Title: In re: Accutane Litigation
Citation: N/A
Docket Number: 
State: new-jersey
Issuer: new-jersey Supreme Court
Date: August 1, 2018

In re: Accutane Litigation Annotate this Case Justia Opinion Summary Accutane was 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 case before the New Jersey Supreme Court here involved over two thousand plaintiffs who alleged 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 was not causally associated with the development of Crohn’s disease. Defendants filed a motion seeking a hearing on the association between Accutane and Crohn’s disease. The issue presented for the New Jersey Supreme Court’s consideration reduced to the admissibility of scientific evidence under the New Jersey Rules of Evidence. Plaintiffs claimed that a causal connection existed between Accutane and Crohn’s disease. The Supreme Court discerned 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.” The Court reconciled 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 cases. Here, the trial court properly excluded plaintiffs’ experts’ testimony. Moreover, the Court reaffirmed 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. Read more Want to stay in the know about new opinions from the Supreme Court of New Jersey? Sign up for free summaries delivered directly to your inbox. Learn More › You already receive new opinion summaries from Supreme Court of New Jersey. Did you know we offer summary newsletters for even more practice areas and jurisdictions? Explore them here . SYLLABUSThis 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, 2018LaVECCHIA, 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 079958IN 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 actionis the admissibility of scientific evidence under the New JerseyRules of Evidence. Plaintiffs claim that a causal connection exists betweenAccutane, a prescription drug used in the treatment of nodularacne, and Crohn’s disease, a chronic gastrointestinal illness.Litigation in New Jersey over Accutane’s side effects hasspanned more than a decade. This action is a continuation inthat series of litigated matters. Since those actions firstcommenced in New Jersey in 2005, a number of epidemiologicalstudies have been published, all concluding that there is nocausal relationship between Accutane and Crohn’s disease.Plaintiffs’ experts dispute the conclusions of those studies,calling them flawed and lacking in value. Having rejected theevidence and conclusions of those epidemiological studies, oneof plaintiffs’ experts, relying on other facts and forms of 3 data, asserts the contrary view that Accutane can in fact causeCrohn’s disease. Defendants challenged the methodology used byboth of plaintiffs’ experts as unreliable and sought theexclusion of that expert testimony. After a Rule 104 pretrial evidentiary hearing, the trialcourt excluded the testimony, holding that plaintiffs’ experts’methodology was unsound because they did not interpret therelevant data and apply it to the facts of this case as wouldother experts in the field. The Appellate Division reversed,concluding that plaintiffs’ experts employed a sound methodologyand simply interpreted the data differently than defendants’experts. Our Court was among the foremost to shift from exclusivereliance on a “general acceptance” standard1 for testing thereliability 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 intoxic tort civil matters to present novel scientific evidence ofcausation if, after the trial court engages in rigorousgatekeeping when reviewing for reliability, the proponentpersuades the court of the soundness of the expert’s reasoning1 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 generalacceptance test in favor of a methodology-based approach thatentrusted trial courts with the role of gatekeeper. Both ourcivil standard and the federal standard moved in the samedirection and towards the same common goal. Although the twostandards are similar both in practice and in overallphilosophy, we have never adopted Daubert or incorporated thefactors identified in Daubert for use by our courts whenperforming the gatekeeper role. We granted certification in this matter to address whetherthe trial court properly excluded plaintiffs’ experts’testimony, whether the Appellate Division employed the correctstandard in reviewing and overturning that decision, and whetherour standard for assessing the reliability of expert witnessesis in need of clarification. It is with regard to the lastissue that we are asked whether the Daubert standard’s factorswould further elucidate our own standard for the admissibilityof expert testimony. We believe that they would. We perceive little distinction between Daubert’s principlesregarding expert testimony and our own, and believe that itsfactors for assessing the reliability of expert testimony will2 Daubert v. Merrell Dow Pharms., Inc., 509 U.S. 579 (1993). 5 aid our trial courts in their role as the gatekeeper ofscientific expert testimony in civil cases. Accordingly, we nowreconcile our standard under N.J.R.E. 702, and relatedlyN.J.R.E. 703, with the federal Daubert standard to incorporateits factors for civil cases. This case -- with its adversarial setting and full record-- provides the appropriate setting for illustrating how courtsshould evaluate the methodology of a credentialed expert whendetermining whether an opinion is based on scientifically soundreasoning. 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 discretionstandard must be applied by an appellate court assessing whethera trial court has properly admitted or excluded expertscientific testimony in a civil case. In this matter, the trialcourt did not abuse its discretion in its evidential ruling and,therefore, the Appellate Division erred in reversing the trialcourt’s exclusion of the testimony of plaintiffs’ experts. I. Before diving into the record and its contested scientificevidence, we set forth some basic background to the evidentialstandards in issue. 6 New Jersey Rules of Evidence 702 and 703 control theadmission of expert testimony. N.J.R.E. 702 provides that“[i]f scientific, technical, or other specialized knowledge willassist the trier of fact to understand the evidence or to determinea fact in issue, a witness qualified as an expert by knowledge,skill, experience, training, or education may testify thereto inthe 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 similarlyworded predecessor, Evidence Rule 56, and identified threeprerequisites to a determination that expert testimony ispermissible: (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 ofexpert testimony. See Official Comments to N.J.R.E. 702 (notingthat N.J.R.E. 702 incorporates standard articulated by Kelly). 7 The Kelly criteria elucidated application of the then-applicable “general acceptance” standard for admittingscientific evidence, which originated in Frye v. United States,293 F. 1013 (D.C. Cir. 1923). In Frye, the then Court ofAppeals for the District of Columbia excluded an expert’stestimony concerning results from an early form of lie-detectortest. Id. at 1013-14 (“[W]hile courts will go a long way inadmitting expert testimony deduced from a well-recognizedscientific principle or discovery, the thing from which thededuction is made must be sufficiently established to havegained general acceptance in the particular field in which itbelongs.”). For many years, the majority of state and federaljurisdictions, including New Jersey, adhered to the “generalacceptance” 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 fordetermining the admissibility of novel scientific evidence” forover seventy years). Then, in 1991, prior to the United StatesSupreme Court’s seminal Daubert decision, in which the Courtinterpreted the Federal Rules of Evidence on expert testimony,our Court moved away from rigid adherence to the generalacceptance standard. This Court held in Rubanick that a court may admit expertscientific 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 ofthe type reasonably relied on by experts in the scientificfield.” 125 N.J. at 449. One year later, in Landrigan, wereinforced that in toxic tort matters involving novel theoriesof causation the trial court is obliged to review data andstudies relied on by experts proffering an opinion in order to“determine whether the expert’s opinion is derived from a soundand well-founded methodology that is supported by some expertconsensus in the appropriate field.” 127 N.J. at 417. In Kemp,we expanded Rubanick to all novel medical causationcircumstances and solidified the requirement of a pretrial Rule104 hearing for assessing an expert’s testimony. 174 N.J. at 430. Presently, a Kemp hearing is a common pretrial occurrencefor 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 determinedthat the contested evidence did not pass muster under ourRubanick evidentiary standard for assessing the reliability ofproffered expert scientific testimony. The court made itsfindings in response to argument by the parties, rejecting thesoundness of plaintiffs’ experts’ methodology. II. A. 9 Accutane is a prescription medication developed bydefendants Hoffman-La Roche Inc. and Roche Laboratories Inc.(defendants) and approved by the FDA in 1982 to treatrecalcitrant nodular acne. Known chemically as isotretinoin,Accutane is part of a family of Vitamin A derivatives calledretinoids. During the pre-approval clinical studies ofAccutane, roughly a fifth of patients suffered some form ofgastrointestinal side effects. Defendants also learned, afterAccutane was on the market, that users were suffering symptomsof gastrointestinal upset such as inflammatory bowel disease(IBD) and peptic ulceration. Defendants eventually amendedAccutane’s warning label in 1984 to add that Accutane was“temporally associated with inflammatory bowel disease.” Accutane’s alleged role as a cause of gastrointestinaldisease ultimately resulted in a series of lawsuits againstdefendants. On May 2, 2005, this Court designated all pendingand future New Jersey actions involving Accutane as a mass tortMulticounty Litigation (MCL) pursuant to Rule 4:38A. All casesinvolving Accutane were subsequently transferred to AtlanticCounty to be heard on a coordinated basis. The present matter, the latest in a series of cases,3involves over two thousand plaintiffs who allege that they3 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. Thefollowing basic information is not a matter of dispute betweenthe parties. Crohn’s disease is a form of IBD characterized byinflammation and ulcers in the digestive tract that can resultin abdominal pain and other complications. Crohn’s disease isdistinguished from ulcerative colitis, the other form of IBD, byits ability to appear in any portion of the digestive tract,such as the esophagus and small intestine, whereas ulcerativecolitis appears only in the large intestine. The scientificcommunity appears to agree that Crohn’s disease and ulcerativecolitis are subject to slightly different risk factors. Theexact cause of Crohn’s disease is unknown. In the years since many of the earlier cases regardingAccutane and IBD were decided, a series of epidemiologicalstudies were published regarding the potential connectionbetween Accutane and IBD, all of which concluded that Accutaneis not causally associated with the development of Crohn’sdisease. On September 23, 2014, defendants filed a motionseeking a Kemp hearing on the association between Accutane andCrohn’s disease. Defendants argued that epidemiological studiespublished in the scientific literature over the last severalyears effectively disproved any general causal associationrelating 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 thosestudies are “the most important and reliable data that exists onAccutane and Crohn’s disease” and are superior to other forms ofevidence previously used in the MCL litigation such as casereports, animal studies, and theories on biological mechanisms. The trial court scheduled a Kemp hearing to begin onFebruary 2, 2015. B. The testimony focused intently on the aforementionedepidemiological studies. Accordingly, some background on theuse of such studies in the formation of causal analyses providescontext for the discussion of the evidence by