Guinn v. ASTRAZENECA PHARMACEUTICALS LP

                                                                  [PUBLISH]

             IN THE UNITED STATES COURT OF APPEALS

                     FOR THE ELEVENTH CIRCUIT           FILED
                      ________________________ U.S. COURT OF APPEALS
                                                         ELEVENTH CIRCUIT
                                                            APRIL 6, 2010
                             No. 09-11104
                                                             JOHN LEY
                       ________________________               CLERK

               D. C. Docket Nos. 07-10291-CV-ORL-22-DAB,
                         06-MD-01769-ACC-DAB

LINDA GUINN,

                                                     Plaintiff-Appellant,

                                  versus

ASTRAZENECA PHARMACEUTICALS LP,
ASTRAZENECA AB,
ASTRAZENECA LP,
ASTRAZENECA PLC,

                                                     Defendants-Appellees.
                       ________________________

                Appeal from the United States District Court
                    for the Middle District of Florida
                     _________________________

                              (April 6, 2010)


Before DUBINA, Chief Judge, BIRCH and BLACK, Circuit Judges.

PER CURIAM:
      Appellant Linda Guinn brought suit against Appellee AstraZeneca

Pharmaceuticals LP (AstraZeneca), claiming her use of the prescription drug

Seroquel caused her to develop diabetes. Prior to trial, AstraZeneca filed a

Daubert motion for the exclusion of the expert testimony of Dr. Jennifer Marks

and a motion for summary judgment. After conducting a Daubert hearing, the

district court entered an order granting both motions. The court found that

summary judgment in favor of AstraZeneca was appropriate because Guinn had

failed to establish a genuine issue of material fact on the issue of causation. The

court based its ruling on two alternative grounds. First, the court held that the

testimony of Dr. Marks, Guinn’s only evidence on the issue of specific causation,

did not satisfy the requirements of Rule 702 of the Federal Rules of Evidence and

therefore should be excluded. Second, the district court held that even if

Dr. Marks’ testimony were admissible, it did not support the conclusion that it was

more likely than not that Seroquel substantially contributed to causing Guinn’s

diabetes. We affirm the district court’s order granting both AstraZeneca’s

Daubert and summary judgment motions.




                                          2
                                  I. BACKGROUND

A.    Procedural History

       Guinn brought suit against AstraZeneca in the District of Massachusetts,

claiming to have developed diabetes as a result of taking Seroquel. Guinn asserted

claims against AstraZeneca for strict products liability, negligence, fraud, and civil

conspiracy. Guinn contended that while her prescribers were unaware of any

increased risk of hyperglycemia or diabetes associated with Seroquel, AstraZeneca

knew Seroquel caused weight gain in approximately one-quarter to one-third of

patients. According to Guinn, despite AstraZeneca’s knowledge of the

relationship between Seroquel and weight gain, the company marketed Seroquel as

having no effect on patients’ weight and failed to include adequate warnings on

Seroquel’s labels as required by United States Food and Drug Administration

(FDA) regulations. Guinn further contended Seroquel is no more effective than

other antipsychotics which she claims pose less of a risk of weight gain.

      The Judicial Panel on Multidistrict Litigation transferred Guinn’s case and

91 other actions involving Seroquel to the Middle District of Florida for

coordinated pretrial proceedings in July 2006. At the time of the district court’s

summary judgment order, the consolidated action had grown to include the claims

of several thousand plaintiffs.

                                          3
B.      Facts

        Seroquel, chemically known as quetiapine fumarate, is an antipsychotic

medication manufactured and distributed by AstraZeneca. Seroquel has been

approved by the FDA for use in the treatment of bipolar disorder and

schizophrenia. Guinn was prescribed Seroquel from May 2002 through April

2007.

        1.       Dr. Marks’ Expert Report

            Dr. Marks, Guinn’s expert witness on specific causation, first gave her

opinion in an expert report submitted to the district court.1 Dr. Marks began her

discussion of Guinn with a review of her medical records dating back to 1998.

