Court Opinion

ID: 3004089
Source: CourtListenerOpinion
Date Created: 2015-09-24 22:35:29.270399+00
Date Added: 2024-06-11T08:03:49.325970
License: Public Domain

In the

United States Court of Appeals
              For the Seventh Circuit

No. 08-2265

B ONNIE J. M ASON, individually and
as co-administrator of the estate of
Tricia M. Mason, deceased, and
W ILLIAM L. M ASON, individually
and as co-administrator of the
estate of Tricia M. Mason, deceased,

                                            Plaintiffs-Appellants,
                               v.

S MITHKLINE B EECHAM C ORPORATION,
doing business as GlaxoSmithKline,
a Pennsylvania corporation,
                                             Defendant-Appellee.

           Appeal from the United States District Court
                for the Central District of Illinois.
            No. 05 C 1252—Michael M. Mihm, Judge.

   A RGUED O CTOBER 5, 2009—D ECIDED F EBRUARY 23, 2010
2                                                 No. 08-2265

 Before E VANS and SYKES, Circuit Judges, and SIMON,
District Judge.
  E VANS, Circuit Judge. Twenty-three-year-old Tricia
Mason committed suicide on March 2, 2003, two days
after she started taking Paxil, a popular antidepressant.
Her parents sued the manufacturer of the drug, the
Smithkline Beecham Corporation, claiming it was
negligent (among other things) for not warning that
taking Paxil increases the risk of suicide, especially
among young adults. The district court granted sum-
mary judgment for the company in 2008. The court con-
cluded that the Masons’ claims were preempted under
federal law because the warnings they say should
have been included about Paxil conflicted with the FDA-
approved warning labeling for the drug.
  One year after the district court granted the defen-
dant’s motion for summary judgment, the Supreme Court
decided Wyeth v. Levine, 555 U.S. ___, 129 S. Ct. 1187 (2009),
a case that represents a sea change in the way courts
are to consider issues of federal preemption. Keeping
the changed landscape in mind, we today consider the
Masons’ appeal in light of Levine.
  Before going further, however, we note that the district
court, on the opening page of its opinion granting sum-
mary judgment, said:


   The Honorable Philip P. Simon, United States District Court
Judge for the Northern District of Indiana, sitting by designa-
tion.
No. 08-2265                                              3

     The Court notes that the portions of the briefs ad-
   dressing statements of undisputed and disputed
   fact that have been submitted by both Plaintiffs
   and Defendant are so replete with argumentative
   posturing that they are essentially useless both in
   determining the basic factual information underlying
   this case, as well as in resolving the pending motions.
   The inclusion of 13 and 11 pages of “Introduction” that
   is reminiscent of closing argument is also wholly
   inappropriate. Counsel should consider themselves
   on notice that future filings of this nature will be
   immediately stricken by the Court.
  Any improvement in the tone and substance of the
briefs on appeal is slight at best. They are still, as the
district court observed, “replete with argumentative
posturing.” That’s unfortunate. At this point in the pro-
ceeding, all that really needs to be said is that Tricia
Mason committed suicide two days after taking Paxil.
The briefs, however, go far beyond this statement. The
plaintiffs paint a rather bright picture of Tricia. The de-
fendant’s picture is much darker.
 The Masons tell us this about their daughter:
     Throughout her life, Tricia Mason was an excellent
   student, she was close with her family and enjoyed
   dancing. She was the salutatorian of her high school
   graduating class, excelled in science and aspired to
   become a pediatrician. She was pursuing a Masters
   degree at Illinois State University.
     On February 27, 2003, Tricia went to a medical clinic
   complaining of a sore throat. During her consultation
4                                              No. 08-2265

