Title: In re: Accutane Litigation

State: new-jersey

Issuer: New Jersey Supreme Court

Document:

SYLLABUS

This syllabus is not part of the opinion of the Court. It has been prepared by the Office of the
Clerk for the convenience of the reader. It has been neither reviewed nor approved by the
Court. In the interest of brevity, portions of an opinion may not have been summarized.)

                      In re: Accutane Litigation (A-25-17) (079958)

Argued April 23, 2018 -- Decided August 1, 2018

LaVECCHIA, J., writing for the Court.

       At issue in this appeal is the admissibility of scientific evidence under the New Jersey
Rules of Evidence. Plaintiffs claim that a causal connection exists between Accutane, a
prescription drug used in the treatment of nodular acne, and Crohn’s disease, a chronic
gastrointestinal illness.

        Accutane is a prescription medication developed by defendants and approved by the
FDA to treat recalcitrant nodular acne. Accutane’s alleged role as a cause of gastrointestinal
disease ultimately resulted in a series of lawsuits against defendants. The present matter
involves over two thousand plaintiffs who allege that they developed Crohn’s disease as a
result of taking Accutane. In the years since many earlier Accutane cases were decided,
epidemiological studies were published, all of which concluded that Accutane is not causally
associated with the development of Crohn’s disease. Defendants in this mass tort litigation
filed a motion seeking a hearing on the association between Accutane and Crohn’s disease.

        The hearing focused on the epidemiological studies. See pp. 12-20. The parties do
not dispute that there is an acknowledged hierarchy of medical evidence and that, generally,
epidemiological studies are preferred to unsystematic clinical observations. Researchers
sometimes look to animal studies for determining a given agent’s toxicity in humans. When
there is a substantial body of epidemiologic evidence that addresses the causal issue, animal
toxicology has much less probative value.

       Plaintiffs produced Dr. Arthur Asher Kornbluth, a gastroenterologist, and Dr. David
Madigan, a statistician. Dr. Kornbluth’s testimony had two themes: explaining why he
found the epidemiological studies unreliable and uninformative regarding causation, and
explaining his reliance on other forms of evidence such as case reports, animal studies,
causality assessments, and his biological mechanism hypothesis. See pp. 20-27. He stated
that most of the studies that looked specifically for Crohn’s disease were fatally flawed
because they did not account for its “prodrome,” or the period between the onset of
symptoms and diagnosis, and that some studies did not have enough patients and thus were
“underpowered.” Dr. Madigan focused on whether the epidemiological studies were
appropriately designed to discover an association between Crohn’s disease and Accutane, if
such an association did exist. See pp. 27-32. He concluded that, after accounting for the
prodrome, the epidemiological studies do not provide statistically reliable information.
                                                1
        Defendants produced gastroenterologist Dr. Maria Oliva-Hemker, and biostatistician
Dr. Steven Goodman. Dr. Oliva-Hemker’s testimony focused on disputing Dr. Kornbluth’s
testimony and explaining why epidemiological studies are preferred to case reports and
animal studies in the hierarchy of evidence. See pp. 32-36. She explained that Crohn’s
disease’s cause is unknown, that any theory regarding a biological mechanism was therefore
unreliable, and that scientists would not ignore the available epidemiological evidence in
favor of a hypothesis about a biological mechanism that has not been submitted for peer
review. She added that the study on which plaintiffs’ experts relied for their determination of
the prodrome was very small and not representative of the average prodromal period. She
also explained why Dr. Kornbluth’s reliance on animal studies was flawed, namely because
dogs cannot get inflammatory bowel disease. Dr. Goodman’s testimony focused on why the
epidemiologic evidence is the best available evidence on the question of Accutane’s causal
relation to Crohn’s disease and why a meta-analysis was a proper way of pooling those study
results to reach a conclusion that Accutane does not cause Crohn’s disease. See pp. 36-41.
His testimony explained why he and others in the scientific community would not regard the
epidemiological studies to be invalid due to a prodrome issue.

        After the hearing, the trial court excluded plaintiffs’ experts’ testimony. The court
regarded the standard established in Rubanick v. Witco Chemical Corp., 
125 N.J. 421
(1991), as requiring an expert opinion to be based on a “sound, adequately-founded scientific
methodology involving data of the type reasonably relied on by experts in the scientific
field.” The court found plaintiffs’ experts’ testimony lacking, determining their examination
of the evidence was a “conclusion-driven” attempt to cherry-pick evidence supportive of
their opinion while dismissing better forms of evidence that did not support their opinion.

       The Appellate Division reversed. 
451 N.J. Super. 153, 163-64 (App. Div. 2017).
While noting the trial court’s opportunity to view the witnesses firsthand, the panel expressed
the view that the trial court’s negative reaction to plaintiffs’ experts was not supported by the
record. Id. at 211. The panel further noted that, although a trial court’s decision to admit or
exclude evidence is subject to an abuse of discretion standard, a reviewing court owes
“somewhat less deference” to determinations regarding expert testimony. Id. at 196-97.

        The Court granted certification in this matter, 
231 N.J. 531 (2017), to address whether
the trial court properly excluded plaintiffs’ experts’ testimony, whether the Appellate
Division employed the correct standard in reviewing that decision, and whether New Jersey’s
standard for assessing the reliability of expert witnesses is in need of clarification. With
regard to the last issue, the Court considers whether the factors set forth in Daubert v. Merrell
Dow Pharmaceuticals, Inc., 
509 U.S. 579 (1993), would further elucidate New Jersey’s
standard for the admissibility of expert testimony.

HELD: There is little distinction between Daubert’s principles regarding expert testimony
and New Jersey’s, and Daubert’s factors for assessing the reliability of expert testimony will
aid New Jersey trial courts in their role as the gatekeeper of scientific expert testimony in
civil cases. Accordingly, the Court now reconciles the standard under N.J.R.E. 702, and
relatedly N.J.R.E. 703, with the federal Daubert standard to incorporate its factors for civil
                                                 2
cases. Analysis of the record in this case leads to a clear result: the trial court properly
excluded plaintiffs’ experts’ testimony. Moreover, the Court reaffirms that the abuse of
discretion standard must be applied by an appellate court assessing whether a trial court has
properly admitted or excluded expert scientific testimony in a civil case. In this matter, the
trial court did not abuse its discretion in its evidential ruling and, therefore, the Appellate
Division erred in reversing the trial court’s exclusion of the testimony of plaintiffs’ experts.

1. New Jersey Rules of Evidence 702 and 703 control the admission of expert testimony. In
State v. Kelly, 
97 N.J. 178, 223 (1984), the Court identified three prerequisites to a
determination that expert testimony is permissible: “(1) the intended testimony must concern
a subject matter that is beyond the ken of the average juror; (2) the field testified to must be
at a state of the art such that an expert’s testimony could be sufficiently reliable; and (3) the
witness must have sufficient expertise to offer the intended testimony.” The Kelly criteria
elucidated application of the then-applicable “general acceptance” standard for admitting
scientific evidence. For many years, the majority of state and federal jurisdictions, including
New Jersey, adhered to the “general acceptance” standard first put forth in Frye v. United
States, 
293 F. 1013 (D.C. Cir. 1923). Then, in 1991, the New Jersey Supreme Court moved
away from rigid adherence to the general acceptance standard. (pp. 6-9)

2. Rubanick marked the broadening of that standard. The Rubanick Court instructed courts
to “consider whether others in the field use similar methodologies,” 
125 N.J. at 449-50, and
explained that the proper inquiry is whether comparable “experts in the field would actually
rely on that information,” id. at 452. In Landrigan v. Celotex Corp., the Court elaborated:
when relying on epidemiological studies, the trial court should review them and “then
determine whether the expert’s opinion is derived from a sound and well-founded
methodology that is supported by some expert consensus in the appropriate field.” 
127 N.J. 404, 417 (1992). Moreover, Landrigan suggested tools for trial courts to use in rendering
gatekeeping determinations about the reliability of an expert’s methodology when the
ultimate scientific opinion is not itself generally accepted, including “reference to
professional journals, texts, conferences, symposia, or judicial opinions accepting the
methodology.” Ibid. Thus, methodology may be assessed for soundness using some of the
same tools as general acceptance identifies for outcome. (pp. 55-58)

3. Not long after those dual holdings, the Supreme Court issued its seminal Daubert opinion,
pronouncing that Frye had been superseded by the adoption of the Federal Rules of
Evidence, 
509 U.S.  at 585-87, and fashioning a new standard that “entails a preliminary
assessment of whether the reasoning or methodology underlying the testimony is
scientifically valid and . . . can be applied to the facts in issue,” id. at 592-93. The Court
noted that “many factors will bear on the inquiry,” which became known as the Daubert
factors. Id. at 593-94. The Court described the trial court’s task as a “flexible” inquiry into
the scientific principles at issue, ibid., one whose “overarching subject is the scientific
validity -- and thus the evidentiary relevance and reliability -- of the principles that underlie a
proposed submission,” id. at 594-95. As in Rubanick and Landrigan, the Daubert Court
underscored that the trial court must focus on the expert’s principles and methodology -- not
on the conclusions they generate. Id. at 595. The Supreme Court elaborated on its Daubert
                                                   3
standard with two cases which, combined, round out the Daubert trilogy: General Electric
Co. v. Joiner, 
522 U.S. 136 (1997), and Kumho Tire Co. v. Carmichael, 
526 U.S. 137 (1999).
Federal Rule of Evidence 702 was amended in 2000 to reflect the Supreme Court’s trilogy of
cases outlining the Daubert standard. A majority of states have adopted some form of the
Daubert standard, either explicitly or implicitly. (pp. 58-65)

4. After the Daubert trilogy, the Court revisited the topic of the trial court’s gatekeeping role
under N.J.R.E. 702. In Kemp ex rel. Wright v. State, 
174 N.J. 412 (2002), the Court held
that the Rubanick standard should apply whenever “a medical cause-effect relationship has
not been confirmed by the scientific community but compelling evidence nevertheless
suggests that such a relationship exists.” Id. at 430. The Court explained that, by requiring a
pretrial Rule 104 evidentiary hearing, the trial court would be able to properly “assess
whether the expert’s opinion is based on scientifically sound reasoning or unsubstantiated
personal beliefs couched in scientific terminology.” Id. at 427. The Kemp Court observed
that New Jersey had not amended N.J.R.E. 702 to include “the three-factor test for the
admissibility of expert testimony that is part of the Federal rule as amended in response to
Daubert.” Id. at 424 n.3. Nor has any such action has been taken since. (pp. 65-67)

5. When the Court modified the general acceptance standard to adopt a more relaxed
approach for causation expert testimony in toxic tort litigation, and later for all medical
cause-effect expert testimony, it envisioned the trial court’s function as that of a gatekeeper
-- deciding what is reliable enough to be admitted and what is to be excluded. Those are not
credibility determinations that are the province of the jury, but rather legal determinations
about the reliability of the expert’s methodology. The Court reinforces the rigor expected of
the trial court in that role under existing New Jersey case law. (pp. 67-70)

6. Here, the Appellate Division panel stated that, although a trial court’s decision to admit or
exclude evidence is subject to an abuse of discretion standard, a reviewing court owes
“somewhat less deference to a trial court’s determination” regarding expert testimony. 
451 N.J. Super. at 197. As support for that proposition, the panel relied on a criminal case that
applied the Frye standard. The Court now reaffirms that the abuse of discretion standard
applies in the appellate review of a trial court’s determination to admit or deny scientific
expert testimony on the basis of unreliability in civil matters. (pp. 70-72)

7. The Court details the assessments made by the trial court in reaching its decision to
exclude the testimony of plaintiffs’ experts in this case. Both Doctors Madigan and
Kornbluth employed a methodology whereby they disregarded eight of nine epidemiological
studies and relied on case reports and animal studies. Despite their expressed concerns
regarding study power -- which is based in part on the size of the study at issue -- in rejecting
the epidemiological studies, plaintiffs’ experts were willing to ignore any such concern when
relying on other studies to form their opinion as to the median prodromal period. The many
contradictions in the experts’ methodology were not lost on the trial court, which concluded
that experts in the scientific community would not accept as consistent with scientific norms
a methodology such as that used by plaintiffs’ experts. Moreover, Dr. Kornbluth never
submitted his ideas concerning biological mechanism or Accutane’s relation to Crohn’s
                                                4
disease for peer review or publication. In sum, the trial court explained its reasons for
concluding that plaintiffs’ experts deviated from core scientific principles and strayed from
their own claimed methodology in order to reach their conclusions. Under the abuse of
discretion standard and the principles of Rubanick, Landrigan, and Kemp, the trial court’s
determination is unassailable. The Appellate Division judgment is reversed. (pp. 72-79)

8. In respect of the gatekeeping role, the Court emphasizes that it expects the trial court to
assess both the methodology used by the expert to arrive at an opinion and the underlying
data used in the formation of the opinion. There is not much light between New Jersey’s
standard and that which has developed in the federal sphere under Daubert’s initial
instruction. Importantly, Daubert identified a non-exhaustive list of factors for courts to
consider using, if helpful. See 
509 U.S.  at 593-95. Distilled, the general factors identified as
perhaps pertinent for consideration, but not dispositive or exhaustive, are: (1) Whether the
scientific theory can be, or at any time has been, tested; (2) Whether the scientific theory has
been subjected to peer review and publication, noting that publication is one form of peer
review but is not a “sine qua non”; (3) Whether there is any known or potential rate of error
and whether there exist any standards for maintaining or controlling the technique’s
operation; and (4) Whether there does exist a general acceptance in the scientific community
about the scientific theory. That last consideration -- general acceptance in the scientific
community -- continues to have a bearing. The Court adopts the use of the Daubert factors
but stops short of declaring New Jersey a “Daubert jurisdiction.” First, to date New Jersey
retains the general acceptance test for reliability in criminal matters. Second, while the
factors are helpful, and while individual cases may be persuasive in appropriate settings,
there are discordant views about the gatekeeping role among Daubert jurisdictions. The
Court’s view of proper gatekeeping in a methodology-based approach to reliability for expert
scientific testimony requires the proponent to demonstrate that the expert applies his or her
scientifically recognized methodology in the way that others in the field practice the
methodology. That approach was employed by the trial court here. (pp. 79-85)

       REVERSED.

CHIEF JUSTICE RABNER and JUSTICES ALBIN, FERNANDEZ-VINA,
SOLOMON, and TIMPONE join in JUSTICE LaVECCHIA’s opinion. JUSTICE
PATTERSON did not participate.

                                               5
                                     SUPREME COURT OF NEW JERSEY
                                       A-
25 September Term 2017
                                                079958

IN RE: ACCUTANE LITIGATION

         Argued April 23, 2018 – Decided August 1, 2018

         On certification to the Superior Court,
         Appellate Division, whose opinion is
         reported at 
451 N.J. Super. 153 (App. Div.
         2017).

