Scharff v. Wyeth et al

Filing 238

MEMORANDUM OPINION AND ORDER. Signed by Chief Judge William Keith Watkins on 9/19/11. (scn, )

IN THE UNITED STATES DISTRICT COURT
FOR THE MIDDLE DISTRICT OF ALABAMA
NORTHERN DIVISION
HAROLD H. SCHARFF,
administrator of the estate of
Kathleen Scharff,
Plaintiff,
v.
WYETH, et al.,
Defendants.

)
)
)
)
)
) CASE NO. 2:10-CV-220-WKW [WO]
)
)
)
)

MEMORANDUM OPINION AND ORDER
On August 2, 2011, the court entered a Memorandum Opinion and Order (Doc.
# 223 (the “Order”)) partially granting Defendants’ (collectively “Wyeth”) motion for
summary judgment.1 In the Order, the court instructed Plaintiff Kathleen Scharff,2
pursuant to Rule 56(f) of the Federal Rules of Civil Procedure, to show cause “why
summary judgment should not be granted on her remaining wanton failure to warn

1

In the Order, the court granted summary judgment for Wyeth on Mrs. Scharff’s
negligence, AEMLD, breach of express warranty, fraud, and civil conspiracy claims. (Order 18,
48.) The ruling was based upon grounds other than a lack of causation, and ruling was reserved
on Wyeth’s causation arguments. (Order 48.)
2

Harold H. Scharff has since been substituted as Plaintiff. (Doc. # 232.) The remaining
claims are referred to as belonging to Mr. Scharff as administrator of Mrs. Scharff’s estate. (Doc.
# 232.)

and wanton design claims.”3 (Order 49 (citing relevant cases).) Mr. Scharff timely
responded with a brief and 173 accompanying exhibits.

(Doc. # 227 (the

“Response”).) Wyeth timely replied with a brief and 59 accompanying exhibits.
(Doc. # 231 (the “Reply”).) After careful consideration of the arguments of counsel,
the applicable law and the voluminous record, summary judgment is due to be granted
in favor of Wyeth on Mr. Scharff’s remaining wantonness claims.
I. FACTS4
The facts pertinent to this opinion are detailed below. The facts in Parts A
through C are incorporated from the court’s earlier factual findings in the Order.5
(Order 6-15.) Part D details the pertinent facts surrounding Wyeth’s alleged
wantonness.

3

Mrs. Scharff was given notice and a reasonable time to respond to the show cause order.
Fed. R. Civ. P. 56(f); Massey v. Congress Life Ins. Co., 116 F.3d 1414, 1417 (11th Cir. 1997)
(District court must give ten days notice for the plaintiff to respond in opposition to sua sponte
summary judgment.).
4

The actual facts may be different than those stated here. See Lee v. Ferraro, 284 F.3d
1188, 1190 (11th Cir. 2002) (“[F]acts, as accepted at the summary judgment stage of the
proceedings, may not be the actual facts of the case. Nevertheless, for summary judgment
purposes, [the] analysis must begin with a description of the facts in the light most favorable to
the plaintiff.” (citation and internal quotation marks omitted)).
In the interest of brevity, discussion of jurisdiction, venue and the standard of review is
omitted because the former is undisputed and the latter is well settled. (Order 2-5.)
5

The evidentiary references in the Order are unchanged here. Though Mr. Scharff has
highlighted additional evidence in the “Brief Factual Background” section of the Response
(Response 13-18), that evidence is not necessary to the wantonness determination at issue in this
opinion.
2

A.

Mrs. Scharff Is Prescribed Prempro
On August 28, 1997, when she was fifty-five years old and a resident of Boaz,

Alabama, Mrs. Scharff was prescribed Prempro by her primary physician, Dr. Andrew
Reiland. (Doc. # 76, Ex. B, at 27 (“Scharff Dep. Vol. I”); Doc. # 88, Ex. A; Doc.
# 88, Ex. B, at 4, 52 (“MDL Fact Sheet”).) Dr. Reiland prescribed Prempro for Mrs.
Scharff because of her menopausal symptoms, including extreme hot flashes and
extreme vaginal dryness. (Doc. # 76, Ex. C, at 121-22 (“Dr. Reiland Dep.”); Doc.
# 76, Ex. A, at 17-18 (“Scharff Dep. Vol. II”); Doc. # 88, Ex. A.) Dr. Reiland did not
prescribe Prempro to Mrs. Scharff to prevent osteoporosis or Alzheimer’s disease, or
for heart protection, nor did he tell her of such benefits. (Scharff Dep. Vol. II, at
21-23.) At the time of her prescription, Mrs. Scharff did not recall receiving a book,
brochure, or other information about menopause from Dr. Reiland. (Scharff Dep.
Vol. II, at 21.) Mrs. Scharff relied solely on Dr. Reiland’s advice in deciding to take
Prempro, and she did not recall seeing any advertisements for Prempro before or
during the period she took Prempro. (Scharff Dep. Vol. I, at 81; Scharff Dep. Vol II,
at 19, 78.) Mrs. Scharff recalled that her Prempro prescription package probably
included the Patient Information Insert, that she probably glanced at it, but that she
did not read it. (Scharff Dep. Vol. I, at 77, 138-39; Scharff Dep. Vol. II, at 26.)

3

1.

Background on Prempro

Prempro comes in pill form and combines Premarin, conjugated estrogens, and
Medroxyprogesterone acetate, a synthetic progestin. (Doc. # 88, Ex. C, at 3120 (1998
Physicians’ Desk Reference (“1998 PDR”)).)

At the time of Mrs. Scharff’s

prescription, Prempro was manufactured by Ayerst Laboratories, Inc., which was then
owned by Wyeth-Ayerst, a predecessor in interest to Wyeth, LLC. (Doc. # 88, at 7;
1998 PDR, at 3124.) In 1994, the Food and Drug Administration (“FDA”) approved
Prempro for the treatment of menopausal symptoms and for the prevention of
osteoporosis. (Doc. # 76, Ex. E (“1994 FDA Approval”).) The language of
Prempro’s 1998 Patient Information Insert is found in the 1998 PDR, which the
parties agree contains substantially the same language as the 1997 PDR and Patient
Information Insert. (Doc. # 88, at 8 & n.3; Doc. # 77, at 4 n.1.) Prempro’s Patient
Information Insert, as reproduced in the 1998 PDR, included the following warning:
WARNINGS
ALL WARNINGS BELOW PERTAIN TO THE USE OF THIS
COMBINATION PRODUCT.
Based on experience with estrogens and/or progestins:
1. Induction of malignant neoplasms Breast Cancer. Some studies have
reported a moderately increased risk of breast cancer (relative risk of 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. The majority of studies, however, have not shown an association
in women who have ever used estrogen replacement therapy. The effect of
added progestins on the risk of breast cancer is unknown, although a
4

moderately increased risk in those taking combination estrogen/progestin
therapy has been reported. Other studies have not shown this relationship. In
a one year clinical trial of PREMPRO, PREMPHASE®, and Premarin alone,
5 new cases of breast cancer were detected among 1377 women who received
the combination treatments, while no new cases were detected among 347
women who received Premarin alone. The overall incidence of breast cancer
in this clinical trial does not exceed that expected in the general population.
In the three year clinical Postmenopausal Estrogen Progestin Intervention
(PEPI) trial of 875 women to assess differences among placebo, unopposed
Premarin, and three different combination hormone therapy regimens, one (1)
new case of breast cancer was detected in the placebo group (n=174), one [(1)]
in the Premarin alone group (n=175), none in the continuous Premarin plus
continuous medroxyprogesterone acetate group (n=174), and two (2) in the
continuous Premarin plus cyclic medroxyprogesterone acetate group (n=174).
Women on hormone replacement therapy should have regular breast
examinations and should be instructed in breast self-examination, and women
over the age of 50 should have regular mammograms.
(1998 PDR at 3121-22; Doc. # 88, at 7-8.) It also warned that:
RISKS OF ESTROGENS AND/OR PROGESTINS
...
Cancer of the Breast. 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 self-examination are recommended for
all women. Regular mammograms are recommended for all women over 50
years of age.
(1998 PDR at 3124; Doc. # 88, at 8.)

5

2.

Dr. Reiland’s Knowledge Concerning Prempro

In 1997, when Dr. Reiland prescribed Prempro to Mrs. Scharff, he had
background knowledge of the risk of breast cancer associated with hormone
replacement therapy. (Dr. Reiland Dep. 39.) Dr. Reiland would discuss this breast
cancer risk with his patients when prescribing hormone replacement therapy, but he
“would always say that the majority of the studies seemed to be reassuring.” (Dr.
Reiland Dep. 108-09.) Dr. Reiland recognized in 1997 that there was conflicting
literature regarding the association of breast cancer and hormone replacement
therapies. (Dr. Reiland Dep. 39-40.) He also indicated that he was a little skeptical
of the 1997/1998 PDR language stating that “the majority of studies have not shown
an association [with a higher risk of breast cancer] in women who have ever used
[estrogen replacement therapy],” because some of those studies may have been
inaccurate. (Dr. Reiland Dep. 39.)
Dr. Reiland also testified that the 1998 PDR label referencing the
Postmenopausal Estrogen Progestin Intervention (“PEPI”) trial did not indicate a
greater chance of breast cancer associated with hormone replacement therapy relative
to the background population, and that he found this to be “somewhat reassuring.”
(Dr. Reiland Dep. 40-41, 43-44.) When asked about Prempro’s 2007 PDR label, Dr.
Reiland found its black box label to be comparably stronger than the 1997-99 PDR
6

labels for Prempro. (Dr. Reiland Dep. 47-50.) He also stated that he wished that he
had had that information available in 1997, and that he would have passed that
information along to Mrs. Scharff. (Dr. Reiland Dep. 47-50.) He also believed that
if Wyeth’s sales representatives had the 2007 label information in 1997 or 1998, they
would have passed it along to him. (Dr. Reiland Dep. 50-51.) Dr. Reiland agreed
that accurate information about a drug was important to a doctor’s risk/benefit
analysis. (Dr. Reiland Dep. 63-65.) If a drug’s risks outweighed its benefits, Dr.
Reiland said that he generally would not have prescribed it, but ultimately the
decision to take a drug would be up to the patient and he would pass along all the
available information to the patient. (Dr. Reiland Dep. 65-66.)
Dr. Reiland’s decision to prescribe Prempro to Mrs. Scharff was not affected
by any Wyeth sales representatives’ calls or promotional materials, though he did
receive sales calls from Wyeth sales representatives before, during, and after his
prescription of Prempro to Mrs. Scharff. (Dr. Reiland Dep, 21-22, 142; Doc. # 88,
Ex. J.) According to Wyeth’s sales records, Dr. Reiland met with Susan Hendrick,
a Wyeth sales representative, on July 1, 1997. She reported in her notes, “[Dr.
Reiland] has used the Premphase and said that we need to have more info on it to give
to the patient[;] I gave him the tear-off sheets and left videos and pamphlets for his
patients. We really do need more give-aways for Premphase for these docs that
7

areusing [sic] it.” (Doc. # 88, Ex. J.) On November 25, 1997, she reported that “[Dr.
Reiland] said that he loves the XXXXXXX and hasn’t heard back from any girls he
has put it on[.] Liked the XXX and said that it was about time that we made it once
a day - much easier[.] Premarin and lowering lipids - he heartily agreed[.]” (Doc.
# 88, Ex. J.)
B.

