Hollander v. Sandoz Pharmaceuticals Corp.

                                                                       F I L E D
                                                                 United States Court of Appeals
                                                                         Tenth Circuit
                                    PUBLISH
                                                                        MAY 10 2002
                  UNITED STATES COURT OF APPEALS
                                                                     PATRICK FISHER
                                                                             Clerk
                               TENTH CIRCUIT



 DEE HOLLANDER and DON
 HOLLANDER,

             Plaintiffs - Appellants,
       v.                                              No. 00-6135
 SANDOZ PHARMACEUTICALS
 CORPORATION, a New Jersey
 corporation; SANDOZ, LTD., a
 foreign corporation; and HCA
 HEALTH SERVICES OF
 OKLAHOMA, INC., an Oklahoma
 corporation, d/b/a/ Presbyterian
 Hospital,

             Defendants - Appellees.


        APPEAL FROM THE UNITED STATES DISTRICT COURT
           FOR THE WESTERN DISTRICT OF OKLAHOMA
                     (D.C. NO. 96-CV-756-T)


Steven R. Hickman (James E. Frasier with him on the briefs), of Frasier, Frasier
& Hickman, LLP, Tulsa, Oklahoma, for the Plaintiffs-Appellants.

Grant J. Esposito of Mayer, Brown & Platt, New York, New York, for Defendant-
Appellee Sandoz Limited; Joe G. Hollingsworth (Katharine R. Latimer and Kirby
T. Griffis of Spriggs & Hollingsworth, Washington, D. C., for Defendant-
Appellee Sandoz Pharmaceuticals Corporation; Richard M. Eldridge and Thomas
E. Steichen of Eldridge Cooper Steichen & Leach, P.L.L.C., Tulsa, Oklahoma, for
Defendants-Appellees Sandoz Pharmaceuticals Corporation and Sandoz Limited,
with them on the brief).
David A. Branscum (Glenn D. Huff with him on the brief) of Foliart, Huff,
Ottaway & Bottom, Oklahoma City, Oklahoma for the Defendant-Appellee HCA
Health Services of Oklahoma, Inc.


Before EBEL and HENRY , Circuit Judges, and       ROGERS , District Judge.    *




HENRY , Circuit Judge.


      Dee and Don Hollander filed this products liability action in the District

Court for Oklahoma County alleging that Parlodel, a drug manufactured by

Sandoz Pharmaceuticals Corporation (“Sandoz”), now known as Novartis

Pharmaceuticals Corporation, and distributed by HCA Health Services of

Oklahoma, Inc., doing business as Presbyterian Hospital (“Presbyterian

Hospital”), caused Ms. Hollander to suffer an intracerebral hemorrhage shortly

after she gave birth to the Hollanders’ second child. After the Oklahoma County

District Court dismissed the Hollanders’ claim against Presbyterian Hospital, the

remaining defendants removed the case to the federal district court.

      The federal district court denied the Hollanders’ motion to remand the case

to state court. It rejected the Hollanders’ arguments that it lacked jurisdiction

over the remaining claims and that the defendants’ removal petition was untimely.

Subsequently, the federal district court dismissed the defendant Sandoz, Ltd. with


      *
         The Honorable Richard D. Rogers, United States District Judge for the
District of Kansas, sitting by designation.

                                         -2-
prejudice, reasoning that the holding company had its principal place of business

in Switzerland and that the court lacked personal jurisdiction over it.

      Finally, applying Daubert v. Merrell Dow Pharmaceuticals, Inc., 509 U.S.

579 (1993), the federal district court ruled that the Hollanders’ expert testimony

regarding the causal connection between Parlodel and intracerebral hemorrhages

lacked the necessary reliability and was therefore inadmissible. See Hollander v.

Sandoz Pharms. Corp., 95 F. Supp. 2d 1230, 1238-39 (W.D. Okla. 2000). As a

result, the court granted summary judgment to Sandoz.

      The Hollanders now appeal those rulings, arguing that: (1) the federal

district court lacked subject matter jurisdiction and therefore erred in denying

their motion to remand the case to the Oklahoma state court; (2) the court erred in

dismissing their claim against the defendant Presbyterian Hospital; (3) the court

abused its discretion in ruling that the testimony of their experts was not

sufficiently reliable to be admissible; (4) the court erred in granting summary

judgment to Sandoz; and (5) the district court erred in dismissing their claim

against Sandoz, Ltd., with prejudice.

      For the reasons set forth below, we conclude that the federal district court

had subject matter jurisdiction. We further hold that the court did not abuse its

discretion in finding that the Hollanders’ expert testimony was not sufficiently

reliable and that the court did not err in granting summary judgment to Sandoz.


                                         -3-
However, we agree with the Hollanders that the federal district court should have

dismissed their claim against Sandoz, Ltd., without prejudice. In light of these

conclusions, we do not address the Hollanders’ challenge to the dismissal of their

claim against Presbyterian Hospital.

      Accordingly, we affirm the district court’s judgment against the Hollanders

and in favor of Presbyterian Hospital and Sandoz. We remand the Hollanders’

claim against Sandoz, Ltd., so that it may be dismissed without prejudice.



                                I. BACKGROUND

      On July 23, 1990, Ms. Hollander gave birth by cesarean section to a healthy

baby boy at Presbyterian Hospital in Oklahoma City. Because Ms. Hollander did

not want to breast feed her son, her obstetrician prescribed a fifteen day course of

Parlodel, to be taken in two 2.5 mg doses per day.

      Parlodel is manufactured by Sandoz. The drug’s active ingredient is

bromocriptine mesylate, a compound derived from ergot (a naturally occurring

substance made from a fungus that attacks cereal grains). The compound blocks

the production of prolactin, a hormone that triggers the secretion of milk in

postpartum women. The Federal Drug Administration (FDA) approved Parlodel

for the suppression of post-partum lactation in 1980, and approximately 9 million

women in the United States have taken it for that purpose. See Siharath v.


                                         -4-
Sandoz Pharms. Corp., 131 F. Supp. 2d 1347, 1349 (N.D. Ga. 2001) (discussing

the history of Parlodel). Parlodel is also prescribed for several other disorders,

including acromegaly (a disease caused by hypersecretion of the pituitary growth

hormone), Parkinson’s disease, and various diseases involving the excessive

production of prolactin.

        Ms. Hollander received her first dose of Parlodel at 6:00 p.m. on July 23,

1990. About two hours later, her blood pressure increased sharply to 180/90. On

the following day, she received her second and third doses of Parlodel, and her

blood pressure returned to the normal range. She continued to take two 2.5 mg

doses of the drug each day. Presbyterian Hospital discharged her on July 27,

1990.

        On the evening of July 28, 1990, Ms. Hollander complained of a severe

headache. By the following morning, she could neither speak nor move her right

side. At Presbyterian Hospital, a CT scan revealed that Ms. Hollander had

suffered an intracerebral hemorrhage in the left basal ganglia area of her brain.

Ms. Hollander’s treating physicians were puzzled as to the cause. One of them

noted that her stroke resembled those caused by hypertension but added that Ms.

Hollander had no history of the disorder. Clinical information revealed no




                                          -5-
pregnancy-related disorders involving hypertension, such as eclampsia or

preeclampsia. 1

      On August 1, 1990, Ms. Hollander’s condition deteriorated. As a result,

her physicians performed an emergency left frontal craniotomy and removed an

intracerebral hematoma. Ms. Hollander slowly improved. She remained in the

hospital for over three weeks and then transferred to a rehabilitation center.

      The Hollanders filed this action against Sandoz, Sandoz, Ltd., and

Presbyterian Hospital in May 1995 in the District Court for Oklahoma County.

They alleged that Ms. Hollander’s stroke was caused by Parlodel, that the drug

was unreasonably dangerous to the ordinary consumer when used as a lactation

suppressant, and that Sandoz, Sandoz, Ltd., and Presbyterian Hospital had failed

to warn of the dangers of the drug. They further alleged that Ms. Hollander had

suffered permanent injuries.

      Presbyterian Hospital filed a motion to dismiss the Hollanders’ claims,

arguing that a hospital could not be held strictly liable for providing a drug

prescribed by a doctor. The Oklahoma County District Court granted Presbyterian


      1
          Preeclampsia involves the “[d]evelopment of hypertension with
albuminuria or edema between the 20th week of pregnancy and the end of the 1st
week postpartum.” The Merck Manual, § 18 at 2057 (17th ed. 1999).
“Albuminuria” refers to “the presence in the urine of serum albumin.” Dorland’s
Illustrated Medical Dictionary at 42 (28th ed. 1994). Eclampsia involves
“[c]onvlusive seizures or coma without other etiology occurring in the same time
period.” The Merck Manual, § 18 at 2057.

                                         -6-
Hospital’s motion to dismiss in an oral ruling at an August 25, 1995 hearing. It

issued a written ruling on May 10, 1996.

      Sandoz filed a notice of removal on May 10, 1996. The Hollanders then

filed a motion to remand the case to the Oklahoma state court, which the district

court denied. See Aplt’s App. vol. I, at 116-17 (District Court Order, filed June

12, 1996). Subsequently, the court dismissed the Hollanders’ claims against

Sandoz, Ltd., reasoning that it was a holding company incorporated in

Switzerland with its principal place of business there, that it had no office,

manufacturing, distribution, or sales facilities in the United States, and that it did

not advertise here. As a result, the court concluded that it lacked personal

jurisdiction over Sandoz, Ltd., and it dismissed with prejudice the claims against

the company. See id. at 354 (District Court Order, filed Dec. 17, 1996).

      The dispute between the Hollanders and Sandoz involves issues that have

been raised in other litigation as well as in regulatory proceedings. See Kuhn v.

Sandoz Pharms. Corp., 14 P.3d 1170, 1174 (Kan. 2001) (describing a

“decade-long disagreement between Sandoz and the [FDA] concerning the use of

Parlodel for the prevention of physiologic lactation”). In 1984 (four years after

first approving the drug as a lactation suppressant), the FDA reported that “the

labeling of Parlodel (bromocriptine) is being revised to reflect reports of

postpartum hypertension, seizures, and cerebrovascular accidents.” Aplt’s App.


                                           -7-
vol. IV-B, at 2401-02 (FDA Drug Bulletin, vol. 14, no. 1, at 3-4). The FDA

explained that it had received seven reports of hypertension alone, seven reports

of seizures, and three cases of cerebrovascular accidents (including one fatality).