         Paul W. Schmidt (Covington & Burling) of
         the District of Columbia bar, admitted pro
         hac vice, argued the cause for appellants
         Hoffmann-La Roche Inc. and Roche Laboratories
         Inc. (Gibbons, Dughi Hewit & Domalewski,
         Covington & Burling, and Peabody & Arnold,
         attorneys; Natalie H. Mantell, Russell L. Hewit,
         Paul W. Schmidt, Michael X. Imbroscio (Covington
         & Burling) of the District of Columbia bar,
         admitted pro hac vice, and Colleen M. Hennessey
         (Peabody & Arnold) of the Massachusetts bar,
         admitted pro hac vice, of counsel and on the
         briefs).

         Bruce D. Greenberg and David R. Buchanan argued
         the cause for respondents Craig Abernethy, et al.
         (Lite DePalma Greenberg, Seeger Weiss, Weitz &
         Luxenberg, and Beggs & Lane, attorneys; Bruce D.
         Greenberg, David R. Buchanan, Peter Samberg, and
         Mary Jane Bass (Beggs & Lane) of the Florida bar,
         admitted pro hac vice, on the briefs).

         Edward J. Fanning, Jr., argued the cause for
         amici curiae HealthCare Institute of New
         Jersey, New Jersey Business & Industry
         Association, Commerce and Industry
         Association of New Jersey, and New Jersey
         Chamber of Commerce (McCarter & English,
         attorneys; Edward J. Fanning, Jr., and David
         R. Kott, of counsel and on the brief, and
         Gary R. Tulp, on the brief).

                               1
Christopher M. Placitella argued the cause
for amicus curiae New Jersey Association for
Justice (Cohen, Placitella & Roth,
attorneys; Christopher M. Placitella and
Jared M. Placitella, of counsel and on the
brief).

Allan Kanner submitted a brief on behalf of
amicus curiae Allan Kanner, Esquire (Kanner
& Whiteley, attorneys).

Diana C. Manning submitted a brief on behalf
of amicus curiae DRI – The Voice of the Defense
Bar (Bressler, Amery & Ross, Plunkett Cooney,
and DRI – The Voice of the Defense Bar,
attorneys; Diana C. Manning, Mary Massaron
(Plunkett Cooney) of the Michigan and New York
bars, admitted pro hac vice, Hilary A.
Ballentine (Plunkett Cooney) of the Michigan
bar, admitted pro hac vice, and John F. Kuppens
(DRI – The Voice of the Defense Bar) of the
South Carolina bar, admitted pro hac vice, on
the brief).

Susan J. Kraham submitted a brief on behalf
of amicus curiae Ironbound Community
Corporation (Morningside Heights Legal
Services, attorneys; Susan J. Kraham and
Edward Lloyd, on the brief).

Shalom D. Stone submitted a brief on behalf
of amicus curiae New Jersey Civil Justice
Institute (Stone Conroy, attorneys).

Melinda Martinson submitted a brief on behalf
of amici curiae American Medical Association,
Medical Society of New Jersey, American Academy
of Dermatology, Society for Investigative
Dermatology, American Acne and Rosacea Society,
and Dermatological Society of New Jersey (Medical
Society of New Jersey and Powers Pyles Sutter &
Verville, attorneys; Melinda Martinson, and Ronald
S. Connelly (Powers Pyles Sutter & Verville) of
the District of Columbia and Maryland bars,
admitted pro hac vice, on the brief).

                      2
         Gavin J. Rooney submitted a brief on behalf
         of amici curiae Kenneth S. Broun, Daniel J.
         Capra, Joanne A. Epps, David L. Faigman,
         Laird Kirkpatrick, Michael M. Martin, Liesa
         Richter, and Stephen A. Saltzburg
         (Lowenstein Sandler, attorneys).

         Gregory S. Chernack submitted a letter brief
         on behalf of amicus curiae Pharmaceutical
         Research and Manufacturers of America
         (Hollingsworth, attorneys).

    JUSTICE LaVECCHIA delivered the opinion of the Court.

    At issue in this appeal involving a civil mass tort action

is the admissibility of scientific evidence under the New Jersey

Rules of Evidence.

    Plaintiffs claim that a causal connection exists between

Accutane, a prescription drug used in the treatment of nodular

acne, and Crohn’s disease, a chronic gastrointestinal illness.

Litigation in New Jersey over Accutane’s side effects has

spanned more than a decade.   This action is a continuation in

that series of litigated matters.   Since those actions first

commenced in New Jersey in 2005, a number of epidemiological

studies have been published, all concluding that there is no

causal relationship between Accutane and Crohn’s disease.

Plaintiffs’ experts dispute the conclusions of those studies,

calling them flawed and lacking in value.   Having rejected the

evidence and conclusions of those epidemiological studies, one

of plaintiffs’ experts, relying on other facts and forms of

                                3
data, asserts the contrary view that Accutane can in fact cause

Crohn’s disease.    Defendants challenged the methodology used by

both of plaintiffs’ experts as unreliable and sought the

exclusion of that expert testimony.

      After a Rule 104 pretrial evidentiary hearing, the trial

court excluded the testimony, holding that plaintiffs’ experts’

methodology was unsound because they did not interpret the

relevant data and apply it to the facts of this case as would

other experts in the field.    The Appellate Division reversed,

concluding that plaintiffs’ experts employed a sound methodology

and simply interpreted the data differently than defendants’

experts.

      Our Court was among the foremost to shift from exclusive

reliance on a “general acceptance” standard1 for testing the

reliability of scientific expert testimony to a methodology-

based approach.    See Landrigan v. Celotex Corp., 
127 N.J. 404,

414 (1992); Rubanick v. Witco Chem. Corp., 
125 N.J. 421, 447

(1991).    We initially took that step to allow the parties in

toxic tort civil matters to present novel scientific evidence of

causation if, after the trial court engages in rigorous

gatekeeping when reviewing for reliability, the proponent

persuades the court of the soundness of the expert’s reasoning

1   Frye v. United States, 
293 F. 1013 (D.C. Cir. 1923).

                                  4
and methodology.   Two years later, with its Daubert2 decision,

the United States Supreme Court also abandoned the general

acceptance test in favor of a methodology-based approach that

entrusted trial courts with the role of gatekeeper.     Both our

civil standard and the federal standard moved in the same

direction and towards the same common goal.   Although the two

standards are similar both in practice and in overall

philosophy, we have never adopted Daubert or incorporated the

factors identified in Daubert for use by our courts when

performing the gatekeeper role.

      We granted certification in this matter to address whether

the trial court properly excluded plaintiffs’ experts’

testimony, whether the Appellate Division employed the correct

standard in reviewing and overturning that decision, and whether

our standard for assessing the reliability of expert witnesses

is in need of clarification.   It is with regard to the last

issue that we are asked whether the Daubert standard’s factors

would further elucidate our own standard for the admissibility

of expert testimony.   We believe that they would.

      We perceive little distinction between Daubert’s principles

regarding expert testimony and our own, and believe that its

factors for assessing the reliability of expert testimony will

2   Daubert v. Merrell Dow Pharms., Inc., 
509 U.S. 579 (1993).
                                  5
aid our trial courts in their role as the gatekeeper of

scientific expert testimony in civil cases.   Accordingly, we now

reconcile our standard under N.J.R.E. 702, and relatedly

N.J.R.E. 703, with the federal Daubert standard to incorporate

its factors for civil cases.

    This case -- with its adversarial setting and full record

-- provides the appropriate setting for illustrating how courts

should evaluate the methodology of a credentialed expert when

determining whether an opinion is based on scientifically sound

reasoning.   See Kemp ex rel. Wright v. State, 
174 N.J. 412, 427

(2002).   Our analysis of this record leads to a clear result:

the trial court properly excluded plaintiffs’ experts’

testimony.   Moreover, we reaffirm that the abuse of discretion

standard must be applied by an appellate court assessing whether

a trial court has properly admitted or excluded expert

scientific testimony in a civil case.   In this matter, the trial

court did not abuse its discretion in its evidential ruling and,

therefore, the Appellate Division erred in reversing the trial

court’s exclusion of the testimony of plaintiffs’ experts.

                                I.

    Before diving into the record and its contested scientific

evidence, we set forth some basic background to the evidential

standards in issue.

                                 6
     New Jersey Rules of Evidence 702 and 703 control the

admission of expert testimony.   N.J.R.E. 702 provides that

“[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.”   N.J.R.E. 703 states that

          [t]he facts or data in the particular case
          upon which an expert bases an opinion or
          inference may be those perceived by or made
          known to the expert at or before the hearing.
          If of a type reasonably relied upon by experts
          in the particular field in forming opinions or
          inferences upon the subject, the facts or data
          need not be admissible in evidence.

     In State v. Kelly, this Court applied Rule 702’s similarly

worded predecessor, Evidence Rule 56, and identified three

prerequisites to a determination that expert testimony is

permissible:

          (1) the intended testimony must concern a
          subject matter that is beyond the ken of the
          average juror; (2) the field testified to must
          be at a state of the art such that an expert’s
          testimony could be sufficiently reliable; and
          (3) the witness must have sufficient expertise
          to offer the intended testimony.

          [
97 N.J. 178, 223 (1984).]

That standard provides the baseline for the admissibility of

expert testimony.   See Official Comments to N.J.R.E. 702 (noting

that N.J.R.E. 702 incorporates standard articulated by Kelly).

                                 7
    The Kelly criteria elucidated application of the then-

applicable “general acceptance” standard for admitting

scientific evidence, which originated in Frye v. United States,

293 F. 1013 (D.C. Cir. 1923).   In Frye, the then Court of

Appeals for the District of Columbia excluded an expert’s

testimony concerning results from an early form of lie-detector

test.   Id. at 1013-14 (“[W]hile courts will go a long way in

admitting expert testimony deduced from a well-recognized

scientific principle or discovery, the thing from which the

deduction is made must be sufficiently established to have

gained general acceptance in the particular field in which it

belongs.”).   For many years, the majority of state and federal

jurisdictions, including New Jersey, adhered to the “general

acceptance” standard first put forth in Frye.   See Daubert v.

Merrell Dow Pharms., Inc., 
509 U.S. 579, 585-87 (1993)

(observing that Frye had been “the dominant standard for

determining the admissibility of novel scientific evidence” for

over seventy years).   Then, in 1991, prior to the United States

Supreme Court’s seminal Daubert decision, in which the Court

interpreted the Federal Rules of Evidence on expert testimony,

our Court moved away from rigid adherence to the general

acceptance standard.

    This Court held in Rubanick that a court may admit expert

scientific evidence on a causation theory in toxic tort

                                 8
litigation so long as “it is based on a sound, adequately-

founded scientific methodology involving data and information of

the type reasonably relied on by experts in the scientific

field.”   
125 N.J. at 449.   One year later, in Landrigan, we

reinforced that in toxic tort matters involving novel theories

of causation the trial court is obliged to review data and

studies relied on by experts proffering an opinion in order to

“determine whether the expert’s opinion is derived from a sound

and well-founded methodology that is supported by some expert

consensus in the appropriate field.”     
127 N.J. at 417.   In Kemp,

we expanded Rubanick to all novel medical causation

circumstances and solidified the requirement of a pretrial Rule

104 hearing for assessing an expert’s testimony.    
174 N.J. at
 430.   Presently, a Kemp hearing is a common pretrial occurrence

for resolving the reliability of expert scientific testimony.

       A Kemp hearing provides the record for the present matter.

After the conclusion of that hearing, the trial court determined

that the contested evidence did not pass muster under our

Rubanick evidentiary standard for assessing the reliability of

proffered expert scientific testimony.    The court made its

findings in response to argument by the parties, rejecting the

soundness of plaintiffs’ experts’ methodology.

                                II.

                                 A.

                                 9
    Accutane is a prescription medication developed by

defendants Hoffman-La Roche Inc. and Roche Laboratories Inc.

(defendants) and approved by the FDA in 1982 to treat

recalcitrant nodular acne.     Known chemically as isotretinoin,

Accutane is part of a family of Vitamin A derivatives called

retinoids.    During the pre-approval clinical studies of

Accutane, roughly a fifth of patients suffered some form of

gastrointestinal side effects.     Defendants also learned, after

Accutane was on the market, that users were suffering symptoms

of gastrointestinal upset such as inflammatory bowel disease

(IBD) and peptic ulceration.     Defendants eventually amended

Accutane’s warning label in 1984 to add that Accutane was

“temporally associated with inflammatory bowel disease.”

    Accutane’s alleged role as a cause of gastrointestinal

disease ultimately resulted in a series of lawsuits against

defendants.   On May 2, 2005, this Court designated all pending

and future New Jersey actions involving Accutane as a mass tort

Multicounty Litigation (MCL) pursuant to Rule 4:38A.     All cases

involving Accutane were subsequently transferred to Atlantic

County to be heard on a coordinated basis.

    The present matter, the latest in a series of cases,3

involves over two thousand plaintiffs who allege that they

3  As noted in the Appellate Division’s opinion in this matter,
this case is one of many mass tort cases spanning over a decade
                                  10
developed Crohn’s disease as a result of taking Accutane.     The

following basic information is not a matter of dispute between

the parties.   Crohn’s disease is a form of IBD characterized by

inflammation and ulcers in the digestive tract that can result

in abdominal pain and other complications.   Crohn’s disease is

distinguished from ulcerative colitis, the other form of IBD, by

its ability to appear in any portion of the digestive tract,

such as the esophagus and small intestine, whereas ulcerative

colitis appears only in the large intestine.   The scientific

community appears to agree that Crohn’s disease and ulcerative

colitis are subject to slightly different risk factors.   The

exact cause of Crohn’s disease is unknown.

    In the years since many of the earlier cases regarding

Accutane and IBD were decided, a series of epidemiological

studies were published regarding the potential connection

between Accutane and IBD, all of which concluded that Accutane

is not causally associated with the development of Crohn’s

disease.   On September 23, 2014, defendants filed a motion

seeking a Kemp hearing on the association between Accutane and

Crohn’s disease.   Defendants argued that epidemiological studies

published in the scientific literature over the last several

years effectively disproved any general causal association

relating to Accutane. In re Accutane Litig., 
451 N.J. Super. 153, 164-65 & n.6 (App. Div. 2017).
                                11
between Accutane and Crohn’s disease.   They contended that those

studies are “the most important and reliable data that exists on

Accutane and Crohn’s disease” and are superior to other forms of

evidence previously used in the MCL litigation such as case

reports, animal studies, and theories on biological mechanisms.

     The trial court scheduled a Kemp hearing to begin on

February 2, 2015.

                                 B.