Mrs. Scharff’s Breast Cancer Diagnosis and Treatment
Ms. Scharff took Prempro as prescribed from August 28, 1997, to January 26,

1999. (MDL Fact Sheet at 4; Scharff Dep. Vol. II, at 24.) Prempro was the only
hormone replacement drug that Mrs. Scharff ever took, and Dr. Reiland was the only
doctor who prescribed it for her. (Scharff Dep. Vol. II, at 72.) Prempro alleviated
Mrs. Scharff’s menopausal symptoms, but those symptoms returned once she stopped
taking the drug. (Scharff Dep. Vol. II, at 72-73.)

On September 24, 1998,

approximately thirteen months after she began taking Prempro, Mrs. Scharff visited
Dr. Reiland and reported that she felt a lump in one of her breasts. (Dr. Reiland Dep.
130; Scharff Dep. Vol. I, at 39.) Dr. Reiland immediately referred Mrs. Scharff to Dr.
Naughton, a local surgeon, for a follow-up on the lump in her breast. (Scharff Dep.
Vol. I, at 39.) On September 25, 1998, she received a mammogram from Dr. Reiland,
and Mrs. Scharff visited Dr. Naughton. (Dr. Reiland Dep. 131; Scharff Dep. Vol. I,
at 39, 42.) According to Mrs. Scharff, Dr. Naughton told her, “Let’s just watch it.
8

It’s probably nothing.” (Scharff Dep. Vol. II, at 32.) Dr. Naughton recalled that he
recommended a short follow-up and a re-evaluation. (Doc. # 88, Ex. L, at 14 (“Dr.
Naughton Dep.”).)
In early January 1999, Dr. Naughton called Mrs. Scharff and told her, “We
have to have that checked.” (Scharff Dep. Vol. II, at 32-33.) On January 12, 1999,
Mrs. Scharff visited Dr. Naughton, who performed a biopsy on the lump in her breast
and sent the biopsy off for analysis. (Dr. Reiland Dep. 132; Scharff Dep. Vol. II, at
32-33; Doc. # 76, Ex. H (“Dr. Naughton January 13, 1999 Record”).) On January 13,
1999, the Gadsden Regional Medical Center Pathology Department issued a
pathology report diagnosing her breast tissue biopsy as:

“BREAST, RIGHT,

SURGICAL BIOPSY: INVASIVE MODERATELY DIFFERENTIATED DUCTAL
CARCINOMA . . . .”6 (Dr. Naughton January 13, 1999 Record.) Plaintiff’s evidence
is that Mrs. Scharff was told of her breast cancer diagnosis on January 18, 1999, by
Dr. Naughton. (Doc. # 88, at 19; Doc. # 88, Ex. M.) At that same time, Dr. Naughton

6

Whether Mrs. Scharff’s breast cancer was ductal or tubular-lobular is hotly contested.
The initial report of ductal cancer is referenced here as it pertains to the date her breast cancer
was diagnosed, but the court does not draw the factual conclusion that her breast cancer was
ductal. Such a factual conclusion is unnecessary to this memorandum opinion.
9

also told her to stop taking Prempro, and she did.7 (Scharff Dep. Vol. I, at 71.) Mrs.
Scharff did not ask Dr. Naughton why he was instructing her to stop taking Prempro,
nor did Dr. Naughton recall Mrs. Scharff asking him if hormone therapy caused her
breast cancer. (Scharff Dep. Vol. II, at 80, 86-87; Dr. Naughton Dep. 32-33.) There
is also no evidence in the record that she asked Dr. Reiland about the cause of her
breast cancer.
After consulting with a radiation oncologist, Mrs. Scharff elected to have a
radical mastectomy done on her right breast. (Dr. Naughton Dep. 31-32; Scharff Dep.
Vol. II, at 34.) Mrs. Scharff’s mastectomy of her right breast was performed by Dr.
Naughton on January 26, 1999.8 (Dr. Reiland Dep. 134; Dr. Naughton Dep. 36-38.)
On February 2, 1999, Mrs. Scharff’s breast cancer was diagnosed as both ER+
(estrogen receptor positive) and PR+ (progestin receptor positive). (Doc. # 88, Ex.
O (“February 2, 1999 Lab Report”).)

7

The MDL fact sheet reflects that Mrs. Scharff ceased taking Prempro on January 26,
1999, over a week after she was told of her cancer diagnosis. (MDL Fact Sheet 4.) However, the
MDL fact sheet also reflects that “[Dr. Naughton] instructed plaintiff to discontinue hormone
therapy” on January 11, 1999. (MDL fact Sheet 54.) These factual inconsistencies are immaterial
here.
8

Mrs. Scharff later elected to have a mastectomy performed on her left breast due to
shoulder pain and general discomfort, and to avoid continued consumption of the drug
tamoxifen. (Scharff Dep. Vol. I, at 61-62; Scharff Dep. Vol. II, at 35-36, 79-80.)
10

C.

The Women’s Health Initiative, Prempro, and Mrs. Scharff
The National Institutes of Health published its report of the Women’s Health

Initiative (“WHI”) on July 9, 2002. (Doc. # 88, Ex. P (“WHI Press Release”).) A
brief description of the WHI study follows:
The estrogen plus progestin trial of the WHI involved 16,608 women
ages 50 to 79 years with an intact uterus. An important objective of the
trial was to examine the effect of estrogen plus progestin on the
prevention of heart disease and hip fractures, and any associated change
in risk for breast and colon cancer. The study did not address the shortterm risks and benefits of hormones for the treatment of menopausal
symptoms.
(WHI Press Release 2.) The WHI Press Release also stated that “[t]he National Heart,
Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) [ ]
stopped early a major clinical trial of the risks and benefits of combined estrogen and
progestin in healthy menopausal women due to an increased risk of invasive breast
cancer.” (WHI Press Release 1.) The study was stopped after an average follow-up
period of 5.2 years. (WHI Press Release 1.) The WHI Press Release explained that
the estrogen plus progestin group in the study experienced a 26 percent increase in
breast cancer compared to the placebo group. (WHI Press Release 4.)
The publication of the WHI study in July 2002 garnered a great deal of media
attention. (See, e.g., Dr. Reiland Dep. 68.) Dr. Reiland testified that the study found
that there was an increased incidence of breast cancer in the study population, which
11

had a profound impact on his understanding of the risks and benefits involved in
hormone replacement therapy. (Dr. Reiland Dep. 68-69.) It was not, however, the
first time he had been made aware of the increased incidence of breast cancer
associated with hormone replacement therapy. (Dr. Reiland Dep. 71.) He noted a
change in the labeling of Prempro after the WHI study was published. (Dr. Reiland
Dep. 72-73.)
Mrs. Scharff did not recall the publication of the WHI study or reading
anything about the findings of that study. (Scharff Dep. Vol. II, at 39-40.) However,
Mrs. Scharff did begin to connect her breast cancer to her consumption of Prempro
sometime between 2003 and 2005 when she “started seeing more articles in the paper
and stuff like that.” (Scharff Dep. Vol. II, at 39, 78.) During that period, she
collected newspaper clippings of articles discussing the association of hormone
replacement therapy and breast cancer. (Scharff Dep. Vol. II, at 39-40.)
D.

Wyeth’s Allegedly Wanton Conduct
The following evidence, relevant to the remaining wantonness claims, was

produced by Mr. Scharff and Wyeth in response to the court’s show cause order.9
In his Response, Mr. Scharff argues that Wyeth’s wanton conduct occurred
along three lines of operation. (Response 26.) First, Wyeth knew that safety studies
9

Evidence from Wyeth is only cited where it is undisputed by Mr. Scharff’s evidence.
12

on estrogen and progestin hormone therapy (“E+P”) were needed, but deliberately
refused to conduct those studies. (Response 26.) Second, Wyeth failed to tell doctors
the truth about the breast cancer risk of E+P based upon the then-existing science, and
took affirmative steps to stop doctors and women from learning the actual risks and
benefits of E+P. (Response 26.) Third, Wyeth promoted its hormone drugs for
untested, unproven and off-label heart and mental benefits. (Response 26.) In light
of the limited scope of the Order and the wantonness claims at issue, the court now
turns to the relevant facts.
1.

Wyeth’s Knowledge of the Need for Additional Studies Concerning the
Risk of Breast Cancer Associated with Combination Estrogen and
Progestin Hormone Replacement Therapy

Mr. Scharff opens his discussion of the facts surrounding Wyeth’s knowledge
of the risk of Prempro with a lengthy discussion of estrogen replacement therapy
(“ERT”) and its effect on endometrial cancer in the 1970s. (Response 27-30.) Mr.
Scharff then turns to Wyeth’s promotion of the combination use of Premarin and a
progestin “off-label” in the 1980s to treat menopausal symptoms. (Response 30-31.)
During this period, long before Mrs. Scharff was prescribed Prempro in 1997 or
Prempro was approved by the FDA in 1994, Wyeth did not conduct any E+P breast
cancer studies. (Response 31.) Following is a chronological summary of evidence of
13

Wyeth’s knowledge concerning the need for additional studies of the breast cancer
associated with E+P.10
In a 1977 study concerning the use of estrogen for osteoporosis, the
Endocrinology and Metabolism Advisory Committee of the FDA noted that “[t]here
is insubstantial evidence that there may be additional risk of increased breast cancer
but this is at this time unsubstantiated.” (Response, Ex. 43, at 1.) A 1983 Wyeth
memorandum stated that “[t]here is not adequate evidence in the literature for any
estrogen / progesterone regimen which would meet FDA standards.”11 (Response, Ex.
44.) At a 1983 “Estrogens Workshop” sponsored by the NHLBI-NIH, Wyeth
representative Dr. John Mullane reported his overall impression that “the participants
in the workshop were favorably disposed to the conduct of a relatively large, longterm, NIH-type study on the effects of estrogens on morbidity and mortality.”
(Response, Ex. 45.) In a 1983 internal memorandum, Wyeth representative Arnold
Somin wrote a memorandum concerning the “Desired Labeling and Indications” of a
product called Prem-Pak. (Response, Ex. 47.) Prem-Pak was an E+P combination

