United States Court of Appeals

FOR THE EIGHTH CIRCUIT

 ___________

 No. 08-2555

 ___________

In re: Prempro Products Liability *

Litigation. *

_____________________ *

*

Donna Scroggin, *

*

Plaintiff/Appellant, *

*

v. *

* Appeals from the United States

Wyeth, and its divisions; Pharmacia & * District Court for the

Upjohn Company, L.L.C., * Eastern District of Arkansas.

*

Defendants/Appellees. *

_____________________ *

*

Barr Laboratories, Inc.; Duramed *

Pharmaceuticals, *

*

Amici on *

Behalf of Appellee, *

*

State of Arkansas; State of Florida; *

State of Idaho; State of Iowa; State of *

Kentucky; State of Maine; State of *

Minnesota; State of Missouri; State of *

Montana; State of Nebraska; State of *

New Hampshire; State of New Jersey; *

State of New Mexico; State of North *

Dakota; State of Oklahoma; State of *

Oregon; State of South Carolina; State *

of South Dakota; State of Utah; *
-2-

Trial Lawyers Association, *

*

Amici on *

behalf of Appellant. *

 ___________

 No. 08-2711

 ___________

In re: Prempro Products Liability *

Litigation. *

_____________________ *

*

Donna Scroggin, *

*

Plaintiff/Appellee, *

*

v. *

*

Wyeth, and its divisions, *

*

Defendant/Appellant, *

*

Pharmacia & Upjohn Company, L.L.C., *

*

Defendant. *

_____________________ *

*

Barr Laboratories, Inc.; Duramed *

Pharmaceuticals, *

*

Amici on *

Behalf of Appellant, *

*

State of Arkansas; State of Florida; *

State of Idaho; State of Iowa; State of *

Kentucky; State of Maine; State of *
-3-

Minnesota; State of Missouri; State of *

Montana; State of Nebraska; State of *

New Hampshire; State of New Jersey; *

State of New Mexico; State of North *

Dakota; State of Oklahoma; State of *

Oregon; State of South Carolina; State *

of South Dakota; State of Utah, *

*

Amici on *

behalf of Appellee. *

 ___________

 No. 08-2713

 ___________

In re: Prempro Products Liability *

Litigation. *

_____________________ *

*

Donna Scroggin, *

*

Appellee, *

*

v. *

*

Wyeth, and its divisions, *

*

Defendant, *

*

Pharmacia & Upjohn Company, L.L.C., *

*

Defendant/Appellant. *

_____________________ *
1

This opinion uses the names “Wyeth” and “Upjohn” to refer to the companies,

their divisions, and their predecessor companies. 

-4-

Barr Laboratories, Inc.; Duramed *

Pharmaceuticals, *

*

Amici on *

Behalf of Appellant, *

*

State of Arkansas; State of Florida; *

State of Idaho; State of Iowa; State of *

Kentucky; State of Maine; State of *

Minnesota; State of Missouri; State of *

Montana; State of Nebraska; State of *

New Hampshire; State of New Jersey; *

State of New Mexico; State of North *

Dakota; State of Oklahoma; State of *

Oregon; State of South Carolina; State *

of South Dakota; State of Utah, *

*

Amici on *

behalf of Appellee. *

___________

Submitted: May 13, 2009

Filed: November 2, 2009

___________

Before WOLLMAN, JOHN R. GIBSON, and MURPHY, Circuit Judges.

___________

WOLLMAN, Circuit Judge.

Donna Scroggin was diagnosed with breast cancer eleven years after she began

taking estrogen and progestin drugs manufactured by Wyeth Pharmaceuticals Inc.

(Wyeth) and Pharmacia & Upjohn Co. (Upjohn).1

 She sued the companies in 2004
-5-

for failure to warn of the risk of breast cancer from combination hormone therapy.

The trial was bifurcated, with liability determined first and punitive damages

determined second. 

A jury returned a verdict finding Wyeth and Upjohn liable and awarding

Scroggin compensatory damages. The district court denied Wyeth’s and Upjohn’s

motions for judgment as a matter of law on liability. Following the second phase of

the trial, the jury awarded Scroggin punitive damages. Wyeth and Upjohn moved to

strike Scroggin’s expert witness’s testimony and for judgment as a matter of law. The

district court granted the motions, vacating the punitive damages award. The district

court ruled in the alternative that, had it denied the motions, it would have granted a

new trial to determine punitive damages. 

Wyeth and Upjohn appeal from the entry of judgment against them on liability,

arguing that Scroggin’s claim was preempted, that the statute of limitations barred her

claim, and that she failed to prove causation. Wyeth and Upjohn also contend that the

district court erred in admitting Scroggin’s expert evidence on specific causation and

in instructing the jury on proximate causation. Scroggin appeals from the district

court’s order striking her expert evidence during the punitive damages phase of the

trial, granting Wyeth’s and Upjohn’s motions for judgment as a matter of law, and

vacating the jury’s punitive damages award.

We affirm the jury verdict and its award of compensatory damages. We also

affirm the disputed evidentiary orders and jury instruction. We affirm the judgment

as a matter of law in favor of Upjohn, but reverse it as to Wyeth, adopting the district

court’s alternative holding and granting Wyeth a new trial on punitive damages.
-6-

I. Factual Background

In 1989, Scroggin began taking combination hormone replacement therapy

drugs to relieve menopausal symptoms, including hot flashes and vaginal atrophy.

Scroggin was prescribed Ogen, an estrogen product produced by Upjohn, and Provera,

a progestin product produced by Upjohn. Dr. Irving Kuperman began treating

Scroggin in 1989, and he continued the prescriptions. In 1992, Dr. Kuperman

changed Scroggin’s estrogen prescription to Premarin, a Wyeth-manufactured drug,

and in 1996 he prescribed Prempro, a Wyeth-manufactured drug that combined

estrogen and progestin. In 1999, Dr. Kuperman returned Scroggin to the

Premarin/Provera combination. When she was diagnosed with ductal carcinoma

breast cancer in both breasts in July 2000, her surgeon, Dr. Jim Hagans, discontinued

hormone replacement therapy because it is contraindicated for breast cancer. 

Scroggin underwent a double mastectomy that removed her breast tissue and

the lymph nodes under each arm. After her incisions healed, she underwent six

months of chemotherapy, experiencing intermittent nausea, anxiety, fatigue, hot

flashes, difficulty sleeping, and continuing memory problems. Chemotherapy was

followed by five years of medication to reduce the risk of her breast cancer returning.

She remains at risk for recurrence and requires extensive annual examinations and lab

work. Scroggin has chosen not to have reconstructive surgery. 

In 2002, the National Institutes of Health (NIH) published the results of its

Women’s Health Initiative (WHI) study, linking the use of hormone replacement

therapy to breast cancer. The WHI study results were widely publicized, and at some

point after their publication Scroggin concluded that her breast cancer was the result

of her long-term use of estrogen and progestin therapy. 
-7-

A. Hormone Replacement Therapy

Hormone replacement therapy, consisting of estrogen plus progestin, is

prescribed to combat the symptoms of menopause. Women’s ovaries typically stop

producing estrogen between the ages of forty-five and fifty-five, commencing the

onset of menopause. Some women develop moderate to severe symptoms, including

intense episodes of heat and sweating, known as hot flashes, as well as vaginal

atrophy. 

In 1942, Wyeth introduced Premarin, a conjugated equine estrogen intended to

replace the estrogen naturally decreasing in women during menopause and reduce the

associated symptoms. In 1959, Upjohn launched Provera, a progestin product

approved for treatment of abnormal uterine bleeding. By the 1970s, studies showed

a link between estrogen replacement drugs such as Premarin and endometrial cancer.

It was later determined that prescribing progestin along with estrogen reduced this

risk. Although the Food and Drug Administration (FDA) had not approved the

combination of estrogen and progestin for treating menopausal symptoms, such

combination hormone therapy became the standard of care. Provera was often

lawfully prescribed for this off-label use in conjunction with Premarin. In 1994,

Wyeth became the first pharmaceutical company to combine estrogen and progestin

into one package with the launch of Prempro. In 1995, Prempro became the first

pharmaceutical that combined the two hormones into a single tablet. As of 2008,

Premarin and Provera were the most common forms of estrogen and progestin

replacement drugs.