Because approximately 500,000 women had used Parlodel to suppress postpartum

lactation, however, the significance of those reports was difficult to assess. The

FDA expressly acknowledged that “[a] cause and effect relationship has not been

established.” Id.

      Sandoz eventually modified the Parlodel package insert to include

information about these cases. However, the company noted that hypertension,

seizures, strokes, and myocardial infarctions regularly occur in postpartum women

who are not treated with bromocriptine. Thus, it maintained, “the number of

cases reported to Sandoz is less that one would expect even in the absence of any

drug effect.” Id. at 2448 (Letter from Sandoz’s Executive Director of Sales, Aug.

20, 1987).

      Over the next few years, the FDA continued to receive reports of adverse

reactions to Parlodel. Sandoz commissioned a study by Epidemiologic Resources,

Inc., regarding the relationship between Parlodel and strokes and seizures (the

“ERI study”). See Aplt’s App. vol. II-D, at 1361-1532 (Kenneth Rothman, et al.,

“An Epidemiologic Evaluation of the Possible Relation Between Bromocriptine,




                                         -8-
Puerperal Seizures and Strokes,” (Sept. 30, 1988)); 2 Siharath, 131 F. Supp. 2d at

1356-57 (discussing the ERI study). Although the ERI study did not find a causal

connection between strokes and seizures, the FDA concluded that the study failed

to allay concerns regarding the drug’s association with seizures and involved too

few individuals to adequately characterize the risk of stroke.

      The FDA further concluded that the possibility that Parlodel might cause

serious adverse reactions in some patients outweighed the limited benefits

associated with its use. As a result, it requested all manufacturers to remove the

indication for lactation suppression from the Parlodel label. Initially, Sandoz

refused to comply with the FDA’s request, arguing that Parlodel should not be

used routinely but should be available in specific circumstances recommended by

physicians. Not satisfied with this position, the FDA initiated formal procedures

for withdrawing its prior approval for the labeling of Parlodel. The FDA

explained its position as follows:

             FDA now has new information suggesting that therapeutic
             use of bromocriptine for the prevention of physiological
             lactation may lead to serious adverse experiences,
             including death and paralysis, in a small but significant
             number of patients. Patients at high risk of experiencing
             these serious adverse experiences cannot be adequately
             predetermined. In light of the limited benefit of using


      2
         The purpureum is “the period from the end of the third stage of labor
until the involution of the uterus is complete, usually lasting 3 to 6 weeks.”
Dorland’s Illustrated Medical Dictionary at 1386.

                                        -9-
            bromocriptine for the prevention of lactation, and the
            effectiveness and lack of serious adverse effects of
            conservative treatments such as breast binding with or
            without mild analgesics, the risk that bromocriptine may
            cause a serious adverse effect in a postpartum woman is
            unacceptable.
                   Accordingly, the Director concludes that the
            potential risks associated with the use of bromocriptine for
            the prevention of physiological lactation outweigh its
            limited benefits and bromocriptine is no longer shown to
            be safe for use in preventing physiological lactation.

59 Fed. Reg. 43347, 43351 (Aug. 24, 1994). Sandoz then agreed to FDA’s

proposal to withdraw the indication for the suppression of postpartum lactation.

      Following the FDA’s approval of Parlodel as a lactation suppressant,

professional medical journals began to publish reports regarding women who had

suffered heart attacks and strokes after taking the drug. For example, one of the

Hollanders’ expert witnesses described two patients who had suffered from

cardiac dysfunction, seizures, and cerebral vasospasm. See Kenneth Kulig,

“Bromocriptine Associated Headache: Possible Life Threatening

Sympathomimetic Intersection,” Obstetrics and Gynecology, 72: 941(1991)

(Aplt’s App. vol. IV-B, at 2444-46). Another expert published case histories

concerning women who had suffered from heart attacks. See, e.g., Leslie Iffy, et

al., “Acute Myocardial Infarction in the Puerperium in Patients Receiving

Bromocriptine,” American Journal of Obstetrics and Gynecology, vol. 155, No. 2,

at 371-72 (1986) (Aplt’s App. vol. IV-D, at 2976-77). Medical researchers also


                                        -10-
published numerous articles reporting the effects of bromocriptine in animals.

See Siharath, 131 F. Supp. 2d at 1366-69 (discussing animal studies), Glastetter v.

Novartis Pharms. Corp., 107 F. Supp. 2d 1015, 1037-1041 (E.D. Mo. 2000)

(same), aff’d, 252 F.3d 986, 991 (8th Cir. 2001). Some of the studies involved

dogs, rats, and pithed animals. See id.; see also Aplt’s App. vol. I-A, at 369-376

(Sandoz’s statement of material facts, filed July 15, 1999) (discussing animal

studies). Some researchers concluded that, contrary to the Hollanders’ allegations

regarding the effect of bromocriptine on Ms. Hollander, the drug actually

decreases blood pressure. See, e.g, Saad Lahlou & Pierre Demenge,

“Contribution of Spinal Dopamine Receptors to the Hypotensive Action of

Bromocriptine in Rats,” Journal of Cardiovascular Pharmacology, vol. 18, 317-

323 (1991) (Aplt’s App. vol. II-E, at 1646-54).

      As the discussion in the scientific literature continued, the controversy over

Parlodel made its way to the courts. In 1994, a Kentucky jury awarded $968,512

in compensatory damages and $1,000,000 in punitive damages to a woman who

alleged that Parlodel had caused her stroke. See Aplt’s App. vol. IV-A, at 2171

(Judgment in Roberts v. Betts, no. 89-CI-653-V, 25th Judicial Dist., Pulaski Cir.

Ct., July 20, 1994). A Kentucky appellate court affirmed that judgment in an

unpublished opinion. See id. at 2175-78. In contrast to the Roberts case, several

recent decisions have rejected claims that Parlodel has caused strokes and heart


                                        -11-
attacks when prescribed as a post-partum lactation suppressant, concluding that

the scientific evidence supporting these claims was not sufficiently reliable under

Daubert. 3 However, several other decisions have reached the opposite

conclusion. 4 See generally Mark Hansen, “When Expert Testimony Fails the Test:

District Courts Disagree on what Defines Causation Evidence in Drug Disability

Cases,” 88 ABA Journal 22 (Jan. 2002) (stating that “[an] Alabama magistrate’s

decision brought to eight the number of products liability suits over Parlodel that

have survived a so-called Daubert challenge to the admissibility of the plaintiffs’

causation evidence [b]ut [an] Illinois judge’s ruling--tantamount to an order of

summary judgment for the defense--marked the seventh trial or appellate decision

to exclude such evidence”).

      In support of their contention that Parlodel caused Ms. Hollander’s stroke,

the Hollanders relied primarily on the testimony of three experts: (1) Dr. Kenneth


      3
        See Glastetter v. Novartis Pharms. Corp., 252 F.3d 986, 989 (8th Cir.
2001); Caraker v. Sandoz Pharms. Corp., 172 F. Supp. 2d 1046 (S.D. Ill. 2001);
Siharath, 131 F. Supp. 2d 1347 (N.D. Ga. 2001); Brumbaugh v. Sandoz Pharms.
Corp., 77 F. Supp. 2d 1153, 1155, (D. Mont. 1999).
      4
          See Brasher v. Sandoz Pharms. Corp., 160 F. Supp. 2d 1291 (N.D. Ala.
2001); Globetti v. Sandoz Pharms. Corp., 111 F. Supp. 2d 1174 (N.D. Ala. 2000);
Aplt’s App. vol. V, at 3184-3213 (Tr. of unpublished ruling in Kittelson v.
Sandoz Pharms. Corp., No. 98-2277 (D. Minn. March 2, 2000) (denying motion to
exclude scientific testimony as unreliable); Kuhn, 14 P.3d 1179-85 (applying the
test for admissibility set forth in Frye v. United States, 293 F. 1013 (D.C. Cir.
1923) and concluding that there were genuine issues of material fact as to whether
Parlodel caused a patient’s death).

                                        -12-
Kulig, a physician who is board-certified in toxicology and emergency medicine

and who has served as the Chairman of the Pharmacy and Therapeutics

Committee and Director of the Porter Regional Toxicology Center at Porter

Adventist Hospital in Denver, Colorado, and as an associate clinical professor in

the Division of Emergency Medicine and Trauma in the Department of Surgery at

the University of Colorado Health Sciences Center; (2) Dr. Leslie Iffy, M.D., a

professor in the Department of Obstetrics and Gynecology of the University of

Medicine and Dentistry of New Jersey; and (3) Dr. Pedro A. Jose, M.D., Ph.D., a

Professor of Pediatrics, Physiology, and Biophysics at Georgetown University and

an expert on the role of dopamine and dopaminergic drugs on the development of

hypertension.

      The parties offered deposition testimony, affidavits, expert reports, and

transcripts of testimony from other cases involving Parlodel. In general, the

experts’ theory was that in certain women, Parlodel causes vasoconstriction (a

narrowing of the blood vessels) and hypertension (high blood pressure).

Vasoconstriction and hypertension, the experts reasoned, can then cause strokes,

as they did in the case of Ms. Hollander.

      In his written report, Dr. Kulig explained that he had reviewed Ms.

Hollander’s medical records, medical literature regarding bromocriptine and other

ergot alkaloids, FDA documents, and marketing, promotional and research


                                        -13-
material complied by Sandoz. He concluded that Ms. Hollander suffered “an

intracerebral hemorrhage secondary to ergot induced vasospasm resulting in blood

vessel rupture in her brain.” Aplt’s App. vol. II-A, at 652 (Dr. Kulig’s Sept. 22,

1998 report, at 3). He added, “It is my opinion with a reasonable degree of

medical certainty that Mrs. Hollander’s stroke was caused by the drug

bromocriptine, and had the patient not been taking the drug, she would not have

had a stroke.” Id. at 653. According to Dr. Kulig, the fact that bromocriptine

could cause strokes was well know to Sandoz at the time that Ms. Hollander

began taking the drug. Id. at 652.

      In an affidavit in another case involving Parlodel, Dr. Kulig provided a

more detailed explanation as to how he had reached his conclusions. See Aplt’s

App. vol. II-E, at 1742-59 (Dr. Kulig’s affidavit in Railey v. Novartis

Pharmaceuticals Corp., 94-1440 (C.D. Ill.)). He noted that bromocriptine is an

ergot, “a class of drugs with known molecular structures and many common

properties,” including the tendency to cause vasoconstriction. See id. at 1745

(stating that “[o]ne needs only to look at the package inserts from Sandoz

regarding other ergot alkaloids it manufactures to understand that

vasoconstriction is indeed the core property of ergot alkaloids”). Bromocriptine

differs from the naturally occurring ergot alkaloid alpha ergocriptine only in that




                                        -14-
the molecule has an additional bromine atom attached to the second carbon atom

of the basic ergot ring. See id.