10

Combined estrogen and progestin hormone therapy is referred to as E+P. Some of the
studies refer to E+P as HRT, while others fold both estrogen replacement therapy (“ERT”) and
E+P under the umbrella of HRT. The court has attempted to be as consistent as possible by
using “E+P” for combination hormone therapy and “estrogen” or “ERT” for non-combination
hormone therapy.
11

Wyeth’s various successors-in-interest are referred to as Wyeth throughout the opinion.
14

therapy consisting of a single package of Premarin and “a progestin for cyclic use.”
(Response, Ex. 47.) Regarding Prem-Pak, Mr. Somin expressed his concern with the
FDA and the consequences “that could arise if the FDA were to take the position that
PREM-PAK is equivalent to a combination drug product of the type requiring
demonstration that the combination does more than its components in regard to each
indication for the combination product. To attempt such demonstration would be very
costly, would take many years, and might in the end not prove successful.” (Response,
Ex. 47.) In fact, he admitted that “the results of the studies that would be needed could
turn out to be embarrassing. To avoid this issue, [Wyeth] ha[s] taken the position that
the progestin is used to prevent or minimize a potential adverse effect of PREMARIN
(endometrial hyperplasia) and, thereby, to enhance the safety of PREMARIN.”
(Response, Ex. 47.)
In 1985, the FDA denied Wyeth’s Prem-Phase New Drug Application.
(Response, Ex. 46.) Wyeth representative John R. Rapoza represented that it was then
the FDA’s opinion “that clinical trials with Prem-Phase will be necessary prior to
approval.” (Response, Ex. 46.) In 1986, Dr. Elizabeth Barrett-Connor published an
article in The Western Journal of Medicine in which she stated: “[T]here are no
studies of adequate design, duration and sample size to determine the risks and
benefits of any prolonged estrogen-progestin combination in post-menopausal
15

women. . . . Given the high prescribing rates reported for progestin, any possible
untoward effects should be quickly researched analyzed in relation to the benefits of
such use.” (Response, Ex. 48, at 2.)
In 1989, Wyeth held its annual symposium in Estoril, Portugal, on the longterm effects of estrogen deprivation. (Response, Ex. 52.) In an article penned in
conjunction with the symposium, Dr. David B. Thomas stated that “prolonged
exposure to a progestin, perhaps in the presence of estrogen, might enhance the risk
[of breast cancer].” (Response, Ex. 52, at 20.) That same author also found that three
studies conducted in Sweden, Great Britain, and Denmark provided some preliminary
results on the risk of E+P. (Response, Ex. 52, at 21-23.) The Swedish study showed
no increase in breast cancer risk among women given estrogen with an unspecified
progestin for more than three years. (Response, Ex. 52, at 21.) The British study
delivered a statistically non-significant result suggesting a slight increase in relative
breast cancer risk (1.2) in women receiving various combinations of estrogens and
progestins for four years or longer. (Response, Ex. 52, at 21.) The Danish study
indicated no increase in breast cancer risk among women who received progestin with
every dose of estrogen. (Response, Ex. 52, at 23.) In closing, the author called for
more studies on the effects of estrogen replacement therapy “for possible
carcinogenic” effects on breast tissue. (Response, Ex. 52, at 23.)
16

In early January 1990, Wyeth submitted an “exhaustive review of the world’s
literature published since 1976 examining the possible relationship between breast
cancer and hormone replacement therapy” to the Division of Metabolism and
Endocrine Drug Products of the FDA. (Response, Ex. 54.) Unfortunately, Mr.
Scharff has only enclosed the cover page of that “exhaustive review.” (Response, Ex.
54.) In the absence of that document, the court assumes that the report is the
“exhaustive review” that it is purported to be.
At a February 1990 meeting of the FDA Fertility and Mental Health Advisory
Committee, Dr. Linda Golden, an FDA medical officer, presented animal evidence
“suggesting that exogenous estrogens as well as progestogens can produce breast
cancer.” (Response, Ex. 55, at 2.) Other doctors presented opposing opinions on the
relationship between hormone replacement therapy and breast cancer. (Response, Ex.
55, at 2.) In the summary minutes of the meeting, the Committee posed the question,
“Does the addition of progestins to estrogen therapy alter the risk of breast cancer in
postmenopausal women?” (Response, Ex. 56, at 3.) The Committee responded
unanimously “that there are insufficient data to answer these questions at this time.”
(Response, Ex. 56, at 3.)
In response to the Committee meeting, a Wyeth employee circulated a
congratulatory internal memorandum stating that it was Wyeth’s goal “to ensure that
17

this meeting was a ‘non-event,’ and that’s exactly what happened.” (Response, Ex.
57, at 1.) Further, the memorandum urged that “[w]e must position Wyeth-Ayerst as
the authoritative information source on HRT. This means that we must more and
more be the providers of new credible medical and scientific information concerning
HRT.” (Response, Ex. 57, at 1.) The memorandum closed: “Eventually the various
questions that this Advisory Committee could not answer conclusively will be
answered, and it is our responsibility and very much to our benefit for Wyeth-Ayerst
to provide the studies, information, and insights to ensure that the answers will be
accurate and balanced.” (Response, Ex. 57, a 1.) In a later internal memorandum to
the Premarin Team, the same Wyeth employee added: “Congratulations on the
success you achieved at the recent FDA Advisory Committee meeting. We are on our
way to making Premarin® a $1 billion drug.” (Response, Ex. 58.)
Later that year in an internal memorandum, Wyeth Director of Regulatory
Affairs Justin Victoria memorialized a meeting he had with an FDA Director and
Compliance Officer. (Response, Ex. 53, at 1.) In that memo, he explained that the
FDA Director and the FDA “remain[ed] unconvinced of the overall safety and
effectiveness of combined estrogen/progestin therapy.” (Response, Ex. 53, at 1.) The
FDA Director noted that there was no approved New Drug Application for
combination Premarin/progestin therapy, and that the FDA would have to approve a
18

full New Drug Application to allow for such a combination. (Response, Ex. 53, at 1.)
The FDA Compliance Office expressed similar concerns. (Response, Ex. 53, at 2.)
Mr. Victoria concluded that, “without adequate clinical data to address the
benefit/risk ratio of combined estrogen/progestin therapy, [the FDA Director] and his
Division will not approve such a combination.” (Response, Ex. 53, at 2.) He also
noted that Wyeth’s “Premarin/MPA clinical program continues to progress on
schedule to meet the 1992 target NDA [New Drug Application] filing.” (Response,
Ex. 53, at 2.)
In April 1990, epidemiologists Drs. Glass and Hoover published a report
entitled Rising Incidence of Breast Cancer: Relationship to Stage and Receptor
Status. (Response, Ex. 59, at 1.) Based on a review of Kaiser Permanente’s
population-based tumor registry, the report analyzed breast cancer incidence from
1960 to 1985. (Response, Ex. 59, at 1.) In the report, Drs. Glass and Hoover found
a 131% increase in ER+ breast tumors between the mid-1970s and the mid-1980s,
“perhaps implicating hormonal factors in the rising incidence of breast cancer.”
(Response, Ex. 59, at 1 (emphasis added).) In absolute terms, this represented a
growth in ER+ cancers from 24.9 per 100,000 population in 1974-1977, to 39.9 per
100,000 population in 1978-1981, to 57.5 per 100,000 population in 1982-1985.
(Response, Ex. 59, at 3.) In comparison, the total breast cancer incidence for all ages
19

grew from 79.3 per 100,000 population in 1970-1974, to 89.2 per 100,000 population
in 1975-1979, to 100.3 per 100,000 population in 1980-1985. (Response, Ex. 59,
at 2.) In the sixty and over age group, the overall breast cancer rate was much higher,
284.2 per 100,000 population in 1970-1974, 287.2 per 100,000 population in 19751979, and 374.6 per 100,000 population in 1980-1985. (Response, Ex. 59, at 2.) The
Glass-Hoover report concluded with the hypothesis that, “[i]f ER + and ER - cancer
have different etiologic factors, hormonal influences could be responsible for the
differential rise in ER + breast cancer over time.” (Response, Ex. 59, at 4.)
In a 1991 letter to the editor in the American Journal of Epidemiology, Drs.
Grady and Ernster called for “additional data on the effect of combination hormone
therapy on breast cancer risk.” (Response, Ex. 60, at 4.) The letter noted that that
edition of the American Journal of Epidemiology included “two large, well-conducted
case-control studies that address the effects of hormone therapy on breast cancer.”
(Response, Ex. 60, at 1.) Drs. Grandy and Ernster found these reports to be
conflicting. One found a small decrease in the relative risk of breast cancer in women

20

treated with E+P, while the other found a small increase in the risk of breast cancer
in women treated with E+P.12 (Response, Ex. 60, at 3.)
In June 1991, the FDA again conducted an Advisory Committee meeting to
review the current status of combined hormone replacement therapy, and Wyeth again
submitted a “comprehensive review of the literature regarding the effects of estrogen
/ progestin therapy in postmenopausal women.” (Response, Exs. 61-62.) Again, Mr.
Scharff has only submitted the cover page of the “comprehensive review.”
(Response, Ex. 61.) The Committee posited the question, “To what degree does the
progestogen in HRT affect . . . the possible risk of breast cancer induced by ERT?”
and responded, “The data are not yet adequate to permit an answer to this question
but such information will be forthcoming.” (Response, Ex. 62.)
In December 1992, Wyeth submitted a New Drug Application for conjugated
estrogens and Medroxyprogesterone Acetate, covering both Prempro and Premphase.
(Response, Ex. 65, at 1.)

