In the

United States Court of Appeals

For the Seventh Circuit

No. 08-2265

BONNIE J. MASON, individually and

as co-administrator of the estate of

Tricia M. Mason, deceased, and

WILLIAM L. MASON, individually

and as co-administrator of the

estate of Tricia M. Mason, deceased,

Plaintiffs-Appellants,

v.

SMITHKLINE BEECHAM CORPORATION,

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.

ARGUED OCTOBER 5, 2009—DECIDED FEBRUARY 23, 2010
2 No. 08-2265

The Honorable Philip P. Simon, United States District Court 

Judge for the Northern District of Indiana, sitting by designation.

Before EVANS and SYKES, Circuit Judges, and SIMON,

District Judge.



EVANS, 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 summary judgment for the company in 2008. The court concluded that the Masons’ claims were preempted under

federal law because the warnings they say should

have been included about Paxil conflicted with the FDAapproved warning labeling for the drug.

One year after the district court granted the defendant’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 summary judgment, said:
No. 08-2265 3

The Court notes that the portions of the briefs addressing 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 proceeding, 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 defendant’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 depression and suicide attempts. Ms. Mason herself

struggled with depression long before her suicide

in March 2003. In 1999-2000, Ms. Mason began experiencing depression during the winter months.

As time progressed, Ms. Mason’s depression worsened. After a New Year’s Eve party, Dones [Ms. Mason’s boyfriend] again told Ms. Mason the relationship 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 corresponded 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 conclude 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 preemption 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). Conflict 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 prescription drug cases. In a number of these cases, the FDA

filed amicus briefs in support of the pharmaceutical industry. 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 different risks involved with the various methods of administering the drug. A jury concluded that Wyeth had

indeed failed to provide an adequate warning about

the significant risks involved when Phenergan is administered 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 Congress’s intent to trust labeling decisions to the expertise

of the FDA. The Supreme Court rejected both contentions 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 prescription drugs. Although the Court found that preemption 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

It’s perhaps worth noting that just a few months ago, the 1

Eighth Circuit rejected, rather summarily, a preemption argument 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.”

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 efficacious. 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 medication is approved, the FDA continues to have authority

over it and its label. 21 C.F.R. 314.80-.81. The manufacturer, 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-
No. 08-2265 9

Section 201.57 was amended in 2006. The standard for 2

“older drugs,” including Paxil, is now located at 21 C.F.R.

§ 201.80(e).

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 “manufacturer bears responsibility for the content of its label at

all times.” Levine, 129 S. Ct. at 1197-98. While it is important 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). It is technically a 2

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 compare it to the administrative history of Paxil. The FDA

approved Phenergan in 1955. Wyeth submitted supple-
10 No. 08-2265

Phenergan causes gangrene when injected into an artery,

3

which was the exact mishap responsible for the injury to the

plaintiff in Levine.

The majority and dissent disagree about the categorization of 4

the warning Wyeth proposed in 1988. Compare, Levine at 1218 n.1

(continued...)

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 and in 1988 when Wyeth submitted a proposed 3

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 characterization of the record or administrative history, we of

course follow the majority’s view. According to the 4
No. 08-2265 11

(...continued) 4

(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.”).

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 considered and reconsidered the strength of Phenergan’s IVpush-related warnings in light of new scientific and

medical data.” Levine, at 1222. The dissent then meticulously lists the various times the FDA considered a different 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 problems of intra-arterial injection. A year later, an FDA

committee recommended an additional IV-pushspecific warning for Phenergan’s label but decided not

to prohibit using the IV-push method. In its labeling
12 No. 08-2265

The Sopranos, of course, was a critically acclaimed drama that 5

aired between 1999 and 2007 (86 episodes) on HBO. It is the

most financially successful cable series in the history of television and is acknowledged as one of the greatest television

series of all time.

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 selective 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 wellknown. 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
No. 08-2265 13

The plaintiffs also allege that GSK contaminated the adminis- 6

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.

One of the difficulties with conducting studies for Paxil is that 7

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.

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 approval to market Paxil for the treatment of depression

in adults. The FDA approved Paxil—without a warning

about suicide.

The plaintiffs allege that the FDA was misled because 6

GSK included suicides and suicide attempts that

occurred during the wash-out phase of the clinical trials 7

for Paxil and counted them as if they occurred during

the actual trial when a subject was on a placebo. Since
14 No. 08-2265

A noncontrolled study is a study where there is no control 8

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 behavior 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.

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 comparison.

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 February 2003, GSK re-analyzed the data by excluding washouts and noncontrolled studies and submitted that data 8

to the FDA. GSK’s analysis found that there was still
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 plaintiffs 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 selfharm 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 Neuropharmacological Drug Products—gave a presentation about the

potential link between suicide and antidepressants and

stated, “[N]obody in the agency dismisses the possibility 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

In medical terminology, an indication is a disease or condi- 9

tion a drug can treat.

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 compelling 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 indications9

for Paxil, each time reviewing all of the safety data about

Paxil, including the suicide data. In particular, GSK
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

REVERSED and the case REMANDED for further proceedings.

2-23-10