Dr. Marks noted that the first weight she had available for Guinn was 194 pounds

in March 1999. According to Dr. Marks’ report, Guinn reached a peak weight of

205 pounds in January 2000 and thereafter her weight, though fluctuating,

generally decreased until June 2002, when she reached her lowest weight of 155

pounds. It was at approximately this time that Guinn began taking Seroquel.

Guinn then gained weight until she was diagnosed with diabetes with a weight of


        1
         Specific causation refers to the issue of whether the plaintiff has demonstrated that the
substance actually caused injury in her particular case. Specific causation is often distinguished
from general causation, which refers to the more general issue of whether a substance has the
potential to cause the plaintiff’s injury. See Knight v. Kirby Inland Marine Inc., 482 F.3d 347,
351 (5th Cir. 2007) (discussing the distinction between specific and general causation).

                                                 4
198 pounds in February 2006. Dr. Marks summarized her review of Guinn’s

medical records by stating she gained approximately forty pounds during her five

years of taking Seroquel.

      After reviewing Guinn’s weight history, Dr. Marks concluded, “based on

reasonable medical probability[,] that Seroquel was a cause of [Guinn’s] diabetes.”

Dr. Marks explained that “exposure to a medication which caused weight gain

worsened her underlying insulin resistance and likely accelerated the onset of

diabetes in such a predisposed individual.”

      2.     Dr. Marks’ Deposition and AstraZeneca’s Daubert Motion

      In Dr. Marks’ deposition, AstraZeneca provided Dr. Marks with additional

information regarding Guinn’s medical history and more fully examined

Dr. Marks’ opinion on causation given this new information. The additional

medical history discussed at the deposition revealed that Guinn had already had a

number of risk factors for diabetes before she began taking Seroquel. Guinn had

struggled with obesity, a significant risk factor for diabetes, and experienced

dramatic weight fluctuations since her teenage years. In fact, Guinn’s weight

fluctuated before, during, and after her use of Seroquel, with her highest recorded




                                          5
weight during each period being roughly equivalent.2 Guinn also had a sedentary

lifestyle, a poor diet, a significant family history of diabetes, hypertension,

hyperlipidemia, schizophrenia, and prediabetes, all of which, in addition to her age

of 61, put her at an increased risk for developing diabetes. Dr. Marks stated she

was not aware of all of Guinn’s risk factors at the time she wrote her initial report

because she had only reviewed medical records provided to her by Guinn’s

attorneys dating back to 1998.3

       At the deposition, Dr. Marks expanded on her theory of causation. She

reiterated her belief that Seroquel caused Guinn’s diabetes through the mechanism

of weight gain. When asked what steps she had taken to determine whether

Seroquel had caused Guinn’s weight gain, she replied that she had considered only

the medical literature showing that Seroquel can cause weight gain and the

temporal proximity of Guinn’s use of the medication. Dr. Marks stated she had

made no attempt to quantify the amount of weight gain she attributed to Seroquel

and had done nothing to rule out other factors as the sole cause of Guinn’s weight




       2
        Guinn’s highest recorded weights before, during and after her use of Seroquel were 208,
205, and 206, respectively. As an example of Guinn’s previous weight fluctuations, she reported
weighing 111 pounds in 1986, 208 pounds in 1994, and 155 pounds in 2002.
       3
        Dr. Marks did not know whether the copy of Guinn’s medical records provided to her by
Guinn’s attorneys was complete.

                                               6
gain. Dr. Marks further acknowledged that Seroquel does not cause weight gain in

approximately two-thirds of the patients who take the drug.

       When asked what she had done to rule out Guinn’s other risk factors as the

sole cause of Guinn’s diabetes, Dr. Marks stated she knew of no methodology for

ruling out alternative causes and thus had not attempted to do so. In fact, Dr.

Marks agreed Guinn’s other risk factors alone were sufficient to explain the onset

of her diabetes. Dr. Marks stated, however, she had “no way of ruling out the

Seroquel any more than [she] c[ould] rule out any other risk factors.”

       Dr. Marks also stated she could not rule out the possibility that Guinn had

diabetes before ever taking Seroquel. According to Dr. Marks, the development of

diabetes is a slow, incremental process that occurs gradually over many years. Dr.