12

Relative risk is defined “as the ratio of the incidence rate (often referred to as
incidence) of disease in exposed individuals to the incidence rate in unexposed individuals.”
Federal Judicial Center, Reference Manual on Scientific Evidence 348 (2d ed. 2000). “The
incidence rate of disease reflects the number of cases of disease that develop during a specified
period of time divided by the number of persons in the cohort under study. Thus, the incidence
rate expresses the risk that a member of the population will develop the disease within a
specified period of time.” Id. at 348-49 (emphasis added).
21

In May 1993, at an industry conference attended by Wyeth officials, Dr. Linda
Golden, an FDA medical officer, offered a presentation on “Quandaries in HRT
Therapy.” (Response, Ex. 64.) According to a Wyeth internal memorandum, Dr.
Golden was concerned that E+P would not offer the same “cardioprotective benefit”
to women as ERT, nor was she “comfortable with the risk/benefit ratio with respect
to breast cancer and prolonged estrogen therapy.” (Response, Ex. 64, at 1.) She also
noted that the FDA was evaluating E+P combination therapy, and that most breast
cancer studies were epidemiologic studies not based on randomized groups.
(Response, Ex. 64, at 1.) Dr. Golden called for well controlled placebo randomized
studies for new uses of estrogen products. (Response, Ex. 64, at 1.) In an October
1993 meeting between Wyeth and the FDA’s Division of Metabolism and Endocrine
Drug Products about Wyeth’s New Drug Application for an E+P product, Dr. Golden
expressed her concerns “about the safety of adding excess progestin, i.e. breast
cancer.” (Response, Ex. 65, at 7.) Therefore, she wanted assurances that Wyeth
would “not exceed the lowest effective dose of MPA for the companion dose of
Premarin.” (Response, Ex. 65, at 7.)
In December 1994, Dr. Golden completed a Medical Officer’s Review of the
Prempro and Premphase New Drug Application submitted by Wyeth. (Response, Ex.
66.) In the Review, Dr. Golden recommended approval of Wyeth’s New Drug
22

Application for both Prempro and Premphase. (Response, Ex. 66, at 74-75.)
However, Dr. Golden noted her concerns with the risk of breast cancer associated
with Prempro and Premphase. (Response, Ex. 66, at 7-8, 74-75.) She noted that
“many more years are still needed before the relationship between HRT and breast
cancer can be definitively determined.” (Response, Ex. 66, at 8.) Further, because
of the growing popularity of HRT use by aging “baby boom” women, she noted that
the public health impact of this safety concern was increasing. (Response, Ex. 66,
at 8.) Therefore, she concluded that “the true effect of HRT on breast cancer
incidence and mortality must be considered the single most important safety issue
concerning this class of drugs.” (Response, Ex. 66, at 8.) She also noted that recent
relative risk estimates for HRT and breast cancer “suggest that concomitant
progestins do not reduce and may exacerbate the risk of breast cancer associated with
ERT.” (Response, Ex. 66, at 8.) However, Dr. Golden approved, with some
modifications, Wyeth’s proposed labeling of Prempro and Premphase, including the
warning about the risk of breast cancer. (Response, Ex. 66, at 62-71; see also Ex. 67,
at 4 (“The final printed labeling (FPL) must be identical to the December 20 and 30,
1994, draft labeling.”).) Therefore, she recommended the Prempro and Premphase
New Drug Application for approval on the condition that Wyeth “will conduct a
comprehensive Phase IV investigation of breast cancer risk in users and non-users of
the NDA regimens.” (Response, Ex. 66, at 74.)
23

On December 30, 1994, the FDA approved Wyeth’s New Drug Application for
Prempro and Premphase, concluding “that adequate information has been presented
to demonstrate that the drug products are safe and effective for use as recommended
in the submitted draft labeling.” (Response, Ex. 67, at 4.) The approval letter also
referenced Wyeth’s “additional Phase 4 commitment made in a December 30
telefacsimile to conduct a comprehensive investigation of breast cancer risk in users
and non-users of the New Drug Application regimens at appropriate and reasonable
cost.” (Response, Ex. 67, at 5.)
Mr. Scharff produced evidence, however, that Wyeth did not undertake or
sponsor an independent, comprehensive study of breast cancer risk associated with
HRT prior to Mrs. Scharff’s consumption of Prempro from 1997 to 1999. (Response,
Ex. 27, at 1914; Ex. 73, at 51-58; Ex. 74, at 695; Ex. 75, at 380, 384; Ex. 76, at 33941; Ex. 77, at 32-33; Exs. 78-79, 81, at 37-51.) Wyeth disputes this evidence, but Mr.
Scharff’s evidence must be credited. (Reply 35-39.)
However, Wyeth produced undisputed evidence that it submitted a proposed
protocol for the Phase IV study to the FDA in 1995, and met with the FDA to review
the proposal. (Reply, Exs. 51-52.) In Wyeth’s minutes from a November 1995
meeting with the FDA, an FDA medical officer noted that “the initiation of any study
would still be a number of years away (8-9 years),” and indicated that he had second
thoughts regarding the feasibility of conducting the Phase IV trial. (Reply, Ex. 52,
24

at 2-3.) Further, another FDA official indicated she would note Wyeth’s due
diligence in meeting its post-approval commitment in spite of the delay in initiating
the trial. (Reply, Ex. 52, at 3.) Ultimately, in November 1997, the FDA relieved
Wyeth of its Phase IV study commitment. (Reply, Ex. 54.) The FDA concluded that
Wyeth’s “support for . . . prospective studies [the Women’s Health Initiative and
Women’s International Study of Long-duration Oestrogen After Menopause] will
fulfill th[e] Phase 4 commitment, and that conduct of the previously discussed casecontrol study is not necessary.” (Reply, Ex. 54.)
2.

Wyeth’s Knowledge Concerning the Risk of Breast Cancer Associated
with E+P

Mr. Scharff claims that the 1994 to 2002 breast cancer warnings on the
Prempro label were inaccurate, and that Wyeth only corrected the breast cancer
warnings after the WHI study was published.13 (Response 38.) Mr. Scharff claims
that Wyeth knew of the inaccuracies because it “learned of studies conducted by
independent researchers in those years [prior to the WHI study] that showed a real
breast cancer risk with E+P.”

(Response 38.)

Because Wyeth’s knowledge

concerning the risk of breast cancer is central to whether it failed to warn of the risk
of breast cancer while conscious that injury would likely or probably result from that

13

The facts surrounding Wyeth’s knowledge of the risk of breast cancer up to January
1999, when Mrs. Scharff was diagnosed with breast cancer and ceased taking Prempro, are
examined here. See Part I.A.1 for the text of the pertinent Prempro breast cancer warning.
25

failure, the court turns to the facts surrounding Wyeth’s knowledge about the risk of
breast cancer.14 See, e.g., Ex parte Capstone Bldg. Corp., No 1090966, 2011 WL
2164027, at *6-7 (Ala. June 3, 2011).
In August 1989, a study entitled “The Risk of Breast Cancer After Estrogen
and Estrogen-Progestin Replacement” (the “Bergkvist Study”) was published in the
New England Journal of Medicine. The Bergkvist Study was a “prospective study
of 23,244 women 35 years of age or older who had had estrogen prescriptions filled
in the Uppsala region of Sweden.”15 (Response, Ex. 88, at 1.) “During the follow-up
period (mean, 5.7 years) breast cancer developed in 253 women.” (Response, Ex. 88,
at 1.) 208 of these women had consumed some form of estrogen or E+P, while 45
reported no use of estrogens despite their prescription. (Response, Ex. 88, at 3.) The
expected number of breast cancers in the cohort was 222.5, giving a relative risk of
breast cancer for all of the participants of 1.1 (95% confidence interval, 1.0 to 1.3).

14

Mr. Scharff also produced evidence concerning Wyeth’s marketing efforts, “ghostwriting,” and other publicity efforts to combat negative studies from 1994 to 1999. (Response
38-49; see also Response 49-57 (Wyeth’s distortion of the risk benefit profile for E+P).)
However, Mr. Scharff has not adequately explained how this evidence is relevant to the material
issue of how Wyeth wantonly failed to warn Dr. Reiland of the risk of breast cancer associated
with Prempro. Further, there is no evidence that Dr. Reiland or Mrs. Scharff read or relied on
any of those articles or studies. (See supra Part I.A; Reply 40-42.)
15

The relative risk of breast cancer was calculated according to the following ratio: (the
number of observed breast cancer cases) / (the number of breast cancer cases expected). The
expected breast cancer calculation was based on the risk of breast cancer among the population
of women in the Uppsala health care region that were not included in the study cohort (4213
breast cancer cases in 2,064,293 person-years of observation). (Response, Ex. 88, at 2.)
26

Though the study consisted primarily of women on ERT, it also included women who
consumed some form of E+P. (Response, Ex. 88, at 2.) With respect to women who
consumed only E+P, the study found a relative risk of breast cancer of 4.4 (95%
confidence interval: .9 to 22.4) among long-term users, those patients with more than
six years of use. (Response, Ex. 88, at 3.) For women who had consumed E+P for
less than six years, the relative risk of breast cancer was less than 1, however.
(Response, Ex. 88, at 3 (Table 3) (less than 6 months use, relative risk .5 (95%
confidence interval: .2-1.8); 7 months to 36 months use, relative risk .7 (95%
confidence interval: .3-1.3); 37-72 months use, relative risk .9 (95% confidence
interval, .3-2.6)).)
In comparison, women who reported no estrogen consumption despite their
prescription nevertheless had a relative risk of breast cancer of 1.6 (95% confidence
interval, 1.1-2.1). In their discussion section, the authors wrote:
Overall, we noted a 10 percent increase in the relative risk of breast
cancer in 23,244 women for whom estrogens were prescribed for
symptoms of menopause. . . . Our study found that the addition of
progestin offered no protection against the development of breast
cancer. This observation raises concern about the long-term treatment
with a combination of estrogens and progestins that has been
proposed for widespread use as prophylaxis against osteoporosis in
menopausal women. . . . Finally, whereas a number of the relative risks
and associated trends in this investigation were statistically significant,
the number of observations on which they are based is relatively small.
Some findings could be due to chance and need to be considered in the
context of the results in other studies. In particular, the higher relative
risks associated with the use of the combination regimen were not
statistically different from the risks of estrogen use alone. Although this
27

result is somewhat worrisome, we currently interpret it as indicating a
lack of evidence that the concomitant use of progestin reduces the
excess risk of breast cancer associated with long-term estrogen use.
However, further research must also investigate the possibility that the
addition of progestins to estrogen therapy may increase the risk of breast
cancer.
(Response, Ex. 88, at 4-5.) In response to the study, Wyeth instructed its sales team
to “Take the time to read the study,” but “[u]nder no circumstances should you initiate
discussions concerning this study.” (Response, Ex. 90.) However, “[i]f questioned
about this issue, your response should be factual.” (Response, Ex. 90.)
In 1994, a Wyeth internal memorandum summarized a telephone conference
between Suzanne Joyner, and Dr. Trudy Bush, a Wyeth consultant. (Response, Ex.
87.) In that memo, Ms. Joyner memorialized Dr. Bush’s report that “data from
Katherine Fletcher at the National Cancer Institute, in a retrospective study conducted
in the 70’s [sic] [,] saw an increased risk of breast cancer in women on HRT any dose
[sic], as compared to ERT.” (Response, Ex. 87.) Dr. Bush also reported that “[t]his
data is not sufficient to rule out the use of estrogen/progestogen cyclic or combined
therapy.” (Response, Ex. 87.)
In 1995, Dr. Graham Colditz published an article entitled “The Use of
Estrogens and Progestins and The Risk of Breast Cancer in Postmenopausal Women”
in the New England Journal of Medicine. (Response, Ex. 94.) This article was a
follow-up on the previous Nurse’s Health Study that began in 1976 with