the parties andthe trial court. Much of the following discussion is taken fromthe Federal Judicial Center’s Reference Manual on ScientificEvidence (3d ed. 2011), a source frequently relied on in thetrial court proceedings.4 Epidemiology “studies the incidence, distribution, andetiology of disease in human populations.” Id. at 551. Moreparticularly, epidemiology focuses on the question of “generalcausation,” that is, whether the agent under study is “capable4 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 ina particular individual. Id. at 552. Epidemiology is premisedon the idea “that disease is not distributed randomly” and thatcertain groups are at increased risk of contracting a particulardisease. Id. at 551. Epidemiological studies are used to test whether exposureto a particular agent causes a harmful effect or disease. Id.at 551-52. Although such studies may reveal an associationbetween a particular agent and a particular disease, “[a]nassociation identified in an epidemiological study may or maynot be causal,” and causation must be assessed in considerationwith the “strengths and weaknesses of the study’s design andimplementation, as well as a judgment about how the studyfindings fit with other scientific knowledge.” Id. at 552-53.When evaluating a study’s evidential value, a basicconsideration is whether the particular study used a soundmethodology, as well as the extent to which the study’s resultsmay be due to “bias, confounding, or sampling error.” Id. at554. Among the different kinds of epidemiological studies,randomized trials are “considered the gold standard fordetermining the relationship of an agent to a health outcome or 13 adverse side effect.” Id. at 555.5 Where randomized trialscannot 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 thefrequency of exposure in the group with the disease (cases) anda similar group without the disease (controls); and (2) a cohortstudy, which compares a group of exposed and unexposedindividuals over a period of time. Id. at 557-59.Observational studies identify a group of individuals exposed tothe agent in question and then compare their rate of disease tothat of an unexposed group. Id. at 556. A weakness in suchstudies is “the possibility of differences in the twopopulations being studied with regard to risk factors other thanexposure to the agent.” Ibid. Investigators generally cannotcontrol for a variety of “confounders” that may distort such astudy’s results. Ibid. A confounder’s influence on a study’sresults therefore must be considered in the study’s design andin 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 inlegal matters, three basic questions arise in the assessment ofa 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 aparticular agent and development of a specific disease,researchers then consider whether that association “reflects atrue cause-effect relationship.” Id. at 597. To do so,researchers look to alternative explanations, such as bias orconfounding factors, and then consider how well-recognized“guidelines for inferring causation from an association apply tothe available evidence.” Id. at 598. However, and importantly,those accepted “guidelines are employed only after a study findsan association to determine whether that association reflects atrue causal relationship.” Id. at 598-99. Commonly referred to 15 as the “Hill criteria” or “Hill factors,”6 they consist of thefollowing: 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 ReferenceGuide on Medical Testimony, which provides a “Hierarchy ofmedical evidence.” Id. at 723. The parties in this matter donot dispute that the Reference Manual and the scientificcommunity as a whole acknowledge such a hierarchy. TheReference Manual summarizes it as follows: “[w]hen ordered fromstrongest to weakest, systematic review of randomized trials(meta-analysis) is at the top, followed by single randomized6 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, singleobservational studies, physiological studies, and unsystematicclinical observations.” Id. at 723-24. Evidence at the bottomof the hierarchy may sometimes be “the first signals of adverseevents or associations that are later confirmed with larger orcontrolled epidemiological studies.” Id. at 724. Finally, in addition to observational epidemiology,researchers sometimes look to animal studies for determining agiven agent’s toxicity in humans. Id. at 563. Such studies“often provide useful information about pathological mechanismsand play a complementary role to epidemiology by assistingresearchers in framing hypotheses and in developing studydesigns for epidemiological studies.” Ibid. However, animalstudies also have significant disadvantages because biologicaldifferences between humans and the animals under observationcreate difficulties in extrapolating data from animal studiesand applying it to humans. Ibid. Even so, “[w]here both animaltoxicologic and epidemiologic studies are available, nouniversal rules exist for how to interpret or reconcile them.”Id. at 564. That said, the Reference Manual acknowledges thatthere are “conflicting lines of cases” regarding the weightcourts tend to give animal studies, which the Reference Manualsuggests may be explained by differences in the available amountof epidemiologic data across different subjects. Id. at 564-65, 17 564 n.48. Specifically, the Reference Manual states that “whenthere is a substantial body of epidemiologic evidence thataddresses the causal issue, animal toxicology has much lessprobative value.” Ibid. On the other hand, “[w]hereepidemiologic evidence is not available, animal toxicology maybe thought to play a more prominent role in resolving a causaldispute.” Ibid. Beginning in 2009, scientists began examining the issue ofAccutane’s causal relationship to Crohn’s disease through thelens of epidemiological studies. The first of those studies,published by Bernstein et al.7 in 2009, examined approximately21,500 subjects and concluded that “[a]lthough there may beanecdotes of [Accutane] causing acute colitis [inflammation ofthe colon], our data suggest that [Accutane] is not likely tocause chronic IBD.” In 2010, a study by Crockett et al.8examining approximately 29,000 subjects found “no apparentassociation between isotretinoin and [Crohn’s disease],” but didfind a statistically significant increased risk betweenisotretinoin and ulcerative colitis. A study published in 20137 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 thatthere was no “increase in the risk for IBD, including UC[ulcerative colitis] or CD [Crohn’s disease], with use ofisotretinoin.” Those same authors also performed a meta-analysis10 of the available data and again concluded that therewas no association between Accutane and Crohn’s disease.Etminan, supra note 9 at 216, 218-20. A study of 46,922subjects treated with Accutane published by Alhusayen et al.11 in2013 found “no significant association between isotretinoin useand IBD.” In 2014, an abstract by Sivaraman et al. examining509 subjects concluded that “Isotretinoin exposure does notappear to confer risk for either UC or CD independent ofantibiotic exposure.” Two other studies -- a 176,889-subject study performed byFenerty et al.12 and a 1078-subject study by Rashtak et al.,139 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 thatAccutane was not causally associated with IBD but did notinclude specific data for Crohn’s disease. Finally, a study ofapproximately 44,000 subjects by Racine et al.14 published in2014 concluded that Accutane use “was associated with adecreased [Crohn’s disease] risk.” The interpretation of thosestudies is the central issue in this appeal. C. Plaintiffs and defendants each produced two expertwitnesses. Plaintiffs produced Dr. Arthur Asher Kornbluth, agastroenterologist, 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 subspecialtyof gastroenterology. He maintains an active clinical practicetreating Crohn’s disease and ulcerative colitis and is also aClinical Professor of Medicine at the Icahn School of Medicineat 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 Accutanecan cause Crohn’s disease. In rendering a general causationopinion on the key question in this matter, he explained that hebased his finding of a causal association on “the pathogenesisand natural history of Crohn’s disease, including the relevantintestinal anatomy on the macroscopic and cellular level,” “thepharmacology of Accutane and its metabolites,” “reports andassessments of Crohn’s disease of acute gastrointestinaltoxicity in patients treated with Accutane or its metabolites,”and “large clinical trials in patients with Crohn’s diseaseevaluating the clinical benefits of blocking the mechanism ofaction of Accutane’s metabolites.” Further, in addition to hisreview of the scientific and medical literature, Dr. Kornbluthalso looked to a number of other materials produced as part ofthe Accutane litigation, including defendants’ internal animalstudies and causality assessments, and post-marketing reports. Dr. Kornbluth’s testimony had two themes: explaining whyhe found the epidemiological studies unreliable anduninformative regarding the issue of causation, and explaininghis reliance on other forms of evidence such as case reports,animal studies, causality assessments, and his biologicalmechanism hypothesis. With regard to the epidemiological studies, Dr. Kornbluthexplained that he would not rely on any study that did not 21 provide separate data for Crohn’s disease. As a result, hefound the Fenerty and Rashtak studies -- both of which analyzeddata for IBD generally and not for Crohn’s disease specifically-- to be uninformative. As for the studies that did lookspecifically for Crohn’s disease, Dr. Kornbluth stated that mostof them, including the Alhusayen, Crockett, Etminan, and Racinestudies, were fatally flawed because they did not account forCrohn’s disease’s “prodrome,” meaning the period between theonset of a disease’s symptoms and its actual diagnosis. Dr.Kornbluth asserted that the median prodrome for Crohn’s diseaseis roughly two-to-four years, and that the studies in questiondid not account for that period because they examined studysubjects only for roughly one year. Because they did notexamine patient data for a sufficient period of time, Dr.Kornbluth argued that those studies missed patients whoseprodromes were longer than the studies’ observation periods,thus biasing the results towards a finding of no associationbetween Accutane and Crohn’s disease. Dr. Kornbluth based hisopinion regarding the median prodromal period on two studies: astudy by Pimentel et. al.15 that contained 45 total subjects with15 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 contained230 total subjects with Crohn’s disease. Dr. Kornbluth detected other problems with theepidemiological studies. He asserted that the Crockett,Bernstein, and Etminan studies did not have enough patients andthus were “underpowered,” meaning that they were not properlydesigned to detect a statistically significant increased risk,even if such a risk actually existed, because the study size wassimply too small. He asserted that the Alhusayen and Etminanstudies did not adjust for certain confounders, such as familyhistory and smoking. With regard to the Racine and Bernsteinstudies, he noted that those studies were performed in Franceand Canada, respectively, and that French and Canadian patientstypically receive half the Accutane dosage that Americanpatients receive. Moreover, he noted that the protective effectfound in the Racine study’s results lessened as the dosagesincreased, indicating a dose toxicity response. He was alsodismissive of the meta-analysis that the Etminan authorsperformed, stating that it suffered from the same limitations asthe studies that went into it and that a meta-analysis based on16 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 notinform the issue. Dr. Kornbluth also noted that the Bernstein and Alhusayenstudies both contained positive “point estimates,”17 indicatingan increased risk. He admitted that the results of both studieswere not regarded as “statistically significant,”18 but heintimated that the lack of statistical significance was due tothe studies’ inherent flaws and biases. In the end, the Sivaraman