B. Wyeth

Premarin is among Wyeth’s most profitable products. The company has

described Premarin as “our most important asset and our most important priority” and

has equated the Premarin marketing efforts with a “Holy War, a Crusade.” At trial,
-8-

Scroggin argued that this devotion led Wyeth to implement a policy of “dismiss and

distract” when it came to the risks associated with the drug. Scroggin asserted that

Wyeth intentionally ignored the breast cancer risk and avoided its study at the same

time as it vigorously promoted Premarin and Prempro. According to Scroggin,

Wyeth’s “dismiss and distract” policy began in 1975.

1. Wyeth’s Reaction to Estrogen Replacement Therapy Being Linked to

Endometrial Cancer

In 1975, the FDA’s Obstetrics and Gynecology Advisory Committee concluded

that there was a link between endometrial cancer and estrogen replacement therapy

drugs such as Premarin. The Committee held public hearings, the evidence presented

at which suggested a 7.6% increased risk for endometrial cancer among women taking

estrogen replacement drugs. This risk decreased to 5.6% for exposure of less than five

years and increased to 13.9% for exposure greater than seven years. Following the

hearings, the FDA notified Wyeth that Premarin’s label would have to be changed to

warn consumers of the risk of endometrial cancer

In response to these hearings and other reports of an endometrial cancer link,

Wyeth penned a “Dear Doctor” letter in December 1975. The letter declared that “it

would be simplistic indeed to attribute an apparent increase in the diagnosis of

endometrial carcinoma, solely to estrogen therapy.” The letter went on to state that

Wyeth “is vitally concerned about the ultimate resolution of conflicting evidence in

this area” and suggested that using the drug as described in the package’s labeling

would minimize any potential risk and allow for continued use. 

Wyeth’s letter “in[c]ensed the FDA at all levels, including the Commissioner.”

Within weeks, FDA officials met with Wyeth executives to discuss the FDA’s

position that the letter misrepresented the available scientific data. The FDA’s

Director of Bureau of Drugs stated that he expected Wyeth to provide a sound medical
2

A boxed warning is defined as “an alert to medical practitioners about

potentially serious adverse drug reactions, contraindications, or other special problems

with a given drug, contained in a ruled box at a site specified within the label format

by the FDA.” PDR Medical Dictionary 2145 (3d ed. 2006). 

3

This evidence, along with certain other evidence relied upon in this section,

was admitted for a limited purpose. The jury was instructed to consider it solely to

determine whether Wyeth was on notice of a duty to test.

-9-

and scientific response to the new information, but instead Wyeth misrepresented

scientific findings. Wyeth failed to propose studies to confront the questions that the

new data raised and failed to refute or confirm the studies that were then available.

The FDA deemed Wyeth’s letter a borderline violation of the Food, Drug, and

Cosmetic Act and issued a Drug Information Bulletin to “stat[e] objectively the

findings linking estrogens in endometrial cancer.” Shortly thereafter, the FDA

required a boxed warning2

 of the endometrial cancer risk with every Premarin

prescription.

2. Wyeth’s Reaction to Hormone Replacement Therapy Being Linked to Breast

Cancer

By 1976, the medical community began questioning whether there was a

connection between estrogens and breast cancer. In an internal memo dated June 14,

1976, Wyeth doctors recognized that “there is valid concern as to whether or not the

use of exogenous estrogen leads to an increase in the incidence of breast cancer,” but

the memo ultimately concluded that “[e]strogen use does not appear to bring about an

increased risk of breast cancer.” The following month, Dr. Robert Hoover of the

National Cancer Institute at the NIH sent a manuscript of his forthcoming study on

menopausal estrogens and breast cancer to Wyeth.3

 Dr. Hoover had concluded that

estrogens may be a risk factor for breast cancer, and the study found a 2.0 relative
4

Relative risk is the risk of an outcome in one group compared with the risk in

another group. The baseline risk is 1.0, meaning that a relative risk of 1.0 or less

indicates no greater incidence of the event. A relative risk of 2.0 would indicate a

doubling of the baseline risk or a 200% increased risk.

5

Stedman’s Medical Dictionary 1852 (28th ed. 2006) defines case-control study

as 

an epidemiologic method that begins by identifying people with the

disease or condition of interest (the cases) and compares their past of

exposure to identified or suspected risk factors with the past history of

similar exposures among those who resemble the cases but do not have

the disease or condition of interest (the controls).

-10-

risk4

 for women using estrogen for fifteen years or more. Dr. Hoover’s letter stated

that his study’s findings were cause for grave concern and that more intensive study

was necessary. 

Faced with the upcoming publication of Dr. Hoover’s study in the New England

Journal of Medicine, Wyeth prepared to defend Premarin. Internal correspondence

stated that it was crucial to formulate a plan to “mitigate the possible adverse effects”

of the study. The correspondence suggested prioritizing the “refutation, or mitigation

of the effects” of Dr. Hoover’s study, concluding that Wyeth could not “afford to wait

for the axe to start its descent before we give serious attention to how we might blunt

its edge.” Internal documents also showed a concern that the breast cancer risk was

being overstated and that the study might affect Premarin’s labeling requirements. A

Wyeth-sponsored case-control study5

 on mammary cancer was considered, but never

materialized. Prescriptions for estrogen in combination with progestin were on the

rise, and as a Wyeth document stated, “the number of published, well-designed studies

[was] small or practically non existent.”

In the late 1980s and early 1990s, additional studies linked hormone

replacement therapy to an increased risk of breast cancer. In 1989, Dr. Leif Bergkvist
6

 The IARC is an agency within the World Health Organization charged with

identifying cancer-causing agents in the environment.

-11-

published the results of his long-term study of the risk of breast cancer following

estrogen and estrogen-progestin replacement. Although the study had a small sample

size, it nonetheless concluded that treatment with estrogens “seems to be associated

with a slightly increased risk of breast cancer, which is not prevented and may even

be increased by the addition of progestins.” This conclusion was contrary to the

prevailing view that progestins might decrease the risk of breast cancer in much the

same way that they decreased the risk of endometrial cancer. 

In 1990, Wyeth obtained information that Dr. Graham Colditz would present

the results of a study showing that Premarin increased the risk of breast cancer by

thirty percent in current users. The presentation was scheduled to take place at a

meeting of the Society of Epidemiologic Research. Wyeth prepared talking points in

advance of the meeting, planning to “effectively position[] the risks vs. benefits so

there is some counterbalance to potential negative news.” Wyeth implemented a

similar plan in response to the International Agency for Research on Cancer’s (IARC)6

announcement that it would evaluate the carcinogenic risks of estrogen replacement

therapy. Justin Victoria, Wyeth’s Associate Director of Regulatory Affairs, proposed

the formation of a task force to “ensure that IARC does not develop a position on a

definitive relationship between breast cancer and estrogen replacement therapy as well

as to ensure that conjugated estrogens are not singled out from other estrogen

replacement therapies as any different in terms of carcinogenic risk.”

Throughout the 1990s, Wyeth remained vigilant in disassociating its product

from cancer. In accordance with company policy, Wyeth denied the Eastern

Cooperative Oncology Group’s 1993 request for a supply of Premarin to conduct a

study of hormone replacement therapy in women who have breast cancer.

Presumably, the request was denied because estrogen is contraindicated for breast
-12-

cancer, but a later memo referred to a custom at Wyeth of denying requests for

Premarin for studies involving breast cancer. In 1994, a Wyeth executive responded

to the suggestion that a respected oncologist chair an upcoming meeting of Wyeth

consultants with “[n]o way having an oncologist chair this. NO NO NO NO & NO.”

In 1995, a British scientist requested mammograms used in previous Wyeth studies

for a study on breast density in estrogen and progestin users. Wyeth agreed on

condition that there be “no review of issues currently under discussion in literature

elsewhere reviewing HRT and breast cancer” and that the Premarin Study Review

Committee “has an absolute and final right to comment on the content, emphasis and

conclusions of any publication(s)” and if there are “any significant differences of

opinion raised” the scientist “will agree to accept the views of the Premarin Study

Review Committee.”

In 1996, an NIH-sponsored study, authored by Dr. Steven Cummings,

concluded that “the risk of breast cancer associated with hormone replacement therapy

may have been substantially underestimated.” Wyeth received an advanced abstract

of the study and established a breast cancer task force in response. Wyeth’s response

plan involved the following strategy: “shift attention to other cancers;” characterize

the study as “just one more paper;” and highlight flaws in the study’s methodology.

The task force’s stated goal for an upcoming meeting of the American Society of

Clinical Oncology was to “[o]vershadow [the] Cummings data” by directing media

attention elsewhere. Handwritten notes regarding the study state “keep US press

busy” and “dismiss/distract.” 

