NOT FOR PUBLICATION WITHOUT THE APPROVAL

OF THE APPELLATE DIVISION

SUPERIOR COURT OF NEW JERSEY

APPELLATE DIVISION

DOCKET NO. A-4698-14T1

 A-0910-16T1

IN RE: ACCUTANE LITIGATION

Argued March 7, 2017 – Decided July 28, 2017

Before Judges Reisner, Koblitz and Sumners.

On appeal from the Superior Court of New 

Jersey, Law Division, Atlantic County, Case 

No. 271 (MCL).

Bruce D. Greenberg and David R. Buchanan 

argued the cause for appellants (Seeger Weiss, 

LLP, Lite, DePalma, Greenberg, LLC, and Weitz 

& Luxenberg, PC, attorneys; Mr. Buchanan and 

Peter Samberg, of counsel; Mr. Buchanan, on 

the briefs).

Paul W. Schmidt (Covington & Burling, LLP) of 

the District of Columbia bar, admitted pro hac 

vice, argued the cause for respondents Hoffman 

LaRoche, Inc. and Roche Laboratories, Inc.

(Gibbons PC, Dughi Hewit & Domalewski, PC and 

Mr. Schmidt, attorneys; Michelle M. Bufano,

Natalie H. Mantell, Russell L. Hewit, Mr. 

Schmidt and Michael X. Imbroscio (Covington & 

Burling, LLP) of the District of Columbia bar, 

admitted pro hac vice, of counsel; Ms. Bufano, 

on the brief).

Hollingsworth LLP, attorneys for amicus curiae 

Pharmaceutical Research and Manufacturers of 

America (Gregory S. Chernack, of counsel and 

on the brief).

APPROVED FOR PUBLICATION

July 28, 2017

APPELLATE DIVISION
2 A-4698-14T1

 

The parties have not filed briefs in A-0910-

16.

The opinion of the court was delivered by

REISNER, P.J.A.D.

Plaintiffs, in these 2076 multicounty litigation (MCL) 

products liability cases, alleged that they developed Crohn's 

disease 1 as a result of taking Accutane (isotretinoin), a 

prescription acne drug manufactured by defendants Hoffman-La Roche 

Inc. and Roche Laboratories Inc. (collectively Roche or 

defendants). After a Kemp2 hearing, the trial court issued a 

February 20, 2015 order granting defendants' omnibus motion to bar

plaintiffs' experts - Dr. David Madigan, a statistician, and Dr. 

Arthur Kornbluth, a gastroenterologist - from testifying, among 

other things, that the epidemiology studies on which the defense 

relied were flawed and unreliable, and that Accutane can cause 

Crohn's disease. The trial court also directed the parties to 

prepare an order listing the lawsuits affected by the ruling, and 

subsequently issued a May 8, 2015 order dismissing 2076 MCL claims 

 

1 Crohn's disease is a form of inflammatory bowel disease (IBD).

2 Kemp ex rel. Wright v. State, 174 N.J. 412, 417 (2002). 
3 A-4698-14T1

 

with prejudice. Plaintiffs appeal from those orders.3 

On this appeal, plaintiffs primarily contend that the trial 

court misapplied its discretion in finding that the methodologies 

Madigan and Kornbluth used were scientifically unreliable and 

inadmissible. After reviewing the record, we reverse the orders 

on appeal and remand this case to the trial court. 

We agree with plaintiffs that the trial court went beyond its 

gatekeeping function, as set forth in Rubanick v. Witco Chemical

Corp., 125 N.J. 421, 449 (1991), Landrigan v. Celotex Corp., 127 

N.J. 404 (1992), and Kemp, supra, 174 N.J. at 412.4 The trial 

court took too narrow a view in determining whether the experts 

were using accepted scientific methodologies to analyze the 

evidence, and improperly determined the weight and credibility of 

the experts' testimony. Among other things, the judge 

 

3 In a second appeal (A-0910-16), ninety-eight plaintiffs appeal 

from a September 19, 2016 order dismissing their complaints on the 

same basis. By order dated December 7, 2016, we granted an 

unopposed motion to consolidate A-0910-16 with the current appeal,

A-4698-14 (the first appeal); however, we excused the parties in 

the second appeal from filing briefs or appendices, based on their 

agreement to be bound by the outcome of the first appeal. 

4 Plaintiffs also argue that the trial court erred as a matter of 

law in applying the strict, scientific certainty admissibility 

standard, instead of the relaxed standard set forth in Rubanick. 

That argument is without sufficient merit to warrant discussion. 

R. 2:11-3(e)(1)(E). 
4 A-4698-14T1

 

inappropriately condemned the experts for relying on relevant 

scientific evidence other than epidemiological studies, despite 

their plausible explanations for doing do.5 Consequently, we 

conclude that the trial court mistakenly exercised discretion in 

barring the experts' testimony. 

In reaching our conclusion, we emphasize that we are not 

placing this court's imprimatur on plaintiffs' experts or on their 

opinions. The experts on both sides are highly reputable 

scientists, who view the evidence differently. We find no basis 

to describe plaintiffs' experts pejoratively as "hired guns," any 

more than the defense experts are "hired guns." Their testimony 

should not have been barred because their analyses emphasized 

different evidence and produced different conclusions than those 

reached by the defense experts. The fact that plaintiffs' experts 

found certain evidence to be critically important did not 

constitute improper "cherry picking," because they provided 

plausible scientific explanations for their choices. See State 

v. Dreher, 302 N.J. Super. 408, 464 (App. Div. 1997) ("Expert 

testimony should not be excluded merely because it fails to account 

 

5 Those same types of evidence were held admissible by a prior 

judge, who had handled the Accutane MCL litigation for a decade. 
5 A-4698-14T1

 

for some condition or fact that the opposing party considers 

relevant."). 

We are not predicting whether a jury will find plaintiffs' 

experts - or defendants' experts - credible or persuasive. That 

is not our role, as it was not the trial court's role in the Kemp

hearing. See Hisenaj v. Kuehner, 194 N.J. 6, 24 (2008) (N.J.R.E. 

104 hearings "are intended to determine admissibility, not 

credibility."). We only hold that, on the record created in the 

Kemp hearing in this case, the plaintiffs' experts provided wellexplained scientific reasons for analyzing the available evidence 

differently from the defense experts, and for relying more heavily 

on different evidence than the defense experts relied on. 

Accordingly, plaintiffs are entitled to present the experts' 

testimony at trial. 

I

This case cannot be viewed in a vacuum. It is one in a long 

series of mass tort litigations concerning Accutane.6 We need not 

 

6 McCarrell v. Hoffman-La Roche, Inc. (McCarrell I), No. A-3280-

07 (App. Div. Mar. 12, 2009), certif. denied, 199 N.J. 518 (2009); 

Kendall v. Hoffman-La Roche, Inc. (Kendall I), No. A-2633-08 (App. 

Div. Aug. 5, 2010), aff'd, 209 N.J. 173 (2012); Sager v. HoffmanLa Roche, Inc., No. A-3427-09 (App. Div. Aug. 7, 2012), certif. 

denied, 213 N.J. 568 (2013); Gaghan v. Hoffman-La Roche, Nos. A2717-11, A-3211-11, A-3217-11 (App. Div. Aug. 4, 2014); McCarrell 
6 A-4698-14T1

 

review the history in detail, as it is set forth in a series of 

previous unpublished opinions issued by different panels of this 

court. We summarize only what is important to this case. 

For more than a decade, the same trial judge had handled the 

Accutane cases. To some extent, that judge's familiarity with the 

prior litigation, and with the multiplicity of scientific issues 

involved, may have shaped the way the parties and their experts 

prepared for the current litigation.7 The first judge's rulings 

no doubt also shaped the parties' litigation strategies. 

In particular, during the course of the litigation, the first 

judge determined that the opinions of plaintiffs' experts, based 

on the same types of evidence relied on by plaintiff's experts in 

this case, would be admissible as scientifically reliable. We 

 

v. Hoffman-La Roche, Inc. (McCarrell II), No. A-4481-12 (Aug. 11, 

2015), rev’d and remanded, 227 N.J. 569 (2017); Kendall v. HoffmanLa Roche, Inc. (Kendall II), No. A-0301-14 (June 16, 2016); 

and Rossitto v. Hoffman-La Roche, Nos. A-1236-13, A-1237-13 (July 

22, 2016), certif. denied, 228 N.J. 419 (2016).

7 Both of the parties' epidemiology experts (Dr. Madigan and Dr. 

Steven N. Goodman) who had testified previously, expressed their 

belief that, to some extent, their current reports and testimony 

would be viewed in light of their testimony in previous Accutane 

trials. 
7 A-4698-14T1

 

affirmed that determination in McCarrell I, supra, A-3280-07,8

finding that animal studies, case reports, analogous medications, 

and other evidence relied on by plaintiffs' experts, were types 

of evidence accepted in the scientific community.9 

In the present case, defendants contend that the existence 

of epidemiological studies now precludes reliance on the other 

types of evidence on which plaintiff's experts had previously 

relied. However, the studies on which defendants rely are not the 

controlled clinical trials that the Federal Judicial Center's 

Research Manual on Scientific Evidence calls "the gold standard" 

of scientific evidence. Rather they are observational studies that 

 

8 Unpublished opinions are not to be cited as legal precedent, and 

we do not do so here. R. 1:36-3. However, it is appropriate to 

consider an unpublished opinion of this court where, as here, it 

forms a part of the history of the case on appeal. See Mountain 

Hill, L.L.C. v. Twp. Comm. of Twp. of Middletown, 403 N.J. Super.

146, 155 n.3 (App. Div. 2008), certif. denied, 199 N.J. 129 (2009). 

Moreover, an unpublished opinion of this court is binding on the 

trial court in the same case. Ibid. The parties have not briefed 

and, hence, we do not decide, whether an unpublished opinion of 

this court is binding on the trial court in the same MCL docket, 

albeit in a different case within that docket. 

9 In a 2014 oral opinion, the first trial judge made a detailed 

analysis of similar testimony by Dr. David Sachar and Dr. Madigan 

concerning the connection between Accutane and ulcerative colitis. 

The first judge concluded that the expert testimony, which relied 

on very similar types of evidence as that used in this case, was 

admissible. That decision was appealed, but was settled before 

we decided the appeal. See Kendall II, supra, A-0301-14. 
8 A-4698-14T1

 

depend on the collection of information from databases or from 

patient questionnaires. Plaintiffs' experts testified that the 

studies are biased and otherwise flawed. We conclude that 

plaintiffs should be entitled to present that testimony at trial, 

along with their affirmative evidence in support of their case. 

II

We begin with some background as to Accutane, the 

epidemiological studies of the drug, and relevant scientific 

principles of epidemiology. 

A. Accutane

In 1982, the Food and Drug Administration (FDA) approved 

defendants' application to market Accutane, the brand name for 

isotretinoin, "to treat recalcitrant nodular acne that has not 

responded to other regimens." Kendall I, supra, 209 N.J. at 180. 

The drug is a retinoid, derived from vitamin A, and is very 

effective in treating severe acne. Ibid. It is well established 

that Accutane "has a number of known side effects, including dry 

lips, skin and eyes; conjunctivitis; decreased night vision; 

muscle and joint aches; elevated triglycerides; and a high risk 

of birth defects if a woman ingests the drug while pregnant." 

Ibid. There is also some evidence that Accutane, which was 
9 A-4698-14T1

 

originally studied for use in treating cancer, has an effect on 

the gastrointestinal tract. 

The MCL cases concern the alleged propensity of Accutane to 

cause IBD, a chronic disease which primarily manifests as one of 

two diseases: Crohn's disease or ulcerative colitis. Id. at 180-

81. Although both ulcerative colitis and Crohn's disease share 

the same core symptoms, including abdominal pain, frequent and 

often bloody bowel movements, and rectal bleeding, there are 

differences in the clinical presentation of the disease and the 

triggers statistically associated for developing it, which include 

family history, infections, frequent use of some antibiotics, 

smoking, and possibly the use of oral contraceptives and 

nonsteroidal anti-inflammatory drugs. Id. at 181. 

The peak onset of the disease occurs during adolescence—the 

same period that individuals are likely to have been prescribed 

Accutane. Ibid. For both diseases there may be a significant 

latency effect (the time from the exposure to the trigger for IBD 

to the first symptom of the disease) and a prodromal period (the 

time from the first symptom of the disease to diagnosis). 

B. Epidemiological studies 

For the first six years of this MCL litigation, from 2003 to 
10 A-4698-14T1

 

2009, there were no epidemiological studies regarding Accutane and 

IBD. In previous trials, the plaintiffs were permitted to present 

expert testimony that relied on animal studies, human clinical 

studies, case reports, class effects, published scientific 

literature, causality assessments, and biological plausibility. 

McCarrell I, supra, slip op. at 86; Kendall I, supra, slip op. at 

85-86; Sager, supra, slip op. at 20. 

