Burst v. Shell Oil Company et al
Filing
141
ORDER AND REASONS granting Defendants' Motion 90 to Exclude Dr. Infante's general causation opinion. Signed by Chief Judge Sarah S. Vance on 6/16/15. (jjs)
UNITED STATES DISTRICT COURT
EASTERN DISTRICT OF LOUISIANA
YOLANDE BURST, individually
and as the legal
representative of BERNARD
ERNEST BURST, JR.
CIVIL ACTION
VERSUS
NO: 14-109
SHELL OIL COMPANY, ET AL.
SECTION: R
ORDER AND REASONS
Defendants Shell Oil Company, Chevron U.S.A. Inc., and Texaco,
Inc.
move
to
exclude
the
testimony
epidemiologist, Dr. Peter Infante.1
of
plaintiff's
expert
The Court has reviewed the
parties' submissions and has conducted a Daubert hearing on the
admissibility of Dr. Infante's general causation opinion.
The
Court grants defendants' motion because it finds that Dr. Infante's
general causation opinion is based on an unreliable methodology.
I. BACKGROUND
Plaintiff Yolande Burst filed this products liability action
against
defendants
Shell,
Chevron
Corporation), and Texaco.2
(as
successor
to
Gulf
Oil
She alleges that her late husband,
Bernard Burst, Jr., worked at various gas stations from 1958
through
1971,
during
1
R. Doc. 90.
2
R. Doc. 1.
which
time
he
regularly
used
products
manufactured,
supplied,
distributed,
and
sold
by
defendants.3
Specifically, she alleges that he regularly came into contact with
gasoline containing benzene.
On June 20, 2013, physicians diagnosed Mr. Burst with acute
myeloid leukemia (AML).4
He was 71 years old.
He passed away as
a result of the leukemia on December 21, 2013.5
Plaintiff alleges that her husband's regular exposure to
gasoline containing benzene during the years he worked as a gas
station attendant and mechanic caused his leukemia.6
that
defendants
containing
negligently
benzene
and
that
manufactured
they
and
negligently
She claims
sold
failed
products
to
warn
foreseeable users about the health hazards associated with these
products.7
She also alleges strict products liability.8
To demonstrate that gasoline containing benzene can cause AML
and that, in this case, it caused Mr. Burst's AML, plaintiff offers
the testimony of epidemiologist Dr. Peter Infante.
In his report,
Dr. Infante seeks to answer whether "occupational exposure to
benzene is a cause of myelodysplastic syndrome (MDS) and acute
3
Id. at 3.
4
R. Doc. 28-5 at 18.
5
R. Doc. 28-6.
6
R. Doc. 1 at 5.
7
Id. at 9.
8
Id. at 10.
2
myelogenous leukemia (AML)."9 Dr. Infante concludes that low-level
benzene exposure from gasoline can cause AML and that Mr. Burst's
exposure to gasoline containing benzene caused his AML. Defendants
now move to exclude Dr. Infante's opinions arguing that they are
unreliable and irrelevant.
II. LEGAL STANDARD
This is a toxic torts case where plaintiff alleges that
gasoline containing benzene caused her husband's AML. Accordingly,
plaintiff must show general causation--that gasoline containing
benzene can cause AML--and specific causation--that defendants'
products caused Mr. Burst's AML. See Knight v. Kirby Inland Marine
Inc., 482 F.3d 347, 351 (5th Cir. 2007) ("General causation is
whether a substance is capable of causing a particular injury or
condition in the general population, while specific causation is
whether a substance caused a particular individual's injury.")
(citation omitted).
A court may admit specific-causation evidence
only after the plaintiff has produced admissible evidence on
general causation.
See id. ("[I]f it concludes that there is
admissible general-causation evidence, the district court must
determine
whether
there
is
admissible
specific
causation
evidence.").
A district court has considerable discretion to admit or
9
R. Doc. 99, Ex. 1 at 1 (“Infante Report”).
3
exclude expert testimony under Rule 702.
See Gen. Elec. Co. v.
Joiner, 522 U.S. 136, 138-39 (1997); Seatrax, Inc. v. Sonbeck
Int'l, Inc., 200 F.3d 358, 371 (5th Cir. 2000).
Rule 702, which
governs the admissibility of expert witness testimony, provides:
A witness who is qualified as an expert by knowledge,
skill, experience, training, or education may testify in
the form of an opinion or otherwise if: (a) the expert's
scientific, technical, or other specialized knowledge
will help the trier of fact to understand the evidence or
to determine a fact in issue; (b) the testimony is based
on sufficient facts or data; (c) the testimony is the
product of reliable principles and methods; and (d) the
expert has reliably applied the principles and methods to
the facts of the case.
Fed. R. Evid. 702.
In Daubert v. Merrell Dow Pharms., Inc., the Supreme Court
held that Rule 702 requires the district court to act as a
gatekeeper to ensure that "any and all scientific testimony or
evidence admitted is not only relevant, but reliable."
509 U.S.
579, 589 (1993); see also Kumho Tire Co., Ltd. v. Carmichael, 526
U.S. 137, 147 (1999) (clarifying that the Daubert gatekeeping
function applies to all forms of expert testimony).
gatekeeping
function
thus
involves
a
two-part
The Court's
inquiry
into
reliability and relevance.
First, the Court must determine whether the proffered expert
testimony is reliable.
The party offering the testimony bears the
burden of establishing its reliability by a preponderance of the
evidence.
See Moore v. Ashland Chem. Inc., 151 F.3d 269, 276 (5th
Cir. 1998).
The reliability inquiry requires the Court to assess
4
whether
the
reasoning
testimony is valid.
or
methodology
underlying
the
See Daubert, 509 U.S. at 592-93.
expert's
The aim is
to exclude expert testimony based merely on subjective belief or
unsupported speculation.
See id. at 590.
The Court in Daubert
articulated a flexible, non-exhaustive, five-factor test to assess
the
reliability
of
an
expert's
methodology:
(1)
whether
the
expert's theory can be or has been tested; (2) whether the theory
has been subject to peer review and publication; (3) the known or
potential rate of error of a technique or theory when applied; (4)
the existence and maintenance of standards and controls; and (5)
the degree to which the technique or theory has been generally
accepted in the scientific community.
Court
has
emphasized,
however,
Id. at 593-95.
that
these
constitute a 'definitive checklist or test.'"
150 (quoting Daubert, 509 U.S. at 593).
The Supreme
factors
"do
not
Kumho, 526 U.S. at
Rather, district courts
"must have considerable leeway in deciding in a particular case how
to go about determining whether particular expert testimony is
reliable."
Id. at 152.
Courts have also considered whether
experts are "proposing to testify about matters growing naturally
and directly out of research they have conducted independent of the
litigation, or whether they have developed their opinions expressly
for purposes of testifying." Daubert v. Merrell Dow Pharms., Inc.,
43 F.3d 1311, 1317 (9th Cir. 1995). They have examined whether the
expert
has
adequately
accounted
5
for
obvious
alternative
explanations.
See Claar v. Burlington N.R.R., 29 F.3d 499, 502
(9th Cir. 1994). They have also asked whether the expert "is being
as careful as he would be in his regular professional work outside
his paid litigation consulting."
Sheehan v. Daily Racing Form,
Inc., 104 F.3d 940, 942 (7th Cir. 1997).
A district court's gatekeeper function does not replace the
traditional adversary system or the role of the jury within this
system.
See Daubert, 509 U.S. at 596.
As the Supreme Court noted
in Daubert: "Vigorous cross-examination, presentation of contrary
evidence, and careful instruction on the burden of proof are the
traditional and appropriate means of attacking shaky but admissible
evidence."
Id.
The Fifth Circuit has held that, in determining
the admissibility of expert testimony, district courts must accord
proper deference to "the jury's role as the proper arbiter of
disputes
between
conflicting
opinions”
and
that,
generally,
“questions relating to the bases and sources of an expert's opinion
affect the weight to be assigned that opinion rather than its
admissibility." United States v. 14.38 Acres of Land, More or Less
Situated in Leflore Cnty., Miss., 80 F.3d 1074, 1077 (5th Cir.
