Opposition Brief — Bourne, a Minor, by and Through His Parents, Next Friends and Natural Guardians, Bourne v. E.I. Du Pont De Nemours & Co

Supreme Court, U.S.

| FILED

(i) JUN 25 2004

No. 03-1586 |_OFFICE OF THE CLERK

IN THE

Supreme Court of the Anited States

ANDREW BOURNE, a minor by and through

his parents, next friends and natural guardians,

CHRIS BOURNE and MAGGIE BOURNE,

Petitioner,

E.I. DUPONT DE NEMOURS & COMPANY,

Respondent.

On Petition for a Writ of Certiorari to the

United States Court of Appeals

for the Fourth Circuit

RESPONDENT’S BRIEF IN OPPOSITION

DAVID B. THOMAS PATRICK W. LEE *

ALLEN, GUTHRIE, MCHUGH, CLIFTON S. ELGARTEN

& THOMAS, PLLC WILLIAM L. ANDERSON

500 Lee Street, East EMMA K. BURTON

Suite 800 CROWELL & MORING LLP

Charleston, W.Va. 25301 1001 Pennsylvania Avenue, N.W.

(304) 345-7250 Washington, DC 20004-2595

(202) 624-2500

* Counsel of Record Counsel for Respondent

WILSON-EPES PRINTING Co., INC. — (202) 789-0096 - WASHINGTON, D. C. 20001

m=] BEST AVAILABLE COPY

QUESTION PRESENTED

Whether the United States Court of Appeals for the Fourth

Circuit correctly affirmed the district court’s decision to

exclude expert testimony where that testimony was based on

speculative extrapolations from in vivo and in vitro studies

that failed to meet the reliability and relevance standards

under Federal Rule of Evidence 702.

(i)

ii

CORPORATE DISCLOSURE STATEMENT

PURSUANT TO RULE 29.6

Respondent E.I. du Pont de Nemours and Company

(“DuPont”) has no parent company, and no publicly held

company owns 10% or more of DuPont's stock. DuPont is a

publicly traded corporation listed on the New York Stock

Exchange.

TABLE OF CONTENTS

PRE OP © PRE EEEY EN ee csnscsessreversessnsscsrsercessosornvenses

RULE 29.6 CORPORATE DISCLOSURE

._s SRSIETETN SESE Sa

Il.

THE DISTRICT COURT PROPERLY EXER-

CISED ITS “GATEKEEPER” FUNCTION IN

FINDING THE PROPOSED METHOD OF

EXTRAPOLATION OF HUMAN TERATO-

GENICITY FROM SINGLE-SPECIES, HIGH

DOSAGE GAVAGE RAT TESTS AND IN

VITRO TESTS UNRELIABLE AND LACK-

oo i a ite ES EE ES eee aD

THE PETITION INCORRECTLY ASSERTS

THAT THE COURT OF APPEALS

CREATED A RULE REQUIRING EPIDE-

MIOLOGY TO BE THE BASIS FOR

EXPERT OPINION TESTIMONY CON-

CERNING CAUSATION IN TOXIC TORT

THERE IS NO CONFLICT BETWEEN TH

DECISION OF THE COURT OF APPEALS

IN THIS CASE AND ANY OTHER

IT siiclidisii eran icdioniniarentntendanerensiniedeumuninanaiien

I actin cin charisshcvsecinsainkaiAbiounboniencwecabaivnsetin

(iii)

10

14

iv

TABLE OF AUTHORITIES

CASES

Ambrosini v. Labaraque, 101 F.3d 129 (D.C. Cir

1996)....ccccssscsssscccssssssssesseessneeessesesseessenssnsnsensoes®

Benedi v. McNeil-P.P.C., Inc., 66 F.3d 1378 (4th

Cir, 1995)....cccccccccoscsssesevsersccnvereseessessrsensvsennesavers

Bourne y. E.L DuPont de Nemours & Co., 189 F.

Supp. 2d 482 (S.D.W. Va. 2002)...

Bourne v. E.L DuPont de Nemours, No. 02 1469,

slip op. (4th Cir. Jan. 27, 2004) (per curium)....