study was the only study uponwhich Dr. Kornbluth was willing to rely. Even so, he disagreed17 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 thestudy’s unadjusted point estimate showed that “patients withCrohn’s disease were five times more likely to have takenAccutane than those who did not,” and that the study’sunadjusted results also showed a statistically significantincreased risk. However, in explaining why he disagreed withthe Sivaraman authors’ conclusion that Accutane does not causeCrohn’s disease, he noted that the Sivaraman authors reachedtheir adjusted point estimate by subtracting out patients whohad taken antibiotics; while that adjusted point estimate stillshowed a heightened risk, the smaller number of patients meantthat the result lost statistical significance. Moreover, hestated that he could not understand why the study authors hadtaken that step because “antibiotics per se did not influencethe likelihood of developing Crohn’s disease.” It was thus “notclear” to him why the authors made such an adjustment. Moving beyond the epidemiological studies, Dr. Kornbluthexamined other lines of evidence that he found supported hiscausation opinion. He began by explaining why he believes it isbiologically plausible for Accutane to cause Crohn’s disease,although he had not published his causation theory or otherwisesubmitted 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 referredto as “challenge/dechallenge/rechallenge,” in which a patientwas given Accutane and then developed a form of intestinalinflammation, which then ceased when Accutane use wasdiscontinued and began again upon resumption of Accutane usage.He regarded that to be “very compelling” evidence of a causativeeffect. He discussed his reliance on MedWatch reports -- “reportsmade by physicians, patients, [and] others to the FDA describingsymptoms that they think were related to ingested medications.”He noted the significant number of such reports relating toCrohn’s disease and other gastrointestinal problems thatcorrelated with the use of Accutane. Similarly, he testifiedthat he relied on defendants’ own internal materials, notingthat defendants’ scientists determined that Accutane should becontraindicated for individuals with certain gastrointestinalproblems and expressed “severe concerns about the likelihood ofpatients having exacerbations of Crohn’s disease or eveninflammatory 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 thoseassessments by defendants’ scientists were supportive of acausal link between Accutane and Crohn’s disease. Finally, Dr. Kornbluth relied on animal studies to supporthis theory of causation. He testified that defendants performedexperimental tests with Accutane on dogs and that those testsshowed a temporal relationship between the administration ofAccutane and gastrointestinal distress. Specifically, he noteda challenge/dechallenge relationship in that certain dogs givenAccutane experienced gastrointestinal problems that ceased aftercessation of Accutane administration. He also noted theindication of a dose toxicity curve, meaning that intestinaldamage appeared more severe in dogs given higher doses ofisotretinoin. However, he conceded that animal studies aremeant only to generate hypotheses about a substance’s effect onhumans, and that a hypothesis is a “supposition that is to befurther tested.” 2. Plaintiffs’ Expert -- Dr. Madigan Plaintiffs’ second expert, Dr. David Madigan, is aprofessor of statistics at Columbia University. Dr. Madigan didnot give a causation opinion. Only Dr. Kornbluth opined oncausation. Dr. Madigan’s testimony and expert report focused solely onwhether the epidemiological studies in question were 27 appropriately designed to discover an association betweenCrohn’s disease and Accutane, if such an association did in factexist. He concluded in his expert report that, after accountingfor the prodrome associated with Crohn’s disease, the availableepidemiological studies do not provide statistically reliableinformation regarding Accutane’s causal relation to Crohn’sdisease. His testimony was consistent with his report. Dr. Madigan explained that he was tasked with examining theavailable epidemiological studies as they pertained to anassociation between Accutane and Crohn’s disease. He analyzedsix of the epidemiological studies: Bernstein, Crockett,Alhusayen, Etminan, Racine, and Sivaraman. He did not analyzethe Rashtak and Fenerty studies because they addressed only IBDand 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 -- werestatistically significant. Dr. Madigan performed a “poweranalysis”20 of the four studies that were not statisticallysignificant. He explained that his purpose in doing so was to“shed some light” on whether the studies were reliable evidencethat there is truly no effect or whether the studies were simply20 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 aneffect exists. Dr. Madigan then examined each study’s statistical power todetect a fifty percent increased risk; he chose fifty percentbecause he considered it to be “an authentically importantincreased risk.” He calculated the power for each of the fourstudies as follows: Bernstein -- 37.8 percent; Crockett -- 18.2percent; Alhusayen -- 89.4 percent; Etminan -- 22.6 percent.Thus, for example, if there is a fifty percent increased risk ofdeveloping Crohn’s disease for Accutane users, the probabilitythat the Bernstein study would find a statistically significantresult is 37.8 percent. It was thus “less likely than not” thatmost of the studies would find an increased risk if such a riskdid in fact exist. Dr. Madigan concluded that this was “more anabsence of evidence than anything.” After accounting for themedian prodromal period, which he derived from the Pimentel andBarratt studies, he determined that the power for three of thefour studies had further decreased: Crockett diminished to 5.12percent; Alhusayen diminished to 36.2 percent; and Etminandiminished to 4.5 percent. According to Dr. Madigan, four of the six studies --Crockett, Alhusayen, Etminan, and Racine -- were totallyunusable because they failed to account for Crohn’s disease’sprodrome. He explained that by failing to account for the 29 prodrome, the studies were failing to observe cases of Crohn’sdisease that developed outside of the studies’ observationperiod. In other words, the studies’ failure to take account ofthe prodrome “biased [the studies] towards the null,” meaningthe studies were systematically biased in favor of not findingany effect. Dr. Madigan therefore concluded that those studieshad an overriding flaw and that he was reluctant to refer totheir results as “findings.” As for the remaining two studies, he explained thatquestionnaire-based studies such as Sivaraman are immune fromthe prodrome issue because they ask patients when their symptomsbegan and, thus, have “no limit going backwards in time.” Healso explained that there was a “diminished concern” for theBernstein study due to its lengthy observation period. However,Dr. Madigan found other flaws in the Bernstein study, and hedeclined to rely on its findings. He stated that the study didnot adjust for “unmeasured confounders” and it was performed inCanada rather than the United States, which created a problem asto “generalizability” due to differences in population and thelower dosage given to Canadian patients. Accordingly, for Dr. Madigan, the Sivaraman study remainedas the only study on which he was willing to rely, but withcaveats. He did not agree with its conclusion. He pointed tothe study’s unadjusted results as showing a statistically 30 significant increased risk of Crohn’s disease for people takingAccutane. Although he acknowledged that the study’s authorsfelt it necessary to adjust for antibiotic exposure, and thattheir adjusted results did not show a statistically significantincreased risk for Crohn’s disease, Dr. Madigan disputed thatthey actually performed an adjustment. He claimed that theyactually performed a “subgroup analysis.” He asserted that theadjusted figure from that analysis still showed an increasedrisk, even though it was no longer statistically significant dueto the smaller number of patients. Accordingly, he chose torely on the unadjusted results because a study based on a largergroup of people will provide a “better estimate.” He furtherexplained that he did not understand why the study authors choseto adjust for antibiotic exposure because the study authorsadmitted in the study’s abstract that “antibiotic exposure wasnot associated with Crohn’s disease.” In sum, Dr. Madigan found the Sivaraman study to be“evidence of a strong association between Accutane and Crohn’sdisease,” discounting all of the other studies on the basis thatthey “represented an absence of evidence” from which one cannotdraw any definitive conclusions. Dr. Madigan also took the position that a meta-analysis ofthe studies would be improper. He stated he did not perform ameta-analysis because most of the studies on which the meta- 31 analysis would be based did not account for prodrome, whichwould render the meta-analysis both misleading andscientifically unreasonable. That is so, he explained, becausea meta-analysis will inherit the flaws, biases, and structuralproblems of the studies upon which it is based. In addition, Dr. Madigan performed a disproportionalityanalysis using the FDA’s spontaneous reporting system database.He explained that a disproportionality analysis is a method ofstudying a spontaneous report database and reviewing theobserved rate for a particular drug and a particular adverseevent. The observed rate is compared with the rate at whichCrohn’s disease was reported for other drugs in the database.Analyzing the available data beginning in 1997, Dr. Madigan’sresults showed a “striking signal of disproportionality”indicative of a “strong association” between Accutane andCrohn’s disease. 3. Defendants’ Expert -- Dr. Oliva-Hemker Defendants’ expert Dr. Maria Oliva-Hemker is a Professor ofPediatric Inflammatory Bowel Disease and Chief of the Divisionof Pediatric Gastroenterology and Nutrition at Johns HopkinsUniversity School of Medicine. Her testimony focused ondisputing Dr. Kornbluth’s testimony and explaining whyepidemiological studies are preferred to case reports and animalstudies in the hierarchy of evidence. 32 During the Kemp hearing, she stated that the availablescientific evidence does not support any causal associationbetween Accutane and Crohn’s disease. Regarding Dr. Kornbluth’stestimony on biological mechanism, she explained that Crohn’sdisease is idiopathic, meaning that its cause is unknown, andthat any theory regarding a biological mechanism was thereforeunreliable. Moreover, she stated that scientists would notignore the available epidemiological evidence in favor of ahypothesis about a biological mechanism. She also addressed plaintiffs’ experts’ opinions concerningthe prodrome for Crohn’s disease. Although admitting that “thediagnosis time can vary” and that there are some patients whoare not diagnosed for several years, she stated that mostpatients are typically diagnosed within a year. She based thatconclusion on a number of population-based studies, all of whichconcluded that the median prodrome is under one year. She wasdismissive of plaintiffs’ experts’ use of the Pimentel study fordetermining the median prodrome for Crohn’s disease, explainingthat the study was very small and not representative of theaverage prodromal period, especially in light of the other,larger studies on the issue. She added that the authors of theepidemiological studies would have been aware of the availablepublished data on the median prodromal period and would haveaccounted for it in designing their studies. 