    with the nurse practitioner, she informed the nurse
    that she was also having difficulty getting up in the
    morning, she was eating less and believed she might
    be suffering from seasonal affective disorder. The
    nurse practitioner diagnosed Tricia with depression
    and gave her some samples of Paxil. On March 2,
    2003, two days after starting Paxil, Tricia committed
    suicide by ingesting cyanide.
Here’s how the defendant paints the picture:
      Tricia Mason had a family history marked by depres-
    sion and suicide attempts. Ms. Mason herself
    struggled with depression long before her suicide
    in March 2003. In 1999-2000, Ms. Mason began ex-
    periencing depression during the winter months.
      As time progressed, Ms. Mason’s depression wors-
    ened. After a New Year’s Eve party, Dones [Ms. Ma-
    son’s boyfriend] again told Ms. Mason the relation-
    ship had no future. Upon hearing that, Ms. Mason
    told Dones she had prepared a mix of lethal chemicals
    and intended to kill herself. Dones made Ms. Mason
    promise she would not commit suicide.
      Ms. Mason’s depression continued throughout
    February 2003. Around Valentine’s Day, Ms. Mason
    told Jason Pemberton, another boyfriend, she
    intended to kill herself.
     ....
      On February 27, 2003, Ms. Mason visited her nurse
    practitioner complaining of cold symptoms. Ms. Mason
No. 08-2265                                               5

    took the opportunity to discuss her depression and
    expressed interest in seeing a counselor. Contrary to
    the suicide threats she had recently expressed,
    Ms. Mason denied she had been having suicidal
    thoughts. The nurse provided Ms. Mason with
    samples and a prescription for Paxil.
      Two days later, on March 2, Ms. Mason corre-
    sponded with Dones by instant messaging. Dones told
    Ms. Mason her behavior over the past few months
    made it “impossible” to continue their relationship.
    Ms. Mason told Dones, “Farewell, my love.” She
    then signed off her computer.
      Hours later, Tricia Mason committed suicide by
    ingesting cyanide. She was 23 years old.
  If this case ever gets to a jury, it will consider all the
facts and circumstances surrounding Tricia’s life and
suicide. We need not concern ourselves with how she
should be viewed. In addition, a jury might well con-
clude that she committed suicide without any help
from Paxil. These are not our concerns. Our issue is a
legal one, and so we soldier on, mindful, however, that
the parties have been extremely partisan in the way
they have presented the case to us.
  The central issue of this case is federal preemption,
which occurs when a state law is invalidated because it
conflicts with a federal law. The constitutional basis for
federal preemption is found in the Supremacy Clause
(Article VI, Clause 2 of the U.S. Constitution), which
states, “[T]he Laws of the United States . . . shall be the
6                                               No. 08-2265

supreme Law of the Land[.]” Preemption comes in
three forms. First, and the easiest to apply, is express
preemption which occurs when Congress clearly declares
its intention to preempt state law. Second, we have
implied preemption which occurs when the “structure
and purpose” of federal law shows Congress’s intent
to preempt state law. Finally, we come to conflict preemp-
tion which occurs when there is an actual conflict
between state and federal law such that it is impossible
for a person to obey both. See English v. Gen. Elec. Co., 496
U.S. 72, 79, 110 S. Ct. 2270, 110 L. Ed. 2d 65 (1990). Con-
flict preemption is the type of preemption at issue in
this case.
   Interestingly enough, the idea of conflict preemption
in prescription drug cases is relatively new. Until the
early 2000s, prescription drug companies infrequently
invoked the preemption defense, and when they did,
it rarely succeeded. See, e.g., Tobin v. Astra Pharm. Prods.,
Inc., 993 F.2d 528, 537 (6th Cir.), cert. denied, 510
U.S. 914 (1993); Hill v. Searle Labs., 884 F.2d 1064, 1068
(8th Cir. 1989). This changed in 2001 when district courts
were inundated with preemption motions in prescrip-
tion drug cases. In a number of these cases, the FDA
filed amicus briefs in support of the pharmaceutical in-
dustry. In 2006, the FDA also released statements and
revised its regulations in an attempt to bolster the drug
manufacturers’ preemption defense. Not surprisingly,
courts began to issue contradicting opinions, which
led the Supreme Court to grant certiorari in Levine to
decide the issue.
No. 08-2265                                              7