Brock v. Merrell Dow Pharm., Inc., 874 F.2d 307

(Sth Cir.), modified on reh’g, 884 F.2d 166

(1989)......cssccsssessssseeessscecsereensseseersssseneesseaneseceess

Cavallo v. Star Enterprise, 100 F.3d 1150 (4th

Cir. 1996).......ccccccssscsscvesssenccenseesesossssoncessnsesesenes

Daubert v. Merrell Dow Pharm., Inc., 43 F.3d

1311 (Oth Cir, 1995) ....ceceseeeseeeeseeeeseeeetenneeeees

Daubert v. Merrell Dow Pharm., Inc., 509 U.S.

579 (1993)..ccsccscssesseseeseeeereeeeeeseeeesesssersneeneneeneenes

DePyper y. Navarro, No. 83-303467-NM, 1995

WL 788828 (Mich. Cir. Ct. Nov. 27, 1995),

aff'd, No. 191949, 1998 WL 1988927 (Mich.

NOv. 6, 1999) .....scccsccssscsssesesseesreesseeseesessonsnesseeens

Ealy v. Richardson-Merrell, Inc., 897 F.2d 1159

(D.C. Cir. 1990)....cccceceeeeeereseeseeseeeeeteeenenenenenenes

Elkins v. Richardson-Merrell, Inc., 8 F.3d 1068

(6th Cir. 1993) ....secsceceeceeeeeerenseeseeeeseeneneneneneenes

Ferebee y. Chevron Chemical Co., 736 F.2d

1529 (D.C. Cir. 1984) ...ceceeeseereeseseeeeseseneenenees

Kumho Tire Co. v. Carmichel, 526 U.S. 137

(1999).....cccssssssesecssssseeeeseeeteeessessenessessenseseeneesees

Lynch v. Merrell-National Lab., 830 F.2d 1190

(Ast Cir, 1987)... ccccceseecesetseseesereeseneeneenennensens

National Bank of Commerce v. Dow Chem. Co.,

965 F. Supp. 1490 (E.D. Ark. 1996), aff'd, 133

F.3d 1132 (8th Cir. 1998)... eeeeseesseeereeereenees

Page

#2, 13

11

passim

2

12

6

12

A SD

Vv

TABLE OF AUTHORITIES—Continued

Page

Oxendine v. Merrell Dow Pharm., Inc., No. 82-

1245, 1996 WL 680992 (D.C. Super. Ct. Oct.

Dh, RR i iccimcnsitticrintiimnmomaen 6

Raynor v. Merrell Pharm, Inc., 104 F.3d 137]

SC. C8, FIM ivkcccitniimiomumaanand 12

Richardson v. Richardson-Merrell, Inc., 857 F.2d

S23 Le, TB hicosetectinicmcerniniseaicn 1Z, ¥2

Turpin v. Merrell Dow Pharm., Inc., 959 F.2d

ESOP Cite Cle. FIED encccteerecesirtvceiaramnnis 12, 13

Wade-Greaux v. Whitehall Labs., Inc., 874 F.

Supp. 1441 D.V.1., aff'd, 46 F.3d 1120 (3d Cir.

PG niciccrcieeioninnncnnvpaaiiaddanaaimmtien 6, 11-12

Wilson v. Merrell Dow Pharm., 893 F.2d 1149

CFO Che, FRI ic esiccciexeperncsannipcinscriicnrseneconcoen 12

RULE

Pen. TB TR rccicccsiiccemmncaan: 1,15

OTHER AUTHORITIES

Robert L. Brent, Utilization of Animal Studies to

Determine the Effects and Human Risks of

Environmental Toxicants (Drugs, Chemicals,

and Physical Agents), Pediatrics 113:984, 987

CDG iin scisisiinaniviaidencncnaviniciesiisaananmnamimenie 6-7, 11

James L. Schardein, Chemically Induced Birth

Defects (3d ed. Rev. 2000) ...........c.cssrsressssscesees 6, 11

Anthony R. Scialli, 4 Clinical Guide to Repro-

ductive and Developmental Toxicity (1992)......4, 6, 11

Thomas H. Shepard, “Proof” of Human

Teratogenicity, Teratology 50: 97-98 (1994)..... 6, 11

Thomas H. Shepard, Catalog of Teratogenic

Agents (10th €d. 2001)......cccsesoscsorvseessesserreseassees 6, 11

Thomas H. Shepard, Catalog of Teratogenic

Agents (Sth ed. 1998)..............ccscrcccrcssereseerenseses 6

vi

TABLE OF AUTHORITIES—Continued

Page

James G. Wilson, Embryotoxicity of Drugs in

Man, in the Handbook of Teratology (1977)

(James C. Wilson and F. Clarke Fraser, eds.).... 1]

IN THE

Supreme Court of the United States

No. 03-1586

ANDREW BOURNE, a minor by and through

his parents, next friends and natural guardians,

CHRIS BOURNE and MAGGIE BOURNE,

Petitioner,

Vv.

