Delayed scrutiny: Problems with birth control device expose gaps in FDA oversight

Kama Sales had two school-aged children and was busy running a day-care center in Hot Springs, Ark., when she and her husband, Steve, decided in 2008 they were done having children.

Sales, now 40, recalls seeing a flier in her OB-GYN's office advertising a new permanent birth control device called Essure, an alternative to the surgical procedure of tubal ligation. It's the only permanent, nonsurgical method approved by the Food and Drug Administration. “What caught my attention was that there was no down time,” she said. “It was easy-in, easy-out. I could have it done on Friday and be at work Monday.”

But that's not how it worked out. Sales described the procedure as “extremely” painful, and she experienced heavy bleeding for a month. She felt sharp abdominal pains, and later experienced joint pain and gained 70 pounds. “I signed up to not have any more children, not to live in pain,” said Sales, who has met with an attorney to discuss possible legal action.

In 2013, she had a hysterectomy to remove the device. Sales is one of a growing number of women opting to take it out. The manufacturer offers physicians no specific training in how to remove Essure.

More than 19,000 women—some of whom call themselves the “E-sisters”—have joined a Facebook support group called Essure Problems. Many have reported debilitating abdominal pain, heavy bleeding and large weight fluctuations. They claim these side effects were not disclosed to them by the manufacturer or their doctors, and that their complaints have been dismissed for years by the device manufacturer, physicians and the federal government. At least five women have filed product liability lawsuits against Bayer Healthcare, the product's manufacturer, in connection with the use of Essure.

Last month, the FDA issued an alert after a search of the agency's Manufacturer and User Facility Device Experience, or MAUDE, database found more than 5,000 reports of adverse events related to Essure, some more serious than the risks listed on the warning label. The database includes reports of unintended pregnancies, complications during removal, and five fetal deaths after Essure failed to prevent pregnancy. An estimated 750,000 women worldwide have had the Essure device inserted.

The FDA recently updated the potential risks of the Essure device on its website. It also scheduled a Sept. 24 public advisory meeting in Washington of its Obstetrics and Gynecology Devices Panel, which will bring together physicians, researchers, patients and industry advocates to review the safety and efficacy of the product.

The agency has asked the committee to provide recommendations regarding appropriate use, product labeling and the potential need for additional post-market clinical studies.

The controversy over Essure is raising broader concerns about how the FDA reviews medical devices; lack of transparency in clinical trials; the adequacy of post-approval surveillance for safety and effectiveness issues; the amount of attention given to patient complaints; and the marketing and financial incentives to doctors aimed at boosting sales of new products.

One major issue is that post-market studies evaluating the long-term and real-life experiences of patients and clinicians following FDA approval of products are sparse. “There are a lot of issues that we never know about because we are not systematically collecting data and learning over time,” said Dr. Harlan Krumholz, a professor of medicine and policy studies at the Yale School of Medicine. “We need to take a good look to determine whether or not the drugs and devices are achieving their promise.”

It may help that the FDA last year began requiring manufacturers of certain high-risk devices to embed electronically readable unique device identifiers to facilitate the tracking of adverse events associated with use of the device. Supporters say this will help reduce medical errors, improve product registries and make device recalls faster and more efficient.

On the other hand, some experts warn that flaws in the FDA approval and post-market surveillance systems could be worsened by fast-moving legislation in Congress designed to speed the development and approval of devices and drugs. Already, new devices, drugs and procedures reach the market with limited clinical trial data, they say.

“Essure exemplifies the dangers,” said Dr. Sanket Dhruva, a clinical scholar at Yale University, who co-wrote a New York Times op-ed piece this month with Dr. Rita Redberg of the University of California at San Francisco warning about the risks of the proposed 21st Century Cures Act. “It has been on the market for over a decade despite serious safety concerns when there are other, safer, contraceptive options.”

Essure could become a poster product for critics of the current regulatory process. Diana Zuckerman, president of the Washington, D.C.-based advocacy group National Center for Health Research, said her group heard Essure complaints from more than 900 women this year when it conducted an online survey. “If even half of what I've heard is true, there are still many problems,” Zuckerman said. The main issue, she added, is the questionable accuracy of the manufacturer's clinical data about the product.

Bayer says the reported adverse events represent only a small fraction of users. But Dhruva said it's a high number given that patient reporting is voluntary, and that the FDA's delay in acting points to the need for more rigorous post-market surveillance.

The FDA said in a written statement that it required five-year follow-up studies when Essure was approved. Neither was a randomized controlled trial. In a phase II trial of Essure with 227 women, 42 women “voluntarily withdrew,” and seven suffered perforations. Of the 518 to have the device inserted in the second trial, adverse events that prevented reliance on the device occurred in 4.5% of the women. According to the manufacturer, however, the studies did not reveal new safety concerns or sound alarms on known ones.

Bayer stands by the safety and effectiveness of its product, noting that it passed the premarket approval process for Class III medical devices, the most stringent type of device marketing review.