      Dr. Kulig explained the significance of the structural differences between

bromocriptine and other ergot alkaloids as follows:

             Although the adding of a bromine atom to the core nucleus
             makes the drug in some patients a vasodilator (the first
             dose may cause a precipitous fall in blood pressure,
             another fact that makes the drug unsafe in the post-partum
             period), it is misleading and inaccurate to suggest that the
             drug can never cause vasoconstriction or hypertension in
             any person. While the addition of a bromine atom to a
             very large organic molecule may change the
             pharmacokinetics and pharmacological dynamics of a drug,
             it would be unlikely to change the core properties of an
             ergot alkaloid from being a vasoconstrictor to a vasodilator
             in all cases. Clinical studies, epidemiologic evidence and
             adverse drug reaction experience with this drug indicates
             that vasoconstriction with bromocriptine unquestionably
             occurs, as would be expected based on the fact that it is an
             ergot that can cause ergotism.

Id. at 1745-46.

      Dr. Kulig also discussed several other categories of evidence on which he

had relied in forming his opinion. These included the pharmacological and

toxicological properties of bromocriptine, studies of the relationship between

bromocriptine and hypertension, and case reports concerning adverse reactions.

      As to pharmacology, Dr. Kulig explained that bromocripitne is “a dopamine

agonist.” Id. In other words, the drug stimulates the release of dopamine, a

neurotransmitter. Dr. Kulig added that bromocriptine is also a “dopamine-1

                                         -15-
antagonist,” inhibiting the effects of dopamine at specific “D-1” receptors. Id.

According to Dr. Kulig, dopamine is a well known vasoconstrictor. However,

activation of the “D-1” dopamine receptors results in vasodilation. Thus, the fact

that bromocriptine stimulates the release of dopamine and that it inhibits the D-1

dopamine receptors is consistent with the drug causing vasoconstriction.

      Moreover, Dr. Kulig reported that bromocriptine “has a very long beta

elimination half-life of about 50 hours.” Id. at 1747. That means that a steady

state is not achieved in someone taking the drug twice a day until about ten days

after leaving the hospital. As a result, one would not expect women who have

taken the drug to suppress post-partum lactation to develop hypertension and

vasospasm until after their discharge from the hospital.

      With regard to hypertension, Dr. Kulig referred to three studies. In the

first, commissioned by Sandoz, nineteen percent of patients demonstrated

increases in blood pressure after taking bromocriptine. In the second study,

published by the FDA in 1984, six out of seven patients who developed

hypertension while on bromocriptine regained normal blood pressure after they

stopped taking the drug. Finally, a study by Dr. Dorothy Watson 5 found that

women with pregnancy-induced hypertension had a higher incidence of post-


      5
        Watson, D.I., et al., “Bromocriptine Mesylate for Lactation Suppression:
A Risk for Postpartum Hypertension?” Obstetrics and Gynecology, 74(4): 573-
576 (1989) (Aplt’s App. vol. II-D, at 1596-97).

                                        -16-
partum hypertension after taking the drug than those women not receiving

bromocriptine. See id. at 1748-49 (stating that “[t]his case control study provides

important evidence that bromocriptine causes post-partum hypertension in women

who had pregnancy-induced hypertension prior to delivery”).

      Finally, Dr. Kulig discussed the adverse reactions to bromocriptine that had

been spontaneously reported to the FDA and Sandoz. These reactions included

hypertension, seizures, strokes, and myocardial infarction. Although he

acknowledged that these reports did not establish causation, he presented them as

an important factor to be considered along with the other scientific evidence.

      In addition to Dr. Kulig, the Hollanders also relied on the opinion of Dr.

Leslie Iffy. See Aplt’s App. vol. II-A, at 733-739 (Dr. Iffy’s written report, July

25, 1997). Dr. Iffy concluded that there was “an overwhelming probability” that

Ms. Hollander’s stroke was caused by bromocriptine. Id. at 738. He listed five

factors that supported his opinion: (1) Ms. Hollander had normal blood pressure

during a prior pregnancy but displayed an episode of hypertension when she took

Parlodel during her first childbirth; (2) she suffered episodes of hypertension

during her second pregnancy and immediately after the birth of her second child;

“[t]his being the case, she was predisposed for the hypertensive effect of

bromocriptine”; (3) when she took Parlodel after the second pregnancy, her blood

pressure increased, “in all probability a bromocriptine effect”; (4) “[t]he time of


                                         -17-
occurrence of the cerebral hemorrhage (sixth day postpartum) was highly

characteristic of bromocriptine related catastrophic side effects”; and (5) “[a]part

from her moderate smoking habit, the patient had no identifiable predisposing

factors for cerebral hemorrhage[;] [t]he absence of evidence of congenital defect

at the site of the hemorrhage further emphasizes the lack of predisposing factors

on the part of the patient.” Id. Dr. Iffy added that, in his view, Sandoz was

aware of the dangers of Parlodel at the time that Ms. Hollander suffered her

stroke. See id. at 739.

      The third expert on whom the Hollanders relied—Dr. Pedro Jose—set forth

a more specific theory of causation. In his written report, Dr. Jose stated, “I think

that the hypertension (which caused the stroke) is probably due to Parlodel; the

hypertension would not have happened if Parlodel was not prescribed.” Aplt’s

App. vol. II-A, at 842 (Dr. Jose’s report, Jan. 23, 1998). Dr. Jose acknowledged

that bromocriptine often decreases blood pressure. However, in deposition

testimony he explained that in instances in which extra-cellular fluid volume is

increased—as is the case in pregnancy—and in which the activity of the

sympathetic nervous system is decreased, bromocriptine has the “paradoxical

effect of increasing blood pressure.” Id. at 801.

      After conducting discovery, Sandoz filed a motion to exclude the opinion

testimony offered by the Hollanders’ experts on the grounds that the testimony


                                         -18-
was insufficiently reliable under Daubert. In the same motion, Sandoz requested

the court to grant summary judgment in its favor. It argued that, in the absence of

the unreliable opinion testimony, the Hollanders could not demonstrate that there

were controverted issues of material fact on the issue of whether Parlodel caused

Ms. Hollander’s stroke.

      The federal district court granted Sandoz’s motion to exclude the

Hollanders’ expert testimony as well as its motion for summary judgment. See

Hollander, 95 F. Supp. 2d at 1235-39. The court set forth four reasons in support

of its evidentiary ruling.

      First, the court observed that the Hollanders’ experts were unable to

explain the physiological mechanism by which Parlodel caused vasoconstriction

and ensuing hypertension and strokes. The court explained that “Dr. Kulig could

only list possible mechanisms for Parlodel causing hypertension,” that “Dr. Jose

could not cite any studies or tests that proved his hypothesis that bromocriptine

might cause high blood pressure,” and that “Dr. Iffy also classified his opinion

that Parlodel caused Mrs. Hollander’s stroke as being a hypothesis, which is not

held by a medical degree of certainty.” See id. at 1235-36 (internal quotation

marks omitted).

      Second, the court reasoned that the kinds of case reports on which the

Hollanders relied have been repeatedly rejected as a scientific basis for


                                        -19-
establishing causation. It stated: “The problems with case reports and adverse

drug experience reports were acknowledged by Dr. Iffy—because they are not

controlled studies and do not eliminate confounding variables, the reported effect

or injury could be due to some other cause than Parlodel.” See id. at 1237.

      Third, the court found that the fact that bromocriptine belongs to a class of

compounds (ergot alkaloids) that have been shown to cause hypertension did not

constitute reliable causation evidence. The court observed that the Hollanders

had failed to refute Sandoz’s evidence that “[t]he chemical diversity of ergot

alkaloids corresponds to the diversity of the biological activities of these

compounds.” Id. at 1238 (internal quotation marks and emphasis omitted).

      Fourth, the animal studies on which the Hollanders’ experts relied were too

dissimilar to the facts of this case. “The studies relied upon involved different

drugs, did not test the systemic effect of the drug, some of the animals were

anaesthetized, and they were neither pregnant nor post-partum. . . . Doctors Jose

and Kulig were unaware of any controlled animal studies in which bromocriptine

caused an increase in blood pressure.” Id. at 1238 (internal citations omitted).

      In light of its conclusion that the Hollanders’ opinion testimony was

insufficiently reliable under Daubert, the district court briefly assessed the state

of the record absent that testimony. It concluded that, without expert opinion

testimony, the Hollanders could not demonstrate that Parlodel caused Ms.


                                         -20-
Hollander’s stroke. The court therefore granted Sandoz’s motion for summary

judgment.



                                  II. DISCUSSION

      In this appeal, the Hollanders primarily challenge the district court’s

assessment of their evidence that Parlodel caused Ms. Hollander’s stroke. In

particular, they challenge both the district court’s application of Daubert to

exclude their expert opinion testimony and the district court’s assessment of the

record absent that testimony. They maintain that “[w]hether or not the experts are

allowed to give their ultimate opinion, there is sufficient evidence that a jury

could find in [their] favor on the issue of causation.” Aplt’s Br. at 28. The

Hollanders also present several other challenges to the district court’s rulings.

      We begin our analysis by addressing the Hollanders’ argument that the

district court lacked subject matter jurisdiction and therefore erred in denying

their motion to remand the case to the Oklahoma state court. Because we

conclude that the federal district court had subject matter jurisdiction, we then

turn to the Hollander’s arguments regarding scientific evidence. Finally, we

address their argument that the district court erred in dismissing their claims

against Sandoz, Ltd., with prejudice.




                                         -21-
                                   A. Jurisdiction

      Focusing on several alleged defects in the removal procedure, the

Hollanders argue that the federal district court erred in denying their motion to

remand. As a result, they contend, that court lacked jurisdiction to adjudicate the

case, and the judgment in favor of the defendants should be vacated so that the

case may be heard in the Oklahoma state court.