Marks explained that about half of the patients who are diagnosed with diabetes

have actually had the disease for approximately five years prior to diagnosis. Dr.

Marks stated that although there was some evidence indicating Guinn may have

had diabetes before taking Seroquel, she believed the evidence was ultimately

inconclusive.4


       4
          Dr. Marks explained that Guinn had two glucose readings shortly before she began
taking Seroquel that were above the threshold for a diagnosis of diabetes. These readings,
however, were unreliable because they were taken during circumstances that could have skewed
the results. Dr. Marks stated that, if she had been Guinn’s physician, she would have conducted
follow-up testing to determine whether Guinn had diabetes at that time.

                                               7
      AstraZeneca filed a Daubert motion seeking to exclude Dr. Marks’

testimony based primarily on statements made at Dr. Marks’ deposition.

AstraZeneca first argued that Dr. Marks had failed to adequately consider and rule

out other potential causes of Guinn’s diabetes. AstraZeneca further contended that

Dr. Marks’ methodology was unreliable because it was based primarily on the

temporal proximity of Guinn’s ingestion of Seroquel to her diagnosis of diabetes.

      3.     Dr. Marks’ Declaration

      Soon after AstraZeneca filed its Daubert motion, Dr. Marks submitted a

declaration to supplement her initial expert report. Dr. Marks explained that

although she had received additional medical records and data regarding Guinn

since her initial report, including information provided to her during her

deposition, “[t]he additional records produced d[id] not substantially alter [her]

conclusions.”

      Likely in response to AstraZeneca’s criticisms, Dr. Marks’ declaration

provided a more complete explanation of her methodology. Dr. Marks explained

that she based her conclusion on:

      the totality of the evidence[,] including the temporal association of
      ingestion of Seroquel with the onset of diabetes, a stable risk factor
      profile without the diagnosis of diabetes prior to use of Seroquel,
      clinical evidence of a pattern of overall weight gain while on Seroquel
      prior to diagnosis of diabetes, . . . evidence of a significantly increased

                                          8
       risk of diabetes as a result of Seroquel ingestion reported in the peer-
       reviewed literature, and the consistency in the clinical presentations of
       [Guinn] compared with those of patients in literature and clinical trials.

Dr. Marks also reiterated that “it [was] not possible or practical to quantify the risk

of each risk factor in each individual plaintiff.”

       4.     The Daubert Hearing

       Dr. Marks’ theory of causation was more fully explored in a Daubert

hearing conducted before the district court. On direct examination, Dr. Marks

again stated that she had considered all of Guinn’s risk factors for diabetes but that

there was no scientific way to determine whether one of the risk factors may have

been the sole cause of her diabetes. Dr. Marks, however, did not elaborate on how

she had considered Guinn’s other risk factors in forming her opinion that Seroquel

substantially contributed to Guinn’s diabetes. Instead, she testified that “[a]ll the

[risk] factors work together.”

       On cross examination, Dr. Marks acknowledged that Guinn’s other risk

factors were sufficient to explain the onset of her diabetes.5 In fact, Dr. Marks

testified that, given Guinn’s risk profile, it was “very likely that she would develop

type II diabetes whether she took Seroquel or not.”


       5
        Dr. Marks also acknowledged, as she had stated earlier in her deposition, that Guinn
may have had diabetes before ever taking Seroquel. Dr. Marks’ deposition was admitted into
evidence at the Daubert hearing and used by AstraZeneca during cross examination.

                                               9
      Dr. Marks also acknowledged on cross examination that specific events in

Guinn’s life could have caused Guinn to gain weight during the time she took

Seroquel. Prior to taking Seroquel, Guinn had lost a significant amount of weight

due to a lack of appetite associated with a period of mental illness. Dr. Marks

explained that she had not been aware of this cause of Guinn’s weight loss at the

time she initially formed her opinion. Dr. Marks acknowledged that as Seroquel

improved Guinn’s mental condition, Guinn reverted to her ordinary eating habits,

which, combined with her sedentary lifestyle, were alone sufficient to explain

Guinn’s weight gain. Moreover, during the time Guinn was taking Seroquel, she

gained approximately ten pounds in the six months after she quit smoking,

something Dr. Marks stated is a known cause of weight gain. Guinn also had two

serious back injuries during the time she took Seroquel, requiring steroid

injections and surgery. Dr. Marks acknowledged that her failure to include

Guinn’s injuries in her report “was an oversight” and that Guinn’s injuries and

consequent recovery time could have contributed to her weight gain.