33 She also discussed the recognized hierarchy of evidence andthat 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 studiesare currently the best available data on the issue of Accutaneand Crohn’s disease and that, from a medical-evidence point ofview, Dr. Kornbluth’s reliance on case reports and animalstudies, which are considered lower forms of evidence, wasinconsistent with recognized methodology. Concerning casereports, she testified that they are hypothesis-generating innature and are “in the bottom tier of medical evidence.” Sheexplained that case reports are subject to “publication bias,”meaning that only correlative events are reported and that thereports are subjective in nature, often contain incompleteinformation, and do not account for random chance. Further, shestated that such reports are difficult to interpret becauseCrohn’s disease is a “relapsing and a remitting condition,” andthus “the natural course of the disease may be mistaken for theresults of removing or reintroducing the medication.” She alsocited to an article by Reddy et al.21 for the proposition that21 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 ofcausality generated by a case report. Finally, Dr. Oliva-Hemker addressed Dr. Kornbluth’sinterpretation of defendants’ animal studies. She stated thatanimal studies may sometimes be important for “generatingcertain hypotheses,” but that they are typically consideredbelow human studies in the hierarchy of medical evidence. Shenoted that it is difficult to extrapolate data from animals tohumans because of differences in metabolism, absorption, andother factors. Moreover, she testified that she would not relyon dog studies in this instance because dogs cannot get IBD andbecause recent research has shown that dogs may havehypersensitive gastrointestinal tracts that can result indistress owing more to the dog’s anatomy than to the actualtoxicity of the substance under observation. In sum, hertestimony concluded that the animal studies are simply notsufficient generally for forming a conclusion about causationhere both because of the nature of the disease at issue andbecause they are merely “hypothesis-generating data.” In contrast to the case reports and animal studies, shetestified that the epidemiological studies are the bestavailable evidence on the issue of Accutane’s relation toCrohn’s disease. Moreover, she testified that it would beentirely proper to consider a meta-analysis of the studies when 35 such analysis is available. She explained that researchers nowhave access to the types of “hypothesis testing” epidemiologicalstudies that were sought for testing the viability of adverseevent case reports and that those studies have all reachedsimilar findings of no causal effect despite variations inpopulations, time, and data sets. 4. Defendants’ Expert -- Dr. Goodman Defendants’ second expert, Dr. Steven Goodman, is aProfessor of Medicine and Health Research and Policy andAssociate Dean for Clinical and Translational Research atStanford University, where he serves as Chief of the Division ofEpidemiology and co-director of Stanford’s Meta-ResearchInnovation Center. Dr. Goodman’s testimony focused on why theepidemiologic evidence is the best available evidence on thequestion of Accutane’s causal relation to Crohn’s disease andwhy a meta-analysis was a proper way of pooling those studyresults to reach a conclusion that Accutane does not causeCrohn’s disease. Dr. Goodman stated, during the Kemp hearing and in hisexpert report, that the epidemiological evidence pertaining tothe causal relationship between Accutane and Crohn’s disease isas strongly negative as epidemiologic evidence can be, and thatthere was no biological evidence, including a causal mechanismor otherwise, to contravene that evidence. He stated that the 36 methods Doctors Madigan and Kornbluth used were flawed becausethey put almost no weight on the epidemiologic evidence andinstead 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 ofepidemiological evidence all pointing towards no causalassociation between Accutane and Crohn’s disease and that theweighing of that body of evidence through use of meta-analysisalso strongly supported the lack of any association or causaleffect between Accutane and Crohn’s disease. Dr. Goodman discussed the hierarchy of medical evidence,stating that observational studies are second only to randomizedcontrolled trials in terms of establishing causality. Like Dr.Oliva-Hemker, he explained that epidemiologic studies are ahypothesis-testing form of evidence, which is a higher form ofevidence than hypothesis-generating data, such as case reportsand animal studies. Moreover, hypothesis-generating evidence istypically used more for developing ideas to later be examinedthrough epidemiological evidence. Accordingly, he wasdismissive of any reliance on case reports here, which he statedare almost never used as a basis for a scientific determinationof causality. As support for that proposition, Dr. Goodmancited 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 epidemiologicalstudies.” For similar reasons, Dr. Goodman was also dismissive of Dr.Kornbluth’s interpretation of animal studies, explaining thatsuch studies are hypothesis-generating in nature and that it isdifficult to extrapolate results from animal studies todetermine the effect a given substance will have on a humansubject. Moreover, he believed that the specific animal studiesdiscussed in this matter were essentially meaningless becausedogs do not develop IBD. He also took issue with Dr.Kornbluth’s invocation of the Hill criteria in assessing thecausal relationship between Accutane and Crohn’s disease becausethe studies here showed no strength of association, and so therewas no “association” in need of study. After reviewing all of the epidemiologic evidence, Dr.Goodman stated that none of the studies showed a statisticallysignificant increased risk of developing Crohn’s disease fromuse of Accutane. In addition to his belief that each studycontained reasonable results, he also noted the importance ofthe fact that all of the studies were concordant with each other-- that all of the studies produced consistent results pointingin the same direction was strong evidence that those results arereliable. 38 With regard to the Sivaraman study, he stated that thestudy should be interpreted according to its adjusted numbers,and that it was proper for the study authors to adjust forantibiotics. He explained that the adjusted number is alwaysbetter because it tends to be less biased and therefore morereliable. Moreover, he found the Sivaraman study to beinsignificant for purposes of his meta-analysis and in theoverall scheme of evidence because of its small size. He also explained the methodology of the meta-analysis heperformed, describing how smaller and more imprecise studies aregiven less weight whereas larger and more precise studies aregiven more weight. He further stated that a meta-analysis is away to increase precision by pooling studies that address thesame question. Moreover, meta-analysis is useful where there isa question about whether independent studies are large enough todetect an effect size. Accordingly, he criticized Dr. Madigan’srefusal to perform a meta-analysis of the studies despitearguing 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 aprotective effect, but with a statistically insignificantconfidence interval. For Crohn’s disease, the meta-analysis 39 again returned a relative risk indicative of a protectiveeffect, with a non-statistically significant confidenceinterval. Dr. Goodman interpreted those results as consistentwith “no effect.” Finally, Dr. Goodman turned his attention to the criticismslevied against the epidemiological studies -- specifically theprodrome issue on which plaintiffs’ experts chiefly relied indisregarding the studies. Dr. Goodman criticized plaintiffs’experts’ reliance on the Pimentel and Barratt studies fordetermining a median prodrome length of at least two-to-fouryears because of the studies’ small size and because thePimentel study’s population was taken from patients whogastroenterologists found difficult to manage and diagnose. Dr.Goodman felt that a study by Chouraki et al.,22 which contained7409 subjects with Crohn’s disease and found a median prodromeof under a year, was much more reliable. Moreover, he statedthat every population-based prodrome study -- which are thestudies he believed most reliable -- found a prodrome of ninemonths or less. He thus concluded that the best availableevidence on the issue consistently pointed towards a median22 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 theepidemiological studies’ use of a one-year observation period.Thus, in his opinion, none of the epidemiological studies wereinvalid due to a prodrome issue. D. After the Kemp hearing, the trial court issued an ordergranting defendants’ omnibus motion to bar plaintiffs’ expertsfrom testifying on, among other things, whether theepidemiological studies on which the defense relied were flawedand unreliable and whether Accutane can cause Crohn’s disease.The trial court also directed the parties to prepare an orderlisting the lawsuits affected by the ruling, and subsequentlyissued a May 8, 2015 order dismissing 2076 affected claims withprejudice. In its decision concerning the exclusion of plaintiffs’expert witnesses, the trial court examined the expert testimonyand scientific studies, laid out the relevant standard for theadmission of expert witness testimony, and determined thatplaintiffs’ experts’ testimony did not meet the applicablestandard. The trial court stated that Rubanick governed theadmissibility of expert witness testimony in toxic tort cases inNew Jersey. The court regarded the Rubanick standard, which itunderstood to be more flexible in assessing medical causation 41 expert testimony than the “general acceptance” test of Fryeotherwise traditionally used in New Jersey courts, as requiringan expert opinion to be based on a “sound, adequately-foundedscientific methodology involving data of the type reasonablyrelied on by experts in the scientific field.” (citingRubanick, 125 N.J. at 449). Thus, to fulfill its duty asgatekeeper, the trial court considered “whether other scientistsin the field [are] using similar methodologies in forming theiropinions.” The trial court applied that standard and found plaintiffs’experts’ testimony lacking.23 Focusing on the epidemiologicalstudies, the trial court concluded that “there is noepidemiological evidence to justify a reasonable inference thatthere is a causal link between isotretinoin and [Crohn’sdisease].” Nor did the court believe that there was anyrational basis for plaintiffs to resist the findings of all theepidemiological studies and to rely instead on case reports andanimal studies, which the trial court determined were seriouslyflawed and a less reliable form of evidence than theepidemiological 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 theirideas for evaluation in the scientific community, either throughpeer review submission or through the scrutiny of the process ofpublication in scientific literature. Specifically regardingDr. Kornbluth, the trial court stated that he “want[ed] to haveit both ways” by rejecting the best available evidence as flawedand 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 forcausation and the Pimentel and Barratt studies for medianprodrome, to the exclusion of all other studies, as an attemptto explain away the body of evidence on causation and on themedian 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 opinionwhile dismissing other, better forms of evidence that did notsupport their opinion. The trial court believed that such a“stratagem cannot bridge the analytical gaps inherent inPlaintiffs’ hypothesis.” Plaintiffs appealed and the Appellate Division reversed,holding that plaintiffs may present the experts’ testimony attrial. 