Wyeth also engaged in the lawful, though questionable, practice of

commissioning ghost written articles. In 2000, Wyeth tapped Dr. John Eden to author

“Breast Cancer and Progestins,” but the true author was a technical writing company,

hired to produce the manuscript for Wyeth’s approval and Dr. Eden’s editing. Wyeth

submitted a project assignment with references, a timetable, and topics to address,

such as “why progestins may not be responsible for the incidence of breast cancer in
7

For a recent report regarding the use of ghost-written articles, see Natasha

Singer, Medical Papers By Ghostwriters Pushed Therapy, N.Y. Times, Aug. 5, 2009,

at A1.

-13-

hormone replacement therapy (HRT) users.” The finished product was published in

the Journal of Obstetrics and Gynecology, apparently without the publication’s

knowledge of the article’s origins and with no reference to Wyeth. Other authors then

cited to the article, including Wyeth’s own Dr. Ginger Constantine, facilitating its

absorption into the collection of reliable medical data.7

 

3. Wyeth’s Interactions with the FDA Regarding Hormone Replacement Therapy

Wyeth sought FDA approval of Prempak, a combination product containing

Premarin and a progestin tablet, in the 1980s. Wyeth did not support its application

with its own study, but instead relied on the then-available studies to substantiate the

efficacy and safety of Prempak. The FDA denied the application, concluding that the

studies were inadequate and that Wyeth was unable to assure “the long term safety of

the combination treatment for human use.” 

By the early 1990s, Wyeth was well aware of the FDA’s position that the data

on estrogen use in combination with progestin was insufficient. In an internal memo

dated August 22, 1990, Justin Victoria explained that the FDA had denied Wyeth’s

applications for combination packaging, informing Wyeth that it could not approve

a combination without an adequate, well-controlled clinical trial that evaluated the

overall benefits and risks of the combination. The memo stated that the FDA

“remain[ed] unconvinced of the overall safety and effectiveness of combined

estrogen/progestin therapy.” Wyeth and Upjohn also attended the 1990 and 1991

meetings that the FDA held to address, among other issues, the concern that hormone

replacement therapy was associated with an increased risk of breast cancer. Both

meetings concluded that the current available evidence was insufficient and

inconclusive, as some studies showed an increased risk and others did not. Scroggin’s
-14-

regulatory expert and a former Chief Medical Officer with the FDA, Dr. Suzanne

Parisian testified at trial that the FDA would have expected Wyeth to take these

meetings seriously and that Wyeth should have viewed the 1990 meeting as a red flag.

Wyeth, however, considered the meeting a success, celebrating it as a “non-event.”

In 1991, Wyeth sought FDA approval of its Premarin marketing plan and the

plan’s centerpiece, a magazine. In a February 21, 1991, letter to Wyeth, the FDA’s

Acting Director of the Division of Drug Advertising and Labeling stated that the FDA

“view[ed] this campaign in its entirety to be a form of extremely insidious hidden

persuasion” and a “marketing ploy masquerading as concern for the health of postmenopausal women.” The letter described the magazine as a “house organ,” faulting

it as misleading for failing to clearly state Wyeth’s sponsorship and for stating that the

magazine was provided by a pharmacy. Moreover, the letter criticized the magazine’s

articles as misleading. The letter remarked that the campaign “intentionally misleads

the reader into thinking that her physician is somehow responsible for providing it to

her.” Wyeth subsequently altered the campaign. 

In 1994, the FDA approved Prempro, a combination packaging of estrogen and

progestin, on the condition that Wyeth perform a post-marketing study on the risk of

breast cancer. Dr. Parisian testified that the FDA cannot force a pharmaceutical

company to perform safety tests and suggested that approval was granted as a means

of compelling the study. Such a study would take eight or nine years to complete. 

Following the FDA’s approval of Prempro, Wyeth requested that its support of

the following two studies satisfy its obligation to study the breast cancer risk: the

WHI study and the Women’s International Study of Long-Duration Oestrogen After

Menopause. The WHI study was underway and was evaluating whether combination

use of estrogen and progestin provided long-touted cardiovascular benefits. Although
8

Scroggin established at trial that Upjohn would have been aware of the same

medical literature and research as Wyeth.

-15-

the FDA had previously expressed skepticism that the WHI study could evaluate the

breast cancer risk, it approved Wyeth’s proposal. 

C. Upjohn

Evidence presented at trial did not show that Upjohn tried to undermine

evidence linking breast cancer to hormone replacement therapy or its progestin,

Provera. Instead, Scroggin argued that Upjohn failed to study whether hormone

replacement therapy increased the risk of breast cancer and that it ignored the growing

evidence indicating that such a risk existed. 

1. Upjohn’s Reaction to Hormone Replacement Therapy Being Linked to Breast

Cancer

As early as 1963, Upjohn was aware that Provera might exacerbate existing

breast cancer.8

 In 1970, Upjohn withdrew Provest, an oral contraceptive containing

estrogen and progestin, after a study showed that progestin caused mammary nodules

in beagle dogs. Recognizing that Provest’s withdrawal might alarm doctors

prescribing combination hormone therapy drugs, Upjohn issued a “Dear Doctor” letter

that assured that there was “no reason to predict human extrapolation of this finding,”

but that there was also no way of disproving it. The letter distinguished Provest, a

contraceptive used for a prolonged period of time for which there were adequate

replacements, from Provera, a “therapeutic agent[] for specific gynecological

disorders.” The letter concluded that Provera’s benefits outweighed the possible risks

and that continued use “poses no unwise risk in this regard to you or your patients.”

In 1990, Upjohn hired the Degge Group to gather and review all available

scientific data concerning the risk of breast cancer with hormone replacement therapy
-16-

involving progestin. The goal was to determine what was known and what areas

needed further research. The Degge Group found that the evidence was inconclusive,

and it identified and recommended areas for further research. The Degge Group

published the results of its research in 1992, in Fertility and Sterility, an obstetrics and

gynecology medical journal. Upjohn, however, did not conduct follow up studies or

research. 

By 1992, Upjohn still did not know the extent of the risk of breast cancer with

progestin use as part of hormone replacement therapy. Between 1982 and 1994,

Upjohn conducted thirty-four studies to prove that Provera protected the

endometrium. The studies were monitored for breast cancer, but they were not

designed to be large enough or long enough in duration to be capable of evaluating the

breast cancer risk.

Until 1995, there remained a prevailing view that progestin’s addition to

estrogen replacement therapy might reduce the incidence of breast cancer in much the

same way that it reduced the risk of endometrial cancer. In 1995, however, a

publication by Dr. Colditz examined available data from 1978 through 1992 and

concluded that there was no benefit. In fact, the study found a slightly higher risk

with the addition of progestin. Dr. Colditz “observed a significant elevation in the risk

of breast cancer among women using conjugated estrogen alone,” a relative risk of

1.32; for estrogen and progestin, the relative risk was 1.41; and for progestin alone,

the relative risk was 2.24. 

2. Upjohn’s Interactions with the FDA Regarding Hormone Replacement Therapy

In 1966, Upjohn applied for FDA approval of Provera’s use with estrogens for

treatment of menopause. The FDA denied the application because Upjohn failed to

justify the requested indication with adequate clinical data. In 1986, Upjohn

submitted a supplemental application to the FDA, again seeking to expand Provera’s
-17-

indications for use of the drug to oppose the endometrial effects of estrogen in

menopausal women receiving estrogen replacement therapy. The FDA denied the

application because Upjohn failed “to provide substantial evidence consisting of

adequate and well-controlled studies . . . that Provera will have the effect it is

represented to have under the conditions of use prescribed, recommended, or

suggested in its proposed labeling.”

Although Provera was not approved for use in treating menopausal symptoms,

Upjohn advertised it as such. In 1984, the FDA called for the immediate cancellation

of Provera advertisements appearing in Contemporary OBGYN. The advertisements

promoted Provera’s off-label use with estrogen replacement therapy and failed to

mention its indicated use, treatment for abnormal uterine bleeding. Upjohn agreed to

limit its advertisements to the approved indication. Notwithstanding that agreement,

the FDA found it necessary to request immediate cancellation of a similar

advertisement in 1985, and another advertisement in 1990, that claimed Provera was

“the other half of hormone replacement therapy.” In 1991, Upjohn submitted

proposed promotional materials to the FDA for approval. The FDA limited the

material because it was potentially misleading. The FDA reminded Upjohn of their

previous discussions “regarding material which suggests that Provera is indicated for

use in postmenopausal replacement therapy for the prevention of endometrial

hyperplasia.” 