The first two epidemiological studies (Crockett and 

Bernstein),10 were published in 2009 and in 2010, finding no 

statistically significant increased risk of developing Crohn's 

disease from the use of Accutane, although the Crockett study 

found ulcerative colitis is associated with exposure to the drug. 

The Crockett and Bernstein studies were addressed in expert 

testimony in Gaghan, McCarrell II, and Rossitto. In Kendall II, 

the expert witnesses addressed four new epidemiological studies 

 

10 Seth D. Crockett et al., Isotretinoin Use and the Risk of 

Inflammatory Bowel Disease: A Case-Control Study, 105 Am. J. 

Gastroenterol. 1986 (Sept. 2010) (ulcerative colitis but not 

Crohn's disease is associated with isotretinoin use); Charles N. 

Bernstein et al., Isotretinoin is not Associated with Inflammatory 

Bowel Disease: A Population-Based Case-Control Study, 104 Am. J. 

Gastroenterol. 2774 (Nov. 2009) (unlikely that isotretinoin use 

is associated with development of IBD). 
11 A-4698-14T1

 

(Etminan, Alhusayen, Fenerty, and Racine).11 After the trial in 

Kendall II, two additional studies were published (Rashtak and 

Sivaraman).12 The epidemiological studies vary in whether they 

show that Accutane increases or decreases the risk of developing 

Crohn's disease. However, with one exception, none of them 

demonstrates a statistically significant increased risk of 

developing Crohn's disease from exposure to Accutane. One small 

study (Sivaraman) did find a statistically significant increased 

risk. However, when the study authors adjusted the study results 

for antibiotic use, the results were no longer statistically 

significant. Plaintiffs' experts questioned the appropriateness 

of that adjustment.

C. Epidemiology

 

11 Mahyar Etminan et al., Isotretinoin and Risk for Inflammatory 

Bowel Disease, 149 JAMA Dermatol. 216 (Feb. 2013) (no increased 

risk for IBD); Raed O. Alhusayen et al., Isotretinoin Use and the 

Risk of Inflammatory Bowel Disease: A Population-Based Cohort 

Study, 133 J. Invest. Dermatol. 907 (2013); Sarah Fenerty et al., 

Impact of Acne Treatment on Inflammatory Bowel Disease, 68 J. Am. 

Acad. Dermatol. 6751 (Apr. 2013); Antoine Racine et al., 

Isotretinoin and Risk of Inflammatory Bowel Disease: A French 

Nationwide Study, 109 Am. J. Gastroenterol. 563 (Apr. 2014).

12 Shadi Rashtak et al., Isotretinoin Exposure and Risk of 

Inflammatory Bowel Disease, 150 JAMA Dermatol. 1322 (Dec. 2014); 

Susil Silverman et al., Risk of Inflammatory Bowel Disease from 

Isotretinoin: A Case Control Study (Oct. 2014). 
12 A-4698-14T1

 

In understanding the epidemiological studies, it is first 

helpful to define the methodology used in conducting such studies 

and the relevant terms, as testified by the experts at the hearing 

and as set forth in the Federal Judicial Center, Reference Manual 

on Scientific Evidence 549, 555 (3d. ed. 2011) (Reference Manual

or Manual).13 "Epidemiology is the field of public health and 

medicine that studies the incidence, distribution, and etiology 

of disease in human populations." Id. at 551. "Epidemiology 

assumes that disease is not distributed randomly in a group of 

individuals and the identifiable subgroups, including those 

exposed to certain agents [such as prescription drugs], are at 

increased risk of contracting particular diseases." Ibid. 

Epidemiological studies identify agents that are associated with 

an increased risk of a disease in groups of individuals, but "is 

not equivalent to causation." Id. at 552. 

There are two types of epidemiological studies: experimental 

and observational. Id. at 555. Experimental studies, or doubleblind randomized control trials, in which one group is exposed to 

 

13 Available at https://www.fjc.gov/sites/default/files/2015/

SciMan3D01.pdf. The epidemiological section was written by 

Michael D. Green, among others, and is entitled Reference Guide 

on Epidemiology.
13 A-4698-14T1

 

an agent and the other is not, are "considered the gold standard 

for determining the relationship of an agent to a health outcome 

or adverse side effect." Ibid. There are, however, no Accutane 

experimental studies because although such studies have the 

potential to provide higher quality evidence, they cannot 

ethically be conducted if researchers suspect that a drug's sideeffects are harmful. Id. at 555-56. 

Instead, all of the Accutane epidemiological studies to date 

are less rigorous observational studies, which are considered to 

be the next best available evidence. Id. at 556. There are two 

types of observational studies: 1) a case-control study, which 

measures and compares the frequency of exposure in the group with 

the disease (cases) and a similar group without the disease 

(controls); and 2) a cohort study, which compares a group of 

exposed and unexposed individuals over a period of time. Id. at 

557-59. In these studies, researchers "observe" individuals who 

have already been exposed to the drug and compare them to a group 

of individuals who have not. Id. at 555-56. 

Unlike experimental studies in which risk factors can be 

controlled, observational studies generally focus on individuals 

living in a community, "for whom characteristics other than the 
14 A-4698-14T1

 

one of interest, such as diet, exercise, exposure to other 

environmental agents, and genetic background, may distort a 

study's results." Id. at 556. "[T]he Achilles' heel of 

observational studies is the possibility of differences in the two 

populations being studied with regard to risk factors other than 

exposure to the agent." Ibid.

Epidemiological studies commonly express the strength of 

association between exposure to a drug and a disease in numerical 

terms as: 1) "relative risk" (RR), the ratio of the incidence 

rate of a disease in exposed individuals to the risk among the 

unexposed; or 2) "odds ratio" (OR), the ratio of the odds that an 

individual with the disease was exposed to the drug to the odds 

that an individual without the disease was exposed. Id. at 566-

69.14 An RR of 1.0 means that the relative risk is equal to the 

"null hypothesis," that is, that the risk in individuals exposed 

to Accutane is the same as the risk in unexposed individuals, or 

that Accutane use is not associated with an increased risk of 

 

14 The Manual explains that an OR is "a convenient way to estimate 

the relative risk in a case-control study when the disease under 

investigation is rare." Id. at 568. Most of the studies at issue 

in this case are case-control studies. An OR is calculated 

somewhat differently in a cohort study but the difference is not 

pertinent here.
15 A-4698-14T1

 

developing Crohn's disease. Id. at 567. If the RR is greater 

than 1.0, the risk in exposed individuals is greater than the risk 

in unexposed individuals. Ibid. For example, an RR of 1.5 means 

that an exposed individual has a 50% greater chance of contracting 

Crohn's disease. If the RR is less than 1.0, the exposed group 

has a decreased risk of contracting the disease. Ibid. Thus, 

an RR of .32 represents a 68% reduction in risk, which might mean 

that the drug had a protective effect on developing the disease. 

The OR or RR is, however, only an estimate of the true value. 

Determining whether an association identified in an 

epidemiological study is causal "requires an understanding of the 

strengths and weaknesses of the study's design and implementation, 

as well as a judgment about how the study findings fit with other 

scientific knowledge." Id. at 553. An assessment must be made 

of the power of the study to detect associations, the role of 

chance, and what sources of error might have produced a false 

result, including sampling variability, bias, and confounding 

variables (extraneous variables that may affect result). Id. at 

566-97. 

Therefore, a showing of an increased relative risk for Crohn's 

disease does not automatically prove that Accutane use creates a 
16 A-4698-14T1

 

higher risk of developing the disease because the discrepancy 

between the exposed and unexposed groups could be the product of 

chance as a result of random sampling error. Id. at 553. In 

determining whether a relative risk greater than 1.0 is a true 

association or the result of random error, researchers consider 

whether the association is statistically significant. Id. at 628. 

In making that assessment, researchers calculate a p-value, which 

"represents the probability that an observed positive association 

could result from random error even if no association were in fact 

present." Id. at 576. The p-value quantifies the statistical 

significance of a relationship; the smaller the p-value the greater 

the likelihood that associations determined in a study do not 

result from chance. Id. at 626. The most commonly used p-value 

is .05, that is for example, that there is a 5% chance that the 

relative risk could have occurred by random error. Id. at 576-

77. 

A more sophisticated approach, which was used in the studies 

at issue in this case, involves calculating a confidence interval 

(CI):

A confidence interval is a range of possible 

values calculated from the results of a study. 

If a 95% confidence interval is specified, the 

range encompasses the results we would expect 
17 A-4698-14T1

 

95% of the time if samples for new studies 

were repeatedly drawn from the same 

population. . . . The advantage of a 

confidence interval is that it displays more 

information than significance testing. 

"Statistically significant" does not convey 

the magnitude of the association found in the 

study or indicate how statistically stable 

that association is. A confidence interval 

shows the boundaries of the relative risk 

based on selected levels of . . . statistical 

significance. . . . [T]he confidence interval 

reveals the likely range of risk estimates 

consistent with random error. 

[Id. at 580.] 

If, for example, a study reveals a RR of 1.5, which represents 

an elevated risk of developing Crohn's disease, that result might 

or might not be considered statistically significant, depending 

on the boundaries of the confidence interval. If the CI includes 

1.0 (the null hypothesis, meaning that taking Accutane neither 

increases nor decreases the risk of developing Crohn's disease), 

then the 1.5 result is said not to be statistically significant. 

However, if the CI is entirely above 1.0, for example if it ranges 

from 1.2 to 3.2, then the 1.5 RR would be considered statistically 

significant. Id. at 580-81.

 In assessing whether the failure of a study to find a 

statistically significant association was exonerative of the drug 

or simply inconclusive, scientists consider the "power" of a study, 
18 A-4698-14T1

 

or "the probability of finding a statistically significant 

association of a given magnitude (if it exists) in light of the 

sample sizes used in the study." Id. at 582. "The power of a 

study depends on several factors: the sample size; the level of 

statistical significance specified; the background incidence of 

disease; and the specified relative risk that the researcher would 

like to detect." Ibid. The higher the power of the study the 

less likely it will show a false negative. Ibid. For example, a 

study with a likelihood of .25 of failing to detect a true RR of 

2.0, has a power of .75, meaning the study has a 75% chance of 

detecting a true RR of 2.0. Ibid. On the other hand, a study 

with low power has a greater likelihood of failing to detect a 

significant relative risk, even though such a risk exists. "With 

large numbers [of individuals included in the study group], the 

outcome of the test is less likely to be influenced by random 

error, and the researcher would have greater confidence in the 

inferences drawn from the data." Id. at 576. 

Under the proper circumstances, researchers can increase the 

power of a series of studies by conducting a meta-analysis, which 

involves pooling the results of different studies, some of which 

are small and lack statistical power, to arrive at a single figure 
19 A-4698-14T1

 

to represent the totality of the studies. Id. at 608. The Manual

indicates, however, that a meta-analysis may produce an unreliable 

result.

The appeal of a meta-analysis is that it 

generates a single estimate of risk (along 

with an associated confidence interval), but 

this strength can also be a weakness, and may 

lead to a false sense of security regarding 

the certainty of the estimate. A key issue 

is the matter of heterogeneity of results 

among the studies being summarized. If there 

is more variance among study results than one 

would expect by chance, this creates further 

uncertainty about the summary measure from the 

meta-analysis. Such differences can arise 

from variations in study quality, or in study 

populations or in study designs. Such 

differences in results make it harder to trust 

a single estimate of effect; the reasons for 

such differences need at least to be 

acknowledged and, if possible, explained. 

People often tend to have an inordinate belief 

in the validity of the findings when a single 

number is attached to them, and many of the 

difficulties that may arise in conducting a 

meta-analysis, especially of observational 

studies such as epidemiologic ones, may 

consequently be overlooked.

[Ibid.]

III

We next address the parties' conflicting testimony on the 

subjects of gastroenterology and epidemiology. As background, the 
20 A-4698-14T1

 

following chart15 summarizes the epidemiological studies at issue 

in this case:

STUDY DATABASE

AND 

SUBJECTS

NO. OF

SUBJECTS

RR for CD

at CI 95%

ACCUTANE 

EXPOSURE

PRIOR TO

DIAGNOSIS

STUDY

RESULTS 

Bernstein

2009

manuscript

(casecontrol)

Canadian

Health

Ins.