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 applicablelegal standards, the panel concluded that “the experts relied onmethodologies and data of the type reasonably relied upon bycomparable experts.” Id. at 199. Comparing the testimony ofplaintiffs’ experts and defendants’ experts, the panel statedthat plaintiffs’ experts evaluated all of the evidence inaccordance with established scientific standards and methodologyand addressed the specific design flaws of the epidemiologicalstudies, all of which are recognized in the scientific communityas capable of producing unreliable results. Id. at 202. Thepanel explained that defendants’ experts merely “interpet[ed]the epidemiological studies differently,” and that a differenceof 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 therelevant data and information, applied appropriate methodologyin analyzing the epidemiological studies, and expressed validreasons for rejecting the conclusions of some of theepidemiological studies and in accepting other studies assupportive of their opinion.” Id. at 205. While noting thetrial court’s opportunity to view the witnesses firsthand, thepanel disagreed with the trial court’s characterization of 44 plaintiffs’ experts as “hired gun[s],” id. at 206, and expressedthe 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’sdecision to admit or exclude evidence is subject to an abuse ofdiscretion standard, a reviewing court owes “somewhat lessdeference to a trial court’s determination[s]” regarding experttestimony. Id. at 196-97. Accordingly, because our evidencerules weigh strongly in favor of admissibility, the panel“conclude[d] that the [trial] court mistakenly applied itsdiscretion 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 grantedamicus status. The New Jersey Business & Industry Association, Commerceand Industry Association of New Jersey, and New Jersey Chamberof Commerce (collectively “the Industry Associations”); KennethS. Broun, Daniel J. Capra, Joanne A. Epps, David L. Faigman,Laird Kirkpatrick, Michael M. Martin, Liesa Richter, and StephenA. Saltzburg (collectively “the Academics”); the AmericanMedical Association, Medical Society of New Jersey, AmericanAcademy of Dermatology, Society for Investigative Dermatology,American Acne and Rosacea Society, and Dermatological Society of 45 New Jersey (collectively “the Medical Associations”); thePharmaceutical Research and Manufacturers of America; the NewJersey Civil Justice Institute (NJCJI); and DRI - The Voice ofthe Defense Bar (DRI), filed briefs supportive of defendants. The New Jersey Association for Justice (NJAJ); theIronbound Community Corporation (ICC); and Allan Kanner, Esq.(Kanner), filed briefs supportive of plaintiffs. III. A. Defendants argue that the Appellate Division’s decisioneffectively nullifies the trial court’s role as the gatekeeperof expert witness testimony and will “allow[] any credentialedexpert to argue their way to a jury.” They contend that theappellate panel did not address the methodologicalinconsistencies inherent in plaintiffs’ experts’ reasoning andadopted a restrictive interpretation of the trial court’s roleas the “gatekeeper” of expert witness testimony that is at oddswith precedent from both New Jersey and courts around thecountry. Defendants assert that the acceptance of such“internally-inconsistent” and “outcome-driven” testimony robsthe expert witness standard of its vitality. They ask us to“bring clarity and consistency to New Jersey expertadmissibility standards, including by addressing whether Daubertstandards and precedent are relevant.” 46 The current lack of clarity, defendants posit, has resultedin “vastly different applications of gatekeeping,” asillustrated by the opposing viewpoints of the trial court andAppellate Division in this matter. Moreover, defendants arguethat, “[a]lthough the Court need not adopt the federal Daubertstandard to find that the Appellate Division erred, this caseillustrates the practical benefits of doing so.” Defendants addthat the extent to which New Jersey courts may look to Daubertfor guidance is currently unclear; they urge this Court toclarify that issue here. With respect to the proffered expert scientific testimony,defendants contend that the Appellate Division failed to applymethodological scrutiny, improperly applying a “relaxed”standard for admissibility despite the existence of “well-developed science.” By doing so, the Appellate Division allowedplaintiffs’ experts to employ a methodology whereby they arguedaway better and more reliable forms of evidence such asepidemiological studies to rely on lesser forms of evidence suchas case reports and animal studies. Thus, they contend that theAppellate Division ignored “key guidelines from this and othercourts for assessing the reliability of expert testimony.” Specifically, defendants argue that the Appellate Divisiondid not consider whether the experts used the data as it is usedby scientists in the field, a requirement mandated by Rubanick; 47 condoned the experts’ failure to adhere to the hierarchy ofevidence; and failed to look for any demonstration of scientificconsensus for the experts’ methods or views, such as peer-reviewed articles or treatises. And, they argue that theAppellate Division did not give appropriate deference to thetrial court’s exercise of discretion, but rather conductedessentially a de novo review. In sum, defendants argue that appellate error has resultedin the allowance of expert testimony that is contradictory,unreliable, and logically incoherent. Defendants emphasize thatnone of the epidemiological studies concluded that there was aconnection between Accutane and Crohn’s disease. DoctorsMadigan and Kornbluth were thus forced to use an inconsistentmethodology whereby they “concocted” a theory on Crohn’sdisease’s prodrome and selectively applied that theory toevidence that did not support their viewpoints. They did thesame for their theories on study power, applying it wherenecessary to refute the evidence, but then ignoring it for thestudies upon which they relied. Defendants argue that theexperts’ “contradictory methodology” should not be allowed to beadvanced before a jury. B. Plaintiffs argue that the Appellate Division appropriatelyemployed Rubanick’s relaxed admissibility standard in this 48 matter and properly assessed the reliability of plaintiffs’experts’ methodology. Plaintiffs cite to the Reference Manualfor the proposition that “epidemiology alone cannot provecausation,” and contend that defendants have falsely categorizedthe nature of the expert testimony due to their erroneous beliefthat the epidemiological studies alone should be considered tothe exclusion of all other evidence. According to plaintiffs,epidemiological studies “are not the be all and end all ofcausation evidence,” but rather “one component of multiple linesof evidence that inform the causation issue.” Thus, byconsidering all of the evidence in addition to the epidemiology,plaintiffs argue their experts employed a methodology based onsound scientific principles accepted in the scientificcommunity. They further argue that the Appellate Divisioncorrectly found that their experts did not ignore theepidemiology, but rather examined the data with properconsideration of the strengths and limitations of the design ofeach of the studies, together with study biases. Accordingly,the Appellate Division properly held that the trial courtexceeded its gatekeeping function in excluding the experttestimony. Furthermore, plaintiffs argue that the Reference Manualdoes not endorse a “strict application” of the hierarchy ofevidence. In fact, the Reference Manual does not suggest that 49 epidemiological studies are “beyond scientific criticism” orthat “no countervailing evidence should be considered.”Plaintiffs thus contend that their experts did not stray fromany “core scientific principles,” but simply considered all ofthe evidence in forming their opinions. Plaintiffs posit thattheir experts merely viewed the epidemiological studiesdifferently than defendants’ experts, and that doing so is notimproper because the “implications of a study are open todebate.” Plaintiffs also dispute the “key guidelines” identified bydefendants for examining expert testimony. Plaintiffs note thatthe law does not require that experts submit their opinions forpeer review in order to be admissible. Plaintiffs also takeissue with defendants’ arguments concerning scientificconsensus, arguing that consensus is not required in toxic tortcases and that, by arguing the issue, defendants are seeking totake New Jersey back to the “general acceptance” standard.Furthermore, plaintiffs contend that defendants’ argument forabandoning Rubanick’s relaxed standard is at odds with thisCourt’s interpretation of the trial court’s gatekeeping role andwould allow a trial court to usurp the role of the jury anddetermine for itself whether to accept an expert’s opinion. Plaintiffs also argue that the Appellate Division gaveappropriate deference to the trial court, explaining that “less 50 deference is owed to a trial court when the issue is theadmissibility of expert proofs.” They claim that the trialcourt failed to adhere to the principles expounded in Rubanick,which provided “well-founded support for the level of reviewthat the Appellate Division employed.” Thus, because the trialcourt substituted its judgment for that of the jury andimproperly weighed the evidence, the Appellate Division properlyreversed by applying a standard of review “long recognized bythis Court.” Finally, plaintiffs argue that there is no reasonto import the Daubert standard into New Jersey law and note thatthis Court has previously declined to adopt the Daubert factors. C. Amici curiae Industry Associations, the Academics, and DRIargue that New Jersey’s expert witness standard is in need ofclarification and urge this Court to join the majority of otherstates by adopting the Daubert standard to ensure meaningfuljudicial gatekeeping and that only reliable and reliably appliedexpert testimony enters New Jersey’s courts. Similarly, amicicuriae NJCJI and the Medical Associations argue that theAppellate Division reached an incorrect decision even underexisting New Jersey law, but maintain that adoption of theDaubert standard will provide helpful guidance and ensuremeaningful and robust gatekeeping in New Jersey trial courts. 51 Specifically, the Industry Associations and the Academicsmaintain that although Daubert and the current standard aresomewhat similar, Daubert provides “concrete guidelines” and amore fulsome analysis that ensures that the expert’s methodologyis reliable and applied in a way that “fits” the facts of acase. Both contend that plaintiffs’ experts’ testimony wouldnot have withstood that more thorough analysis. Moreover, bothargue that tying New Jersey closer to the Daubert standard woulddiscourage forum shopping. Finally, the Academics assert thatthe Appellate Division should have applied a pure abuse ofdiscretion standard in reviewing the trial court’s ruling. The Medical Associations argue that the Appellate Divisionincorrectly applied New Jersey’s expert witness standard byignoring the hierarchy of evidence and the unanimity ofepidemiological evidence in favor of plaintiffs’ experts’ “un-vetted postulations.” They point to a scientific consensus inthe medical literature that Accutane does not cause Crohn’sdisease, and argue that plaintiffs’ experts were forced toinvert the hierarchy of scientific evidence to overcome thescientific consensus on the issue by relying on inferior formsof evidence such as case reports and animal studies. NJCJI similarly argues that the Appellate Divisionpermitted plaintiffs’ experts to present their unsubstantiated“outlier viewpoint” without any meaningful judicial scrutiny or 52 investigation of their methodology. NJCJI claims that theAppellate Division’s decision improperly left the question ofmethodological soundness to the jury while limiting the trialcourt’s gatekeeping function “to exclude only the most extremeand obvious forms of junk science.” NJCJI and DRI emphasize that robust gatekeeping isnecessary because juries struggle to absorb complex scientificconcepts and are poorly equipped to assess methodologicalsoundness. Both amici express the concern that juries may bemisled by highly-qualified experts who offer opinions that arenot supported by the wider scientific community and that juriesfaced with complex scientific evidence may simply “fall back” onan expert’s credentials as a basis for evaluating the testimonyat issue. To guard against that risk, DRI argues that expertsshould be required to prove not only that their methodology issound, but that such methodology is reliably applied to thefacts of the case. Finally, amicus curiae Pharmaceutical Research andManufacturers of America submitted a brief detailing thescientific principles at issue here and arguing that the trialcourt correctly excluded plaintiffs’ experts’ testimony. D. Amici curiae NJAJ, ICC, and Kanner argue that this Courtshould not adopt the Daubert standard because the current New 53 Jersey