In 1998, Provera was finally approved “for the reduction of endometrial

hyperplasia in postmenopausal women” who are receiving estrogen. Testimony at

trial revealed that Upjohn did not conduct any breast cancer studies from 1960 until

the time of trial. 
-18-

D. The Women’s Health Initiative Study

The WHI study began in 1991. The study consisted of multiple components,

one of which was an evaluation of the use of estrogen and progestin in

postmenopausal women. Primarily, this component evaluated whether estrogen and

progestin use decreased the incidence of cardiovascular disease. Secondarily, the

study assessed numerous safety issues, including the risk of breast cancer. The study

was organized as a randomized placebo-controlled trial, meaning that one group of

women received the drugs and the other a placebo. The average age of the participants

was sixty-three, and it included women who were already on hormone replacement

therapy, as well as women who began treatment at the start of the study. The study

had a predetermined stopping point if the incidence of breast cancer exceeded a

certain point. In 2002, three years short of its scheduled completion, the NIH

terminated the study, finding an unacceptably high incidence of invasive breast cancer

among the participants. 

In July 2002, the initial results of the WHI study were published in the Journal

of the American Medical Association. The study reported a relative risk of breast

cancer of 1.24 over 5.6 years of estrogen and progestin use. Stated differently, the

estrogen plus progestin group was twenty-four percent more likely to develop breast

cancer than the control group. This result was consistent with estimates from pooled

epidemiological data. Wyeth’s Dr. Constantine described the relative risk of increased

incidence of breast cancer as small and Scroggin’s medical expert, Dr. Don Austin,

described it as slightly elevated. The study also found that the risk of breast cancer

decreased after stopping the hormone therapy.

These initial results, however, contained variables not accounted for in the 1.24

relative risk. Dr. Austin testified that the 1.24 number was misleading, particularly

for women using hormone replacement therapy for long periods of time. He noted

that although randomized clinical trials assist in showing causal relationships, they
-19-

may not be accurate in reporting the size of the risk. The 1.24 relative risk was based

on the “intent to treat” group, meaning the women who had signed up to participate

in the study, but it did not account for those who had dropped out during the course

of the study. According to the WHI, all of the women had been enrolled for 3.5 years,

with an average enrollment of 5.2 years, and a maximum enrollment of 8.5 years.

Forty-two percent of estrogen plus progestin users and thirty-eight percent of the

placebo group ceased participating during the course of the study. The initial WHI

results, however, calculated the relative risk as if these women had remained in the

study. 

In 2006, Dr. Garnet Anderson, who had worked on the WHI study, published

a report that accounted for these variables. When she accounted for confounding

variables, the relative risk was 1.96. She found that women who had been taking

hormone replacement therapy prior to commencement of the study had a relative risk

of 2.78 and that women who were taking the medication for more than five years had

a relative risk of 2.5. When Dr. Anderson analyzed only the women who remained

in the study and adhered to the treatment, she found a relative risk of 3.56. 

Dr. Austin testified that “the true value is somewhere between 1.18 and 10.73,

but the best estimate is 3.56.” Dr. Colditz asserted that the relative risk is somewhere

between 2.0 and 4.0 depending on use and duration. Both Dr. Colditz and Dr. Austin

agreed that estrogen plus progestin use causes breast cancer. Additionally, the IARC

has classified estrogen plus progestin as a carcinogen of the breast. 

E. Wyeth’s and Upjohn’s Breast Cancer Warnings

The FDA requires drug information to be sent directly to the physician as well

as provided to the patient with each prescription. In 1992, both the physician labeling

and patient information sheet for Premarin provided the following warning: “Some

studies have suggested a possible increased incidence of breast cancer in those women
9

The Prempro label had the following modification: “Some studies have

reported a moderately increased risk of breast cancer (relative risk 1.3 to 2.0) in those

women on estrogen replacement therapy taking higher doses, or in those taking lower

doses for prolonged periods of time, especially in excess of 10 years.” 

-20-

on estrogen therapy taking higher doses for prolonged periods of time. The majority

of studies, however, have not shown an association with the usual doses used for

estrogen replacement therapy.” Similar language was included in the physician label

and patient information sheet accompanying Prempro prescriptions.9

 The Premarin

labeling did not provide any information concerning the combined use of estrogen

plus progestin. Both Dr. Parisian and Dr. Kuperman testified that this label did not

convey a significant risk of breast cancer associated with the use of estrogen or

progestin. 

The Prempro information sheet included this additional information:

Most studies have not shown a higher risk of breast cancer in women

who have ever used estrogens. However, some studies have reported

that breast cancer developed more often (up to twice the usual rate) in

women who used estrogens for long periods of time (especially more

than 10 years), or who used high doses for shorter time periods. The

effects of added progestin on the risk of breast cancer are unknown.

Some studies have reported a somewhat increased risk, even higher than

the possible risk associated with estrogens alone. Others have not.

Regular breast examinations by a health professional and monthly selfexamination are recommended for all women. Regular mammograms

are recommended for all women over 50 years of age.

Dr. Parisian testified that the Prempro warning was confusing and did not clearly

convey a risk to patients. She also testified that it falsely implied that Wyeth had

conducted studies to analyze the risk. Dr. Kuperman testified that the warning

provided no clear indication of a breast cancer risk and instead implied that the risk

was unresolved and that there was likely a low correlation.
-21-

In 1999, the Prempro label continued to provide the warning contained in the

Premarin label, but added, “[t]he effect of added progestins on the risk of breast

cancer is unknown, although a moderately increased risk in those taking combination

estrogen/progestin therapy has been reported.” The label provided an example of a

clinical trial and concluded that “[t]he overall incidence of breast cancer in this

clinical trial does not exceed that expected in the general population.”

Upjohn’s Provera provided no warning of breast cancer, and none was required

by the FDA until 1999. At that time, the label informed patients of the results of the

study on beagle dogs and concluded that the “significance with respect to humans has

not been established.”

F. Current Status of Hormone Replacement Therapy

 

Premarin, Provera, and Prempro continue to be prescribed today, and the FDA

still considers the drugs safe and effective. The FDA now requires, however, the

drugs’ labels to reflect the results of the WHI study, and all three medications now

contain a boxed warning of the risk of breast cancer. Following the release of the

WHI results, the number of prescriptions dropped significantly. This drop in

prescriptions was accompanied by a corresponding reduction in the number of cases

of breast cancer diagnosed in the United States. Likewise, a retrospective review has

since shown that breast cancer increased as prescriptions for hormone replacement

therapy increased. 

Dr. Kuperman’s prescription habits have also changed. Although he testified

that he has always warned of the known risks and prescribed the lowest effective dose,

he now relies on the WHI study and subsequent studies to provide a more accurate

assessment of the risks to his patients. As a result of the study, Dr. Kuperman aims

to keep the duration of estrogen plus progestin use to less than five years, and he no
-22-

longer prescribes hormone replacement therapy for durations of ten or fifteen years.

Instead, he tries to wean patients off hormone replacement therapy. Following the

study results, Dr. Kuperman told Wyeth sales representatives who had routinely

visited his office that he had a negative opinion of Prempro and no longer wanted

samples. Since 2002, his prescriptions for estrogen plus progestin have decreased.

G. Procedural Background

After a nearly three-week-long trial, the jury found that Wyeth and Upjohn had

inadequately warned about a known or knowable risk of breast cancer from ingestion

of Premarin, Provera, and Prempro and that this failure to warn was the proximate

cause of Scroggin’s breast cancer. The jury awarded Scroggin compensatory damages

in the amount of $2.7 million. Following a three-day trial, the jury found Wyeth liable

for $19.36 million and Upjohn liable for $7.76 million in punitive damages. The

district court granted Wyeth’s and Upjohn’s motions for judgment as a matter of law

as to punitive damages, finding that much of Dr. Parisian’s punitive damages

testimony should not have been admitted and that the remaining evidence did not

support the verdict. 

II. Analysis

Wyeth and Upjohn raise a number of issues regarding the liability phase of the

trial, which we examine in turn. Scroggin appeals the district court’s post-judgment

order striking her expert’s testimony and related exhibits on punitive damages phase

and granting Wyeth’s and Upjohn’s motion for judgment as a matter of law on

punitive damages. 
-23-

A. Preemption

Wyeth and Upjohn contend that Scroggin’s state law claim for failure to warn

is preempted by federal law. Because the FDA regulates pharmaceutical products and

oversees labeling requirements, they argue that there can be no heightened duty under

Arkansas law and that they could not comply with state law without violating FDA

requirements. 

