Have These Symptoms? Buy This Drug by Pauline W. Chen, M.D.
It began suddenly a little over 10 years ago. With impressive fluency, friends, family members and patients started asking me about random medications, the odd syncopations of those invented, polysyllabic pharmaceutical brand names – Viagra, Lipitor — rolling perfectly off their tongues.
The questions they asked about those drugs did not reflect breaking news or the results of scientific studies. Rather, they were a reflection of sound bites, advertisements and the draw of celebrities who endorsed them, all part of carefully conceived marketing schemes.
There’s no question that Americans like their prescription medications. We spend nearly twice as much per person on pharmaceuticals as patients in other developed countries do, and we account for nearly half of all sales worldwide. But in 1997, when the Food and Drug Administration loosened its regulations and the United States became one of only four countries to allow direct-to-consumer advertising (the others are New Zealand, Bangladesh and South Korea), we entered a new era in pharmaceutical consumerism.
Players in the drug industry began aiming their advertisements at patients, and their goal was to define in the minds of patients not only the beneficial effects of the drugs but also the diseases they were designed to treat.
As Vince Parry, a well-known marketing expert, counseled his colleagues, “If you can define a particular condition and its associated symptoms in the minds of physicians and patients, you can also predicate the best treatment for that condition.”
The phenomenon is sometimes referred to as “disease mongering,” redefining what is normal and abnormal in a way that widens potential markets for those who sell treatments. And, as detailed in a recent study in the journal Social Science & Medicine, one marketing strategy has accomplished more in this regard than any other by using what has come to be the very symbol of quality and reliability for doctors and patients everywhere: the checklist.
Placed on Web sites, on downloadable apps and in pamphlets in doctors’ offices, these checklists of symptoms have become a critical part of every major pharmaceutical marketing campaign. What makes them so attractive is that they make it easy for patients to diagnose their own ailments, to take some control over their own health.
What makes the checklists so powerful is their ability to influence patient preferences.
The makers of Yaz, a birth control pill, for example, used a checklist to help promote the use of their drug as a treatment for premenstrual dysphoric disorder, a controversial diagnosis said to affect up to 10 percent of women. Alongside links to articles on fashion, makeup, hair and celebrity news, Yaz’s Web site offered a “Body Diary” checklist to help patients determine whether they suffer from the disorder.
Taking its cues from the Diagnostic and Statistical Manual of Mental Disorders, or D.S.M., which mental health professionals use to diagnose disease, the checklist offered watered-down and potentially more inclusive descriptions. A symptom described in the D.S.M. as “persistent and marked anger or irritability or increased interpersonal conflicts” appeared in the Yaz questionnaire as “Felt angry, or irritable.” “Marked change in appetite, overeating, or specific food cravings” became “Had increased appetite or overate; or had cravings for specific foods.” The printable results that patients could then take to their doctors (the site has since been taken down) were on a form emblazoned with the birth control brand.
“The whole point of tools like this one is to confine people’s experiences into these categories in order to make a diagnosis in line with the branded drug,” said the author of the study, Mary Ebeling, an assistant professor of sociology at Drexel University in Philadelphia who got interested in the use of checklists while doing research at a marketing firm. “I became really intrigued when I saw a group of marketers sitting around a table in Midtown Manhattan and coming up with symptoms.”
Some symptom checklists are clearly branded, so patients and clinicians can easily discern the pharmaceutical interests involved. But many are less obvious or are used as part of advocacy groups’ materials or awareness events. For example, National Depression Screening Day, held annually at college campuses, military sites and community centers across the country, uses a symptom checklist called the Patient Health Questionnaire, or PHQ-9. The nine questions are based on a well-known anxiety screening tool, but its copyright is held by Pfizer, maker of the antidepressant Zoloft.
It’s difficult to ascertain whether efforts aimed directly at consumers ultimately translate into real sales. A recent marketing study found that fewer than 3 percent of patients mentioned a marketed drug by name and less than 1 percent asked for a prescription. However, a separate study comparing patients in Canada, where direct-to-consumer marketing is illegal, with those in the United States found that American patients were more than twice as likely to request advertised medications.
But sales may not be the only measure of success for these campaigns. “The whole point of this marketing and branding is that the name ends up in the minds of the consumers,” Dr. Ebeling said.
While the Obama administration is looking to force pharmaceutical companies to disclose any payments to doctors that might influence their treatment decision, marketing efforts directed at patients are likely to continue to grow. And with those efforts comes a widening, not shrinking, circle of interests that can influence their care.
“There are pharmaceutical marketers, medical device makers, health insurers and whoever is involved in the health industry sitting in the exam room, not just the doctor and patient,” Dr. Ebeling said.
She added, “I find that disturbing, because it’s our health and the quality of our lives that are at stake.”