1996) (quoting Viterbo v. Dow Chem. Co., 826 F.2d 420, 422 (5th
Cir. 1987)) (internal quotation marks omitted).
Nonetheless,
expert testimony “must be reliable at each and every step or else
it is inadmissible,” and “[t]he reliability analysis applies to all
aspects of an expert's testimony: the methodology, the facts
6
underlying the expert's opinion, the link between the facts and the
conclusion, et alia.”
marks omitted).
Knight, 482 F.3d at 355 (internal quotation
If the “expert's opinion is based on insufficient
information, the analysis is unreliable.”
Paz v. Brush Engineered
Materials, Inc., 555 F.3d 383, 388 (5th Cir. 2009).
In Joiner, the Supreme Court explained that "nothing in either
Daubert or the Federal Rules of Evidence requires a district court
to admit opinion evidence that is connected to existing data only
by the ipse dixit of the expert."
522 U.S. at 146.
Rather, "[a]
court may conclude that there is simply too great an analytical gap
between the data and the opinion proffered." Id.; see also LeBlanc
v. Chevron USA, Inc. 396 F. App'x 94, 98 (5th Cir. 2010).
The Court next considers whether the expert's reasoning or
methodology
is
relevant.
The
question
here
is
whether
the
reasoning or methodology "fits" the facts of the case and will
thereby assist the trier of fact to understand the evidence.
See
Daubert, 509 U.S. at 591.
In fulfilling its role as a gatekeeper, the Court recognizes
that “the courtroom is not the place for scientific guesswork, even
of the inspired sort.”
(7th Cir. 1996).
it.”
Id.
Rosen v. Ciba-Geigy Corp., 78 F.3d 316, 319
Rather, “[l]aw lags science; it does not lead
The Court is mindful of the Supreme Court's guidance
that
there are important differences between the quest for
truth in the courtroom and the quest for truth in the
7
laboratory.
Scientific conclusions are subject to
perpetual revision. Law, on the other hand, must resolve
disputes finally and quickly. The scientific project is
advanced by broad and wide-ranging consideration of a
multitude of hypotheses, for those that are incorrect
will eventually be shown to be so, and that in itself is
an advance. Conjectures that are probably wrong are of
little use, however, in the project of reaching a quick,
final, and binding legal judgment--often of great
consequence--about a particular set of events in the
past. We recognize that, in practice, a gatekeeping role
for the judge, no matter how flexible, inevitably on
occasion will prevent the jury from learning of authentic
insights and innovations.
That, nevertheless, is the
balance that is struck by Rules of Evidence designed not
for the exhaustive search for cosmic understanding but
for the particularized resolution of legal disputes.
Daubert, 509 U.S. at 596-97.
III. DISCUSSION
A. Introduction
Defendants contend that there is no scientific basis for
concluding that gasoline containing benzene causes AML.
While
benzene is a known human carcinogen, defendants assert that the
scientific literature does not demonstrate that gasoline can cause
AML.
As the record indicates, gasoline is a mixture of many
substances
including
benzene.
While
the
benzene
content
of
gasoline varies depending on a number of factors, the record
indicates that the benzene concentration of gasoline may have
ranged from under 1% to as high as 4% or 5% between 1958 and 1971
when Mr. Burst worked as a service station attendant and mechanic.
8
To prove that gasoline containing benzene can cause AML,
plaintiff offers the testimony of epidemiologist Dr. Infante.
As
to general causation, Dr. Infante concludes: "[I]t is my opinion
that exposure to very low level benzene from gasoline can cause
damage to the DNA of bone marrow cells as well as AML . . . .
The
data related to gasoline exposure and risk of AML are consistent
with the epidemiological data on benzene exposure that demonstrate
an elevated risk of MDS/AML . . . ."10
Under Daubert, the Court's focus is Dr. Infante's methodology.
The reported basis for Dr. Infante's opinion is his "review of the
epidemiological
industry
and
documents,
toxicological
related
developing blood diseases."11
to
literature,
benzene
exposure
plus
and
internal
risk
of
Dr. Infante states he "followed the
methodology of the International Agency for Research on Cancer
(IARC) and of the Occupational Safety and Health Administration
(OSHA) in evaluating epidemiological studies, case reports and
toxicological studies of benzene exposure and its effect on the
hematopoietic system."12
Dr. Infante provides no other explanation
of his methodology.
Epidemiology provides the best evidence of general causation
in toxic tort cases.
10
Id. at 79.
11
Id. at 4.
12
See Brock v. Merrell Dow Pharms., Inc., 874
Id.
9
F.2d 307, 311 (5th Cir. 1989), modified by 884 F.3d 166 (5th Cir.
1989); Norris v. Baxter Healthcare Corp., 397 F.3d 878, 882 (10th
Cir. 2005) (stating "that epidemiology is the best evidence of
general causation in a toxic tort case").
This is not to say that
epidemiologic evidence "is a necessary element in all toxic tort
cases," but "it is certainly a very important element." Brock, 874
F.2d at 313.
Epidemiology is the study of "the incidence, distribution, and
etiology of disease in human populations."
Federal Judicial
Center, Reference Manual on Scientific Evidence 551 (3d ed. 2011).
As explained by the Fifth Circuit:
Epidemiology attempts to define a relationship between a
disease and a fact suspected of causing it . . . . To
define that relationship, the epidemiologist examines the
general population, comparing the incidence of the
disease among those people exposed to the factor in
question to those not exposed. The epidemiologist then
uses statistical methods and reasoning to allow her to
draw a biological inference between the factor being
studied and the disease's etiology.
Brock, 874 F.2d at 311.
To determine whether a causal relationship exists between an
agent and a disease, an epidemiologist must first identify an
association.
An
association
occurs
when
"two
events
(e.g.,
exposure to a chemical agent and development of disease) . . .
occur more frequently together than one would expect by chance."
Reference Manual at 552 n.7.
equivalent to causation.
An association, by itself, is not
Id. at 552.
10
Unlike an association,
"[c]ausation is used to describe the association between two events
when one event is a necessary link in a chain of events that
results in the effect."
Id. at 552 n.7.
The Reference Manual
indicates that "[a]ssesssing whether an association is causal
requires an understanding of the strengths and weaknesses of a
study's design and implementation, as well as a judgment about how
the study’s findings fit with other scientific knowledge."
Id. at
553. Because "all studies have 'flaws' in the sense of limitations
that add uncertainty about the proper interpretation of results,"
the key questions in evaluating epidemiologic evidence "are the
extent to which a study's limitations compromise its findings and
permit inferences about causation."
Id. at 553.
Once an association is found, "researchers consider whether
the association reflects a true cause-effect relationship;" that
is, whether "an increase in the incidence of disease among the
exposed subjects would not have occurred had they not been exposed
to the agent."
Id. at 597-98.
Alternative explanations, "such as
bias or confounding factors," should first be considered.
598.
Id. at
If alternative explanations are not present, researchers
apply the Bradford Hill criteria to evaluate whether an agent could
be a cause of a disease.
See In re Breast Implant Litig., 11 F.
Supp. 2d 1217, 1233 (D. Colo. 1998).
The Bradford Hill criteria
are: (1) temporal relationship; (2) strength of the association;
(3) dose-response relationship; (4) replication of findings; (5)
11
biological
plausibility;
(6)
consideration
of
alternative
explanations; (7) cessation of exposure; (8) specificity of the
association; and (9) consistency with other knowledge.
Manual at 600.
Reference
The Reference Manual cautions:
There is no formula or algorithm that can be used to
assess whether a causal inference is appropriate based on
these guidelines. One or more factors may be absent even
when a true causal relationship exists. Similarly, the
existence of some factors does not ensure that a causal
relationship exists. Drawing causal inferences after
finding an association and considering these factors
requires judgment and searching analysis, based on
biology, of why a factor or factors may be absent despite
a causal relationship, and vice versa. Although the
drawing of causal inferences is informed by scientific
expertise, it is not a determination that is made by
using an objective or algorithmic methodology.