The Supreme Court’s recent decision in Wyeth v. Levine, 129 S. Ct. 1187

(2009), has foreclosed this preemption argument. In Levine, a Vermont jury found

that Wyeth had inadequately warned about the risk of irreversible gangrene arising

from the intravenous push administration of its drug, Phenergan. Id. at 1193. The

Court rejected Wyeth’s preemption arguments, noting that federal regulations do not

prohibit drug manufacturers from strengthening their warnings prior to FDA approval

to reflect new developments and comply with state laws. Id. at 1196-97. 

[I]t has remained a central premise of federal drug regulation that the

manufacturer bears responsibility for the content of its label at all times.

It is charged both with crafting an adequate label and with ensuring that

its warnings remain adequate as long as the drug is on the market.

Id. at 1197-98. As in Levine, there is no evidence that the FDA would not have

permitted the strengthening of the labels of Premarin, Prempro, and Provera in a

manner consistent with Arkansas law.

Likewise, Wyeth and Upjohn have not shown that state requirements obstruct

the purposes of federal drug labeling regulation. Given the limited resources of the

FDA and the extensive assortment of pharmaceutical products on the market, “the

FDA [has] traditionally regarded state law as a complementary form of drug

regulation.” Id. at 1202. Congress is aware of the potential for conflict and has
-24-

enacted an express preemption provision for medical devices, but there is no such

enactment for prescription drugs, id. at 1200, and none will be implied. 

B. Statute of Limitations

Wyeth and Upjohn appeal from the district court’s denial of their motion for

judgment as a matter of law on their statute of limitations defense, arguing that

Scroggin was aware of the risk of breast cancer while taking hormone replacement

therapy and that her claim thus began to accrue when she was diagnosed with breast

cancer. We review de novo a district court’s determination on a motion for judgment

as a matter of law. Carter v. Kan. City S. Ry. Co., 456 F.3d 841, 846 (8th Cir. 2006).

“We apply the same standards as the district court, giving the nonmoving party all

reasonable inferences and viewing the facts in the light most favorable to the

nonmoving party. If conflicting inferences reasonably can be drawn from evidence,

the jury is in the best position to determine which inference is correct.” Christensen

v. Titan Distrib., Inc., 481 F.3d 1085, 1092 (8th Cir. 2007) (citations and internal

quotations omitted). 

Arkansas law provides a three year statute of limitations on product liability

actions. Ark. Code Ann. § 16-116-103. 

A cause of action accrues when the plaintiff first becomes aware of her

condition, including both the fact of the injury and the probable causal

connection between the injury and the product’s use, or when the

plaintiff by the exercise of reasonable diligence, should have discovered

the causal connection between the product and the injuries suffered. 

Uhiren v. Bristol-Myers Squibb Co., 346 F.3d 824, 828 (8th Cir. 2003) (relying on

Arkansas law) (citations and internal quotations omitted). Scroggin contends that

discovery of a probable causal connection was not possible until the WHI findings

were released.
10The WHI study was the subject of Time Magazine’s July 22, 2002 cover story,

“The Truth About Hormones: A large, federally funded study provides definitive

proof that estrogen and progestin are not age-defying wonder drugs. What’s a woman

to do?” The New York Times recently reported that the “[u]se of treatment plunged

after [the WHI] findings were reported.” Study Cites Hormones As Cancer Risk, N.Y.

Times, July 15, 2009, at A13.

-25-

Wyeth and Upjohn argue that the WHI findings revealed nothing significant to

Scroggin; therefore, whatever Scroggin knew in 2002, she knew in 2000 when she

was diagnosed with breast cancer. We conclude that a jury could find that Scroggin’s

cause of action accrued at some point after the publication of the WHI study’s results.

Wyeth and Upjohn changed their products’ labeling significantly following the

publication of the WHI findings, devoting substantial label space to the results of the

study. Moreover, the WHI results were widely covered in mainstream media,10 and

Prempro sales have dropped by fifty percent since 2001, suggesting that the WHI

study did more than affirm that which was already known.

Wyeth and Upjohn also contend that Scroggin should have known of the breast

cancer risk because she received the product warnings, she read the warnings, and Dr.

Kuperman discussed these warnings with her. Two doctors testified that the labels

Scroggin would have read did not convey a significant risk of breast cancer, and Dr.

Kuperman thought the labels indicated that the evidence was inconclusive. Thus,

Scroggin presented sufficient evidence for the jury to find that the warnings were

inadequate, contradictory, and confusing. 

Wyeth and Upjohn also assume knowledge on Scroggin’s part because Dr.

Hagans instructed her to stop taking hormone replacement therapy when he diagnosed

her with breast cancer. This argument fails, for the Premarin and Prempro labels

stated that women already known to have breast cancer should not use Premarin or

Prempro. The label included that instruction because estrogen is contraindicated for
-26-

women with breast cancer, meaning that it can exacerbate their existing breast cancer

and, as Justin Victoria testified, not because it suggests a causal connection. Cf. Roth

v. G.D. Searle & Co., 27 F.3d 1303, 1308 (8th Cir. 1994) (noting that the doctor’s

statement that the plaintiff never should have had the second intrauterine device

inserted, coupled with unchallenged, plainly stated product warnings, put the plaintiff

on inquiry notice).

The assertion that Scroggin would have been aware of the risk through her own

due diligence is also without merit, for it ascribes to Scroggin the duty of being aware

of not simply the possibility that her hormone replacement therapy caused her breast

cancer, but that a causal connection was probable. The jury could reasonably

conclude that if medical doctors were unsure of the risk, it is highly unlikely that a

layperson would be more aware of that risk. See Deutsch v. Wyeth, Inc., No. MID-L998-06 MT (N.J. Super. Ct. June 14, 2007) (order denying Wyeth’s motion for

summary judgment based on statute of limitations) (“It is . . . entirely unreasonable

to require a patient without medical training to make the logical connection between

her ingestion of HRT drugs and her breast cancer and possess a reasonable belief that

she could sue Wyeth for her injuries before the WHI findings were released to the

public.”). 

C. Causation

Wyeth and Upjohn assert that Scroggin failed to prove that their drugs were the

cause of her injury. As part of her failure to warn claim, Scroggin was required to

show both specific causation—that the hormone replacement therapy caused her

injury—and proximate causation—that she would not have taken the combination

therapy had Wyeth and Upjohn provided adequate warnings. See Ashley County v.

Pfizer, Inc., 552 F.3d 659, 667 (8th Cir. 2009). Wyeth and Upjohn argue that the

district court erred in admitting the testimony of Scroggin’s specific causation expert,

in instructing the jury on proximate cause, and in denying their motion for judgment
11Daubert sets forth the following four factors for consideration, which do not

constitute a definitive checklist or test: (1) whether the theory or technique applied

can be tested, (2) whether the theory or technique has been subject to peer review or

publication, (3) the known or potential rate of error, and (4) general acceptance. 

Daubert, 509 U.S. at 593-95. 

-27-

as a matter of law because the evidence showed that Scroggin would not have done

anything differently if an adequate warning had been provided.

1. Admission of Dr. Naftalis’s Expert Testimony

Wyeth and Upjohn argue that the district court erred in admitting the testimony

of Dr. Elizabeth Naftalis, Scroggin’s expert witness on specific causation. “[A]bsent

a clear and prejudicial abuse of discretion,” we will not reverse a district court’s

determination on the admissibility of expert testimony. Bland v. Verizon Wireless,

L.L.C., 538 F.3d 893, 896 (8th Cir. 2008).

Federal Rule of Evidence 702 provides for the admission of an expert opinion

if it “will assist the trier of fact to understand the evidence or to determine a fact in

issue,” provided the expert is qualified to render the opinion and offers sufficient

factual basis for her opinion, forms her opinion on reliable principles and methods,

and applies these principles or methods to the facts of the case. Rule 702 reflects a

“relax[ation of] the traditional barriers to opinion testimony,” and the court’s inquiry

is intended to be flexible. Daubert v. Merrell Dow Pharms., Inc., 509 U.S. 579, 588,

594 (1993) (internal quotations omitted). The district court must assess whether the

methodology used by the proposed expert is valid and whether it was properly

applied.11 Id. at 592-93. “There is no single requirement for admissibility as long as

the proffer indicates that the expert evidence is reliable and relevant.” Unrein v.