21,500

(total)

1118

(CD)

 1.15 

(0.61-2.02)

2.6 years Positive 

association

(increased risk),

but not SS 

Crockett

2010

manuscript

(casecontrol)

US Health

Ins. (55 

million)

29,000

(total)

3664

(CD)

 0.68

(0.28-1.68)

 

 0.89

(0.32-2.52)

1 year

2 year 

Negative 

association

(decreased risk)

Negative 

association

(decreased risk)

Etminan

2013

manuscript

(casecontrol)

(metaanalysis)

US Health

Ins. (women 

who had 

taken oral 

contraceptives)

45,000

(total)

1103

(CD)

1.05

(0.5501.98)

 0.91

(0.37-2.25)

 

 0.75

(0.46-1.24)

1 year Positive 

unadjusted 

association

Negative adjusted 

association 

(decreased risk)

Negative 

association (metaanalysis)

Racine

2014

manuscript

(casecontrol)

French 

Health

Ins. (47 

million)

44,000

(total)

2829

(CD)

 0.45

(0.24-0.85)

1 to 2

years 

SS protective 

association

(reduced risk)

Alhusayen

2013

manuscript 

(cohort)

Canadian

Database

(4.5 

million)

46,922

(treated

with 

Accutane)

 1.17

(0.90-1.52)

1 year Positive 

association 

(increased risk), 

but not SS

 

15 For purposes of the chart, we abbreviate Crohn's disease as "CD" 

and statistical significance as "SS."
21 A-4698-14T1

 

STUDY DATABASE

AND 

SUBJECTS

NO. OF

SUBJECTS

RR for CD

at CI 95%

ACCUTANE 

EXPOSURE

PRIOR TO

DIAGNOSIS

STUDY

RESULTS 

Sivaraman

2014 

abstract/

poster

(casecontrol)

US Patient

Questionnaire

from three 

clinics

509

(total)

 5.6 

(1.1-28.0)

 

 4.8

(0.3-70)

unknown Positive 

unadjusted 

association and

SS for CD 

Positive adjusted 

association, but 

not SS for CD

Fenerty

2013

abstract/

power-point

(casecontrol)

Marketscan

Medicaid

Database

176,889

(total)

324

(CD)

For IBD

 0.57

(0.28-1.16)

Not reported

for CD

Negative

association for

IBD (decreased 

risk)

Rashtak

2014

manuscript 

(cohort)

Mayo Clinic

patients

1078

(total)

For IBD

 0.28

(0.10-0.79)

Not reported

for CD

Negative

association for 

IBD

(decreased risk)

A. Gastroenterology experts

1. Dr. Asher Kornbluth

Plaintiffs' expert, Dr. Kornbluth, was a highly qualified 

expert who was board-certified in internal medicine and 

gastroenterology and was a professor of medicine at Mount Sinai, 

the preeminent hospital for IBD. He had specialized in Crohn's 

disease for twenty-seven years, conducted research on IBD, 

conducted clinical trials on several drugs intended for use in the 

management of IBD, treated between 5,000 and 10,000 patients with 

Crohn's disease, been retained as a consultant to pharmaceutical 
22 A-4698-14T1

 

companies, and published more than 100 articles on IBD in peerreviewed scientific journals, textbooks, and other publications. 

Kornbluth opined that Accutane can cause Crohn's disease in 

humans. In reaching that conclusion, Kornbluth relied on his 

personal experience in treating thousands of patients with the 

disease. Additionally, he relied on some of the same evidence 

that Dr. David Sachar, a previous plaintiffs' expert, had relied 

on in seven previous Accutane trials in this MCL docket, 16

including animal studies, case reports, class effects of Vesanoid, 

biological plausibility, scientific articles, internal studies, 

causality assessments, and epidemiological studies. However, as 

more fully discussed infra, both Dr. Kornbluth and Dr. Madigan 

testified that most of the epidemiological studies done to date 

were fundamentally flawed, thus warranting greater reliance on 

other forms of scientific evidence. 

Evidence of an Association

In accord with what he testified was the established 

scientific methodology, Kornbluth first considered whether there 

was an association between Accutane and Crohn's disease. In making 

 

16 McCarrell I and II, Kendall I and II, Sager, Gaghan, and 

Rossitto. 
23 A-4698-14T1

 

that determination, he reviewed scientific articles, MedWatch 

reports, epidemiological studies, and causality assessments, which 

he found reflected a strong association between Accutane and 

Crohn's disease. 

a. Scientific articles

Kornbluth reviewed articles published in peer-reviewed 

scientific journals, many of which analyzed a single anecdotal 

case report, which he found supported a finding that there was an 

association between Accutane and Crohn's disease.17 For example, 

an article by Reddy and several colleagues reported that of the 

 

17 P. Martin et al., Isotretinoin-Associated Proctosigmoiditis, 93 

Gastroenterology 606 (1987) (case report); Philippe Deplaix et al., 

Acute Hemorrhagic Colitis Probably Due to Isotretinoin with 

Recurrence Following Reintroduction of Treatment, 20 

Gastroenterol. Clin. Biol. 113 (1996) (case report); Marianne Melki 

et al., Granulomatous Colitis Probably Due to Isotretinoin, 25 

Gastroenterol. Clin. Biol. 433 (2001) (case report); J.L.M. Passier 

et al., Isotretinoin-Induced Inflammatory Bowel Disease, 64 Neth. 

J. Med. 52 (Feb. 2006) (case reports); Deepa Reddy, M.D. et al., 

Possible Association Between Isotretinoin and Inflammatory Bowel 

Disease, 101 Am. J. Gastroenterol. 1569 (July 2006) (adverse event 

reports); Cristiano Spada, M.D. et al., Isotretinoin-associated 

Pan-enteritis, 42 J. Clin. Gastroenerol. 923 (Sept. 2008) (case 

report); Matthew Shale et al., Isotretinoin and Intestinal 

Inflammation: What Gastroenterologists Need To Know, 58 Gut 737, 

739 (June 2009) (study of adverse event reports concluding 

isotretinoin may act as trigger for IBD in susceptible patients); 

and Michael B. Brodin, M.D., Inflammatory Bowel Disease and 

Isotretinoin, 14 J. Am. Acad. Dermatol. 843 (1986) (letter to 

editor).
24 A-4698-14T1

 

approximately four or five million people that took Accutane 

between 1997 and 2002, the FDA received eighty-five reports of 

IBD. Using the Naranjo ADR probability scale, the authors found 

that "4 cases (5%) scored in the 'highly probable' range for 

isotretinoin as the cause of IBD, 58 cases (68%) were 'probable,' 

23 cases (27%) were 'possible,' and no cases were doubtful." 

Reddy, supra note 17, at 1571. The authors concluded that 

"isotretinoin appears to be a potential precipitant of IBD." Id.

at 1572.

b. MedWatch reports

Kornbluth next reviewed a series of MedWatch reports, reports 

which are made by physicians, patients and others to the FDA 

listing among other information, a description of the adverse 

event and whether it abated after the patient stopped using 

Accutane and returned after reintroduction (referred to as 

challenge/dechallenge/rechallenge). He found that if corrected 

for underreporting, the number of MedWatch reports suggested a 

strong association between Accutane and Crohn's disease. 

c. Epidemiological studies

Kornbluth also reviewed six observational epidemiological 

studies (Bernstein, Crockett, Alhusayen, Etminan, Racine, and 
25 A-4698-14T1

 

Sivaraman), only one of which (Sivaraman) found a statistically 

significant positive association (before adjustment for antibiotic 

use) between Accutane and Crohn's disease, one found a 

statistically significant negative association (Racine) and no 

study concluded that Accutane use presents an increased risk for 

developing Crohn's disease. 18 Kornbluth opined that despite 

"significant flaws" in five of those studies that distorted the 

results, the studies nonetheless provided some evidence of an 

association between Accutane and Crohn's disease. 

Kornbluth relied on the unadjusted results of the Sivaraman 

study, which was summarized in a published abstract (not manuscript 

form), and selected by the American College of Gastroenterology 

to be presented as a poster at their annual conference to enable 

peers and colleagues to discuss the findings with the researchers. 

In that small study (509 patients), the authors initially found a 

statistically significant association between Accutane and Crohn's 

disease: that the risk of developing the disease was more than 

five times higher in the group exposed to Accutane. The authors 

 

18 The studies yielded different results for ulcerative colitis: 

Crockett found a statistically significant association; Bernstein, 

Etminan, Racine, and Alhusayen found a positive association, but 

not a statistically significant association; and Fenerty and 

Rashtak found a negative association.
26 A-4698-14T1

 

collected data using a questionnaire, which included information 

about use of antibiotics, family history of IBD, and smoking, 

thereby accounting for confounding variables. The authors then 

"adjusted" the analysis to remove subjects who had taken 

antibiotics, which Kornbluth said still yielded a "very striking 

increased risk" of developing Crohn's disease from Accutane use, 

although the adjusted sample size was too small to demonstrate 

statistical significance. The authors concluded that 

"isotretinoin exposure does not appear to confer risk for Crohn's 

disease independent of antibiotic exposure." Kornbluth and 

Madigan both questioned the basis for the adjustment the authors 

made.19

Kornbluth opined that the results of the other five studies 

(Bernstein, Crockett, Alhusayen, Etminan, and Racine), were 

inconclusive because they: failed to account for the prodrome 

(see section 1 below); were insufficiently "powered"; or contained 

design flaws that biased or distorted the results to show a reduced 

risk of developing Crohn's disease. Nonetheless, Kornbluth found 

 

19 The authors noted that taking antibiotics alone did not appear 

to affect the risk of developing Crohn's disease. Nonetheless, 

they removed the subjects who had taken antibiotics when they 

recalculated the study results. 
27 A-4698-14T1

 

that the studies were informative in determining causation, noting 

that four of the studies (Bernstein, Etminan (unadjusted), 

Alhusayen, and Sivaraman) found a positive association between the 

drug and the disease. 

1. Prodrome

Kornbluth opined that four of the studies (Crockett, 

Alhusayen, Etminan, and Racine) had not followed patients for long 

enough to detect an effect from Accutane exposure and thus had 

failed to account for the prodrome of Crohn's disease, that is, 

the delay between the time of the first or early symptoms and the 

diagnosis. He opined, based on his decades of experience as a 

treating gastroenterologist, that the average prodrome for Crohn's 

disease was from two to four years. He found support for that 

opinion in several studies, including: 1) the Pimentel study,20 a 

referral-based study (45 of the 66 subjects had Crohn's disease), 

in which the authors found the mean prodrome for Crohn's disease 

was 6.9 years; and 2) the Barratt study,21 in which the authors 

 

20 Mark Pimentel, M.D. et al., Identification of a Prodromal Period 

in Crohn's Disease but Not Ulcerative Colitis, 95 Am. J. 

Gastroenterol. 3458 (Dec. 2000).

 

21 S.M. Barratt et al., Prodromal Irritable Bowel Syndrome May Be 

Responsible For Delays In Diagnosis In Patients Presenting With 
28 A-4698-14T1

 

found the mean prodrome was four years. He distinguished the 

findings of a larger study by Chouraki22 in which the authors found 

a three-month prodrome, based upon the selection of the patients 

for the study and the use of patient charts as opposed to patient 

questionnaires, as used in the Barratt and Pimentel studies. 

Kornbluth explained that because the prodrome for Crohn's 

disease is two to four years, a study that looks back only oneyear from diagnosis would not capture patients who developed 

Crohn's disease from Accutane exposure 366 days to four years 

after taking the drug. He noted, for example, that in the Crockett 

study the odds ratio increased from 0.68 (one-year analysis) to 

0.89 (two-year analysis), which he said was likely a result of 

capturing more patients who had developed the disease. Similarly, 

the Bernstein study, which looked back approximately 2.6 years, 

found a positive association between Accutane and Crohn's disease, 

which Kornbluth opined may also have resulted from capturing more 

 

Unrecognized Crohn's Disease And Celiac Disease, But Not 

Ulcerative Colitis, 56 Dig. Dis. Sci. 3270 (Nov. 2011).

22 V. Chouraki et al., The changing pattern of Crohn's disease 

incidence in northern France: a continuing increase in the 10- to 

19-year-old age bracket (1988-2007), 33 Aliment. Pharmacol. Ther.

1133 (2011). Chouraki was not a study of the prodrome for Crohn's 

disease. It was a study of the increased incidence of the disease 

in northern France. 
29 A-4698-14T1

 

Crohn's disease patients than the other shorter studies. He found 

that these four studies were not designed to accurately account 

for all of the Accutane patients who had developed Crohn's disease, 

thereby distorting the results. He opined that if the studies had 

been designed to account for the long prodrome, the results would 

have shown a greater increased risk of developing Crohn's 

disease.23 

2. Power

Next, Kornbluth opined that three of the studies (Bernstein, 

Crockett, and Etminan), were insufficiently powered to detect a 

statistically significant association; in other words, that the 

sample size was not large enough to make a definitive conclusion 

as to whether there was a statistically significant risk. For 

example, in the Bernstein study, a large case-control study using 

a Canadian database, the study population only comprised 1118 

Crohn's disease cases out of a control population of 19,419. He 

calculated that the "power" of the Bernstein study was low (about 

25% to 30%), that is, there was only a 25% to 30% chance of 

 

23 Kornbluth's view about the length of the prodrome was hardly 

unique to him or scientifically unorthodox. It was supported by 

the Pimentel and Barratt studies, references in Passier, supra

note 17, at 52, and admissions made by defendant's expert, Dr. 

Oliva-Hemker.
30 A-4698-14T1

 

detecting a statistically significant association (greater than 

2%) between Accutane and Crohn's disease. He explained that 80% 

power was appropriate for a study. He opined that if these studies 

had not been underpowered, the results would have been 

statistically significant for an increased risk of developing the 

disease. 