     The testimony focused intently on the aforementioned

epidemiological studies.    Accordingly, some background on the

use of such studies in the formation of causal analyses provides

context for the discussion of the evidence by the parties and

the trial court.    Much of the following discussion is taken from

the Federal Judicial Center’s Reference Manual on Scientific

Evidence (3d ed. 2011), a source frequently relied on in the

trial court proceedings.4

     Epidemiology “studies the incidence, distribution, and

etiology of disease in human populations.”    Id. at 551.   More

particularly, epidemiology focuses on the question of “general

causation,” that is, whether the agent under study is “capable

4  Three sections of the Reference Manual are relevant to this
appeal: the Reference Guide on Statistics, by David H. Kaye and
David A. Freedman; the Reference Guide on Epidemiology by
Michael D. Green et al.; and the Reference Guide on Medical
Testimony by John B. Wong et al. For ease of reference, we
refer to the Reference Manual as a single document.
                                 12
of causing disease,” and does not focus on specific causation in

a particular individual.    Id. at 552.   Epidemiology is premised

on the idea “that disease is not distributed randomly” and that

certain groups are at increased risk of contracting a particular

disease.   Id. at 551.

       Epidemiological studies are used to test whether exposure

to a particular agent causes a harmful effect or disease.      Id.

at 551-52.   Although such studies may reveal an association

between a particular agent and a particular disease, “[a]n

association identified in an epidemiological study may or may

not be causal,” and causation must be assessed in consideration

with the “strengths and weaknesses of the study’s design and

implementation, as well as a judgment about how the study

findings fit with other scientific knowledge.”    Id. at 552-53.

When evaluating a study’s evidential value, a basic

consideration is whether the particular study used a sound

methodology, as well as the extent to which the study’s results

may be due to “bias, confounding, or sampling error.”     Id. at

554.

       Among the different kinds of epidemiological studies,

randomized trials are “considered the gold standard for

determining the relationship of an agent to a health outcome or

                                 13
adverse side effect.”     Id. at 555.5   Where randomized trials

cannot be performed, researchers rely on “observational”

studies.   Id. at 555-57.    There are two types of such studies:

(1) a case-control study, which measures and compares the

frequency of exposure in the group with the disease (cases) and

a similar group without the disease (controls); and (2) a cohort

study, which compares a group of exposed and unexposed

individuals over a period of time.       Id. at 557-59.

Observational studies identify a group of individuals exposed to

the agent in question and then compare their rate of disease to

that of an unexposed group.     Id. at 556.    A weakness in such

studies is “the possibility of differences in the two

populations being studied with regard to risk factors other than

exposure to the agent.”     Ibid.   Investigators generally cannot

control for a variety of “confounders” that may distort such a

study’s results.   Ibid.    A confounder’s influence on a study’s

results therefore must be considered in the study’s design and

in the interpretation of its results.       Ibid.

5  As the Reference Manual explains, a randomized trial is
performed by randomly assigning study subjects into one of two
groups: one group is exposed to the agent in question and the
other group is not. Id. at 555. The group not exposed to the
agent is given a placebo, an inactive ingredient. Ibid. The
feasibility of such studies is often limited due to the
potentially harmful side effects associated with a particular
agent. Ibid.

                                    14
    Thus, when it comes to using epidemiological studies in

legal matters, three basic questions arise in the assessment of

a study’s methodological soundness:

         1. Do the results of an epidemiologic study
         or studies reveal an association between an
         agent and disease?

         2. Could this association have resulted from
         limitations of the study (bias, confounding,
         or sampling error), and, if so, from which?

         3. Based on the analysis of limitations in
         Item 2, above, and on other evidence, how
         plausible is a causal interpretation of the
         association?

         [Id. at 554.]

    Once an association has been found between exposure to a

particular agent and development of a specific disease,

researchers then consider whether that association “reflects a

true cause-effect relationship.”       Id. at 597.   To do so,

researchers look to alternative explanations, such as bias or

confounding factors, and then consider how well-recognized

“guidelines for inferring causation from an association apply to

the available evidence.”     Id. at 598.    However, and importantly,

those accepted “guidelines are employed only after a study finds

an association to determine whether that association reflects a

true causal relationship.”    Id. at 598-99.     Commonly referred to

                                  15
as the “Hill criteria” or “Hill factors,”6 they consist of the

following:

               1.    Temporal relationship,

               2.    Strength of the association,

               3.    Dose-response relationship,

               4.    Replication of the findings,

               5.    Biological plausibility (coherence
                     with existing knowledge),

               6.    Consideration of alternative
                     explanations,

               7.    Cessation of exposure,

               8.    Specificity of the association, and

               9.    Consistency with other knowledge.

               [Id. at 600.]

     The Reference Manual contains a section entitled Reference

Guide on Medical Testimony, which provides a “Hierarchy of

medical evidence.”    Id. at 723.    The parties in this matter do

not dispute that the Reference Manual and the scientific

community as a whole acknowledge such a hierarchy.       The

Reference Manual summarizes it as follows:      “[w]hen ordered from

strongest to weakest, systematic review of randomized trials

(meta-analysis) is at the top, followed by single randomized

6  The guidelines initially were proposed by the Surgeon General
in 1964 and were later expanded upon by Sir Austin Bradford Hill
in 1965. Reference Manual at 600.
                                    16
trials, systematic reviews of observational studies, single

observational studies, physiological studies, and unsystematic

clinical observations.”   Id. at 723-24.    Evidence at the bottom

of the hierarchy may sometimes be “the first signals of adverse

events or associations that are later confirmed with larger or

controlled epidemiological studies.”    Id. at 724.

    Finally, in addition to observational epidemiology,

researchers sometimes look to animal studies for determining a

given agent’s toxicity in humans.    Id. at 563.     Such studies

“often provide useful information about pathological mechanisms

and play a complementary role to epidemiology by assisting

researchers in framing hypotheses and in developing study

designs for epidemiological studies.”      Ibid.   However, animal

studies also have significant disadvantages because biological

differences between humans and the animals under observation

create difficulties in extrapolating data from animal studies

and applying it to humans.   Ibid.   Even so, “[w]here both animal

toxicologic and epidemiologic studies are available, no

universal rules exist for how to interpret or reconcile them.”

Id. at 564.   That said, the Reference Manual acknowledges that

there are “conflicting lines of cases” regarding the weight

courts tend to give animal studies, which the Reference Manual

suggests may be explained by differences in the available amount

of epidemiologic data across different subjects.      Id. at 564-65,

                                17
564 n.48.   Specifically, the Reference Manual states that “when

there is a substantial body of epidemiologic evidence that

addresses the causal issue, animal toxicology has much less

probative value.”     Ibid.   On the other hand, “[w]here

epidemiologic evidence is not available, animal toxicology may

be thought to play a more prominent role in resolving a causal

dispute.”   Ibid.

     Beginning in 2009, scientists began examining the issue of

Accutane’s causal relationship to Crohn’s disease through the

lens of epidemiological studies.        The first of those studies,

published by Bernstein et al.7 in 2009, examined approximately

21,500 subjects and concluded that “[a]lthough there may be

anecdotes of [Accutane] causing acute colitis [inflammation of

the colon], our data suggest that [Accutane] is not likely to

cause chronic IBD.”    In 2010, a study by Crockett et al.8

examining approximately 29,000 subjects found “no apparent

association between isotretinoin and [Crohn’s disease],” but did

find a statistically significant increased risk between

isotretinoin and ulcerative colitis.        A study published in 2013

7  Charles N. Bernstein et al., Isotretinoin is Not Associated
with Inflammatory Bowel Disease: A Population-Based Case-
Control Study, 104 Am. J. Gastroenterol. 2774 (2009).

8  Seth D. Crockett et al., Isotretinoin Use and the Risk of
Inflammatory Bowel Disease: A Case-Control Study, 105 Am. J.
Gastroenterol. 1986 (2010).

                                   18
by Etminan et al.9 examining roughly 45,000 women found that

there was no “increase in the risk for IBD, including UC

[ulcerative colitis] or CD [Crohn’s disease], with use of

isotretinoin.”   Those same authors also performed a meta-

analysis10 of the available data and again concluded that there

was no association between Accutane and Crohn’s disease.

Etminan, supra note 9 at 216, 218-20.   A study of 46,922

subjects treated with Accutane published by Alhusayen et al.11 in

2013 found “no significant association between isotretinoin use

and IBD.”   In 2014, an abstract by Sivaraman et al. examining

509 subjects concluded that “Isotretinoin exposure does not

appear to confer risk for either UC or CD independent of

antibiotic exposure.”

     Two other studies -- a 176,889-subject study performed by

Fenerty et al.12 and a 1078-subject study by Rashtak et al.,13

9  Mahyar Etminan et al., Isotretinoin and Risk for Inflammatory
Bowel Disease, 
149 JAMA Dermatol. 216 (2013).

10 A meta-analysis is a form of epidemiological study whereby
the study authors pool separate studies together and then
interpret the results. See Reference Manual at 289.

11 Raed O. Alhusayen et al., Isotretinoin Use and the Risk of
Inflammatory Bowel Disease: A Population-Based Cohort Study,
133 J. Investigative Dermatol. 907 (2013).
12 Sarah Fenerty et al., Impact of Acne Treatment on
Inflammatory Bowel Disease, 68 J. Am. Acad. Dermatol. AB5
(2013).
13 Shadi Rashtak et al., Isotretinoin Exposure and Risk of
Inflammatory Bowel Disease, 
150 JAMA Dermatol. 1322 (2014).
                                19
published in 2013 and 2014, respectively -- concluded that

Accutane was not causally associated with IBD but did not

include specific data for Crohn’s disease.     Finally, a study of

approximately 44,000 subjects by Racine et al.14 published in

2014 concluded that Accutane use “was associated with a

decreased [Crohn’s disease] risk.”   The interpretation of those

studies is the central issue in this appeal.

                                C.

     Plaintiffs and defendants each produced two expert

witnesses.   Plaintiffs produced Dr. Arthur Asher Kornbluth, a

gastroenterologist, and Dr. David Madigan, a statistician.

Defendants produced gastroenterologist Dr. Maria Oliva-Hemker,

and biostatistician Dr. Steven Goodman.

               1. Plaintiffs’ Expert -- Dr. Kornbluth

     Plaintiffs’ expert Dr. Arthur Asher Kornbluth is a board-

certified physician in internal medicine and in the subspecialty

of gastroenterology.   He maintains an active clinical practice

treating Crohn’s disease and ulcerative colitis and is also a

Clinical Professor of Medicine at the Icahn School of Medicine

at Mount Sinai Hospital in New York City.

14 Antoine Racine et al., Isotretinoin and Risk of Inflammatory
Bowel Disease: A French Nationwide Study, 109 Am. J.
Gastroenterol. 563 (2014).

                                20
    Dr. Kornbluth opined that there is evidence that Accutane

can cause Crohn’s disease.   In rendering a general causation

opinion on the key question in this matter, he explained that he

based his finding of a causal association on “the pathogenesis

and natural history of Crohn’s disease, including the relevant

intestinal anatomy on the macroscopic and cellular level,” “the

pharmacology of Accutane and its metabolites,” “reports and

assessments of Crohn’s disease of acute gastrointestinal

toxicity in patients treated with Accutane or its metabolites,”

and “large clinical trials in patients with Crohn’s disease

evaluating the clinical benefits of blocking the mechanism of

action of Accutane’s metabolites.”   Further, in addition to his

review of the scientific and medical literature, Dr. Kornbluth

also looked to a number of other materials produced as part of

the Accutane litigation, including defendants’ internal animal

studies and causality assessments, and post-marketing reports.

    Dr. Kornbluth’s testimony had two themes:    explaining why

he found the epidemiological studies unreliable and

uninformative regarding the issue of causation, and explaining

his reliance on other forms of evidence such as case reports,

animal studies, causality assessments, and his biological

mechanism hypothesis.

    With regard to the epidemiological studies, Dr. Kornbluth

explained that he would not rely on any study that did not

                                21
provide separate data for Crohn’s disease.    As a result, he

found the Fenerty and Rashtak studies -- both of which analyzed

data for IBD generally and not for Crohn’s disease specifically

-- to be uninformative.   As for the studies that did look

specifically for Crohn’s disease, Dr. Kornbluth stated that most

of them, including the Alhusayen, Crockett, Etminan, and Racine

studies, were fatally flawed because they did not account for

Crohn’s disease’s “prodrome,” meaning the period between the

onset of a disease’s symptoms and its actual diagnosis.      Dr.

Kornbluth asserted that the median prodrome for Crohn’s disease

is roughly two-to-four years, and that the studies in question

did not account for that period because they examined study

subjects only for roughly one year.     Because they did not

examine patient data for a sufficient period of time, Dr.

Kornbluth argued that those studies missed patients whose

prodromes were longer than the studies’ observation periods,

thus biasing the results towards a finding of no association

between Accutane and Crohn’s disease.    Dr. Kornbluth based his

opinion regarding the median prodromal period on two studies:      a

study by Pimentel et. al.15 that contained 45 total subjects with

15 Mark Pimentel et al., Identification of a Prodromal Period in
Crohn’s Disease but Not Ulcerative Colitis, 95 Am. J.
Gastroenterol. 3458 (2000).

                                22
Crohn’s disease, and a study by Barratt et al.16 that contained

230 total subjects with Crohn’s disease.

     Dr. Kornbluth detected other problems with the

epidemiological studies.   He asserted that the Crockett,

Bernstein, and Etminan studies did not have enough patients and

thus were “underpowered,” meaning that they were not properly

designed to detect a statistically significant increased risk,

even if such a risk actually existed, because the study size was

simply too small.   He asserted that the Alhusayen and Etminan

studies did not adjust for certain confounders, such as family

history and smoking.   With regard to the Racine and Bernstein

studies, he noted that those studies were performed in France

and Canada, respectively, and that French and Canadian patients

typically receive half the Accutane dosage that American

patients receive.   Moreover, he noted that the protective effect

found in the Racine study’s results lessened as the dosages

increased, indicating a dose toxicity response.   He was also

dismissive of the meta-analysis that the Etminan authors

performed, stating that it suffered from the same limitations as

the studies that went into it and that a meta-analysis based on

16 S.M. Barratt et al., Prodromal Irritable Bowel Syndrome May
Be Responsible for Delays in Diagnosis in Patients Presenting
with Unrecognized Crohn’s Disease and Celiac Disease, but Not
Ulcerative Colitis, 
56 Dig. Dis. Sci. 3270 (2011).

                                23
studies that did not perform an “adequate analysis” could not

inform the issue.

     Dr. Kornbluth also noted that the Bernstein and Alhusayen

studies both contained positive “point estimates,”17 indicating

an increased risk.   He admitted that the results of both studies

were not regarded as “statistically significant,”18 but he

intimated that the lack of statistical significance was due to

the studies’ inherent flaws and biases.