Timesavers, Inc., 394 F.3d 1008, 1011 (8th Cir. 2005). 
-28-

Wyeth and Upjohn did not challenge Dr. Naftalis’s qualifications as an expert

witness before the district court, and they do not argue that the method she used,

differential diagnosis, is not a sound and accepted methodology. Instead, they argue

that differential diagnosis cannot be used to prove the cause of breast cancer because

no one knows the cause of breast cancer. They note that Dr. Naftalis was not familiar

with the details of Scroggin’s family history of breast cancer until trial, and they argue

that she did not properly account for Scroggin’s various risk factors for breast cancer,

such as breast density, her age, weight, and her smoking history.

Scroggin suffered from hormone-dependent breast cancer. Dr. Mariann

Harrington, Scroggin’s oncologist, tested the tumors in Scroggin’s breasts for

hormone receptors to inform her treatment. Both the left and right tumors were one

hundred percent positive for estrogen and progesterone receptors. There was no

dispute at trial that hormone-receptor-positive tumors are dependent upon hormones

for their growth. Moreover, published research had concluded that hormone-receptorpositive tumors need hormones to grow, that menopausal symptoms result from

hormone deficiency, and that there is a link between breast cancer and hormone

replacement therapy. See Lauzon v. Senco Prods., Inc., 270 F.3d 681, 693 (8th Cir.

2001) (noting that “scientific reliability can also be shown by proof that the research

and analysis supporting the proffered conclusions have been subjected to normal

scientific scrutiny through peer review and publication”). 

Knowing that Scroggin’s breast cancer was hormone dependent, Dr. Naftalis’s

differential diagnosis sought to determine the cause of Scroggin’s breast cancer by

ruling out the two possible sources of these hormones: (1) Scroggin produced the

hormones herself, or (2) they came from the hormone replacement therapy she had

taken for the past eleven years. Scroggin presented evidence that her menopausal

symptoms were relieved by hormone replacement therapy, confirming that her own

body was unable to produce sufficient hormones and therefore could not be the
12Although Wyeth presented evidence disputing this association, the factual

basis of an expert opinion is assessed by the jury, Larson v. Kempker, 414 F.3d 936,

941 (8th Cir. 2005), and the jury may have been persuaded by Wyeth’s own

documents asserting a link between hormone deficiency and uncomfortable

menopausal symptoms. Further, Wyeth has not disputed that vaginal atrophy is

caused by estrogen deficiency.

-29-

cause.12 The remaining source was the combination of Premarin, Provera, and

Prempro. Accordingly, Scroggin presented evidence establishing a causal link

between breast cancer and estrogen plus progestin use, particularly for the length of

time Scroggin was taking the drugs.

We find unpersuasive the contention that Dr. Naftalis’s testimony should not

have been admitted because Scroggin has some breast cancer risk factors and a family

history of breast cancer. Dr. Naftalis sufficiently established that hormones were

necessary to the development of Scroggin’s tumors and conducted her differential

diagnosis from this starting point. Although not necessary to the formation of her

opinion, Dr. Naftalis addressed the known causes of breast cancer and possible risk

factors. Wyeth and Upjohn argue that this review was insufficient, but Dr. Naftalis’s

“explanations as to conclusions not ruled out went to weight and not admissibility.”

Id. at 694. Additionally, Scroggin submitted to every available genetic test for breast

cancer, all of which came back negative for the most common breast cancer genes.

Wyeth’s genetics expert testified that he continues to believe that genetics caused

Scroggin’s breast cancer, but the jury concluded otherwise. 

Wyeth’s and Upjohn’s reliance on Bland v. Verizon Wireless, L.L.C. is

misplaced. 538 F.3d 893 (8th Cir. 2008). In that case, expert testimony was offered

to show that the plaintiff’s recent exposure to freon caused her exercise-induced

asthma. Id. at 897. The exact cause of exercise-induced asthma is not known, and the

plaintiff’s expert could not provide a reliable opinion as to what caused the plaintiff’s

asthma. Id. at 898. The proximity in time between the plaintiff’s exposure to freon
13The Minnesota Court of Appeals’s recent unpublished opinion, Zandi v.

Wyeth, Inc., No. 27-CV-06-6744, 2009 WL 2151141 (Minn. Ct. App. July 21, 2009)

(unpublished), is distinguishable. Although Zandi involves similar facts, Minnesota

law requires a more conservative review of expert testimony than the liberal thrust of

the Federal Rules of Evidence and relies on a variant of the standard abandoned in

Daubert. To the extent that Zandi excludes an expert opinion that relies on differential

diagnosis to determine the cause of hormone-receptor-positive breast cancer in an

individual with hormone-dependent breast cancer, we respectfully disagree. 

-30-

and her resulting asthma was the only basis for her doctor’s opinion; the doctor failed

to investigate other possible causes, including Bland’s home or other environments.

Id. Conversely, Dr. Naftalis was able to testify that Scroggin’s breast cancer would

not have developed without hormone replacement therapy because Scroggin’s body

was not producing sufficient amounts of hormones to allow hormone-receptorpositive tumors to develop. Thus, Dr. Naftalis ruled out the other possible cause of

Scroggin’s breast cancer, and her expert testimony was properly admitted.13 Wyeth

and Upjohn had the opportunity to expose the testimony’s weaknesses through

vigorous cross-examination and the presentation of contrary evidence. See Daubert,

509 U.S. at 596. 

2. Jury Instruction on Aggravation of Preexisting Condition and Promotion

Wyeth and Upjohn argue that the district court erred in modifying the Arkansas

Model Instruction on proximate cause to reflect Scroggin’s theory that estrogen plus

progestin use promotes preexisting abnormal cells into malignancies. “We review a

district court’s decision on jury instructions for abuse of discretion, looking to the

instructions as a whole to determine whether they fairly submitted the issues to the

jury.” Boerner v. Brown & Williamson Tobacco Co., 394 F.3d 594, 603 (8th Cir.

2005). “We afford the district court broad discretion in choosing the form and

language of the instructions and will reverse a jury verdict only if the erroneous

instruction affected a party’s substantial rights.” In re Prempro Prods. Liab. Litig.,
-31-

514 F.3d 825, 829 (8th Cir. 2008) (internal quotations omitted) (quoting Slidell v.

Millenium Inorganic Chems., Inc., 460 F.3d 1047, 1054 (8th Cir. 2006)).

“Model jury instructions are just that, models. They are not mandatory.”

United States v. Wilson, 565 F.3d 1059, 1067 (8th Cir. 2009). The district court was

not required to precisely follow Arkansas’s Model Instruction, but only to “fully and

properly instruct upon all the elements of the case in light of controlling Arkansas

law.” Wright v. Farmers Co-op of Ark. & Okla., 620 F.2d 694, 698 (8th Cir. 1980)

(internal quotations omitted) (citing Stafford v. S. Farm Bureau Cas. Ins. Co., 457

F.2d 366, 367 (8th Cir. 1972) (per curiam)). 

Under Arkansas law, “proximate cause is that cause which, in a natural and

continuous sequence, produces damage.” Sluder v. Steak & Ale of Little Rock, Inc.,

206 S.W.3d 213, 218 (Ark. 2005) (internal quotations omitted) (citing AMI Civ. 3d

501; Bull v. Manning, 433 S.W.2d 145 (Ark. 1968); Ben M. Hogan & Co. v. Krug,

351 S.W.2d 451 (Ark. 1961)). The district court’s instruction included this precise

language, as well as the following definitions: 

A ‘producing’ cause is one that in natural and continuous sequence

causes or initiates injury and without which the injury would not have

occurred. A ‘promoting’ cause is one that in natural and continuous

sequence aggravates a pre-existing condition or disease and without

which the full extent of the injury would not have occurred. 

The court then clarified that the jury was to view the evidence in light of these

definitions rather than how they may have been used during the trial. 
14Upjohn adopted by reference Wyeth’s argument regarding the proximate

cause instruction. See Fed. R. App. P. 28(i).

-32-

Wyeth’s argument14 acknowledges only two possible theories of Scroggin’s

case: either Scroggin already had breast cancer and the hormone replacement therapy

aggravated it, or the therapy initiated the transformation of normal cells into cancerous

cells. Given these alternatives, Wyeth asserts that including “promoting” in the

instruction unfairly elevated Scroggin’s presentation of the evidence and that the

instruction was not supported by the evidence. Wyeth has refused to recognize

Scroggin’s theory of causation. Scroggin presented evidence that she had abnormal

or susceptible cells, which were a pre-existing condition. In other words, she had

these cells prior to her regimen of estrogen plus progestin. She also presented

evidence that estrogen and progestin caused these cells to become cancerous. Dr.

