T.M. AND BRENDATINKHAM APPELLANTS
JANSSEN PHARMACEUTICALS INC.; JOHNSON & JOHNSON; JANSSEN RESEARCH & DEVELOPMENT, LLC; EXCERPTA MEDICA, INC.; AND ELSEVIER INC.,
from the Judgment Entered December 4, 2017 In the Court of
Common Pleas of Philadelphia County Civil Division at No(s):
1076 May Term, 2013
BEFORE: BOWES, J., STABILE, J., and MCLAUGHLIN, J.
and his mother, Brenda Tinkham, ("Plaintiffs")
appeal from the December 4, 2017 judgment entered in favor of
Janssen Pharmaceuticals, Inc., Johnson & Johnson, Janssen
Research & Development, LLC ("Janssen"),
following entry of a compulsory nonsuit in
their action seeking damages for the drug manufacturer's
failure to adequately warn of the risk of gynecomastia
associated with Risperdal use in children. We vacate the
judgment, reverse the order entering a compulsory nonsuit,
and remand for a new trial.
glean the following from the evidence offered by Plaintiffs
at trial. In 2004, T.M. was seven years old and living with
his family in Wichita Falls, Texas. When he began acting out in
school, his parents arranged for a mental health evaluation
at the Rose Street Mental Health Clinic. Physician Assistant
John Dewar diagnosed him with attention deficit hyperactivity
disorder ("ADHD"), oppositional defiant disorder
("ODD"), and depression, and under the supervision
of pediatric psychiatrists Harvey Martin, M.D. and Brian
Wieck, M.D., prescribed Risperdal for T.M. Risperdal was not
approved by the Food and Drug Administration
("FDA") for use in children, or for the indication
for which it was prescribed. As approved, the drug was
indicated only for adults with schizophrenia. Thus, Risperdal
was prescribed for T.M. for an off-label use. At the time,
Risperdal was known to cause increased prolactin levels
associated with gynecomastia and other endocrine disorders.
T.M. remained on Risperdal for three and one-half years. In
2006, T.M. developed breasts.
2013, Plaintiffs filed the instant case against Janssen, the
manufacturer and distributor of Risperdal, alleging negligent
failure to provide adequate warnings of the known risk of
gynecomastia associated with its drug,  and fraud. A jury
trial commenced on November 28, 2016.
trial, Plaintiffs offered the testimony of David Kessler,
M.D, a physician specializing in pediatric medicine and
public health, who served as the Commissioner of the FDA from
1990 through 1997, and who was formerly a biostatistics
professor at the University of California and Dean of the
Yale Medical School. Dr. Kessler provided expert testimony
establishing that Janssen had a duty to warn of the known
risks of gynecomastia with Risperdal use, and that it
breached that duty. Dr. Kessler traced the history of
Risperdal, explaining that it was a second-generation
antipsychotic drug manufactured and marketed by Janssen. It
was first approved by the FDA in 1993 for the treatment of
adults with psychotic disorders such as schizophrenia. In
1996, Janssen asked the FDA for permission to include dosing
information for children on the label as it was "aware
that Risperdal was being utilized in children in
adolescence" for off-label uses such as ADHD. Videotaped
Deposition of David Kessler, M.D. 12/2/16, at
The FDA refused the request, citing "inadequate support
for the changes sought." Id. at 40.
Specifically, the FDA cited the "meager safety
data" for Risperdal's pediatric use, and it feared
that the proposed labeling would promote use in pediatric
patients without justification. Id. at 41-42;
see also Plaintiffs' Exhibit 8 (letter from Paul
Leber, M.D. to Janssen, 9/17/97).
offered into evidence the 2002 package insert for Risperdal,
often referred to as the "label." Plaintiffs'
Exhibit 2. Dr. Kessler pointed to language therein that the
drug's "[s]afety and effectiveness in children have
not been established." Id. Under
"Precautions," the label listed
"hyperprolactinemia," a condition in which one has
higher than normal serum levels of the hormone prolactin, the
main function of which is to stimulate breast milk production
after childbirth. The label also provided that "[a]s
with other drugs that antagonize dopamine D receptors,"
elevated prolactin levels persisted "during chronic
administration." Id. at 42. The label
acknowledged that although disturbances such as galactorrhea
(the expression of breast milk), amenorrhea (absence of
menstrual period), impotence, and gynecomastia (feminization
of the male breast) had been reported with
prolactin-elevating compounds, it stated that, "the
clinical significance of elevated prolactin levels is unknown
for most patients." Id. at 18, 21. The contents
of the Risperdal label remained the same until 2006.