Have These Symptoms? Buy This Drug by Pauline W. Chen, M.D.
Correction: An earlier version of this article incorrectly listed Pakistan as one of four countries that allow direct-to-consumer advertising of pharmaceuticals. The four countries are the United States, New Zealand, South Korea and Bangladesh, not Pakistan.
Did FDA Panelist with Ties to BAYER prevent a YAZ RECALL?
THE YAZ MEN: MEMBERS OF FDA PANEL REVIEWING THE RISKS OF POPULAR BAYER CONTRACEPTIVE HAD INDUSTRY TIES.
January 09, 2012 9:24 AM
Last month, the U.S. Food and Drug Administration convened a committee of medical experts to weigh new evidence concerning the potential dangers of drospirenone, a synthetic hormone contained in popular birth control pills including Bayer AG’s Yaz and Yasmin. In a decision that helped ensure the continued presence of these drugs on American pharmacy shelves, the committee concluded by a four-vote margin that the benefits of drugs with drospirenone outweigh the risks. However, an investigation by the Washington Monthly and the British medical journal BMJ has found that at least four members of the committee have either done work for the drugs’ manufacturers or licensees or received research funding from them. The FDA made none of those financial ties public.
Yaz and Yasmin are among Bayer’s top selling pharmaceutical products. According to the German drug manufacturer, over 4 million women worldwide use Yasmin alone. But the drug has also sparked growing controversy in recent months. A series of studies published in BMJ have shown that users of pills containing drospirenone have an increased risk of blood clots, which can cause deep vein thrombosis, pulmonary embolism, stroke, heart attack and death. And thousands of women have filed a lawsuit against Bayer, saying they were injured by Yaz or Yasmin.
Other Bayer products containing the hormone drospirenone are Beyaz and Safyral. In addition, four companies—Bayer, Teva, Watson and Sandoz—sell five generic versions of the drugs evaluated by the committee last month.
The FDA’s decision not to reveal its advisors’ relationships with the drugs’ manufacturers and Bayer raises serious questions about the agency’s treatment of potential conflicts of interest, a historically problematic area for the department. In 2004, controversy erupted over another FDA advisory hearing—involving the painkiller Vioxx—when it became clear that advisors with financial conflicts of interest were more likely than those without conflicts to vote that Vioxx was safe and should be allowed to stay on the market. The drug was ultimately withdrawn after a study showed it was associated with approximately 60,000 deaths. In 2008, partly in response to this uproar, the agency issued a new guidance on how to handle conflicts of interest among its advisors, stating that it wanted to reduce “bias” and to be more “transparent.”
The agency’s handling of the drospirenone hearings casts major doubt on how far it has gone to attain those goals.
What’s more, interviews and records also show that the drospirenone advisory committee, when it voted last month, lacked significant information about increased risks to the health of women using contraceptives containing drospirenone.
The FDA ordered the safety review of drugs containing the hormone after three articles published in the BMJ found an increased incidence of blood clots among users of the pills. The advisors were given these studies prior to the December 8 meeting. However, the panel was not shown documents from a report by David Kessler, a former FDA commissioner and an expert witness in the lawsuit filed against Bayer on behalf the women who say they were injured by Yaz and Yasmin. Kessler’s report cites internal Bayer corporate documents that suggest the company had withheld safety data from the FDA.
The documents show that in 2004, Bayer scientists reported in a draft analysis that Yasmin incurs a “several-fold increase” in reporting rates for blood clots compared to three other oral contraceptives, and that Yasmin’s rate of all serious adverse events was “10 fold higher” than that of other products.
In his report, Kessler writes that Bayer failed to report safety data to the FDA, engaged in off-label promotion of the pills, and paid $450,000 to a high profile gynecologist to sponsor her book tour in which she promoted such off-label uses.
Kessler’s report, originally under seal, was not released until December 6, two days prior to the advisory meeting. The FDA said it could not give the advisors the information because the date to submit documents had passed.
The FDA relies on some 50 advisory committees to obtain “independent” expert advice and “maintain the public trust.” Recommendations on evidence for safety and efficacy can lead to drug approvals and withdrawals; while nonbinding, recommendations by such committees can move stock prices and are generally regarded as indicators of official FDA action.
Under FDA guidelines, when advisory committee members have a financial relationship with a drug company whose product is under review, the agency can issue waivers that acknowledge the advisors’ links to industry but allow them to vote if their expertise is needed and no other specialists are available. Such waivers often serve as the only public signal that advisors have financial conflicts of interest. In the hearings on drospirenone, the FDA issued none.
And yet, according to public records, recently unsealed court documents, and interviews with some of the FDA advisors, at least four of the advisory committee members in this case have served as paid researchers, consultants, “key opinion leaders,” or speakers for Bayer or other manufacturers or licensees of drospirenone. A fifth advisor agreed to serve as a consultant but never executed the agreement. A sixth received consulting fees from a law firm representing Bayer.