Id.
Under Daubert, "courts must carefully analyze the studies on
which experts rely for their opinions before admitting their
testimony."
Knight, 482 F.3d at 355; see also Brock, 874 F.2d at
309-10 ("[C]ourts must critically evaluate the reasoning process by
which experts connect data to their conclusions in order for courts
to consistently and rationally resolve the disputes before them.");
Wagoner v. Exxon Mobil Corp., 813 F. Supp. 2d 771, 799 (E.D. La.
2011) ("Whether epidemiological studies support an expert's opinion
on the question of general causation in a toxic tort case is
critical to determining the reliability of the opinion.").
Courts
"may exclude expert testimony based on epidemiological studies
where the studies are insufficient, whether considered individually
12
or collectively, to support the expert's causation opinion." Baker
v. Chevron USA, Inc., 680 F. Supp. 2d 865, 875 (S.D. Ohio 2010)
(citing Joiner, 522 U.S. at 156-57). A court cannot exclude expert
testimony
simply
because
it
disagrees
with
the
expert's
conclusions, but the Supreme Court has recognized that
conclusions and methodology are not entirely distinct
from one another. Trained experts commonly extrapolate
from existing data. But nothing in either Daubert or the
Federal Rules of Evidence requires a court to admit
opinion evidence that is connected to existing data only
by the ipse dixit of the expert. A court may conclude
that there is simply too great an analytical gap between
the data and the opinion offered.
Joiner, 522 U.S. at 146.
Courts have excluded expert opinions on causation based on
epidemiologic and other scientific studies for a number of reasons.
First, studies that "do not represent statistically significant
results"
may
not
provide
a
reliable
foundation
for
an
epidemiologist’s general causation opinion in a toxic torts case.
LeBlanc, 396 F. App’x at 99 (citing Joiner, 522 U.S. at 145
(holding
that
a
study
showing
a
statistically
insignificant
increase in disease incidence following exposure to the alleged
causal chemical can properly be rejected by the district court as
a
foundation
for
the
expert's
opinion)).
The
results
of
epidemiologic studies are often expressed in terms of a relative
risk (RR),13 an odds ratio (OR),14 or a standardized morality ratio
13
"The relative risk is a number which describes the
increased or decreased incidence of the disease in question in
13
(SMR).15
An RR, OR, or SMR of 1.0 indicates that the number of
observed incidences of disease/death equals that of expected cases.
In contrast, a figure higher than 1.0 indicates that the number of
observed incidences exceeds that of expected cases; in other words,
it indicates a positive association.
A study is considered
statistically significant only when the results--e.g., RR, OR, or
SMR--are expressed with a 95% confidence interval,16 and when that
the population exposed to the factor as compared to the control
population not exposed to the factor. . . . A relative risk of
1.0 means that the incidence of [the disease] in the two groups
were the same. A relative risk greater than 1.0 means that there
[was more disease in the group exposed to the factor]." Brock,
874 F.2d at 312.
14
"A measure of association, often used in epidemiology.
For example, if 10% of all people exposed to a chemical develop a
disease, compared with 5% of people who are not exposed, then the
odds of the disease in the exposed group are 10/90 = 1/9,
compared with 5/95 = 1/19 in the unexposed group. The odds ratio
is (1/9)/(1/19) = 19/9 = 2.1. An odds ratio of 1 indicates no
association." Reference Manual at 291.
15
"SMR, or standardized mortality ratio, in epidemiology
is the ratio of observed deaths to expected deaths according to a
specific health outcome in a population. The calculation used to
determine the SMR is simple: number of observed deaths/number of
expected deaths. The SMR may be quoted as either a ratio or a
percentage. If the SMR is quoted as a ratio and is equal to 1.0,
then this means the number of observed deaths equals that of
expected cases. If higher than 1.0, then there is a higher number
of deaths than would be expected under normal circumstances.
Similarly, an SMR of 100 would mean that the risk in the study
population is equal to that of the general population. For
example, an SMR of 641 represents a relative risk of dying from a
particular cancer that is 6.4 times greater than that of the
general population." Taylor v. Airco, Inc., 494 F. Supp. 2d 21,
25 n.4 (D. Mass. 2007).
16
Studies may also employ a 90% confidence interval.
14
interval does not include the number 1.0.
312.
See Brock, 874 F.2d at
As the Fifth Circuit has explained:
[I]f a study concluded that the relative risk for [a
disease] was 1.30, which is consistent with a 30%
elevated risk of harm, but the confidence interval was
from 0.95 to 1.82, then no statistically significant
conclusions could be drawn from this study because the
relative risk, when adjusted by the confidence interval,
includes 1.0. Again, it is important to remember that
the
confidence
interval
attempts
to
express
mathematically the magnitude of possible error, due to
the above mentioned sources as well as others, and
therefore a study with a relative risk of greater than
1.0 must always be considered in light of its confidence
interval before one can draw conclusions from it.
Id.
Some courts require opinions on general causation to be
grounded in studies demonstrating a statistically significant
relative risk greater than 2.0.
See Daubert, 43 F.3d at 1321
(requiring a relative risk of greater than 2.0 for an epidemiology
study to show causation under a preponderance standard); Siharth v.
Sandoz Pharms. Corp., 131 F. Supp. 2d 1347, 1356 (N.D. Ga. 2001)
("[I]n the world of epidemiology, the threshold for concluding that
an agent was more likely than not the cause of a disease is a
relative risk greater than 2.0.").
The Fifth Circuit has not
adopted such a requirement.
Second,
a
study
that
provides
merely
"a
suggestion
or
possibility of a relationship is insufficient for a causation
opinion."
In re Breast Implant Litig., 11 F. Supp. at 1233; see
also Knight, 482 F.3d at 353 ("Although the study's 'suggestion'
could theoretically provide some basis for the conclusion that
15
diesel exhaust causes bladder cancer, it does not, as appellants
argue, 'clearly support' that conclusion.").
The same is true of
a study that "only provides an arguable inferential starting point"
for finding a causal relationship.
LeBlanc, 396 F. App’x at 99.
Studies that are inconclusive and merely recommend that further
studies be done are likely to fall into this category.
Breast Implant Litig., 11 F. Supp. at 1231.
that
studies
must
unequivocally
See In re
This is not to suggest
support
a
general
causation
opinion, but they must provide more than a hypothesis.
Third, a study that notes "that the subjects were exposed to
a range of substances and then nonspecifically note[s] increases in
disease incidence" can be disregarded.
LeBlanc, 396 F. App’x at
99; see also Joiner, 522 U.S. at 146 (holding that an expert's
reliance on a study was misplaced when the subjects of the study
"had been exposed to numerous potential carcinogens"); Knight, 482
F.3d at 353 ("Of all the organic solvents the study controlled for,
it
could
not
cancer . . . .
determine
which
led
to
an
increased
risk
of
The study does not provide a reliable basis for the
opinion that the types of chemicals appellants were exposed to
could cause their particular injuries in the general population.").
Likewise, studies that do not examine the precise disease at issue
may
not
provide
good
grounds
for
an
expert's
opinion.
See
Henricksen v. Conoco Phillips Co., 605 F. Supp. 2d 1142, 1171-75
(E.D. Wa. 2009) (calling into question the relevance of studies
16
that did not study the specific disease at issue).
Fourth, when a study's authors expressly disclaim the causal
relationship that the expert relies upon the study to prove, the
study likely does not provide a reliable basis for the expert's
opinion.
See Joiner, 522 U.S. at 145 (holding that a study did not
support an expert's opinion on causation when the study was
"unwilling to say that PCB exposure had caused cancer"); LeBlanc,
396 F. App’x at 100 ("The district court properly rejected the
studies as supporting causation because the authors of the studies
concluded that there was no proof of causation."); McClain v.
Metabolife Int'l, Inc., 401 F.3d 1233, 1248 (11th Cir. 2005)
(criticizing an expert for drawing "unauthorized conclusions from
limited data--conclusions the authors of the study do not make").