      In light of the Supreme Court’s decision in Caterpillar, Inc. v. Lewis, 519

U.S. 61 (1996), we need not address the Hollanders’ specific arguments. In

Caterpillar, the Court held that “a district court’s error in failing to remand a case

improperly removed is not fatal to the ensuing adjudication if federal

jurisdictional requirements are met at the time judgment is entered.” Id. at 64;

see also Feichko v. Denver & Rio Grande W. R.R. Co., 213 F.3d 586, 590-91

(10th Cir. 2000) (discussing Caterpillar). The Court reasoned that, despite

deficiencies in the removal process, “[to] wipe out the adjudication postjudgment,

and return to state court a case now satisfying the federal jurisdictional

requirements, would impose an exorbitant cost on our dual court system, a cost

incompatible with the fair and unprotracted administration of justice.”

Caterpillar, 519 U.S. at 77.

      Here, as the defendants observe, complete diversity existed between the

remaining parties at the time that the federal district court entered judgment: the


                                          -22-
Hollanders resided in Arkansas and the defendant Sandoz was a Delaware

corporation with its principal place of business in New Jersey. Thus, the alleged

deficiencies in the removal procedure do not divest the district court of subject

matter jurisdiction. We therefore proceed to the merits.



     B. Admissibility of the Hollanders’ Experts’ Testimony Under Daubert

      Rule 702 of the Federal Rules of Evidence provides:

             [i]f scientific, technical, or other specialized knowledge
             will assist the trier of fact to understand the evidence or to
             determine a fact in issue, a witness qualified as an expert
             by knowledge, skill, experience, training, or education,
             may testify thereto in the form of an opinion or otherwise,
             if (1) the testimony is based upon sufficient facts or data,
             (2) the testimony is the product of reliable principles and
             methods, and (3) the witness has applied the principles and
             methods reliably to the facts of the case.


Fed. R. Evid. 702.

      In Daubert, the Supreme Court concluded that Rule 702 superseded the

“general acceptance” standard for the admissibility of scientific evidence first set

forth in Frye, 293 F. at 1014. 6 Under Daubert, when faced with a proffer of

expert scientific testimony, a district court “must determine at the outset, pursuant


      6
        The Frye test required district courts to exclude evidence when the
underlying scientific principles were not “sufficiently established to have gained
general acceptance in the particular field in which [they belong].” Frye, 293 F. at
1014.

                                         -23-
to [Fed. R. Evid.] 104(a), whether the expert is proposing to testify to (1)

scientific knowledge that (2) will assist the trier of fact to understand or

determine a fact in issue.” Daubert, 509 U.S. at 592. Thus, under Daubert, the

district court performs an important gatekeeping role in assessing scientific

evidence. See Macsenti v. Becker, 237 F.3d 1223, 1230-34 (10th Cir. 2001)

(discussing the district court’s gatekeeping function under Daubert).

       The Daubert standard ensures that the proffered evidence is both “reliable”

and “relevant.” See Daubert, 509 U.S. at 589. Reliability is determined by

assessing “whether the reasoning or methodology underlying the testimony is

scientifically valid.” Id. at 592-93. Relevance depends upon “whether [that]

reasoning or methodology properly can be applied to the facts in issue.” Id. at

593.

       We review the district court’s application of Daubert to exclude expert

opinion evidence for an abuse of discretion. See General Electric v. Joiner, 522

U.S. 136, 143 (1997); Mitchell v. Gencorp Inc., 165 F.3d 778, 780 (10th Cir.

1999). Thus, we must afford substantial deference to the district court’s

application of Daubert. See Kumho Tire Co. v. Carmichael, 526 U.S. 137, 152

(1999) (“the trial judge must have considerable leeway in deciding in a particular

case how to go about determining whether particular expert testimony is

reliable”); Joiner, 522 U.S. at 143 (noting that the court of appeals “failed to give



                                          -24-
the trial court the deference that is the hallmark of abuse-of-discretion review”).

Under the abuse of discretion standard, “a trial court’s decision will not be

disturbed unless the appellate court has a definite and firm conviction that the

lower court made a clear error of judgment or exceeded the bounds of permissible

choice in the circumstances.” McEwen v. City of Norman, Okla., 926 F.2d 1539,

1553-54 (10th Cir. 1991); see also Summers v. Missouri Pacific R.R. System, 132

F.3d 599, 603 (10th Cir. 1997) (stating that, under the abuse of discretion

standard, “[w]e will not disturb the trial court’s determination “absent a distinct

showing it was based on a clearly erroneous finding of fact or an erroneous

conclusion of law or manifests a clear error of judgment”).

       Here, the Hollanders focus on the district court’s application of the

“reliability” prong of the Daubert inquiry. They invoke two methods of causation

analysis: one promulgated by Sandoz’s Drug Monitoring Center and the other set

forth by a professor of medical statistics, Sir Austin Bradford Hill. See Aplt’s

App. vol. IV-B, at 2378-79 (Sandoz’s classifications of evidence of causation);

vol. IV-D, at 2949-52 (Bradford Hill, “The Environment and Disease: Association

or Causation?,” Proceedings of the Royal Society of Medicine, vol. 58 no. 5 (May

1965)). 7

       7
         Under the Sandoz scheme, there are four main categories of causation:
(a) not related; (b) remote; (c) probable; and (d) definite. The Hollanders focus
on the standard for “probable” causation.
                                                                       (continued...)

                                         -25-
      Relying primarily on Dr. Kulig’s testimony, the Hollanders maintain that

his opinion that Parlodel caused Ms. Hollander’s stroke comports with these

general standards of causation analysis. Accordingly, they reason, Dr. Kulig’s

testimony is sufficiently scientific to be admissible under Daubert. See Aplt’s Br.

at 24 (“[I]t cannot be gainsaid that Dr. Kulig’s methodology—how he takes the

information available and analyzes it in a scientific manner—is good science and

would be helpful to a jury of laymen.”).

      Additionally, the Hollanders note that Dr. Kulig criticized some of

Sandoz’s own evidence on scientific grounds. They point to his testimony that

the studies invoked by Sandoz do not demonstrate that there is an increased risk

of stroke in the post-partum period generally. As a result, they maintain, the

evidence is disputed as to whether Ms. Hollander’s stroke may be explained by


      7
        (...continued)
       An adverse reaction is considered to be “probably related to a drug” if the
reaction: (1) “occurs within a reasonable time interval following the
administration of the drug”; (2) “could not readily be attributed to the patient’s
clinical condition/underlying disease, concomitant therapy, or to environmental or
toxic factors”; (3) “follows a known pattern of response to the drug”; and (4)
“disappears or improves following cessation of treatment or dose reduction.” See
Aplt’s App. vol. IV-B, at 2378-79.
            Sir Bradford Hill sets forth nine factors that should be considered
“before deciding that the most likely interpretation [of the association] is
causation.” These factors are: strength, consistency, specificity, temporality,
dose response, biological plausibility, coherence, experimental evidence and
analogy. See Aplt’s App. vol. IV-D, at 2949-52 (Bradford Hill paper); vol. II-E,
at 1751-55 (Dr. Kulig’s affidavit). Dr. Kulig applies the Bradford Hill criteria in
reaching his opinion that Parlodel caused Ms. Hollander’s stroke.

                                           -26-
this generally increased risk during the post-partum period, as Sandoz contends,

rather than by her taking Parlodel.

      Finally, the Hollanders contend that Drs. Kulig, Iffy, and Jose applied the

methodology generally employed by experts in the relevant fields. Thus, by

relying on scientific principles, professional publications, animal studies,

differential diagnoses, and case reports, these experts did what Daubert requires:

they grounded their conclusions in “the methods and procedures of science” rather

than “subjective belief or unsupported speculation.” Daubert, 509 U.S. at 590.

      In order to assess the Hollanders’ argument, we begin with an overview of

the standards for reliability under Daubert and its progeny. Then we turn to an

examination of the scientific opinion evidence at issue here.



1. Scientific Reliability Under Daubert

      Under Daubert’s reliability prong, “an inference or assertion must be

derived by the scientific method . . . [and] must be supported by appropriate

validation--i.e. ‘good grounds,’ based on what is known.” Id. The Supreme

Court listed four nonexclusive factors that the trial court may consider in

assessing reliability: (1) whether the opinion at issue is susceptible to testing and

has been subjected to such testing; (2) whether the opinion has been subjected to

peer review; (3) whether there is a known or potential rate of error associated



                                          -27-
with the methodology used and whether there are standards controlling the

technique’s operation; and (4) whether the theory has been accepted in the

scientific community. See id.

      The list is not exclusive, and district courts applying Daubert have broad

discretion to consider a variety of other factors. See Kumho Tire, 526 U.S at 150

(“[W]e can neither rule out, nor rule in, for all cases and for all time the

applicability of the factors mentioned in Daubert, nor can we now do so for

subsets of cases categorized by category of expert or by kind of evidence. Too

much depends upon the particular circumstances of the particular case at issue.”).

Generally, the district court should focus on the experts’ methodology rather than

the conclusions that they generate. See Daubert, 509 U.S. at 595. However, the

experts’ conclusions are not immune from scrutiny: “A court may conclude that

there is simply too great an analytical gap between the data and the opinion

proffered.” Joiner, 522 U.S. at 147 (“[N]othing 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.”). Regardless of

the specific factors at issue, the purpose of the Daubert inquiry is always the

same: “[t]o make certain that an expert, whether basing testimony upon

professional studies or personal experience, employs in the courtroom the same




                                          -28-
level of intellectual rigor that characterizes the practice of an expert in the

relevant field.” 8 Kumho Tire, 526 U.S. at 152. 9



2. The Hollanders’ Scientific Evidence

      We assess the Hollanders’ challenge to the district court’s Daubert ruling

by examining the opinions of their three primary experts: Drs. Kulig, Iffy, and

Jose. As to each expert, we must assess the grounds that they provide for their

opinion that Parlodel causes stroke, asking whether those grounds involve “the




      8
         As Justice Breyer has observed, the requirement that the district court
assess reliability and relevance under Daubert “will sometimes ask judges to make
subtle and sophisticated determinations about scientific methodology and its
relation to the conclusions an expert witness seeks to offer--particularly when a
case arises in an area where the science itself is tentative or uncertain, or where
testimony about general risk levels in human beings or animals is offered to prove
individual causation.” Joiner, 522 U.S. at 147-48 (Breyer, J., concurring). Even
though judges usually do not have the formal scientific training to assist them in
making these decisions, there are Rules of Evidence and Civil Procedure that may
assist them in making the necessary determinations. “Among these techniques are
an increased use of pretrial conference authority [pursuant to Fed. R. Civ. P. 16]
to narrow the scientific issues in dispute, pretrial hearings where potential experts
are subject to examination by the court, and the appointment of special masters
and specially trained law clerks.” Id. at 149 (citations omitted).
      9
         Judge Posner has expressed a similar view. “When the Supreme Court in
Daubert told judges to distinguish between real and courtroom science, it was not
with the object of discovering the essence of “science,” if there is such an
essence. The object . . . was to make sure that when scientists testify in court they
adhere to the same standards of intellectual rigor that are demanded in their
professional work.” Rosen v. C-G Corp., 78 F.3d 316, 318 (7th Cir 1996).

