FDA Safety Communication: UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse

“A South Carolina judge has upheld a $327 million civil penalty against health giant Johnson & Johnson, which in March was found guilty by a jury of overstating the safety and effectiveness of its former blockbuster antipsychotic drug, Risperdal.
Attorneys for the state said Wednesday that it’s the biggest verdict in the country over the marketing of Risperdal. The pill for schizophrenia and bipolar disorder once brought J&J more than $3.4 billion in annual sales.”

To read the entire article, click here.

Bayer Withheld Yasmin Data From U.S., Former Agency Chief Tells Court

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By Margaret Cronin Fisk and Jef Feeley - Dec 6, 2011 12:01 AM ET

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·         A Bayer AG unit withheld from U.S. regulators findings by company researchers of increased reports of blood clots in users of its Yasmin birth-control pills, the former head of the Food and Drug Administrationsaid.

David Kessler, the former FDA commissioner, in a document unsealed yesterday in federal court in Illinois, said Bayer didn’t include an analysis “that demonstrated an increase in the U.S. reporting rate” for venous thromboembolism, or clots, in a 2004 review of Yasmin’s safety provided to the agency.

The report also didn’t include an earlier draft opinion by company researchers that “spontaneous reporting data do signal a difference in the VTE rates for Yasmin” compared with other oral contraceptives, Kessler said, quoting the draft.

“Bayer presented a selective view of the data, and that presentation obscured the potential risks associated with Yasmin,” Kessler said. The company also promoted the oral contraceptive for unapproved uses, particularly for treatment of premenstrual syndrome, Kessler said.

Kessler’s report and four other expert opinions were released yesterday by lawyers representing former users of Bayer’s Yasmin family of contraceptives. The experts were paid by the plaintiffs’ lawyers, who submitted the reports to the FDA, which is considering safety findings on Yasmin and its sister product Yaz at a hearing Dec. 8.

‘Matters of Litigation’

Rose Talarico, a U.S.-based spokeswoman for Bayer, said the company doesn’t comment on ongoing lawsuits. “We have nothing further to add as these are matters of litigation,” she said in an e-mailed statement. “We expect them to be addressed further at trial.”

Morgan Liscinsky, an FDA spokeswoman, didn’t immediately comment on the unsealed documents about the drugmaker’s handling of the contraceptives.

The FDA didn’t accept the documents for the hearing, according to an e-mail sent to plaintiffs’ lawyer Ned McWilliams late yesterday.

“The deadline for all written submissions was on November 23, 2011,” Kalyani Bhatt, of the FDA’s Division of Advisory Committee and Consultant Management, wrote. “We will not be able to accept any written submission at this time.”

McWilliams said in an e-mail response to Bhatt, “I think the American public would want to know why the FDA has refused to consider important safety information that Bayer did not consent to be released to the public or the FDA until after the submission deadline.”

“Why not look at the documents and make your own independent objective evaluation?” McWilliams said.

Bhatt didn’t return a call after regular business hours yesterday seeking comment on that e-mail.

10,000 Lawsuits

Bayer faces more than 10,000 lawsuits over injuries allegedly caused by the contraceptives. Lawyers suing the drugmaker cited FDA reports of at least 50 deaths tied to the pills from 2004 to 2008. The first trials are scheduled for next month in federal court in Illinois and state court in Philadelphia.

Bayer’s contraceptives generated $1.58 billion (1.17 billion euros) in sales last year, making them the company’s biggest-selling drugs after Betaseron, a multiple sclerosis medication. The contraceptives, which contain the hormone drospirenone, have been the focus of regulators who question their safety. Bayer’s Yasmin was the No. 4 oral contraceptive in the U.S. this year as of September, with 4.6 percent of the market, according to data from IMS Health.

In October, the FDA warned that women taking the pills were 74 percent more likely to suffer blood clots than women on other low-estrogen contraceptives. The FDA examined data on 835,826 women who took pills containing the hormone, including Bayer’s Yasmin line of birth-control pills, according to the FDA report. The agency set the Dec. 8 hearing to discuss the findings.

Health Risks

The lawsuits claim Bayer didn’t sufficiently warn patients of the health risks of the Yasmin family of birth-control pills. They also claim Bayer’s Berlex Laboratories Inc., acquired in the 2006 purchase of Schering AG, marketed the drug for unapproved uses.