In a 15-to-11 vote, the committee decided that the benefits of drospirenone outweighed its risks.Had those members with undisclosed conflicts of interest voted the other way, the committee would have come to the opposite conclusion. The committee also voted 21 to 5 to change the drug labels to warn that the hormone can cause blood clots. But the panel stopped short of recommending that the labels should warn that they are more likely than other contraceptive pills to cause blood clots. Instead the experts suggested that the labels say that the evidence about blood clots is “conflicting.”
Ironically, while the FDA allowed voting by advisors with business connections to drospirenone, the agency did bar another advisor—Sidney M. Wolfe, the panel’s lone consumer advocate—on the grounds that he has an “intellectual conflict of interest.” Wolfe, a former researcher, is a frequent critic of FDA practices on behalf of the advocacy group Public Citizen. Wolfe, the author of the consumer guide Good Pills, Bad Pills, had marked Yaz with a “do not take” advisory to readers. Jerome Hoffman, professor emeritus of medicine at UCLA, questioned Wolfe’s exclusion from the panel: “The idea that because he has an opinion on data that already exist he should be prevented from voting is nutty.”
Each of the advisors with ties to manufacturers told the Washington Monthly andBMJ that they fully disclosed their ties to the FDA, and there are no indications that the advisors failed to make required disclosures to the agency. The FDA, however, has declined to make public advisors’ financial conflict of interest forms, explaining that the forms are “confidential” and no information from them can be shared under a section of the Ethics in Government Act.
When asked whether the agency was aware of any financial ties between its advisors and manufacturers or distributors of drospirenone, FDA spokeswoman Morgan Liscinsky said, “No waivers were issued.”
But the committee’s financial ties to Bayer begin with no less than its acting chair. Julia Johnson, a professor of obstetrics and gynecology at the University of Massachusetts Medical School, conducted four clinical trials—including one of drospirenone as hormone replacement—for Bayer or its subsidiary Berlex, a manufacturer of drospirenone. She said in an e-mail, “The FDA is very vigilant on examining potential conflicts of interest and was aware of all my research.” When asked for an interview, she said, “The U.S. FDA states that I cannot speak about the meeting.”
Another advisor with ties to industry is Paula Hillard, a professor of obstetrics and gynecology at Stanford School of Medicine who has served as a paid consultant to Bayer Schering. Dr Hillard said she had fully complied with all FDA disclosures and referred the Washington Monthly and BMJ to the FDA for further questions. The FDA declined to respond to any questions, again citing the confidentiality clause of the Ethics in Government Act.
Elizabeth Raymond, a senior medical associate at Gynuity Health Projects in New York and another member of the committee, conducted studies funded by Barr, which has a licensing agreement with Bayer for generic versions of Yaz. Dr Raymond said that the FDA was “fully aware of all of my relevant current and past activities.”
Anne E. Burke, an assistant professor of gynecology and obstetrics at Johns Hopkins University in Baltimore, has received research funding from Bayer-Berlex and Duramed, which has a licensing agreement with Bayer for generic Yaz and Yasmin. Dr Burke said that she fully disclosed this to the agency.
According to Dr Kessler’s report, an internal Bayer document indicated that a fifth advisor received payment from Bayer, but that advisor told the Washington Monthlyand BMJ that although she initially agreed to serve as a consultant for Bayer, the company never pursued the agreement. She said FDA records indicated that she had ties to Bayer due to her disclosure about her agreement, but after she was nominated to be on the drospirenone advisory committee, she corrected the error.
A sixth advisor, meanwhile, confirmed that he received consulting fees from a law firm representing Bayer in 2006. He told BMJ and the Washington Monthly that he did not disclose the information to the FDA because the FDA “did not require information for that time frame for consulting unrelated to the meeting topic.”
Bayer spokesperson, Rosemarie Yancosek, said in an e-mailed statement: “Bayer had no input on who serves on the U.S. FDA Advisory Committee panel as the FDA has its own process for selecting panel members. Furthermore, it is Bayer’s understanding that the FDA has a procedure for determining conflicts of interest for potential panel members.”
The FDA does indeed have such a procedure, but critics argue that its guidelines define conflicts of interest too narrowly and provide too much flexibility in how they are applied. The guidelines are technically “suggested or recommended, but not required” provisions (http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM125646.pdf). Whether an advisor can participate depends on “whether the discussion at the meeting or outcomes of the meeting will have a direct and predictable effect on the individual’s interest.” For instance, someone who was previously involved in another role for a manufacturer, or whose university received money from a manufacturer, may be allowed to participate. Even having a contract for $100,000 over a five-year period would not necessarily exclude an advisor, according to the guidelines.