Kessler testified that, in 2004, when Risperdal was
prescribed off-label for T.M., Janssen was actively marketing
the drug to physicians for off-label use in children.
Janssen's July 29, 2002 business plan listed strategic
initiatives associated with gaining acceptance of the usage
of antipsychotics in child and adolescent psychology.
Plaintiffs' Exhibit 19. This included "establishing
Risperdal as having a favorable risk/benefit ratio" and
"neutralizing] safety and tolerability concerns."
Id.) Videotaped Deposition of David Kessler, M.D.,
supra at 82.
2006, the Risperdal label was changed. Pediatric use fell
under the "Precautions" section of the 2006 label.
The label indicated that Risperdal was approved by the FDA
for use in children to treat irritability associated with
autism, and that its safety and efficacy in treating children
with schizophrenia and bipolar mania had not been
established. It reported that Risperdal's safety and
efficacy had been established in short-term clinical trials
in autistic children ages five to sixteen; longer term
studies in autistic children; and other short-term and
long-term studies of children with other psychiatric
disorders. For the first time, the label disclosed that
Risperdal was associated with higher prolactin levels than
other antipsychotic drugs in the same class. Again, it warned
of hyperprolactinemia, and the conditions associated with it,
including gynecomastia, but stated that the risk of such side
effects was "rare."Plaintiffs' Exhibit 3 (2006
Label). In 2007, the label was updated to warn that the
incidence of gynecomastia with the use of Risperdal was 2.3
Kessler then surveyed the studies and clinical trials Janssen
had undertaken to test the safety and efficacy of Risperdal
in young children and adolescents. Janssen carried out two
short-term double-blind studies of children and adolescents
ages five to seventeen years of age, completed in 2000, which
demonstrated that forty-nine percent of the children who
received Risperdal had elevated prolactin levels as compared
to two percent of children who received a placebo. From the
foregoing, the expert concluded that the results showed a
statistically significant association between ingestion of
Risperdal and higher prolactin levels and, further, that
higher prolactin levels were known to be associated with
certain conditions, including gynecomastia.
Kessler explained that, in 2000, Janssen initiated an
international study known as RIS-INT-41, which was intended
to pay special attention to gynecomastia in boys and other
prolactin-related events in children taking Risperdal.
Risperdal was administered in two different doses to children
with various levels of mental retardation and conduct
disorder. The interim results showed that of the 266 males,
ten were diagnosed with gynecomastia, an incidence rate of
3.75 percent. Sixteen of 319 patients had a prolactin-related
adverse effect, a rate of 5 percent. In Dr. Kessler's
opinion, this finding was a "red flag." Videotaped
Deposition of David Kessler, M.D., supra at 56.
RIS-INT-41 study continued for another year. As of August
2001, there were twenty-six documented cases of
prolactin-related adverse events in 504 children, an
incidence of 5.15 percent. Twenty-four of the twenty-six
children with prolactin-related adverse events had
gynecomastia, and twenty-three of them were male. Dr. Kessler
opined that there was an obligation on the part of Janssen
"certainly by July 2001" to convey this information
to physicians who were prescribing the drug off-label to
children. Id. at 65.
initiated a second study, RIS-INT-70, which was an extension
of RIS-INT-41. Dr. Kessler reported that there were four
additional cases of gynecomastia in children who participated
in both studies, a risk of 8.3 percent. The children who
participated only in RIS-INT-70 had an incidence of
gynecomastia of 12.5 percent. Id. at 70.
the early 2000s, Janssen conducted eighteen clinical studies
with pediatric patients, some of which were double-blind,
i.e., involved a placebo, and others that were
open-lab studies. Six of the studies lasted up to six months.
RIS-INT-41 and RIS-INT-70 were the only long-term studies,
and the only studies that paid special attention to
prolactin-related adverse events such as gynecomastia. The
eighteen studies encompassed 1, 885 subjects from five to
eighteen years of age. In the double-blind studies, no
children who received a placebo were diagnosed with
gynecomastia. Eight of nine cases of gynecomastia reported
were related to the long-term studies. Dr. Kessler testified
that the studies indicated that gynecomastia was manifested
over time after exposure and that short-term studies did not
capture the actual number of related cases. Id. at
72-79; Plaintiffs' Exhibit 17. Dr. Kessler informed the
jury that, in January 2002, Janssen's own studies showed
a significant association of 4.4% between hyperprolactinemia
and gynecomastia in young males.
