European Study Says Depakote Caused Thousands of Severe Birth Defects

A new European study finds that pregnant women who took epilepsy drug valproate — sold in the US as Depakote — were four times more likely to give birth to a baby with birth defects.

The report, jointly issued by the French National Agency for the Safety of Medicines (ANSM) and the national health insurance administration, confirmed that the drug is “highly teratogenic”, meaning that it can disturb the development of an embryo.

A total of 129 lawsuits, involving about 698 plaintiffs, have been filed against Abbott Laboratories in In Re Depakote, Case No. 12-CV-52-NJR-SCW, in the Southern District of Illinois before US District Judge Nancy J. Rosenstengel.

  • Plaintiffs recovered $38 million in punitive and compensatory damages against Abbot in May 2015. Attorneys from Williams Kherkher argued that Abbott underplayed the risk of birth defects, making it appear that Depakote had about the same level as other anti-epileptic drugs available.  As attorneys John Eddie and John Boundas were able to argue, in reality it was the most dangerous anti-epileptic drug.
  • Last November there was a £10.7m ($13.8 million) settlement in France for people harmed by sodium valproate during pregnancy.

On the market since 1967

Valproate — known in France under the brand name Depakine — has been on sale there since 1967, and in Britain under the name Epilim since 1973. In the US, Depakote was approved by the FDA in June 1996 to treat epilepsy.

Valproate products are FDA-approved drugs to treat seizures, and manic or mixed episodes associated with bipolar disorder (manic-depressive disorder), and to prevent migraine headaches. They are also used off-label (for unapproved uses) for other conditions, particularly for other psychiatric conditions.

The FDA warned doctors in December, 2009, that fetal exposure to valproate sodium (Depacon, Abbott), valproic acid (Depakene, Stavzor, Abbott), and divalproex sodium (Depakote, Depakote CP, Depakote ER, Abbott) is associated with birth defects, according to the US Food and Drug Administration (FDA).

The FDA said the drug can cause birth defects including neural tube, craniofacial, and cardiovascular defects, and warned doctors to “inform women of childbearing potential about these risks, and consider alternative therapies, especially if using valproate to treat migraines or other conditions not usually considered life-threatening.”

Depakote litigation

The first cases were filed in state court in 2010 and removed to federal court on January 18, 2012. Judge Rosenstengel said, “the bellwether process and global settlement efforts have failed,” after several trial dates fell through. As a result, “The Court intends to hold joint trials as to common issues of fact and law to the maximum extent possible.”

The judge intends to try the majority of the cases in joint trials by the end of 2017.

Judge Rosenstengel dismissed nine cases on April 12 under the Indiana repose issue, ruling that all the acts leading to the alleged birth defects in the nine cases took place in Indiana, and that Indiana’s 10-year statute of repose therefore applied. An Illinois statute favored by the plaintiffs would have allowed the claims to go forward.

Abbott agreed to pay $1.5 billion to settle civil claims and criminal charges from the FDA that the drugmaker misbranded Depakote and Depakote ER between 1998 and 2006. Abbott also received repeated notices from the FDA between 1982 and 2009 that the company was misbranding the drug or promoting it for unapproved uses, the plaintiffs said.

The plaintiffs are represented by Christopher Cueto and Michael Gras of the Law Office of Christopher Cueto Ltd., Janet G. Abaray of Burg Simpson Eldredge Hersh & Jardine PC, John T. Boundas of Williams Kherkher Hart Boundas, and Bruce L. Sampson Jr. of Bracewell LLP.

 

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All Eyes on 3rd Circuit in Zoloft Expert Appeal

Nicholas P. Jewell
Nicholas P. Jewell

Will Nicholas Jewell, a renowned Ph.D. biostatistician, get his chance to testify in In re Zoloft Products Liability Litigation? More than 300 mothers in 45 states who charge that the antidepressant caused heart defects in their newborns hope he will.

It’s up to the Third US Circuit Court of Appeals, which will decide whether US District Judge Cynthia M. Rufe of the Eastern District of Pennsylvania erroneously excluded him as a causation expert last April. The judge also granted summary judgment to defendant Pfizer and effectively wiped out the caseload in MDL 2342.

Judge is “armchair scientist”

Calling the judge an “armchair scientist,” the plaintiffs argue that the court “superimposed its own standard of sound science,” and disregarded Jewell’s 40 years of experience.

The case is Jennifer Adams v. Wolters Kluwer, No. 16-2247 in the Third Circuit. Leading the effort to revive the litigation are plaintiff attorneys Mark P. Robinson, Jr. of Robinson Calcagnie, Inc. in Newport Beach, CA, Dianne M. Nast of Nastlaw LLC in Philadelphia, PA, and David C. Frederick, Derek T. Ho and Hilary P. Gerzhoy of Kellogg, Huber, Hansen, Todd, Evans & Figel, PLLC in Washington, D.C.

Jewell is highly qualified:

  • He has been a professor of biostatistics (the statistical design and analysis of studies that investigate risk factors for disease) for nearly four decades, first at Princeton University.
  • For the last 33 years, he has been a professor at the University of California (Berkeley).
  • He authored a widely used textbook, Statistics for Epidemiology, and 160 peer-reviewed articles on biostatistics.
  • He is also the editor of the Journal of the American Statistical Association, the country’s preeminent peer-reviewed statistics journal.

Zoloft triples the risk

Jewell reviewed multiple peer-reviewed epidemiological studies involving hundreds of thousands of women, and concluded that taking Zoloft (sertraline) during pregnancy can as much as triple the risk for having babies with serious, life-altering heart defects.