However, Kornbluth admitted that where individual studies are 

underpowered to detect outcomes, studies can be pooled using a 

meta-analysis, to increase the power to detect a risk. One such 

study was done by Etminan, which combined the Bernstein, Crockett, 

Etminan (case-control study) and Racine studies, and found a pooled 

RR of .75 with a CI of 0.46 to 1.24, indicating no increased risk 

of developing Crohn's disease. Another study was done by Goodman, 

defendants' expert, as discussed more fully infra, who found a 

pooled RR of 0.87 with a CI of 0.59 to 1.28, or, again, no 

statistically significant increased risk of developing Crohn's 

disease. However, Kornbluth, like Madigan, rejected the results 

of these meta-analyses, explaining that a meta-analysis using 

underpowered and flawed studies (as he said existed in this case), 

which did not account for the prodrome, are not informative and 

should not be relied upon by scientists in determining causation. 
31 A-4698-14T1

 

3. Design flaws 

Kornbluth also found the results of the five studies were 

inconclusive because they had design flaws, including differences 

in the populations and the failure to account for confounding 

variables. For example, he opined that the Bernstein study, a 

Canadian study, was flawed because of the differences in 

recommended doses between the United States (higher dose) and 

Canada (lower dose). He expected that given that difference there 

would be far fewer cases of Crohn's disease in Canada thereby 

decreasing the relative risk ratio. Similarly, there were 

differences in recommended doses between the United States 

(higher) and France (lower), which Kornbluth testified could 

account for the Racine study's finding of a protective effect. 

Next, Kornbluth found that most of the studies had failed to 

account for smoking and family history confounders, that is, 

alternative causes of Crohn's disease unrelated to Accutane 

exposure that can bias the study by making the association appear 

higher or lower than it actually is.24 For example, the Alhusayen 

 

24 Many of the studies had accounted for other confounders, 

including gender, oral contraceptive use, use of NSAIDs, and 

antibiotics. And the Etminan study adjusted, in part, for patients 

who had made a claim for tobacco cessation counseling.
32 A-4698-14T1

 

study, which comprised 46,922 patients treated with Accutane, 

reported an unadjusted RR for Crohn's disease of 1.40, and an 

adjusted (for antibiotic use) RR of 1.17. He testified that the 

study should have adjusted for more relevant confounders, 

including family history and smoking, which presumably would have 

yielded a higher risk ratio of developing Crohn's disease from 

Accutane. In other words, removing all of the individuals who had 

a family history of Crohn's disease from the sample would yield a 

better measure of whether Accutane use is associated with Crohn's 

disease. 

Lastly, Kornbluth did not consider the results of two 

additional studies (Rashtak and Fenerty), because those studies 

were designed to only report general IBD results, and did not 

calculate the relative risk of developing Crohn's disease, which 

has different triggers than ulcerative colitis and therefore did 

not provide reliable information on the risk of developing Crohn's 

disease. 

d. Causality assessments

Next, Kornbluth considered defendants' internal causality 

assessments of adverse drug experience (ADE) reports of Crohn's 

disease in patients taking Accutane, in which defendants had 
33 A-4698-14T1

 

concluded that there was an association between Accutane and the 

disease. For example, in an internal causality assessment dated 

December 17, 2002, defendants reported that there were 159 reports 

of adverse events from exposure to Accutane received from worldwide 

sources; of those patients, sixty-four had Crohn's disease, of 

which Roche assessed causality as "related" in twenty-seven cases, 

with the remainder designated either as unrelated or unknown. 

Additionally, defendants concluded in an internal report dated 

November 16, 2000, that "[i]sotretinoin has been found to be 

causally associated with inflammatory bowel disease, including 

colitis." 

Similarly, in its "general data memo," a document that 

reflected the company's scientific and medical opinion about 

Accutane, defendants provided that IBD "is a possible side effect 

of ROACCUTANE in very rare cases, possibly in patients predisposed 

to inflammatory gastro-intestinal diseases," and that although the 

side-effect "does not seem to represent a serious problem in 

practice," it is "reasonable to conclude" that the drug is 

"basically contraindicated" for patients "in the active phase" of 

IBD. Kornbluth testified that those "strong statement[s]" by 

defendants, who had a great deal of pharmacovigilance experience 
34 A-4698-14T1

 

in assessing ADE reports, were significant in assessing whether 

Accutane use was associated with Crohn's disease. In its core 

data sheet, which is a compilation of information set forth in 

labels or in reports sent to regulatory boards, defendants also 

stated that IBD had been reported in Accutane users and that 

adverse events are dose-related. 

Existence of a Causal Relationship

After determining that there was an association between 

Accutane and Crohn's disease based on the literature, MedWatch 

reports, epidemiological studies, and causality assessments, 

Kornbluth then considered whether that association reflected a 

causal relationship. 

a. Bradford Hill

As set forth above, epidemiology cannot prove causation. 

Reference Manual, supra, at 598. In making the causation 

determination, Kornbluth considered, among other factors, the 

widely recognized criteria identified by Sir Austin Bradford Hill 

(Bradford Hill criteria): (1) strength of the association; (2) 

temporal relationship; (3) consistency of relationship; (4) 

biological plausibility; (5) consideration of alternative 

explanations; (6) specificity; (7) dose-response relationship; (8) 
35 A-4698-14T1

 

replication; and (9) cessation of exposure. Sir Arthur Bradford

Hill, The Environment and Disease: Association or Causation, 58 

Proc. Royal Soc'y of Med. 295, 299 (1965). In assessing these 

criteria

[t]here is no formula or algorithm that can 

be used to assess whether a causal inference 

is appropriate based on these guidelines. One 

or more factors may be absent even when a true 

causal relationship exists. Similarly, the 

existence of some factors does not ensure that 

a causal relationship exists. Drawing causal 

inferences after finding an association and 

considering these factors requires judgment 

and searching analysis, based on biology, of 

why a factor or factors may be absent despite 

a causal relationship, and vice versa. 

Although the drawing of causal inferences is 

informed by scientific expertise, it is not a 

determination that is made by using an 

objective or algorithmic methodology.

[Reference Manual, supra, at 600.]

1. Strength of association

Kornbluth opined that the association evidence (scientific 

literature, MedWatch reports, epidemiological studies and 

causality assessments) reflected a strong association between 

Crohn's disease and Accutane, even though no medical organization 

or epidemiological study had concluded that Accutane causes 

Crohn's disease. He found that although the epidemiological 

studies had "some major shortcomings," most of the studies 
36 A-4698-14T1

 

nonetheless showed a "fairly substantial increased risk of 

Accutane causing Crohn's disease." 

2. Temporal relationship

Kornbluth found that the medical literature, MedWatch 

reports, and animal studies supported a finding that there was a 

temporal relationship between Accutane exposure and Crohn's 

disease, that is, the timing of the exposure to the drug and the 

onset of the disease was consistent with the lengthy latency and 

prodromal period for the disease. 

3. Biological plausibility

Although the precise mechanism by which Accutane could cause 

Crohn's disease is unknown, Kornbluth opined that there was a 

biologically plausible mechanism by which Accutane could cause 

Crohn's disease, namely, that Accutane may cause the migration of 

inflammatory T cells to the intestinal tract. Kornbluth explained 

that retinoic acid, which is a metabolite of Accutane, causes and 

perpetuates Crohn's disease by directing inflammatory T-cells, 

using "antenna" known as "alpha 4 beta 7," to the intestines and 

allowing the T-cells to bind to "receptors" (or "mucosal addressing 

cell adhesion molecules" ("MAdCAMs")), which then spurs invasion 

of inflammatory cells into the lining of the intestines. Without 
37 A-4698-14T1

 

retinoic acid, the antenna (alpha 4 beta 7), does not imprint on 

the T-cells and are not guided back to the intestines. He said 

that studies have shown that blocking retinoic acid prevents 

intestinal inflammation, which is characteristic of Crohn's 

disease. In other words, without alpha 4 beta 7, one cannot "get 

Crohn's disease, because the T cells that are the driver of the 

inflammation have no way of getting into the small intestine."25 

In fact, he noted that two new drugs (Vedolizumab and 

Natalizumab), which Kornbluth said had been very effective in 

treating Crohn's disease, operated to block the retinoic acid 

antenna (alpha 4 beta 7), thereby preventing the T-cells from 

binding to the MAdCAMs and entering the intestine where they cause 

damage. The success of these drugs indicated to Kornbluth "that 

retinoic acid is a damaging toxic pathway for patients with Crohn's 

disease," because inhibition of the harmful molecule caused the 

patient to get better. 

Moreover, he noted that a Canadian case-control 

epidemiological study on children supported his opinion on 

biological plausibility because it reported that children 

 

25 Kornbluth's explanation as to biological plausibility had some 

support in scientific literature. See, e.g., Spada, supra note 

17, at 24; Shale, supra note 17, at 737-39.
38 A-4698-14T1

 

ingesting dietary supplements of retinol (vitamin A), a compound 

related to Accutane, which also breaks down into retinoic acid, 

had a statistically significant (two-fold) increased risk of 

developing Crohn's disease.26 There was a dose effect, in that 

only the children taking higher than normal doses of retinol showed 

an increased risk of developing Crohn's disease. 

4. Dose relationship

Next, Kornbluth testified that there was a dose-related 

relationship between Accutane and gastrointestinal injury—higher 

doses cause greater injury—as set forth in the Core Data sheet, 

dog studies, MedWatch reports, and epidemiological studies. He 

explained that "a dose-response curve" is "scientific evidence" 

of causation. 

5. Consistency, coherence, and specificity

Lastly, Kornbluth testified that he had observed consistency 

across different lines of evidence supporting a causal 

relationship, including the MedWatch reports, dog studies, and the 

epidemiological studies, which except for the Racine study, 

 

26 Devendra K. Amre et al., Imbalances in Dietary Consumption of 

Fatty Acids, Vegetables, and Fruits Are Associated with Risk for 

Crohn's Disease in Children, 102 Am. J. Gastroenterol. 2016 (Sept. 

2007).
39 A-4698-14T1

 

reported an increased risk of developing the disease. 

He also found that the evidence was coherent with the 

scientific understanding of the cause and presentation of the 

disease. For example, evidence from the dog studies was consistent 

with the knowledge of the pathogenesis of the disease in that a 

breakdown of the epithelium (as observed in some of the dogs) can 

serve as a trigger for Crohn's disease. The Vedolizumab and 

Natalizumab studies demonstrated that blocking the effect of 

retinoic acid (an Accutane metabolite) vastly improved a patient's 

Crohn's disease. 

Kornbluth did not, however, find any specificity for Crohn's 

disease because the disease is not caused solely by Accutane use, 

and it is not the only side-effect of taking the drug. 

b. Other evidence of a causal relationship

1. Animal studies

In reaching his conclusion on causation, Kornbluth relied on 

studies in which dogs were given high doses of Accutane (the dogs 

achieved similar levels of the active metabolite as humans because 

a dogs' metabolism is different). The studies reported 

gastrointestinal upset, diarrhea, bloody mucoid stools, intestinal 

adhesions, thickening of the mucosa, and epithelial damage, with 
40 A-4698-14T1

 

crypt abscess formation as seen in Crohn's patients, in the treated 

dogs. He explained that even though dogs cannot develop IBD, the 

studies showed that Accutane can cause "significant obvious 

symptomatic damage to the gastrointestinal tract" because a dog's 

intestine "is quite analogous to the human intestinal tract." 

2. Challenge/dechallenge/rechallenge reports

Kornbluth opined that the challenge/dechallenge/rechallenge 

reports contained in the medical literature (Martin, Deplaix, and 

Melki) and in the MedWatch reports were "very compelling" evidence 

of causation. He explained that the reports of positive 

rechallenges were significant because they were essentially a nondeliberate human experiment, in that a potentially toxic substance 

was reintroduced to a patient resulting in further injury. 

3. Class effects

Kornbluth also reviewed side effects reported from use of 

Vesanoid, a chemically similar retinoid manufactured by Roche used 

to treat acute promyelocytic leukemia (APL). Chemically, Vesanoid 

is tretinoin, an all-trans retinoic acid. Accutane, or 

isotretinoin, another retinoid, metabolizes into tretinoin and 4-

oxo-isotretinoin. The Vesanoid package insert indicates that 

gastrointestinal disorders, including gastrointestinal 
41 A-4698-14T1

 

hemorrhage, were reported in thirty-four percent of clinical trial 

patients. These results were significant because such a high 

percentage of gastrointestinal disorders would not be expected, 

even in APL patients, who have a "tremendous tendency to bleed." 

Thus, he testified that this evidence supported his opinion that 

Accutane can cause gastrointestinal injuries. 

2. Dr. Maria Oliva-Hemker

Like Dr. Kornbluth, defendant's gastroenterology expert, Dr. 

Oliva-Hemker, was highly qualified. She was board certified in 

gastroenterology and was a professor of medicine at Johns Hopkins 

University. She had treated hundreds of children who suffered 

from IBD, published more than seventy peer-reviewed scientific 

articles on IBD, and chaired various gastroenterology committees. 