  In Levine, the Supreme Court restored the preemption
landscape to its pre-2001 form. The plaintiff in Levine
was severely injured (she developed gangrene and her
forearm had to be amputated) when a physician’s
assistant injected her artery with the antinausea drug
Phenergan by using the “IV-push” method of injection.
She sued Wyeth, the manufacturer of Phenergan, for
failing to provide an adequate warning about the dif-
ferent risks involved with the various methods of ad-
ministering the drug. A jury concluded that Wyeth had
indeed failed to provide an adequate warning about
the significant risks involved when Phenergan is admin-
istered by using the IV-push method.
  On appeal, Wyeth argued that the plaintiff’s state law
failure-to-warn claims were preempted because it was
impossible for the manufacturer to comply with both
state law duties and federal labeling obligations. It also
argued that the state law suits would undermine Con-
gress’s intent to trust labeling decisions to the expertise
of the FDA. The Supreme Court rejected both conten-
tions and held that there was no preemption in either
instance. In fact, the Court noted that state law claims
are an important complement to the FDA’s Herculean
task of regulating the safety and effectiveness of all pre-
scription drugs. Although the Court found that preemp-
tion did not exist in Levine, it held that there could
be preemption if the manufacturer met the stringent
standard of proving that there was clear evidence the FDA
would have rejected the proposed change in the drug’s
label. The Supreme Court, however, did not clarify what
8                                                      No. 08-2265

constitutes “clear evidence.” Therefore, the only thing
we know for sure is that the evidence presented in
Levine did not meet this exacting standard.1
  The journey to deciphering the “clear evidence” standard
begins with understanding how drug manufacturers
receive approval to market new prescription drugs
and to change a label once it has been approved. Before
marketing a new drug, the manufacturer must submit
a New Drug Application to the FDA, which demonstrates
by “substantial evidence” that the medication is effica-
cious. 21 U.S.C. 355(d)(5). The FDA’s approval is then
conditioned on the manufacturer’s use of the label it
suggests. 21 C.F.R. § 314.105(b). Even after the medica-
tion is approved, the FDA continues to have authority
over it and its label. 21 C.F.R. 314.80-.81. The manu-
facturer, however, has the ability to change the label
without FDA approval through a “changes being effected”
(CBE) labeling change. The CBE regulation allows a
manufacturer to modify a label to “add or strengthen a
contraindication, warning, precaution, or adverse reac-

1
  It’s perhaps worth noting that just a few months ago, the
Eighth Circuit rejected, rather summarily, a preemption argu-
ment fairly close to the one Smithkline Beecham advances in
this case. In In re Prempro Products Liability Litigation, 586 F.3d
547 (8th Cir. 2009), the plaintiff alleged that as a result of taking
estrogen and progestin drugs, she developed breast cancer.
She sued the drug manufacturers for failure to warn of the risk
of breast cancer. In rejecting preemption in less than half a page,
the Eighth Circuit said, “The Supreme Court’s recent decision
in [Levine] has foreclosed this preemption argument.”
No. 08-2265                                                9

tion” or to “add or strengthen an instruction about
dosage and administration that is intended to increase
the safe use of the drug product” and to do so when it
files its supplemental application, before the FDA has
the opportunity to consider whether or not it will accept
the change. 21 C.F.R. § 314.70(c)(6)(iii)(A), (C). The
ability to make CBE labeling changes underscores a
central premise of federal drug regulation: A “manufac-
turer bears responsibility for the content of its label at
all times.” Levine, 129 S. Ct. at 1197-98. While it is impor-
tant for a manufacturer to warn of potential side effects,
it is equally important that it not overwarn because
overwarning can deter potentially beneficial uses of the
drug by making it seem riskier than warranted and can
dilute the effectiveness of valid warnings. Therefore,
warnings may only be added when there is “reasonable
evidence of an association of a serious hazard with the
drug.” 21 C.F.R. § 201.57(e)(2003).2 It is technically a
violation of federal law to propose a CBE that is not
based on reasonable evidence. 18 U.S.C. § 1001.
  Since Levine is our intellectual anchor—if the evidence
here is less compelling than it was in Levine, we will not
find preemption—we must look at the long and fairly
extensive administrative history of Phenergan and com-
pare it to the administrative history of Paxil. The FDA
approved Phenergan in 1955. Wyeth submitted supple-