E.I. DUPONT DE NEMOURS & COMPANY.

Respondent.

On Petition for a Writ of Certiorari to the

United States Court of Appeals

for the Fourth Circuit

RESPONDENT?’S BRIEF IN OPPOSITION

STATEMENT OF THE CASE

This is a products liability case in which Petitioner Andrew

Bourne alleges that his ocular and other birth defects were

caused by his mother’s dermal exposure to Benlate while she

was pregnant. Benlate is a plant fungicide manufactured by

DuPont and sold worldwide for more than 30 years.

Pursuant to Federal Rule of Evidence 702, DuPont

moved to exclude the testimony of Petitioner’s causation

experts, Drs. Howard and Tackett. DuPont explained that

Drs. Howard’s and Tackett’s asserted methodology for deter-

mining the human teratogenicity of a substance was specula-

2

tive, scientifically invalid, unreliable, and not relevant. Fol-

lowing briefing, and agreement by the parties that the record

was complete and a hearing was not needed, the district court

granted DuPont’s motion without a hearing.

In a Memorandum Order dated January 11, 2002, the dis-

trict court held that Petitioner’s experts’ method of attempting

to extrapolate causation of human birth defects from single-

species, high dose gavage animal (rat) and in vitro (cell

culture) studies was neither reliable nor relevant. Petitioner

then requested, without objection from DuPont, that the

evidentiary deposition of an epidemiologist, Dr. Ozonoff—

another designated expert of Pefitioner—be made a part of

the record and considered by the court. After granting

Petitioner's request and considering Dr. Ozonoffs testi-

mony,’ the district court reissued its Memorandum Order,

revised in minor respects to reflect its further consideration of

Dr. Ozonoff’s testimony, and granted DuPont’s motion to

exclude on the same basis set forth in its original order. See

Bourne v. E.I. DuPont de Nemours & Co., 189 F. Supp. 2d

482, 496-501 (S.D.W. Va. 2002), Pet. App. at 71-84. Absent

proof of causation for Petitioner’s claim, the district court

granted DuPont’s motion for summary judgment and dis-

missed the case.

Petitioner appealed to the United States Court of Appeals

for the Fourth Circuit. The court of appeals concluded that in

“excluding the proffered testimony, the district court properly

exercised its ‘gate-keeper’ function by focusing on the

methodology employed by the expert rather than the conclu-

sions they reached ... we can not say that the district court

abused its discretion.” See Bourne v. E.1. DuPont de

Nemours, No. 02-1469, slip op. at 6 (4th Cir. Jan. 27, 2004)

' As the January 11, 2002, order reflects, the district court had already

considered Dr. Ozonoffs views (based on an earlier discovery

deposition). See January 11, 2002 Memorandum Order at 21-23.

3

(per curium), Pet. App. at 7. On that basis the Fourth Circuit

affirmed the decision of the district court excluding the

testimony of Drs. Howard and Tackett. /d. Petitioner filed a

petition for rehearing which was denied on February 23,

2004.

This petition followed.

REASONS FOR DENYING WRIT

The Court should decline to grant the petition for a writ of

certiorari. The district court properly exercised its “gate-

keeper” function in finding that the Petitioner's experts’

proposed method of extrapolation of human teratogenicity

from single-species, high dosage gavage rat tests and in vitro

tests was unreliable and lacked “fit.” This case does not

present the question that Petitioner advertises—even assu:a-

ing that such a question would warrant certiorari. Contrary to

Petitioner’s assertions, the court of appeals’ decision does not

require “positive” epidemiology as a basis for expert opinion

testimony concerning causation in a toxic tort case. Even if

the court of appeals had required “positive” epidemiology in

this case, such a holding would not conflict with the decisions

of other federal courts of appeal in teratology cases.

I. THE DISTRICT COURT PROPERLY EXER-

CISED ITS “GATEKEEPER” FUNCTION IN

FINDING THE PROPOSED METHOD OF

EXTRAPOLATION OF HUMAN. TERATO-

GENICITY FROM SINGLE-SPECIES, HIGH

DOSAGE GAVAGE RAT TESTS AND IN VITRO

TESTS UNRELIABLE AND LACKING IN “FIT”.