Case reports, which anecdotally describe an occurrence, often
on an individual basis, cannot establish general causation "because
they simply describe[] reported phenomena without comparison to the
rate at which the phenomena occur in the general population or in
a defined control group; do not isolate and exclude potentially
alternative causes; and do not investigate or explain the mechanism
of causation."
Casey v. Ohio Med. Prods., 877 F. Supp. 1380, 1385
(N.D. Cal. 1995); see also Siharath, 131 F. Supp. 2d at 1361
(collecting cases).
As to the conclusions and guidance of regulatory and advisory
bodies that a substance is carcinogenic, courts have cautioned that
17
they, alone, do not provide a reliable basis for establishing legal
causation.
The Fifth Circuit has explained:
Regulatory and advisory bodies such as IARC, OSHA and EPA
utilize a "weight of the evidence" method to assess the
carcinogenicity of various substances in human beings and
suggest or make prophylactic rules governing human
exposure. This methodology results from the preventive
perspective that the agencies adopt in order to reduce
public exposure to harmful substances.
The agencies'
threshold of proof is reasonably lower than that
appropriate in tort law, which "traditionally make[s]
more particularized inquiries into cause and effect" and
requires a plaintiff to prove "that it is more likely
than not that another individual has caused him or her
harm."
Allen v. Pa. Eng’g Corp., 102 F.3d 194, 198 (5th Cir. 1996)
(quoting Wright v. Williamette Indus., Inc., 91 F.3d 1105, 1107
(8th Cir. 1996)); see also Baker, 680 F. Supp. 2d at 880 ("The mere
fact that Plaintiffs were exposed to benzene emissions in excess of
mandated limits is insufficient to establish causation."); Parker
v. Mobil Oil Corp., 7 N.Y. 3d 434, 450 (N.Y. 2006) (finding that
"standards
promulgated
by
regulatory
agencies
as
protective
measures are inadequate to demonstrate legal causation"); David L.
Eaton, Scientific Judgment and Toxic Torts--A Primer in Toxicology
for
Judges
and
Lawyers,
12
J.
L.
&
Pol'y
5,
36
(2003)
("[R]egulatory levels are of substantial value to public health
agencies charged with ensuring the protection of the public health,
but are of limited value in judging whether a particular exposure
was a substantial contributing factor to a particular individual's
disease or illness.").
18
B. Analysis
The Court has performed an extensive review of the parties'
briefings and submissions, Dr. Infante's report and testimony, and
the relevant scientific literature.
After this review, the Court
finds that Dr. Infante's general causation opinion is not grounded
in a reliable methodology.
Dr. Infante's methodology is flawed
because he relies on multiple studies that do not reliably support
or do not otherwise "fit" his conclusion.
Ultimately, there is
simply too great an analytical gap between the underlying data and
the opinion offered.
1. Dr. Infante's Reliance on Benzene Studies
The majority of the literature on which Dr. Infante relies in
formulating
his
general
causation
opinion
relates
to
studies
examining the risks associated with exposure to benzene in general,
not
studies
gasoline.
examining
the
risks
associated
with
exposure
to
Out of Dr. Infante's 102-page report, he devoted 54
pages to literature pertaining to benzene exposure generally and
only 14 pages to literature pertaining specifically to gasoline
exposure.
gasoline
But here, Mr. Burst allegedly sustained exposure to
containing
benzene,
substance containing benzene.
not
pure
benzene
or
any
other
The question here, therefore, is
whether exposure to gasoline containing benzene can cause AML, not
whether
exposure
to
benzene
generally
can
cause
AML.
See
Henricksen, 605 F. Supp. 2d at 1156 ("This is a products liability
19
action and Defendant's product is gasoline.").
Dr. Infante does
discuss the gasoline literature and he does conclude that gasoline
exposure can cause AML. But, contrary to Dr. Infante's contention,
the data related to gasoline exposure is far from consistent with
the data related to benzene exposure.
Because benzene is a known human carcinogen and because all
gasoline contains benzene, the Court recognizes that literature
pertaining to benzene is generally relevant to the causation
question at issue.
Still, there are important reasons to question
the sufficiency of this knowledge as it relates to Dr. Infante’s
general causation opinion.
The
parties
do
not
dispute
exposure, benzene can cause AML.
that,
at
certain
levels
of
Dr. David Pyatt, defendants'
expert toxicologist, recognized that benzene is one of the most
studied substances in the world, and that it is a carcinogen is
widely accepted.
The EPA, OSHA, IARC, Agency for Toxic Substances
and Disease Registry (ATSDR), and other scientific bodies all
categorize benzene as a human carcinogen.
no
scientific
carcinogen.
authority
has
classified
Despite this consensus,
gasoline
as
a
human
For example, IARC has concluded: "There is inadequate
evidence for the carcinogenicity in humans of gasoline."
IARC,
Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol.
45, Occupational Exposures in Petroleum Refining; Crude Oil and
Major Petroleum Fuels (1989) (emphasis in original). Likewise, the
20
ATSDR Toxicological Profile for Gasoline (1995) concluded that
there is no conclusive evidence to support a finding that gasoline
causes cancer.17
Specifically, the ATSDR report stated:
Benzene, a component of gasoline, is a known human
carcinogen that has been shown to cause an increased
incidence of hematopoietic cancers (leukemia) in
occupational exposed workers . . . . However, . . . the
evidence for an association between increased incidence
of cancer (including leukemia) and exposure to gasoline
in humans is inadequate.
Further, while there is
sufficient evidence that benzene is carcinogenic in rats,
causing an increased incidence of tumors at multiple
sites . . . , gasoline has only been shown to cause
increased incidences of renal cell tumors in male rats (a
finding that is not considered relevant to humans) and
liver tumors in female mice.
Therefore, there is no
conclusive evidence to support or refute the carcinogenic
potential of gasoline in humans or animals based on the
carcinogenicity of one of its components, benzene.18
To explain why gasoline has not been found to be carcinogenic,
defendants proffer two explanations. First, defendants assert that
because gasoline contains only small concentrations of benzene,
individuals cannot be exposed to sufficient levels of benzene from
gasoline to be at risk for AML.
Second, defendants assert that
because gasoline is a mixture of substances, including benzene and
toluene, "competitive inhibition" between the different substances
may impede the metabolism of benzene.
17
For example, Dr. Pyatt,
Although the ATSDR published this report in 1995, it
remains the current position of the agency. See ATSDR, Public
Health Statement for Automotive Gasoline,
http://www.atsdr.cdc.gov/PHS/PHS.asp?id=466&tid=83 (last visited
June 16, 2015) (“[T]here is no evidence that exposure to gasoline
causes cancer in humans.”).
18
Defense Ex. A-2 at 87.
21
citing multiple studies, hypothesizes that competitive inhibition
occurs between toluene and benzene whereby co-exposure to the
substances, as opposed to exposure to just benzene, results in the
reduced metabolism of benzene.19
Consistent with defendants' contention that the literature
pertaining to gasoline exposure is most relevant and that Dr.
Infante's
reliance
on
the
benzene
literature
is
improper,
a
district court, addressing the same general causation opinion
offered by Dr. Infante, stated that while "evaluations of both
gasoline and its toxic component benzene are obviously relevant to"
plaintiff's
case,
"the
court
cannot
simply
presume
that
the
qualitative toxic and carcinogenic effects of benzene from any
source are the same."
Henricksen, 605 F. Supp. 2d at 1156; see
also Rider v. Sandoz Pharm. Corp., 295 F.3d 1194, 1201 (11th Cir.
2002) ("Even minor deviations in chemical structure can radically
change a particular substance's properties and propensities."). In
Henricksen, the district court held that "[i]f it is possible to
extrapolate from studies of benzene or other benzene-containing
products conclusions regarding gasoline, then it will be incumbent
upon [plaintiff] to explain and demonstrate why the extrapolation
is scientifically proper."