2
  Section 201.57 was amended in 2006. The standard for
“older drugs,” including Paxil, is now located at 21 C.F.R.
§ 201.80(e).
10                                                No. 08-2265

mental new drug applications in 1973 and 1976 which
the FDA approved after proposing labeling changes. In
1981 Wyeth submitted a third supplemental application
in response to a new FDA rule governing drug labels. The
Court then notes that “[o]ver the next 17 years, Wyeth
and the FDA intermittently corresponded about
Phenergan’s label.” Levine, at 1192. The most notable of
these correspondences occurred in 1987 when the FDA
suggested alternative warnings regarding arterial
exposure 3 and in 1988 when Wyeth submitted a proposed
label which incorporated the suggestions. The FDA
did not contact Wyeth again until 1996 when it told
Wyeth to retain the wording on its current label. In 1990,
the FDA finally approved Wyeth’s 1981 application and
mandated that the wording on the label must be
identical to the package insert. On April 7, 2000, the
plaintiff in Levine received the dose of Phenergan that
caused her injury.
  While the opinion in Levine covers the administrative
history and record, the dissent delves even deeper. When
the dissent and the majority disagree in the characteri-
zation of the record or administrative history, we of
course follow the majority’s view.4 According to the

3
  Phenergan causes gangrene when injected into an artery,
which was the exact mishap responsible for the injury to the
plaintiff in Levine.
4
  The majority and dissent disagree about the categorization of
the warning Wyeth proposed in 1988. Compare, Levine at 1218 n.1
                                                 (continued...)
No. 08-2265                                                  11

dissent, “For at least the last 34 years, the FDA has focused
specifically on whether IV-push administration of
Phenergan is ‘safe’ and ‘effective’ . . . . And the record
contains ample evidence that the FDA specifically con-
sidered and reconsidered the strength of Phenergan’s IV-
push-related warnings in light of new scientific and
medical data.” Levine, at 1222. The dissent then meticu-
lously lists the various times the FDA considered a dif-
ferent warning label regarding the IV-push method. It
begins in 1975 when several people from Wyeth and
several members of the FDA met regarding Phenergan’s
label and the FDA proposed that Phenergan should not
be injected via Tubex, which is a syringe system used
exclusively for IV push. Instead of banning the use of IV
push altogether, both parties agreed that there was
instead a need for better instruction regarding the prob-
lems of intra-arterial injection. A year later, an FDA
committee recommended an additional IV-push-
specific warning for Phenergan’s label but decided not
to prohibit using the IV-push method. In its labeling

4
   (...continued)
(Alito, J., dissenting) (“Indeed, respondent conceded below
that Wyeth did propose an adequate warning of Phenergan’s
risks. Specifically, respondent noted: ’In 1988, Wyeth proposed
language that would have prevented this accident by requiring
a running IV and explaining why a running IV will address
and reduce the risk [of intra-arterial injection].’ ”) (internal
citations omitted), with Levine at 1199 n.6 (“The dissent’s
suggestion that the FDA intended to prohibit Wyeth from
strengthening its warning does not fairly reflect the record.”).
12                                                  No. 08-2265

order, the FDA cited numerous sources describing the
costs and benefits of IV push including published case
reports from 1960 about cases of gangrene caused by the
intra-arterial injection of Phenergan. Taking Levine as a
whole, it is clear from the ample administrative record
that the FDA strongly considered a similar warning to
the one the plaintiff proposed and the Court still did not
find preemption.
  Now that we know what falls short of “clear evidence,”
we turn our attention to the administrative record of
Paxil and see if it is any more compelling. Paxil belongs
to a class of prescription antidepressants known as selec-
tive serotonin re-uptake inhibitors (SSRIs). SSRIs operate
by controlling the manner in which serotonin is
processed by brain cells. They force serotonin to stay
longer between brain cells, which allegedly improves the
mood of patients. Prozac, the first SSRI, is quite well-
known. Anyone who has ever watched The Sopranos5
knows that it’s the drug Dr. Jennifer Melfi prescribed for
Tony Soprano after telling him “no one needs to
suffer from depression with the wonders of modern
pharmacology.”
  Smithline Beecham (we’ll refer to the company from
now on as “GSK,” the initials of an entity that it does