As the district court observed, “Drs. Howard and Tackett

have derived their general causation theory, that benomyl is

teratogenic to humans, based solely upon in vivo rat gavage

studies and in vitro tests.” Bourne, 189 F. Supp. 2d at 495,

Pet. App. at 71. The district court then identified the scien-

4

tific and factual shortcomings of the methodology that they

had used. These included:

Significant differences between species in terato-

genic response to chemicals. /d. at 496-97, Pet. App.

73-75.

Petitioner's experts’ disavowal of and inability to

explain the results of benomyl tests on two other

animal species—rabbit and mouse—that showed no

ocular birth defects in the offspring. /d. at 496-97,

Pet. App. at 73-75.

The absence of tests on species closely related to

humans. /d. at 496-97, Pet. App. at 72-75.

The use of high dosages in the rat tests, far in ex-

cess of human exposures. /d. at 498-99, Pet. App. at

76-78.

In vitro test exposures at high levels for 24 hours, far

in excess of human exposures. /d. at.498-99, Pet.

App. at 76-78.

A mode of exposure, direct injection into the stom-

achs of rats, unlike the human dermal exposure that

was at issue in this case. /d. at 498-500, Pet. App. at

76-83.

Petitioner’s experts’ unfounded rejection of human

data contrary to their position. /d. at 493, 495, 497,

Pet. App. at 72-73, 75-77, 80-83.

The district court discussed the fact that teratologists (and

other courts) have rejected in vivo animal and in vitro tests as.

a basis for finding human teratogenicity in birth defect cases.

2

? See also Anthony R. Scialli, A Clinical Guide to Reproductive and

Developmental Toxicity at 60-61 (1992) (teratologists do not accept posi-

tive results in animal tests as proof of human teratogenicity because there

are (1) species differences in the pharmacokinetics/handling of chemicals

(difference in absorption, distribution, metabolism, elimination); (2) spe-

cies differences in fetal and embryo susceptibility, and (3) differences in

5

Id. at 496-97, Pet. App. at 73-77. This analysis of the facts,

science, and law relating to the methodology employed by

Petitioner’s experts—extrapolation of human teratogenicity

from single-species, high dosage gavage animal tests and in

vitro tests—is precisely the kind of “gate-keeping”

contemplated by this Court’s Daubert decision. The court of

appeals opinion recognizes that the district court’s “well-

reasoned opinion” reflects the type of “gate-keeping” that this

Court’s decisions mandate. See Bourne, slip. op. at 6, Pet.

App. at 7.

Il. THE PETITION INCORRECTLY ASSERTS

THAT THE COURT OF APPEALS CREATED A

RULE REQUIRING EPIDEMIOLOGY TO BE

THE BASIS FOR EXPERT OPINION TESTI-

MONY CONCERNING CAUSATION IN TOXIC

TORT CASES.

Petitioner asserts that this case presents the question

“whether Daubert requires positive epidemiology to support a

finding of causation in a toxic tort case.” Petition at 7. That

assertion misstates the holdings of both the district court and

the court of appeals. Neither court held that epidemiological

evidence was a prerequisite to expert opinion testimony on

causation in such cases.

The district court did not require epidemiological evidence

as a basis of expert opinion testimony offered as proof of

causation in this case. Rather, the district court focused on

the specific methodology employed by Drs. Howard and

Tackett—extrapolation of human teratogenicity from rat

gavage tests and extrapolation of human teratogenic dose

levels from in vitro cell tests—and held that such extrapola-

tion was unreliable and irrelevant. Bourne, 189 F. Supp. 2d

at 496, 497-54 (Pet. App. 72, 73-84). Epidemiological evi-

the dose and route of exposure (e.g., gavage v. dermal) as between

humans and laboratory test animals).