Despite the FDA’s frequent claims that there aren’t enough experts independent of industry, a list of over 100 industry-independent experts has been presented to the agency - yet none of those experts has been tapped as an advisor.
The Project on Government Oversight, a Washington-based nonpartisan watchdog group, plans to raise concerns about the FDA’s conflict of interest policies in a letter to the agency’s top official, Margaret Hamburg.
“It shouldn’t require a lawsuit and investigative journalism to learn about these kinds of conflicts,” said the group’s executive director, Danielle Brian. “The Yaz case puts FDA’s feckless ethics policy into stark relief. It also reveals the human impact of conflicts of interest and why we need an FDA that shuns even the appearance of such conflicts.”
The organization intends to urge the FDA to routinely disclose industry ties and more aggressively determine whether an advisor has a conflict. “Right now,” said Brian, “the bar for considering whether an advisor has a conflict is too high.”
NBC Nightly News with Brian Williams explores #DRSP (#DROSPIRENONE) containing birth control pills on 12.8.11, following FDA Advisory Committee Hearings evaluating the elevated, and confirmed, risk of blood clots per FDA funded study.
MARKETPLACE, CANADA’S CONSUMER WATCHDOG, investigates #YASMIN, #YAZ birth control pills that contain #DRSP #DROSPIRENONE. HEALTH CANADA announced this week that it had concluded a ‘safety review’ of the pills and found they presented a 1.5x to 3.0x higher risk of blood clots than other pills. This story was aired prior to this announcement in early 2011. FDA is holding hearings 12.8.11-12.9.11 to consider blood clot risks of these pills and other contraceptives. In May 2011, the EMA (European Medicines Agency) announced the pills presented a 1.5x to 3.0x higher risk of blood clots. FDA funded studies concluded the pills were 74%, or 1.74x. higher risk in comparison to other hormonal contraceptives it considered.
Vermont Journalism Trust reports on 11.21.11 death of April Bapp allegedly linked to #DRSP (#DROSPIRENONE) birth control generic OCELLA. FDA hearings on increased blood clot risks are set for 12.8.11.
Editor’s note: This article, by Tena Starr, was first published in the Barton Chronicle.
On late Saturday afternoon, Nov. 12, when April Bapp of Brownington got a phone message from her daughter Rebecca, who didn’t feel well and was having trouble breathing. She was working that day at Community College of Vermont in Newport, and there was no one else in the building. She didn’t think she could get herself to a doctor, so her parents drove to Newport and brought her to North Country Hospital.
Six hours later Rebecca was dead. She was 21 years old.
“She couldn’t get enough oxygen in her lungs,” Mrs. Bapp said. “Her sugar was high. They weren’t sure what was going on. She was on a breathing machine, sedated, they wanted to do a CT to see what was going on, and she coded.”
The hospital had planned to Medivac her to the Dartmouth Hitchcock Medical Center in Lebanon, N.H., but Rebecca coded again. The third time, doctors couldn’t bring her back, and she died that night.
Baffled, her family asked for an autopsy. The medical examiner’s report said she died of a blood clot in her heart, April Bapp said. “And the secondary cause of death was her oral contraceptive.”
Rebecca had been taking Ocella, a relatively new and controversial type of birth control pill that is the subject of a federal advisory committee hearing this week. The prescription is also known by its popular generic brand name YAZ.
YAZ has been the suspected cause for deaths around the country, according to the Public Citizens Health Research Group.
Dr. Sidney Wolfe, director of the watchdog organization, said, “there have been a number of published studies not connected with the company that have found problems with the product.”
The organization, which Wolfe founded 40 years ago with consumer advocate and former presidential hopeful Ralph Nader, has placed YAZ on its list of “do not use” drugs.
Public Citizen’s Worst Pills, Best Pills website says that GIANVI, YASMIIN, YAZ, and ZARAH are on the “do not use” list because they can cause increased blood levels of potassium and are no more effective than other oral contraceptives in preventing pregnancy.
The federal Food and Drug Administration’s Drug Safety and Risk Management Advisory Committee, of which Dr. Wolfe is a member, will receive a briefing on this week regarding the newest information about third-generation birth control pills, Dr. Wolfe said.
The advisory committee will examine whether the product should even be on the market, he said. New information will be available on the FDA’s website later this week. (Public Citizen sued the FDA some time ago, forcing the agency to post information on its website in a timely fashion.
For her part, April Bapp said YAZ and its relative Ocella were highly marketed products that her daughter and her doctor apparently trusted. “Those ads came across as being great and wondrous,” she said. “This is the brand they’re pushing to young girls.”
April Bapp is shocked by the sudden death of her daughter, and she is hoping that, by talking about it, she can prevent the unnecessary death of another young woman.