This marketing campaign, according to the documents unsealed yesterday, included paying $450,000 to Los Angeles gynecologist Judith Reichman to sponsor a tour for a book she was writing on women’s health issues, among other items, Kessler said.

Kessler said the Bayer unit withheld information about Yasmin’s risks of clots before the drug was approved by the FDA in 2001.

Internal Study

Bayer didn’t report to the FDA details on the risks of clots from an internal study and two cases of clots in patients on the pill prior to the drug’s approval by the agency, Kessler said.

“Had I, or a medical review officer, known these facts prior to approval, further investigation would be warranted before a decision on Yasmin’s NDA could be made,” he said, referring to the company’s new drug application.

“These facts would impact the agency’s risk-benefit equation about the drug and whether it could be approved,” Kessler said.

The FDA told Bayer in June 2003 that it was “very concerned” about the number of adverse events, particularly deaths, reported in Yasmin users, Kessler said, citing an agency letter to the company. This included six deaths in the U.S., five of which were first reported to the FDA after April 2, 2003, the agency said.

“Because of these recent reports, we believe that a change in Yasmin labeling and possibly additional actions are now warranted,” the FDA wrote to Bayer, according to the Kessler report.

‘White Paper’

Bayer responded that its data didn’t show a higher risk for Yasmin. Internally, the company decided to produce a “White Paper,” to the FDA, which would be “a scientific write-up that lays out the issues,” according to a Bayer document quoted by Kessler.

The white paper would compare Yasmin to other oral contraceptives, or OCs, covering multiple adverse events including venous thromboembolism (VTE) and pulmonary embolism (PT).

In an early draft of that report, Bayer employees wrote, according to Kessler, “Compared to the three other OCs, Yasmin has a several fold increase in the reporting rates for DVT, PE, ATE and confirmed VTEs.”

In this draft, the employees added: “When considering only serious AEs (adverse events), the reporting rate for Yasmin was 10 fold higher than with the other products.” The total rate of confirmed VTEs per year was three or four times higher than the other three oral contraceptives reviewed, according to the data in the draft, Kessler said. The raw numbers were 6.9 per year for Yasmin and 1.5 for two of the other pills, according to the draft.

‘Spontaneous Reporting’

In a later draft, the Bayer employees said that “spontaneous reporting data do signal a difference in the VTE rates for Yasmin and other OC users.”

Such data wasn’t the “preferred approach to assess the safety of a single product,” the researchers wrote. They said data from a direct comparison, such as two then-ongoing studies “should provide more insight.”

“The spontaneous reporting do NOT signal a difference in VTE rates for Yasmin,” another Berlex employee wrote to company colleagues in commenting on the draft, Kessler said. “Those comments were not accompanied by any additional data,” Kessler said.

Media Attention

Kessler agreed that spontaneous reporting of incidents has limitations, because of the voluntary nature of the reports, effects of media attention, different times of introduction for drugs, among other factors. The information still should have been included, he said.

“Even with its limitations, analysis of spontaneous reporting data is an important, recognized and vitally used tool by the FDA and the pharmaceutical industry for detecting safety signals” Kessler said in his report.

“Bayer’s spontaneous reporting analysis demonstrated a safety signal about Yasmin and VTE risk,” he said. “Bayer had a duty to present a full and balanced view of all the data and analysis concerning Yasmin to the FDA and health-care professionals and failed to do so.”

Women suing Bayer over its line of birth-control pills contend the company and its units went to unusual lengths to market the medication for unapproved uses, according to court papers.

Marketing Drugs

Bayer’s Berlex unit came up with a plan to hire Judith Reichman, a Los Angeles-based gynecologist who writes a blog about women’s health issues, “to engage in off-label promotion” of the Yasmin line of contraceptives, John Abramson, a Harvard medical school professor, concluded in his report.

Abramson was hired by plaintiffs’ lawyers to review materials Bayer turned over about the marketing of the drugs. His report was also unsealed yesterday by a federal judge in Illinois who is overseeing a consolidation of Yaz cases.

Berlex officials said in an e-mail they’d agreed to pay Reichman $450,000 in return for her willingness to “mention off-label benefits of our products,” Abramson noted. The doctor was planning an upcoming book on women’s health issues.