       Dr. Marks again stated on cross examination that she had not attempted

either to quantify the amount of Guinn’s weight gain that could be attributed to

Seroquel or to rule out other factors as the sole cause of Guinn’s weight gain.

When Dr. Marks was asked if she had used any methodology to determine whether

                                         10
Guinn’s weight gain while on Seroquel was caused by the medication rather than

normal weight fluctuations, Dr. Marks once again replied she knew “of no method

to prove that Seroquel caused the weight gain.” Dr. Marks also stated that

although she ordinarily would have a detailed conversation with a patient

regarding issues such as diet and exercise to determine the cause of a patient’s

weight gain, she did not personally examine or speak with Guinn when forming

her opinion.

C.    The District Court’s Order

      After the Daubert hearing, the district court entered an order granting

summary judgment in favor of AstraZeneca. The court held Guinn had failed to

establish a genuine issue of material fact on the issue of specific causation based

on two separate grounds.

      First, the district court granted summary judgment on the basis of its

exclusion of Dr. Marks’ testimony, Guinn’s only evidence on the issue of specific

causation. The court held that Dr. Marks failed to satisfy the reliability

requirement of Federal Rule of Evidence 702, as elucidated in Daubert v. Merrell

Dow Pharmaceuticals, Inc., 509 U.S. 579, 113 S. Ct. 2786 (1993). The district

court stated “Dr. Marks was unable to articulate any scientific methodology for

assessing whether, and to what extent, Seroquel contributed to Guinn’s weight

                                          11
gain and diabetes.” Guinn v. AstraZeneca Pharm. LP, 598 F. Supp. 2d 1239, 1243

(M.D. Fla. 2009). The court also found that Dr. Marks’ opinion on causation

“amounts to nothing more than inadmissible ipse dixit, as ‘the only connection

between the conclusion and the existing data is the expert’s own assertions.’” Id.

(quoting McDowell v. Brown, 392 F.3d 1283, 1300 (11th Cir. 2004)). The court

ultimately held that excluding Dr. Marks’ testimony was a basis for granting

summary judgment because “Guinn has no other expert upon whose testimony she

can rely to establish specific causation, and ‘this type of proof requires expert

testimony.’” Id. at 1243 n.25 (quoting McClain v. Metabolife Int’l Inc., 401 F.3d

1233, 1237 (11th Cir. 2005)).

      Second, the district court held that, even if Dr. Marks’ testimony was

admissible, her statements were insufficient to establish a genuine issue of

material fact with respect to specific causation. The court noted Dr. Marks

testified that factors other than Seroquel could have caused Guinn’s weight gain,

Guinn’s pre-existing risk factors alone could have caused her diabetes, and

Dr. Marks had made no attempt to determine the relative contribution of the

various potential causes of Guinn’s weight gain and diabetes. The district court

held that, given this testimony, no reasonable juror could conclude that Seroquel

more likely than not played a role in causing Guinn’s diabetes.

                                          12
                           II. STANDARD OF REVIEW

      This Court reviews a district court’s decision regarding the admissibility of

expert testimony for an abuse of discretion. United States v. Frazier, 387 F.3d

1244, 1258 (11th Cir. 2004). We review a district court’s grant of summary

judgment de novo. Midrash Sephardi, Inc. v. Town of Surfside, 366 F.3d 1214,

1222–23 (11th Cir. 2004).

                                  III. DISCUSSION

      As explained above, the district court based its order granting summary

judgment on two separate holdings. Because alternative holdings are accorded

precedential value in this Circuit, Bravo v. United States, 532 F.3d 1154, 1162–63

(11th Cir 2008), we will address each of the district court’s rulings in turn.

