In the summer of 2002, the pharmaceutical company Organon unveiled what it believed would be a game-changer in the multibillion-dollar birth control industry. Its product, NuvaRing, was the first hormonal contraceptive vaginal ring in the world. An easy-to-use device that relieved women of the burden of taking a pill on a daily basis, it was hailed as the greatest advance in contraception since the introduction of the pill in 1960.
“We’ve never seen anything like this in my lifetime,” Dr. Carolyn Westhoff, a professor of obstetrics and gynecology who worked on NuvaRing’s clinical trials, told Newsday that August.
“It’s really an exciting time for contraceptive users,” Dr. David Grimes, a clinical professor of obstetrics and gynecology at the University of North Carolina, told The Washington Post. “It’s a new era.”
Before NuvaRing could be marketed in the United States, however, it needed the approval of the Food and Drug Administration, and the FDA had some concerns. Most hormonal contraceptives carry a risk of blood clots, with a higher risk of cardiovascular events among women who smoke, especially if they are over the age of 35. But in one of the clinical trials for NuvaRing, a healthy woman in her 20s had developed a blood clot — a surprising occurrence that an investigator determined was probably related to the birth control device.
As a result, the FDA said Organon should include a statement in NuvaRing’s packaging insert specifically mentioning the clinical trial and warning women and health care providers that the ring might carry a higher risk of causing blood clots — formally known as venous thromboembolism, or VTE — compared with other hormonal contraceptives.
Organon executives adamantly opposed such a statement. They had invested major resources in developing the new device and had secured a patent that promised to bring in billions of dollars in profits if it became a success. They were planning to market it not only as innovative and easy to use but as delivering lower, and thus safer, doses of hormones. An elevated VTE warning label would have been a huge blow. Such a warning might have discouraged women from using NuvaRing and made doctors less inclined to prescribe it — significantly cutting into the potential return on investment.
“We should really try to get it out of the text,” Wim Mens, from Organon’s regulatory affairs division at company headquarters in Oss, Netherlands, wrote to colleagues in an email in the fall of 2000.
Americans may assume that the fine print in a drug’s packaging represents the collective scientific knowledge about that medication, allowing doctors and patients to make informed health care decisions. In fact, negotiations between pharmaceutical companies and the FDA over warning labels are common during the drug approval process, with drugmakers endeavoring to cherry-pick what’s included in order to present their products in the best possible light.
“There’s always a tug between the FDA and the manufacturer as to what the label is,” Sidney Wolfe, founder and senior adviser of Public Citizen’s Health Research Group, a public health advocacy organization, told The Huffington Post.
It’s a process that’s skewed in favor of the drug companies. The FDA relies on the manufacturers to provide clinical trial results and other data the agency uses to evaluate their drugs and devices, and 70 percent of the funds for FDA reviews comes directly from the industry through user fees. As a result, Wolfe said, “these battles are tilted even further against public health and safety.”
In the case of NuvaRing, Edwina Muir, Organon’s director of regulatory affairs in the United States, suggested in 2000 that they agree to some of the FDA’s other recommendations, such as including data from animal testing in the packaging insert, as a “bargaining chip” so that they could exclude “more important issues” such as the VTE warning and bleeding data from the clinical trial, according to internal company emails.
By the end of 2000, negotiations with the FDA appeared to be turning Organon’s way. Since clinical trials are designed primarily to test for efficacy, rather than safety, the drugmaker argued that the results of the trial should not be taken as evidence that NuvaRing was unsafe. The FDA backed off its initial recommendation and suggested noting simply that it was “unknown” whether NuvaRing had an increased risk of blood clots.
“The label change looks much better,” David Stern, Organon’s director of U.S. reproductive marketing, wrote in an email to his colleagues on Dec. 22, 2000, “however, I am still unhappy with the VTE section of the label. Obviously the case that we presented to them has made some impact, in that they have added the statement about [it] being unknown if NuvaRing has this increased risk.”
Still, Stern asked his colleagues, “What are the chances that this section can be removed altogether?”
While NuvaRing has proven effective for the majority of its users, a growing number of women have come forward with allegations that the birth control device has caused blood clots and other severe side effects.
Lyndsey Agresta, a 27-year-old resident of Cleveland, had been using NuvaRing for barely a month when she began experiencing migraines. She found the pain so unbearable that in June 2008, she called her mother at 3 o’clock one morning to take her to the emergency room and look after her 5-year-old son, Dominic. She said she “couldn’t take it anymore,” her mother, Diane Agresta, told HuffPost. That was the night, Diane said, that “everything just changed.”
Doctors discovered that Lyndsey was hemorrhaging in her brain, and she suffered a massive stroke as a result. The cause was a blood clot, which doctors believed developed from Lyndsey’s use of NuvaRing, Diane said. They surgically removed two-thirds of her right cerebral hemisphere and transferred Lyndsey to a long-term acute care hospital, where, paralyzed, she was confined to her bed.
She remained there for six months and underwent additional surgeries, but nothing more could be done. In January 2009, doctors determined that Lyndsey had fewer than six months to live and recommended hospice care. She died one week after being admitted to hospice.
Lyndsey’s death has been especially difficult for Dominic to comprehend, her mother said. Diane said her grandson continues to struggle with Lyndsey’s absence, and it pains her that Lyndsey might still be alive had she been better informed about NuvaRing’s side effects.
Merck spokeswoman Kelley Dougherty disputed the claim that NuvaRing’s manufacturers misled consumers about its side effects.
“The company has provided appropriate and timely information about NuvaRing to consumers and the medical, scientific and regulatory communities,” Dougherty told HuffPost. “We remain confident in the safety and efficacy profile of NuvaRing — which is supported by extensive scientific research — and we will continue to always act in the best interest of patients.”
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