“If we can prevent someone else from dying, then it may help us make some sense of Rebecca’s death,” she said in a letter to the Chronicle.
“She worked at the Farm Service Agency, she worked at CCV on Saturdays, she helped out the town clerk,” April Bapp said. “She was working on her bachelor’s degree at Johnson State College. There was so much potential.”
More than 300 people attended Rebecca’s funeral.
“Everybody said how smart she was,” April Bapp said. “Rebecca’s boyfriend, they were all there on short notice for her death. It’s just not what you think is going to happen when your daughter calls and says she doesn’t feel good.”
Although April Bapp was aware that birth control pills carry health risks, her daughter’s death and the autopsy results prompted Mrs. Bapp to question the risk associated with this particular birth control pill.
YAZ, which the FDA approved in 2006, is among a newer line of birth control pills that includes other brand names such as Yasmine and Ocella. The difference between those brands and older birth control pills is that YAZ and its counterparts contain drospirenone, a progestin — basically a hormone — that is not contained in older birth control pills.
Information from the FDA is contradictory. It says that several studies have been conducted, and some indicate a higher risk for blood clots, stroke, and other problems when taking YAZ, and some do not.
“All birth control pills pose a risk of blood clots,” a September FDA website posting on the product says. “Several epidemiological studies have reported that the risk of blood clots for women who use birth control pills containing drospirenone is higher than that for women who use birth control pills containing the progestin levonorgestrel. Other studies have not reported an increase in risk.”
Levonorgestrel is the hormone in an older generation of birth control pills.
Later studies indicate an increased risk, according to the FDA, which commissioned yet another study. The results are being finalized and may be reviewed later this week by the advisory committee. Recent articles in the British Medical Journal reported a two- to three-fold greater risk of blood clots and other serious problems in women who use oral contraceptives containing drospirenone.
YAZ has been the suspected cause for deaths around the country, according to the Public Citizens Health Research Group.
An article posted on the Worst Pills website said that studies funded by the industry found lower risks of blood clots than did studies that were publicly funded. It says that drospirenone is “a close chemical cousin of spironolactone, a diuretic or water pill that causes the body to retain potassium. A 3-milligram dose of drospirenone, the amount in a daily contraceptive pill, is equivalent to 25 milligrams of spironolactone.”
A 2008 “warning” letter to Bayer HealthCare Pharmaceuticals, Inc., the company that manufactures and markets YAZ, is posted on the FDA’s website. Thomas Abrams, director of the Division of Drug Marketing, Advertising, and Communications at the U.S. Department of Health and Human Services wrote that the company was, at the time, engaged in misleading advertising practices.
“The TV ads are misleading because they broaden the drug’s indication, overstate the efficacy of YAZ, and minimize serious risks associated with the use of the drug,” the letter says. “These violations are concerning from a public health perspective because they encourage use of YAZ in circumstances other than those in which the drug has been approved, over-promise the benefits and minimize the risks associated with YAZ.”
The ads indicated that YAZ not only was an effective birth control pill, but also treated severe acne and premenstrual syndrome. Apparently, it does benefit acne problems to some extent, and also helps with premenstrual dysphoric disorder, a serious form of PMS.
The FDA warned that some of the television ads were over the top. One, called “Not Gonna Take It,” started by saying, “We all know that birth control pills are 99 percent effective and can give you shorter, lighter periods. But did you know there’s a pill that could do more?”
“It then displays images of energetic, euphoric, playful women singing ‘We’re not gonna take it’ as they kick, punch and push words describing symptoms such a irritability, moodiness, bloating, and feeling anxious away from the screen…” Abrams writes in his letter to Bayer.
He goes on to say that the product is not approved to treat severe acne or PMS, and the ads do not appropriately explain the risks involved in taking the product.
A New York Times article says that YAZ is the “go-to-selling” birth control pill in the U.S. and owes much of its popularity to a multi-million-dollar ad campaign that promotes it as a quality-of-life treatment that combats acne and severe premenstrual depression, as well as preventing pregnancy. The story goes on to say that the American unit of Bayer rigorously defends the safety of the product and says it has been extensively studied.
A New Jersey Business magazine article tells a story that resembles that of the Bapps’. It says that Michelle Pfleger, a teenager, asked for the birth control pill YAZ when she visited her doctor before going off to college. She’d seen the advertisements on television. The young woman died after a blood clot lodged in her lung while she was on her way to class at Elon University in North Carolina, the article says. Ms. Pfleger was 18.
The article says that more than 900 lawsuits have been filed in Bergen County, New Jersey , and that hundreds of other cases have been lodged in Philadelphia, California and Illinois.
Contacted Tuesday, a spokesman for Bayer did not comment except to say the company does not make Ocella.