Colditz has described estrogen plus progestin’s effect on these abnormal cells as

“acting like a fertilizer to get them to grow rapidly and progress on to cancer.” Dr.

Naftalis testified that combination hormone therapy has a “promotion effect” on the

“susceptible cell and turns it into cancer.” Dr. Colditz stated that the epidemiologic

field accepts promotion as the mechanism by which hormone replacement therapy

causes breast cancer. Thus, the instruction was appropriately tailored to the facts. See

Pershern v. Fiatallis N. Am., Inc., 834 F.2d 136, 139 (8th Cir. 1987).

The court showed no bias in its instruction. The producing-cause definition

reflects Wyeth’s theory of the case—that hormone replacement therapy does not

initiate the first abnormal cells or turn normal cells into cancerous cells—and is

appropriately supported by the evidence Wyeth presented. Scroggin argued

promotion, Wyeth argued initiation, and the court instructed the jury on both theories.

The court also instructed the jury that it could not award damages for any injury that

did not occur as a result of Scroggin’s taking Prempro or Premarin and Provera. The

instruction contains the substantive requirements of proximate cause; what remains
-33-

is form and language, which we leave to the court’s broad discretion. In re Prempro

Prods. Liab. Litig., 514 F.3d at 829.

3. Denial of Wyeth’s and Upjohn’s Motions for Judgment as a Matter of Law on

Proximate Causation

The district court denied Wyeth’s and Upjohn’s motion for judgment as a

matter of law based on their claim that Scroggin did not prove that their failure to

warn of the risk of breast cancer proximately caused her breast cancer. We review the

denial of their motions de novo, “viewing the evidence in the light most favorable to

the prevailing party and making all reasonable inferences in favor of the jury’s

verdict.” Boerner, 394 F.3d at 598. “Judgment as a matter of law is only appropriate

when no reasonable jury could have found for the nonmoving party.” Mattis v. Carlon

Elec. Prods., 295 F.3d 856, 860 (8th Cir. 2002). Ordinarily proximate cause is a

question of fact, except where the evidence is such that reasonable minds cannot

differ. Ashley County, 552 F.3d at 667 (citing Wilson v. Evans, 679 S.W.2d 205, 206

(Ark. 1984)).

Wyeth and Upjohn argue that the evidence was not sufficient to show that an

adequate warning would have prevented Scroggin’s breast cancer. The parties

disagree about who had the burden to show what effect an adequate warning would

have had. Specifically, they argue about the application of the heeding

presumption—the presumption that a person would have heeded an adequate warning

if given—and whether it applies to pharmaceutical cases. Notably, neither party asked

Dr. Kuperman if he would have prescribed the medication to Scroggin if there had

been an adequate warning. 

Scroggin argues that the heeding presumption is a rebuttable presumption,

shifting the burden to Wyeth and Upjohn to show that an adequate warning would not

have prevented Scroggin’s injuries. Although Arkansas law generally applies the
15Wyeth and Upjohn rely primarily on Thomas v. Hoffman-LaRoche, Inc., 949

F.2d 806 (5th Cir. 1992). In Thomas, the Fifth Circuit acknowledged that no

Mississippi Court applied the heeding presumption to a medical drug case, noting that

state case law “strongly suggests that a presumption does not exist under Mississippi

law.” Id. at 813. In Ackermann v. Wyeth Pharm., 526 F.3d 203 (5th Cir. 2008), the

Fifth Circuit stated that Texas had “explicitly rejected the . . . read-and-heeded

presumption.” Id. at 212-13 (citations and internal quotations omitted). 

-34-

heeding presumption in this manner, see Smith v. Rogers Group, Inc., 72 S.W.3d 450,

458 (Ark. 2002), Arkansas has yet to consider the presumption in a pharmaceutical

case. Wyeth argues that the presumption should only imply that the physician would

have considered it, but that the burden remains on the plaintiff to show that an

adequate warning would have altered the physician’s decision to prescribe the product

and the plaintiff’s decision to take it.15 

The Tenth Circuit noted in a pharmaceutical case that “[t]he vast majority of

jurisdictions hold that where a warning is inadequate, the plaintiff is entitled to a

rebuttable presumption that an adequate warning would have been heeded if one had

been given.” Thom v. Bristol-Myers Squibb Co., 353 F.3d 848, 855 (10th Cir. 2003).

Given the current application of the heeding presumption in Arkansas and the majority

view, we conclude that Arkansas likely would require Wyeth and Upjohn to rebut the

presumption even in a case involving pharmaceutical products. Moreover, Wyeth and

Upjohn rely on Eck v. Parke, Davis & Co., 256 F.3d 1013, 1019 (10th Cir. 2001)

(relying on Oklahoma law), which required the drug manufacturer defendants to rebut

the presumption by showing that the additional information “would not have changed

the prescribing physician’s course of treatment.” Wyeth and Upjohn failed to

establish that Dr. Kuperman would have prescribed the hormone replacement therapy

despite an adequate warning.

 

Although conflicting, the evidence on proximate causation was sufficient to

allow the jury to find that a failure to warn was the proximate cause of Scroggin’s
-35-

injuries. Dr. Kuperman testified that he still prescribes estrogen plus progestin to

menopausal women and that the initially reported results of the WHI study indicated

a slight relationship. On the other hand, his prescription practices for these drugs have

changed since the WHI study. Since 2002, Dr. Kuperman has written fewer

prescriptions for hormone replacement therapy drugs. Moreover, he tries to keep the

prescription duration to below five years, as the breast cancer risk increases with use.

Dr. Naftalis testified that Scroggin would not have developed breast cancer if she had

taken the therapy for five years rather than eleven. Accordingly, the jury could

reasonably conclude that had Wyeth and Upjohn adequately warned of the breast

cancer risk, Scroggin would have been among Dr. Kuperman’s patients who do not

take hormone replacement therapy drugs or among those who take them for a shorter

period of time. 

Dr. Kuperman also testified that he would respect a patient’s wishes and not

prescribe hormone replacement therapy if she was concerned about the risk of breast

cancer. Thus, the jury could have concluded that Scroggin would have chosen not to

take the drugs if the warnings had been adequate. Although Wyeth and Upjohn focus

on Scroggin’s acknowledgment that she would have accepted a “small” risk and that

she did not know that estrogen plus progestin use “causes” breast cancer, the jury was

not so limited. The jury heard Scroggin explain her understanding of risk as anything

that could possibly happen, even if highly unlikely, and how the equivocal language

in the pre-WHI labels reassured her that the risk was small. The current labels do not

simply identify the 1.24 relative risk reported from the WHI study, but also include

a boxed warning, with straightforward language, and devote substantial attention to

the risk of breast cancer. Scroggin testified that she would not have taken hormone

replacement therapy if she had known of the risk as it was currently understood. 
-36-

D. Punitive Damages

Scroggin’s argument during the punitive damages phase of the trial was two

fold: (1) Wyeth and Upjohn were aware that estrogen plus progestin could cause

breast cancer but had consciously disregarded the risk, and (2) Wyeth downplayed the

risk, campaigning against its acceptance within the scientific community, the FDA,

and the general population. In support of her argument, Scroggin presented Dr.

Parisian as an expert witness on FDA regulations and Wyeth’s and Upjohn’s lack of

compliance therewith.

The district court ordered Dr. Parisian to base her opinion “on her observations

over the years and her understanding of the regulations referenced in her expert report,

her deposition, and the supplemental briefs.” During Dr. Parisian’s testimony, the

district court expressed frustration that she was not linking her testimony to FDA

regulations. Because Dr. Parisian’s testimony consisted mostly of her reading

documents, and not expert analysis, the district court concluded that “most of Dr.

Parisian’s punitive damages testimony should have been excluded.” Thus, although

it had denied Wyeth’s and Upjohn’s motions to strike during the trial, the district court

granted their post-trial motions and struck much of Dr. Parisian’s testimony and

related exhibits.