                                          -29-
methods and procedures of science,” Daubert, 509 U.S. at 590, and “the level of

intellectual rigor of the expert in the field.” Kumho Tire, 526 U.S. at 152.

       In doing so, we note that the scope of our review is quite narrow: we may

reverse the district court’s ruling only if we conclude that it abused its discretion

in applying Daubert to exclude opinions of the Hollanders’ experts. Because the

district court has discretion to consider a variety of factors is assessing reliability

under Daubert, and because, in light of that discretion, there is not an extensive

body of appellate case law defining the criteria for assessing scientific reliability,

we are limited to determining whether the district court’s application of the

Daubert manifests a clear error of judgment or exceeds the bounds of permissible

choice in the circumstances. See McEwen, 926 F.2d at 1553-54 (discussing

appellate review for an abuse of discretion). Thus, when coupled with this

deferential standard of review, Daubert’s effort to safeguard the reliability of

science in the courtroom may produce a counter-intuitive effect: different courts

relying on the essentially the same science may reach different results. See

generally Federal Judicial Center, Reference Manual on Scientific Evidence 27

(2d ed. 2000) (observing that, in light of the abuse of discretion standard of

review for Daubert determinations of reliability, “in theory judges are free to

select different procedures and apply different factors to a particular expert or

type of expertise than their colleagues do in the same district or circuit” and that



                                          -30-
“[a]s a consequence, similar cases could be resolved differently on the basis of

inconsistent determinations about admissibility”); see also Brasher, 160 F. Supp.

2d at 1298 n.17 (observing that the Eighth Circuit’s decision in Glastetter, 252

F.3d at 989-92, affirming the exclusion of Parlodel evidence as unreliable “does

not necessarily [establish] that an inconsistent holding by this court would

constitute an abuse of discretion”). 10



      a. Similarity to other ergot alkaloids

      We begin our analysis with Dr. Kulig’s testimony that bromocriptine is an

ergot alkaloid. According to Dr. Kulig, this fact supports his theory that

bromocriptine causes vasoconstriction.

      As the district court observed, neither Dr. Kulig nor the Hollanders’ other

experts disputed the fact that bromocriptine has a different chemical structure

than ergot alkaloids known to cause vasoconstriction. Moreover, neither Dr.

Kulig nor the Hollanders’ other experts disputed the scientific literature stating

that small differences in chemical structure may produce substantial differences in

physiological effects.

      10
        Conflicting decisions in the district courts regarding the reliability of
opinion testimony about Parlodel further illustrate this point. Compare Siharath,
131 F. Supp. 2d 1347 (evidence regarding Parlodel’s adverse effects unreliable);
and Brumbaugh, 77 F. Supp. 2d 1153 (same); with Brasher, 160 F. Supp. 2d 1291
(Parlodel evidence reliable); and Globetti v. Sandoz Pharms., Corp., 111 F. Supp.
2d 1174 (N.D. Ala. 2000) (same).

                                          -31-
      In light of these considerations, several courts have agreed with the district

court’s conclusion that the fact that bromocriptine is an ergot alkaloid does not

constitute reliable scientific evidence that it causes vasoconstriction and

associated adverse reactions like heart attacks and strokes. See Glastetter, 252

F.3d at 990 (“[T]his generic assumption that bromocriptine behaves like other

ergot alkaloids carries little scientific value. Even minor deviations in molecular

structure can radically change a particular substance’s properties and

propensities.”); 11 Brumbaugh, 77 F. Supp. 2d at 1156 (“Testimony extending

general conclusions about similar drugs does not meet Daubert’s requirement of

reliability.”); Siharath, 131 F. Supp. 2d at 1363-65 (finding a lack of reliable

evidence that bromocriptine acts like other ergot alkaloids). Moreover, in a

similar case, this circuit has rejected the argument that one chemical’s

resemblance to another known to have deleterious effects constituted reliable

causation evidence. See Mitchell, 165 F.3d at 782 (“Missing from [the plaintiff’s

evidence] is additional testimony explaining what these similarities are and how

the similarities cause the human body to respond to Defendant’s chemicals in a

manner similar to benzene.”).


      11
         The Eighth Circuit also noted that “one leading treatise on medical
toxicology concludes that bromocriptine has no vasoconstrictive properties.”
Glastetter, 252 F. 3d at 990 (emphasis in original) (citing Matthew J. Ellenhorn,
Ellenhorn’s Medical Toxicology: Diagnosis and Treatment of Human Poisoning
1879, table 74-23 (2d ed.1997)).

                                         -32-
      These decisions support the district court’s analysis. Accordingly, the

district court did not abuse its discretion in finding that bromocriptine’s similarity

to other ergot alkaloids constituted an unreliable basis on which to conclude that

the drug causes vasoconstriction and ensuing adverse effects like Ms. Hollander’s

stroke.



      b. Pharmacology of bromocriptine

      In important respects, the Hollanders’ experts’ discussion of the specific

pharmacological properties of bromocriptine is similarly speculative. For

example, Dr. Kulig’s affidavit refers to the drug’s known effects on dopamine and

serotonin, and notes that these neurotransmitters are known to trigger

vasoconstriction and vasospasm. However, although he states that the effect of

Parlodel on serotonin receptors “has been demonstrated in company studies,”

Aplt’s App. vol. II-E, at 1747, Dr. Kulig provides no details on the methodology

or conclusions of these studies. Moreover, the mere fact that Parlodel acts on

serotonin and dopamine receptors does not establish that Parlodel itself, as

opposed to some other agent that triggers either the release of these

neurotransmitters or some other physiological mechanism, causes

vasoconstriction, hypertension, and stroke.




                                         -33-
      The testimony of Dr. Jose (the expert on peripheral dopamine receptors)

reveals similar deficiencies. Although he presented an elegant theory of the way

in which bromocriptine might have the paradoxical effect of causing

vasoconstriction and increased blood pressure, he acknowledged that there were a

number of animal studies that concluded that bromocriptine decreases blood

pressure. Dr. Jose attempted to distinguish these studies by observing that the

specific conditions that he had posited as necessary to trigger the paradoxical

effects of bromocriptine were not present. However, he acknowledged that his

thesis had not been tested. See Aplt’s App. vol. II-A, at 802 (“I have bits and

pieces proving that bromocriptine can increase sodium reabsorption, bits and

pieces that can show that bromocriptine can decrease blood flow; but to put all of

them together [to demonstrate that bromocriptine can cause high blood pressure]

no, that has not been tested.”). Accordingly, the district court did not exercise

manifestly unreasonable judgment in concluding that the opinions of the

Hollanders’ experts did not meet the Daubert reliability standard insofar as those

opinions were based on the pharmacology of bromocriptine.



      c. Studies of hypertension

      Both Dr. Kulig and Dr. Iffy relied on studies regarding the relationship

between bromocriptine and hypertension. Dr. Kulig referred to a 1981 study



                                         -34-
commissioned by Sandoz in which women received the drug to treat amennorrhea-

galactorrhea syndrome. 12 Dr. Kulig states that nineteen percent of those women

reported increases in blood pressure. Both experts invoke a study by

D.I. Watson, which concluded that women with pregnancy-induced hypertension

who then took bromocriptine after giving birth had a higher incidence of

postpartum hypertension than women who did not receive the drug. 13

      Again, it is not an abuse of discretion to conclude that there is “simply too

great an analytical gap” between these studies and the experts’ conclusion that

Parlodel caused Ms. Hollander’s stroke. See Joiner, 522 U.S. at 146. The studies

in question do not directly address the relationship between Parlodel and stroke.

Moreover, the Hollanders presented no expert analysis as to how one might

extrapolate from bromocriptine’s effect on a small group of women with

amennorrhea-galactorrhea syndrome to determine the effect that the drug would

have on women like Ms. Hollander who took the drug as a postpartum lactation

suppressant.




      12
         Amenorrhea refers to an “absence or abnormal stoppage of the menses.”
See Dorland’s Illustrated Medical Dictionary 55. Galactorrhea is the “excessive
or spontaneous flow of milk” or the “persistent secretion of milk irrespective of
nursing.” Id. at 672.
      13
         D.I. Watson, et al., supra, Obstetrics and Gynecology, 74(4): 573-576
(Aplt’s App. vol. II-D, at 1596-97).

                                        -35-
      As to the Watson study, Dr. Iffy admitted that it did not claim a “high

degree of reliability.” Aplt’s App. vol. II-A, at 698. Dr. Iffy acknowledged that,

under the study’s criteria for determining which women had pregnancy-induced

hypertension, Ms. Hollander herself would not qualify. Id. Thus, she was not in

the class of patients whose blood pressure increased after taking Parlodel.



      d. Animal Studies

      According to the Hollanders’ experts, there are certain animal studies that

also provide evidence that bromocriptine may cause vasoconstriction,

hypertension, and stroke. These studies included those performed on isolated

veins, on animals that were unconscious, and on pithed animals. Many involved

large doses of bromocriptine, relatively much greater than the doses taken by Ms.

Hollander.

      Several recent decisions considering these studies have agreed with the

district court’s analysis. The studies suggest only that bromocriptine may act as a

vasoconstrictor in very specific circumstances in certain kinds of animals; the

studies do not constitute reliable evidence that bromocriptine causes strokes. See

Glastetter, 252 F.3d at 991 (noting that one of the plaintiff’s experts concluded

that “not a single animal study had ever concluded that [intracerbral hemorrhage]

was associated with bromocriptine”); Caraker v. Sandoz Pharms. Corp., 172 F.



                                        -36-
Supp. 2d 1046, 1050-51 (S.D. Ill. 2001) (noting that “some [studies] involved

animals that had a steel rod injected down their spinal cord to destroy it so the

animal has no intact nervous system, some involved bromocriptine’s reaction

locally (e.g., in a single isolated vein of an animal) as opposed to a systemic

administration; and some were poorly documented”); Siharath, 131 F. Supp. 2d at

1367-69 (discussing three animal studies in detail and concluding that they did

not constitute a reliable basis for experts’ opinions that Parlodel caused the

plaintiff’s stroke).