She opined that the available scientific evidence did not 

support a finding that Accutane can cause Crohn's disease. She 

testified that the scientific evidence supported a finding that 

retinoic acid had an anti-inflammatory or protective effect on the 

gastrointestinal tract. Moreover, she testified that all of the 

epidemiological data--the best available evidence--reported no 

increased risk of Crohn's disease associated with Accutane, which 

was consistent with the biological evidence of a protective effect. 
42 A-4698-14T1

 

She testified that Kornbluth had failed to follow well-recognized 

principles of medical evidence hierarchy by relying on lower-level 

data (such as case reports and animal studies), instead of higherlevel epidemiological evidence. 

However, on cross-examination, Oliva-Hemker admitted that 

Crohn's disease often has a lengthy prodrome. In fact, she 

admitted that information was reflected in her own professional 

writings. 

B. Biostatistical and epidemiological experts

1. Dr. David Madigan

Plaintiff's expert, Dr. Madigan, had a Ph.D. in statistics, 

taught statistics at Columbia University, had published more than 

150 papers on biostatistics and pharmacovigilance, and served as 

an investigator on an FDA pilot program to monitor the safety of 

FDA-regulated medical products. He did not testify as to 

causation, but rather explained the process of conducting 

epidemiological studies, and examined the six epidemiological 

studies on Accutane and Crohn's disease (Crockett, Bernstein, 

Alhusayen, Etminan, Racine, and Sivaraman). 

Madigan was critical of the design of the epidemiological 

studies. He found that the studies were biased toward a finding 
43 A-4698-14T1

 

of decreased risk as a result of: 1) power (Crockett, Alhusayen, 

and Etminan); 2) prodrome (Crockett, Etminan, Racine, and 

Alhusayen); and 3) unmeasured confounders (Bernstein (dose and 

duration), Crockett (exposure and outcome), Alhusayen (allowing 

reentry of patients after 12-month period), Etminan (confined to 

contraceptive users), Racine (dose), and Sivaraman (dose and 

duration)). 

For example, he found that the power of the studies, or "the 

power to detect a true effect of a particular size," was low. In 

reaching that determination, he employed standard statistical 

techniques and determined that the Accutane studies were not 

sufficiently powered to detect even a 50% increased risk -- a 

"meaningful" measure of risk. He calculated the nominal power of 

the four studies (that did not find a statistically significant 

risk to detect a 50% increased risk of Crohn's disease) as follows: 

Bernstein (37.8%); Crockett (18.2%); Alhusayen (89.4%); and 

Etminan (22.6%). In other words, the Bernstein study had only a 

37.8% chance of finding a statistically significant increase when 

there is a 50% increased risk, or a 62.2% chance of finding a 

false negative.

He also opined that because Crohn's disease has a long 
44 A-4698-14T1

 

variable prodrome (ranging from a few months to several years), 

these studies, which focused on a short observation window to 

measure exposure, failed to account for all of the patients who 

developed Crohn's disease as a result of ingesting Accutane. 

Madigan explained that failing to account for just a few patients 

will "introduce bias into the study" toward a showing of no or 

decreased risk and will decrease the power of the study. 

Accounting for a 6.9-year prodrome (which he derived from the 

Pimentel study), Madigan calculated that the power of some of the 

studies further decreased to: Crockett (5.12%); Alhusayen 

(36.2%); and Etminan (4.5%). He found that only Bernstein (with 

its 2.6-year study) and Sivaraman (with its questionnaire format) 

had addressed prodrome through their study designs. 

Moreover, Madigan testified, that it was not scientifically 

"appropriate to conduct a meta-analysis in this context, because 

of concerns with the individual studies." He explained that the 

purpose of a meta-analysis is to combine the results of 

epidemiological studies "to make a combined estimate," however, 

he noted that you cannot "make the bias" in a study "disappear" 

by combining several biased studies. Madigan, like Kornbluth, 

found that all of the studies in this case were "biased towards 
45 A-4698-14T1

 

the null," that is, "systematically biased to lower the estimated 

effect" and thus combining the studies would not yield an accurate 

result. 

Instead, Madigan conducted a statistical disproportionality 

analysis of the spontaneous ADE reports for Accutane and Crohn's 

disease contained in the FDA's ADE reporting system database. He 

explained that spontaneous ADE reports "serve as a primary data 

source with which we, as a society, study drug safety concerns," 

and is an important component of drug safety investigation even 

though the data has limitations due to its reliance on voluntary 

reporting. He said that a disproportionality analysis is 

"standard" in analyzing ADE reports and is routinely used by the 

FDA and the pharmaceutical industry in assessing emerging safety 

concerns. 

In his disproportionality analysis, which he conducted using 

the same methods as he used in conducting an analysis for the 

pharmaceutical industry, Madigan compared the observed rate of 

reporting for Accutane and Crohn's disease with the rate at which 

Crohn's disease was reported for other drugs in that database. He 

found that from 1997 to the present, there was a "striking signal 

of disproportionality" or a "strong association" between Accutane 
46 A-4698-14T1

 

use and Crohn's disease. Further, when Madigan removed the ADE 

reports generated through litigation by lawyer reporting, or 

approximately 88% of the reports, the results still showed a 

moderate increased risk of developing the disease. 

He testified that a similar disproportionality analysis had 

been conducted, by researchers affiliated with the World Health 

Organization (WHO), of the WHO's drug safety database (Uppsala 

Monitoring Centre) in which the researchers compared the observed 

rate of ADE reports of Crohn's disease for Accutane to the observed 

rate of reports of Crohn's disease for other drugs in the WHO 

database.27 They found a statistically significant increased risk 

(nineteen times greater) for developing Crohn's disease from 

Accutane use. 

2. Dr. Steven N. Goodman

The defense expert, Dr. Goodman, had an M.D. degree, as well 

as a Ph.D. in epidemiology, was a professor and associate dean for 

clinical research at Stanford University, and had published 

numerous peer-reviewed scientific articles. He opined that the 

epidemiological evidence supported a finding that there was a 

 

27 The findings are cited in an article on case reports, Passier, 

supra note 17, at 52. 
47 A-4698-14T1

 

"strongly negative" association between Accutane and Crohn's 

disease, and that there was no biologic evidence or scientifically 

accepted causal mechanism that outweighed the results of the 

epidemiological studies. He opined that Kornbluth's and Madigan's 

methodology was not scientifically valid because they placed "very 

little weight" on the epidemiological studies, which were the 

highest tier of evidence in this case, and placed much more weight 

on "lesser forms of evidence," including case reports, animal 

studies, and causality assessments. 

In forming his opinion, Goodman reviewed nine epidemiological 

studies (Bernstein, Crockett, Etminan (case-control and metaanalysis), Alhusayen, Racine, Rashtak, Sivaraman, and Fenerty). 

He considered the overall results of these studies for IBD as well 

as the results for Crohn's disease, because ulcerative colitis and 

Crohn's disease share a variety of risk factors and because it is 

difficult to distinguish between the diseases in the early stages. 

He opined that although the Sivaraman study showed an unadjusted 

statistically significant association between the drug and the 

disease, the study was too small to have any significance. He 

also opined that, viewed collectively, the epidemiological studies 

were consistent with Accutane having "either [a] potentially 
48 A-4698-14T1

 

protective effect" or "no effect."

To increase the power of the epidemiological studies, Goodman 

conducted a meta-analysis of Accutane and IBD (both ulcerative 

colitis and Crohn's disease), in which the larger more precise 

studies were given more weight. He found an RR of developing IBD 

of 0.87 (0.65-1.17), a negative association. He also conducted a 

meta-analysis of Accutane and Crohn's disease, and found a similar 

RR of 0.87 (0.59-1.28), another negative association. 

Further, Goodman found that the epidemiological studies 

properly accounted for the prodrome of Crohn's disease. In 

determining the prodrome, Goodman reviewed several epidemiological 

studies, including the Chouraki study, and concluded that the 

average prodrome for Crohn's disease was nine months or less. He 

criticized Madigan's reliance on what Goodman characterized as the 

outlier non-population-based Pimentel study (6.9-years prodrome), 

which Goodman said was too small to provide any valid information. 

He concluded that the nine epidemiological studies, which applied 

a prodrome from one to two years, were properly designed and 

powered, and strongly supported a finding of no association between 

Accutane and Crohn's disease. 
49 A-4698-14T1

 

IV

Before we address plaintiffs' appellate arguments, it is 

helpful to review the legal principles applicable to the 

admissibility of expert testimony in toxic tort and similar cases. 

To establish liability, plaintiffs must prove through expert 

testimony that ingestion of Accutane can cause Crohn's disease in 

humans (general causation). In addition, each individual 

plaintiff must prove specific causation, i.e., that Accutane was 

the cause of his or her disease. See DeLuca v. Merrell Dow Pharm., 

Inc., 911 F.2d 941, 958 (3d Cir. 1990). See also Perry v. Novartis 

Pharm. Corp., 564 F. Supp. 2d 452, 463 (E.D. Pa. 2008) ("Courts 

in toxic tort cases often separate the causation inquiry into 

general causation -- whether the substance is capable of causing 

the observed harm in general -- and specific causation -- whether 

the substance actually caused the harm a particular individual 

suffered."). The Kemp hearing at issue here concerned general, 

not specific, causation. 

The admissibility of scientific evidence is governed by 

N.J.R.E. 702, which provides that "[i]f scientific, technical, or 

other specialized knowledge will assist the trier of fact to 

understand the evidence or to determine a fact in issue, a witness 
50 A-4698-14T1

 

qualified as an expert by knowledge, skill, experience, training, 

or education may testify thereto in the form of an opinion or 

otherwise." The Rule imposes three requirements: 

(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.

[Hisenaj, supra, 194 N.J. at 15.]

The second requirement is at issue here, that is, whether 

Kornbluth's causation testimony and Madigan's statistical analysis 

testimony was sufficiently reliable in the field of scientific 

research to be admitted. Ibid. 

In most cases, the proponent of scientific evidence must 

demonstrate that the opinions are "generally accepted, within the 

relevant scientific community" (the Frye standard). State v. 

Chun, 194 N.J. 54, 91, cert. denied, 555 U.S. 825, 129 S. Ct. 158, 

172 L. Ed. 2d 41 (2008); State v. Harvey, 151 N.J. 117, 169-70

(1997) (citing Frye v. United States, 293 F. 1013, 1014 (D.C. Cir. 

1923)), cert. denied, 528 U.S. 1085, 120 S. Ct. 811, 145 L. Ed.
51 A-4698-14T1

 

2d 683 (2000).28 See also Hisenaj, supra, 194 N.J. at 17. "That 

acceptance entails the strict application of the scientific 

method, which requires an extraordinarily high level of proof 

based on prolonged, controlled, consistent, and validated 

experience." Rubanick, supra, 125 N.J. at 436. 

However, our Supreme Court has relaxed the "general 

acceptance" standard in tort cases involving injuries caused by 

toxic substances or medications, involving new or developing 

theories of causation. Kemp, supra, 174 N.J. at 430-31; Landrigan, 

supra, 127 N.J. at 414; Rubanick, supra, 125 N.J. at 449. Under 

the relaxed standard, "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 

 

28 In 1993, the United States Supreme Court, construing the Federal 

Rules of Evidence, held that Federal Rule of Evidence 702 

superseded Frye and mandated that the federal courts apply a more 

relaxed scientific reliability standard. Daubert v. Merrell Dow 

Pharm., Inc., 509 U.S. 579, 113 S. Ct. 2786, 125 L. Ed. 2d 469 

(1993). Daubert was a pharmacological tort case involving the 

drug Benedictin. Id. at 582, 113 S. Ct. at 2791, 125 L. Ed. 2d 

at 476. In criminal cases, New Jersey courts have not followed 

Daubert, but continue to strictly apply the Frye test, i.e., 

whether the scientific community generally accepts the reliability 

of the proffered evidence. See Harvey, supra, 151 N.J. at 168. 

As noted, in civil cases involving toxic torts, our courts use the 

relaxed standard set forth in Rubanick. See Kemp, supra, 174 N.J.

at 430-31. 
52 A-4698-14T1

 

methodology involving data and information of the type reasonably 

relied on by experts in the scientific field." Rubanick, supra, 

125 N.J. at 449. Thus, the Court "changed the focus of the inquiry 

from the scientific community's acceptance of the substance of the 

opinion to its acceptance of the methodology and reasoning 

underlying it." Clark v. Safety-Kleen Corp., 179 N.J. 318, 337 

(2004). The Rubanick standard does not require the 

"extraordinarily high level of proof[,]" ordinarily required 

before a scientific theory will attain general acceptance in the 

scientific community. Rubanick, supra, 125 N.J. at 436. 

The rationale behind relaxation of the standard was "the 

extraordinary and unique burdens facing plaintiffs who seek to 

prove causation” in such cases. Id. at 433.29 The task of proving 

causation in toxic tort cases "is invariably made more complex 

because of the long latency period of illnesses caused by 

carcinogens or other toxic chemicals." Ayers v. Jackson, 106 N.J.