     In the end, the Sivaraman study was the only study upon

which Dr. Kornbluth was willing to rely.   Even so, he disagreed

17 As plaintiffs’ experts explained, a point estimate serves as
a way to calculate a single value for a sample of data and is
the researchers’ “best guess” as to the level of risk of a
specific health effect from the substance being studied. A
point estimate of 1.0 is indicative of no effect; a point
estimate above 1.0 is indicative of increased risk; and a point
estimate below 1.0 is indicative of decreased risk. For more
information, see generally Reference Manual at 292. We note
that the experts in this case do not distinguish between the
term “point estimate” and the related concepts of “relative
risk” and “odds ratio.” For a discussion of those concepts, see
generally id. at 566-69.
18 As plaintiffs’ experts explained, statistical significance is
measured through use of a confidence interval, which reflects a
range of possible values calculated from the results of a
particular study. A confidence interval that ranges from below
1.0 to above 1.0 is considered not to be statistically
significant. Thus, even where a study’s point estimate is
indicative of either a decreased or increased risk, that result
would not be considered statistically significant if the
confidence interval ranges both above and below 1.0. On the
other hand, a study will be considered statistically significant
where the confidence interval is entirely above or entirely
below 1.0. For more information, see generally Reference Manual
at 574-83, 621.
                                24
with the study authors’ conclusion.    He explained that the

study’s unadjusted point estimate showed that “patients with

Crohn’s disease were five times more likely to have taken

Accutane than those who did not,” and that the study’s

unadjusted results also showed a statistically significant

increased risk.   However, in explaining why he disagreed with

the Sivaraman authors’ conclusion that Accutane does not cause

Crohn’s disease, he noted that the Sivaraman authors reached

their adjusted point estimate by subtracting out patients who

had taken antibiotics; while that adjusted point estimate still

showed a heightened risk, the smaller number of patients meant

that the result lost statistical significance.    Moreover, he

stated that he could not understand why the study authors had

taken that step because “antibiotics per se did not influence

the likelihood of developing Crohn’s disease.”    It was thus “not

clear” to him why the authors made such an adjustment.

     Moving beyond the epidemiological studies, Dr. Kornbluth

examined other lines of evidence that he found supported his

causation opinion.   He began by explaining why he believes it is

biologically plausible for Accutane to cause Crohn’s disease,

although he had not published his causation theory or otherwise

submitted it for peer review.19   He then discussed case reports,

19  To summarize his detailed explanation, Dr. Kornbluth asserts
that retinoic acid, a breakdown product of Accutane, marks
                                  25
studied by other researchers, that illustrate what he referred

to as “challenge/dechallenge/rechallenge,” in which a patient

was given Accutane and then developed a form of intestinal

inflammation, which then ceased when Accutane use was

discontinued and began again upon resumption of Accutane usage.

He regarded that to be “very compelling” evidence of a causative

effect.

    He discussed his reliance on MedWatch reports -- “reports

made by physicians, patients, [and] others to the FDA describing

symptoms that they think were related to ingested medications.”

He noted the significant number of such reports relating to

Crohn’s disease and other gastrointestinal problems that

correlated with the use of Accutane.   Similarly, he testified

that he relied on defendants’ own internal materials, noting

that defendants’ scientists determined that Accutane should be

contraindicated for individuals with certain gastrointestinal

problems and expressed “severe concerns about the likelihood of

patients having exacerbations of Crohn’s disease or even

inflammatory cells known as “T cells” with a compound known as
“alpha 4 beta 7.” That binding process allows the inflammatory
T-cells to then travel through the digestive tract and bind to
another receptor known as “MadCAM.” The process of inflammatory
T-cells traveling through the digestive tract and binding to the
other receptors on the intestinal wall then creates the
inflammation that results in Crohn’s disease. He also explained
that two drugs currently used in treating Crohn’s disease --
vedolizumab and natalizumab -- are believed to work by blocking
alpha 4 beta 7 from binding to the T-cells.
                               26
developing it de novo.”    Dr. Kornbluth asserted that those

assessments by defendants’ scientists were supportive of a

causal link between Accutane and Crohn’s disease.

    Finally, Dr. Kornbluth relied on animal studies to support

his theory of causation.   He testified that defendants performed

experimental tests with Accutane on dogs and that those tests

showed a temporal relationship between the administration of

Accutane and gastrointestinal distress.    Specifically, he noted

a challenge/dechallenge relationship in that certain dogs given

Accutane experienced gastrointestinal problems that ceased after

cessation of Accutane administration.     He also noted the

indication of a dose toxicity curve, meaning that intestinal

damage appeared more severe in dogs given higher doses of

isotretinoin.   However, he conceded that animal studies are

meant only to generate hypotheses about a substance’s effect on

humans, and that a hypothesis is a “supposition that is to be

further tested.”

                2. Plaintiffs’ Expert -- Dr. Madigan

    Plaintiffs’ second expert, Dr. David Madigan, is a

professor of statistics at Columbia University.     Dr. Madigan did

not give a causation opinion.   Only Dr. Kornbluth opined on

causation.

    Dr. Madigan’s testimony and expert report focused solely on

whether the epidemiological studies in question were

                                 27
appropriately designed to discover an association between

Crohn’s disease and Accutane, if such an association did in fact

exist.   He concluded in his expert report that, after accounting

for the prodrome associated with Crohn’s disease, the available

epidemiological studies do not provide statistically reliable

information regarding Accutane’s causal relation to Crohn’s

disease.   His testimony was consistent with his report.

     Dr. Madigan explained that he was tasked with examining the

available epidemiological studies as they pertained to an

association between Accutane and Crohn’s disease.   He analyzed

six of the epidemiological studies:   Bernstein, Crockett,

Alhusayen, Etminan, Racine, and Sivaraman.   He did not analyze

the Rashtak and Fenerty studies because they addressed only IBD

and did not have separate results for Crohn’s disease.

     Dr. Madigan noted that of the six studies he considered,

only two -- Racine and the unadjusted Sivaraman results -- were

statistically significant.   Dr. Madigan performed a “power

analysis”20 of the four studies that were not statistically

significant.   He explained that his purpose in doing so was to

“shed some light” on whether the studies were reliable evidence

that there is truly no effect or whether the studies were simply

20 As Dr. Madigan explained, a power analysis examines for the
risk that a study’s outcome was a “false negative.”
                                28
insufficiently powered to discover an effect even if such an

effect exists.

    Dr. Madigan then examined each study’s statistical power to

detect a fifty percent increased risk; he chose fifty percent

because he considered it to be “an authentically important

increased risk.”     He calculated the power for each of the four

studies as follows:    Bernstein -- 37.8 percent; Crockett -- 18.2

percent; Alhusayen -- 89.4 percent; Etminan -- 22.6 percent.

Thus, for example, if there is a fifty percent increased risk of

developing Crohn’s disease for Accutane users, the probability

that the Bernstein study would find a statistically significant

result is 37.8 percent.     It was thus “less likely than not” that

most of the studies would find an increased risk if such a risk

did in fact exist.     Dr. Madigan concluded that this was “more an

absence of evidence than anything.”     After accounting for the

median prodromal period, which he derived from the Pimentel and

Barratt studies, he determined that the power for three of the

four studies had further decreased:     Crockett diminished to 5.12

percent; Alhusayen diminished to 36.2 percent; and Etminan

diminished to 4.5 percent.

    According to Dr. Madigan, four of the six studies --

Crockett, Alhusayen, Etminan, and Racine -- were totally

unusable because they failed to account for Crohn’s disease’s

prodrome.   He explained that by failing to account for the

                                  29
prodrome, the studies were failing to observe cases of Crohn’s

disease that developed outside of the studies’ observation

period.    In other words, the studies’ failure to take account of

the prodrome “biased [the studies] towards the null,” meaning

the studies were systematically biased in favor of not finding

any effect.   Dr. Madigan therefore concluded that those studies

had an overriding flaw and that he was reluctant to refer to

their results as “findings.”

    As for the remaining two studies, he explained that

questionnaire-based studies such as Sivaraman are immune from

the prodrome issue because they ask patients when their symptoms

began and, thus, have “no limit going backwards in time.”     He

also explained that there was a “diminished concern” for the

Bernstein study due to its lengthy observation period.     However,

Dr. Madigan found other flaws in the Bernstein study, and he

declined to rely on its findings.     He stated that the study did

not adjust for “unmeasured confounders” and it was performed in

Canada rather than the United States, which created a problem as

to “generalizability” due to differences in population and the

lower dosage given to Canadian patients.

    Accordingly, for Dr. Madigan, the Sivaraman study remained

as the only study on which he was willing to rely, but with

caveats.    He did not agree with its conclusion.   He pointed to

the study’s unadjusted results as showing a statistically

                                 30
significant increased risk of Crohn’s disease for people taking

Accutane.   Although he acknowledged that the study’s authors

felt it necessary to adjust for antibiotic exposure, and that

their adjusted results did not show a statistically significant

increased risk for Crohn’s disease, Dr. Madigan disputed that

they actually performed an adjustment.     He claimed that they

actually performed a “subgroup analysis.”     He asserted that the

adjusted figure from that analysis still showed an increased

risk, even though it was no longer statistically significant due

to the smaller number of patients.     Accordingly, he chose to

rely on the unadjusted results because a study based on a larger

group of people will provide a “better estimate.”     He further

explained that he did not understand why the study authors chose

to adjust for antibiotic exposure because the study authors

admitted in the study’s abstract that “antibiotic exposure was

not associated with Crohn’s disease.”

    In sum, Dr. Madigan found the Sivaraman study to be

“evidence of a strong association between Accutane and Crohn’s

disease,” discounting all of the other studies on the basis that

they “represented an absence of evidence” from which one cannot

draw any definitive conclusions.

    Dr. Madigan also took the position that a meta-analysis of

the studies would be improper.     He stated he did not perform a

meta-analysis because most of the studies on which the meta-

                                 31
analysis would be based did not account for prodrome, which

would render the meta-analysis both misleading and

scientifically unreasonable.     That is so, he explained, because

a meta-analysis will inherit the flaws, biases, and structural

problems of the studies upon which it is based.

    In addition, Dr. Madigan performed a disproportionality

analysis using the FDA’s spontaneous reporting system database.

He explained that a disproportionality analysis is a method of

studying a spontaneous report database and reviewing the

observed rate for a particular drug and a particular adverse

event.   The observed rate is compared with the rate at which

Crohn’s disease was reported for other drugs in the database.

Analyzing the available data beginning in 1997, Dr. Madigan’s

results showed a “striking signal of disproportionality”

indicative of a “strong association” between Accutane and

Crohn’s disease.

               3. Defendants’ Expert -- Dr. Oliva-Hemker

    Defendants’ expert Dr. Maria Oliva-Hemker is a Professor of

Pediatric Inflammatory Bowel Disease and Chief of the Division

of Pediatric Gastroenterology and Nutrition at Johns Hopkins

University School of Medicine.    Her testimony focused on

disputing Dr. Kornbluth’s testimony and explaining why

epidemiological studies are preferred to case reports and animal

studies in the hierarchy of evidence.

                                  32
    During the Kemp hearing, she stated that the available

scientific evidence does not support any causal association

between Accutane and Crohn’s disease.    Regarding Dr. Kornbluth’s

testimony on biological mechanism, she explained that Crohn’s

disease is idiopathic, meaning that its cause is unknown, and

that any theory regarding a biological mechanism was therefore

unreliable.   Moreover, she stated that scientists would not

ignore the available epidemiological evidence in favor of a

hypothesis about a biological mechanism.

    She also addressed plaintiffs’ experts’ opinions concerning

the prodrome for Crohn’s disease.    Although admitting that “the

diagnosis time can vary” and that there are some patients who

are not diagnosed for several years, she stated that most

patients are typically diagnosed within a year.    She based that

conclusion on a number of population-based studies, all of which

concluded that the median prodrome is under one year.    She was

dismissive of plaintiffs’ experts’ use of the Pimentel study for

determining the median prodrome for Crohn’s disease, explaining

that the study was very small and not representative of the

average prodromal period, especially in light of the other,

larger studies on the issue.   She added that the authors of the

epidemiological studies would have been aware of the available

published data on the median prodromal period and would have

accounted for it in designing their studies.

                                33
     She also discussed the recognized hierarchy of evidence and

that certain types of data are meant to “generate hypotheses,”

whereas other, more reliable forms of evidence are meant to

“test hypotheses.”   She stated that the epidemiological studies

are currently the best available data on the issue of Accutane

and Crohn’s disease and that, from a medical-evidence point of

view, Dr. Kornbluth’s reliance on case reports and animal

studies, which are considered lower forms of evidence, was

inconsistent with recognized methodology.   Concerning case

reports, she testified that they are hypothesis-generating in

nature and are “in the bottom tier of medical evidence.”     She

explained that case reports are subject to “publication bias,”

meaning that only correlative events are reported and that the

reports are subjective in nature, often contain incomplete

information, and do not account for random chance.   Further, she

stated that such reports are difficult to interpret because

Crohn’s disease is a “relapsing and a remitting condition,” and

thus “the natural course of the disease may be mistaken for the

results of removing or reintroducing the medication.”   She also

cited to an article by Reddy et al.21 for the proposition that

21 Deepa Reddy et al., Possible Association Between Isotretinoin
and Inflammatory Bowel Disease, 101 Am. J. Gastroenterol. 1569
(2006).
                                34
epidemiological evidence is needed to confirm the inference of

causality generated by a case report.

    Finally, Dr. Oliva-Hemker addressed Dr. Kornbluth’s

interpretation of defendants’ animal studies.    She stated that

animal studies may sometimes be important for “generating

certain hypotheses,” but that they are typically considered

below human studies in the hierarchy of medical evidence.      She

noted that it is difficult to extrapolate data from animals to

humans because of differences in metabolism, absorption, and

other factors.     Moreover, she testified that she would not rely

on dog studies in this instance because dogs cannot get IBD and

because recent research has shown that dogs may have

hypersensitive gastrointestinal tracts that can result in

distress owing more to the dog’s anatomy than to the actual

toxicity of the substance under observation.    In sum, her

testimony concluded that the animal studies are simply not

sufficient generally for forming a conclusion about causation

here both because of the nature of the disease at issue and

because they are merely “hypothesis-generating data.”

    In contrast to the case reports and animal studies, she

testified that the epidemiological studies are the best

available evidence on the issue of Accutane’s relation to

Crohn’s disease.    Moreover, she testified that it would be

entirely proper to consider a meta-analysis of the studies when

                                  35
such analysis is available.   She explained that researchers now

have access to the types of “hypothesis testing” epidemiological

studies that were sought for testing the viability of adverse

event case reports and that those studies have all reached

similar findings of no causal effect despite variations in

populations, time, and data sets.

              4. Defendants’ Expert -- Dr. Goodman

    Defendants’ second expert, Dr. Steven Goodman, is a

Professor of Medicine and Health Research and Policy and

Associate Dean for Clinical and Translational Research at

Stanford University, where he serves as Chief of the Division of

Epidemiology and co-director of Stanford’s Meta-Research

Innovation Center.   Dr. Goodman’s testimony focused on why the

epidemiologic evidence is the best available evidence on the

question of Accutane’s causal relation to Crohn’s disease and

why a meta-analysis was a proper way of pooling those study

results to reach a conclusion that Accutane does not cause

Crohn’s disease.

