Before selling Essure to the public, Conceptus had to submit the device to scientific and regulatory review by the FDA’s Center for Devices and Radiological Health. The Center, which was established in 1976 in the wake of the crisis over the Dalkon Shield — an intrauterine device that caused several deaths and generated thousands of lawsuits because of its design, materials and lack of testing — has different requirements for approval of medical devices than the Center for Drug Evaluation and Research, which reviews drugs. “The legal standard for approving a drug explicitly requires adequate and well-controlled clinical investigations,” says Patricia Zettler, former associate chief counsel for the FDA, who now teaches food and drug law at Georgia State University. In contrast, for devices, the standard is “reasonable assurance” of safety and effectiveness, she says, which is subject to interpretation.
Conceptus applied for approval of Essure in the category of Class III medical devices, which, according to the FDA, “are generally the highest risk devices and are therefore subject to the highest level of regulatory control.” This class goes through the most rigorous application process for devices, known as premarket approval. But it is also the only class of device shielded from most lawsuits, thanks to a 2008 Supreme Court decision that makes it difficult for patients to sue in state court for devices that have received premarket approval. In addition, the FDA granted Essure expedited review, a legacy of AIDS activism intended to speed access to potentially lifesaving therapies, in which the FDA puts a treatment at the beginning of a review queue and provides advice on clinical trial design. The FDA fast-tracked Essure, it said, “because this device offers significant advantages over existing approved alternatives.”
Although Class III devices are protected from most lawsuits and undergo the most rigorous approval process, they are not required to undergo randomized controlled trials — in which one randomly assigned group of patients gets the treatment, another group gets a different treatment, and the outcomes are compared. The FDA said in a written statement to me that it did not believe a control group was necessary for Essure because, at the time, “effectiveness and safety outcomes for laparoscopic tubal ligation were well known from years of clinical use” and could be used for comparison. Sanket Dhruva, a Yale University cardiologist and researcher of high-risk medical devices, strongly disagrees. “We all know the most rigorous data in clinical medicine is through randomization,” control groups and follow-through, he says. Ideally, he explains, the researchers would have given 1,000 women Essure and another 1,000 women laparoscopic sterilization and followed them for five years to compare rates of pregnancy, complications, hysterectomy and repeat surgeries. Without a real-time comparison, he says, “we just didn’t have the data.”
For its third, “pivotal” trial, the most important for achieving approval, Conceptus reported on 439 women. None of the women became pregnant, for an effectiveness rate of 100 percent — though Conceptus noted that “no method of contraception is 100% effective, and pregnancies are expected to occur in the commercial setting.” The company compared this to a long-term study of 10,000 women who elected tubal ligations, which found a rate of pregnancy of 5.5 per 1,000 for the first year. A “serious adverse event” — in which the Essure device perforated the fallopian tube, was expelled or wasn’t placed correctly — occurred in 4.6 percent of participants. After one year of use, according to the data, 9 percent of women reported back pain, 3.8 percent reported abdominal pain and cramps, and 3.6 percent reported painful sexual intercourse.
ncG1vJloZrCvp2PEor%2FHoqWgrJ%2BjvbC%2F02eaqKVfqLNwv9Oyo55nYmV%2BeHuPcGZrbl%2BawLTB0Z5m