557, 585 (1987). And, in some drug cases, causation may not have 

 

29 Rubanick relied heavily on persuasive federal court opinions, 

in rejecting the general acceptance test. Rubanick, supra, 125 

N.J. at 445 (citing United States v. Downing, 753 F.2d 1224, 1237 

(3d Cir. 1985), and DeLuca, supra, 911 F.2d at 941). See also

Ferebee v. Chevron Chem. Co., 736 F.2d 1529 (D.C. Cir.), cert. 

denied, 469 U.S. 1062, 105 S. Ct. 545, 83 L. Ed. 2d 432 (1984) 

(cited in Rubanick, supra, 125 N.J. at 440). 
53 A-4698-14T1

 

been "confirmed by the scientific community but compelling 

evidence nevertheless suggests that such a relationship exists." 

Kemp, supra, 174 N.J. at 430. 

V

Against that legal backdrop, we consider plaintiffs' 

contention that the trial court erred in barring their experts' 

testimony. Plaintiffs assert that: 1) their experts relied on 

methodologies and data of the type relied on by comparable experts; 

2) the judge substituted his judgment on the epidemiological 

studies for that of the expert scientists; 3) the experts' reliance 

on the studies involved a methodology generally followed by 

comparable experts; 4) Kornbluth appropriately considered the 

epidemiological studies in assessing the relationship between 

Accutane and Crohn's disease; 5) the judge mischaracterized 

Madigan's testimony; 6) the judge impermissibly weighed evidence 

of ADE reports and animal studies; and 7) the judge abused his 

discretion in assessing the credibility of plaintiffs' experts. 

We agree that the judge erred in excluding the experts' testimony.

Under the relaxed standard, as applicable here, the trial 

court assesses "the soundness of the proffered methodology and the 

qualifications of the expert." Kemp, supra, 174 N.J. at 426 
54 A-4698-14T1

 

(quoting Rubanick, supra, 125 N.J. at 454). The focus of the 

trial court's inquiry must be "solely on principles and 

methodology, not on the conclusions that they generate." Ibid. 

(quoting Daubert, supra, 509 U.S. at 594-95, 113 S. Ct. at 2797, 

125 L. Ed. 2d at 484). In evaluating the methodology, "courts 

should consider whether others in the field use similar 

methodologies." Rubanick, supra, 125 N.J. at 449.

In making that determination the court should not "directly 

and independently determine as a matter of law that a controversial 

and complex scientific methodology is sound." Id. at 451. "The 

critical determination is whether comparable experts accept the 

soundness of the methodology, including the reasonableness of 

relying on this type of underlying data and information. Great 

difficulties can arise when judges, assuming the role of scientist, 

attempt to assess the validity of a complex scientific 

methodology." Ibid. Nor is it appropriate for the trial judge 

to second-guess an expert's interpretation of the underlying data. 

Ibid. For example, in Rubanick the Court found that:

the trial court . . . "independently reviewed" 

each of the thirteen studies on which Dr. 

Balis relied, and decided that they "do not 

say what plaintiff's expert concludes." In 

engaging in such an analysis, the court 

substituted its own assessment of the studies 
55 A-4698-14T1

 

for that of an acknowledged expert. . . . 

"[t]he interpretation of the data . . . is the 

function of the qualified expert . . . . 

[C]ourts should be loath to determine whether 

the particular expert has properly relied upon 

data which experts in the field generally rely 

on." Thus, the inquiry is not the reliability 

of the expert's ultimate opinion nor is it 

whether the expert thought his or her own 

reliance on the underlying data was 

reasonable, nor whether the court thinks that 

the expert's reliance was reasonable[.] The 

proper inquiry is whether comparable "experts 

in the field [would] actually rely" on that 

information.

[Id. at 451-52 (quoting Ryan v. KDI Sylvan 

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

(additional citations omitted).] 

The qualifications of the expert must also "be factored into the 

determination of the soundness of the methodology used." Id. at 

452. 

"If epidemiological studies are to provide the basis for an 

expert's opinion, they must have been 'soundly and reliably 

generated' and be 'of a type reasonably relied on by comparable 

experts in the particular field.'" Landrigan, supra, 127 N.J. at 

419-20 (quoting Rubanick, supra, 125 N.J. at 447). When an expert 

relies on epidemiological studies, the "court should review the 

studies, as well as other information proffered by the parties, 

to determine if they are of a kind on which such experts ordinarily 
56 A-4698-14T1

 

rely." Id. at 417. Significantly, the court must "examine the 

manner in which experts reason from the studies and other 

information to a conclusion[,]" which "must derive from a sound 

methodology that is supported by some consensus of experts in the 

field." Id. at 420. See In re Zoloft Prods. Liab. Litig., 26 F. 

Supp. 3d 449, 460 (E.D. Pa. 2014) (excluded expert whose "opinion 

regarding class effects is not evidence based, and is directly 

contrary to the findings of her own peer-reviewed, published 

research"); In re Rezulin Prods. Liab. Litig., 369 F. Supp. 2d 

398, 425 (S.D.N.Y. 2005) (court excluded expert testimony where 

expert selectively chose his support from scientific literature 

and failed to "acknowledge or account for" evidence that tended 

to refute his theory).

A court's assessment of scientific expert evidence should 

include an evaluation of the studies upon which the experts rely, 

but the court must not substitute "its own assessment of the 

studies for that of an acknowledged expert." Rubanick, supra, 125 

N.J. at 451. "Although trial courts are expected to act as 

gatekeepers to the proper admission of expert testimony," courts 

are not expected "to investigate sua sponte the extent to which 

the scientific community holds in esteem the particular analytical 
57 A-4698-14T1

 

writings or research that a proponent of testimony advances as 

foundational to an expert opinion." Hisenaj, supra, 194 N.J. at 

16. "The court's function is to distinguish scientifically sound 

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

scientific terminology to present unsubstantiated personal 

beliefs." Landrigan, supra, 127 N.J. at 414. The plaintiff bears 

the burden of proof in establishing admissibility. Kemp, supra, 

174 N.J. at 429. 

Ordinarily, the admission or exclusion of expert testimony 

is "committed to the sound discretion of the trial court[,]" 

Townsend v. Pierre, 221 N.J. 36, 52 (2015), and we review the 

decision for abuse of discretion. Hisenaj, supra, 194 N.J. at 12. 

However, we owe somewhat less deference to a trial court's 

determination in a case of this type. See State v. Torres, 183 

N.J. 554, 567 (2005). "Although 'the trial court is in a better 

position to shape the record and make credibility determinations,' 

an 'appellate court need not be as deferential to the trial court's 

ruling on the admissibility of expert scientific evidence as it 

should be with the admissibility of other forms of evidence.'" 

State v. J.R., 227 N.J. 393, 410 (2017) (quoting Torres, supra, 

183 N.J. at 567). In determining whether the trial court 
58 A-4698-14T1

 

misapplied discretion, we consider whether the court's analysis 

of the evidence was faithful to the principles set forth in 

Rubanick, or whether the court misapplied the standards. See

State v. Darby, 174 N.J. 509, 518 (2002) (no deference is to be 

accorded to the trial court's decision to admit other-crime 

evidence, nor is that decision entitled to be reviewed under an 

abuse of discretion standard, where the trial judge failed to 

apply applicable law); Konop v. Rosen, 425 N.J. Super. 391, 401 

(App. Div. 2012) (appellate review is de novo when the trial court 

fails to apply the proper test in analyzing the admissibility of 

proffered evidence). See also Pressler & Verniero, Current N.J. 

Court Rules, comment 4.7 on R. 2:10-2 (2017) ("When the trial 

court fails to apply the proper test in analyzing the admissibility 

of proffered evidence, the de novo standard of review . . . 

applies").

 Here, the court found that although both of plaintiffs' 

experts were "eminently qualified, their reasoning and methodology 

is slanted away from objective science and in the direction of 

advocacy." The court found that Kornbluth's methodology was not 

supported by the scientific community because he interpreted the 

Sivaraman study differently than its authors did. Similarly, the 
59 A-4698-14T1

 

court found that Madigan placed undue weight on the Sivaraman 

study, and "ignored" the other studies. The judge also criticized 

Madigan for failing to perform a meta-analysis of all of the 

studies. 

 The court further reasoned that plaintiffs' experts had failed 

to follow valid scientific methodology in relying on the Sivaraman 

and Pimentel studies to the exclusion of the larger populationbased epidemiological studies, concluding that the "scientific 

literature does not support reliance upon such insignificant 

studies to arrive at conclusions." The court concluded that 

Kornbluth's "contrived reasoning is not supported by the 

scientific community as a reliable basis for making causal 

determinations," and Madigan's opinions were not methodology 

based, but rather conclusion-driven. 

Additionally, the court found that Kornbluth's testimony was 

"replete with what can be described as convenient assumptions. 

When he needs to bridge an analytical gap in his methodology he 

assumes facts, events and conclusions as he wants them to be in 

support of his hypothesis." For example,

in response to counsel's questioning regarding 

the results of various studies, Dr. Kornbluth 

assumed: (a) that all the patients in the two 

studies upon which he relied filled out their 
60 A-4698-14T1

 

questionnaires correctly; (b) despite the fact 

that the authors of the Sivaraman study got 

it wrong as to their adjustment for 

antibiotics, he assumed they got everything 

else correct; (c) he assumed that in the 

Rashtak Study, the patients with Accutane 

exposure were followed for less time than the 

control group; and (d) he assumed the size of 

the doses of Accutane given to the subjects 

in various studies.

 

With regard to biological plausibility, the court found 

Kornbluth's discussion of his hypothesis for 

the biological mechanism of the development 

of CD [Crohn's disease] as caused by 

Isotretinoin falls far short of being 

"compelling." His basis for the discussion 

are the medications Natalizumab and 

Vedolizumab. He attempts to extrapolate 

causation of CD by Isotretinoin by discussing 

treatment of CD by these other medications. 

Dr. Oliva-Hempker [sic] explained the inherent 

weakness of trying to rely upon the data on 

Natalizumab and Vedolizumab as being probative 

of causation. In essence, treating a 

"pathway" that develops once a disease occurs, 

does not mean that . . . a particular treatment 

mechanism informs as to the original cause of 

the disease. She also pointed out that this 

hypothesis is contrary to a significant body 

of scientific literature showing that Retinoic 

acid is actually anti-inflammatory . . .

 

The court described Madigan as "an expert on a mission," and 

criticized Kornbluth's approach as being less convincing than 

Oliva-Hemker's analysis as to causation. He was also critical of 

plaintiffs' experts' reliance on lines of evidence other than 
61 A-4698-14T1

 

epidemiological studies:

[C]oursing through Plaintiffs' presentation 

is a refrain that is a ruse. Repeatedly, 

counsel for the Plaintiffs and their witnesses 

spoke of "lines of evidence," emphasizing that 

their experts examined the same "lines of 

evidence" as did the experts for the Defense. 

Counsels' sophistry is belied by the fact that 

the examination of the "lines of evidence" by 

Plaintiffs' experts was highly selective, 

looking no further than they wanted to --

cherry picking the evidence -- in order to 

find support for their conclusion-driven 

testimony in support of a hypothesis made of 

disparate pieces, all at the bottom of the 

medical evidence hierarchy. This crafty 

stratagem cannot bridge the analytical gaps 

inherent in Plaintiffs' hypothesis.

 

Plaintiffs contend that, whether or not the trial judge found 

their experts opinions persuasive in substance, the experts relied 

on methodologies and data of the type reasonably relied upon by 

comparable experts. We agree. 

A. Data and Information

Whether or not it persuades a jury, it is clear to us that 

in forming their conclusions Kornbluth and Madigan relied on the 

types of data and information reasonably relied on by comparable 

experts in the scientific field, and by the experts in previous 

Accutane cases in this docket. That evidence includes 

epidemiological studies, scientific articles, case studies, 
62 A-4698-14T1

 

clinical studies, animal studies, and causality assessments. 

It is well-established that epidemiological studies, 

published in peer-reviewed scientific journals, as were considered 

in this case, are the type of data reasonably relied on by the 

scientific community to determine whether exposure to a drug is 

associated with a disease. Landrigan, supra, 127 N.J. at 419-20. 

Properly conducted epidemiological studies are a significant 

factor in establishing causation in toxic tort cases. See Reference 

Manual, supra, at 551 n.2. "[E]pidemiology is a well-established 

branch of science and medicine, and epidemiological evidence has 

been accepted in numerous cases." DeLuca, supra, 911 F.2d at 954. 

See Magistrini v. One Hour Martinizing Dry Cleaning, 180 F. Supp.

2d 584, 591 (D.N.J. 2002) (epidemiological studies), aff'd o.b., 

68 Fed. App'x 356 (3d Cir. 2003). Notably, although 

epidemiological evidence is not required to prove causation, if 

it exists, an expert cannot ignore it. Perry, supra, 564 F. Supp.

2d at 465. However, the existence of inconclusive epidemiological 

studies does not preclude an expert from relying on alternative 

data, such as animal studies. Id. at 466. 

