T.M. v. Janssen Pharm. Inc.
| Decision Date | 16 July 2019 |
| Docket Number | No. 184 EDA 2018,184 EDA 2018 |
| Court | Pennsylvania Superior Court |
| Parties | T.M. and Brenda Tinkham Appellants v. JANSSEN PHARMACEUTICALS INC.; Johnson & Johnson; Janssen Research & Development, LLC; Excerpta Medica, Inc.; and Elsevier Inc. |
Charles L. Becker, Philadelphia, for appellants.
Robert C. Heim, Philadelphia, for appellees.
T.M. 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"),1 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.2 We vacate the judgment, reverse the order entering a compulsory nonsuit, and remand for a new trial.
We 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.3 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.4 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.
In May 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,5 and fraud. A jury trial commenced on November 28, 2016.
At 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 36.6 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).
Plaintiffs 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.
Dr. 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 "neutraliz[ing] safety and tolerability concerns." Id. ; Videotaped Deposition of David Kessler, M.D., supra at 82.
In 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."7 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 percent.
Dr. 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.
Dr. 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.
The 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.
Janssen 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.8
During 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.
In May 2002, Janssen conducted a post hoc analysis of data from five of the eighteen earlier studies. RIS-INT-41 data was included; RIS-IN...
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