He employed a “weight of the evidence” methodology using established criteria developed by English epidemiologist Sir Austin Bradford Hill. This methodology has been generally accepted in the scientific community for decades.

However Judge Rufe ruled that a causation opinion must be supported by “repeated, consistent, statistically significant human epidemiological findings.”

In fact, four published peer-reviewed studies did find a statistically significant increased risk of cardiac birth defects with Zoloft use during pregnancy.

Further, the plaintiffs argue that the judge’s doubt about Jewell’s methodology usurps the role of the jury, and that questions about his analysis are properly left to cross-examination and trial.

For 30 years, the scientific community has been aware that serotonin reuptake inhibitiors (SSRIs), including Zoloft, are potential teratogens (i.e., agents that affect the development of eggs, sperm, or embryos and therefore increase the risk of birth defects).

In 1988, a Pfizer report warned that “[s]ertraline should not be administered to pregnant or lactating females.” In 1995, the Food and Drug Administration sent a letter to Pfizer that it was “necessary to change the pregnancy category of Zoloft® from B to C” (drugs that have caused or may be suspected of causing, harmful effects on the human fetus).

The four studies that the court disregarded include:

Colvin (2011). Lyn Colvin, et al., Dispensing Patterns and Pregnancy Outcomes for Women Dispensed Selective Serotonin Reuptake Inhibitors in Pregnancy, 91 Birth Defects Res. A Clin. Mol. Teratol. 142 (2011), a study including 123,405 pregnancies from 2002 to 2005 in Western Australia, found a positive association between Zoloft exposure and cardiovascular defects.

Ban (2014). Lu Ban, et al., Maternal depression, antidepressant prescriptions, and congenital anomaly risk in offspring: a population-based cohort study, 121 BJOG 1471 (2014), a study including 349,127 births from 1990 to 2009 in the U.K., found a positive association between Zoloft exposure and cardiovascular defects.

Huybrechts (2014). Krista F. Huybrechts, et al., Antidepressant Use in Pregnancy and the Risk of Cardiac Defects, 370 N. Engl. J. Med. 2397 (2014), a study that included 949,504 U.S. pregnancies from 2000 to 2007, found a positive association between Zoloft exposure and cardiac malformations.

Furu (2015). Kari Furu, et al., Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design, 350 British Med. J. 1798 (2015), a study that included 2.3 million births in Denmark, Finland, Iceland, Norway, and Sweden from 1996 to 2010, found a positive association between Zoloft exposure and all cardiac defects.

“Under the correct legal standard, Dr. Jewell’s analysis easily clears Rule 702’s bar for admissibility,” the plaintiffs argue.

 

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Stifle the Telephone Background Racket, Judge Orders Lawyers in Zofran Litigation

Shh quiet background noise
The judge said, “Counsel should also avoid placing the Court on hold, which may have the unfortunate effect of playing “hold” music to all participants and throughout the courtroom.”

US District Judge F. Dennis Saylor IV on July 15, 2016 had to remind attorneys about the rules governing the attendance and participation by telephone in any court proceedings in In Re: Zofran (Ondansetron) Products Liability Litigation, MDL 2657,

“Because of the high volume of telephone attendance, counsel attending by telephone should endeavor to minimize background noise and other interference during the call. Counsel should normally mute their telephones, so that they can hear the proceeding but other participants will not hear any unwanted noise or interference. Counsel should also avoid placing the Court on hold, which may have the unfortunate effect of playing “hold” music to all participants and throughout the courtroom. The cooperation of all counsel in observing these requirements is greatly appreciated,” he wrote

Judge Saylor is hearing 260 Zofran Cases Filed Against GlaxoSmithKline in federal court in Massachusetts.

Concealing information

Plaintiffs accuse GlaxoSmithKline of concealing information tying Zofran to birth defects. They assert:

  • That since 1992, the company has received hundreds of reports of children who were born with serious abnormalities following pre-natal exposure to the drug.
  • That as early as 2006, studies have suggested that Zofran crosses the placental barrier in significant amounts when taken by pregnant women, which may potentially harm a developing fetus.
  • That Zofran has never been approved to treat pregnancy-related nausea and vomiting, and accuse Glaxo of improperly marketing the medication for this purpose.

In 2012, the drug maker agreed to pay $3 billion to resolve illegal marketing charges with the U.S. Department of Justice that involved a number of its medications. Among other things, the company had been accused of illegally promoting Zofran as an off-label treatment for morning sickness.

Fraudulent marketing campaign

In Flynn v. GlaxoSmithKline, the plaintiffs charge that because of GSK’s fraudulent marketing campaign, Zofran was placed into the hands of unsuspecting pregnant women throughout the US. These women ingested the drug because they innocently believed that Zofran was an appropriate drug for use in their circumstance. When they ingested the drug, these pregnant women had no way of knowing that Zofran had never been studied in pregnant women, much less shown to be a safe and effective treatment for pregnancy-related nausea

In contrast, GSK knew that Zofran was unsafe for ingestion by expectant mothers. In the 1980s, GSK conducted animal studies which revealed evidence of toxicity, intrauterine deaths and malformities in offspring, and further showed that Zofran’s active ingredient transferred through the placental barrier of pregnant mammals to fetuses. A later study conducted in humans confirmed that ingested Zofran readily crossed the human placenta and exposed fetuses in substantial concentrations. GSK did not disclose this information to pregnant women or their physicians.

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