A.    The Admissibility of Dr. Marks’ Expert Testimony

      Rule 702 of the Federal Rules of Evidence governs the admission of expert

testimony. This Circuit applies a three-part inquiry to determine whether an expert

has met the requirements of Rule 702. Frazier, 387 F.3d at 1260. Under this test,

a court must consider whether: (1) the expert is sufficiently qualified to testify on

the issues he intends to address; (2) the expert’s methodology is “sufficiently

reliable as determined by the sort of inquiry mandated in Daubert; and (3) the

testimony assists the trier of fact, through the application of scientific, technical, or

                                           13
specialized expertise, to understand the evidence or to determine a fact in issue.”

Id. (citing City of Tuscaloosa v. Harcros Chems., Inc., 158 F.3d 548, 562 (11th

Cir. 1998)).

      Neither the district court nor the parties in this case dispute that Dr. Marks

is qualified to testify as an expert on diabetes causation. There is also no dispute

that expert testimony regarding the cause of Guinn’s diabetes would assist the trier

of fact because the testimony “concerns matters that are beyond the understanding

of the average lay person.” See id. at 1262 (citing United States v. Rouco, 765

F.2d 983, 995 (11th Cir 1985)). Dr. Marks’ testimony is thus admissible under

Rule 702 if her methodology is sufficiently reliable.

      1.       The Methodology of Differential Diagnosis

      On appeal, Guinn contends Dr. Marks’ testimony is reliable because she

employed the scientifically accepted methodology of differential diagnosis.

Differential diagnosis “is accomplished by determining the possible causes for the

patient’s symptoms and then eliminating each of these potential causes until

reaching one that cannot be ruled out or determining which of those that cannot be

excluded is the most likely.” Westberry v. Gislaved Gummi AB, 178 F.3d 257, 262

(4th Cir. 1999); see also McClain, 401 F.3d at 1252 (describing differential




                                          14
diagnosis as “a process of identifying external causes by a process of

elimination”).6

       Although a reliable differential diagnosis need not rule out all possible

alternative causes, it must at least consider other factors that could have been the

sole cause of the plaintiff’s injury. As the Fourth Circuit explained in Westberry, a

“differential diagnosis that fails to take serious account of other potential causes

may be so lacking that it cannot provide a reliable basis for an opinion on

causation.” 178 F.3d at 265; see also In re Paoli R.R. Yard PCB Litig., 35 F.3d

717, 759 (3d Cir.1994) (“[A]t the core of differential diagnosis is a requirement

that experts at least consider alternative causes—this almost has to be true of any

technique that tries to find a cause of something.”). As other circuits have

recognized, an expert “must provide a reasonable explanation as to why ‘he or she

has concluded that [any alternative cause suggested by the defense] was not the

sole cause’” of the plaintiff’s injury. Best v. Lowe’s Home Ctrs., Inc., 563 F.3d

171, 179 (6th Cir. 2009) (quoting Paoli, 35 F.3d at 758 n.27); see also Lauzon v.

Senco Prods., Inc., 270 F.3d 681, 694 (8th Cir. 2001) (stating an expert must “be


       6
          Technically, differential diagnosis refers to a method of determining which of two
diseases a patient suffers from, whereas differential etiology is a term used to describe the
process by which the cause of an injury is determined. Following the trend among federal courts,
however, we will use the term differential diagnosis to refer to both concepts. See McClain, 401
F.3d at 1252.

                                              15
able to explain why other conceivable causes are excludable”); Westberry, 178

F.3d at 265 (holding an expert must provide some explanation of why other

potential causes were not the sole cause); Kanneankeril v. Terminix Int’l, Inc., 128

F.3d 802, 808 (3d Cir. 1997) (holding that after a defendant identifies a plausible

alternative cause, it is “necessary for the plaintiff's expert to offer a good

explanation as to why his or her conclusion remains reliable”).