2002, Janssen conducted a post hoc analysis of data
from five of the eighteen earlier studies. RIS-INT-41 data
was included; RIS-INT-70 data was not. Dr. Kessler opined
that Janssen was attempting to prove that Risperdal was not
related to elevated prolactin levels, but the data proved
otherwise. Analysis of the data showed a rate of 4.4% of
gynecomastia. Plaintiffs' Exhibit 22. More importantly,
he focused on one particular item of Janssen's supporting
documentation, Table 21, which revealed that there were more
prolactin-related side effects in Risperdal patients whose
prolactin levels were higher. Dr. Kessler explained that
Table 21 demonstrated a causal correlation between high
prolactin levels and "prolactin related adverse
effects," called PRAE, one of which was gynecomastia. He
opined that the correlation was statistically significant, as
there was a 98.5% likelihood that the side effects did not
occur randomly. Internal Janssen emails confirmed, according
to Dr. Kessler, that Janssen was aware of the significance of
the findings. Based on the foregoing evidence of a causal
connection between Risperdal and elevated levels of
prolactin, and higher levels of prolactin and gynecomastia,
Dr. Kessler opined that Janssen had a duty to warn physicians
who were prescribing the drug off-label to children and to
notify the FDA. Id. at 121.
to Dr. Kessler, Janssen breached its duty to disclose Table
21 to the FDA, and withheld data showing the correlation
between elevated prolactin levels and prolactin related
adverse effects such as gynecomastia from its own
endocrinologist and psychiatrist consultants. The expert
demonstrated how Janssen manipulated the study data in such a
way as to reduce the statistical significance of the
association between Risperdal and boys with gynecomastia, and
alleged that Janssen funded the publishing of a misleading
article in the Journal of Clinical Psychiatry. Id. at
also offered the expert testimony of Mark Solomon, M.D., a
plastic surgeon with expertise in gynecomastia and diseases
of the breast. He examined T.M., who was at the time was
twenty-one years of age, and confirmed that T.M. suffered
from true gynecomastia. After reviewing the medical
literature about Risperdal, T.M.'s family history, his
medical records, and ruling out other possible causes of
T.M.'s gynecomastia, Dr. Solomon concluded, with a
reasonable degree of medical certainty, that Risperdal was
the cause of T.M.'s gynecomastia. N.T. Trial (Jury),
12/7/16, at 71. He explained that, although T.M.'s family
physician in Nebraska only diagnosed him with gynecomastia on
May 19, 2010, his breasts had started to develop in 2006. Dr.
Solomon opined that the timing was consistent with the
development of breast tissue generally, and that T.M.'s
early breast development could be seen in photographs from
Plaintiffs attempted to elicit additional testimony from Dr.
Solomon about two studies he had reviewed and relied upon in
reaching his opinions, Janssen objected to the testimony on
the ground that Dr. Solomon had not identified them in his
expert report. N.T. Trial (Jury), 12/7/16, at 53.
Janssen maintained that it lacked fair notice of Dr.
Solomon's testimony in this regard. Plaintiffs countered
that since Janssen had cross-examined Dr. Solomon in other
trials and depositions regarding the same articles, there was
no surprise and no prejudice. Moreover, Plaintiffs argued
that Janssen had been afforded the opportunity to depose Dr.
Solomon in this case, but had declined. The trial court
sustained Janssen's objection under Pa.R.C.P. 4003.5,
finding that the expert's testimony regarding the
literature and studies he relied upon was beyond the fair
scope of his expert report, and precluded the expert's
testimony in this regard. However, on cross-examination, Dr.
Solomon testified that his opinion that Risperdal caused
elevated prolactin levels was informed by his review of the
literature, the package inserts, and Janssen's documents.
N.T. Trial (Jury), 12/7/16, at 91.