“We looked at all the data and came to the conclusion that it is a very safe and effective method of permanent contraception,” said Dr. Edio Zampaglione, vice president of medical affairs for women's health at Germany-based Bayer Healthcare, which in 2013 acquired the firm that developed Essure for $1.1 billion. “We still have that same conclusion.”

Problems that may have arisen with Essure have more to do with physicians' skills and competency in working with the device than with the device itself, he said. “We are not in the business of training physicians,” he said. “Those are skills the physicians should already have.”

Essure was developed by Conceptus, a Mountain View, Calif.-based device manufacturer, and approved by the FDA in 2002 for women ages 21 to 45. The device is a small, soft, flexible coil made out of nickel that is inserted into each fallopian tube. Scar tissue forms around the coils, blocking the tubes and preventing eggs from becoming fertilized or getting into the uterus. It uses no hormonal agents and requires no surgery or anesthesia to insert. The procedure can be done in an OB-GYN's office in less than an hour.

During the first three months after having the Essure device inserted, women must use an alternative birth control method. Then they must return to the doctor's office to undergo a follow-up X-ray of the uterus and fallopian tubes to make sure the device has been placed properly and the tubes are fully blocked. At that point the method is considered 99.83% effective.

In July, Bayer received FDA approval for clinicians to use transvaginal ultrasound as an alternate test to make sure the device has been properly placed. The company said that all physicians who provide the device are expected to be trained or retrained by mid-2016.

After the Essure device was approved and placed on the market, it rapidly gained popularity among women who didn't want to get pregnant. “For years we had been waiting for a vaginal approach to sterilization, so when Essure hit the market, it was exciting,” said Dr. Shawn Tassone, an OB-GYN based in Austin, Texas, who used to insert as many as 10 of the devices a month and trained other doctors on how to do the procedure.

Within five years, Conceptus' net sales of Essure topped $15 million, according to earnings reports. Sales soared to $140 million by 2012. A 2009 study in the journal Contraception comparing the cost of having Essure placed in-office versus surgical tubal ligation found Essure was 33% cheaper, offering savings of $1,178 per procedure.

Essure's original labeling warned of potential long-term risks such as chronic pelvic pain, slippage of the device from the fallopian tubes to the lower abdomen, and allergic reactions to nickel. It also said there was a rare chance of getting pregnant despite having the device inserted.

But the FDA's MAUDE database contains reports of more serious problems, including fetal deaths, uterine perforations due to broken or unwound coils, and air embolism during removal. The agency cautions, however, that it's difficult to confirm that the Essure device directly caused the reported problems noted in the database.

“Yes, there are risks. There are risks with any medical procedure,” said Dr. Elizabeth Hicks, an assistant professor of obstetrics and gynecology at the University of Washington. “Patients need to be properly counseled and providers trained to minimize complications and deal with them when they occur.”

But the National Center for Health Research's Zuckerman said it's not enough for physicians to provide counseling based on the existing clinical data about Essure. “It doesn't do any good to share data if the data you are sharing are inaccurate,” she said.

The MAUDE database includes reports from women who said they visited multiple doctors who offered varying approaches for removing the Essure device. The original labeling for the device noted the lack of data on the safety and effectiveness of surgery to remove the device.

Amanda Dykeman, 33, a stay-at-home mom who lives in Coal Valley, Ill., said she experienced many of the problems other women have reported, including bloating, heavy bleeding and pain in her abdomen. She said she asked doctors about having the device removed. But they “either didn't know anything about the device, or couldn't believe it could be the source of my problems,” said Dykeman, who is an administrator on the Essure Problems Facebook support group.

Bayer's Zampaglione acknowledged that there is no specific training for doctors on how to remove the Essure device. But he added that the product labeling includes directions about which patients should have the device removed and general guidance on how to do it.

This is hardly the first time an FDA-approved device or procedure has generated patient-safety and effectiveness concerns years after it has been approved. A recent study published in JAMA Neurology found that between 2005 and 2009, Medicare beneficiaries who underwent carotid artery stenting—a procedure that gained FDA approval in 2004—had a 32% mortality rate within two years of the procedure. That study concluded that more evidence is needed to support the use of the procedure outside of randomized clinical trials.

In their New York Times op-ed, Redberg and Dhruva warned that the 21st Century Cures Act would severely weaken the FDA's “already ineffective regulatory scheme for medical devices,” shifting the burden of evidence for safety and effectiveness to post-market studies. But such studies are often delayed months or years and many are never completed or published.

Yale's Krumholz said that what's needed is a national commitment to systematically collecting data to identify problems with medical products in general clinical use. “Small issues become large when millions of different kinds of people are exposed to them,” he said.

Others say the U.S. needs a better system for regulators, manufacturers, healthcare providers and researchers to hear and respond to reports from patients who experience adverse events. Dykeman said feeling unheard is one of the most common complaints of women on the Essure Problems Facebook page.

Tassone, the OB-GYN who used to insert a lot of Essure devices, said he stopped offering the procedure after dozens of his patients complained about adverse effects, asked for removal, or got pregnant. “As physicians, our responsibility is to listen,” he said. “You have to be open to that.”