       In light of these characteristics of the animal studies, the district court’s

conclusion that they were unreliable does not “exceed[] the bounds of permissible

choice in the circumstances.” McEwen, 926 F.2d at 1553-54. We therefore

discern no abuse of discretion in the court’s analysis.



       e. Case studies and differential diagnosis

       The next methodologies employed by the Hollanders’ experts present a

closer question. “Differential diagnosis” refers to the process by which a

physician “‘rule[s] in’ all scientifically plausible causes of the plaintiff’s injury.

The physician then ‘rules out’ the least plausible causes of injury until the most

likely cause remains.” Glastetter, 252 F.3d at 989 (8th Cir. 2001). The remaining

cause is the expert’s conclusion. Id. In conducting a differential diagnosis,



                                          -37-
physicians often use case reports—“a doctor’s account of a particular patients’

reaction to a drug or other stimulus, accompanied by a description of the relevant

surrounding circumstances.” Id.

      Here, Drs. Kulig, Iffy, and Jose performed a differential diagnosis,

reviewing Ms. Hollander’s medical history and medical records, excluding other

causes of her stroke, and then attributing the stroke to Parlodel. They relied in

part on case reports, both those filed with the FDA and those published in the

professional literature. Dr. Kulig expressed the view that the onset of Ms.

Hollander’s initial symptom (i.e., developing a headache several days after giving

birth) and the timing of her stroke (several days after her discharge from the

hospital) fit a general pattern seen in patients suffering adverse reactions to

Parlodel and was also consistent with the pharmokinetics of the drug.

      With regard to differential diagnoses, courts have reached contrasting

conclusions as to reliability under Daubert. Compare Westberry v. Gislaved

Gummy GB, 178 F.3d 257, 262-66 (4th Cir. 1999) (holding that “[a] reliable

differential diagnosis provides a valid basis for an expert opinion on causation”

and concluding that the district court did not abuse its discretion in admitting a

physician’s opinion testimony based on differential diagnosis) with Glastetter,

252 F.3d at 989 (holding that a district court did not abuse of discretion in

excluding a differential diagnosis that was “scientifically invalid”); see also



                                         -38-
Federal Judicial Center, Reference Manual on Scientific Evidence 34 (2d. ed.

2000) (noting that “[j]udges disagree on whether a physician relying on the

methodology of clinical medicine can provide adequate proof of causation in a

toxic tort action”). Courts have also reached contrasting conclusions as to the

reliability of case reports. Compare Glaser v. Thompson Med. Co., 32 F.3d 969,

975 (6th Cir. 1994) (holding that the district court abused its discretion in

excluding physician’s opinion testimony based in part on case reports) with

Casey v. Ohio Med. Prods., 877 F. Supp. 1380, 1385 (N.D. Cal.1995) (stating that

“case reports are not reliable scientific evidence of causation, because they simply

described 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”); see generally Federal Judicial Center,

Reference Manual on Scientific Evidence 475 (noting that “[c]ausal attribution

based on case studies must be regarded with caution” but that “such studies may

be carefully considered in light of other information available, including

toxicological data,” and citing cases reaching contrasting conclusions on their




                                         -39-
admissibility under Daubert). 14 Our circuit does not appear to have addressed the

reliability of differential diagnosis and case reports under Daubert.

      In the instant case, the district court made short shrift of the Hollanders’

experts’ differential diagnoses and reliance on case reports. The court stated that

“[b]ecause of their limitations, case reports have been repeatedly rejected as a

scientific basis for a conclusion regarding causation.” Hollander, 95 F. Supp. 2d

at 1237.

      Because the Daubert reliability inquiry is case-specific, we need not

address, in general terms, the reliability of differential diagnoses and case reports.

See Kumho Tire, 526 U.S. at 150. Instead, we must only decide whether the

district court abused its discretion by characterizing the specific diagnoses and

case reports at issue here as unreliable under Daubert.

      Again, we conclude that the district court did not abuse its discretion. In

many of the decisions in which a differential diagnosis has been deemed reliable,

the party relying on the diagnosis has offered independently reliable evidence that


      14
          The conflicting views of the reliability of differential diagnosis are
apparent in the Parlodel cases too. Compare Brasher, 160 F. Supp. 2d at 1296
(concluding that differential diagnosis constitutes a reliable methodology under
Daubert) and Globetti, 111 F. Supp. 2d at 1178 (characterizing differential
diagnosis as “a well-recognized and widely-used technique relied on by medical
clinicians worldwide to identify and isolate the causes of disease”) with
Glastetter, 252 F.3d at 1362 (concluding that differential diagnosis and case
reports did not establish reliable proof of causation), and Siharath, 131 F. Supp.
2d at 1361-63 (same).

                                         -40-
the allegedly dangerous drug or substance had harmful effects. See, e.g.,

Zuchowicz v. United States, 140 F.3d 381, 385-87 (2d Cir. 1998) (affirming

admission of differential diagnosis based in part on scientific articles regarding

the effects of a drug); Kennedy v. Collagen Corp., 161 F.3d 1226, 1228-30 (9th

Cir. 1998) (holding that the district court abused its discretion in excluding expert

opinion based on differential diagnosis when the diagnosis was supported by

scientific and clinical studies regarding the connection between collagen and

autoimmune disorders). That is not the case here. In order to “rule in” Parlodel

as a scientifically plausible cause of Ms. Hollander’s stroke, the Hollanders’

experts would need to present reliable evidence that the drug can cause strokes,

and for the reasons we have discussed, the district court did not abuse its

discretion in concluding that the experts did not do so. See Glastetter, 252 F.3d

at 989 (affirming the district court’s exclusion of a differential diagnosis); cf.

Siharath, 131 F. Supp. 2d at 1362-63 (“[A] fundamental assumption underlying

this method is that the final, suspected ‘cause’ remaining after this process of

elimination must actually be capable of causing the injury. That is, the expert

must ‘rule in’ the other suspected cause as well as ‘rule out’ other possible

causes. And, of course, expert opinion on this issue of general causation must be

derived from scientifically valid methodology.”) (internal quotation marks

omitted).



                                          -41-
      We take a similar view of the case reports regarding other women suffering

various injuries after taking Parlodel. Many of these case reports contain only

limited information regarding the medical histories of the patients and the nature

of the injuries they suffered. In addition, given the large number of women who

took Parlodel and the variety of possible causes for many of these injuries, it was

not unreasonable for the district court to characterize the reports as unreliable

evidence of causation. See Siharath, 131 F. Supp. 2d at 1361 (noting that “case

reports . . . do not isolate and exclude potentially alternative causes; and do not

investigate or explain the mechanism of causation” and that, as to Parlodel, “the

modest number of case reports associating the drug with stroke or even

postpartum hypertension is not what would be expected if there was a significant

increased risk ”) (internal quotation marks omitted).

      In holding that the district court did not abuse its discretion in excluding

the particular differential diagnoses and case reports submitted by the Hollanders,

we emphasize that, in other litigation, there may well be differential diagnoses

and case reports that do not suffer from the same deficiencies noted by the district

court here. For example, if the case reports in this record contained more detailed

information about other women who suffered strokes and heart attacks after

taking Parlodel, and if there were a substantially larger number of such detailed

reports, that information might have provided support for the theories of Drs.



                                         -42-
Kulig, Iffy, and Jose. In that instance, a district court might well be justified in

finding opinion testimony like that of Drs. Kulig, Iffy, and Jose reliable under

Daubert. See Caraker, 172 F. Supp. 2d at 1050 (stating that “an overwhelming

amount of case reports of a temporal proximity between a very specific drug and a

very specific adverse event might . . . be enough to make a general causation

conclusion sufficiently reliable” but adding that “[i]n this case, however, we have

a scant number of case reports”).

      Moreover, as the Eighth Circuit has written:

             [W]e do not believe that a medical expert must always cite
             published studies on general causation in order to reliably
             conclude that a particular object caused a particular
             illness. The first several victims of a new toxic tort should
             not be barred from having their day in court simply
             because the medical literature, which will eventually show
             the connection between the victims’ condition and the
             toxic substance, has not yet been completed. If a properly
             qualified medical expert performs a reliable differential
             diagnosis through which, to a reasonable degree of medical
             certainty, all other possible causes of the victims'
             condition can be eliminated, leaving only the toxic
             substance as the cause, a causation opinion based on that
             differential diagnosis should be admitted.

Turner v. Iowa Fire Equip. Co., 229 F.3d 1202, 1209 (8th Cir. 2000) (internal

quotation marks omitted); see also Westberry, 178 F.3d at 262 (holding that a

reliable differential diagnosis alone may provide a valid foundation for a

causation opinion, even when no epidemiological studies, peer-reviewed

published studies, animal studies, or laboratory data are offered in support of the

                                          -43-
opinion). However, in light of the deficiencies of the particular differential

diagnoses and case reports in this record, the district court’s analysis was not

unreasonable.



      f. Rechallenge and dechallenge reports

      Ms. Hollanders’ experts also presented several accounts of rechallenge and

dechallenge. Rechallenge occurs when a patient is exposed to the same drug

thought to have previously caused an adverse reaction. Dechallenge occurs when

the drug is removed. As the Eighth Circuit has noted, rechallenge and

dechallenge resemble controlled experiments in some ways, and thus may be more

valuable than typical case reports. Glastetter, 252 F.3d at 990-91. Occasionally

the results may appear quite dramatic. For example, one Sandoz employee

described a rechallenge-dechallenge report as “‘the smoking gun’ we have looked

for so diligently.” Aplt’s App. vol. IV-B, at 2364. 15

      Nevertheless, by the Hollanders’ account, there were only three such

reports. See Aplt’s Br. at 31. Of these three, only one involved vasoconstriction




      15
         A physician reported to Sandoz that he had induced vasoconstriction of
the cerebral blood vessels by administering small doses of Parlodel to a woman
who had previously suffered a stroke after taking the drug. See Aplt’s App. vol.
IV-B, at 2364-65 (memorandum from Dr. William F. Westin, dated Sept 17,
1987). There appears to be no further discussion of this report in the record.

