district court “may conclude that
there is simply too great an analytical gap between the data and the opinion
proffered.” Gen. Elec. Co. v. Joiner, 522 U.S. 136, 146 (1997).
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Here, after giving Boehm ample opportunity to supplement Dr. Kruszewski’s
initial, inadequately supported opinion, the district court reasonably concluded that
Boehm had not provided sufficient scientific support for that opinion. The internet
materials in the first supplement provided no supporting data or sources for their
general assertions relating to Zyprexa; the Woods study, while peer-reviewed, was
not designed to establish a TD incidence rate for Zyprexa and in fact contained
findings that undermined Dr. Kruszewski’s opinion that Zyprexa causes TD in bipolar
patients at the same 15-20% rate as first-generation antipsychotics. On this record,
we conclude that it was well within the district court’s substantial discretion to
exclude Dr. Kruszewski’s 15% risk opinion.
IV.
Boehm further argues the district court erred in granting summary judgment
dismissing the failure-to-warn claim, even without Dr. Kruszewski’s 15% risk
opinion. The learned intermediary doctrine does not apply, Boehm argues, because
he presented substantial evidence that Lilly’s warning to physicians as to the risk of
developing TD after long-term use of Zyprexa was inadequate. The district court
carefully summarized “the essential and undisputed material facts” that warranted the
grant of summary judgment absent reliable scientific evidence of a known 15% risk
factor for long-term use of Zyprexa:
Lilly’s package insert warned the prescribing doctors that, though [TD]
was an infrequent side effect, the risk that it would occur and become
irreversible . . . was believed to increase as treatment continued over
time and the patient’s total cumulative dose increased. . . . No studies
or other evidence existed to guide prescribers about deploying the drug
for more than one month. . . . Drs. Miller and Kaczenski knew all these
risks from reading the Zyprexa package insert and from their experience
with first and second generation anti-psychotic medicines. They
prescribed Zyprexa for Timothy Boehm across many years because,
weighing the risks against the benefits of treating his bipolar disorder,
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in their opinion the drug helped him. These two main prescribers
thought Lilly’s warning adequate. Both are still prescribing Zyprexa to
other patients.
After careful consideration of the extensive summary judgment record, we agree. On
appeal, Boehm places great emphasis on the testimony in which Dr. Miller agreed
that prescribing Zyprexa for three years was “too long” given the 15% risk of
developing TD. But that testimony was based on Boehm’s counsel instructing Dr.
Miller that a 15% risk factor for Zyprexa users had been established by Dr.
Kaczenski’s testimony, which was untrue. On this record, the district court properly
applied the learned intermediary doctrine in dismissing the failure-to-warn claim.
V.
Boehm further argues the district court erred in rejecting his contention that
Lilly’s overpromotion of Zyprexa negated an otherwise adequate warning of the risk
that users will develop movement disorders including TD. A few courts have
recognized an overpromotion “exception” to the learned intermediary doctrine. The
Supreme Court of Arkansas has not addressed the issue. The exception applies in
“unusual cases” where a plaintiff can “establish with individualized proof” that a drug
manufacturer’s excessive promotion of its product “caused the [plaintiff’s] physician
to initiate or maintain the prescription at issue.” In re Zyprexa Prods. Liab. Litig.,
649 F. Supp. 2d 18, 33 (E.D.N.Y. 2009) (emphasis in original).
Here, the district court expressed doubt that the Supreme Court of Arkansas
would recognize an overpromotion exception to the learned intermediary doctrine.
But in any event, the court concluded, the exception would not apply in this case
because Boehm presented “no evidence that any representation by a salesperson
affected a prescribing doctor’s decision to continue Boehm on Zyprexa,” and because
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“[t]here is no reliable evidence that Zyprexa had significantly more risk of movement
disorders than the drug reps allegedly said it had.” We agree.
The summary judgment record includes substantial evidence that Lilly
aggressively marketed Zyprexa to doctors, including Dr. Miller and Dr. Kaczenski,
instructing its marketing representatives to make personal calls to promote Zyprexa
by discussing bipolar symptoms and stressing Zyprexa’s “safety,” “efficacy,” and
“ease of use” for treating bipolar patients. But there is no evidence that any
representative made statements to Dr. Miller or to Dr. Kaczenski that negated the
package insert warning, and there is no evidence their prescribing decisions were
affected by the Lilly representatives’ statements regarding the risk of TD. Therefore,
even if Arkansas would recognize this exception, Boehm failed to prove that Lilly
overpromoted Zyprexa, that its promotional efforts negated the written warnings, or
that these promotional efforts had any effect on the decisions by Dr. Miller and Dr.
Kaczenski to prescribe Zyprexa for the continued treatment of Boehm’s bipolar
disorder. Accord Dean v. Eli Lilly & Co., 387 Fed. App’x 28, 30 (2d Cir. 2010)
(unpublished); Patteson v. AstraZeneca, L.P., 876 F. Supp. 2d 27, 34-37 (D.D.C.
2012); In re Zyprexa Litigation, 649 F. Supp. 2d at 33.
The judgment of the district court is affirmed.
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