standard is well-settled and strikes an appropriatebalance between proper judicial gatekeeping and the admission ofnovel scientific concepts. NJAJ claims that the Daubertstandard is a “patchwork” of case law that has been appliedinconsistently by both state and federal courts. NJAJ andKanner further contend that the Daubert standard requires judgeswho are unfamiliar with scientific principles to make scientificjudgments outside of their area of expertise. NJAJ and ICCargue that Daubert imposes undue and unnecessary burdens oncourts and litigants by encouraging frivolous challenges toexpert witness testimony. Both ICC and Kanner claim thatadoption of the Daubert standard will lead to unjust resultsbecause 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 witnessstandard does not require any clarification or correction andthat state trial courts have reliably applied it for manydecades. NJAJ contends that defendants have provided nosubstantive reason why this Court should abandon the expertwitness standards that it pioneered and “which continue tofairly promote just results.” Furthermore, NJAJ disputes thatNew Jersey’s current expert witness standard promotes the filingof cases in New Jersey by out-of-state plaintiffs, arguing thatthere is no evidence to support such an assertion. Finally, 54 NJAJ, ICC, and Kanner maintain that the Appellate Division hereapplied the proper standard and properly found that the trialcourt exceeded its gatekeeping role by excluding plaintiffs’experts based on nothing more than personal disagreements as totheir conclusions. IV. A. Our Court was in the vanguard of courts to be persuadedthat adherence to the Frye general acceptance standard as thesole test for assessing reliability of scientific experttestimony was unsatisfactorily constricting for fairly assessingreliability in certain areas of novel or emerging fields ofscience.24 Rubanick marked the broadening of our standard, when thisCourt concluded that resort to a methodology-based standardwould be appropriate for assessing reliability with respect toemerging scientific theory on causation in toxic tortlitigation. 125 N.J. at 454. Justice Handler, writing for theCourt, 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 othersin the field use similar methodologies. 'What is necessary isthat the expert arrived at his causation theory by relying uponmethods that other experts in his field would reasonably relyupon in forming their own, possibly different opinions, aboutwhat caused the patient’s disease.’” Id. at 449-50 (quotingOsburn v. Anchor Labs., Inc., 825 F.2d 908, 915 (5th Cir.1987)). 56 In remanding to the trial court for re-evaluation ofdisallowed expert testimony, the Rubanick Court explained thatthe proper inquiry is not whether the expert thought hisreliance on the underlying data from thirteen studies regardingexposure to a potential carcinogen was reasonable or whether thetrial court thought that reliance was reasonable; rather, theproper 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 forthe Court, applied the same approach and again remanded for ahearing on the disputed epidemiologic testimony about asbestosand colon cancer. 127 N.J. at 418-23. The Court stated that,for its purposes, it did not need to “describe in detail how tostructure an epidemiological study, analyze the data, drawconclusions about the study population, and, if possible,extrapolate from statistical results inferences about specificindividual subjects[, i.e., determine specific causation].” Id.at 417. But, Justice Pollock elaborated on the Court’sdirection to trial courts when assessing the reliability of amethodology used by an expert proffering scientific evidence:“epidemiologists, like experts generally, must be able toidentify the factual bases for their conclusions, explain their 57 methodology, and demonstrate that both the factual bases and themethodology are scientifically reliable.” Ibid. When relyingon such studies, the trial court should review them and “thendetermine whether the expert’s opinion is derived from a soundand well-founded methodology that is supported by some expertconsensus in the appropriate field.” Ibid. (citing Rubanick,125 N.J. at 449-50). Moreover, Landrigan provided suggested tools for trialcourts to use in rendering gatekeeping determinations about thereliability of an expert’s methodology when the ultimatescientific opinion is not itself generally accepted. Landriganexplains that “[d]efined landmarks guide a trial court in makingthis determination. Support may be demonstrated by reference toprofessional journals, texts, conferences, symposia, or judicialopinions accepting the methodology.” Ibid. (citing Kelly, 97 N.J. at 210-11). Additionally, the Court allowed forconsideration of professional associations’ acknowledgedacceptance and recognition of a methodology’s use. Ibid. Thus,methodology may be assessed for soundness using some of the sametools as general acceptance identifies for outcome. B. Not long after those dual holdings by our Court, theSupreme Court issued its seminal Daubert opinion in 1993pronouncing that Frye had been superseded by the adoption of the 58 Federal Rules of Evidence. 509 U.S. at 585-87. The DaubertCourt explained that the Federal Rules of Evidence do not makeany mention of a general acceptance standard and that such astandard was at odds with the “liberal thrust of the FederalRules and their general approach of relaxing the traditionalbarriers to opinion testimony.” Id. at 588 (internal quotationsomitted). Thus, although Federal Rule of Evidence 702“contemplates some degree of regulation of the subjects andtheories about which an expert may testify,” the subject of thescientific testimony does not have to be known to a certainty solong as it is derived from the scientific method and “supportedby appropriate validation.” Id. at 589-90. Moreover, inaddition to a methodology derived from the scientific method,the Court added that the testimony must be relevant to the factsat hand -- it must “assist the trier of fact to understand theevidence or to determine a fact in issue.” Id. at 591 (quotingFed. R. Evid. 702). Tying the principles together, the Court fashioned a newstandard: 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 FederalRules regarding expert testimony are “premised on an assumptionthat the expert’s opinion will have a reliable basis in theknowledge and experience of his discipline.” Id. at 592. TheCourt noted that “[m]any factors will bear on the inquiry,” andthen proceeded to offer some observations on factors it believedmost relevant in such evaluations. Id. at 593. Those becameknown as the Daubert factors. First, trial courts may look to whether the scientifictheory at issue can be, or has been, tested. Ibid. Second, acourt may also consider whether the scientific theory has beenpublished or subjected to some form of peer review. Ibid. Thatsaid, the Court did not consider publication as “a sine qua nonof admissibility,” but rather one form of peer review. Ibid.The Court reasoned that “submission to the scrutiny of thescientific community is a component of 'good science,’ in partbecause it increases the likelihood that substantive flaws inmethodology will be detected.” Ibid. As a third factor, courtsmay also consider any “known or potential rate of error,” andany “standards controlling the technique’s operation,” id. at594, which may be important in pattern testing and similar areas 60 of science. Finally, the Daubert Court stated that generalacceptance remains a consideration; accordingly, a techniquethat has garnered only minimal support within the scientificcommunity “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 theprinciples that underlie a proposed submission,” id. at 594-95.As this Court did in Rubanick and Landrigan, the Supreme Courtunderscored in Daubert that the trial court must focus on theexpert’s principles and methodology -- not on the conclusionsthey generate. Id. at 595. The trial court’s task is thus toensure “that an expert’s testimony both rests on a reliablefoundation and is relevant to the task at hand” by assuring thatthe evidence is based on valid scientific principles. Id. at597.25 Although acknowledging that its decision was controversial,the Court asserted that it had struck a proper balance, statingthat the adversarial process would provide proper safeguards inplace 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 forthe quick and decisive resolution of legal disputes. Id. at596-97. The Supreme Court elaborated on its Daubert standard forassessing reliability with two cases which, combined, round outthe Daubert trilogy. In General Electric Co. v. Joiner, the Court held that anabuse of discretion standard applies when reviewing a trialcourt’s decision to admit or exclude expert testimony, evenwhere that determination may be outcome determinative. 522 U.S. 136 , 138-39 (1997). The Court also reinforced that trial courtsare the “gatekeeper” tasked with screening such testimony. Id.at 142. The Court stated that, in its gatekeeper role, a trialcourt is free to exclude expert testimony where the expert’sconclusions are not sufficiently tethered to the facts or drawnfrom the applicable data. Id. at 146-47. A trial court maydetermine in a given case that “there is simply too great ananalytical gap between the data and the opinion proffered” forthe expert testimony to be considered reliable. Id. at 146(explaining that expert’s conclusions and methodology “are notentirely distinct from one another” and that “nothing in eitherDaubert or the Federal Rules of Evidence requires a districtcourt to admit opinion evidence that is connected to existingdata only by the ipse dixit of the expert”). 62 In Kumho Tire Co. v. Carmichael, the Court extended theDaubert approach to technical and other specialized knowledgeadmissible as expert testimony under Federal Rule of Evidence702. 526 U.S. 137 , 147-48 (1999). Justice Breyer summarizedDaubert as holding “that Federal Rule of Evidence 702 imposes aspecial obligation upon a trial judge to 'ensure that any andall scientific testimony . . . is not only relevant, butreliable.’” Id. at 147 (ellipsis in original) (quoting Daubert,509 U.S. at 589). The Kumho Court reasoned that Rule 702 -- andthus Daubert’s methods for assessing reliability -- had to applyto all forms of expert testimony because the evidence rules“grant expert witnesses testimonial latitude unavailable toother witnesses on the 'assumption that the expert’s opinionwill have a reliable basis in the knowledge and experience ofhis discipline.’” Id. at 148 (quoting Daubert, 509 U.S. at 592). Importantly, the Court in Kumho emphasized again that theDaubert standard is flexible, explaining that (1) the Daubertfactors do not necessarily apply “to all experts or in everycase,” id. at 141; (2) that “the law grants a district court thesame broad latitude when it decides how to determine reliabilityas it enjoys in respect to its ultimate reliabilitydetermination,” id. at 142; (3) that the Daubert factors are nota “definitive checklist or test,” id. at 150 (quoting Daubert, 63509 U.S. at 593); and (4) that the gatekeeping inquiry must be“'tied to the facts’ of a particular 'case,’” ibid. (quotingDaubert, 509 U.S. at 591). Thus, a trial court “can neitherrule out, nor rule in, for all cases and for all time theapplicability of the factors mentioned in Daubert . . . . Toomuch depends upon the particular circumstances of the particularcase at issue.” Ibid. Ultimately, Kumho underscores that the objective ofDaubert’s gatekeeping requirement “is to make certain that anexpert, whether basing testimony upon professional studies orpersonal experience, employs in the courtroom the same level ofintellectual rigor that characterizes the practice of an expertin the relevant field.” Id. at 152. Accordingly, “the trialjudge must have considerable leeway in deciding in a particularcase how to go about determining whether particular experttestimony is reliable.” Ibid. Federal Rule of Evidence 702 was amended in 2000 to reflectthe Supreme Court’s trilogy of cases outlining the Daubertstandard. 