      When properly conducted, differential diagnosis can be a reliable

methodology under Daubert. See Best, 563 F.3d at 178 (“An overwhelming

majority of the courts of appeals . . . have held that a medical opinion on causation

based upon a reliable differential diagnosis is sufficiently valid to satisfy the

[reliability] prong of the Rule 702 inquiry.”); Westberry, 178 F.3d at 262 (finding

differential diagnosis “has widespread acceptance in the medical community, has

been subject to peer review, and does not frequently lead to incorrect results”);

Paoli, 35 F.3d at 758 (same). However, “an expert does not establish the

reliability of his techniques or the validity of his conclusions simply by claiming

that he performed a differential diagnosis on a patient.” McClain, 401 F.3d at




                                           16
1253.7 We therefore must examine whether Dr. Marks correctly applied the

differential diagnosis methodology.

       2.      Dr. Marks’ Application of the Differential Diagnosis Methodology

       The district court did not abuse its discretion by finding that Dr. Marks’

differential diagnosis was unreliable under Daubert because she failed to

adequately consider possible alternative causes of Guinn’s weight gain and

diabetes. Dr. Marks has presented two possible ways in which she has considered

alternative causes. First, in her supplemental declaration, Dr. Marks stated she

believed other potential causes were not solely responsible because Guinn had

gained weight and developed diabetes soon after taking Seroquel when Guinn’s

other risk factors remained constant.8 Dr. Marks’ reliance on the temporal

proximity of the introduction of an additional risk factor, however, does not satisfy

the requirement that a differential diagnosis consider possible alternative causes

on the facts of this case.




       7
         Guinn’s contention that the shortcomings found in Dr. Marks’ analysis should go to the
weight and credibility of her testimony rather than its admissibility since Dr. Marks conducted a
differential diagnosis is therefore without merit.
       8
         At the Daubert hearing, Guinn’s counsel similarly characterized Dr. Marks’ conclusions
by stating that Dr. Marks “ruled all those other risk factors out as being the [sole] cause of the
diabetes on the day it occurred because they hadn’t caused it earlier.”

                                               17
        Temporal proximity is generally not a reliable indicator of a causal

relationship. This Circuit has held that “[t]he temporal connection between

exposure to chemicals and an onset of symptoms, standing alone, is entitled to

little weight in determining causation.” McClain, 401 F.3d at 1254 (quoting

Moore v. Ashland Chem. Inc., 151 F.3d 269, 278 (5th Cir. 1998)); see also, e.g.,

Black v. Food Lion, Inc., 171 F.3d 308, 313 (5th Cir. 1999) (holding that using

temporal proximity to establish causation “is not an exercise in scientific logic but

in the fallacy of post-hoc propter-hoc reasoning, which is as unacceptable in

science as in law.”); Cartwright v. Home Depot U.S.A., Inc., 936 F. Supp. 900, 906

(M.D. Fla. 1996) (“It is well settled that a causation opinion based solely on a

temporal relationship is not derived from the scientific method and is therefore

insufficient to satisfy the requirements of Fed. R. Evid. 702.”). Although temporal

proximity may constitute probative evidence in certain circumstances, see

Westberry, 178 F.3d at 265, several factors make it especially unreliable in this

case.

        First, the temporal relationship at issue in this case does not strongly

suggest that Seroquel played a role in causing Guinn’s diabetes. According to

Dr. Marks’ testimony, the development of diabetes occurs gradually over many

years, and approximately half of the patients who are diagnosed with diabetes

                                           18
have actually had the disease for about five years prior to diagnosis. Because

Guinn was diagnosed with diabetes only four years after beginning to take

Seroquel, the temporal relationship in this case does not provide strong evidence

of causation; in fact, it appears to equally indicate that Guinn may have already

developed diabetes before ever taking Seroquel.

      Second, Guinn’s numerous other risk factors for diabetes make it hard to

draw any inferences from the temporal proximity of Guinn’s weight gain to her

diagnosis of diabetes. Dr. Marks states these other risk factors were likely not the

sole cause of Guinn’s diabetes because they remained constant during the time she

took Seroquel. Dr. Marks, however, does not explain why having a stable risk

profile makes it unlikely that preexisting factors caused Guinn’s diabetes when

such factors put her at an extremely high risk for diabetes. Moreover, one

important risk factor—Guinn’s age—did not remain constant.