Without that evidence, the district court determined that Scroggin “failed to

present clear and convincing evidence warranting punitive damages” and granted

Wyeth’s and Upjohn’s motions for judgment as a matter of law. The district court

ruled that if it had not granted those motions, it would have granted a new trial on

punitive damages.
-37-

1. Post-Judgment Exclusion of Dr. Parisian’s Punitive Damages Testimony and

Accompanying Exhibits

Scroggin argues that the district court erred in striking Dr. Parisian’s testimony.

We review a district court’s decision to exclude expert testimony for an abuse of

discretion. Larson, 414 F.3d at 940. Federal Rule of Evidence 702 permits expert

testimony to assist the jury in understanding technical or scientific evidence.

 As an initial matter, we disagree with Scroggin’s contention that Wyeth and

Upjohn did not preserve their objection to Dr. Parisian’s testimony. The district court

stated that the defendants “submitted motions to exclude, lodged numerous objections

during the punitive damages stage, and requested, both orally and in writing, that Dr.

Parisian’s punitive damages testimony be stricken or excluded.” That Wyeth and

Upjohn did not object during Dr. Parisian’s testimony until the court expressed its

own concerns did not waive their objection, for as the court noted, “their specific

points had been made and were well-known to [the court] and [Scroggin’s] counsel.”

Dr. Parisian’s testimony began with a brief overview of some federal

regulations, followed by discussion of specific exhibits, largely devoid of regulatory

analysis. The record reflects that often Dr. Parisian simply read the contents of

exhibits, thus undermining the asserted basis for expert testimony. At a sidebar

conference during the testimony, the district court instructed Scroggin’s counsel to

relate the testimony to FDA guidelines; nevertheless, the testimony continued in the

same manner. Accordingly, we cannot say that the district court abused its discretion

in striking Dr. Parisian’s testimony. 
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2. Grant of Judgment as a Matter of Law Dismissing Jury’s Punitive 

 Damages Award

Scroggin asserts that even without the excluded testimony and related exhibits,

the evidence was sufficient to support the jury’s award of punitive damages. We

review de novo a court’s grant of judgment as a matter of law. Carter, 456 F.3d at

846. “Judgment as a matter of law is only warranted where the evidence at trial is

wholly insufficient to support a jury finding.” Id. 

Arkansas law allows for punitive damages when a defendant “knew or ought

to have known . . . that his or her conduct would naturally and probably result in

injury or damage and that he or she continued the conduct with malice or in reckless

disregard of the consequences from which malice may be inferred.” Ark. Code. Ann.

§ 16-55-206. “[M]alice is not necessarily personal hate; it is, rather, an intent and

disposition to do a wrongful act greatly injurious to another.” Yeakley v. Doss, 257

S.W.3d 895, 899 (Ark. 2007) (citing Fegans v. Norris, 89 S.W.3d 919 (Ark. 2002)).

“A claim for punitive damages is properly submitted to the jury under Arkansas law

where the claim is supported by substantial evidence.” Morris v. Union Pac. R.R.,

373 F.3d 896, 903 (8th Cir. 2004) (internal quotations omitted) (citing D’Arbonne

Constr. Co. v. Foster, 123 S.W.3d 894, 898 (Ark. 2003)).

a. Upjohn

We affirm the district court’s grant of judgment as a matter of law to Upjohn.

Most of the evidence presented during the punitive damages phase concerned Wyeth,

and the evidence related to Upjohn focused on its efforts to market Provera as “the

other half of estrogen replacement therapy.” These advertisements violated federal

regulations, but there is no dispute that prescribing progestin along with estrogen had

become the standard of care in hormone replacement therapy. Scroggin also contends

that a jury could infer malice because Upjohn failed to conduct an in-house study of
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the breast cancer risk after the Degge Group found that further study was needed.

Upjohn, however, did not conceal or restrict the dissemination of the information. It

allowed the Degge Group to publish its findings, thus informing the scientific

community of the current state of the science. On this record, then, there was not

substantial evidence showing that Upjohn acted with “such a conscious indifference

to the consequences that malice may be inferred.” D’Arbonne Constr. Co., 123

S.W.3d at 898.

b. Wyeth

We adopt the district court’s alternative holding as to Wyeth and remand for a

new trial on punitive damages. Scroggin presented sufficient evidence to submit the

question of punitive damages to the jury, even without Dr. Parisian’s testimony.

Moreover, many of the stricken exhibits had been admitted prior to Dr. Parisian’s

testimony and without any requirement that they be presented in relation to Dr.

Parisian’s knowledge of FDA regulations. Accordingly, the jury could have

considered those exhibits and drawn its own conclusions. 

In ruling on the post-verdict motions, the district court set forth a detailed

analysis of the evidence, explaining that each piece failed to present clear and

convincing evidence of reckless indifference. We conclude that this individualized

treatment of the evidence may inadvertently have obscured the full scope of Wyeth’s

conduct that the evidence collectively portrayed. Although Wyeth’s failure to

organize one study to allow for adequate evaluation of the breast cancer risk, or its

attempts to undermine the results of one adverse publication, may not reflect reckless

disregard, a consistent pattern of such conduct might do so. A jury could find that

although each study added to the evidence suggesting a risk of breast cancer, Wyeth

nevertheless continued to engage in a practice of both inaction and mitigation.
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The district court noted that the evidence showed that Wyeth attempted to

convey that there was no definitive link between estrogen plus progestin hormone

replacement therapy and breast cancer. But Scroggin’s claim also rested on the theory

that Wyeth deliberately avoided studying hormone replacement therapy’s effect on

breast cancer. Moreover, a jury could reasonably construe Wyeth’s documents as

repeated efforts over many years to undermine information and studies that attempted

to show a breast cancer link. A jury reasonably could find that these efforts allowed

Wyeth to promote the false understanding that hormone replacement therapy was not

linked to breast cancer and then to promote reliance on this understanding. Viewed

as a whole, then, the evidence presented could allow a jury to find or infer that Wyeth

was guilty of malicious conduct within the meaning of Arkansas law. 

There is also merit to Scroggin’s assertion that the district court characterized

certain evidence in Wyeth’s favor. In entertaining a motion for judgment as a matter

of law, the court “must draw all reasonable inferences in favor of the nonmoving

party, and it may not make credibility determinations or weigh the evidence.” Reeves

v. Sanderson Plumbing Prods., Inc., 530 U.S. 133, 150 (2000). The law requires the

district court to “disregard all evidence favorable to the moving party that the jury is

not required to believe.” Id. at 151. The court, however, credited Justin Victoria’s

characterization of Wyeth’s response to the 1976 Hoover study, thus ignoring Wyeth’s

efforts to refute and mitigate the results of the study. Likewise, the documents

suggesting that Wyeth had a policy of refusing drug samples for breast cancer studies

are not as clear as Wyeth would have the jury believe. These documents, and many

of the stricken documents, were Wyeth’s internal documents and thus not capable of

being rebutted or characterized by Scroggin’s witnesses. The jury could have

concluded that the documents spoke for themselves and rejected Wyeth’s selfinterested explanation. Cf. Wilcox v. State Farm Mut. Auto Ins. Co., 253 F.3d 1069,

1070-71 (8th Cir. 2001) (noting that it would not be obvious error to credit employer’s

affidavit detailing employee’s performance deficiencies when employee was given a

clear opportunity to contradict the affidavit). 
-41-

For these reasons, we conclude that there was sufficient evidence upon which

a jury could conclude that Wyeth acted with reckless disregard to the risk of injury,

even without Dr. Parisian’s testimony. The admission and the jury’s consideration of

Dr. Parisian’s testimony, however, amounted to prejudicial error, and thus the

appropriate remedy is a new trial. Because a new trial may be had on punitive

damages alone without injustice to the parties, we adopt the district court’s alternative

judgment granting a new trial to Wyeth on the punitive damages claim. See Eng. v.

Gulf & W. Mfg. Co., 728 F.2d 1026, 1029 (8th Cir. 1984) (citing Gasoline Prods. Co.

v. Champlin Ref. Co., 283 U.S. 494, 500 (1931)). 

We have considered Wyeth’s and Upjohn’s assertion that a new trial on the

liability phase is required due to district court errors and conclude that none of the

alleged errors affected Wyeth’s or Upjohn’s substantial rights. 

III. Conclusion

The judgment against Wyeth and Upjohn on Scroggin’s claim for compensatory

damages is affirmed. The order granting judgment as a matter of law to Upjohn on

Scroggin’s claim for punitive damages is affirmed. We vacate the order granting

judgment to Wyeth on Scroggin’s claim for punitive damages, adopt the alternative

judgment, and remand the case to the district court for a new trial on punitive

damages. 

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