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 ascurrently 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 Daubertstandard, 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) (enbanc) (adopting Daubert and noting that standard is “widelyused”). C. In 2002, after the Daubert trilogy, we revisited the topicof the trial court’s gatekeeping role under our current N.J.R.E.702.2626 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 ofRubanick beyond toxic tort cases. Kemp holds that the Rubanickstandard for assessing the reliability of proffered experttestimony on scientific evidence should apply whenever “amedical cause-effect relationship has not been confirmed by thescientific community but compelling evidence neverthelesssuggests that such a relationship exists.” Id. at 430. The Kemp decision further holds that a trial court has anindependent obligation to ensure that plaintiffs have sufficientprocess for defending their evidentiary submissions. The Courtexplained that, by requiring a pretrial Rule 104 evidentiaryhearing, the trial court would be able to properly “assesswhether the expert’s opinion is based on scientifically soundreasoning or unsubstantiated personal beliefs couched inscientific terminology.” Id. at 427 (citing Landrigan, 127 N.J.at 414). We note, in concluding this section, that the Kemp Courtobserved in 2002 that New Jersey had not amended N.J.R.E. 702 toinclude “the three-factor test for the admissibility of experttestimony that is part of the Federal rule as amended inresponse to Daubert.” Id. at 424 n.3. The Court added that itsdecision was not intended “to incorporate the Daubert factorsinto N.J.R.E. 702.” Ibid. Although the question of whether toincorporate the Daubert factors into N.J.R.E. 702’s standard for 66 admissibility, or to otherwise revise N.J.R.E. 702 toincorporate evolving state case law on the reliability part ofour standard, has arisen from time to time in the Court’sinteractions with the Supreme Court Committee on the Rules ofEvidence, no action on such topics has been taken. V. We intend by this case to clarify and reinforce the properrole for the trial court as the gatekeeper of expert witnesstestimony. Defendants and several amici have good reason to askfor clarification of the judicial gatekeeping role to beperformed in New Jersey courtrooms. When this Court modified the general acceptance standard toadopt a more relaxed approach for causation expert testimony intoxic tort litigation, and later for all medical cause-effectexpert testimony, it envisioned the trial court’s function asthat of a gatekeeper -- deciding what is reliable enough to beadmitted and what is to be excluded. Those are not credibilitydeterminations that are the province of the jury, but ratherlegal determinations about the reliability of the expert’smethodology. We now reinforce the rigor expected of the trialcourt 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-seekingfunction of our system of justice, while still allowing for new 67 or developing opinions on medical causation that may not yethave gained general acceptance. See Rubanick, 125 N.J. at 436-38 (discussing commentators’ and courts’ acknowledgement ofareas in medical causation where scientific method cannotaccommodate general acceptance standard). Resolved not tostifle innovation in the tort system in such areas, this Courtcrafted its own broadened approach to the demonstration ofreliability for an expert’s testimony. The trial court is thespigot that allows novel expert testimony in areas of evolvingmedical causation science, provided the proponent of the expertcan demonstrate that the expert adheres to scientific norms indistinct ways that we have identified. In Rubanick, we said that the court must ensure compliancewith the requirement of “some expert consensus that themethodology and the underlying data are generally followed byexperts in the field.” Id. at 450. In Landrigan, we chargedthe trial court with the obligation to “distinguishscientifically sound reasoning from that of the self-validatingexpert.” 127 N.J. at 414. And, in Kemp, we reinforced theprohibition against allowing in “unsubstantiated personalbeliefs.” See 174 N.J. at 427. The gatekeeping role requires care. The process of makingsuch 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 theoryin medical cause-and-effect cases. See id. at 451-53(distinguishing between methodology and credibilityassessments). Properly exercised, the gatekeeping functionprevents the jury’s exposure to unsound science through thecompelling voice of an expert. See State v. Cavallo, 88 N.J. 508, 518 (1982) (“The danger of prejudice through introductionof unreliable expert evidence is clear. While juries would notalways accord excessive weight to unreliable expert testimony,there is substantial danger that they would do so, preciselybecause the evidence is labeled 'scientific’ and 'expert.’”).As explained in Landrigan, “the key to admission of the opinionis the validity of the expert’s reasoning and methodology.” 127 N.J. at 414. Difficult as it may be, the gatekeeping role must berigorous. In resolving issues of reliability of an expert’smethodology in a new and evolving area of medical causation, wecautioned that “the trial court should not substitute itsjudgment for that of the relevant scientific community. Thecourt’s function is to distinguish scientifically soundreasoning from that of the self-validating expert, who usesscientific terminology to present unsubstantiated personalbeliefs.” Ibid. We have repeatedly stressed that thegatekeeper’s “critical determination is whether comparable 69 experts accept the soundness of the methodology, including thereasonableness of relying on [the] type of underlying data andinformation.” Rubanick, 125 N.J. at 451; see Landrigan, 127 N.J. at 417. That said, we can and should have more clear direction tocourts on how the gatekeeping function is properly performed.Recognizing proper gatekeeping when it is performed provides adiscernible pathway for other courts to follow. We endeavor todo that with this matter. We add further clarification andassistance to trial courts, concerning performance of thegatekeeping role, when reviewing scientific expert testimonyinvolving medical causation issues in civil matters, later inthis opinion through our adoption of the Daubert factors forpermissible use in such matters. See, infra, Section VII, ___(slip op. at 79-85). VI. In turning back to the matter before us to consider thetrial court’s exclusion of plaintiffs’ experts’ testimony, webegin by addressing the appropriate standard of review. A. A reviewing court must apply an abuse of discretionstandard to a trial court’s determination, after a full Rule 104hearing, 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 ofreview. The Appellate Division stated that, although a trialcourt’s decision to admit or exclude evidence is subject to anabuse of discretion standard, a reviewing court owes “somewhatless deference to a trial court’s determination” regardingexpert testimony. In re Accutane, 451 N.J. Super. at 197.However, as support for that proposition, the panel relied onState v. Torres, which was a criminal case that applied the Fryestandard in determining the admissibility of expert witnesstestimony. 183 N.J. 554, 568 (2005) (stating that “the field ofinquiry must be generally accepted such that an expert’stestimony would be sufficiently reliable” for expert testimonyto be admissible); see also State v. J.R., 227 N.J. 393, 410(2017) (relying on Torres for proposition that appellate courtneed not be as deferential on admissibility of expert scientificevidence). That proposition has, to date, carried weight in thecontext of a court applying the general acceptance test in acriminal matter, see State v. Harvey, 151 N.J. 117, 167-70(1997), but it is not appropriate in the context of a civil masstort case, where the trial court has been entrusted withmethodology-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 applya pure abuse of discretion standard in civil matters concerningexpert 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 experttestimony, reviewing it against an abuse of discretionstandard.’” (alteration in original) (quoting Pomerantz PaperCorp. v. New Cmty. Corp., 207 N.J. 344, 371-72 (2011))). We reaffirm that the abuse of discretion standard appliesin the appellate review of a trial court’s determination toadmit or deny scientific expert testimony on the basis ofunreliability in civil matters. We now apply that standard tothe determination of the trial court in this matter. B. An expert must demonstrate the validity of his or herreasoning. Landrigan, 127 N.J. at 414. Defendants argued, andpresented experts who supported the argument, that plaintiffs’experts failed to meet our expert witness standard because theyapplied a contradictory and selective form of reasoning in whichthey used certain arguments to discredit the epidemiologicalevidence, only to abandon those arguments when relying on weakerevidence. The trial court essentially agreed with thatassessment in conducting a properly performed robust analysis ofthe methodology advanced by plaintiffs’ experts. 72 The trial court concluded that Dr. Kornbluth failed topersuade it of the soundness of his reasoning in support of hiscausation opinion. As his is the only causation opinionproffered, we focus on the court’s rejection of Dr. Kornbluth’smethodology used to support his opinion, particularly thecourt’s reasoning and the bases on which the testimony wasdeclared to be unsound. Although Dr. Kornbluth offered the onlyopinion on causation of plaintiffs’ two experts, both expertsoffered interlocking expert testimony, and so our analysis ofboth is intertwined. The following assessments were made by thetrial 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 methodologywhereby they disregarded eight of nine epidemiological studiesand relied on case reports and animal studies to support theiropinion. It is clear that case reports are “at the bottom ofthe evidence hierarchy,” Reference Manual at 724, and othercourts 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 itsdiscretion by “discounting [expert’s] reliance on case reportsin the face of the overwhelming contrary epidemiologicalevidence 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 ofstatistically significant epidemiological studies, thatgenerally “[c]ase reports are not reliable scientific evidenceof causation, because they simply describe[] reported phenomenawithout comparison to the rate at which the phenomena occur inthe general population or in a defined control group; do notisolate and exclude potentially alternative causes; and do notinvestigate or explain the mechanism of causation.” (secondalteration in original) (quoting Casey v. Ohio Med. Prods., 877 F. Supp. 1380 , 1385 (N.D. Cal. 1995))). And while animalstudies may be helpful in “framing hypotheses,” the ReferenceManual intimates that such evidence is far less probative in theface of a “substantial body of epidemiologic evidence.” Id. at563, 564-65, 564 n.48. Such was the case here; initial animalstudies may have suggested a possible causal connection betweenAccutane and Crohn’s disease, but since that time a uniform bodyof epidemiological evidence has dispelled any such theory. SeeSiharath, 131 F. Supp. 2d at 1366-68 (explaining why courtviewed animal studies with suspicion in absence of confirmatoryepidemiological studies and adding generally that extrapolationto humans is “not considered reliable in the absence of acredible scientific explanation of why such extrapolation iswarranted”). Thus, we do not mean to suggest that animalstudies and case reports can never be relied upon for forming an 74 opinion on causation, but we find ample support for the trialcourt’s determination that it was not proper to do so here inlight of the uniform body of epidemiological evidence. As for the one study on which they did rely -- Sivaraman --plaintiffs’ experts disagreed with the authors’ ultimateconclusions and instead focused on unadjusted results. In sodoing, plaintiffs’ experts dismissed published studies examiningthousands of subjects as underpowered and biased in favor ofrelying on portions of a single unpublished study that examined509 total subjects.27 In explaining their reasoning for disregarding the resultsof so many epidemiological studies that