Henricksen, 605 F. Supp. 2d at 1156.
The Court finds that although evaluation of the benzene
19
In contrast, Dr. Infante cites animal studies which he
contends show that simultaneous exposure to toluene and benzene
may enhance the toxicity of benzene. Infante Report at 42.
22
literature is generally relevant to Dr. Infante's ultimate opinion,
see Dickson v. Nat'l Maint. & Repair of Ky., Inc., No. 5:08-CV00008, 2011 WL 12538613, at *6 (W.D. Ky. April 28, 2011) ("Benzene
may be considered a causative agent despite only being a component
of the alleged harm."), it, alone, cannot provide a reliable basis
for
Dr.
Infante's
opinion.
While
seemingly
all
scientific
authorities recognize benzene as a carcinogen, none recognizes
gasoline as a carcinogen, and defendants have offered several
justifications for why exposure to benzene in gasoline should be
evaluated differently than exposure to benzene generally. As such,
while the Court recognizes the general relevance of these studies,
they alone do not provide sufficient grounds to reliably support
Dr. Infante’s general causation opinion.
2. Dr. Infante's Reliance on the Gasoline Literature
The Court now turns to Dr. Infante’s review of and reliance on
the gasoline literature.20 After an extensive review of the studies
on which Dr. Infante relied, the Court concludes that Dr. Infante’s
methodology is deficient for a number of reasons.
First, Dr.
Infante relies on a number of studies that did not isolate exposure
to gasoline, the relevant product at issue, or did not provide
exposure metrics.
Second, Dr. Infante relies on studies that did
not exhibit statistically significant results or did not indicate
20
While Dr. Infante cites numerous sources in his report,
the Court primarily limits its discussion to the relevant
literature discussed at the Daubert hearing.
23
a positive association between gasoline exposure and AML.
Third,
Dr. Infante relies on studies that did not specifically examine
AML, the disease at issue, and instead examined leukemia generally
or other types of leukemia.
Finally, in several instances, Dr.
Infante cherry-picked data from studies that did not otherwise
support his conclusion, failed to explain contrary results, reached
conclusions the authors of the study did not themselves make, and
manipulated data without providing any evidence of his work.
Exacerbating Dr. Infante’s methodological failings is that even in
light of the inconsistent and conflicting studies on which he
relies and the paucity of scientific literature supporting his
conclusion, he fails to provide a meaningful analysis in which he
reconciles
conflicting
studies
or
applies
the
Bradford
Hill
criteria to the gasoline-specific studies.
a. Studies that Do Not Isolate Gasoline Exposure or
that Do Not Provide Exposure Metrics
Dr.
Infante’s
reliance
on
studies
that
did
not
isolate
gasoline exposure from exposure to other substances cannot reliably
support his opinion.
See LeBlanc, 393 F. App’x at 99 (noting a
study indicating “that the subjects were exposed to a range of
substances and then nonspecifically not[ing] increases in disease
incidence” can be disregarded); ATSDR Toxicological Profile on
Gasoline
(1995)
potentially
(highlighting
carcinogenic
“concurrent
substances
exposure
(i.e.,
service
to
other
station
attendants are also exposed to motor oils, diesel fuel oils, and
24
solvents as well as automobile and truck engine exhaust)” as a
characteristic of studies containing “inherent limitations that
preclude their use as evidence for an association between gasoline
exposure and cancer in humans”).
isolates
exposure
to
gasoline
In other words, unless a study
from
other
products
containing
benzene, it cannot support the conclusion that the benzene in
gasoline is the causative agent. As an example, Dr. Infante relied
on
Schwartz,
E.,
Proportionate
Mortality
Ratio
Analysis
of
Automobile Mechanics and Gasoline Service Station Workers in New
Hampshire, 12 AM. J. INDUS. MED. 91 (1987).21
In his report,
without any notation or caution, Dr. Infante stated that the study
demonstrated “[w]orkers in the gasoline service station industry
experienced a leukemia mortality excess of more than 3-fold which
was statistically significant (PMR = 3.28, p < 0.05).”22
Dr.
Infante failed to acknowledge that the workers in the study
sustained potential exposure to gasoline vapor, benzene, solvents,
lubricating oils, asbestos, welding fumes, and car and truck
exhaust, or that Schwartz concluded that "the results of this
analysis suggest that one or more of the exposures experienced by
automobile
mechanics
carcinogenic risk."
and
service
station
workers
poses
a
Likewise, Dr. Infante did not acknowledge the
study’s guidance that "[m]ore definitive epidemiologic studies are
21
Plaintiff's Ex. 8.
22
Infante Report at 67.
25
required to determine if the leukemia excess is associated with
exposure to benzene, gasoline, or other workplace substances." Dr.
Infante’s reliance on a number of other studies is similarly
flawed.
See Hunting, K., et al., Haematopoietic Cancer Mortality
Among Vehicle Mechanics, 52 OCCUP. ENVTL. MED. 673 (1995)23 (noting
that,
in
addition
to
gasoline,
workers
sustained
potential
exposures to degreasing agents, diesel fuel, asbestos from brake
work, used motor oils, Varsol, spray cans of brake, battery, or
carburetor cleaner, and that some workers also experienced other
exposures
during
welding,
spray
painting,
sheet
metal
work,
carpentry, and tire repair operations); Lindquist, R., et al.,
Acute Leukemia in Professional Drivers Exposed to Gasoline and
Diesel, 42 EUR. J. HAEMATOL. 98 (1991)24
(noting professional
drivers were exposed to petroleum products, including gasoline,
diesel, aircraft fuels, and their combustion products, and finding
“an etiological relationship between the development of acute
leukemia and exposure to petroleum products as fuel and exhaust”);
Sathiakamur, N., et al., A Case Control Study of Leukemia Among
Petroleum
Workers,
37
J.
OCCUP.
&
ENVTL.
MED.
1269
(1995)25
(examining risks associated with exposure to crude oil).
Dr.
Infante’s
reliance
23
Plaintiff's Ex. 14.
24
Plaintiff's Ex. 22.
25
on
Plaintiff's Ex. 23A.
26
studies
that
do
not
quantify
gasoline exposure is equally problematic.
Profile
on
Gasoline
(1995)
See ATSDR Toxicological
(highlighting
studies’
“lack
of
information on levels of exposure to gasoline vapor” as one of
“several inherent limitations that preclude their use as evidence
for
an
association
humans”).
between
gasoline
exposure
and
cancer
in
For example, many of the studies on which Dr. Infante
relied examined workers in certain occupations, such as petroleum
distribution
workers
or
gasoline
service
station
attendants,
instead of examining gasoline exposure directly. See Terry, P., et
al., Occupation, Hobbies, and Acute Leukemia in Adults, 29 LEUKEMIA
RES. 1117 (2005)26 (examining the association between AML and
employment as a gasoline station attendant and employment in the
petroleum
industry);
Schnatter,
A.,
et
al.,
A
Retrospective
Mortality Study among Canadian Petroleum Marketing and Distribution
Workers,
101
association
ENVTL.
HEALTH
between
truck
PERSP.
85
drivers
(1993)27
(examining
exposed
to
the
“finished
hydrocarbons” and leukemia, but acknowledging that they had “no
knowledge concerning the actual levels of benzene experienced by
these truck drivers”); Schnatter, A., et al., Myelodysplastic
Syndrome
and
Benzene
Exposure
Among
Petroleum
Workers:
An
International Pooled Analysis, 104 J. NAT’L CANCER INST. 1724
26
Plaintiff's Ex. 16.
27
Plaintiff's Ex. 18.
27
(2012)28 (examining the association between AML and ever working as
a tanker truck driver without any elaboration as to the substances
to which the drivers were exposed).
While such professions may
serve as an imprecise proxy for gasoline exposure, it is impossible
to tell, and the studies do not indicate, to what substances and at
what levels the workers were actually exposed.
As stated, even
gasoline service station attendants, the most relevant group of
workers in this case, may be exposed to numerous substances in
addition to gasoline.