No one from Tava, which does, responded to email.
Mrs. Bapp is doing the best she can these days.
“You try to put on a good front when you’re out,” she said. “But it’s devastating.”
Her other daughter has posted the cause of her sister’s death on Facebook in the hope of informing people.
Other contraceptives that contain drospirenone are Angeliq, Beyaz, Gianvi, Safyral, and Zarah.
Consumers may report serious problems with oral contraceptives or other products to the FDA’s MedWatch Adverse Event Reporting program at (800) FDA-1088, or www.accessdata.fda.gov/scripts/medwatch/medwatch-online.tm.
Units of Bayer AG (BAYN), Germany’s largest drugmaker, may have sought to market the Yasmin family of birth- control pills for unapproved uses and misled women about the health risks the drug posed, according to company e-mails.
Bayer unit officials discussed promoting the contraceptive known as Yaz, a spinoff of Yasmin, for treatment of all types of premenstrual syndrome, according to company files provided to lawyers for women suing Bayer. U.S. regulators approved Yaz only for the most severe form of PMS. Salespeople for Bayer unit Berlex Laboratories Inc., acquired in the 2006 purchase of Schering AG, received an e-mail that year from a company official citing a Woman’s Day magazine article about Yaz.
“This article is a nice way of using YAZ for PMS treatment instead of just focusing on the specific” class of women battling premenstrual dysphoric disorder, the most severe form of PMS, wrote Matt Sample, a Berlex sales consultant, according to a copy of the e-mail produced as evidence.
The message and other internal company files were disclosed as part of litigation claiming the drug caused blood clots, heart attacks and strokes. Bayer faces more than 10,000 lawsuits over injuries allegedly caused by the contraceptives. Lawyers suing the drugmaker cited Food and Drug Administration reports of at least 50 deaths tied to the pills from 2004 to 2008.
‘Safe and Effective’
“Bayer’s oral contraceptives have been and continue to be extensively studied worldwide and are safe and effective when used as directed and according to product labeling,” said Rose Talarico, a U.S.-based spokeswoman for the company, in an e- mail. She declined to comment further on the litigation.
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.
Last month, 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 has set a Dec. 8 hearing to discuss the findings.
Besides the off-label marketing allegations, attorneys for women suing Bayer alleged internal company files show Berlex and Schering officials withheld some information from patients, doctors and regulators about the drug’s risk for blood-clots. The lawyers also claim in court filings that company officials wrongfully touted Yasmin and Yaz to be just as safe as rival birth-control pills.
The drugmaker and its units “sacrificed women’s health in its rush for profit and they continue to do so every day,” said Paul Pennock, a New York-based lawyer representing women suing over the contraceptives.
In January, Bayer is scheduled to face the first trials of lawsuits in which Yaz and Yasmin are alleged to have caused blood clots, which can lead to heart attacks and strokes. The trials are to take place in Illinois and Pennsylvania.
Bayer fell 1.01 euros, or 2.2 percent, to 45.25 euros at 2:03 p.m. in Frankfurt trading.
Bayer turned over Sample’s e-mail and other documents obtained by Bloomberg News to the plaintiffs’ lawyers as part of discovery, or the pre-trial exchange of evidence and information, in the consolidated Yaz cases.
The lawyers contend Sample’s e-mail about the Woman’s Day article amounts to an effort to have Yaz promoted for a use not approved by the FDA. Under U.S. law, a doctor can prescribe a medicine for any condition, as long as it’s licensed by the FDA and proven safe and effective.
Drug companies, however, aren’t allowed to promote a drug for uses other than those approved by the regulator.
In the e-mail, Sample encourages Berlex’s sales representatives to use the article to ask doctors “what percentage of your patient population suffers from” symptoms common to PMS, versus the more severe form of the disorder, and to seek information on “what they think the impact of Yaz will be.”
The women’s lawyers also rely on a May 2002 e-mail from Kimberly Schillace, then a Berlex executive, about a contract with Dr. Judith Reichman, a Los Angeles-based gynecologist who writes a blog about women’s health issues. A copy of the e-mail was included in the litigation discovery files.
The attorneys contend the e-mail supports their arguments that the drugmaker sought to market the Yasmin line of contraceptives for unapproved uses.
In the e-mail, Schillace noted that she spoke with Reichman, who appeared regularly on NBC’s “Today” show as a contributor on women’s health.
“She definitely will mention the off-label benefits of our products,” Schillace said, according to the copy of the e-mail.
“Attached please find the contract,” the e-mail states. The message doesn’t contain details of the agreement.
Sample couldn’t be immediately reached for comment. It is unclear whether he is employed by Bayer, which didn’t respond to requests for comment on his status. Schillace, referred to in a 2006 Schering press release as Kimberly Schillace Wix, declined to comment, saying only she is no longer with Bayer.