                                         -44-
of the cerebral blood vessels. 16 Moreover, as to that incident, the only

information to which the Hollanders’ have directed us is a second-hand account

by a Sandoz physician. Thus, the district court conclusion here —that there were

too few of these reports for them to constitute reliable evidence of causation

under Daubert—was not unreasonable. Cf. Glastetter, 252 F.3d at 990 (finding

rechallenge and dechallenge data to be more potent proof of causation than did

the district court but further concluding that the district court did not abuse its

discretion in excluding it).



      g. The Risks of Stroke in the Postpartum period

      A linchpin of Sandoz’s defense was that there is an increased risk of stroke

in the postpartum period generally. Sandoz relied heavily on a study concluding

that there is a 28.3 relative risk of stroke for women in the postpartum period, as

compared with non-pregnant women. See Steven J. Kittner, et al., Pregnancy and

the Risk of Stroke, New Eng. J. Med. 768-74 (1996) (Aplt’s App. vol. II-C, at

1335-41). 17


      16
         One of the incidents involved the vasoconstriction of a coronary artery
and another involved hypertension.
      17
           One authority explains the concept of “relative risk” as follows:

               [Relative risk] is defined as the ratio of the incidence rate
               (often referred to as incidence) of disease in exposed
                                                                           (continued...)

                                           -45-
17
     (...continued)
           individuals to the incidence rate in unexposed individuals.

          ....

                  The incidence rate of disease reflects the number of
          cases of disease that develop during a specified period of
          time divided by the number of persons in the cohort under
          study. Thus, the incidence rate expresses the risk that a
          member of the population will develop the disease within
          a specified period of time.
                  For example, a researcher studies 100 individuals
          who are exposed to an agent and 200 who are not exposed.
          After one year, 40 of the exposed individuals are
          diagnosed as having a disease, and 20 of the unexposed
          individuals are also diagnosed as having the disease. The
          relative risk of contracting the disease is calculated as
          follows:
                  -The incidence rate of disease in the exposed
          individuals is 40 cases per year per 100 persons (40/100),
          or 0.4
                  -The incidence rate of disease in the unexposed
          individuals is 20 cases per year per 200 persons (20/200),
          or 0.1.
                   A relative risk of 4.0 indicates that the risk of
          disease in the exposed group is four times as high as the
          risk of disease in the unexposed group.

          ....

                 Although a relative risk is a straightforward concept,
          care must be taken in interpreting it. Researchers should
          scrutinize their results for error. Error in the design of the
          study could yield an incorrect relative risk. Sources of
          bias and confounding should be examined. Whenever an
          association is uncovered, further analysis should be
          conducted to determine if the association is real or due to
          an error or bias. Similarly, a study that does not find an
                                                                       (continued...)

                                      -46-
Thus, according to Sandoz, Ms. Hollander’s stroke could well have been the

result of the increased risk to which all women are exposed during the postpartum

period rather than an adverse reaction to Parlodel.

      In the district court proceedings, the Hollanders challenged this argument

primarily through the testimony of Dr. Kulig, who stated that the Kittner study

(and others reaching similar conclusions about the risks of the postpartum period)

did not control for bromocriptine use or for specific conditions that increase the

risk of stroke, such as eclampsia. According to Dr. Kulig, when these factors are

excluded, the Kittner study does not establish that there is an increased risk of

stroke in the postpartum period.

      The district court acknowledged Dr. Kulig’s criticisms of the study.

However, the court found that “the postpartum incidence of stroke is a factor that

should be considered.” See Hollander, 95 F. Supp. 2d at 1238 n.21.




      17
           (...continued)
                 association between an agent and disease may be
                 erroneous because of bias or random error.

Federal Judicial Center, Reference Manual on Scientific Evidence 348-49.

        Thus, in the instant case, the study cited by Sandoz concluded that women
in the postpartum period were 28.3 times more likely than non-pregnant women to
have suffered a stroke.




                                         -47-
      The Hollanders now argue that the district court erred in its qualified

affirmation of the Kittner study in the face of Dr. Kulig’s critique of it. If this

case required Sandoz to prove that there was an increased risk of stroke during

pregnancy, we might agree. However, no such burden is imposed on Sandoz here.

Instead, it is the Hollanders who have the burden of demonstrating the harmful

effect of Parlodel. Accordingly, it was not unreasonable for the district court to

conclude that Dr. Kulig’s attack on the Kittner study did not constitute reliable

evidence that Parlodel caused Ms. Hollander’s stroke.

      In summary, we agree with the court’s assessment in Siharath: the

Hollanders have done the best they could with the available data and the scientific

literature. See 131 F. Supp. 2d at 1373. The data on which they rely might well

raise serious concerns in conscientious clinicians seeking to decide whether the

benefits of the drug outweigh its risks. However, in deriving their opinions that

Parlodel caused Ms. Hollander’s stroke from the various sources we have

outlined, Drs. Kulig, Iffy, and Jose all made several speculative leaps. As a

result, the district court did not abuse its discretion in excluding their testimony

under Daubert.




                                          -48-
                     C. Grant of Summary Judgment to Sandoz

      In a related argument, the Hollanders maintain that, even if the district

court did not abuse its discretion in excluding their experts’ testimony, the court

nevertheless erred in granting summary judgment to Sandoz.

      According to the Hollanders, the following evidence demonstrates that

there are controverted issues of material fact as to whether Parlodel caused her

stroke: (1) the FDA’s determination that Parlodel had not been shown to be safe

when prescribed as a postpartum lactation suppressant; (2) the judgment entered

against Sandoz in a case in Kentucky involving Parlodel; (3) incidents of

dechallenge and rechallenge; (4) case reports; (5) studies of hypertension; (6) the

fact that bromocriptine is an ergot; (7) animal studies; and (8) epidemiological

studies.

      We engage in de novo review of the district court’s summary judgment

ruling, applying the same standard as the district court under Fed. R. Civ. P.

56(c). See Adler v. Wal-Mart Stores, Inc., 144 F.3d 664, 670 (10th Cir. 1998).

Summary judgment is appropriate “if the pleadings, depositions, answers to

interrogatories, and admissions on file, together with the affidavits, if any, show

that there is no genuine issue as to any material fact and that the moving party is

entitled to a judgment as a matter of law.” Rule 56(c). We view the facts and the




                                         -49-
reasonable inferences to be drawn from them in the light most favorable to the

nonmoving party. Adler, 144 F.3d at 670.

      Under Oklahoma law, which we apply in this diversity case, see Wood v.

Eli Lilly & Co., 38 F.3d 510, 512 (10th Cir. 1994), “[a] plaintiff seeking recovery

for an injurious side effect from a properly manufactured prescription drug must

prove that the drug caused the injury and that the manufacturer breached a duty to

warn of possible detrimental reactions.” McKee v. Moore, 648 P.2d 21, 23 (Okla.

1982). Causation is established if “in a natural and continuous sequence,

unbroken by an independent cause” the drug produces an injury that would not

have occurred if it had not been administered. See Gaines v. Providence

Apartments, 750 P.2d 125, 126-27 (Okla. 1987) (defining proximate cause).

      We need not address the Hollanders’ argument in detail. We have already

ruled that five of the eight categories of evidence on which they rely did not

constitute sufficiently reliable grounds under Daubert for their experts’

opinions. 18 As a result, these categories of evidence do not raise questions of fact

on issues of causation.

      Moreover, under Oklahoma law, a plaintiff must introduce expert testimony

if “the fact in issue is not within the realm of ordinary experience of mankind.”


      18
         These categories of evidence are as follows: incidents of dechallenge and
rechallenge; case reports; studies of hypertension; the fact that bromocriptine is
an ergot; and animal studies.

                                        -50-
Strubhart v. Perry Mem’l Hosp. Trust Auth., 903 P.2d 263, 274 (Okla. 1995).

Here, the alleged effect of Parlodel is not within the realm of ordinary experience:

in order to assess the arguments regarding the alleged effects of the drug, the

factfinder would be required to assess the wide variety of scientific evidence that

we have discussed here. As a result, the Hollanders cannot prove their claim

without expert testimony.

      Finally, we consider briefly the three categories of evidence that we have

not yet addressed—the FDA determination, the judgment in the Roberts case, and

the epidemiological studies. None of this evidence provides sufficient support for

the Hollanders’ claims.

      As to the FDA determination, this circuit has noted that differing standards

militate against applying regulatory actions to the elements of tort law. See

Mitchell, 165 F.3d at 783 n.3 (10th Cir. 1999). In assessing a district court’s

application of Daubert, we discounted a state agency’s classification of a

substance as a carcinogen, stating that the methodology employed by the agency

“results from the preventive perspective that the agencies adopt in order to reduce

public exposure to harmful substances,”and that “[t]he agencies’ threshold of

proof is reasonably lower than that appropriate in tort law.” Id. (internal

quotation marks omitted).




                                         -51-
      Moreover, several courts have concluded that this specific FDA ruling

about Parlodel is not relevant to the causation question. See Glastetter, 252 F.3d

at 991 (noting that the FDA ruling is not reliable evidence of causation for two

reasons: (1) because the FDA “balanced Parlodel’s possible harm against its

limited beneficial use,” an irrelevant consideration in the Daubert inquiry; and (2)

because “[t]he FDA will remove drugs from the marketplace upon a lesser

showing of harm to the public than the standards used to assess tort liability”);

Siharath, 131 F. Supp. 2d at 1366 (rejecting the plaintiff’s reliance on the FDA

ruling). Moreover, the language used in the FDA ruling regarding the withdrawal

of Parlodel indicates that the agency did not make a determination that Parlodel

causes seizures and strokes. 19 Accordingly, we conclude that the FDA ruling does

not establish that there are controverted factual issues as to whether Parlodel

caused Ms. Hollanders’ stroke. 20


      19
          The FDA ruling states that the evidence received by the FDA “calls into
question bromocriptine’s safety,” that bromocriptine “may be an additional risk
factor in patients who are already at risk for seizures and stroke,” and that the
FDA had obtained new evidence “suggesting that therapeutic use of
bromocriptine for the prevention of physiological lactation may lead to serious
adverse experiences . . . .” 59 Fed. Reg. 43348, 43351 (Aug. 24, 1994) (emphasis
added).
      20
           Our conclusion about the FDA’s decision to withdraw the indication for
Parlodel as a lactation suppressant should not be read to suggest that, as a general
rule, regulatory decisions lack the intellectual rigor necessary under the Daubert
reliability inquiry. Indeed, some authorities view the review process in the
regulatory area as typically “far more careful and systematic” than the peer review
                                                                        (continued...)