28

questionnaires sent to 121,700 female registered nurses, and continued with followups sent every two years. (Response, Ex. 94, at 2.) The analysis of the participants
of the Nurse’s Health Study was extended to 1992 to address unresolved issues
including “the risks associated with estrogen plus progestins.” (Response, Ex. 94,
at 2.) The article summary opened, “The effect of adding progestins to estrogen
therapy on the risk of breast cancer in post-menopausal women is controversial.”
(Response, Ex. 94, at 2.)
The study found a significant elevation in the risk of breast cancer among
participants using conjugated estrogens alone (adjusted relative risk, 1.32; 95%
confidence interval, 1.14 to 1.54), and estrogens plus progestin (adjusted relative risk,
1.41; 95% confidence interval, 1.15 to 1.74), as compared to those who had never
used such therapy. (Response, Ex. 94, at 3.) In 725,550 person-years of follow-up,
the study identified 1935 cases of invasive breast cancer among 69,586 postmenopausal women. (Response, Ex. 94, at 3.) 972 of those cases involved women
who had never used hormone therapy, accounting for 374,197 person-years of followup; and the remaining 963 cases involved women who were taking or had taken some
form of hormone therapy, accounting for 351,353 person-years of follow-up.
(Response, Ex. 94, at 3-4.) The study found that “[t]he increase in [breast cancer] risk
was most pronounced among women over the age of 55 and was largely limited to the
29

women who had used hormone therapy for five or more years.” (Response, Ex. 94,
at 4.) The study concluded:
Our data indicate that the addition of progestins to post-menopausal
estrogen therapy does not reduce the risk of breast cancer. Estrogen
alone, estrogen plus progestin, and progestins alone all appear to raise
the risk of breast cancer. The significant increase in the risks of breast
cancer and of death due to breast cancer among postmenopausal women
over 55 who are currently taking hormones and who have used this
therapy for five or more years suggests that the risks and benefits of
hormone therapy among older women should be carefully assessed.
(Response, Ex. 94, at 5.)
In 1996, Dr. Steven Cummings published an article entitled “Bone Mineral
Density Predicts the Risk of Breast Cancer in Older Women.” (Response, Ex. 101,
at 1.) In that article, Dr. Cummings explained that “[b]oth breast cancer and bone
mineral density (BMD) are related to exposure to estrogens.” (Response, Ex. 101,
at 1.) The study found that the “age-related relative risk of breast cancer increased
by 30 to 40% for each standard deviation increase in distal radius BMD: relative risk
1.40; 94% confidence interval, 1.16 to 1.68.” (Response, Ex. 101, at 1.) Dr.
Cummings also posited that “[o]ur findings suggest that the risk of breast cancer
associated with hormone replacement therapy may have been substantially
underestimated since osteoporosis is a primary indication for its use.” (Response, Ex.
101, at 1.)

30

In October 1997, the Collaborative Group on Hormonal Factors in Breast
Cancer published an article in The Lancet titled “Breast Cancer and Hormone
Replacement Therapy: Collaborative Reanalysis of Data from 51 Epidemiological
Studies of 52,705 Women with Breast Cancer and 108,411 Women Without Breast
Cancer.” (Response, Ex. 108, at 1 (the “Collaborative Group Study”).) The
Collaborative Group’s main finding was that the “risk of breast cancer is increased
in women using HRT and increases with increased duration of use, but that this
excess risk is reduced after use ceases and has largely, if not completely, disappeared
after about 5 years.” (Response, Ex. 108, at 8.) Among current users of HRT, the
Collaborative Group found a relative risk of breast cancer of 1.21. (Response, Ex.
108, at 6.) Among women who had ever used HRT, the Collaborative Group found
a relative risk of breast cancer of 1.14. (Response, Ex. 108, at 6.)
Most importantly for the purposes of this motion, the Collaborative Group also
expressed these numbers in terms of the actual incidence of breast cancer as a result
of continuous use of HRT by post-menopausal women. (Response, Ex. 108, at 11
(See Table 3 and Figure 9).) First, in North America and Europe in the mid-1980s,
the cumulative incidence of breast cancer between the ages of 50 and 70 for those
who had never used HRT was about 45 per 1000 women. (Response, Ex. 108, at 11.)
Measured against that baseline, the Collaborative Group found that “[u]se of HRT for
31

5 years is associated with an estimated cumulative excess of 2 (95% CI 1-3) breast
cancers for every 1000 users[;] use for 10 years with a cumulative excess of 6 (3-9)
for every 1000 users; [and] use for 15 years is associated with a cumulative excess of
12 (5-20) breast cancers for every 1000 users.” (Response, Ex. 108, at 11.)
For 55-year-old women, the age of Mrs. Scharff at the time of her Prempro
prescription, the cumulative incidence of breast cancer among those who had never
used HRT was 27 per 1000 women. (Response, Ex. 108, at 11 (Table 3).) For 55year-old women who had begun using HRT at 50 (5 years of use), the cumulative
incidence of breast cancer increased from 27 per 1000 women to 28 per 1000 women.
(Response, Ex. 108, at 11 (Table 3).) The Collaborative Group Study did note,
however, that the average date of breast cancer diagnosis for the women in the study
was 1985, when the type of HRT in predominant use was estrogen only, with only
12% of the women having mainly used an E+P combination.16 (Response, Ex. 108,
at 11.) Table 3 and Figure 9 from the Collaborative Group Study are reproduced
below:17

16

The lack of E+P data in this 1997 study is noted, but that disparity is irrelevant for
purposes of this opinion, which turns on Wyeth’s knowledge of the risk of breast cancer from
1997 to 1999 when Prempro was prescribed to Mrs. Scharff.
17

Collaborative Group on Hormonal Factors in Breast Cancer, Breast Cancer and
Hormone Replacement Therapy: Collaborative Reanalysis of Data from 51 Epidemiological
Studies of 52,705 Women with Breast Cancer and 108,411 Women Without Breast Cancer, 350
The Lancet 1047, 1057 (1997).
32

33

In June 1998, Dr. Graham Colditz published “Relationship Between Estrogen
Levels, Use of Hormone Replacement Therapy, and Breast Cancer” in The Journal
of the National Cancer Institute. (Response, Ex. 115.) In the article, Dr. Colditz
posed the clinical question, “Does long term use of hormone replacement increase
risk of breast cancer and, if so, how soon after use has begun does risk increase?”
(Response, Ex. 115, at 1.) Throughout the article, Dr. Colditz relied heavily on the
data and conclusions of the Collaborative Group Study and his 1995 Nurse’s Health
Study, while also briefly mentioning the Bergkvist Study. (Response, Ex. 115,
at 1-6.) He concluded that “existing evidence supports a causal relationship between
use of estrogens and progestins, levels of endogenous estrogens, and breast cancer
incidence in post-menopausal women. Hormones may act to promote the late stages
of carcinogenesis among postmenopausal women to facilitate the proliferation of
malignant cells.” (Response, Ex. 115, at 1.)
However, Dr. Colditz also noted that the decision whether to prescribe E+P in
light of the risk of breast cancer was not a simple one, because of the then-understood
net mortality-reducing benefits of E+P. (Response, Ex. 115, at 7.) He posed the
dilemma in balancing the risk of breast cancer with the then-understood benefits of
E+P:

34

Women who used postmenopausal hormones for 10 or more years had
a 20% reduction in mortality that was statistically significant. This
benefit of hormones was most pronounced among women who were at
higher risk for cardiovascular disease. However, to achieve a reduction
in mortality, some women within the population will pay the price of a
breast cancer that they would not otherwise have developed. That is to
say, some individuals experience a disadvantage as a result of an attempt
to improve the overall health of the population. Thus, the action that
will benefit public health and the individual’s best choice may differ.
Further work is needed to improve our understanding and
communication of these considerations.
(Response, Ex. 115, at 7.)
In 2002, the Women’s Health Initiative changed the menopause market, caused
the FDA to require Wyeth to make substantial changes to the breast cancer warnings
on the Prempro label, and changed the E+P product actually marketed by Wyeth.
(Response 17-18.) Because Mr. Scharff relies on the WHI studies to show the
inadequacies of the pre-WHI Prempro label as it relates to the breast cancer risk, the
statistical results of this study are pertinent to the factual issue of likely or probable
injury.18
The primary conclusion of the WHI study was that the “[o]verall health risks
exceeded benefits from use of combined estrogen plus progestin for an average 5.2
year follow-up among healthy postmenopausal US women.” (Response, Ex. 16, at 1.)

18

See Part I.A.2 for discussion of the WHI study’s effect on Dr. Reiland’s understanding
of the risk of breast cancer associated with E+P.
35

The WHI researchers also concluded that the “risk-benefit profile found in this trial
is not consistent with the requirements for a viable intervention for primary
prevention of chronic diseases, and the results indicate that this regimen should not
be initiated or continued for primary prevention of [coronary heart disease].”
(Response, Ex. 16, at 1.) The study found that women who had consumed E+P had
a relative risk of developing breast cancer of 1.26 (95% confidence interval, 1.001.59).19 (Response, Ex. 16, at 7.) Among the study participants, there were 166
invasive breast cancers among the 8506 women taking E+P (1.95% overall breast
cancer rate), and 124 invasive breast cancers among the 8102 women taking the
placebo (1.53% overall breast cancer rate). (Response, Ex. 16, at 7 (Table 2).) In
terms of annualized percentages, .30% of the placebo group developed breast cancer
per year compared to .38% of E+P group.20 (Response, Ex. 16, at 7 (Table 2).)

19

Wyeth notes that the 2003 Chlebowski article Influence of Estrogen Plus Progestin on
Breast Cancer and Mammography in Healthy Postmenopausal Women: The Women’s Health
Initiative Randomized Trial adjusted the WHI based relative risk of breast cancer down to 1.24.
(Reply 26 & Ex. 11.) Likewise, in that breast cancer specific follow-up on the WHI study, there
were 199 invasive breast cancers among 8506 women taking E+P (2.33% breast cancer rate), and
150 invasive breast cancers among 8102 women taking placebo (1.85% breast cancer rate).
Though the differences between the studies are small, the court relies on the study cited by Mr.
Scharff.
20

Dr. Colditz testified that the relative risk difference of 1.24 in the 2003 Chlebowski
article “in this particular population translates to a risk difference of . . . 8/100ths of one percent.”
(Reply, Ex. 27 at 392-93.) That statistical explanation applies equally to the annualized
percentages presented in the 2003 Cheblowski article (Reply, Ex. 11, at 3249 (Table 3)) and the
2002 JAMA article (Response, Ex. 16, at 7 (Table 2)).
36

Finally, Mr. Scharff’s evidence also includes an unattributed spreadsheet that
purports to show that 32 of the 43 pre-WHI studies concerning E+P found “Increased
Breast Cancer Risk” versus “NO Breast Cancer Risk.” (Response 41 & Ex. 91.) In
Torkie-Tork v. Wyeth, a breast cancer hormone therapy case, District Judge T.S. Ellis,
III confronted the same argument, reviewed the statistical data cited in each of the
cases in light of statistical principles, construed that review in the light most favorable
to the plaintiff, and found that 23 of the 43 pre-WHI breast cancer studies did not in
fact show a statistically significant association between breast cancer and the use of
estrogen replacement theory.21 739 F. Supp. 2d 895, 902-904 (E.D. Va. 2010)
(discussing statistical principles and citing Federal Judicial Center, Reference Manual
on Scientific Evidence 360 (2d ed. 2000)). The court finds that review persuasive.