    Dr. Goodman stated, during the Kemp hearing and in his

expert report, that the epidemiological evidence pertaining to

the causal relationship between Accutane and Crohn’s disease is

as strongly negative as epidemiologic evidence can be, and that

there was no biological evidence, including a causal mechanism

or otherwise, to contravene that evidence.   He stated that the

                                36
methods Doctors Madigan and Kornbluth used were flawed because

they put almost no weight on the epidemiologic evidence and

instead relied heavily on the much lesser forms of evidence,

which is not how any scientific body would have proceeded.      Dr.

Goodman emphasized that there is now a consistent body of

epidemiological evidence all pointing towards no causal

association between Accutane and Crohn’s disease and that the

weighing of that body of evidence through use of meta-analysis

also strongly supported the lack of any association or causal

effect between Accutane and Crohn’s disease.

    Dr. Goodman discussed the hierarchy of medical evidence,

stating that observational studies are second only to randomized

controlled trials in terms of establishing causality.      Like Dr.

Oliva-Hemker, he explained that epidemiologic studies are a

hypothesis-testing form of evidence, which is a higher form of

evidence than hypothesis-generating data, such as case reports

and animal studies.   Moreover, hypothesis-generating evidence is

typically used more for developing ideas to later be examined

through epidemiological evidence.    Accordingly, he was

dismissive of any reliance on case reports here, which he stated

are almost never used as a basis for a scientific determination

of causality.   As support for that proposition, Dr. Goodman

cited the Reference Manual, which states that case reports are

“at the bottom of the evidence hierarchy” and must later be

                                37
“confirmed with larger, more controlled epidemiological

studies.”

    For similar reasons, Dr. Goodman was also dismissive of Dr.

Kornbluth’s interpretation of animal studies, explaining that

such studies are hypothesis-generating in nature and that it is

difficult to extrapolate results from animal studies to

determine the effect a given substance will have on a human

subject.    Moreover, he believed that the specific animal studies

discussed in this matter were essentially meaningless because

dogs do not develop IBD.    He also took issue with Dr.

Kornbluth’s invocation of the Hill criteria in assessing the

causal relationship between Accutane and Crohn’s disease because

the studies here showed no strength of association, and so there

was no “association” in need of study.

    After reviewing all of the epidemiologic evidence, Dr.

Goodman stated that none of the studies showed a statistically

significant increased risk of developing Crohn’s disease from

use of Accutane.   In addition to his belief that each study

contained reasonable results, he also noted the importance of

the fact that all of the studies were concordant with each other

-- that all of the studies produced consistent results pointing

in the same direction was strong evidence that those results are

reliable.

                                 38
    With regard to the Sivaraman study, he stated that the

study should be interpreted according to its adjusted numbers,

and that it was proper for the study authors to adjust for

antibiotics.     He explained that the adjusted number is always

better because it tends to be less biased and therefore more

reliable.   Moreover, he found the Sivaraman study to be

insignificant for purposes of his meta-analysis and in the

overall scheme of evidence because of its small size.

    He also explained the methodology of the meta-analysis he

performed, describing how smaller and more imprecise studies are

given less weight whereas larger and more precise studies are

given more weight.     He further stated that a meta-analysis is a

way to increase precision by pooling studies that address the

same question.    Moreover, meta-analysis is useful where there is

a question about whether independent studies are large enough to

detect an effect size.    Accordingly, he criticized Dr. Madigan’s

refusal to perform a meta-analysis of the studies despite

arguing that most of the studies were underpowered because meta-

analysis was “in a sense invented” to address power concerns.

    He then went through the results of his meta-analysis,

which he performed for both IBD and Crohn’s disease.     For IBD,

the meta-analysis resulted in a relative risk indicative of a

protective effect, but with a statistically insignificant

confidence interval.     For Crohn’s disease, the meta-analysis

                                  39
again returned a relative risk indicative of a protective

effect, with a non-statistically significant confidence

interval.   Dr. Goodman interpreted those results as consistent

with “no effect.”

     Finally, Dr. Goodman turned his attention to the criticisms

levied against the epidemiological studies -- specifically the

prodrome issue on which plaintiffs’ experts chiefly relied in

disregarding the studies.     Dr. Goodman criticized plaintiffs’

experts’ reliance on the Pimentel and Barratt studies for

determining a median prodrome length of at least two-to-four

years because of the studies’ small size and because the

Pimentel study’s population was taken from patients who

gastroenterologists found difficult to manage and diagnose.        Dr.

Goodman felt that a study by Chouraki et al.,22 which contained

7409 subjects with Crohn’s disease and found a median prodrome

of under a year, was much more reliable.     Moreover, he stated

that every population-based prodrome study -- which are the

studies he believed most reliable -- found a prodrome of nine

months or less.     He thus concluded that the best available

evidence on the issue consistently pointed towards a median

22 V. Chouraki et al., The Changing Pattern of Crohn’s Disease
Incidence in Northern France: a Continuing Increase in the 10-
to 19-Year-Old Age Bracket (1988-2007), 33 Aliment. Pharmacol.
Ther. 1133 (2011).
                                  40
prodrome of less than a year, which justified the

epidemiological studies’ use of a one-year observation period.

Thus, in his opinion, none of the epidemiological studies were

invalid due to a prodrome issue.

                                D.

    After the Kemp hearing, the trial court issued an order

granting defendants’ omnibus motion to bar plaintiffs’ experts

from testifying on, among other things, whether the

epidemiological studies on which the defense relied were flawed

and unreliable and whether Accutane can cause Crohn’s disease.

The trial court also directed the parties to prepare an order

listing the lawsuits affected by the ruling, and subsequently

issued a May 8, 2015 order dismissing 2076 affected claims with

prejudice.

    In its decision concerning the exclusion of plaintiffs’

expert witnesses, the trial court examined the expert testimony

and scientific studies, laid out the relevant standard for the

admission of expert witness testimony, and determined that

plaintiffs’ experts’ testimony did not meet the applicable

standard.

    The trial court stated that Rubanick governed the

admissibility of expert witness testimony in toxic tort cases in

New Jersey.   The court regarded the Rubanick standard, which it

understood to be more flexible in assessing medical causation

                                41
expert testimony than the “general acceptance” test of Frye

otherwise traditionally used in New Jersey courts, as requiring

an expert opinion to be based on a “sound, adequately-founded

scientific methodology involving data of the type reasonably

relied on by experts in the scientific field.”     (citing

Rubanick, 
125 N.J. at 449).     Thus, to fulfill its duty as

gatekeeper, the trial court considered “whether other scientists

in the field [are] using similar methodologies in forming their

opinions.”

     The trial court applied that standard and found plaintiffs’

experts’ testimony lacking.23    Focusing on the epidemiological

studies, the trial court concluded that “there is no

epidemiological evidence to justify a reasonable inference that

there is a causal link between isotretinoin and [Crohn’s

disease].”   Nor did the court believe that there was any

rational basis for plaintiffs to resist the findings of all the

epidemiological studies and to rely instead on case reports and

animal studies, which the trial court determined were seriously

flawed and a less reliable form of evidence than the

epidemiological studies.

23 The trial court’s determination was based solely on
plaintiffs’ experts’ methodology. The experts’ credentials were
not in issue at any point.
                                  42
    The trial court viewed Dr. Kornbluth and Dr. Madigan as

“self-validating expert[s]” who were unwilling to subject their

ideas for evaluation in the scientific community, either through

peer review submission or through the scrutiny of the process of

publication in scientific literature.   Specifically regarding

Dr. Kornbluth, the trial court stated that he “want[ed] to have

it both ways” by rejecting the best available evidence as flawed

and yet relying on inferior forms of evidence.   As for Dr.

Madigan, the trial court viewed his refusal to perform a meta-

analysis and to instead rely on the Sivaraman study for

causation and the Pimentel and Barratt studies for median

prodrome, to the exclusion of all other studies, as an attempt

to explain away the body of evidence on causation and on the

median prodromal period.

    The trial court therefore determined that plaintiffs’

experts’ examination of the evidence was a “conclusion-driven”

attempt to cherry-pick evidence supportive of their opinion

while dismissing other, better forms of evidence that did not

support their opinion.     The trial court believed that such a

“stratagem cannot bridge the analytical gaps inherent in

Plaintiffs’ hypothesis.”

    Plaintiffs appealed and the Appellate Division reversed,

holding that plaintiffs may present the experts’ testimony at

trial.   In re Accutane Litig., 
451 N.J. Super. 153, 163-64 (App.

                                 
43 Div. 2017).   After providing an overview of plaintiffs’ experts’

testimony, underlying scientific principles, and applicable

legal standards, the panel concluded that “the experts relied on

methodologies and data of the type reasonably relied upon by

comparable experts.”   Id. at 199.   Comparing the testimony of

plaintiffs’ experts and defendants’ experts, the panel stated

that plaintiffs’ experts evaluated all of the evidence in

accordance with established scientific standards and methodology

and addressed the specific design flaws of the epidemiological

studies, all of which are recognized in the scientific community

as capable of producing unreliable results.    Id. at 202.   The

panel explained that defendants’ experts merely “interpet[ed]

the epidemiological studies differently,” and that a difference

of opinion between the experts did not mean that plaintiffs’

experts failed to rely upon a sound methodology.    Id. at 202-03.

    The panel found plaintiffs’ experts to be “extremely well-

qualified” and underscored that they “considered all of the

relevant data and information, applied appropriate methodology

in analyzing the epidemiological studies, and expressed valid

reasons for rejecting the conclusions of some of the

epidemiological studies and in accepting other studies as

supportive of their opinion.”   Id. at 205.   While noting the

trial court’s opportunity to view the witnesses firsthand, the

panel disagreed with the trial court’s characterization of

                                44
plaintiffs’ experts as “hired gun[s],” id. at 206, and expressed

the view that the trial court’s negative reaction to plaintiffs’

experts was not supported by the trial record, id. at 211.

    The panel further noted that, although a trial court’s

decision to admit or exclude evidence is subject to an abuse of

discretion standard, a reviewing court owes “somewhat less

deference to a trial court’s determination[s]” regarding expert

testimony.   Id. at 196-97.   Accordingly, because our evidence

rules weigh strongly in favor of admissibility, the panel

“conclude[d] that the [trial] court mistakenly applied its

discretion in excluding the expert scientific testimony.”    Id.

at 206.

    We granted defendants’ petition for certification.      
231 N.J. 531 (2017).   In addition, numerous parties were granted

amicus status.

    The New Jersey Business & Industry Association, Commerce

and Industry Association of New Jersey, and New Jersey Chamber

of Commerce (collectively “the Industry Associations”); Kenneth

S. Broun, Daniel J. Capra, Joanne A. Epps, David L. Faigman,

Laird Kirkpatrick, Michael M. Martin, Liesa Richter, and Stephen

A. Saltzburg (collectively “the Academics”); the American

Medical Association, Medical Society of New Jersey, American

Academy of Dermatology, Society for Investigative Dermatology,

American Acne and Rosacea Society, and Dermatological Society of

                                 45
New Jersey (collectively “the Medical Associations”); the

Pharmaceutical Research and Manufacturers of America; the New

Jersey Civil Justice Institute (NJCJI); and DRI - The Voice of

the Defense Bar (DRI), filed briefs supportive of defendants.

    The New Jersey Association for Justice (NJAJ); the

Ironbound Community Corporation (ICC); and Allan Kanner, Esq.

(Kanner), filed briefs supportive of plaintiffs.

                               III.

                                A.

    Defendants argue that the Appellate Division’s decision

effectively nullifies the trial court’s role as the gatekeeper

of expert witness testimony and will “allow[] any credentialed

expert to argue their way to a jury.”    They contend that the

appellate panel did not address the methodological

inconsistencies inherent in plaintiffs’ experts’ reasoning and

adopted a restrictive interpretation of the trial court’s role

as the “gatekeeper” of expert witness testimony that is at odds

with precedent from both New Jersey and courts around the

country.   Defendants assert that the acceptance of such

“internally-inconsistent” and “outcome-driven” testimony robs

the expert witness standard of its vitality.    They ask us to

“bring clarity and consistency to New Jersey expert

admissibility standards, including by addressing whether Daubert

standards and precedent are relevant.”

                                46
    The current lack of clarity, defendants posit, has resulted

in “vastly different applications of gatekeeping,” as

illustrated by the opposing viewpoints of the trial court and

Appellate Division in this matter.    Moreover, defendants argue

that, “[a]lthough the Court need not adopt the federal Daubert

standard to find that the Appellate Division erred, this case

illustrates the practical benefits of doing so.”    Defendants add

that the extent to which New Jersey courts may look to Daubert

for guidance is currently unclear; they urge this Court to

clarify that issue here.

    With respect to the proffered expert scientific testimony,

defendants contend that the Appellate Division failed to apply

methodological scrutiny, improperly applying a “relaxed”

standard for admissibility despite the existence of “well-

developed science.”   By doing so, the Appellate Division allowed

plaintiffs’ experts to employ a methodology whereby they argued

away better and more reliable forms of evidence such as

epidemiological studies to rely on lesser forms of evidence such

as case reports and animal studies.    Thus, they contend that the

Appellate Division ignored “key guidelines from this and other

courts for assessing the reliability of expert testimony.”

    Specifically, defendants argue that the Appellate Division

did not consider whether the experts used the data as it is used

by scientists in the field, a requirement mandated by Rubanick;

                                47
condoned the experts’ failure to adhere to the hierarchy of

evidence; and failed to look for any demonstration of scientific

consensus for the experts’ methods or views, such as peer-

reviewed articles or treatises.    And, they argue that the

Appellate Division did not give appropriate deference to the

trial court’s exercise of discretion, but rather conducted

essentially a de novo review.

    In sum, defendants argue that appellate error has resulted

in the allowance of expert testimony that is contradictory,

unreliable, and logically incoherent.   Defendants emphasize that

none of the epidemiological studies concluded that there was a

connection between Accutane and Crohn’s disease.    Doctors

Madigan and Kornbluth were thus forced to use an inconsistent

methodology whereby they “concocted” a theory on Crohn’s

disease’s prodrome and selectively applied that theory to

evidence that did not support their viewpoints.    They did the

same for their theories on study power, applying it where

necessary to refute the evidence, but then ignoring it for the

studies upon which they relied.    Defendants argue that the

experts’ “contradictory methodology” should not be allowed to be

advanced before a jury.

                                  B.