consistently failed toshow an association between Accutane and Crohn’s disease,plaintiffs’ experts asserted that the prodrome for Crohn’sdisease is two years or more. They based that assessment on twosmaller studies, Pimentel and Barratt, even though there wereother larger studies, such as Chouraki, which had found a muchshorter median prodromal period -- a median of approximatelyless than one year. Thus, despite their expressed concernsregarding study power -- which is based in part on the size of27 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 whenrelying on the Pimentel and Barratt studies to form theiropinion as to the median prodromal period. Moreover, as thetrial court observed, plaintiffs’ experts could have performed ameta-analysis to account for the power issue but refused. The many contradictions in the experts’ methodology werenot lost on the trial court, which concluded that experts in thescientific community would not accept as consistent withscientific norms a methodology such as that used by plaintiffs’experts. In particular, the court found the methodology unsoundbecause it relied on Sivaraman and Pimentel to the exclusion ofother evidence. The trustworthiness of plaintiffs’ experts’methodology was further undermined by internal inconsistencies,including the experts’ refusal to examine the Rashtak andFenerty studies on the ground that those studies did not reportspecific data for Crohn’s disease while Dr. Kornbluth tetheredhis own causation opinion to case reports not specific toCrohn’s disease and to studies performed on animals incapable ofhaving any form of irritable bowel disease. The trial court reasoned that the overall approach taken byDr. Kornbluth -- rejecting the evidence from the epidemiologicalstudies, which all found no causal association, and profferinghis own alternative opinion that a causal association was 76 present based on lesser forms of evidence -- was based on anunsound methodology. That conclusion comports with thedecisions of many other courts that experts cannot selectivelychoose lower forms of evidence in the face of a large body ofuniform epidemiological evidence. See, e.g., In re Lipitor, ___F.3d ___ (4th Cir. 2018) (slip op. at 16) (“Result-drivenanalysis, or cherry-picking, undermines principles of thescientific method and is a quintessential example of applyingmethodologies (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 didnot abuse its discretion in excluding expert testimony whereexpert 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 therecognized hierarchy of evidence in the Reference Manual andaccepted generally in the scientific community. Indeed, evenplaintiffs’ experts acknowledged the scientific community’sacceptance of a hierarchy of evidence, but they deviated fromit. Moreover, as the court noted and found to be compelling,Dr. Kornbluth never submitted his ideas concerning biologicalmechanism or Accutane’s relation to Crohn’s disease for peerreview or publication. In fact, he previously expressedconcern, in an e-mail to a colleague admitted into the record in 77 this matter, about any connection between Accutane and Crohn’sdisease after the Bernstein study, the first of theepidemiological studies, was published in 2009. Finally, it bears noting that Dr. Kornbluth organized histestimony to support his personal view that a causal associationexisted between Accutane and Crohn’s disease through use of theHill guidelines. However, those guidelines are invoked onlyafter an association between an agent and a particular diseasehas been determined to be present; their pointed purpose is todetermine whether a detected association reflects truecausality, it is not to create an association that has notalready been detected through appropriate studies. SeeReference Manual at 598-99 (explaining that Hill “guidelines areemployed only after a study finds an association to determinewhether that association reflects a true causal relationship”).Here, not one of the epidemiological studies found anystatistically significant association between Accutane andCrohn’s disease. In sum, the trial court explained its reasons forconcluding that plaintiffs’ experts deviated from corescientific principles and strayed from their own claimedmethodology in order to reach their conclusions. That the trialcourt deemed their testimony to be unreliable and excluded itfrom being presented is unsurprising. Ample evidence in the 78 record supports that conclusion. Applying the abuse ofdiscretion standard and the principles of Rubanick, Landrigan,and Kemp, we conclude that the trial court’s determination isunassailable. The Appellate Division judgment, reversing thetrial court’s exclusion of the expert testimony, is reversed. VII. The divergent outcomes reached by the Appellate Divisionand the trial court in this matter provoked the debate among theparties and amici over whether our case law on the gatekeepingfunction is in need of clarification. Further, we are asked toconsider adopting the Daubert standard, or to at leastincorporate use of its factors, as a means to bring greaterconsistency to the gatekeeping function. First, in respect of the gatekeeping role, we emphasizethat we expect the trial court to assess both the methodologyused by the expert to arrive at an opinion and the underlyingdata used in the formation of the opinion. That will ensurethat the expert is adhering to norms accepted by fellow membersof the pertinent scientific community. Methodology, in all itsparts, 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 scientificcommunity’s acceptance of the substance of the opinion to itsacceptance of the methodology and reasoning underlying it.”). 79 It is not for a trial court to bless new “inspired” sciencetheory; the goal is to permit the jury to hear reliable scienceto support the expert opinion. Cf. Rosen v. Ciba-Geigy Corp.,78 F.3d 316, 319 (7th Cir. 1996) (“[T]he courtroom is not theplace for scientific guesswork, even of the inspired sort.”).In this basic goal, there is not much light between our standardand that which has developed in the federal sphere underDaubert’s initial instruction. Our law moved first, but in thesame direction and with the same general goal as that noted bythe Supreme Court in its Daubert trilogy. Both lines of initialdecisions recognized the drawback of limiting expert testimonyexclusively through the filter of general acceptance. For thisCourt, 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 arealigned in their general approach to a methodology-based testfor reliability. Both ask whether an expert’s reasoning ormethodology underlying the testimony is scientifically valid.Daubert, 509 U.S. at 594-95 (explaining that inquiry into expertwitness testimony requires examination of “scientific validity”of “the principles that underlie a proposed submission” and thatcourt’s focus “must be solely on principles and methodology”);Rubanick, 125 N.J. at 449 (holding that scientific theory ofcausation may be found sufficiently reliable where “it is based 80 on a sound, adequately-founded methodology”). Moreover, bothstandards look to whether that reasoning or methodology properlycan 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 experttestimony must be sufficiently tied to facts of case in order toaid 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 demonstratedprofessional capability to assess the scientific significance ofthe underlying data and information, to apply the scientificmethodology, and to explain the bases for the opinion reached.”(emphasis added)). Importantly, Daubert identified a non-exhaustive list offactors for courts to consider using, if helpful, when itexpanded on its test for assessing the reliability of scientificexpert testimony. See 509 U.S. at 593-95. Distilled, thegeneral factors identified as perhaps pertinent forconsideration, 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”; 81 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 scientificcommunity -- continues to have a bearing because, minimally, itpermits the identification of a relevant scientific communityand facilitates an express determination of a particular degreeof acceptance within that community, or contrarily permits atechnique with minimal support to be viewed with skepticism.See id. at 594. We are persuaded that the factors identified originally inDaubert should be incorporated for use by our courts. Thefactors dovetail with the overall goals of our evidentialstandard and would provide a helpful -- but not necessary ordefinitive -- guide for our courts to consider when performingtheir gatekeeper role concerning the admission of experttestimony. Several are aimed at achieving the same examinationfor peer acceptance of a methodology (but not the outcomereached from that methodology) described in our earlieropinions. See Landrigan, 127 N.J. at 417; Rubanick, 125 N.J. at 449-50. 82 In adopting use of the Daubert factors, we stop short ofdeclaring ourselves a “Daubert jurisdiction.” Like severalother states, we find the factors useful, but hesitate toembrace the full body of Daubert case law as applied by stateand federal courts. See, e.g., People v. Shreck, 22 P.3d 68, 70(Colo. 2001) (en banc) (abandoning Frye test and holding thattrial court “may consider” Daubert factors); McDaniel v. CSXTransp., 955 S.W.2d 257, 265 (Tenn. 1997) (finding factorsuseful in determining reliability but not expressly adoptingDaubert). First, we have already broadened our approach to testingfor the reliability of expert testimony for certain areas incivil law, see Kemp, 174 N.J. at 430; but, to date, we retainthe general acceptance test for reliability in criminal matters,see Harvey, 151 N.J. at 167-70. Second, there is no monolithicbody of case law uniformly or even consistently applyingDaubert, as others have noted. See, e.g., Motorola, 147 A.3d at757. We hesitate to sweep in adherence to the variousapproaches taken among the circuits and state jurisdictions whenapplying the Daubert factors. Thus, we do not adopt a“standard” that we cannot fully discern in its application atthis time. While the factors are helpful, and while individualcases may be persuasive in appropriate settings, we cannotignore that there are discordant views about the gatekeeping 83 role among Daubert jurisdictions. See ibid.; see generallyDavid E. Bernstein & Eric G. Lasker, Defending Daubert: It’sTime to Amend Federal Rule of Evidence 702, 57 Wm. & Mary L.Rev. 1, 26-36 (2015). Our view of proper gatekeeping in a methodology-basedapproach to reliability for expert scientific testimony requiresthe proponent to demonstrate that the expert applies his or herscientifically recognized methodology in the way that others inthe field practice the methodology. When a proponent does notdemonstrate the soundness of a methodology, both in terms of itsapproach to reasoning and to its use of data, from theperspective of others within the relevant scientific community,the gatekeeper should exclude the proposed expert testimony onthe 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 bewary that expert has not faithfully applied methodology whereexpert’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 expertswho selectively choose from scientific landscape); Freeman, 911 N.W 2d at 596-98. Importantly, that approach -- namely, to determine whetherthe scientific community would accept the methodology employed 84 by plaintiffs’ experts and would use the underlying facts anddata as did plaintiffs’ experts -- was employed by the trialcourt here. We approve of the court’s methodological analysis.There was no encroachment on the factfinding function here. Thetrial court did the type of rigorous gatekeeping that isnecessary when faced with a novel theory of causation,particularly one, as here, that flies in the face of consistentfindings of no causal association as determined by higher levelsof scientific proof. For all the reasons expressed herein, we conclude that thetrial court’s exclusion of plaintiffs’ experts’ testimony waswell-supported and well-reasoned. There was no abuse ofdiscretion by the trial court in its evidential ruling. VIII. We reverse the judgment of the Appellate Division, whichhad 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. 85