See ATSDR Toxicological Profile on Gasoline
(1995) (noting that “service station attendants are also exposed to
motor oils, diesel fuel oils, and solvents as well as automobile
and truck engine exhaust”).
In one of the few gasoline studies
reviewed by Dr. Infante that actually made quantitative exposure
estimates, Wong, O., et al., Health Effects of Gasoline Exposure.
II. Mortality Patterns of Distribution Workers in the United
States, 101 ENVTL. HEALTH PERSP. SUPPL. 6 (1993),29 the authors
observed no statistically significant increased risk for AML in
workers exposed to gasoline.
b. Studies that Do
Significant Results
Not
Exhibit
Statistically
Dr. Infante’s reliance on studies exhibiting results that are
not
statistically
significant
28
Plaintiff's Ex. 27.
29
does
Plaintiff's Ex. 19.
28
not
reliably
support
his
opinion.
See Joiner, 522 U.S. at 145; LeBlanc, 396 F. App’x at 99.
While Dr. Infante’s report generally acknowledges when a study did
not demonstrate statistically significant results, he testified
that such studies provide “some evidence” of an association thereby
exhibiting his reliance upon them. For example, Rushton, L., A 39Year Follow-up of the U.K. Oil Refinery and Distribution Center
Studies: Results for Kidney Cancer and Leukemia, 101 ENVTL. HEALTH
PERSP.
SUPPL.
77
(1993),30
did
not
observe
a
statistically
significant increased risk of AML in workers employed at oil
refineries.
Nevertheless, Dr. Infante testified that this study
provides “some evidence” that gasoline causes AML.
The Court
recognizes, as explained by Dr. Infante, that studies that do not
demonstrate statistically significant results may be relied upon
within the epidemiologic community in certain instances, but the
guidance of the Supreme Court and the Fifth Circuit instructs that
such studies do not reliably support epidemiologists’ general
causation opinions in the context of toxic tort litigation.
of
the
studies
on
which
Dr.
Infante
relied
did
not
Many
produce
statistically significant results and his reliance on them is
therefore questionable.
See Wong, O., et al., Health Effects of
Gasoline Exposure. II. Mortality Patterns of Distribution Workers
in the United States, 101 ENVTL. HEALTH PERSP. SUPPL. 6 (1993);31
30
Plaintiff's Ex. 17.
31
Plaintiff's Ex. 19.
29
Sorahan, T., et al., Mortality of United Kingdom Oil Refinery and
Petroleum Distribution Workers, 1951-1998, 52 OCCUP. MED. 333
(2002);32 Wong, O., et al., A Hospital-Based Case-Control Study of
Acute Myeloid Leukemia in Shanghai: Analysis of Environmental and
Occupational Risk Factors by Subtypes of the WHO Classification,
184 CHEMICO-BIOLOGICAL INTERACTIONS 112 (2010);33 Lynge, E., et al.,
Risk of Cancer and Exposure to Gasoline Vapors, 145 AM. J. EPID.
449 (1997) (Dr. Infante relied on the non-significant results
pertaining to the Swedish cohort); Lagorio, S., et al., Mortality
of Filling Station Attendants, 20 SCAND. J. WORK ENVTL. HEALTH 331
(1994).34
c. Studies that Do Not Examine AML Specifically
Third, many of the studies on which Dr. Infante relied did not
examine the risk for AML specifically, and instead examined the
risk of leukemia generally or other specific types of leukemia.
Because Mr. Burst’s physicians diagnosed him with AML, not some
other type of leukemia, and because the specific type of leukemia
is relevant to the general causation question at issue, Dr.
Infante’s reliance on such studies does not reliably support his
opinion that gasoline causes AML.
See ATSDR Toxicological Profile
on Gasoline (1995) (“It is very difficult to draw any definitive
32
Plaintiff's Ex. 24.
33
Plaintiff's Ex. 42.
34
Plaintiff's Ex. 9.
30
conclusions
from”
a
study
where
“several
different
types
of
leukemia were reported.”); Wong, O., et al., Health Effects of
Gasoline Exposure. II. Mortality Patterns of Distribution Workers
in the United States, 101 ENVTL. HEALTH PERSP. SUPPL. 6 (1993)35
(“Several previous epidemiologic studies indicate that exposure to
benzene or petroleum products containing benzene may result in an
increased risk of acute myeloid leukemia but not other cell
types.”). For example, Schwartz, E., Proportionate Mortality Ratio
Analysis of Automobile Mechanics and Gasoline Service Station
Workers in New Hampshire, 12 AM. J. INDUS. MED. 91 (1987), did not
examine
AML,
but,
instead,
leukemia
generally.
Likewise,
a
significant number of studies on which Dr. Infante relied did not
examine AML specifically.
See Spivey, unpublished Union Oil
internal report (1983)36 (examining leukemia generally); Naizi, GA,
Fleming, AF, Blood Dyscrasia in Unofficial Vendors of Petrol and
Heavy Oil and Motor Mechanics in Nigeria, 19 TROP. DOCT. 55 (1989)
(examining anemia, microcytosis, hypocromia, thrombocyotopenia, and
neutropenia); Hunting, K., et al., Haematopoietic Cancer Mortality
Among
Vehicle
Mechanics,
52
OCCUP.
ENVTL.
MED.
673
(1995)37
(examining leukemia and aleukemia and, while noting one case of
AML, not providing any separate analysis for the risk of AML);
35
Plaintiff's Ex. 19.
36
Plaintiff's Ex. 7.
37
Plaintiff's Ex. 14.
31
Schnatter, AR, et al., A Retrospective Mortality Study among
Canadian Petroleum Marketing and Distribution Workers, 101 ENVTL.
HEALTH PERSP. 85 (1993)38 (examining leukemia generally); Lindquist,
R., et al., Acute Leukemia in Professional Drivers Exposed to
Gasoline and Diesel, 42 EUR. J. HAEMATOL. 98 (1991)39 (examining
acute
leukemia
generally);
Brandt,
P.,
et
al.,
Occupational
Exposure to Petroleum Products in Men with Acute Non-Lymphocytic
Leukaemia, 1 BRITISH MED J 553 (1978)40 (examining acute nonlymphocytic leukemia (ANLL), which Dr. Infante testified is not
strictly limited to AML); Australian Health Watch, 10th (1998)41 and
11th (2000)42 Reports (examining leukemia generally).
d. Dr. Infante Cherry-Picks
Explain Contrary Results
Dr.
Infante
cherry-picks
data
from
Data
and
studies
in
Fails
to
several
significant instances and fails to explain contrary results in a
manner that belies the reliability of his methodology.
example, Dr. Infante cites Sandler, DP,
et al.,
For
Exposure to
Chemical and Risk for Myelodoysplastic Syndrome, Abstract # S60,
28th Annual Meeting, Society for Epidemiologic Research, Snowbird,
38
Plaintiff's Ex. 18.
39
Plaintiff's Ex. 22.
40
Plaintiff's Ex. 6.
41
Plaintiff's Ex. 44.
42
Plaintiff's Ex. 25.
32
Utah (1995),43 for its examination of the risk of myeldodysplastic
syndrome (MDS) from exposure to gasoline, kerosene, and petroleum
distillates.
Absent
from
Dr.
Infante's
report
is
any
acknowledgment that this study separately examined the risk for AML
and did not find a statistically significant increased risk.
The
Court can only speculate as to why Dr. Infante neglected to discuss
this pertinent finding in his report.
Similarly, at the hearing, Dr. Infate cited Wong, O., et al.,
A Hospital-Based Case-Control Study of Acute Myeloid Leukemia in
Shanghai: Analysis of Environmental and Occupational Risk Factors
by Subtypes of the WHO Classification, 184 CHEMICO-BIOLOGICAL
INTERACTIONS 112 (2010),44 for its observation of an increased risk
of
AML
in
“unloading
workers”
home/workplace renovations.
workers
were
likely
exposed
and
workers
involved
in
Dr. Infante explained that these
to
benzene
and
gasoline,
and,
therefore, concluded that the study supported his opinion.