    Plaintiffs argue that the Appellate Division appropriately

employed Rubanick’s relaxed admissibility standard in this

                                  48
matter and properly assessed the reliability of plaintiffs’

experts’ methodology.    Plaintiffs cite to the Reference Manual

for the proposition that “epidemiology alone cannot prove

causation,” and contend that defendants have falsely categorized

the nature of the expert testimony due to their erroneous belief

that the epidemiological studies alone should be considered to

the exclusion of all other evidence.    According to plaintiffs,

epidemiological studies “are not the be all and end all of

causation evidence,” but rather “one component of multiple lines

of evidence that inform the causation issue.”   Thus, by

considering all of the evidence in addition to the epidemiology,

plaintiffs argue their experts employed a methodology based on

sound scientific principles accepted in the scientific

community.   They further argue that the Appellate Division

correctly found that their experts did not ignore the

epidemiology, but rather examined the data with proper

consideration of the strengths and limitations of the design of

each of the studies, together with study biases.    Accordingly,

the Appellate Division properly held that the trial court

exceeded its gatekeeping function in excluding the expert

testimony.

    Furthermore, plaintiffs argue that the Reference Manual

does not endorse a “strict application” of the hierarchy of

evidence.    In fact, the Reference Manual does not suggest that

                                 49
epidemiological studies are “beyond scientific criticism” or

that “no countervailing evidence should be considered.”

Plaintiffs thus contend that their experts did not stray from

any “core scientific principles,” but simply considered all of

the evidence in forming their opinions.    Plaintiffs posit that

their experts merely viewed the epidemiological studies

differently than defendants’ experts, and that doing so is not

improper because the “implications of a study are open to

debate.”

    Plaintiffs also dispute the “key guidelines” identified by

defendants for examining expert testimony.    Plaintiffs note that

the law does not require that experts submit their opinions for

peer review in order to be admissible.    Plaintiffs also take

issue with defendants’ arguments concerning scientific

consensus, arguing that consensus is not required in toxic tort

cases and that, by arguing the issue, defendants are seeking to

take New Jersey back to the “general acceptance” standard.

Furthermore, plaintiffs contend that defendants’ argument for

abandoning Rubanick’s relaxed standard is at odds with this

Court’s interpretation of the trial court’s gatekeeping role and

would allow a trial court to usurp the role of the jury and

determine for itself whether to accept an expert’s opinion.

    Plaintiffs also argue that the Appellate Division gave

appropriate deference to the trial court, explaining that “less

                               50
deference is owed to a trial court when the issue is the

admissibility of expert proofs.”     They claim that the trial

court failed to adhere to the principles expounded in Rubanick,

which provided “well-founded support for the level of review

that the Appellate Division employed.”     Thus, because the trial

court substituted its judgment for that of the jury and

improperly weighed the evidence, the Appellate Division properly

reversed by applying a standard of review “long recognized by

this Court.”   Finally, plaintiffs argue that there is no reason

to import the Daubert standard into New Jersey law and note that

this Court has previously declined to adopt the Daubert factors.

                                C.

    Amici curiae Industry Associations, the Academics, and DRI

argue that New Jersey’s expert witness standard is in need of

clarification and urge this Court to join the majority of other

states by adopting the Daubert standard to ensure meaningful

judicial gatekeeping and that only reliable and reliably applied

expert testimony enters New Jersey’s courts.     Similarly, amici

curiae NJCJI and the Medical Associations argue that the

Appellate Division reached an incorrect decision even under

existing New Jersey law, but maintain that adoption of the

Daubert standard will provide helpful guidance and ensure

meaningful and robust gatekeeping in New Jersey trial courts.

                                51
    Specifically, the Industry Associations and the Academics

maintain that although Daubert and the current standard are

somewhat similar, Daubert provides “concrete guidelines” and a

more fulsome analysis that ensures that the expert’s methodology

is reliable and applied in a way that “fits” the facts of a

case.   Both contend that plaintiffs’ experts’ testimony would

not have withstood that more thorough analysis.   Moreover, both

argue that tying New Jersey closer to the Daubert standard would

discourage forum shopping.   Finally, the Academics assert that

the Appellate Division should have applied a pure abuse of

discretion standard in reviewing the trial court’s ruling.

    The Medical Associations argue that the Appellate Division

incorrectly applied New Jersey’s expert witness standard by

ignoring the hierarchy of evidence and the unanimity of

epidemiological evidence in favor of plaintiffs’ experts’ “un-

vetted postulations.”   They point to a scientific consensus in

the medical literature that Accutane does not cause Crohn’s

disease, and argue that plaintiffs’ experts were forced to

invert the hierarchy of scientific evidence to overcome the

scientific consensus on the issue by relying on inferior forms

of evidence such as case reports and animal studies.

    NJCJI similarly argues that the Appellate Division

permitted plaintiffs’ experts to present their unsubstantiated

“outlier viewpoint” without any meaningful judicial scrutiny or

                                52
investigation of their methodology.    NJCJI claims that the

Appellate Division’s decision improperly left the question of

methodological soundness to the jury while limiting the trial

court’s gatekeeping function “to exclude only the most extreme

and obvious forms of junk science.”

    NJCJI and DRI emphasize that robust gatekeeping is

necessary because juries struggle to absorb complex scientific

concepts and are poorly equipped to assess methodological

soundness.    Both amici express the concern that juries may be

misled by highly-qualified experts who offer opinions that are

not supported by the wider scientific community and that juries

faced with complex scientific evidence may simply “fall back” on

an expert’s credentials as a basis for evaluating the testimony

at issue.    To guard against that risk, DRI argues that experts

should be required to prove not only that their methodology is

sound, but that such methodology is reliably applied to the

facts of the case.

    Finally, amicus curiae Pharmaceutical Research and

Manufacturers of America submitted a brief detailing the

scientific principles at issue here and arguing that the trial

court correctly excluded plaintiffs’ experts’ testimony.

                                 D.

    Amici curiae NJAJ, ICC, and Kanner argue that this Court

should not adopt the Daubert standard because the current New

                                 53
Jersey standard is well-settled and strikes an appropriate

balance between proper judicial gatekeeping and the admission of

novel scientific concepts.    NJAJ claims that the Daubert

standard is a “patchwork” of case law that has been applied

inconsistently by both state and federal courts.     NJAJ and

Kanner further contend that the Daubert standard requires judges

who are unfamiliar with scientific principles to make scientific

judgments outside of their area of expertise.    NJAJ and ICC

argue that Daubert imposes undue and unnecessary burdens on

courts and litigants by encouraging frivolous challenges to

expert witness testimony.    Both ICC and Kanner claim that

adoption of the Daubert standard will lead to unjust results

because it will result in the exclusion of reliable evidence,

which will bar access to justice for innocent victims.

    The NJAJ further argues that New Jersey’s expert witness

standard does not require any clarification or correction and

that state trial courts have reliably applied it for many

decades.   NJAJ contends that defendants have provided no

substantive reason why this Court should abandon the expert

witness standards that it pioneered and “which continue to

fairly promote just results.”    Furthermore, NJAJ disputes that

New Jersey’s current expert witness standard promotes the filing

of cases in New Jersey by out-of-state plaintiffs, arguing that

there is no evidence to support such an assertion.     Finally,

                                 54
NJAJ, ICC, and Kanner maintain that the Appellate Division here

applied the proper standard and properly found that the trial

court exceeded its gatekeeping role by excluding plaintiffs’

experts based on nothing more than personal disagreements as to

their conclusions.

                                  IV.

                                  A.

     Our Court was in the vanguard of courts to be persuaded

that adherence to the Frye general acceptance standard as the

sole test for assessing reliability of scientific expert

testimony was unsatisfactorily constricting for fairly assessing

reliability in certain areas of novel or emerging fields of

science.24

     Rubanick marked the broadening of our standard, when this

Court concluded that resort to a methodology-based standard

would be appropriate for assessing reliability with respect to

emerging scientific theory on causation in toxic tort

litigation.    
125 N.J. at 454.   Justice Handler, writing for the

Court, explained the impetus for the holding:

             [T]oxic-tort litigation does not frequently
             encounter   well-established  and   widely-

24 As Frye garnered considerable criticism through the years,
the United States Supreme Court ultimately resolved a split
among the circuit courts and held that Frye was superseded by
the adoption of the Federal Rules of Evidence. Daubert, 
509 U.S.  at 585-87. We discuss Daubert in greater detail later in
this opinion.
                                  55
          accepted scientific theories of causation that
          can, at the level demanded by the scientific
          method, precisely delineate the causal path
          between   the   toxin   and   the   pathology.
          Nevertheless, in such litigation there is
          often available data and information of a type
          that is used and relied on by experts in the
          field; further, there are reputable and highly
          qualified experts who, drawing on such data
          and information, have the proficiency to apply
          sound scientific methods sufficient to reach
          creditable opinions with respect to causation.
          We are thus strongly persuaded that a standard
          that accounts for those considerations should
          be employed to determine the reliability of
          expert opinion testimony relating to causation
          in toxic-tort litigation.

               Accordingly, we hold that in toxic-tort
          litigation, a scientific theory of causation
          that has not yet reached general acceptance
          may be found to be sufficiently reliable if it
          is based on a sound, adequately-founded
          scientific methodology involving data and
          information of the type reasonably relied on
          by experts in the scientific field.

          [Id. at 449.]

The Court further instructed courts to “consider whether others

in the field use similar methodologies. 'What is necessary is

that the expert arrived at his causation theory by relying upon

methods that other experts in his field would reasonably rely

upon in forming their own, possibly different opinions, about

what caused the patient’s disease.’”   Id. at 449-50 (quoting

Osburn v. Anchor Labs., Inc., 
825 F.2d 908, 915 (5th Cir.

1987)).

                               56
    In remanding to the trial court for re-evaluation of

disallowed expert testimony, the Rubanick Court explained that

the proper inquiry is not whether the expert thought his

reliance on the underlying data from thirteen studies regarding

exposure to a potential carcinogen was reasonable or whether the

trial court thought that reliance was reasonable; rather, the

proper inquiry is whether comparable “'experts in the field

[would] actually rely’ on that information.”   Id. at 451-52

(alteration in original) (quoting Ryan v. KDI Sylvan Pools,

Inc., 
121 N.J. 276, 289 (1990)).

    One year later, in Landrigan, Justice Pollock, writing for

the Court, applied the same approach and again remanded for a

hearing on the disputed epidemiologic testimony about asbestos

and colon cancer.   
127 N.J. at 418-23.   The Court stated that,

for its purposes, it did not need to “describe in detail how to

structure an epidemiological study, analyze the data, draw

conclusions about the study population, and, if possible,

extrapolate from statistical results inferences about specific

individual subjects[, i.e., determine specific causation].”     Id.

at 417.   But, Justice Pollock elaborated on the Court’s

direction to trial courts when assessing the reliability of a

methodology used by an expert proffering scientific evidence:

“epidemiologists, like experts generally, must be able to

identify the factual bases for their conclusions, explain their

                                57
methodology, and demonstrate that both the factual bases and the

methodology are scientifically reliable.”    Ibid.   When relying

on such studies, the trial court should review them and “then

determine whether the expert’s opinion is derived from a sound

and well-founded methodology that is supported by some expert

consensus in the appropriate field.”    Ibid. (citing Rubanick,

125 N.J. at 449-50).

    Moreover, Landrigan provided suggested tools for trial

courts to use in rendering gatekeeping determinations about the

reliability of an expert’s methodology when the ultimate

scientific opinion is not itself generally accepted.     Landrigan

explains that “[d]efined landmarks guide a trial court in making

this determination.    Support may be demonstrated by reference to

professional journals, texts, conferences, symposia, or judicial

opinions accepting the methodology.”    Ibid. (citing Kelly, 
97 N.J. at 210-11).   Additionally, the Court allowed for

consideration of professional associations’ acknowledged

acceptance and recognition of a methodology’s use.     Ibid.   Thus,

methodology may be assessed for soundness using some of the same

tools as general acceptance identifies for outcome.

                                 B.

    Not long after those dual holdings by our Court, the

Supreme Court issued its seminal Daubert opinion in 1993

pronouncing that Frye had been superseded by the adoption of the

                                 58
Federal Rules of Evidence.    
509 U.S.  at 585-87.   The Daubert

Court explained that the Federal Rules of Evidence do not make

any mention of a general acceptance standard and that such a

standard was at odds with the “liberal thrust of the Federal

Rules and their general approach of relaxing the traditional

barriers to opinion testimony.”    Id. at 588 (internal quotations

omitted).    Thus, although Federal Rule of Evidence 702

“contemplates some degree of regulation of the subjects and

theories about which an expert may testify,” the subject of the

scientific testimony does not have to be known to a certainty so

long as it is derived from the scientific method and “supported

by appropriate validation.”    Id. at 589-90.   Moreover, in

addition to a methodology derived from the scientific method,

the Court added that the testimony must be relevant to the facts

at hand -- it must “assist the trier of fact to understand the

evidence or to determine a fact in issue.”      Id. at 591 (quoting

Fed. R. Evid. 702).

    Tying the principles together, the Court fashioned a new

standard:

            Faced with a proffer of expert scientific
            testimony . . . the trial judge must determine
            at the outset . . . 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. This entails a preliminary assessment
            of whether the reasoning or methodology
            underlying the testimony is scientifically

                                  59
         valid and of whether that reasoning or
         methodology properly can be applied to the
         facts in issue.

         [Id. at 592-93 (footnotes omitted).]

The Court based that standard on the concept that the Federal

Rules regarding expert testimony are “premised on an assumption

that the expert’s opinion will have a reliable basis in the

knowledge and experience of his discipline.”    Id. at 592.     The

Court noted that “[m]any factors will bear on the inquiry,” and

then proceeded to offer some observations on factors it believed

most relevant in such evaluations.    Id. at 593.   Those became

known as the Daubert factors.

    First, trial courts may look to whether the scientific

theory at issue can be, or has been, tested.    Ibid.   Second, a

court may also consider whether the scientific theory has been

published or subjected to some form of peer review.     Ibid.    That

said, the Court did not consider publication as “a sine qua non

of admissibility,” but rather one form of peer review.     Ibid.

The Court reasoned that “submission to the scrutiny of the

scientific community is a component of 'good science,’ in part

because it increases the likelihood that substantive flaws in

methodology will be detected.”   Ibid.   As a third factor, courts

may also consider any “known or potential rate of error,” and

any “standards controlling the technique’s operation,” id. at

594, which may be important in pattern testing and similar areas

                                 60
of science.   Finally, the Daubert Court stated that general

acceptance remains a consideration; accordingly, a technique

that has garnered only minimal support within the scientific

community “may properly be viewed with skepticism.”    Ibid.

     In sum, the Court described the trial court’s task as a

“flexible” inquiry into the scientific principles at issue,

ibid., one whose “overarching subject is the scientific validity

-- and thus the evidentiary relevance and reliability -- of the

principles that underlie a proposed submission,” id. at 594-95.

As this Court did in Rubanick and Landrigan, the Supreme Court

underscored in Daubert that the trial court must focus on the

expert’s principles and methodology -- not on the conclusions

they generate.   Id. at 595.   The trial court’s task is thus to

ensure “that an expert’s testimony both rests on a reliable

foundation and is relevant to the task at hand” by assuring that

the evidence is based on valid scientific principles.    Id. at

597.25

     Although acknowledging that its decision was controversial,

the Court asserted that it had struck a proper balance, stating

that the adversarial process would provide proper safeguards in

place of the more “uncompromising 'general acceptance’ test,”

25 The Court also acknowledged that other evidence rules pertain
in the analysis in addition to Rule 702, including Rules 703 and
403. Id. at 595.
                                 61
and that the trial judge’s role as gatekeeper was essential for

the quick and decisive resolution of legal disputes.    Id. at

596-97.