‘May Be Helpful’
Reichman noted in a November 2003 MSNBC.com article that some studies showed Berlex’s Yasmin “may be helpful in diminishing PMS-like symptoms.” 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.
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 didn’t return calls seeking comment on the e-mail.
The FDA said Bayer made misleading claims about Yaz in television advertising, which prompted the drugmaker to spend $20 million on corrective spots. U.S. regulators said in 2008 that Bayer overstated the pill’s effectiveness and minimized “serious risks associated” with it in two 60-second television ads. The regulator said the spots misled viewers about approved uses for the drug.
FDA officials ordered the company to pull the ads. The following year, Bayer agreed to run new ads stating Yaz hadn’t been approved as a treatment for all forms of PMS or acne as part of a settlement of a claims brought by 27 U.S. state attorneys general.
Nearly 12 million women in the U.S. and more than 100 million women worldwide use oral contraceptives, Scott Monroe, an FDA official, said last year.
Bayer bought Schering, then a rival German drugmaker, and its New Jersey-based Berlex unit for $21.8 billion to acquire the Yasmin line of contraceptives and Bataseron. North American revenue from the birth-control pills has fallen as the pharmaceutical company, based in Leverkusen, faces competition from generics made by Teva Pharmaceutical Industries Ltd. (TEVA)
The first trial over the pills is to start Jan. 9 in federal court in East St. Louis, Illinois. The plaintiff, Kerry Sims of Belleview, Illinois, contends she developed a blood clot and a lung disorder after taking Bayer’s medicine in July 2008.
Bayer “denies that any of the plaintiff’s alleged injuries were caused by Yas and/or Yasmin,” the company said in a Nov. 16 filing in the suit. “The labeling for Yaz and Yasmin provides appropriate warnings regarding the risks.”
“All birth control pills approved for use in the U.S. are associated with reports of adverse events, including death,” lawyers for the company said.
About 10,400 suits have been filed over injuries allegedly caused by the contraceptives, Bayer officials said last month in a filing with the U.S. Securities and Exchange Commission. Some of the cases have been consolidated before U.S. District Judge David Herndon in East St. Louis.
The FDA scheduled its December hearing on drospirenone- laden contraceptives, such as the Yasmin line, because of “the conflicting nature of the findings from six published studies evaluating this risk,” the agency said in September.
‘Benefits and Risks’
The FDA advisory committee will discuss “the benefits and risks” of contraceptives such as Yasmin and Yaz “in light of the emerging safety concern that the risk of venous thromboembolism (blood clots that can break loose and move within the circulatory system) associated with use of these products may be higher compared to oral contraceptives that contain the progestin, levonorgestrel,” Morgan Liscinsky, an FDA spokeswoman, said in a Nov. 18 e-mailed statement.
Plaintiffs’ lawyers said company-sponsored studies downplayed potential side effects. A Schering-sponsored study of 58,684 women using contraceptives such as the Yasmin line found no increased risk of clots.
The lead author of the European Active Surveillance Study was Juergen Dinger, then director of the Center for Epidemiology and Health Research in Berlin. Dinger previously was a Schering vice president overseeing drugs used in gynecology and played a role in the development of the Yasmin contraceptives, according to the documents provided by plaintiffs’ lawyers.
Dinger’s tenure at Schering and his involvement with the Yasmin birth-control pills weren’t disclosed in the study when the final results were published in the medical journal Contraception in 2007.
Plaintiffs’ lawyers alleged that the EURAS study was structured to minimize the number of clots linked to the contraceptives. The study results helped support sales of Yasmin and Yaz, the women’s attorneys claimed.
Maureen Cronin, a Schering executive, said in a 2005 e-mail that she met with Dinger and “reached agreement on the future reporting on EURAS” study results. The e-mail was included as an exhibit in an Oct. 27 request that the court unseal additional documents.
“One major reason for providing only tables and a synopsis is that we do not want to imply that we have a VTE problem but emphasize the fact that the study results indicate that Yasmin’s VTE/ATE is comparable to other” contraceptives, Cronin wrote, according to a copy of the e-mail. VTE refers to venous thomboembolisms, while ATE refers to clots in patient arteries.
‘Out of Context’
“The document has been taken out of context,” Dinger said Nov. 18 in an e-mail. Other e-mails to which he doesn’t have access would support him, he said.
Cronin didn’t respond to a call or e-mail seeking comment about her work on the Yasmin line. She left Bayer in 2010 to become the global head of medical affairs for Vifor Pharma, a Swiss drugmaker, according to a copy of her resume posted on the Internet. A call to her there wasn’t returned.