21

Notably, it appears that the plaintiff’s counsel in Torkie-Tork included all of the 43 preWHI studies in a consolidated exhibit to permit the district court to review all of the evidence.
Torkie-Tork, 739 F. Supp. 2d at 903 (all the cited studies, save one, were consolidated in Exhibits
71H-LL). In this case, Mr. Scharff’s Exhibit 91 consists only of an excel spreadsheet listing the
“Author/Publication,” the “Date,” and a binary categorization of each article as “Increased Breast
Cancer Risk” or “NO Breast Cancer Risk.” (Response, Ex. 91.) No other data is provided, nor
are the pertinent parts of the articles attached. The court is without evidence to verify or adopt
Plaintiff’s unattributed factual position. See Federal Judicial Center, Reference Manual on
Scientific Evidence 55 (2d ed. 2000) (“[A] declaration containing a mere conclusory statement of
opinion by an expert unsupported by facts does not suffice to raise a triable issue.”).
37

3.

Wyeth’s Distortion of the Risk/Benefit Ratio

Finally, Mr. Scharff produced evidence regarding Wyeth’s alleged distortion
of doctors’ risk/benefit analysis through its marketing representatives, ghost-written
medical articles, Dear Doctor letters, promotional materials, and conferences.
(Response 49-56.) The evidence has been reviewed, but as will be seen below, it is
not probative of Wyeth’s knowledge of the likely or probable risk of breast cancer
caused by E+P therapy. It is, therefore, not relevant to Mr. Scharff’s wanton failure
to warn claim. Nor has Mr. Scharff produced evidence that Dr. Reiland relied on any
of this “distorted” evidence when he prescribed Prempro to Mrs. Scharff in 1997.
II. DISCUSSION
The Discussion proceeds in two parts. In Part A, the analysis begins with the
lack of genuine issues of material fact supporting Mr. Scharff’s wanton failure to
warn claim. In Part B, the court briefly dispenses with Mr. Scharff’s wanton design
claim.
A.

Mr. Scharff’s Wanton Failure to Warn Claim
In Alabama, the term “wantonness” is statutorily defined, for purposes of

punitive damages, as “[c]onduct which is carried on with a reckless or conscious
disregard of the rights or safety of others.” Ala. Code § 6-11-20(b)(3). The contours
of a cause of action arising out of wanton conduct, however, are delineated by
38

common law.

The Alabama Supreme Court defined the cause of action for

wantonness as:
the conscious doing of some act or the omission of some duty, while
knowing of the existing conditions and being conscious that, from doing
or omitting to do an act, injury will likely or probably result. To prove
wantonness, it is not essential to prove that the defendant entertained a
specific design or intent to injure the plaintiff.
Ex parte Capstone, 2011 WL 2164027, at *6 (citing Ala. Mut. Ins. Co. v. Roush, 723
So. 2d 1250, 1256 (Ala. 1998) (internal citations omitted)). “The ‘knowledge’ [of
risk of injury] of the defendant is ‘the sine qua non of wantonness.’” Blakley v.
Johnson, No. 2090507, 2010 WL 4262303, at *7 (Ala. Civ. App. Oct. 29, 2010)
(bracketed comments in Blakley) (quoting Norris v. City of Montgomery, 821 So. 2d
149, 156 n.9 (Ala. 2001)). The defendant’s knowledge “may be proved by showing
circumstances from which the fact of knowledge is a reasonable inference; it need not
be proved by direct evidence.” Hamme v. CSX Transp., Inc., 621 So. 2d 281, 283
(Ala. 1993).
The degree to which the defendant either knew about, should have known
about, or was conscious of the risk is central to a wantonness claim. “Wantonness is
not merely a higher degree of culpability than negligence.” Ex parte Capstone, 2011
WL 2164027, at *6 (internal quotation marks and citation omitted). “[N]egligence
and wantonness are qualitatively different tort concepts.” Id.; Ferguson v. Baptist
Health Sys., Inc., 910 So. 2d 85, 92 (Ala. 2005). Wantonness involves an “act done
39

or omitted with knowledge of the probable consequence and with reckless disregard
of such consequence.” Ex parte Capstone, 2011 WL 2164027, at *6 (emphasis
changed). On the other hand, negligence consists of “intentionally doing an act with
knowledge that it contains a risk of harm to others,” but for an actor “to be reckless
[he] must recognize that his conduct involves a risk substantially greater in amount
than that which is necessary to make his conduct negligent.” Restatement (Second)
of Torts § 500 (comment g) (cited in Ex parte Capstone, 2011 WL 2164027, at *7
n.3). “The difference between reckless misconduct and conduct involving only such
a quantum of risk as is necessary to make it negligent is a difference in the degree of
the risk, but this difference of degree is so marked as to amount substantially to a
difference in kind.” Restatement (Second) of Torts § 500 (comment g) (quoted in Ex
parte Capstone, 2011 WL 2164027, at *7 n.3).22
While it may be difficult to define the exact point at which the
probability of harm is sufficient to support a jury’s finding of
22

The difference in the degree of risk necessary for wantonness was also emphasized by
the concurring justices in Ex parte Capstone. 2011 WL 2164027, at *14 (“‘It is enough [for
wantonness] that [the defendant] realizes or, from the facts which he knows, should realize that
there is a strong probability that harm may result, even though he hopes or even expects that his
conduct will prove harmless.’”) (Murdock, J., concurring specially) (quoting Restatement
(Second) of Torts § 500 (1965) (comment f)); id. (“[R]eckless misconduct results when a person,
with no intent to cause harm, intentionally performs an act so unreasonable and dangerous that he
or she knows or should know it is highly probable that harm will result.”) (Murdock, J.,
concurring specially) (quoting 57A Am. Jur. 2d Negligence § 276 (2004)) (emphasis added); id.
at *15 (“[T]he defendant who acts in the belief or consciousness that the act is causing
appreciable risk of harm to another may be negligent, and if the risk is great the conduct may be
characterized as reckless or wanton . . . .”) (Murdock, J., concurring specially) (quoting W. Page
Keeton et al., Prosser & Keeton on the Law of Torts § 8, p. 36 (4th ed. 1984)) (emphasis
changed); see also id. at *16 (Main, J., concurring specially).
40

wantonness, courts and juries must attempt to discern that line in light
of the fact that wantonness is distinct from negligence, and punitive
damages are meant “to punish [the defendant] for his outrageous
conduct and to deter him and others like him from similar conduct in the
future.”
Salter v. Westra, 904 F.2d 1517, 1527 (11th Cir. 1990) (quoting Restatement
(Second) of Torts § 908(1) (1979)); see also Richards v. Michelin Tire Corp., 21 F.3d
1048, 1057-58 (11th Cir. 1994).
The analysis proceeds in three sections. Part II.A.1 begins with whether Mr.
Scharff has produced evidence that breast cancer was a likely or probable injury for
women taking E+P. Part II.A.2 turns to whether Mr. Scharff has produced evidence
that Wyeth knew, should have known, or was recklessly indifferent to the likely or
probable risk of breast cancer associated with E+P. Part II.A.3 concludes with
analysis of whether Mr. Scharff has created a genuine issue of material fact that the
Prempro breast cancer warning provided to Dr. Reiland was wantonly inadequate.
1.

No Genuine Issue of Material Fact that Breast Cancer Was a Likely
or Probable Injury from Prempro Consumption

Mr. Scharff argues that Wyeth had knowledge that “E+P users were developing
breast cancer” and “Wyeth learned of studies conducted by independent researchers
in [the years prior to the 2002 WHI study] that showed a real breast cancer risk with

41

E+P.” (Response 23, 38.) He also argues that Alabama case law supports imposition
of punitive damages to punish a defendant for wanton conduct based on the common
element of “the defendant’s knowledge of the potential injury or harm that could
result from the defendant’s acts or failure to act.” (Response 20.)23 Wyeth replies
that it could not have been conscious that the risk of developing breast cancer was
likely or probable, because the risk of breast cancer associated with E+P, as identified
in the WHI study, is too small to say that breast cancer is likely.
In Toole v. McClintock, 999 F.2d 1430 (11th Cir. 1993) (“Toole I”), the
Eleventh Circuit explained that under Alabama law, “[w]antonness means knowledge
that an act or failure to act does not merely increase risk of injury, but that the act
makes injury ‘likely’ or ‘probable.’” Id. at 1435 (emphasis added). In that case, the
plaintiff received breast implants from a surgeon. Scar tissue later accumulated and
contracted around her implants, and she returned to that surgeon seeking treatment.
Id. at 1431. The surgeon treated the hardness by performing a “closed capsulotomy,”
a procedure in which the surgeon compresses the affected breast to rupture the scar
tissue. Id. When the plaintiff’s surgeon performed the closed capsulotomy, the

23

This argument is unpersuasive because it ignores that a wantonness claim requires a
demonstration of a likely or probable risk of injury. The cases cited by Mr. Scharff do not
eliminate this requirement. (Response 20-21.)