    The Supreme Court elaborated on its Daubert standard for

assessing reliability with two cases which, combined, round out

the Daubert trilogy.

    In General Electric Co. v. Joiner, the Court held that an

abuse of discretion standard applies when reviewing a trial

court’s decision to admit or exclude expert testimony, even

where that determination may be outcome determinative.    
522 U.S. 136, 138-39 (1997).    The Court also reinforced that trial courts

are the “gatekeeper” tasked with screening such testimony.        Id.

at 142.   The Court stated that, in its gatekeeper role, a trial

court is free to exclude expert testimony where the expert’s

conclusions are not sufficiently tethered to the facts or drawn

from the applicable data.    Id. at 146-47.   A trial court may

determine in a given case that “there is simply too great an

analytical gap between the data and the opinion proffered” for

the expert testimony to be considered reliable.    Id. at 146

(explaining that expert’s conclusions and methodology “are not

entirely distinct from one another” and that “nothing in either

Daubert or the Federal Rules of Evidence requires a district

court to admit opinion evidence that is connected to existing

data only by the ipse dixit of the expert”).

                                 62
       In Kumho Tire Co. v. Carmichael, the Court extended the

Daubert approach to technical and other specialized knowledge

admissible as expert testimony under Federal Rule of Evidence

702.    
526 U.S. 137, 147-48 (1999).   Justice Breyer summarized

Daubert as holding “that Federal Rule of Evidence 702 imposes a

special obligation upon a trial judge to 'ensure that any and

all scientific testimony . . . is not only relevant, but

reliable.’”   Id. at 147 (ellipsis in original) (quoting Daubert,

509 U.S. at 589).   The Kumho Court reasoned that Rule 702 -- and

thus Daubert’s methods for assessing reliability -- had to apply

to all forms of expert testimony because the evidence rules

“grant expert witnesses testimonial latitude unavailable to

other witnesses on the 'assumption that the expert’s opinion

will have a reliable basis in the knowledge and experience of

his discipline.’”    Id. at 148 (quoting Daubert, 
509 U.S. at
 592).

       Importantly, the Court in Kumho emphasized again that the

Daubert standard is flexible, explaining that (1) the Daubert

factors do not necessarily apply “to all experts or in every

case,” id. at 141; (2) that “the law grants a district court the

same broad latitude when it decides how to determine reliability

as it enjoys in respect to its ultimate reliability

determination,” id. at 142; (3) that the Daubert factors are not

a “definitive checklist or test,” id. at 150 (quoting Daubert,

                                 63

509 U.S. at 593); and (4) that the gatekeeping inquiry must be

“'tied to the facts’ of a particular 'case,’” ibid. (quoting

Daubert, 
509 U.S. at 591).    Thus, a trial court “can neither

rule out, nor rule in, for all cases and for all time the

applicability of the factors mentioned in Daubert . . . .    Too

much depends upon the particular circumstances of the particular

case at issue.”   Ibid.

    Ultimately, Kumho underscores that the objective of

Daubert’s gatekeeping requirement “is to make certain that an

expert, whether basing testimony upon professional studies or

personal experience, employs in the courtroom the same level of

intellectual rigor that characterizes the practice of an expert

in the relevant field.”   Id. at 152.   Accordingly, “the trial

judge must have considerable leeway in deciding in a particular

case how to go about determining whether particular expert

testimony is reliable.”   Ibid.

    Federal Rule of Evidence 702 was amended in 2000 to reflect

the Supreme Court’s trilogy of cases outlining the Daubert

standard.   See, e.g., Calhoun v. Yamaha Motor Corp., U.S.A., 
350 F.3d 316, 320-21, 320 n.8 (3d Cir. 2003).    That rule as

currently written provides:

            A witness who is qualified as an expert by
            knowledge, skill, experience, training, or
            education may testify in the form of an
            opinion or otherwise if:

                                  64
              (a) the expert’s scientific, technical,
              or other specialized knowledge will help
              the trier of fact to understand the
              evidence or to determine a fact in issue;

              (b) the testimony is based on sufficient
              facts or data;

              (c) the testimony is the product       of
              reliable principles and methods; and

              (d) the expert has reliably applied the
              principles and methods to the facts of
              the case.

          [Fed. R. Evid. 702.]

A majority of states have adopted some form of the Daubert

standard, either explicitly or implicitly.   See, e.g., State v.

Porter, 
698 A.2d 739, 746 (Conn. 1997) (adopting Daubert); M.G.

Bancorp. v. Le Beau, 
737 A.2d 513, 522 (Del. 1999) (same);

Motorola, Inc. v. Murray, 
147 A.3d 751, 756-57 (D.C. 2016) (en

banc) (adopting Daubert and noting that standard is “widely

used”).

                                 C.

     In 2002, after the Daubert trilogy, we revisited the topic

of the trial court’s gatekeeping role under our current N.J.R.E.

702.26

26 In 1992, this Court adopted N.J.R.E. 702 to replace Evidence
Rule 56(2) and tracked the language of the then-existing version
of Federal Rule of Evidence 702. The Official Comment to
N.J.R.E. 702 notes that our Rule followed the then-existing
federal rule verbatim, with a minor language change.

                                 65
    In Kemp, 
174 N.J. 412, we extended the applicability of

Rubanick beyond toxic tort cases.     Kemp holds that the Rubanick

standard for assessing the reliability of proffered expert

testimony on scientific evidence should apply whenever “a

medical cause-effect relationship has not been confirmed by the

scientific community but compelling evidence nevertheless

suggests that such a relationship exists.”     Id. at 430.

    The Kemp decision further holds that a trial court has an

independent obligation to ensure that plaintiffs have sufficient

process for defending their evidentiary submissions.     The Court

explained that, by requiring a pretrial Rule 104 evidentiary

hearing, the trial court would be able to properly “assess

whether the expert’s opinion is based on scientifically sound

reasoning or unsubstantiated personal beliefs couched in

scientific terminology.”   Id. at 427 (citing Landrigan, 
127 N.J.

at 414).

    We note, in concluding this section, that the Kemp Court

observed in 2002 that New Jersey had not amended N.J.R.E. 702 to

include “the three-factor test for the admissibility of expert

testimony that is part of the Federal rule as amended in

response to Daubert.”   Id. at 424 n.3.    The Court added that its

decision was not intended “to incorporate the Daubert factors

into N.J.R.E. 702.”   Ibid.   Although the question of whether to

incorporate the Daubert factors into N.J.R.E. 702’s standard for

                                 66
admissibility, or to otherwise revise N.J.R.E. 702 to

incorporate evolving state case law on the reliability part of

our standard, has arisen from time to time in the Court’s

interactions with the Supreme Court Committee on the Rules of

Evidence, no action on such topics has been taken.

                                V.

    We intend by this case to clarify and reinforce the proper

role for the trial court as the gatekeeper of expert witness

testimony.   Defendants and several amici have good reason to ask

for clarification of the judicial gatekeeping role to be

performed in New Jersey courtrooms.

    When this Court modified the general acceptance standard to

adopt a more relaxed approach for causation expert testimony in

toxic tort litigation, and later for all medical cause-effect

expert testimony, it envisioned the trial court’s function as

that of a gatekeeper -- deciding what is reliable enough to be

admitted and what is to be excluded.   Those are not credibility

determinations that are the province of the jury, but rather

legal determinations about the reliability of the expert’s

methodology.   We now reinforce the rigor expected of the trial

court in that role under our existing case law.

    Charged with determining whether to admit expert testimony,

the trial court is responsible for advancing the truth-seeking

function of our system of justice, while still allowing for new

                                67
or developing opinions on medical causation that may not yet

have gained general acceptance.     See Rubanick, 
125 N.J. at 436-

38 (discussing commentators’ and courts’ acknowledgement of

areas in medical causation where scientific method cannot

accommodate general acceptance standard).    Resolved not to

stifle innovation in the tort system in such areas, this Court

crafted its own broadened approach to the demonstration of

reliability for an expert’s testimony.    The trial court is the

spigot that allows novel expert testimony in areas of evolving

medical causation science, provided the proponent of the expert

can demonstrate that the expert adheres to scientific norms in

distinct ways that we have identified.

    In Rubanick, we said that the court must ensure compliance

with the requirement of “some expert consensus that the

methodology and the underlying data are generally followed by

experts in the field.”    Id. at 450.   In Landrigan, we charged

the trial court with the obligation to “distinguish

scientifically sound reasoning from that of the self-validating

expert.”    
127 N.J. at 414.   And, in Kemp, we reinforced the

prohibition against allowing in “unsubstantiated personal

beliefs.”   See 
174 N.J. at 427.

    The gatekeeping role requires care.     The process of making

such determinations is “complicated,” and we knew it would be

“difficult.”   Rubanick, 
125 N.J. at 449.    The gatekeeping role

                                   68
necessitates examination of a methodology espousing a new theory

in medical cause-and-effect cases.    See id. at 451-53

(distinguishing between methodology and credibility

assessments).   Properly exercised, the gatekeeping function

prevents the jury’s exposure to unsound science through the

compelling voice of an expert.   See State v. Cavallo, 
88 N.J.
 508, 518 (1982) (“The danger of prejudice through introduction

of unreliable expert evidence is clear.   While juries would not

always accord excessive weight to unreliable expert testimony,

there is substantial danger that they would do so, precisely

because the evidence is labeled 'scientific’ and 'expert.’”).

As explained in Landrigan, “the key to admission of the opinion

is the validity of the expert’s reasoning and methodology.”      
127 N.J. at 414.

    Difficult as it may be, the gatekeeping role must be

rigorous.   In resolving issues of reliability of an expert’s

methodology in a new and evolving area of medical causation, we

cautioned that “the trial court should not substitute its

judgment for that of the relevant scientific community.    The

court’s function is to distinguish scientifically sound

reasoning from that of the self-validating expert, who uses

scientific terminology to present unsubstantiated personal

beliefs.”   Ibid.   We have repeatedly stressed that the

gatekeeper’s “critical determination is whether comparable

                                 69
experts accept the soundness of the methodology, including the

reasonableness of relying on [the] type of underlying data and

information.”   Rubanick, 
125 N.J. at 451; see Landrigan, 
127 N.J. at 417.

    That said, we can and should have more clear direction to

courts on how the gatekeeping function is properly performed.

Recognizing proper gatekeeping when it is performed provides a

discernible pathway for other courts to follow.    We endeavor to

do that with this matter.   We add further clarification and

assistance to trial courts, concerning performance of the

gatekeeping role, when reviewing scientific expert testimony

involving medical causation issues in civil matters, later in

this opinion through our adoption of the Daubert factors for

permissible use in such matters.     See, infra, Section VII, ___

(slip op. at 79-85).

                                VI.

    In turning back to the matter before us to consider the

trial court’s exclusion of plaintiffs’ experts’ testimony, we

begin by addressing the appropriate standard of review.

                                A.

    A reviewing court must apply an abuse of discretion

standard to a trial court’s determination, after a full Rule 104

hearing, to exclude expert testimony on unreliability grounds.

Hisenaj v. Kuehner, 
194 N.J. 6, 12, 16 (2008).    Here, the

                                70
Appellate Division was persuaded to veer off that standard of

review.

    The Appellate Division stated that, although a trial

court’s decision to admit or exclude evidence is subject to an

abuse of discretion standard, a reviewing court owes “somewhat

less deference to a trial court’s determination” regarding

expert testimony.   In re Accutane, 
451 N.J. Super. at 197.

However, as support for that proposition, the panel relied on

State v. Torres, which was a criminal case that applied the Frye

standard in determining the admissibility of expert witness

testimony.   
183 N.J. 554, 568 (2005) (stating that “the field of

inquiry must be generally accepted such that an expert’s

testimony would be sufficiently reliable” for expert testimony

to be admissible); see also State v. J.R., 
227 N.J. 393, 410

(2017) (relying on Torres for proposition that appellate court

need not be as deferential on admissibility of expert scientific

evidence).

    That proposition has, to date, carried weight in the

context of a court applying the general acceptance test in a

criminal matter, see State v. Harvey, 
151 N.J. 117, 167-70

(1997), but it is not appropriate in the context of a civil mass

tort case, where the trial court has been entrusted with

methodology-based review as the gatekeeper of expert testimony.

Neither Rubanick, nor Landrigan, nor Kemp speaks to any such

                                71
less-deferential standard, and this Court has continued to apply

a pure abuse of discretion standard in civil matters concerning

expert testimony.     See, e.g., Townsend v. Pierre, 
221 N.J. 36,

52-53 (2015) (“As this Court has noted, 'we apply [a]

deferential approach to a trial court’s decision to admit expert

testimony, reviewing it against an abuse of discretion

standard.’”    (alteration in original) (quoting Pomerantz Paper

Corp. v. New Cmty. Corp., 
207 N.J. 344, 371-72 (2011))).

    We reaffirm that the abuse of discretion standard applies

in the appellate review of a trial court’s determination to

admit or deny scientific expert testimony on the basis of

unreliability in civil matters.    We now apply that standard to

the determination of the trial court in this matter.

                                  B.

    An expert must demonstrate the validity of his or her

reasoning.    Landrigan, 
127 N.J. at 414.   Defendants argued, and

presented experts who supported the argument, that plaintiffs’

experts failed to meet our expert witness standard because they

applied a contradictory and selective form of reasoning in which

they used certain arguments to discredit the epidemiological

evidence, only to abandon those arguments when relying on weaker

evidence.     The trial court essentially agreed with that

assessment in conducting a properly performed robust analysis of

the methodology advanced by plaintiffs’ experts.

                                  72
    The trial court concluded that Dr. Kornbluth failed to

persuade it of the soundness of his reasoning in support of his

causation opinion.     As his is the only causation opinion

proffered, we focus on the court’s rejection of Dr. Kornbluth’s

methodology used to support his opinion, particularly the

court’s reasoning and the bases on which the testimony was

declared to be unsound.     Although Dr. Kornbluth offered the only

opinion on causation of plaintiffs’ two experts, both experts

offered interlocking expert testimony, and so our analysis of

both is intertwined.    The following assessments were made by the

trial court in reaching its decision to exclude the testimony,

and are supported by the record in this case.