Moreover, although the Sivaraman epidemiological study was 

published as an abstract and not a full article, and was presented 
63 A-4698-14T1

 

at a conference, our courts recognize that "[s]upport for an 

expert's methodology may be found in professional journals, texts, 

conferences, symposia, or judicial opinions accepting the 

methodology." Kemp, supra, 174 N.J. at 427. In accord with 

accepted scientific methodology, Kornbluth also considered other 

forms of evidence in determining causation, including animal 

studies, case reports, challenge/dechallenge/rechallenge reports, 

causality assessments, class effects, and published scientific 

literature. Although case reports and causality assessments 

should be interpreted with caution, there was nothing so inherently 

unreliable about the materials Kornbluth cited as to preclude 

their consideration as part of a scientific expert's methodology 

under N.J.R.E. 702. Further, the experts did not elevate this 

evidence over the epidemiological studies, but rather considered 

this evidence in forming their opinions. 

B. Methodology and Reasoning

We also conclude that the methodology used by Kornbluth and 

Madigan to reach their conclusions was consistent with sound 

scientific principles and methodologies accepted in the medical 

and scientific community. Rubanick, supra, 125 N.J. at 449; Kemp, 

supra, 174 N.J. at 431. In making that determination the court 
64 A-4698-14T1

 

must "examine the manner in which experts reason from the studies 

and other information to a conclusion." Landrigan, supra, 127 

N.J. at 420. The experts' conclusions "must derive from a sound 

methodology that is supported by some consensus of experts in the 

field." Ibid. The experts must identify the factual bases for 

their conclusions, explain their methodology, and demonstrate that 

both the factual bases and the methodology are reliable. Kemp, 

supra, 174 N.J. at 427; Rubanick, supra, 125 N.J. at 449-50. 

The primary focus in this appeal is upon Kornbluth's and 

Madigan's analysis of the epidemiological studies. Those studies 

indicated that the relationship between Accutane and Crohn's 

disease is more tenuous than the relationship between the drug and 

ulcerative colitis. For example, Crockett (a large study) found 

a statistically significant association between Accutane and 

ulcerative colitis, and four studies (Bernstein, Etminan, Racine 

and Alhusayen) found a positive association between the drug and 

the disease. 

In contrast, only one small study (Sivaraman) found a 

statistically significant positive association (before adjustment 

for antibiotic use) between Accutane and Crohn's disease, two 

found a positive association (Bernstein and Alhusayen), three 
65 A-4698-14T1

 

found a negative association (Crockett, Etminan, and Racine), and 

one (Racine) found a statistically significant association for a 

protective effect. The degree to which this contrary opinion 

dominates the epidemiological studies is relevant to the 

reliability inquiry. DeLuca, supra, 911 F.2d at 955. However, 

demonstrable flaws in the studies may undercut their significance. 

Ibid. 

In other words, does the relevant scientific community accept 

the process by which Kornbluth and Madigan reasoned to a conclusion 

that the epidemiological studies (despite the lack of a 

statistically significant association) and the other relevant 

evidence supported a finding of a causal relationship between 

Accutane and Crohn's disease? In some cases, a court may conclude 

that there is simply too great an analytical gap between the data 

and the expert's opinion. See Gen. Elec. Co. v. Joiner, 522 U.S.

136, 146, 118 S. Ct. 512, 519, 139 L. Ed. 2d 508, 519 (1997). 

However, in this case, we conclude that the data was sufficient 

to permit the experts to testify, and any weaknesses in their 

opinions can be explored through cross-examination. 

It is well-established that "[t]he usefulness of an 

epidemiological study depends on the quality of the underlying 
66 A-4698-14T1

 

data, the reliability of the methodology, and the validity of the 

interpretations." Landrigan, supra, 127 N.J. at 420 (quoting 

Michael Dore, A Commentary on the Use of Epidemiological Evidence 

in Demonstrating Cause-in-Fact, 7 Harv. Envtl. L. Rev. 429, 432 

(1983)). An expert should, under sound scientific methodology, 

evaluate the study in assessing its validity. See ibid. We infer 

from the Manual that an expert should consider a study's possible 

flaws and weaknesses before deciding whether to rely on it. 

Reference Manual, supra, at 553. Further, an expert can rely on 

the data generated from a study even if he or she disagrees with 

the author's conclusion, and need not subject his or her own 

analysis to peer review. DeLuca, supra, 911 F.2d at 954. 

Here, in contrast to the court's finding, Kornbluth and 

Madigan, in accordance with established scientific methodology, 

evaluated all of the epidemiological and prodrome studies, not 

just Sivaraman and Pimentel. They testified at length as to the 

design flaws and limitations of the epidemiological studies, 

including the failure to account for the prodrome, insufficient 

power, and design flaws, which are all recognized in the scientific 

community as capable of producing an erroneous association in an 

epidemiological study. See Reference Manual, supra, at 583. For 
67 A-4698-14T1

 

example, a poorly conceived or conducted study that disproves the 

null hypothesis at a high level of significance may be far less 

reliable than a well-conceived and conducted study that is 

significant at a lower level. DeLuca, supra, 911 F.2d at 955.30 

Moreover, the fact that defendants' experts interpret the 

epidemiological studies differently does not, standing alone, 

indicate that Kornbluth and Madigan failed to rely upon a sound 

methodology. "Indeed, 'in most cases, objections to the 

inadequacies of a study are more appropriately considered an 

objection going to the weight of the evidence rather than its 

admissibility.'" Rosenfeld v. Oceania Cruises, Inc., 654 F.3d 

1190, 1193 (11th Cir. 2011) (quoting Hemmings v. Tidyman's Inc., 

285 F.3d 1174, 1188 (9th Cir. 2002), cert. denied, 537 U.S. 1110, 

123 S. Ct. 854, 154 L. Ed. 2d 781 (2003)). 

That said, certainly, as the trial judge correctly observed, 

 

30 DeLuca was "a diversity action brought under New Jersey law" 

against the manufacturer of Benedictin. Id. at 942-43. 

Anticipating Daubert, the Third Circuit Court of Appeals rejected 

the Frye standard, and reversed a trial court decision barring 

testimony from an expert whose approach was remarkably similar to 

that of plaintiffs' experts in this case. Id. at 955. Although 

DeLuca is not binding on us, we find it persuasive. As previously 

noted, DeLuca was also one of the seminal federal cases cited with 

approval in Rubanick as being "compatible with our own rules of 

evidence." Rubanick, supra, 125 N.J. at 445, 447. 
68 A-4698-14T1

 

larger studies enable researchers to form a more accurate 

conclusion and reduce the chance of random error in their results. 

Reference Manual, supra, at 576. However, Kornbluth could, in 

applying accepted scientific methodology, properly consider one 

small well-designed study over larger seriously flawed studies as 

a basis for drawing an inference about the studied subject.31 

Further, Kornbluth did not ignore the results of the larger studies 

in favor of the smaller Sivaraman study, but considered the 

relative risk and the bounds of the 95% confidence interval in 

reviewing the conclusions. He also found that although the results 

of the studies were inconclusive, they were informative on his 

theory of causation. For example, he noted that four of the studies 

(Bernstein, Etminan (unadjusted), Alhusayen, and Sivaraman) found 

a positive association between Accutane use and Crohn's disease, 

and that one of the studies (Bernstein) showed an increased 

association when accounting for a two-year but not a one-year 

prodrome. 

 

31 Scientific acceptance of small studies is not unknown. A 

treatise on pharmacoepidemiology, which is included in the 

parties' appendices, notes that "using case control studies, one 

can study rare diseases with markedly smaller sample sizes. . . . 

For example, the classic study of diethylstilbestrol and clear 

cell adenocarcinoma required only 8 cases and 40 controls." (Brian 

L. Strom, Pharmacoepidemiology 23 (4th ed. 2006)). 
69 A-4698-14T1

 

Similarly, Kornbluth testified at length as to the results 

of both the Pimentel (6.9-year prodrome) and Barratt (four-year 

prodrome) prodrome studies and opined that the results of those 

studies were in agreement with his decades of experience treating 

thousands of Crohn's disease patients. Kornbluth and Madigan 

rejected, but did not ignore, the findings of the Chouraki study 

based on the selection of patients and the use of patient charts. 

Further, Madigan testified that the Pimentel study, which utilized 

questionnaires, contained the most useful and relevant data, 

including raw data from which he could compute age-specific 

estimated prodromes.32

Kornbluth's methodology in analyzing the epidemiological 

studies was also bolstered by Madigan, who presented detailed 

testimony as to the insufficient power of the epidemiological 

studies. Further, Madigan testified that the decision whether to 

conduct a meta-analysis is a scientific judgment, and explained 

 

32 Our reading of the Pimentel article supports Kornbluth's 

description of the authors' very meticulous approach to gathering 

and verifying information about the subjects. We cannot agree 

with the trial judge's view that Kornbluth was "cherry picking" 

in relying on Pimentel. Kornbluth cogently explained why he 

believed that the authors' methodology was reliable, and 

consistent with his own medical practice in diagnosing Crohn's 

disease patients. 
70 A-4698-14T1

 

that such an analysis would not yield reliable results in this 

case. Instead, he conducted and reviewed a disproportionality 

analysis, which while not without limitations, is a validated 

method in drug safety research and surveillance. 

Both Kornbluth and Madigan explained in considerable detail 

why most of the studies were biased toward "the null" or no effect, 

and were otherwise inadequate to reliably demonstrate whether or 

not there was a statistically significant connection between 

Accutane and Crohn's disease. They also explained why the 

statistically significant initial results of the Sivaraman study 

were more reliable than the adjusted results. 

The reliability of Kornbluth's opinion on causation was also 

strengthened by his consideration of other evidence (including 

case reports, animal studies, and causality assessments), and most 

notably, because he presented a biologically plausible mechanism 

for how Accutane causes Crohn's disease. See Reference Manual, 

supra, at 604 ("When biological plausibility exists, it lends 

credence to an inference of causality"). Once Kornbluth found 

that there was an association between Accutane and Crohn's disease 

based on his reading of the epidemiological studies, in addition 

to the scientific articles, MedWatch reports, and causality 
71 A-4698-14T1

 

assessments, he then considered whether that association was 

causal, utilizing the Bradford Hill criteria. Under that analysis, 

he considered, among other criteria, whether there was a 

biologically plausible mechanism by which Accutane could cause 

Crohn's disease—an important factor for determining a causal 

relationship. 

Kornbluth, like plaintiffs' causation expert in previous 

Accutane trials, presented a biologically plausible mechanism 

supported by scientifically authoritative sources. He opined, 

based on his experience as a board-certified gastroenterologist 

and in conducting clinical trials on several drugs intended for 

use in the management of IBD, that retinoic acid, a metabolite of 

Accutane, "is a damaging pathway for patients with Crohn's 

disease." He found support for that opinion in the fact that two 

new drugs (Vedolizumab and Natalizumab) were effective in treating 

Crohn's disease and in a Canadian case-control epidemiological 

study that reported an increased risk of Crohn's disease from 

retinoic acid. Olivia-Hemker disagreed with that opinion and 

cited to other studies that supported a finding that retinoic acid 

had an anti-inflammatory or protective effect on the intestines, 

but that dispute goes to the weight, not the admissibility of the 
72 A-4698-14T1

 

testimony. See Harvey, supra, 151 N.J. at 178.

In conclusion, Kornbluth and Madigan, who are indisputably 

extremely well-qualified experts, considered all of the relevant 

data and information, applied appropriate methodology in analyzing 

the epidemiological studies, and expressed valid reasons for 

rejecting the conclusions of some of the epidemiological studies 

and in accepting other studies as supportive of their opinion. 

Although the relationship between the epidemiological scientific 

evidence and the experts' opinions is more tenuous than the 

evidence as to ulcerative colitis, the studies do not render the 

experts' testimony inadmissible. The manner in which plaintiffs' 

experts reasoned from the results of the epidemiological studies 

and other data is sufficiently sound to be reliable. Landrigan, 

supra, 127 N.J. at 420. Further, the experts did not ignore the 

findings of the larger epidemiological studies but explained the 

scientific bases for their criticism of the studies. Defendants' 

criticisms of the experts' choices as to the evidence on which 

they relied, can be addressed during cross-examination at trial. 

Hisenaj, supra, 194 N.J. at 24. 

We also cannot agree with the trial court's view that because 

Kornbluth had not submitted his "current hypothesis" to a peer-
73 A-4698-14T1

 

reviewed publication, he must have generated his opinion solely 

as a result of litigation and was a mere "hired gun." An expert 

is not required to submit her own analysis to peer review in order 

for a court to consider it. See DeLuca, supra, 911 F.2d at 954. 

We also do not subscribe to the trial court's characterization of 

Madigan as a hired gun whose testimony "was needed to clear the 

way for Dr. Kornbluth's hypothesis and that was the role he played, 

without regard to whether or not his efforts led the discussion 

any closer to scientific truth." Madigan carefully explained his 

methodology and his testimony should not have been discounted 

because defendants heavily contested his conclusions. 

