Benita Pledger dabbed at her tears as she sat in a wooden chair outside a court room in Philadelphia's City Hall early Thursday evening.
"I'm just having a hard time right now," she said, "hearing what the pharmaceutical company was doing."
Pledger had just finished a full day of listening to her attorney, Thomas Kline, and former U.S. Food and Drug Administration commissioner Dr. David Kessler discuss documents that showed Johnson & Johnson's Janssen Pharmaceutical subsidiary tried to manipulated data in versions of reports to hide evidence that the company's antipsychotic drug Risperdal had caused boys like her son to grow breasts.
"The most important thing for me, as someone who worked for the FDA, as a physician and as somebody who served on the boards of pharmaceutical companies, is you tell the truth and you tell the whole truth," Kessler said on the stand. "You tell the whole story. You make sure the data supports the message. What they want to convey doesn't match what the data shows and to me, that doesn't tell the whole story. Make sure the FDA knows and make sure the doctors know. Tell them the good and the bad."
Pledger and her husband sued J&J in Philadelphia's Court of Common Pleas, alleging that Risperdal caused their son to grow breasts, a condition called gynecomastia. Judge Ramy Djerassi is presiding over the trial, which might run four weeks.
Kline and Kessler focused Thursday on a 2001 study conducted by Janssen that showed some children (under 12) and adolescents (12 and older), who were already taking Risperdal, had higher-than-normal incidence of gynecomastia. Company emails and drafts of manuscripts being prepared for publication, which were shown in court Thursday, indicate an effort to re-analyze data so as to downplay the prevalence of gynecomastia.
"Janssen appropriately analyzed and reported data from clinical trials," Janssen spokeswoman Robyn Reed Frenze said in a statement. "Risperdal continues to help countless children and adults around the world who suffer from the debilitating effects of schizophrenia, bipolar mania and irritability associated with autistic order in children.
Risperdal was originally approved in 1993 only to treat psychotic disorders in adults. "On March 3, 2002, the approved use was narrowed to treatment of schizophrenia only," phrasing used by the Justice Department in 2013 in its statement after J&J agreed to pay $2.2 billion for settle one criminal charge and other allegations that it illegally promoted Risperdal for unapproved uses.
Doctors are allowed to prescribe medicine as they see fit, including "off-label," meaning for conditions not approved by the FDA and on the official label. Drug companies are not supposed to promote drugs for illnesses or for a group of patients for whom the drug is not approved and not on the label. But the squishiness of definitions of mental illness opens the door even wider for drug companies do such promotion.
Pledger's son is severely autistic. He is 20 now. He was eight when she filled the first prescription in August 2002 at Walmart near the family's home in Alabama. Benita Pledger was reluctant to try medicine when the subject was first raised by her son's pediatric neurologist, but her son's behavior problems, the melt-downs at home and school, prompted her to eventually try Risperdal. He used it until April 2007.
Risperdal was not FDA approved for use in children for any illness until 2006, so officially Janssen could not promote the use of the drug in children. But Jan Mathisen, the pediatric neurologist for Pledger's son, testified Monday that a Janssen sales rep came to his office 20 times between 2002 and 2004. He said he knew he was the most frequent prescriber of the drug in the state. But he also wanted samples for his patients, especially those with challenging financial circumstances. In her 2012 deposition, Benita Pledger said her husband was a self-employed mechanic and the family had no health insurance. She heard about gynecomastia on TV. When the J&J attorney asked in deposition if she had explored Risperdal on the Internet before suing, Benita Pledger said the family had no Internet access.
One of the challenges with many drug candidates for children is that parents are reluctant to have a drug tested on their children. It is perhaps telling that in 2001, when Janssen was pushing for approval to expand the approved uses on its existing official label and sell Risperdal for use in autistic children, it had plenty of children to use in clinical trials to answer FDA questions.
Prolactin is a hormone produced by the pituitary gland and is normally present in low amounts in men and non-pregnant women. Prolactin's primary role is to promote lactation.
Kline and Kessler focused on a Janssen study that showed higher prolactin levels and incidence of gynecomastia, especially in boys but also in a few girls taking Risperdal. They went through emails, company plans, changes to plans and multiple versions of a manuscript the company hoped would be published in a peer review journal to help its case with the FDA.
Kessler testified that based on the documents, Janssen appeared to have changed how it grouped patients in the one study and then merged the data with other studies to report a less significant potential risk.
"You certainly don't want to change your plan after you know your results," Kessler said.
J&J's attorney, Diane Sullivan, who declined comment after court Thursday, fought all week to keep the emails, documents and draft manuscripts from being submitted as evidence, shown to the jury and used as a basis for questioning of Kessler. Trying again Thursday, she said drug companies can't unilaterally change the label on a drug, that the label and any warnings must be decided in conjunction with the FDA.
Technically that is correct, Kessler said, but not in reality.
"A manufacturer can always warn about a safety issue and should warn about a safety issue," Kessler said. "There is nothing in the federal register that prevents a manufacturer from warning about a safety problem and there are many different ways. If somebody is sending a sales rep into a doctor's office, into a pediatric neurologist's office and doing it multiple times, you have an obligation to provide adequate direction. If you have information on a safety issue, you have to communicate that. Tell the good. Tell the bad."