6

dence would present a way of bridging the gap the court

correctly saw in Petitioner's methodology in assessing

causation, but nowhere did it hold that epidemiology was

mandated. It held that what was presented by Petitioner’s

experts was not acceptable because it was unreliable and

irrelevant. The court of appeals, without referring to epi-

demiology at all, approved the district court opinion as “well

reasoned” an4 held that that “the district court properly exer-

cised its ‘gate-keeper’ function by focusing on the method-

ology employed by the experts rather than the conclusion

they reached.” Bourne, slip. op. at 6, Pet. App. at Sa

3 While it was not the basis for the district court’s exclusion of

Drs. Howard’s and Tackett’s opinion testimony or the basis for the court

of appeals’ decision affirming that exclusion, the absence of any human

evidence of Benlate teratogenicity reflects a major methodological failure

in the derivation of Petitioner’s experts’ opinions. The generally ac-

cepted, peer reviewed, methodology employed by clinical teratologists

requires positive human studies to establish human teratogenicity of a

substance, as numerous trial courts have recognized. See Wade-Greaux v.

Whitehall Labs., Inc., 874 F. Supp. 1441, 1451 (D.V.L), aff'd, 46 F.3d

1120 (3d Cir. 1994); National Bank of Commerce v. Dow Chem. Co., 965

F. Supp. 1490, 1497 n. 14, 1499-1500 (E.D. Ark. 1996), aff'd, 133 F.3d

1132 (8th Cir. 1998); DePyper v. Navarro, No. 83-303467-NM, 1995 WL

788828, at *32 (Mich. Cir. Ct. Nov. 27, 1995), aff'd, No. 191949, 1998

WL 1988927 (Mich. Nov. 6, 1999); Oxendine v. Merrell Dow Pharms.,

Inc., No. 82-1245, 1996 WL 680992, at *7 (D.C. Super. Ct. Oct. 24,

1996).

Daubert and Kumho establish that, in assessing the reliability of expert

testimony, a trial court should look to the principles of the discipline or

field in which the opinion is being offered. Kumho Tire Co. v. Carmichel,

526 US. 137, 152 (1999); Daubert v. Merrell Dow Pharm., Inc., 509 U.S.

579, 591-95 (1993); see also Cavallo v. Star Enterprise, 100 F.3d 1150,

1159 (4th Cir. 1996) (Daubert factors “require that the methodology and

reasoning used by a witness have a significant place in the discourse of

experts in the field.”) The field of teratology requires epidemiology for a

determination that a substance is a human teratogen. See, ¢.g., Thomas

H. Shepard, “Proof” of Human Teratogenicity, Teratology 50: 97-98

(1994); Thomas H. Shepard, Catalog of Teratogenic Agents at xxiv (10th

7

The Petition does not address the actual holding of the

court of appeals or the holdings of the district court which

were affirmed by the court of appeals. Nor does the Petition

state a question for review that arises from those decisions.

The lack of connection between the arguments of Petitioner

and the holdings of the courts below is apparent from the

following comparison:

‘Actual District Court Hold-

ings Affirmed By The Cou

Petitioner’s Argument As To

What The District Court and

Court of Appeals Held Of Appeals .

“Nonetheless, the principal “(T]he extrapolations of

reason the District Court

excluded the testimony of

Drs. Howard and Tackett

was their reliance on

Dr. Ozonoff's conclusion

that these epidemiological

studies were flawed and

irrelevant.” (Petition at 8)

“fY]Jet the District Court

Drs. Howard and Tackett,

from high-dosage, single

species in vivo testing and

lengthy benomyl exposure

in vitro testing, to conclude

that benomyl is a human

teratogen and to establish

the levels at which it is

alleged to be teratogenic,

are neither reliable, pursu-

ant to the first prong of

Daubert, nor relevant, un-

der the second prong.”

used Ozonoff’s analysis of

the existing Benlate epide-

miology as the primary

ed. 2001); James L. Schardein, Chemically Induced Birth Defects, at

43-44 (3d ed. Rev. 2000), quoting Thomas H. Shepard, Catalog of

Teratogenic Agents (8th ed. 1998); Robert L. Brent, Utilization of Animal

Studies to Determine the Effects and Human Risks of Environmental

Toxicants (Drugs, Chemicals, and Physical Agents), Pediatrics 113:984,

987 (2004). If the district court and the court of appeals had recognized

such a requirement for expert testimony on the human teratogenicity of a

substance, that ruling would have been correct and would not have been

an abuse of discretion. The lower courts in this case did not, however,

reach that issue and they need not have done so. It was a sufficient basis

for their decisions that they examined the methodology in fact used by

Drs. Howard and Tackett, rejecting it as unreliable and irrelevant.

basis to exclude Howard

and Tackett’s testimony.”