The company also planned to purchase 10,000 copies of the book, which contained “off-label claims” about the Yasmin line of contraceptives, the doctor noted. The purchase was part of a “strategy to have the book appear on the New York Times bestseller list,” Abramson added.

In her 2005 book, “Slow Your Clock Down,” Reichman wrote that Yasmin may help women with PMS-related symptoms such as “fluid accumulation and bloat,” or with depression.

Publicity

The FDA approved Yasmin only as a contraceptive. The regulator hasn’t cleared it as a treatment for any form of PMS or other ailments, according to the agency’s website. Reichman was unavailable to comment about her work with Bayer because her husband died, her assistant, Deborah Cannon, said in an e-mail.

Berlex officials understood the value of such publicity, Abramson noted. For example, Talarico, a then-spokeswoman for Berlex, flagged a copy of a 2006 story about Yaz in Allure magazine that touted the benefits of Yaz for treating PMS.

Richard Salem, Berlex’s vice president for communications, congratulated Talarico for getting the article placed in the magazine.

“The value of these placements is astronomical,” Salem said in an e-mail, according to court filings.

Commercial Success

Internal e-mails also show officials of Bayer and its Berlex unit engaged in an extensive public relations campaign to market Yaz that was “designed to circumvent FDA restrictions on marketing” because they saw the limits “as a threat to the commercial success of Yaz,” Abramson said in his report.

The Kessler and Abramson reports were sent to the FDA by McWilliams, a lawyer with Levin, Papantonio, Thomas, Mitchell, Rafferty & Proctor PA in Pensacola, Florida.

“Although these reports were prepared for litigation, they contain relevant information obtained from Bayer that has not been previously provided to the FDA that will assist the committee and the FDA in its own evaluation of the benefits and risks of drospirenone-containing oral contraceptives,” McWilliams wrote to the agency.

The case is In re Yasmin and Yaz (Drospirenone) Marketing, Sales Practices and Product Liability Litigation, 09-md-02100, U.S. District Court, U.S. District Court, Southern District of Illinois (East St. Louis).

Even without appellate case law to provide guidance on the discoverability of information on Facebook, the standard is becoming clear: Post at your own risk. Three courts in Pennsylvania have now decided that, if a party in a civil case posts information on his or her Facebook page that appears to contradict statements in discovery or testimony, then the party’s Facebook page falls within the scope of discovery. In the most recent case, Largent v. Reed, a judge ordered a plaintiff in an auto accident case to turn over her Facebook username and password to the defendant, on the ground that her postings brought up questions about the extent of her injuries.

What do you think?

The Third U.S. Circuit Court of Appeals has again thrown out the Federal Communications Commission’s $550,000 fine against CBS Corp. for televising Janet Jackson’s “wardrobe malfunction” during the 2004 Super Bowl halftime show. The panel said nothing about the U.S. Supreme Court’s ruling in the indecency case of FCC v. Fox Television Studios changed its initial analysis that the fining was done done without sufficient notice that the FCC was changing its policy to allow for sanctions for fleeting expletives or indecent images. But the author of that first opinion — Judge Anthony Scirica — now dissents, saying the Fox decision requires the Third Circuit to revise its previous holding that the FCC violated the Administrative Procedure Act by arbitrarily and capriciously changing its policy.

:31-2-3987 Gronwald v. Modica, App. Div. (Buchsbaum, J.S.C.) (5 pp.) Plaintiff arrived at defendant’s farm to pick pumpkins when, due to the morning dew or frost on the grass, she slipped and fell. Plaintiff seeks damages for her injuries. In his motion for summary judgment, defendant contends that he is immune from liability pursuant to the farmers immunity statute. Plaintiffs oppose the summary judgment motion asserting that defendant owes a separate legal duty to provide a reasonably safe means of ingress and egress for business invitees. Here, Mrs. Gronwald entered defendant’s land for the purpose of picking pumpkins. Pumpkins, as horticultural products, fall within the purview of the statute. It is natural in the course of pumpkin-picking for patrons to park their vehicles and walk across the land to reach the farm. Further, dew and frost is a natural condition of the land. Thus, immunity applies because plaintiff’s entry on the land was for horticultural purposes as her injury resulted from a natural condition of the land. Defendant’s motion for summary judgment is granted.