5
  The Sopranos, of course, was a critically acclaimed drama that
aired between 1999 and 2007 (86 episodes) on HBO. It is the
most financially successful cable series in the history of televi-
sion and is acknowledged as one of the greatest television
series of all time.
No. 08-2265                                                     13

business under) recounts the regulatory history of Paxil
to show that there is clear evidence that the FDA
would not have approved the labeling change the
plaintiffs say was necessary. GSK filed a “New Drug
Application” (NDA) with the FDA in 1989 seeking ap-
proval to market Paxil for the treatment of depression
in adults. The FDA approved Paxil—without a warning
about suicide.
  The plaintiffs allege6 that the FDA was misled because
GSK included suicides and suicide attempts that
occurred during the wash-out phase7 of the clinical trials
for Paxil and counted them as if they occurred during
the actual trial when a subject was on a placebo. Since

6
   The plaintiffs also allege that GSK contaminated the adminis-
trative history of Paxil by using the term “emotional lability” to
disguise suicidal behavior that was reported during the clinical
trials. GSK does not deny that it coded data as “emotional
lability” but maintains that when the FDA analyzed this
data in February of 2003—a month before Tricia’s death—it
included all of the proper suicide data regardless of coding
and still did not find any relationship between suicidal
behavior and Paxil. Therefore, this allegation does not call
into question the data the FDA used to evaluate Paxil.
7
  One of the difficulties with conducting studies for Paxil is that
the participants are frequently taking other medications when
they begin the study. In order to start the study with a clean
slate, there is a “wash-out” phase that usually lasts for one or
two weeks where everyone in the study is given a placebo to
make sure their old drugs are out of their systems and
are not responsible for any changes in mood or behavior.
14                                                No. 08-2265

the wash-out phase occurs before the study begins, events
that occur during that phase should not be counted. By
attributing the negative outcomes that occurred during
this period to the placebo, Paxil looks better by compari-
son.
  This allegation is partially true. In its 1989 NDA, GSK
presents the suicide data in a table that counts wash-out
suicidal behavior as if it occurred during the study
while subjects were taking placebos. However, each
erroneous datum had a star by it which noted that part
of the suicidal behavior occurred during the wash-out
phase. It appears that Dr. Brecher, the FDA scientist
who reviewed GSK’s application, understood that the
wash-out events were included when he analyzed the
data and found no relationship between Paxil and
suicidal behavior. Furthermore, in May 2002 and Feb-
ruary 2003, GSK re-analyzed the data by excluding wash-
outs and noncontrolled 8 studies and submitted that data
to the FDA. GSK’s analysis found that there was still

8
  A noncontrolled study is a study where there is no control
group. In other words, a noncontrolled study is a study in
which all of the participants take a prescription drug and none
of them take a placebo. Having a control group is important
when analyzing suicidal behavior data because suicidal behav-
ior is a symptom of depression and related diseases. Therefore,
a certain number of depressed people who are not taking
medication will exhibit suicidal behavior. Having a control
group establishes a baseline with which the manufacturer
can compare the suicidal behavior rate of participants taking
the prescription drug.
No. 08-2265                                               15

no relationship between suicide and Paxil. Overall, the
plaintiffs’ allegations do not taint the administrative
history of Paxil.
   That the FDA initially approved Paxil after considering
the proper data does not provide much, if any, evidence
that the FDA would have rejected the warning the plain-
tiffs say should have been in place before Tricia took
her life. In Levine, the Court held that FDA approval by
itself does not warrant preemption. Levine, 129 S. Ct.
at 1191. Furthermore, since GSK, not the FDA, retains
responsibility for Paxil’s label, the FDA’s initial approval,
more than a decade before, isn’t a great comfort to
GSK’s case.
  Next, GSK highlights that the FDA had been thoroughly
reviewing the data available about SSRIs and suicide
and concluded there was not an increased risk of self-
harm from SSRIs. In particular, it points out that on
three separate occasions the FDA rejected a citizen
petition for a labeling change for Prozac that would have
included a warning about suicide. The FDA’s rejection
of the Prozac warnings, however, is not as clear-cut as
GSK would have us believe. During a meeting of the
FDA’s psychopharmacological drug committee, Dr. Paul
Leber—the Director of the Division of Neuropharmaco-
logical Drug Products—gave a presentation about the
potential link between suicide and antidepressants and
stated, “[N]obody in the agency dismisses the possi-
bility that antidepressants in general and fluoxetine in
particular may have—and I emphasize ‘may’—the capacity
to cause untoward injurious behaviors, acts, and/or
16                                                No. 08-2265