This
same study, however, separately examined the relationship between
gasoline exposure and AML and did not observe a statistically
significant association (OR 1.07 95% CI 0.72-1.61).45
43
Plaintiff's Ex. 15.
44
That Dr.
Plaintiff's Ex. 42.
45
Notably, despite not finding a statistically
significant association between gasoline and AML, the study
observed a statistically significant increased risk between
benzene exposure and AML (OR 1.43 95% CI 1.05-1.93).
33
Infante disregards this directly applicable result in favor of
other
data
involving
workers
with
exposures
to
unidentified
substances is problematic and suggests a methodology driven by an
attempt to achieve a particular result.
Finally, Dr. Infante cites Lynge, E., et al., Risk of Cancer
and Exposure to Gasoline Vapors, 145 AM. J. EPID. 449 (1997), the
largest study of service station workers occupationally exposed to
gasoline and gasoline vapors. The authors studied cancer incidence
in a cohort of 19,000 gasoline service station workers from
Denmark, Norway, Sweden, and Finland.
The authors identified
workers from the 1970 censuses and followed them for 20 years.
According to the authors, the benzene content in gasoline in Nordic
countries at this time ranged from 2% to 6%.
The study observed
“no excess risk of leukemia or specifically of acute myeloid
leukemia.” Despite this finding, Dr. Infante stated that the study
provides “some evidence in support of an association”46 because one
of
the
cohorts
demonstrated
a
non-statistically
significant
increased risk of AML (8 cases observed versus 3.86 expected in the
Swedish cohort).
Dr. Infante relied on this result despite the
authors’ conclusion that the attendants’ gasoline exposure posed
“no excess risk of leukemia or specifically of acute myeloid
leukemia.”
46
Infante Report at 70.
34
e. Dr. Infante Does Not Justify His Manipulation of
Data
In other instances, Dr. Infante manipulated data in a manner
not performed by the authors of the study.
Even if, as Dr. Infante
urges, this practice is common in the field of epidemiology, Dr.
Infante
repeatedly
failed
a
to
reliable
show
that
he
performed
manner
or
that
they
are
these
manipulations
in
even
appropriate.
For example, Rushton, L., Romaniuk, H., A Case-
Control Study to Investigate the Risk of Leukaemia Associated with
Exposure to Benzene in Petroleum Marketing and Distribution Workers
in the United Kingdom, 54 OCCUP. ENVTL. MED. 152 (1997),47 examined
petroleum distribution workers exposed to low levels of benzene.
Dr. Infante relied on Table 5 of the study, which presented results
based on cumulative exposure to benzene.
There, the authors
observed no statistically significant increased risk of acute
myeloid or monocytic leukemia whether the workers were exposed to
less than 0.45 ppm-years benzene, 0.45-4.49 ppm-years benzene, or
4.5-44.9 ppm-years benzene.
While not statistically significant,
the study observed an increased risk for the two lower exposure
groups.
Dr.
Infante
testified
that
the
non-statistically
significant increased risk for the two lower exposure groups "in
and of itself provides evidence that low cumulative exposure to
benzene is associated with an elevated risk of AML."
47
Plaintiff's Ex. 50.
35
Dr. Infante
also stated that if one combines the data from the 0.45-4.49 ppmyears
group
and
the
4.5-44.9
association is observed.
ppm-years
group,
a
positive
Dr. Infante stated that he did not
perform an analysis for statistical significance on this figure,
but asserted that the result would be statistically significant if
he had. Unfortunately, the authors themselves did not perform this
calculation, and Dr. Infante provides no indication of how he
performed this calculation or whether it is appropriate.
At the
hearing, Dr. Infante explained that he performed the calculation on
a
“sticky
note.”
The
Court
cannot
credit
Dr.
Infante's
calculations which involve calculating different results from
separate data sets from this study without, at the very least,
evidence of his calculations, let alone some indication of why this
calculation is appropriate when the authors of the study chose not
to perform it themselves.
Dr. Infante’s combination of two
separate data sets from the Spivey study, an unpublished Union Oil
internal report from 1983,48 suffers from the same problem.49
48
Plaintiff's Ex. 7.
49
There, Dr. Spivey examined the risk of leukemia
associated with work as a garage and gas station attendant, fork
lift and tow motor operator, petroleum engineer, painter, and
auto mechanic. The study did not demonstrate a statistically
significant excess risk of leukemia and did not specifically
examine the risk of AML. In his report, Dr. Infante purports to
combine the data from the garage and gas station attendants and
the auto mechanics to produce a statistically significant result.
Notably, Dr. Infante's calculation was not performed by the
author of the study, and Dr. Infante does not provide any
evidence of his own calculations. Without this, the Court is
36
Similarly, Dr. Infante adjusted the results of Wong, O., et
al., Health Effects of Gasoline Exposure. II. Mortality Patterns of
Distribution Workers in the United States, 101 ENVTL. HEALTH PERSP.
SUPPL. 6 (1993).50
There, the authors studied a cohort of 18,135
gasoline distribution workers with potential exposure to gasoline
for at least one year at land-based terminals or on marine vessels
between 1946 and 1985.
petroleum
industry,"
"[U]nlike most previous studies in the
the
authors
made
estimates" as to the workers' exposures.
"quantitative
exposure
This, the authors noted,
permitted an analysis of whether a dose-response relationship
existed,
"one
causation."
of
the
most
important
criteria
in
determining
The authors concluded:
The results of this study indicate that there was no
increased mortality from . . . leukemia among marketing
and marine distribution employees in the petroleum
industry, who were exposed to gasoline, when compared to
the general population. Furthermore, based on internal
comparisons, there was no association between mortality
from . . . leukemia and various indices of gasoline
exposure. In particular, neither duration of gasoline
exposure, cumulative exposure, frequency of peak
exposures, nor average intensity of exposure had any
effect on . . . leukemia mortality.
The study observed a non-significant mortality increase from AML in
land-based terminal employees, "but no trend was detected when the
data were analyzed by various gasoline exposure indices."
unable to evaluate Dr. Infante's methodology.
50
Plaintiff's Ex. 19.
37
The
authors noted that "[t]his nonsignificant excess was limited to
land-based terminal employees hired before 1948" when benzene
levels in the industry were likely higher.
Because the overall mortality of the cohort was only half of
what was expected, Dr. Infante adjusted the land-based terminal
employees results of this study for the "healthy worker effect."
The healthy worker effect describes a phenomenon that can occur
when studying occupational disease: "Workers usually exhibit lower
overall
death
rates
than
the
general
population
because
the
severely ill and chronically disabled are ordinarily excluded from
employment." Last, J., A Dictionary of Epidemiology (3d ed. 1995).
Because the workers may be healthier than the general population,
comparing the incidence of disease or death in the workers to that
of the general population may result in a bias.
By adjusting for
the healthy worker effect, Dr. Infante concluded that the excess
rate of AML was in fact statistically significant, contrary to what
Wong found.
Dr.
Infante's
adjustment
problematic in this instance.
for
healthy
worker
effect
is
First, Dr. Infante provides no
indication of how he adjusted for the healthy worker effect. Thus,
the Court has no basis to evaluate his methodology to determine
whether it is reliable.
Second, Wong expressly acknowledged the
impact of a healthy worker effect and chose not to adjust for it.
Wong explained: "[B]ecause internal comparisons do not involve an
38
external comparison population [e.g., the general population, which
is presumably less healthy than the working population under
study], our analyses and interpretation based on these internal
comparisons would not be affected by the choice of an external
comparison population."
In other words, Wong explained that by
comparing the data to both the general population and to internal
subgroups, they accounted for potential bias created by healthy
worker effect.51
Dr. Infante provides no acknowledgment of this
discussion or explanation of why his adjustment is appropriate in
lieu of it.
Dr. Infante also adjusted the results of Sorahan, T., et al.,
Mortality of United Kingdom Oil Refinery and Petroleum Distribution
Workers, 1951-1998, 52 OCCUP. MED. 333 (2002),52 for healthy worker
effect.