    Both Doctors Madigan and Kornbluth employed a methodology

whereby they disregarded eight of nine epidemiological studies

and relied on case reports and animal studies to support their

opinion.   It is clear that case reports are “at the bottom of

the evidence hierarchy,” Reference Manual at 724, and other

courts have been skeptical of their value in proving causation,

see, e.g., Allison v. McGhan Med. Corp., 
184 F.3d 1300, 1316

(11th Cir. 1999) (holding that district court did not abuse its

discretion by “discounting [expert’s] reliance on case reports

in the face of the overwhelming contrary epidemiological

evidence presented”); Siharath v. Sandoz Pharms. Corp., 
131 F. Supp. 2d 1347, 1361 (N.D. Ga. 2001) (commenting, when rejecting

                                  73
experts’ reliance on case reports in the absence of

statistically significant epidemiological studies, that

generally “[c]ase reports are not reliable scientific evidence

of causation, because they simply describe[] reported phenomena

without comparison to the rate at which the phenomena occur in

the general population or in a defined control group; do not

isolate and exclude potentially alternative causes; and do not

investigate or explain the mechanism of causation.”   (second

alteration in original) (quoting Casey v. Ohio Med. Prods., 
877 F. Supp. 1380, 1385 (N.D. Cal. 1995))).   And while animal

studies may be helpful in “framing hypotheses,” the Reference

Manual intimates that such evidence is far less probative in the

face of a “substantial body of epidemiologic evidence.”      Id. at

563, 564-65, 564 n.48.   Such was the case here; initial animal

studies may have suggested a possible causal connection between

Accutane and Crohn’s disease, but since that time a uniform body

of epidemiological evidence has dispelled any such theory.      See

Siharath, 
131 F. Supp. 2d   at 1366-68 (explaining why court

viewed animal studies with suspicion in absence of confirmatory

epidemiological studies and adding generally that extrapolation

to humans is “not considered reliable in the absence of a

credible scientific explanation of why such extrapolation is

warranted”).   Thus, we do not mean to suggest that animal

studies and case reports can never be relied upon for forming an

                                74
opinion on causation, but we find ample support for the trial

court’s determination that it was not proper to do so here in

light of the uniform body of epidemiological evidence.

     As for the one study on which they did rely -- Sivaraman --

plaintiffs’ experts disagreed with the authors’ ultimate

conclusions and instead focused on unadjusted results.     In so

doing, plaintiffs’ experts dismissed published studies examining

thousands of subjects as underpowered and biased in favor of

relying on portions of a single unpublished study that examined

509 total subjects.27

     In explaining their reasoning for disregarding the results

of so many epidemiological studies that consistently failed to

show an association between Accutane and Crohn’s disease,

plaintiffs’ experts asserted that the prodrome for Crohn’s

disease is two years or more.    They based that assessment on two

smaller studies, Pimentel and Barratt, even though there were

other larger studies, such as Chouraki, which had found a much

shorter median prodromal period -- a median of approximately

less than one year.     Thus, despite their expressed concerns

regarding study power -- which is based in part on the size of

27 The trial court explained that the Sivaraman study appeared
only as an abstract in the American Journal of Gastroenterology,
and a written report detailing the study’s findings has never
been published. As defendants noted, the study remains
unpublished today, and it has not been cited in any published
opinion other than the present case.
                                  75
the study at issue -- in rejecting the epidemiological studies,

plaintiffs’ experts were willing to ignore any such concern when

relying on the Pimentel and Barratt studies to form their

opinion as to the median prodromal period.    Moreover, as the

trial court observed, plaintiffs’ experts could have performed a

meta-analysis to account for the power issue but refused.

    The many contradictions in the experts’ methodology were

not lost on the trial court, which concluded that experts in the

scientific community would not accept as consistent with

scientific norms a methodology such as that used by plaintiffs’

experts.   In particular, the court found the methodology unsound

because it relied on Sivaraman and Pimentel to the exclusion of

other evidence.   The trustworthiness of plaintiffs’ experts’

methodology was further undermined by internal inconsistencies,

including the experts’ refusal to examine the Rashtak and

Fenerty studies on the ground that those studies did not report

specific data for Crohn’s disease while Dr. Kornbluth tethered

his own causation opinion to case reports not specific to

Crohn’s disease and to studies performed on animals incapable of

having any form of irritable bowel disease.

    The trial court reasoned that the overall approach taken by

Dr. Kornbluth -- rejecting the evidence from the epidemiological

studies, which all found no causal association, and proffering

his own alternative opinion that a causal association was

                                76
present based on lesser forms of evidence -- was based on an

unsound methodology.     That conclusion comports with the

decisions of many other courts that experts cannot selectively

choose lower forms of evidence in the face of a large body of

uniform epidemiological evidence.      See, e.g., In re Lipitor, ___

F.3d ___ (4th Cir. 2018) (slip op. at 16) (“Result-driven

analysis, or cherry-picking, undermines principles of the

scientific method and is a quintessential example of applying

methodologies (valid or otherwise) in an unreliable fashion.”);

Allison, 184 F.3d   at 1316; Freeman v. Hoffman-La Roche, Inc.,

911 N.W.2d 591, 596-98 (Neb. 2018) (holding that trial court did

not abuse its discretion in excluding expert testimony where

expert employed inconsistent methodology and “cherry[-]pick[ed]

studies from an overwhelmingly contrary body of literature”).

The trial court found it to be demonstrably contrary to the

recognized hierarchy of evidence in the Reference Manual and

accepted generally in the scientific community.     Indeed, even

plaintiffs’ experts acknowledged the scientific community’s

acceptance of a hierarchy of evidence, but they deviated from

it.   Moreover, as the court noted and found to be compelling,

Dr. Kornbluth never submitted his ideas concerning biological

mechanism or Accutane’s relation to Crohn’s disease for peer

review or publication.    In fact, he previously expressed

concern, in an e-mail to a colleague admitted into the record in

                                  77
this matter, about any connection between Accutane and Crohn’s

disease after the Bernstein study, the first of the

epidemiological studies, was published in 2009.

    Finally, it bears noting that Dr. Kornbluth organized his

testimony to support his personal view that a causal association

existed between Accutane and Crohn’s disease through use of the

Hill guidelines.   However, those guidelines are invoked only

after an association between an agent and a particular disease

has been determined to be present; their pointed purpose is to

determine whether a detected association reflects true

causality, it is not to create an association that has not

already been detected through appropriate studies.     See

Reference Manual at 598-99 (explaining that Hill “guidelines are

employed only after a study finds an association to determine

whether that association reflects a true causal relationship”).

Here, not one of the epidemiological studies found any

statistically significant association between Accutane and

Crohn’s disease.

    In sum, the trial court explained its reasons for

concluding that plaintiffs’ experts deviated from core

scientific principles and strayed from their own claimed

methodology in order to reach their conclusions.     That the trial

court deemed their testimony to be unreliable and excluded it

from being presented is unsurprising.   Ample evidence in the

                                78
record supports that conclusion.     Applying the abuse of

discretion standard and the principles of Rubanick, Landrigan,

and Kemp, we conclude that the trial court’s determination is

unassailable.   The Appellate Division judgment, reversing the

trial court’s exclusion of the expert testimony, is reversed.

                               VII.

    The divergent outcomes reached by the Appellate Division

and the trial court in this matter provoked the debate among the

parties and amici over whether our case law on the gatekeeping

function is in need of clarification.     Further, we are asked to

consider adopting the Daubert standard, or to at least

incorporate use of its factors, as a means to bring greater

consistency to the gatekeeping function.

    First, in respect of the gatekeeping role, we emphasize

that we expect the trial court to assess both the methodology

used by the expert to arrive at an opinion and the underlying

data used in the formation of the opinion.     That will ensure

that the expert is adhering to norms accepted by fellow members

of the pertinent scientific community.     Methodology, in all its

parts, is the focus of the reliability assessment, not outcome.

See Clark v. Safety-Kleen Corp., 
179 N.J. 318, 337 (2004)

(“Rubanick changed the focus of the inquiry from the scientific

community’s acceptance of the substance of the opinion to its

acceptance of the methodology and reasoning underlying it.”).

                                79
    It is not for a trial court to bless new “inspired” science

theory; the goal is to permit the jury to hear reliable science

to support the expert opinion.   Cf. Rosen v. Ciba-Geigy Corp.,

78 F.3d 316, 319 (7th Cir. 1996) (“[T]he courtroom is not the

place for scientific guesswork, even of the inspired sort.”).

In this basic goal, there is not much light between our standard

and that which has developed in the federal sphere under

Daubert’s initial instruction.   Our law moved first, but in the

same direction and with the same general goal as that noted by

the Supreme Court in its Daubert trilogy.   Both lines of initial

decisions recognized the drawback of limiting expert testimony

exclusively through the filter of general acceptance.   For this

Court, certain areas of law cried out for greater flexibility.

For the federal courts, a broader reach was extended.

    Importantly, both our law and the Daubert trilogy are

aligned in their general approach to a methodology-based test

for reliability.   Both ask whether an expert’s reasoning or

methodology underlying the testimony is scientifically valid.

Daubert, 
509 U.S.  at 594-95 (explaining that inquiry into expert

witness testimony requires examination of “scientific validity”

of “the principles that underlie a proposed submission” and that

court’s focus “must be solely on principles and methodology”);

Rubanick, 
125 N.J. at 449 (holding that scientific theory of

causation may be found sufficiently reliable where “it is based

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on a sound, adequately-founded methodology”).    Moreover, both

standards look to whether that reasoning or methodology properly

can be applied to facts in issue.     Daubert, 
509 U.S.  at 591

(explaining that Rule 702 requires that there be proper “fit”

between expert testimony and facts of case and that expert

testimony must be sufficiently tied to facts of case in order to

aid jury in resolving matters at issue (citing United States v.

Downing, 
753 F.2d 1224, 1242 (3d Cir. 1985))); Rubanick, 
125 N.J. at 449 (“The expert must possess a demonstrated

professional capability to assess the scientific significance of

the underlying data and information, to apply the scientific

methodology, and to explain the bases for the opinion reached.”

(emphasis added)).

    Importantly, Daubert identified a non-exhaustive list of

factors for courts to consider using, if helpful, when it

expanded on its test for assessing the reliability of scientific

expert testimony.    See 
509 U.S.  at 593-95.   Distilled, the

general factors identified as perhaps pertinent for

consideration, but not dispositive or exhaustive, are:

    1) Whether the scientific theory can be, or at any
       time has been, tested;

    2) Whether the scientific theory has been subjected
       to peer review and publication, noting that
       publication is one form of peer review but is
       not a “sine qua non”;

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    3) Whether there is any known or potential rate of
       error and whether there exist any standards for
       maintaining or controlling the technique’s
       operation; and

    4) Whether there does exist a general acceptance in
       the scientific community about the scientific
       theory.
That last consideration -- general acceptance in the scientific

community -- continues to have a bearing because, minimally, it

permits the identification of a relevant scientific community

and facilitates an express determination of a particular degree

of acceptance within that community, or contrarily permits a

technique with minimal support to be viewed with skepticism.

See id. at 594.

    We are persuaded that the factors identified originally in

Daubert should be incorporated for use by our courts.     The

factors dovetail with the overall goals of our evidential

standard and would provide a helpful -- but not necessary or

definitive -- guide for our courts to consider when performing

their gatekeeper role concerning the admission of expert

testimony.    Several are aimed at achieving the same examination

for peer acceptance of a methodology (but not the outcome

reached from that methodology) described in our earlier

opinions.    See Landrigan, 
127 N.J. at 417; Rubanick, 
125 N.J. at
 449-50.

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       In adopting use of the Daubert factors, we stop short of

declaring ourselves a “Daubert jurisdiction.”     Like several

other states, we find the factors useful, but hesitate to

embrace the full body of Daubert case law as applied by state

and federal courts.    See, e.g., People v. Shreck, 
22 P.3d 68, 70

(Colo. 2001) (en banc) (abandoning Frye test and holding that

trial court “may consider” Daubert factors); McDaniel v. CSX

Transp., 
955 S.W.2d 257, 265 (Tenn. 1997) (finding factors

useful in determining reliability but not expressly adopting

Daubert).

       First, we have already broadened our approach to testing

for the reliability of expert testimony for certain areas in

civil law, see Kemp, 
174 N.J. at 430; but, to date, we retain

the general acceptance test for reliability in criminal matters,

see Harvey, 
151 N.J. at 167-70.    Second, there is no monolithic

body of case law uniformly or even consistently applying

Daubert, as others have noted.    See, e.g., Motorola, 147 A.3d   at

757.    We hesitate to sweep in adherence to the various

approaches taken among the circuits and state jurisdictions when

applying the Daubert factors.     Thus, we do not adopt a

“standard” that we cannot fully discern in its application at

this time.    While the factors are helpful, and while individual

cases may be persuasive in appropriate settings, we cannot

ignore that there are discordant views about the gatekeeping

                                  83
role among Daubert jurisdictions.     See ibid.; see generally

David E. Bernstein & Eric G. Lasker, Defending Daubert:     It’s

Time to Amend Federal Rule of Evidence 702, 57 Wm. & Mary L.

Rev. 1, 26-36 (2015).

    Our view of proper gatekeeping in a methodology-based

approach to reliability for expert scientific testimony requires

the proponent to demonstrate that the expert applies his or her

scientifically recognized methodology in the way that others in

the field practice the methodology.    When a proponent does not

demonstrate the soundness of a methodology, both in terms of its

approach to reasoning and to its use of data, from the

perspective of others within the relevant scientific community,

the gatekeeper should exclude the proposed expert testimony on

the basis that it is unreliable.    See, e.g., In re Lipitor, ___

F.3d at ___ (slip op. at 16); Lust v. Merrell Dow Pharms., Inc.,

89 F.3d 594, 598 (9th Cir. 1996) (noting that courts should be

wary that expert has not faithfully applied methodology where

expert’s conclusions are “anomalous”); In re Rezulin Prods.

Liab. Litig., 
369 F. Supp. 2d 398, 425 (S.D.N.Y. 2005)

(explaining that courts typically exclude testimony from experts

who selectively choose from scientific landscape); Freeman, 
911 N.W 2d at 596-98.

    Importantly, that approach -- namely, to determine whether

the scientific community would accept the methodology employed

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by plaintiffs’ experts and would use the underlying facts and

data as did plaintiffs’ experts -- was employed by the trial

court here.   We approve of the court’s methodological analysis.

There was no encroachment on the factfinding function here.     The

trial court did the type of rigorous gatekeeping that is

necessary when faced with a novel theory of causation,

particularly one, as here, that flies in the face of consistent

findings of no causal association as determined by higher levels

of scientific proof.

    For all the reasons expressed herein, we conclude that the

trial court’s exclusion of plaintiffs’ experts’ testimony was

well-supported and well-reasoned.      There was no abuse of

discretion by the trial court in its evidential ruling.

                               VIII.

    We reverse the judgment of the Appellate Division, which

had reversed the trial court’s exclusion of plaintiffs’ experts’

testimony.

     CHIEF JUSTICE RABNER and JUSTICES ALBIN, FERNANDEZ-VINA,
SOLOMON, and TIMPONE join in JUSTICE LaVECCHIA’s opinion.
JUSTICE PATTERSON did not participate.

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