“Bayer has sponsored several independently-conducted, large-scale, prospective, observational safety studies on the use of combined oral contraceptives,” Talarico, the U.S. spokeswoman for the drugmaker, said in her statement. “The EURAS study was designed with input and approval from the European regulatory authorities.”
“Bayer affirms that the benefit-risk profile of its oral contraceptives, based on an established body of well-grounded data, shows the risk of venous thromboembolism (VTE) is comparable to the other combined oral contraceptives studied,” she said.
The company’s assessment “is supported by consistent clinical findings over a 15-year period and up to 10 years of post-marketing study results,” Talarico said.
Pennock, the plaintiffs’ lawyer, claimed Dinger’s involvement casts doubt on the legitimacy of the science Bayer relies on to show its birth-control pills are safe.
“Schering bought and paid for allegedly independent, favorable science that was neither independent nor correct,” Pennock said in an interview. “Bayer continues to foist the myth that these drugs are not more dangerous upon millions of unsuspecting patients and doctors.”
Pennock and other plaintiffs’ attorneys asked Judge Herndon to unseal Bayer’s files about the design and handling of the EURAS study. The lawyers said they wanted to present the materials to the FDA panel reviewing Yaz next month.
Herndon rejected that request Nov. 10, finding Bayer had a right to keep the materials related to the EURAS study confidential.
The case is In Re Yasmin and Yaz (Drospirenone) Marketing, Sales Practices and Product Liability Litigation, 09-md-02100, U.S. District Court for the Southern District of Illinois (East St. Louis).
To contact the editor responsible for this story: Michael Hytha at firstname.lastname@example.org
Additional background information on the status of FDA investigation of the blood clot risk of YAZ BIRTH CONTROL and YAZ SIDE EFFECTS is available from the sponsor of this blog and post at YAZRecall.com The sponsor of this post and blog is Gabriel F. Zambrano, P.A.
WASHINGTON — Safety concerns about the popular birth control pill Yaz increased Thursday as federal health scientists reported that the Bayer drug and other newer birth control treatments appear to increase the risk of dangerous blood clots more than older medications.
A new study released by the Food and Drug Administration reviewed the medical history of more than 800,000 U.S. women taking different forms of birth control between 2001 and 2007. On average, woman taking Yaz had a 75 per cent greater chance of experiencing a blood clot than women taking older birth control drugs.
Yaz contains estrogen along with a next-generation synthetic hormone called drospirenone, which is known to increase potassium levels in the blood. FDA compared medical records of women taking the drug with those taking the older drug levonorgestrel.
Yaz, Yasmin and related drospirenone-containing pills were Bayer’s second-bestselling franchise last year at $1.6 billion in global sales.
In 2009, the FDA took the unusual step of ordering Bayer to run corrective TV advertisements for Yaz on the ground that the drugmaker’s marketing campaign overstated the drugs’ ability to prevent acne and premenstrual syndrome.
Bayer Healthcare, a division of the German conglomerate, said it “is currently evaluating this publication and cannot comment at this point in time.”
The agency also reported higher complications in women using the Ortho Evra patch from Johnson & Johnson and the Nuvaring vaginal ring from Merck & Co. Inc. Those drugs combine estrogen, which is present in all birth control pills, with two other synthetic hormones launched in the last decade.
The FDA said it has no final conclusion on the drugs’ safety but will hold a meeting with scientific advisers on Dec. 8.
Consumer safety advocates have criticized the agency for approving newer, more expensive birth control drugs when cheaper generic drugs with established safety records are widely available.
“At a certain point we have to ask why the FDA continues to approve drugs that are less safe and have no benefit compared to drugs already on the market,” said Dr. Diana Zuckerman, president of the National Center for Women and Families, a consumer group for women’s health issues. “With all these different birth control options, why take the most expensive one that can also kill you?”
Recent studies have reached differing conclusions on the risks of newer birth control pills.
A study published this week involving more than 1 million Danish women found that women taking Yaz and other newer medications had twice the risk of blood clots as women taking the older hormone levonorgestrel. The findings appeared Tuesday in the British Medical Journal.
However, two studies published in 2007, conducted as part of the post-marketing requirements of the FDA or European regulators, did not find any difference in blood clotting between the two comparable groups.
Birth-control pills that contain drospirenone include Bayer’s Yaz, Yasmin, Beyaz, Safyral; Sandoz’s Syeda and Loryna; as well as Barr Laboratories’ Ocella, Watson Pharmaceuticals’ Zarah and Teva Pharmaceuticals’ Loryna.
#YAZ #YASMIN #BEYAZ #SAFYRAL are all part of the #DRSP #DROSPIRENONE containing family of oral contraceptives at the hear of an ongoing FDA investigation, and pending hearings, relating to the significantly higher risk of blood clots they pose to consumers. More information available here http://www.drospirenonelawsuits.com