42

procedure ruptured her breast implants, causing her serious injuries. Id. She sued the
manufacturer of the implants and others, claiming that they had negligently and
wantonly failed to adequately warn her of the risk associated with the implants. Id.
at 1432, 1435.
The case was tried to a jury, and the jury returned punitive damages against the
manufacturer on the wanton failure to warn claim. Id. at 1432, 1435. The district
court upheld the award of punitive damages, finding that the evidence showed “‘the
company had knowledge that the implants were likely to rupture when closed
capsulotomies were performed.’” Id. at 1435 (quoting the district court record). The
Eleventh Circuit vacated the punitive damages award, in part because the evidence
“showed that the actual incidence of implant ruptures from closed capsulotomies is
probably slightly less than one percent.” Id. (emphasis added). The court explained
that, although implant rupture can be serious when it occurs, “rupture is no ‘likely’

43

event, even for patients undergoing closed capsulotomies.” Id. (emphasis added).24
In relying on the one percent figure, the Eleventh Circuit also noted that the pertinent
statistic for the wantonness risk analysis is the likelihood of the actual injury suffered
by the plaintiff, not the overall rate of complications associated with the defendant’s
product. Id. at 1435 n.13.
Mr. Scharff claims that Toole I is factually distinguishable from this case, but
otherwise does not directly address the wantonness requirement that the risk of injury
is likely or probable, nor does he address Toole I’s reasoning on that point.
(Response 22-23.) Wyeth argues that “the risk [of breast cancer] is too small to say

24

Toole I stands in contrast to the reasoning of Scroggin v. Wyeth, 586 F.3d 547 (8th Cir.
2009), where the Eighth Circuit allowed the issue of punitive damages to go to the jury on the
plaintiff’s malicious failure to warn claim. (See Response 9-10.) Scroggin was decided under
Arkansas law, which allows punitive damages when the 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.’” Scroggin, 586 F.3d at 571 (quoting Ark. Code. Ann. § 1655-206) (emphasis added). Reviewing the evidence in that case, which is similar to the evidence
in this case, the court concluded that “there was sufficient evidence upon which a jury could
conclude that Wyeth acted with reckless disregard to the risk of injury.” Scroggin, 586 F.3d
at 573 (emphasis added). Notably, the Eighth Circuit’s analysis of the relevant evidence and
Arkansas law ignored the probability of injury and defendant’s knowledge of probable risk
requirements in the plain language of the Arkansas statute. See Scroggin, 586 F.3d at 571-573
(no discussion of probability of injury or actual incidence of breast cancer in determining that the
plaintiff’s evidence was sufficient to support a jury question on punitive damages).
Toole I relied on and analyzed the totality of Alabama’s definition of wantonness,
including the “probable” or “likely” risk of injury requirement, and importantly is binding
precedent, unlike Scroggin. Accordingly, the court relies on Toole I.

44

that breast cancer was (or is) a likely event[,]” and therefore he “cannot meet Toole
I’s ‘likely’ requirement.” (Reply 27.) Wyeth has the better argument.
Mr. Scharff’s evidence is insufficient to create a genuine issue of material fact
that breast cancer is a likely or probable event for those consuming Prempro. Though
the WHI study reported that E+P consumption increased the relative risk of invasive
breast cancer by 26% over the background risk exhibited by the control group, that
increased risk resulted in an actual incidence of breast cancer of 1.95% for E+P
consumers during the life of the study.25 Viewing the evidence in the light most
favorable to Mr. Scharff by assuming that E+P consumption actually caused every
additional breast cancer in the E+P group beyond the background incidence of breast
cancer,26 the court finds that the actual incidence of invasive breast cancer attributable

25

See supra note 12 for the definition of “relative risk.”

26

Viewing the evidence in the light most favorable to the plaintiff, the court assumes that
E+P caused every additional invasive breast cancer beyond the background risk rate reported in
all of the studies discussed in this opinion. See, e.g., Federal Judicial Center, Reference Manual
on Scientific Evidence 384 (2d ed. 2000) (“The threshold for concluding that an agent was more
likely than not the cause of an individual’s disease is a relative risk greater than 2.0. . . . When
the relative risk reaches 2.0, the agent is responsible for an equal number of cases of disease as
all other background causes. Thus, a relative risk of 2.0 (with certain qualifications noted below)
implies a 50% likelihood that an exposed individual’s disease was caused by the agent.”).
However, that causal assumption should not be mistaken for a ruling on the parties’ general and
specific causation arguments, which need not be reached in this opinion.

45

to E+P was .42%.27 Breast cancer was no likely or probable event for those women
who consumed E+P in the WHI study. Even if the court were to attribute all of the
invasive breast cancers in the E+P group to E+P consumption, thereby ignoring the
inherent risk of breast cancer faced by all post-menopausal women (as represented
by the 1.53% breast cancer rate in the placebo group), the actual incidence of breast
cancer in the E+P group was 1.95%. And, even construing the evidence through that
heavily jaundiced lens, far beyond the light most favorable to the plaintiff
requirement, the actual incidence of breast cancer remains too small as a matter of law
for a reasonable jury to find that breast cancer was a likely or probable event for
women undergoing E+P treatment.

27

(.153 background breast cancer rate * 8506 women taking E+P) = 130.18 background
invasive breast cancers. (166 E+P breast cancers - 130 background cancers) = 36 additional
invasive breast cancers out of 8506 women. (36 additional breast cancers / 8506 women taking
E+P) = .42% actual incidence of additional invasive breast cancers experienced by the E+P
group. Or more simply: (1.95% E+P group breast cancer rate - 1.53% placebo breast cancer
rate) = .42% actual incidence of additional invasive breast cancers experienced by the E+P group
during the life of the WHI study.
Applying the results of the WHI study to women who had taken Prempro for the eightyear life of the drug at the time the study was published yields a similarly small actual incidence
of breast cancer. For women consuming E+P for 8 years, the actual incidence of invasive breast
cancers would be 3.04%. ((8 years * .38% annual incidence of invasive breast cancer) = 3.04%)
For women consuming the placebo, the actual incidence of invasive breast cancer would be
2.4%. ((8 years * .30% annual incidence of invasive breast cancer) = 2.4%) Thus, the actual
incidence of additional invasive breast cancers faced by the E+P group after eight years would be
.64%. (See Response, Ex. 16, at 7 (Table 2); cf. Response, Ex. 16, at 10 (Table 4) (relative risk
of invasive breast cancer for “Year 6 and Later” E+P group was actually 1.12, less than the 1.26
figure the annualized breast cancer incidence percentages were based on).)

46

If the court were examining this evidence under negligence and negligence’s
far less rigorous standard of foreseeability, a jury question would have resulted. See
Part II.A. However, Mr. Scharff’s negligence claims are time-barred, as found in the
court’s prior Order, and, thus, the negligence standard is inapplicable. Given Mr.
Scharff’s evidence, and applying the plain meaning of “likely,” “probable,” “risk
substantially greater in amount than that which is necessary [for negligence],” “strong
probability,” “highly probable,” and “the risk is great,” there is no genuine issue of
material fact tending to show that breast cancer was a likely or probable result of
Prempro consumption.28
2.

No Genuine Issue of Material Fact that Wyeth Knew Breast Cancer
Was a Likely or Probable Injury from Prempro Consumption

In Part I.A, the analysis turned on whether Mr. Scharff had produced evidence
sufficient to show a genuine issue of material fact on the key question of whether the
risk of breast cancer is likely or probable from E+P consumption. In that analysis, the
court purposefully ignored the sine qua non of wantonness, Wyeth’s knowledge, and

28

“‘[L]ikely’ is defined as ‘[l]ogically or expectedly about to occur; imminent.’”
Henderson v. Ala. Power Co., 627 So. 2d 878, 903 (Ala. 1993) (abrogated on other grounds by
Ex parte Apicella, 809 So. 2d 865, 874 (Ala. 2001) (Houston, J., dissenting) (quoting The
American Heritage Dictionary of the English Language, 757 (1969)). “‘[P]robably’ is defined as
‘[m]ost likely; in all probability; presumably.’” Id. (quoting The American Heritage Dictionary
of the English Language, 1043 (1969)); see also Part II.A & n.22.

47

instead looked purely at the risk of injury based on Mr. Scharff’s evidence from the
landmark WHI study. The lack of evidence that breast cancer is a likely or probable
injury from Prempro consumption is sufficient alone to dispose of Mr. Scharff’s
wantonness claims. In the interest of completeness, however, the court (assuming
arguendo that Mr. Scharff established the risk of injury) now examines whether Mr.
Scharff has produced a genuine issue of material fact that Wyeth either knew or was
recklessly indifferent to the risk that breast cancer would likely or probably result
from its failure to adequately warn of the risk of breast cancer associated with
Prempro.
The knowledge inquiry turns on what Wyeth knew, or should have known,
about the risk of breast cancer associated with Prempro before January 1999, when
Mrs. Scharff was diagnosed with breast cancer. Mr. Scharff argues that Wyeth knew
of inaccuracies in the Prempro label and of the risk of breast cancer associated with
Prempro during this period because it “learned of studies conducted by independent
researchers in those years [prior to the WHI study] that showed a real breast cancer
risk with E+P.” (Response 38 (emphasis added).) Mr. Scharff’s evidence shows that
Wyeth either knew about or should have known about all of the studies cited in the
Response. The court has carefully reviewed the pre-1999 ERT and HRT breast

48

cancer studies provided by Mr. Scharff. Review of these studies shows that no
reasonable jury could find that, as of January 1999, Wyeth knew or should have
known that breast cancer was a likely or probable result of its failure to adequately
warn of the risk of breast cancer.
To begin, the 1989 Bergkvist Study is insufficient to establish a genuine issue
of material fact on Wyeth’s knowledge of a likely or probable injury for three reasons.
First, its finding of a relative risk of breast cancer of 4.4 for women who consumed
E+P for over six years was not statistically significant. The 95% confidence interval
for that relative risk calculation was .9 to 22.4, and it thus included a relative risk of
1.0. Federal Judicial Center, Reference Manual on Scientific Evidence 389 (2d ed.
2000) (“Where the confidence interval contains a relative risk of 1.0, the results of the
study are not statistically significant.”). Second, it also reported a negative relative
risk of breast cancer for E+P consumption for less than six years, though those
findings were also not statistically significant. Though the Bergkvist study was
important and called for further research into the “possibility that the addition of
progestins to estrogen therapy may increase the risk of breast cancer,” its results
concerning the breast cancer risk for E+P consumption were statistically inconclusive
and contradictory on the overall temporal relative risk of breast cancer. The

49

Bergkvist study is insufficient to create a genuine issue of material fact that Wyeth
knew or should have known that breast cancer was a likely or probable result of
Prempro consumption.
Next, the 1995 Nurse’s Health Study includes no data tending to show that
breast cancer was a likely or probable result from E+P consumption. Though the
study did conclude that E+P “appear[s] to raise the risk of breast cancer,” the increase
observed in that study did not result in an actual incidence of breast cancer
approaching a likely or probable result. The study found an annualized incidence of
breast cancer of .25% for women who had never taken hormone replacement therapy,
.27% for women who were taking or had taken hormone replacement therapy, and
.31% for the subset of women currently taking hormone replacement therapy.29 Again
assuming causation for the additional breast cancers in the group that was currently
taking E+P, the study found a .06% increase in the actual incidence of breast cancers
per year. In a group of 10,000 women consuming E+P, that would mean an actual
incidence of 6 additional breast cancers per year over the background annual
29

Annualized actual incidence of breast cancer for non-HRT takers: (972 cases/374,197
years of follow-up) = .25%.
Annualized actual incidence of breast cancer for current or former HRT takers: (963
cases/351,353 years of follow-up) = .27%.
Annualized actual incidence of breast cancer for current HRT takers: (513 cases/163,204
years of follow-up) = .31%. (See Response, Ex. 94, at 3-4 (Table 2).)