(Petition at 13)

“But in affirming the Dis-

trict Court’s decision, the

Fourth Circuit, . . . implic-

itly overruled its own ear-

lier decisions holding that

epidemiological — support

was not a prerequisite to

establishing causation in

toxic tort cases.” (Petition

at 7)

(Bourne, 189 F. Supp. 2d

at 496, Pet. App. at 72)

“The court concludes that

Drs. Howard and Tackett

have failed to offer suffi-

cient support for the other-

wise suspect single species

in vivo tests and in vitro

tests to render method-

ologically sound an extra-

polation of human terato-

genicity.” (Bourne, 189

F. Supp. 2d at 497-98, Pet.

App. at 76)

“Moreover, the rat gavage

studies and the in vitro

tests relied upon by

Drs. Howard and Tackett,

using injections of high-

levels of benomyl directly

into the stomach of rats

and high-level in vitro

dosing of cells of both rats

and humans in benomy] for

24 hours, do not ‘fit? with

the facts of the case as

alleged.” (nuurne, 189

F.Supp. 2d at 498, Pet.

App. at 76)

The district court, in arriving at its conclusions, discussed

some of the reasons that teratologists do not accept extra-

polation of human teratogenicity from animal and in vitro

tests. See Bourne, 189 F. Supp. 2d at 496-98, Pet. App. at 72-

77; see also discussion, supra, at 3-4. In the context of that

discussion, the district court noted as well that, “in the

Ere

9

absence of other strong indicators of the reliability of in vivo

and in vitro tests, including supporting epidemiological

studies, testing on closely related species, and the use of

comparable dosages, courts have overwhelmingly found un-

reliable the methodology of extrapolating human teratogenic-

ity from in vivo and in vitro tests.” Bourne, 189 F. Supp. 2d

at 496, Pet. App. at 73. In other words, the court properly

recognized that the type of testing done here involving ultra-_

high doses given to rats by gavage, is not generally accepted

as a basis for extrapolating human teratogenicity under the

standards of the relevant discipline. Rather, teratologists

require additional indicia of reliability, including epidemic-

ology. See supra notes 2 and 3. The district court’s factual

observations that teratologists and other courts reject extrapo-

lation of human teratogenicity from single-species, high

dosage gavage animal tests and in vitro tests are not holdings

by the district court that epidemiology is an essential basis for

expert opinion offered to prove causation in a case involving

toxic torts; they are recognition that such extrapolation is

not generally accepted in the field of teratology Signifi-

cantly, Petitioner cites no case under Daubert an Rule 702

challenging the court’s observation that other courts, like

teratologists, do not accept such extrapolation.

Nor was the district court’s additional observation that the

existing Benlate epidemiological evidence is contrary to

Petitioner’s position, (id. at 497 & n.23, Pet. App. at 75 &

n.23), a holding that epidemiology is affirmatively required to

demonstrate causation."

* The district court’s determination that Drs. Howard’s and Tackett’s

rejection of Benlate epidemiological studies—which find no association

between Benlate exposure and birth defects—was unfounded, Bourne,

189 F. Supp. 2d at 493, Pet. App. 30, does not constitute a holding by the

district court that epidemiology is a prerequisite to proof of causation.

The district court ruling that Drs. Howard’s and Tackett’s rejection of

epidemiology that is contrary to their position is unfounded—the sole

focus of the Petition—is irrelevant to whether Petitioner’s experts could

10

The court of appeals’ affirmance of the district court’s

actual holdings does not convert these separate factual obser-

vations by the district court into rulings by the court of

appeals that epidemiology is a prerequisite to opinion testi-

mony on causation in toxic tort cases. Petitioner has mis-

characterized the basis for the district court’s holding on the

unreliability and lack of “fit” of Drs. Howard’s and Tackett’s

methodology. The Petition ignores the fact that the opinion of

the court of appeals says nothing, explicitly or implicitly,

about the place of epidemiology in proving causation in toxic

tort cases. Petitioner’s stated questions for review do not arise

from and are unrelated to the court of appeals decision in

this case.

Ill. THERE IS NO CONFLICT BETWEEN THE

DECISION OF THE COURT OF APPEALS IN

THIS CASE AND ANY OTHER CIRCUIT.

There is no circuit conflict.