intensify them.” Additionally, in the very letter that
rejected a citizen petition to change the label on Prozac, the
FDA noted that more research needs to occur to explore
the relationship between antidepressants and suicidality.
Overall, we do not find the FDA’s rejection of the
citizen petitions or its call to do more research very com-
pelling for either side. Even the latest of these findings
was made several years before Tricia’s suicide. This
temporal gap is especially important in the analysis of
prescription drugs because it constantly evolves as
new data emerges. Furthermore, even though Prozac and
Paxil are both SSRIs, they are different drugs made by
different manufacturers. Therefore, we give little weight
to the administrative history of Prozac when we are
concerned with whether there is clear evidence that the
FDA would have rejected a labeling change in Paxil.
  GSK also tries to show that the FDA’s inaction, as in its
failure to mandate a warning about the risk of suicide,
around the time of Tricia’s death is clear evidence that
the FDA would not have approved the change in the
label the plaintiffs seek. GSK highlights that after Paxil’s
approval, it submitted a detailed annual report that
included postmarketing adverse events and clinical
investigations of Paxil to the FDA. Additionally, it
points out that the FDA approved nine new indications 9
for Paxil, each time reviewing all of the safety data about
Paxil, including the suicide data. In particular, GSK

9
   In medical terminology, an indication is a disease or condi-
tion a drug can treat.
No. 08-2265                                              17

emphasizes that it submitted the available data on
Paxil and suicide ten months and one month prior
(May 2002 and February 2003) to Tricia’s suicide, and
three months after (June 2003) Tricia’s suicide the FDA
published a press release that concluded there was no
increased risk of suicide in adults. GSK maintains that
the FDA appropriately failed to issue a warning about
Paxil and suicidality because there was no evidence to
merit it from the information available. While what GSK
points out is true, it only tells one side of the story.
For example, GSK ignores the main purpose of the
June 2003 press release, which was to recommend
that doctors stop using Paxil to treat pediatric major
depressive disorder (MDD) because the FDA was
currently reviewing reports of increased risks of suicide
and suicidal behavior with the drug. Then, in October
of 2003, the FDA informed health care providers of a
possible increased risk of suicidality in pediatric, but not
adult, patients. Therefore, it seems unlikely that the
FDA would have refused to allow GSK to warn about a
possible risk of suicide for young adults when it had
already warned the public that Paxil was potentially
unsafe for 17-year-olds with MDD.
  Finally, in 2006, using a CBE labeling change, GSK
warned that Paxil was associated with an increased risk
of suicide in adults. Then, in May of 2007, the FDA
ordered all antidepressant manufacturers to include
an additional warning about the increased likelihood of
suicidality in young adults under the age of 24. GSK
maintains that the methods used to analyze the data
were not available at the time of Tricia’s death. Further-
18                                            No. 08-2265

more, it claims that it did not have access to the pool
of data that the FDA used to determine that these
risks exist. Since these events occurred well after
Tricia’s suicide, they are not persuasive in determining
whether there was clear evidence that the FDA would
have rejected the proposed warning at the time of Tricia’s
death. To the extent these subsequent events have any
sway, however, they clearly cut towards making it less
likely that the FDA would have rejected the plaintiffs’
proposed warning in 2003. Therefore, in light of the
extensive showing required by Levine, we conclude that
GSK did not meet its burden of demonstrating by clear
evidence that the FDA would have rejected a label
change warning about the risk of suicide by young adults
before Tricia’s life came to an end at 23. Consequently,
the plaintiffs’ claims are not preempted.
  For these reasons, the judgment of the district court is
R EVERSED and the case R EMANDED for further proceedings.

                          2-23-10