50

incidence of breast cancer (25) faced by all post-menopausal women. Though that
breast cancer risk may be real, no reasonable jury could find that such an injury was
likely or probable, or that it put Wyeth on notice that such a result was likely or
probable.
Another study, the 1997 Collaborative Group Study, also shows that the actual
incidence of breast cancer for E+P consumers was not a likely or probable event.
The Collaborative Group Study found that “[u]se of HRT for 5 years is associated
with an estimated cumulative excess of 2 (95% CI 1-3) breast cancers for every 1000
users[;] use for 10 years with a cumulative excess of 6 (3-9) for every 1000 users;
[and] use for 15 years is associated with a cumulative excess of 12 (5-20) breast
cancers for every 1000 users.” (Response, Ex. 108, at 11.) Further, “[u]se of HRT
for about 4 years would therefore result in one extra breast cancer being diagnosed
in every 1000 users, and use for about 13 years would result in one extra cancer being
diagnosed in every 100 users.” (Response, Ex. 108, at 11.) Looking at the extreme
case, a woman consuming hormone replacement therapy for 15 years, the actual
incidence of breast cancers associated with that fifteen-year E+P consumption was
12/1000 = 1.2%. Again, the data from the Collaborative Group Study is insufficient
as a matter of law to put Wyeth on notice that breast cancer was a likely or probable

51

result from E+P consumption. (See also Response, Ex. 108, (Figure 9) (illustrating
the marginal increase in the actual incidence of breast cancer associated with E+P
consumption).)
Finally, the data in the 1998 Colditz study are likewise insufficient to create a
genuine issue of material fact on Wyeth’s knowledge. Though the study found that
“existing evidence supports a causal relationship between use of estrogens and
progestins, levels of endogenous estrogens and breast cancer incidence in postmenopausal women[,]” it did not produce data sufficient for a reasonable juror to find
that breast cancer was a likely or probable result of Prempro consumption.
(Response, Ex. 115, at 1.) Rather, the study found a relative risk of breast cancer of
1.35 for E+P consumption for five years or longer, which as explained above is
insufficient, given the background risk and actual incidence of breast cancer in the
general post-menopausal population, to create a factual dispute on likely or probable
injury or Wyeth’s knowledge of such. (Response, Ex. 115, at 4 (quoting the actual
incidence data from the Collaborative Group Study (see Response, Ex. 108, at 11)).)
Notably, Mr. Scharff did not argue that these studies show that Wyeth should
have known that the risk of breast cancer was likely or probable. Rather, he argued
that “Wyeth learned of studies conducted by independent researchers in those years

52

that showed a real breast cancer risk with E+P.” (Response 38.) The difference
between a real, or “appreciable,” risk of injury and a likely or probable risk of injury
is one of the key differences between a negligence claim and a wantonness claim. See
Part II.A (discussing that difference in Alabama law). Again, if the court were
deciding summary judgment on the issue of Wyeth’s knowledge of the risk of breast
cancer under a negligence standard, the issue would be one for the jury. However,
viewing these studies collectively and attributing complete knowledge of their results
to Wyeth simply does not establish that Wyeth knew or should have known during
the times relevant to this cause of action that breast cancer was a likely or probable
event from its failure to adequately warn about the risks of breast cancer associated
with Prempro.30

30

Just as viewing these studies collectively does not create a genuine issue of material
fact on Wyeth’s knowledge of sufficient risk of breast cancer, viewing them in light of the
universe of research on the risk of breast cancer available prior to the WHI study only heightens
the lack of factual support for Mr. Scharff’s wantonness claims. See Torkie-Tork, 739 F. Supp.
2d at 904 (Viewed in the light most favorable to the plaintiff, “23 of 43 pre-WHI studies did not
show a statistically significant association between breast cancer in women who have ever used
estrogen replacement therapy.”).
Further, the court also notes that the aforementioned lack of genuine issues of material
fact critical to Mr. Scharff’s common law wantonness claims would apply equally to the
“wantonness under AEMLD” claims the court previously found untimely. (Order 46-48.)

53

3.

No Genuine Issue of Material Fact that the Prempro Breast Cancer Warning
Was Inadequate
Mr. Scharff argues that he has produced evidence that Wyeth’s breast cancer

warnings were “watered down” and inaccurate and, thus, inadequate under Alabama
law. (Response 23-25 (citing Globetti v. Sandoz Pharm. Corp., No. CV-98-TMP2649-S, 2001 U.S. Dist. Lexis 2093, at *34 (N.D. Ala. Feb. 2, 2001) (Putnam, M.J.));
see also Response 38-49.) Wyeth replies that there is no genuine issue of material
fact on the adequacy of the Prempro breast cancer warning because: (1) it warned
about breast cancer, the main harm suffered by Mrs. Scharff; and (2) it complied with
FDA requirements for warning about the risk of breast cancer associated with
Prempro.31 (Reply 19-25.)
Under Alabama law, a wanton failure to warn claim focuses on whether the
defendant “consciously and intentionally failed to give reasonable and adequate
warnings with knowledge of, or reckless indifference to, the fact that the lack of
warnings made [the plaintiff’s] injury likely or probable.” Richards, 21 F.3d at 1058.
31

Wyeth’s argument that its compliance with FDA requirements bars a jury question on a
wanton failure to warn claim lacks merit. See Richards, 21 F.3d at 1059 (The defendant’s
“compliance with both federal regulations and industry practices is some evidence of due care.”)
(emphasis added); Cessna Aircraft Co. v. Trzcinski, 682 So. 2d 17, 22 (Ala. 1996) (finding that
all of the wantonness evidence, including that Cessna’s testing and inspection procedures which
were approved by the FAA, was insufficient to support a jury verdict for punitive damages under
the clear and convincing evidence standard).

54

“‘[T]he existence of a duty to warn and the adequacy of a warning are questions of
fact for the jury.’”32 Toole I, 999 F.2d at 1433 (quoting State Farm Fire & Casualty
Co. v. J.B. Plastics, 505 So. 2d 1223, 1227 (Ala. 1987)); see also Deere & Co. v.
Grose, 586 So. 2d 196, 198 (Ala. 1991); Globetti, 2001 U.S. Dist. Lexis 2093, at *34.
A jury may find a warning inadequate on a negligent failure to warn theory when the
warning “understate[s] the risk” of injury suffered by the plaintiff. Toole I, 999 F.2d
at 1433; Globetti, 2001 U.S. Dist. Lexis 2093, at *38. Moreover, “[u]nder the
‘learned intermediary doctrine,’ the adequacy of [Wyeth’s] warning is measured by
its effect on the physician, [Dr. Reiland], to whom [Wyeth] owed a duty to warn, and
not by its effect on [Mrs. Scharff].” Toole I, 999 F.2d at 1433 (quoting Stone v.
Smith, Kline & French Lab., 447 So. 2d 1301, 1304-05 (Ala. 1984)).
However, “the issue of punitive damages [on a wanton failure to warn theory]
should not go to the jury when a manufacturer took steps to warn plaintiff of the
potential danger that injured him; those facts bar a finding that defendant was
consciously indifferent.” Toole I, 999 F.2d at 1436; Richards, 21 F.3d at 1059; but
see Globetti, 2001 U.S. Dist. Lexis 2093 at *36-39 (relying on Toole I’s negligent
failure to warn reasoning, but not discussing Toole I’s holding that the issue of

32

The parties do not dispute that Wyeth had a duty to warn about the risk of breast cancer
associated with the use of Preempro.

55

punitive damages on a wanton failure to warn claim cannot go to the jury where the
defendant took steps to warn the plaintiff of the main harm she suffered and the way
she came to suffer that harm).
Toole I prevents Mr. Scharff’s wanton failure to warn claim from surviving
summary judgment. It is undisputed that Wyeth warned Dr. Reiland that “[t]he effect
of added progestins [to estrogen replacement therapy] on the risk of breast cancer is
unknown, although a moderately increased risk [of breast cancer] in those taking
combination estrogen/progestin therapy has been reported.” (1998 PDR at 3121-22.)
Further, Wyeth also warned,
The effects of added progestin [to estrogen replacement therapy] 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 self-examination are recommended
for all women.
(1998 PDR at 3124 (emphasis added).) Wyeth’s Prempro label referenced the relative
risk associated with estrogens alone, 1.3 to 2.0, which is a relative risk that actually
exceeded that found for E+P in the WHI study (1.26). Wyeth warned Dr. Reiland that
the risks of breast cancer associated with E+P consumption were unknown, but that
some studies had reported a moderately increased risk, even greater than the relative
risk associated with estrogens alone (1.3 to 2.0). The Prempro warning described the

56

main harm that Mrs. Scharff suffered, breast cancer; warned Dr. Reiland that there
was a potential for a relative risk of breast cancer greater than 1.3 to 2.0; and forecast
how she came to suffer that harm, consumption of combination estrogen/progestin
therapy. Under Toole I, it may be that “[m]ore could have been done or said” by
Wyeth, but on these facts, “[Wyeth] did not exhibit indifference toward safety.”33 999
F.2d at 1436. Accordingly, Wyeth did not act wantonly as a matter of law, and, thus,
summary judgment in Wyeth’s favor is appropriate.34
In sum, and for the foregoing reasons in Part II.A, summary judgment is due
to be granted in favor of Wyeth on Mr. Scharff’s wanton failure to warn claim.
B.

Wanton Design Claim
Wyeth argues that Mr. Scharff “has not provided any reasons why the Court

should not grant summary judgment as to the [wanton defective design claim].”
(Reply 43.) Wyeth is correct. Mr. Scharff has not argued that summary judgment is
due to be denied on this claim, nor has he produced any evidence sufficient to create
a genuine issue of material fact. Notably, Mr. Scharff did not produce evidence that
33

The reasoning for granting summary judgment for Wyeth on Mr. Scharff’s common
law wanton failure to warn claim would apply equally to his “wantonness under AEMLD” claim
(failure to warn theory), which the court previously found untimely. (Order 46-48.)
34

Again, if this were a negligent failure to warn claim, the evidence likely would present
a question for the jury; however, Mr. Scharff’s negligence claims are time-barred, as found by the
court in its prior Order.

57

Wyeth “consciously and intentionally refused to employ available technology (some
safer, practical, alternative design) in reckless disregard of the fact that its failure to
do so made the risk of [breast cancer] probable or likely.” Richards, 21 F.3d at 1058.
Accordingly, summary judgment is due to be granted on the wanton defective
design claim, and the court need not address Wyeth’s argument that Mr. Scharff
cannot maintain a common law wanton defective design claim involving a
prescription drug. (Reply 43-44.)
III. CONCLUSION
Based on the foregoing, and pursuant to Rule 56(f) of the Federal Rules of
Civil Procedure, it is ORDERED that summary judgment is GRANTED for
Defendants on Plaintiff’s remaining wantonness claims. A separate judgment will be
issued.
DONE this 19th day of September, 2011.
/s/ W. Keith Watkins
CHIEF UNITED STATES DISTRICT JUDGE

58