addition to the foregoing proof regarding the inadequacy of
the Risperdal label, Janssen's failure to accurately
report the drug's role in elevating prolactin levels and
gynecomastia, and ingestion of Risperdal as the cause of
T.M.'s gynecomastia, Plaintiffs offered the following
proof to rebut the presumption under the TPLA that the label
was adequate. The prescribed use in T.M., a child, was
off-label and not approved by the FDA. Furthermore, it was
not FDA-approved for ADHD or conduct disorders. Dr. Martin,
Dr. Wieck, and Physician Assistant Dewar testified that
Janssen had actively promoted the use of Risperdal in
children, and that the marketing had influenced them to
prescribe Risperdal for T.M. for an off-label use. Dr. Wieck,
the psychiatrist who supervised the prescribing of Risperdal
for T.M., attended a Janssen meeting, all expenses paid, in
Miami Beach. In addition, just days before Dr. Wieck
prescribed Risperdal for T.M., he had a visit from a Janssen
representative, who talked about the use of Risperdal to
treat younger children with agitation and anxiety and conduct
disorders generally. The prescribers testified that if they
had been aware that the real risk of gynecomastia with
Risperdal was frequent rather than rare, and that Risperdal
was linked to a greater elevation of prolactin levels than
other antipsychotic drugs in the same class, they would have
prescribed another medication instead. Brenda Tinkham
testified that she was not told of the risk of gynecomastia
or breast development when Risperdal was recommended for T.M.
N.T. Trial (Jury), 12/8/16, at 60. Had she known, she stated
she would not have agreed to its administration to T.M.
Id. at 44, 60.
December 9, 2016, at the close of Plaintiffs' case,
Janssen orally moved for a nonsuit. It alleged first that
Plaintiffs failed to produce sufficient evidence to rebut the
presumption under the TPLA that the FDA-approved warning was
adequate. Specifically, Janssen maintained that Plaintiffs
failed to prove that Janssen promoted or advertised Risperdal
for an indication not approved by the FDA, or that plaintiff
used it for an off-label use, and that Janssen's
off-label promotion caused the prescriber to prescribe it for
the off-label use.
Janssen argued that Dr. Solomon's opinions did not meet
the general or specific causation requirements for scientific
reliability under Texas law, including proof of two
epidemiological studies demonstrating a statistically
significant doubling of the relative risk. Janssen maintained
that the 2007 photographs of T.M. that Dr. Solomon testified
showed budding breasts could not overcome the fact that T.M.
stopped the medication in 2008 and was first diagnosed with
gynecomastia in 2010. Finally, Janssen argued that there was
a complete failure of proof as to fraud.
countered that they could maintain the action as they had
rebutted the presumption under Texas's Products Liability
Act that the warnings were adequate by introducing proof that
Janssen promoted Risperdal for an indication that was not
approved by the FDA; that the drug was used as promoted; and
that T.M.'s gynecomastia was causally related to the
promoted off-label use of Risperdal. See Tex. Civ.
Prac. & Rem. Code § 82.OO7(b)(3)(A-C).
argued that Texas law did not require proof of
epidemiological studies to prove general or specific
causation. Furthermore, they maintained that Texas's
standards governing the reliability of scientific evidence of
general or specific causation under Texas law were not
substantive. They maintained that Pennsylvania adheres to
Frye v. United States, 293 F. 1013 (D.C. Cir. 1923),
and that the issue was one of procedure and not a question
governed by Texas substantive law.
trial court granted the nonsuit, finding that Texas law as
enunciated in MerrellDow Pharm. v. Havner, 953
S.W.2d 706 (Tex. 1997), and Merck & Co. v.
Garza, 347 S.W.3d 256, 266 (Tex. 2011), governed the
issue of the sufficiency of expert scientific testimony
regarding medical causation. It then construed
Havner and Garza as strictly requiring
Plaintiffs to introduce the following proof of causation: 1)
two epidemiological studies proving general causation,
i.e., that exposure to a particular agent causes or
increases the risk of the injury sustained; 2) that those
studies demonstrated a doubling of the relative risk; and 3)
that the plaintiff is similarly situated to the study
participants. The trial court ruled that Dr. Solomon failed
to introduce at least two epidemiological studies
demonstrating a doubling of the risk for purposes of general
causation and testify that T.M.'s circumstances were
similar to those of the study subjects. The court reasoned
that Plaintiffs could not rely upon Janssen's clinical
trials, RIS-INT-41 and RIS-INT-70, to meet the requirement
set forth in Havner because the studies did not show
a doubling of the risk for gynecomastia or demonstrate that
the subjects of those studies were similar to T.M. Thus, the
court concluded that Plaintiffs' evidence was
insufficient under Texas law to make out a prima
facie failure to warn claim as it lacked the scientific
reliability to prove that exposure to Risperdal caused
gynecomastia, and that T.M. developed gynecomastia due to his
ingestion of Risperdal.
filed a post-trial motion, which the trial court denied.
Plaintiffs appealed, both Plaintiffs and the trial court
complied with Pa.R.A.P. 1925, and the matter is ripe for our
1. Did the trial court improperly enter nonsuit given the
evidence introduced at trial ...