First, the court of appeals’ decision in this case does not

require that expert testimony concerning causation in toxic

tort cases be based on “positive” epidemiology. The appellate

opinion says nothing on that subject. Nor does its affirmance

of the district court decision implicitly or “effectively”

suggest that result as Petitioner argues. The district court

decision excluding the testimony of Drs. Howard and Tackett

is based on the fact that their methodology—extrapolation of

human teratogenicity from single-species, high dosage

gavage animal tests and in vitro tests—is unreliable and

irrelevant; it is not based on the failure of the experts in this

case to rely on “positive” epidemiology. The opinion of the

district court does not say or imply that the court is requiring

properly extrapolate human teratogenicity from rat and in vitro tests.

Such extrapolation is not a reliable methodology in the field of teratology

and the district court properly so held. See id. at 497 n.21, Pet. App. at

75 n.21.

11

experts to base their opinions on “positive” epidemiology in

order to prove causation in toxic tort cases. The court of

appeals decision cannot, therefore, be in conflict with

decisions of other circuits regarding lack of need for “posi-

tive” epidemiology in some toxic tort cases.

Second, even if the Fourth Circuit had required “positive”

epidemiology, such a holding would not conflict with the

decisions of other federal courts of appeal in feratology cases.

In evaluating the circuit conflict issue that Petitioner seeks to

raise, it is important to distinguish teratology cases from other

toxic tort cases. Some fields of science or medicine involved

in other toxic torts may not in fact rely heavily or at all on

epidemiology.” That is not the case with respect to teratology.

The generally accepted methodology for determining human

teratogenicity of a substance involves: (1) identifying a

specific pattern of malformation associated with exposure to

the substance; (2) consistent human studies (epidemiology)

and occurrence of the specific pattern of malformation;

(3) repeated positive animal tests in multiple species at doses

and routes of exposure similar to those involved in human

exposures; (4) in vitro tests identifying a mechanism of

action; and (5) biological plausibility that the agent’s mecha-

nism of action could cause the pattern of defects associated

with exposure.”

* See, e. g., Benedi v. McNeil-P.P.C., Inc., 66 F.3d 1378 (4th Cir. 1995)

(where issue was_whether liver damage was caused by Tylenol/alcohol

consumption or by herpes, epidemiology was unnecessary and a meth-

odology consisting of identifying a history of Tylenol/alcohol use, labora-

tory tests showing presence of Tylenol in blood, and microscopic exami-

nation of liver tissue samples to confirm whether tissue damage was or

was not characteristic of damage caused by Tylenol was acceptable for

diagnostic purposes concerning causation).

-° See Thomas H. Shepard, “Proof” of Human Teratogenicity, Tera-

tology 50:97-98 (1994); Thomas H. Shepard, Catalog of Teratogenic

Agents at xxiv (10th ed. 2001); Robert L. Brent, Utilization of Animal

Studies to Determine the Effects and Human Risks of Environmental

12

The case law of the various circuits is uniform in acknowl-

edging that epidemiology is an essential basis for expert

opinion testimony concerning causation in feratology cases.’

Thus, even if the Fourth Circuit decision in this case were

interpreted to require that expert opinion in the field of

teratology be supported in part by epidemiology, that inter-

pretation would create no conflict among the circuits.

Third. none of the cases cited by Petitioner demonstrate

any controversy about the role of epidemiology in teratology

cases. With two exceptions, those cases do not involve

expert testimony in the field of teratology. One exception is

Ambrosini® While it is a teratology case, it provides

Petitioner no support for his argument that there is a conflict

in the circuits. In Ambrosini, there was “positive” epidemiol-

ogy indicating an association between the type of drug in-

volved, a progestin, and birth defects; the plaintiff's expert so

asserted in an affidavit filed in opposition to a motion for

Toxicants (Drugs, Chemicals, and Physical Agents), Pediatrics 103:984,

987 (2004); James L. Schardein, Chemically Induced Birth Defects at 44

(3d ed. Rev. 2000); Anthony R. Scialli, 4 Clinical Guide to Reproductive

and Developmental Toxicology at 60, 65, 84 (1992); James C. Wilson,

Embryotoxicity of Drugs in Man, in the Handbook of Teratology at 311-

12 (1977) (James C. Wilson and F. Clarke Fraser, eds.); Wade-Greaux,

Inc., 874 F. Supp. at 1450-55; National Bank of Commerce v. Dow Chem.

Co., 965 F. Sups. at 1497 n. 14, 1499-1500; see also cases cited in note 7,

infra.

’ See Raynor v. Merrell Pharm, Inc., 104 F.3d 1371, 1375 (D.C. Cir.