      Third, not only do Guinn’s numerous risk factors for diabetes make it hard

to draw any inference regarding causation, but the various other potential causes

of Guinn’s weight gain also make it hard to conclude that Seroquel even caused

Guinn to gain weight. The record indicates many other events, including back

surgery, quitting smoking, recovering from mental illness, and normal weight

fluctuations, may have played a role in Guinn’s weight gain during the time she

                                         19
was taking Seroquel. Although it would be unreasonable to require Dr. Marks to

conclusively rule out all alternative causes, she has provided no explanation of

how she concluded that, based on reasonable medical probability, Seroquel played

a role in Guinn’s weight gain despite these other possible explanations.

        After considering the nature of the temporal relationship at issue in this

case, we conclude Dr. Marks did not adequately consider possible alternative

causes simply by noting the temporal proximity between Guinn’s ingestion of

Seroquel and subsequent development of diabetes. We do not hold that a temporal

relationship can never be used to consider alternative causes of a plaintiff’s injury;

instead, we merely find that temporal proximity is not sufficient on the facts of this

case.

        Dr. Marks provided a second possible explanation of her consideration of

alternative causes by testifying that “[a]ll the [risk] factors [for diabetes] work

together.” Here Dr. Marks appears to be contending that since diabetes can have

multiple concurrent causes, she need not analyze the role played by each cause.

        An expert, however, cannot merely conclude that all risk factors for a

disease are substantial contributing factors in its development. “The fact that

exposure to [a substance] may be a risk factor for [a disease] does not make it an

actual cause simply because [the disease] developed.” Cano v. Everest Minerals

                                           20
Corp., 362 F. Supp. 2d 814, 846 (W.D. Tex. 2005). “[A]lthough the differential

diagnosis technique is well accepted . . . [, a finding] that all possible causes are

causes does not appear to have gained general acceptance in the medical and

scientific communities.” Id. While multiple factors can work together to cause

diabetes, Dr. Marks was still required to provide some analysis of why she

concluded that, more likely than not, Seroquel substantially contributed to Guinn’s

weight gain and such weight gain was among the factors that substantially

contributed to her diabetes.

      3.     Deviation from Standard Diagnostic Practices

      The reliability of Dr. Marks’ methodology is further called into question by

her failure to conduct the standard diagnostic techniques she normally used to rule

out potential alternative causes. See Best , 563 F.3d at 179; Paoli, 35 F.3d at 760.

Dr. Marks admitted that although she would normally conduct an interview to

determine the cause of a patient’s weight gain, she had only reviewed selections

from Guinn’s medical records prepared by her attorneys. Not only does this cast

doubt on Dr. Marks’ differential diagnosis, but it also violates a primary purpose

of Daubert: to ensure the expert “employs in the courtroom the same level of

intellectual rigor that characterizes the practice of an expert in the relevant field.”

Kuhmo Tire Co. v. Carmichael, 526 U.S. 137, 152, 119 S. Ct. 1167, 1176 (1999).

                                           21
       4.      Connection between Dr. Marks’ Conclusion and the Facts

       The district court did not abuse its discretion by alternatively holding that,

even if Dr. Marks’ differential diagnosis methodology was acceptable, her

testimony was unreliable because her conclusions were not logically supported by

the facts of this case. As the Supreme Court explained in General Electric

Company v. Joiner, “nothing in either Daubert or the Federal Rules of Evidence

requires a district court to admit opinion evidence which is connected to existing

data only by the ipse dixit of the expert. A court may conclude that there is simply

too great an analytical gap between the data and the opinion proffered.” 522 U.S.

136, 146, 118 S. Ct. 512, 519 (1997); see also McDowell v. Brown, 392 F.3d 1283,

1301–02 (11th Cir. 2004) (“[A]n expert opinion is inadmissible when the only

connection between the conclusion and the existing data is the expert’s own

assertions . . . .”).9

       In determining that the existing data did not support Dr. Marks’

conclusions, the district court noted Dr. Marks’ testimony established the

       9
          Guinn’s argument that the district court erred by applying the wrong state law causation
standard when excluding Dr. Marks’ testimony improperly conflates Daubert’s reliability
requirement with the showing necessary to survive summary judgment. See City of Tuscaloosa
v. Harcros Chems., Inc., 158 F.3d 548, 564–65 (11th Cir. 1998) (holding that courts should avoid
“the confusion and conflation of admissibility issues with issues regarding the sufficiency of the
plaintiff’s evidence to survive summary judgment”). Under Joiner, the facts of the case must
merely support the expert’s conclusions, which may or may not satisfy the plaintiff’s ultimate
burden on causation.