There, the authors performed a cohort study of 28,630 oil
refinery workers and 16,480 petroleum distribution workers.
The
authors observed a SMR of 1.51 (95% CI 0.97-2.24) for AML and
distribution
significant.
workers,
but
the
result
was
not
statistically
The authors themselves recognized that “there is
evidence of a healthy worker effect,” but did not adjust their
results.
In two instances, the authors stated that “[i]t is
51
Referring to another study, Dr. Infante separately
noted at the hearing that one would not observe much of a healthy
worker effect if a cohort is compared to other workers instead of
the general population.
52
Plaintiff's Ex. 24.
39
important to gauge the size of this effect.”
According to Dr.
Infante, “the SMR for all causes demonstrated a significant”
healthy worker effect, so he adjusted the results accordingly.53
Dr. Infante provided no explanation of how he adjusted for the bias
or to what extent he did so, and instead, simply stated: “When this
adjustment is made, the SMRs for total leukemia and for AML
specifically are both statistically significant.
1.61 (95% CI = 1.03-2.39).”54
For AML, SMR =
The Court has no basis from which to
evaluate whether Dr. Infante performed the adjustment correctly,
or, for example, whether he reliably gauged the size of the effect.
The
Court
emphasizes
that
it
does
not
question
whether
combining data sets and adjusting for bias such as that arising
from
the
healthy
epidemiology.
worker
effect
is
accepted
in
the
field
of
In such instances, however, when an expert performs
after-the-fact manipulations of published data, it is particularly
important for the expert to provide not only a justification for
doing so, but also some evidence of his work and the reliability of
his method. An expert’s solitary assurances do not allow the Court
to ensure that the methodology is reliable.
f. Summary
In light of the Court’s examination of the studies on which
Dr. Infante relied, it is clear that Dr. Infante relied on a
53
Infante Report at 73.
54
Id.
40
universe of divergent studies that either did not examine the
substance at issue, did not examine the disease at issue, or did
not exhibit statistically significant results.
Moreover, Dr.
Infante exhibited a willingness to ignore or disregard contrary
results, and to manipulate data in a manner not supported by any
evidence of his work or independent justification and, in one
instance, inconsistent with the authors’ own discussion.
Compounding Dr. Infante’s methodological failings is that,
despite analyzing a collection of studies inconsistent in both
subject
matter
and
results,
Dr.
Infante
did
not
present
a
meaningful analysis in which he reconciled this conflicting group
of studies.
Instead of providing a rigorous analysis explaining
how he came to his conclusion from the gasoline literature, Dr.
Infante simply provides a literature review, at times supplemented
by his own commentary, and states a conclusion.
Infante
employs
no
overall
application
of
the
Notably, Dr.
Bradford
Hill
criteria, a bedrock of epidemiological methodology for determining
issues of general causation, in analyzing the gasoline literature.
While this approach may suffice in cases where numerous consistent
studies produce similar results, this is not the case here.
It
bears emphasis that an expert’s extrapolation from studies that are
not directly on point or that do not unequivocally support his
conclusion is not necessarily grounds to exclude the opinion as
unreliable. Such practice may be appropriate in certain instances,
41
particularly when combined with other supporting information. But,
as is the case here, when an expert exhibits wholesale reliance on
such studies without any differentiation or attempt to explain why
the studies remain relevant in light of their inconsistency with
the facts of the case, the methodology is unreliable.
The Court’s focus is Dr. Infante’s underlying methodology, but
the
Court
also
notes
that
there
is
a
paucity
of
scientific
literature supporting Dr. Infante’s opinion that gasoline can cause
AML.
See Henricksen, 605 F. Supp. 2d at 1175 (“None of the studies
relied upon have concluded that gasoline has the same toxic effect
as benzene, and none have concluded that the benzene component of
gasoline is capable of causing AML.”); Castellow v. Chevron USA, 97
F. Supp. 2d 780, 796 (S.D. Tex. 2000) (“Plaintiffs here have not
shown that the relevant scientific or medical literature supports
the conclusion that workers exposed to benzene, as a component of
gasoline, face a statistically significant risk of an increase in
the rate of AML.”); Parker, 7 N.Y. 3d at 450 (“[N]o significant
association has been found between gasoline exposure and AML.
Plaintiff’s experts were unable to identify a single epidemiologic
study finding an increased risk of AML as a result of exposure to
gasoline.”).
Moreover,
no
regulatory
or
advisory
body
has
concluded that gasoline can cause AML, see Henricksen, 605 F. Supp.
2d. at 1151 (noting that "no authoritative source (organization or
regulatory agency) has identified gasoline as cancer-causing"),
42
even though, as noted by the Fifth Circuit, regulatory bodies apply
a lower threshold of proof in determining issues of causation than
is “appropriate in tort law.”
Allen, 102 F.3d at 198.
The dearth
of supporting literature renders a significant void that makes Dr.
Infante’s methodological failings even more problematic.
Further, even if the Court's sifting of the literature yielded
a few studies that could plausibly support Dr. Infante's opinion,55
the vast majority of studies do not fit Dr. Infante's conclusion
55
For example, Jakobsson, R., et al., Acute Myeloid
Leukemia Among Petrol Station Attendants, 48 ARCH. ENVTL. HEALTH
255 (1993), studied the risk of AML within different occupations
using occupational information obtained from the Swedish census
of 1970. The study observed 10 cases of AML in male petrol
station attendants versus 2.8 expected, yielding a statistically
significant odds ratio of 3.6 (95% CI 1.7-6.6). The authors
posited that "[a] reasonable hypothesis was that exposure to
benzene from petrol had contributed to the excess risk of AML,
given that petrol in Sweden has contained up to 5% of benzene for
several decades." The authors later noted, however, that two of
the ten workers with AML had handled other petroleum products.
Further, the district court in Henricksen recognized that "[t]his
study has been criticized for various reasons by other
scientists, including for the discovery that [three] of the
reported AML cases never worked as petrol service attendants and
three others only did so for a short time." Henricksen, 605 F.
Supp. at 1173.
Talbot, EO, et al., Risk of Leukemia as a Result of
Community Exposure to Gasoline Vapors: A Follow-Up Study, 111
ENVTL. RES. 597 (2011), examined the risk of leukemia and AML in
residents of a Pennsylvania community affected by a gasoline
spill in the 1990s. The study produced statistically significant
SIRs of 7.69 and 11.54 for leukemia and AML, respectively, in the
highest exposure area, which the authors concluded "suggest[s] a
possible association between chronic low level benzene exposure
and increased risk of leukemia among residents" of the gasoline
spill site. The authors noted that "[t]he lack of specific
individual level exposures . . . is a limitation of the study."
43
and his reliance on them makes his opinion unreliable. See Knight,
482 F.3d at 355 ("Even if one of the studies relied on by [the
expert] provided a plausible basis for general causation, the
district court, after weighing the 'reliability' and 'relevance' of
such evidence, finding one or the other lacking, could still reach
the conclusion that the evidence was inadmissible.").
The Court
must examine an expert's overall methodology to determine whether
it is reliable, and not simply accept an otherwise deficient
methodology because there is a scintilla of material that might
arguably support the expert’s opinion. This is especially the case
here because “[i]t is important that a study be replicated in
different populations and by different investigators before a
causal
relationship
scientists.”
is
accepted
by
epidemiologists
and
other
Reference Manual at 604.
Because the Court excludes Dr. Infante's opinion on general
causation and there is no other admissible general causation
evidence in this case, his specific causation testimony is also
inadmissible.
See Knight, 482 F.3d at 351 (stating that a court
may admit specific-causation evidence only after the plaintiff has
produced admissible evidence on general causation).
44
IV. CONCLUSION
For the foregoing reasons, the Court GRANTS defendants' motion
to exclude Dr. Peter Infante.
New Orleans, Louisiana, this 16th day of June, 2015.
___
____________________________________
SARAH S. VANCE
UNITED STATES DISTRICT JUDGE
45
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