1997); Daubert v. Merrell Dow Pharm., Inc., 43 F.3d 1311, 1321 (9th Cir.

1995) (Daubert II); Ealy v. Richardson-Merrell, Inc., 897 F.2d 1159 (D.C.

Cir. 1990); Wilson v. Merrell Dow Pharm., 893 F.2d 1149, 1154 (10th

Cir. 1990); Brock v. Merrell Dow Pharm., Inc., 874 F.2d 307, 313 (Sth

Cir.), modified on reh'g, 884 F.2d 166 (1989), Richardson v. Richardson-

Merrell, Inc., 857 F.2d 823, 830-31 (D.C. Cir. 1988); Lynch v. Merrell-

National Lab., 830 F.2d 1190 (Ist Cir. 1987); cf Elkins v. Richardson-

Merrell, Inc., 8 F.3d 1068, 1071 (6th Cir. 1993); Turpin v. Merrell Dow

Pharm., Inc., 959 F.2d 1349, 1360 (6th Cir. 1992).

8 4mbrosini v. Labaraque, 101 F.3d 129 (D.C. Cir 1996).

13

summary judgment.’ Ambrosini specifically relied on the fact

the plaintiff experts had based their conclusions concerning

causation of birth defects on “human” (epidemiological)

evidence.'!° Thus, anything the Ambrosini court may have

said about the lack of necessity for epidemiology’ | was dicta

unrelated to the decision in the case. Indeed, in Ambrosini

the D.C. Circuit discussed its prior Richardson decision with

approval.'? That case held that animal tests, in vitro tests, and -

recalculated epidemiology studies that are at odds with the

underlying epidemiology studies are not relied on by experts

in the field of teratology.

The only other teratology case cited by Petitioner to

suggest a conflict in the circuits, Turpin, is not about “posi-

tive” epidemiology or about failure of plaintiff experts to rely

on “positive” epidemiology to prove causation in a teratology

case.'> The epidemiology in that case was 35 negative stud-

ies relied on by defendant to demonstrate no causal relation

between the drug Bendectin and birth defects. Turpin did not

hold that plaintiff experts need not rely on epidemiology;

rather, Turpin held that defendant’s epidemiology studies in

that case were not so conclusive that they warranted grant of

summary judgment for defendant. “

The Fourth Circuit has not yet addressed the issue whether

epidemiology is a required basis of expert testimony concern-

ing causation in a teratology case. Neither of the Fourth

Circuit cases cited by Petitioner to suggest a conflict within

9 Id. at 132, 136, 139.

10 Td. at 141.

'! The material quoted by Petitioner as if it were from Ambrosini is

actually from another case, Ferebee v. Chevron Chemical Co., 736 F.2d

1529 (D.C. Cir. 1984), which is not a teratology case.

\2 Ambrosini, 101 F.3d at 138, 140.

'3 Turpin v. Merrell Dow Pharm., Inc., 959 F.2d 1349 (6th Cir. 1992).

* Id. at 1353-57.

14

the Fourth Circuit’s own case law—Westberry and Benedi—

are teratology cases. Thus, there would be no conflict in the

Fourth Circuit’s own case law even had the court of appeals

in this case required that expert testimony in teratology cases

be based in part on epidemiology."

CONCLUSION

The petition for writ of certiorari should be denied.

Respectfully submitted,

DAVID B. THOMAS PATRICK W. LEE *

ALLEN, GUTHRIE, MCHUGH, CLIFTON S, ELGARTEN

& THOMAS, PLLC WILLIAM L. ANDERSON

500 Lee Street, East EMMA K. BURTON

Suite 800 CROWELL & MORING LLP

Charleston, W.Va. 25301 1001 Pennsylvania Avenue, N.W.

(304) 345-7250 Washington, DC 20004-2595

(202) 624-2500

* Counsel of Record Counsel for Respondent

June 25, 2004

'S Petitioner's argument (at 20-21) that the “disparate decision” of the

Florida Supreme Court in Castillo “cr[ies] out for intervention by this

Court” to provide guidance and promote uniformity ignores the fact that

Castillo was decided under the Frye standard while the decision in this

case was guided by Rule 702 and the Daubert standard. Uniformity of

decisions under Frye and under Daubert cannot be expected because of

the differences in the two rules and thus, Petitioner's argument from

Castillo does not support a writ of certiorari.

I |