Given that our evidence rules embody a strong preference for 

admissibility, we conclude that the court mistakenly applied its 

discretion in excluding the expert scientific testimony. See

N.J.R.E. 702; N.J.R.E. 401; State v. Jenewicz, 193 N.J. 440, 454 

(2008) (noting "Rule 702's tilt in favor of the admissibility of 

expert testimony"); State v. Granskie, 433 N.J. Super. 44, 47-48 

(App. Div. 2013); Kuehn v. Pub Zone, 364 N.J. Super. 301, 320 

(App. Div. 2003) (expert's testimony was relevant to issues under 

consideration), certif. denied, 178 N.J. 454 (2004). 
74 A-4698-14T1

 

VI

In concluding, we emphasize the following observations. The 

trial court's decision, and our decision of this appeal, must be 

viewed in the context of this particular MCL litigation. It 

presents a close question concerning the survival of plaintiffs' 

cause of action in the face of new scientific information about 

Accutane and IBD. 

In deciding this appeal, we bear in mind that science is 

constantly evolving, and that under our State's legal precedents, 

legal decision making in toxic tort and similar cases may vary 

from scientific decision making. The opportunity of thousands of 

plaintiffs, claiming injury from Accutane, to have their day in 

court may rest on that difference and must be decided now. 

In general . . . clinical, regulatory, 

commercial, and legal decisions need to be 

made based on the best evidence available at 

the time of the decision. To quote Sir Austin 

Bradford Hill:

All scientific work is incomplete -

whether it be observational or 

experimental. All scientific work 

is liable to be upset or modified 

by advancing knowledge. That does 

not confer upon us a freedom to 

ignore the knowledge we already 

have, or to postpone the action that 

it appears to demand at a given 

time. 
75 A-4698-14T1

 

Who knows, asked Robert 

Browning, but the world may end 

tonight? True, but on available 

evidence, most of us make ready to 

commute on the 8:30 next day. 

[Pharmacoepidemiology, supra, at 26-27 

(quoting Hill, supra, at 295-300).] 

The parties in this case differ sharply on the question of 

what constitutes "the best evidence available at the time of the 

decision." Id. at 26. In particular, the case presents the 

question whether, in the face of several epidemiological studies 

that do not demonstrate a statistically significant relationship 

between taking Accutane and developing Crohn's disease, plaintiffs 

can continue to rely on other types of evidence - which in this 

same MCL docket they were previously permitted to use - to prove 

general causation. We also consider whether they can rely in part 

on information from some of the epidemiological studies that show 

a positive correlation, albeit not reaching the level of 

statistical significance. 

We conclude that in this case, the epidemiology studies are 

not a conclusive bar to plaintiffs' case, and that their experts 

should be allowed to testify. Although epidemiological studies 

are considered as high on the tier of evidence bearing on the 
76 A-4698-14T1

 

question of causation, like any other form of scientific evidence, 

any particular study is only valuable if it is conducted in a 

scientifically reliable manner. Any party - plaintiff or defendant 

- has the right to challenge the methodology and, hence the 

results, of an epidemiological study. 

In fact, the Reference Manual on Scientific Evidence cautions 

that 

[A]ll [epidemiological] studies have "flaws" 

in the sense of limitations that add 

uncertainty about the proper interpretation of 

the results. Some flaws are inevitable given 

the limits of technology, resources, the 

ability and willingness of persons to 

participate in a study, and ethical 

constraints. In evaluating epidemiologic 

evidence, the key questions, then, are the 

extent to which a study's limitations 

compromise its findings and permit inferences 

about causation. 

[Reference Manual, supra, at 553.]

After explaining some of the most common biases that may affect 

observational epidemiological studies, the Manual states that 

["t]here are dozens of other potential biases that can occur in 

observational studies, which is an important reason why clinical 

studies (when ethical) are often preferable." Id. at 590. Thus 

it can be expected that, as in this case, the methodology and 

limitations of epidemiological studies - particularly 
77 A-4698-14T1

 

observational studies - will be fertile ground for disagreement 

among experts. 

Moreover, the Manual supports plaintiffs' continued reliance 

on other types of evidence to prove their case, particularly given 

their well-explained opinions that most of the epidemiological 

studies are fundamentally flawed. Contrary to the trial judge's 

view, the Manual does not discount the value of live animal 

studies. While noting some potential weaknesses of the studies, 

the Manual states that toxicological studies, of which animal 

studies are one type, are "often . . . the only or best available 

evidence of toxicity." Id. at 564. The Manual also cautions that 

"[w]here both animal toxicologic and epidemiologic studies are 

available, no universal rules exist for how to interpret or 

reconcile them. Careful assessment of the methodological validity 

and power of the epidemiologic evidence must be undertaken, and 

the quality of the toxicologic studies and the questions of 

interspecies extrapolation and dose-response relationship must be 

considered." Id. at 564-65. 

The judge, and defendants, relied heavily on a section of the 

Manual captioned "Hierarchy of medical evidence" (the medical 

hierarchy section). Id. at 723. However, that section does not 
78 A-4698-14T1

 

appear in the Reference Guide on Epidemiology. Rather, the section 

appears in the Reference Guide on Medical Testimony, as part of a 

chapter on medical decision-making. That chapter describes how 

doctors make decisions about diagnosing and treating patients and 

discusses the difficulties they face in making those decisions. 

Id. at 704. We do not construe the medical hierarchy section of 

the Manual as prescribing a rigid hierarchy for the acceptance or 

rejection of evidence in a legal setting. See Matrixx Initiatives, 

Inc. v. Siracusano, 563 U.S. 27, 40-42, 131 S. Ct. 1309, 1318-20, 

179 L. Ed. 2d 398, 410-12 (2011); DeLuca, supra, 911 F.2d at 957.

In fact, the preface to the Manual cautions judges as to "the 

proper use of the reference guides. They are not intended to 

instruct judges concerning what evidence should be admissible or 

to establish minimum standards for acceptable scientific 

testimony." Reference Manual, supra, at xv. As significantly, 

nothing in the Manual suggests that once epidemiological studies 

have been done, they are beyond scientific criticism, and no 

countervailing evidence should be considered. 

We cannot agree with the trial judge's observation that 

plaintiff's experts "ignored" the epidemiological studies in favor 

of less reliable evidence. The experts did not ignore the studies. 
79 A-4698-14T1

 

Rather, in extensive and detailed testimony, they opined that most 

of the studies were unreliable, and they explained in considerable 

detail the reasons for those opinions. 

In their testimony, both of plaintiffs' experts raised 

fundamental objections to the way the studies were conducted -

particularly the length of time for which the studies followed the 

subjects. Based both on a prodrome study he found reliable and 

on the decades he has spent treating thousands of Crohn's patients, 

Dr. Kornbluth testified that the prodrome for Crohn's disease is 

much longer than the one-year time frame covered by most of the 

studies. Defendant's biostatistical expert, Dr. Goodman, admitted 

that if Dr. Kornbluth was correct about the prodrome, then all of 

the epidemiological studies on which the defense relied would be 

flawed. 

Kornbluth also explained in detail other weaknesses of 

several of the studies. For example, the Alhusayan study treated 

subjects exposed to Accutane as being non-exposed after a one-year 

period following treatment. Thus, if those subjects developed IBD 

after a year and a day, the study reported them as though they had 
80 A-4698-14T1

 

never taken Accutane.33 Kornbluth also explained that studies from 

other countries would not necessarily reflect the experience of 

United States subjects, because the standard dose of Accutane 

given to patients in those other countries is half that given to 

patients in the United States. 

Kornbluth's view on the prodrome issue was actually bolstered 

by some of the defense testimony. During her cross-examination, 

Dr. Oliva-Hemker was confronted with her own book, which answered 

the question "How long have I had my IBD" by advising that: "Some 

people have years of symptoms before the diagnosis [of IBD] is 

made, while in others, these symptoms appear suddenly. Both groups 

may have had intestinal inflammation for days, months, or years, 

even though they didn't experience any symptoms at all for most 

of that time." She then clarified that "we traditionally apply 

that more to Crohn's patients rather than ulcerative colitis 

patients in terms of [it taking] years" to diagnose the disease. 

She was also confronted with a book written by a recognized expert 

who referred to "the four-year average delay of diagnosis of 

 

33 Although the study authors downplayed the results, the Alhusayan 

study also discovered what the authors characterized as a "weak" 

but statistically significant connection between Accutane and the 

development of IBD in teenagers, ages twelve to nineteen.
81 A-4698-14T1

 

Crohn's disease." 

Oliva-Hemker also confirmed that IBD affects about one 

percent of the population in the United States; Crohn's disease 

is a small subset of IBD, so the proportion of persons with Crohn's 

is much smaller than one percent. Those admissions support the 

view of plaintiff's experts that a study's failure to detect even 

a small number of "exposed cases," i.e., persons with Crohn's 

disease who had taken Accutane, could produce skewed results.

Further, when it suits their litigation strategy, defendants 

do not treat epidemiological studies as the last word in scientific 

proof. During the cross-examination of Oliva-Hemker, she admitted 

that in earlier Accutane litigation, when four epidemiological 

studies - concerning the lack of connection between antibiotics 

and ulcerative colitis - did not support her opinion that the 

plaintiff's UC was caused by antibiotics rather than Accutane, she 

relied on evidence of biological plausibility instead. It took 

almost four pages of repetitive questioning before Oliva-Hemker 

finally admitted that the methodology she used was valid. Yet, 

in this litigation, she criticized Kornbluth for relying on 

evidence of biological plausibility and placing less weight on the 

epidemiological studies. 
82 A-4698-14T1

 

Additionally, during the cross-examination of defendant's 

epidemiology expert, Dr. Goodman, he admitted that some of the 

epidemiological studies in this case had biases and weaknesses. 

He admitted, for example, that none of the studies controlled for 

family history, even though that is recognized as a strong factor 

in a person's potentially developing Crohn's disease. He contended 

that scientific judgment was required to evaluate how important 

those biases or weaknesses were. Goodman was also confronted with 

some of his own writings, in which he stated that, "If bias is 

present in each or some of the individual studies, meta-analysis 

will simply compound the errors and produce a wrong result that 

may be interpreted as having more credibility." That same point 

was made by plaintiff's epidemiology expert, Dr. Madigan, and it 

finds support in the Manual. 

We appreciate that the trial judge had the opportunity, which 

we did not, to see the witnesses testify firsthand. However, his 

extreme negative reaction to plaintiffs' witnesses is not 

supported by the trial record. See J.R., supra, 227 N.J. at 410; 

Torres, supra, 183 N.J. at 567. In reviewing Madigan's testimony, 

we cannot agree with the judge that Madigan was a biased expert 

"on a mission." His testimony was coherent and consistent, and the 
83 A-4698-14T1

 

attorney who cross-examined him made little headway in 

discrediting his direct testimony. 

The judge's disapproval of plaintiffs' experts' reliance on 

"lines of evidence" seems misplaced, because the defense used 

the same terminology and considered the same evidence. Dr. OlivaHemker agreed that she and Dr. Kornbluth looked at the same lines 

of evidence, although they reached different conclusions from the 

evidence. Further, the defense experts generally agreed with the 

proposition that, in looking at the issue of causation, it is 

appropriate to consider all of the pertinent evidence and not just 

the epidemiological studies. The judge also criticized 

plaintiffs' experts for their skepticism about the use of metaanalysis. However, the Manual cautions that "when meta-analysis 

is applied to observational studies - either case-control or cohort 

- it becomes more controversial" due to the "methodological 

differences among studies." Reference Manual, supra, at 607. 

In summary, the purpose of a Kemp hearing is to weed out 

"junk science," not to shield jurors from hearing expert testimony 

that is scientifically-based but unpersuasive to the trial judge. 

Landrigan, supra, 127 N.J. at 417; Kemp, supra, 174 N.J. at 427. 

"[R]egardless of a trial judge's view of the weight a party's 
84 A-4698-14T1

 

evidence deserves, the judge should trust the jury to evaluate 

witness credibility and decide what weight to give each side's 

evidence." State v. Stubblefield, __ N.J. Super. __, __ n.6 (App. 

Div. 2017) (slip op. at 21 n.16). It is the jury's core function 

to weigh the credibility of expert witnesses, and the trial court 

should not use a Kemp hearing as a vehicle to dismiss a case the 

court perceives as weak." Vigorous cross-examination, 

presentation of contrary evidence, and careful instruction on the 

burden of proof are the traditional and appropriate means of 

attacking shaky but admissible evidence." Daubert, supra, 509 

U.S. at 596, 113 S. Ct. at 2798, 125 L. Ed. 2d at 484. 

We conclude that the trial court misapplied its discretion 

in barring Dr. Kornbluth and Dr. Madigan from testifying. 

Accordingly, the orders entered in A-4698-14 and A-0910-16, 

barring their testimony and dismissing the complaints on summary 

judgment, are reversed and these cases are remanded to the trial 

court for further proceedings. We do not retain jurisdiction.

Reversed and remanded.