                                        -52-
      As to the judgment in the Roberts case, the Hollanders fail to explain its

relevance. The case was decided under Kentucky law, and our decision is

governed by different law and different facts. Moreover, in light of the district

court’s broad discretion in these matters, the fact that different courts reach

difference conclusions as to reliability under Daubert does not establish that a

legal error has been made by one or the other. See Brasher, 160 F. Supp. 2d at

1299 n.17 (noting that inconsistent rulings Daubert rulings do not necessarily

establish an abuse of discretion).

      Finally, the epidemiological studies in question do not support the

Hollanders’ claim. The district court accurately observed that the Hollanders’

own experts did not rely on these studies. Moreover, as the district court further

noted, “[a]though several studies have been conducted regarding Parlodel and

stroke, none has shown a statistically significant link between them.” Hollander,

95 F. Supp. at 1236. See also Siharath, 131 F. Supp. at 1356-59 (discussing four

studies finding no statistically significant association). 21


      20
         (...continued)
process employed by scientific journals. See Kenneth R. Foster & Peter W.
Huber, Judging Science: Scientific Knowledge in the Federal Courts 174 (1997).
“Regulators require that documents submitted to them contain far more detail than
is typically found in papers submitted to professional journals . . . . [and]
administrative reports—not peer reviewed journals—may provide parties with the
solidest available data.” Id. at 174-75.
      21
           The Hollanders also suggest that a totality of the circumstances approach
                                                                        (continued...)

                                          -53-
      Accordingly, we conclude that the district court properly granted Sandoz’s

motion for summary judgment.



                          D. Dismissal of Sandoz, Ltd.

      Prior to ruling on the Daubert and summary judgment motions, the district

court dismissed the Hollanders’ claims against the defendant Sandoz, Ltd., a

company incorporated in Switzerland with its principal place of business there.

Prior to January 1, 1990, Sandoz, Ltd. sold Parlodel in bulk to the defendant

Sandoz Corporation. However, after that date, Sandoz, Ltd. became a holding

company, conducting no advertising in the United States and owing no

manufacturing, distribution, or sales facilities here. In granting Sandoz’s motion

to dismiss, the district court reasoned that Sandoz, Ltd. “does not have a bank

account, a telephone number or any employees, officers or directors in this

country; and that it does not actively advertise in the United States.” Aplt’s App.

vol. I, at 344 (Dist. Ct. Order, filed Dec. 10, 1996, at 1). Accordingly, the court

      21
        (...continued)
establishes that there are controverted issues of material fact. In essence they
maintain that even though each individual category of evidence may be
insufficient, all of the evidence considered as a whole raises factual questions as
to whether Parlodel caused her stroke. The Hollanders cite no legal authority in
support of this approach, and in our view, this argument is inconsistent with
Daubert. To suggest that those individual categories of evidence deemed
unreliable by the district court may be added to form a reliable theory would be to
abandon “the level of intellectual rigor” of the expert in the field. Kumho Tire,
526 U.S. at 152.

                                         -54-
concluded that it lacked personal jurisdiction over Sandoz, Ltd., and it dismissed

the claims against Sandoz, Ltd. with prejudice.

      On appeal, the Hollanders argue that, because Sandoz, Ltd. sold Parlodel to

its United States subsidiary (Sandoz) prior to January 1, 1990, Sandoz, Ltd.

should be deemed to have continued to do business in the United

States through July 1990, when Ms. Hollander suffered her stroke. They contend

that it is unlikely that Sandoz, Ltd. would have completely ceased doing business

in the United States in the seven month period beginning in January 1990 (when it

became a holding company) and July 1990 (when Ms. Hollander took Parlodel).

Additionally, the Hollanders argue that the district court erred in dismissing the

claims against Sandoz, Ltd. with prejudice.

      The Hollanders’ challenge to the court’s jurisdictional ruling raises a legal

question that we review de novo. See Wenz v. Memery Crystal, 55 F.3d 1503,

1505 (10th Cir. 1995). Their argument is undermined by precedent that imposes

the burden of proof on the party asserting jurisdiction. See id. Because they

have offered no evidence to rebut Sandoz, Ltd.’s evidence that it did not do

business in the United States after January 1, 1990, we conclude that the district

court properly held that it lacked jurisdiction over the company.

      However, we further conclude that the district court should not have

dismissed the Hollanders’ claim against Sandoz, Ltd. with prejudice. Its



                                         -55-
jurisdictional ruling did not address the merits of the Hollanders’ allegations as to

Sandoz, Ltd., and, as a result, the claim against Sandoz, Ltd. should have been

dismissed without prejudice to filing in an appropriate forum. See Posner v.

Essex Ins. Co., Ltd., 178 F.3d 1209, 1221 (11th Cir. 1999) (concluding that the

district court erred in dismissing claims against a party with prejudice on

jurisdictional grounds and instructing the district court to dismiss the claims

without prejudice); Arrowsmith v. United Press Int’l, 320 F.2d 219, 221 (2d Cir.

1963) (“A dismissal for lack of jurisdiction . . . does not preclude a subsequent

action in an appropriate forum.”).



                                III. CONCLUSION

      This case illustrates the continuing importance of the Supreme Court’s

observation in Daubert:

             [T]here are . . . differences between the quest for truth in
             the courtroom and the quest for truth in the 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

                                         -56-
             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. Thus, in Judge Posner’s words, “the courtroom is

not the place for scientific guesswork, even of the inspired sort. Law lags

science; it does not lead it.” Rosen, 78 F.3d at 319.

      Here, the district court characterized the Hollanders’ evidence as such

guesswork, and that characterization was not unreasonable. The Hollanders’

evidence provided support for the FDA’s decision to withdraw the indication for

Parlodel as a postpartum lactation suppressant, as well as for the decisions of

experienced clinicians that the apparent risks of Parlodel outweighed the limited

benefits of prescribing the drug as a lactation suppressant. However, the district

court did not abuse its discretion in ruling that the Hollanders’ evidence did not

satisfy the Daubert standard of reliability.

      Additionally, the district court did not err in denying the Hollanders’

motion to remand the case to the Oklahoma state courts or in dismissing the claim

against Sandoz, Ltd. However, the court did err in dismissing the claim against

Sandoz, Ltd. with prejudice.




                                         -57-
      Accordingly, we AFFIRM the judgment of the district court in all respects

EXCEPT that we REMAND the Hollanders’ claim against Sandoz, Ltd. with

instructions to dismiss that claim without prejudice. 22

      22
          In light of our conclusion that the federal district court did not abuse its
discretion in concluding that Hollanders’ expert testimony was unreliable under
Daubert, as well as our conclusion that the court did not err in granting summary
judgment to Sandoz, we need not address the Hollanders’ challenge to the
dismissal of their products liability claim against Presbyterian Hospital. Even
assuming that the dismissal was improper, the Hollanders have failed to explain
why the same reliability problems noted by the federal district court do not defeat
the Hollanders’ products liability claim against Presbyterian Hospital.
          We do note, as Presbyterian Hospital observes in its response brief, that
an overwhelming majority of jurisdictions have refused to apply strict liability
principles to claims against hospitals and physicians involving the distribution of
allegedly dangerous drugs or medical devices. See, e.g, Royer v. Catholic Med.
Ctr., 741 A.2d 74 (N.H. 1999) (affirming the dismissal of a products liability
claim based on an allegedly defective prosthesis and reasoning that where “a
health care provider in the course of rendering health care services supplies a
prosthetic device to be implanted into a patient, the health care provider is ‘not
engaged in the business of selling’ prostheses for purposes of strict products
liability”); Cafazzo v. Central Med. Health Servs., Inc., 668 A.2d 521, 525 (Pa.
1995) (rejecting products liability claim based on a prosthesis and reasoning that
“hospitals and physicians are not sellers, providers, suppliers, or distributors of
products such as to activate 402A” and that the policy reasons for strict liability
are not present); Ayyash v. Henry Ford Health Sys., 533 N.W.2d 353, 354 (Mich.
Ct. App. 1995) (rejecting products liability claim against a hospital based on an
allegedly defective temporomandibular joint implant and reasoning that when “a
putative defendant uses a defective product in the course of providing a service,
the courts must decide whether the ‘transaction’ is primarily a sale or a service”
and concluding that “[i]n the case of a physician or hospital rendering medical
care courts typically have characterized the ‘transaction’ as a service” and
adopting that characterization for policy reasons); see generally Linda A. Sharp,
Annotation, Liability of Hospital or Medical Practitioner under Doctrine of Strict
Liability in Tort or Breach of Warranty, for Harm Caused by Drug, Medical
Instrument, or Similar Device Used in Treating Patient, 65 ALR 5th 357, 371 §
2(b) (1999) (noting “the continued reluctance by most courts to apply no-fault
                                                                         (continued...)

                                         -58-
      22
         (...continued)
products liability principles in actions against medical defendants for injuries
caused by medical products). But see Thomas v. St. Joseph Hosp., 618 S.W.2d
791 (Tex. Civ. App. 1981) (hospital held strictly liable where hospital gown
ignited when lighted match fell on it); Silverhart v. Mount Zion Hosp., 20 Cal.
App. 3d 1022 (Cal. App. 1st Dist. 1971) (hospital would be found liable where
not engaged in activities integrally related to primary function of providing
medical services—selling a defective product in its gift shop).
         Although Oklahoma courts do not appear to have answered this particular
question, we have no reason to believe that those courts would disagree with the
majority rule and extend products liability to hospitals in circumstances like those
in the case at bar. Cf. Allenberg v. Bentley Hedges Travel Serv., Inc., 22 P.3d
223, 230-31 (Okla. 2001) (holding that commercial sellers of used products may
not be held strictly liable, “at least if the alleged defect was not created by the
seller, and the product is sold in essentially the same condition as when it was
acquired for resale”). For that reason, and because the Hollanders did not seek
certification in the district court proceedings, we DENY their motion for
certification to the Oklahoma Supreme Court. See Boyd Rosene & Assocs., Inc.
v. Kansas Municipal Gas Agency, 178 F.3d 1363, 1365 (10th Cir. 1999)
(observing that “[c]ertification is never compelled, even when there is no state
law governing an issue”); Massengale v. Oklahoma Bd. of Examiners in
Optometry, 30 F.3d 1325, 1331 (10th Cir. 1994) (stating that “[w]e generally will
not certify questions to a state supreme court when the requesting party seeks
certification only after having received an adverse decision from the district
court”).


                                        -59-