                                               22
following facts: Dr. Marks knew of no method to determine whether Guinn’s

weight gain was due to Seroquel or normal fluctuations in weight Guinn had

experienced throughout her life; it was “hard to know for sure” whether the point

in time Guinn developed diabetes had anything to do with Seroquel; Guinn had

numerous pre-existing health conditions that could have caused her weight gain;

Guinn had numerous risk factors for diabetes; these risk factors were sufficient to

cause Guinn’s diabetes; Dr. Marks had made no attempt to quantify the relative

contribution of Guinn’s risk factors; and Guinn likely would have developed

diabetes whether or not she ever took Seroquel. See Guinn, 598 F. Supp. 2d at

1246–47. Given this evidence, the district court did not abuse its discretion by

holding that Dr. Marks’ opinion was unsupported by the evidence.

      On appeal, Guinn has identified no evidence of specific causation other than

Dr. Marks’ testimony. The district court therefore did not err by holding that the

exclusion of Dr. Marks’ testimony is a basis for granting summary judgment in

favor of AstraZeneca. See Allison v. McGhan Medical Corp., 184 F.3d 1300,

1304 (11th Cir. 1999); Haggerty v. The Upjohn Co., 950 F. Supp. 1160, 1168

(S.D. Fla. 1996).




                                         23
B.     Failure of Dr. Marks’ Testimony to Create a Genuine Issue of Material Fact

       Alternatively, the district court did not err by holding that, even if

Dr. Marks’ testimony were admissible, her statements would not have created a

genuine issue of material fact with regard to specific causation. Under Florida

law, a plaintiff:

       must introduce evidence which affords a reasonable basis for the
       conclusion that it is more likely than not that the conduct of the
       defendant was a substantial factor in bringing about the result. A
       mere possibility of such causation is not enough; and when the matter
       remains one of pure speculation or conjecture, or the probabilities are
       at best evenly balanced, it becomes the duty of the court to direct a
       verdict for the defendant.

Gooding v. Univ. Hosp. Bldg., Inc., 445 So.2d 1015, 1018 (Fla. 1984) (quoting

Prosser, Law of Torts § 41 (4th Ed.1971)); see also Christopher v. Cutter Labs.,

53 F.3d 1184, 1191 (11th Cir. 1995) (further discussing the Florida standard for

proving causation).

       The district court did not err by holding that Dr. Marks’ testimony amounted

to mere speculation as to whether Seroquel was a substantial contributing factor in

causing Guinn’s diabetes. Dr. Marks’ testimony reveals several facts that cast

substantial doubt on whether Seroquel contributed to Guinn’s development of

diabetes, including the following: approximately two-thirds of all patients who

take Seroquel do not experience weight gain; many other factors plausibly could

                                           24
have caused Guinn’s weight gain; about half of all patients have diabetes five

years prior to diagnosis (which would have been before Guinn began taking

Seroquel); Guinn had multiple risk factors that could have been the sole cause of

Guinn’s diabetes; and Dr. Marks was unable to determine the relative risk of each

factor. Given these facts, the district court did not err by holding that no

reasonable juror could find Seroquel was, more likely than not, a substantial

contributing factor in causing Guinn’s diabetes.10

                                    IV. CONCLUSION

       For the reasons stated above, we hold the district court did not err by

excluding Dr. Marks’ testimony and holding that Guinn failed to establish a

genuine issue of material fact on the issue of specific causation. We therefore

affirm the district court.

       AFFIRMED.




       10
          On appeal, the parties dispute whether Florida law also requires Guinn to show that but
for her ingestion of Seroquel, she would not have developed diabetes. As the district court held,
however, this issue of Florida law need not be addressed because Guinn has failed to meet her
burden under the more lenient substantial contributing factor test.

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