After years of controversy and debate, the FDA has finalized its regulatory guidance on Essure and other hysterescopically-implanted birth control implants. In a new document released on October 31, 2016, the federal agency outlines precise requirements for a “black box” warning that should be included on the implant’s packaging, along with a patient decision checklist for women to complete before having the procedure.

Essure’s New “Black Box” Warning

The FDA does not mandate precise language for the new warning, although an example consistent with the agency’s recommendations is provided. Along the FDA’s guidelines, the packaging of any hysteroscopically-placed tubal implant intended for sterilization should:

  • Note the types of significant and / or common adverse events that my be associated with the device and its insertion, use, and / or removal procedure, including those noted in clinical trials, as well as those reported in other device use experience
  • Include a statement noting that these risks should be conveyed to the patient during the decision-making process

Here’s the black box warning example provided by the FDA, which mentions Essure explicitly, rather than the general category of hysteroscopic sterilization implants:

WARNING: Some patients implanted with the Essure System for Permanent Birth Control have experienced and / or reported adverse events, including perforation of the uterus and / or fallopian tubes, identification of inserts in the abdominal or pelvic cavity, persistent pain, and suspected allergic or hypersensitivity. If the device needs to be removed to address such an adverse event, a surgical procedure will be required. This information should be shared with patients considering sterilization with the Essure System for Permanent Birth Control during discussion of the benefits and risks of the device.

Has The Warning Changed Since March?

Yes, the new warning is notably different from the one included in a draft guidance published by the FDA on March 4, 2016.

  • Where the initial warning only said that “some patients implanted with […] Essure […] have reported adverse events,” the new language acknowledges that women have both “reported” and “experienced” these side effects.
  • The language around “intraabdominal or pelvic device migration” has been changed to “identification of inserts in the abdominal or pelvic cavity.”
  • In the new warning, FDA downgraded “allergy or hypersensitivity reactions” to “suspected allergic or hypersensitivity reactions” [emphasis added].
  • The warning for secondary surgery has also been altered. While FDA’s initial draft guidance read, “some of these reported events resulted in device removal that required abdominal surgery,” the new warning takes a far stronger stance: “if the device needs to be removed to address such an adverse event, a surgical procedure will be required.”

Do Black Box Warnings Work?

Boxed warnings represent the strictest warning measure available to the FDA, one “designed to call attention to serious or life-threatening risks.” The FDA applies “black box” warnings only to products that have a demonstrated risk of significant patient harm, discovered either through clinical studies, which involve human subjects, or data on animal toxicity if no human studies are available.

Warning Signs

Boxed warnings are well-understood by most patients as a sign of serious risk. As a result, the sales and use of a drug or medical device tend to fall sharply after it receives a “black box.”

When the FDA placed a “black box” warning on the prescription drug rosiglitazone, for example, use of the antidiabetic drug fell by 70%. Even so, nearly 4 million people were still being prescribed rosiglitazone on a regular basis, despite the FDA’s warning that the drug could increase the risk of heart attacks by up to 43%.

What Stops Dangerous Drugs & Medical Devices?

For better or worse, it is often media exposure that tips the scales for patients, but this creates the possibility that the media will focus a majority of its attention on a single dangerous drug or device, while ignoring other products with similar risks.

Rosiglitazone is not the only antidiabetic drug that can increase the risk of heart attacks. Nor was it the only antidiabetic drug that the FDA warned patients and healthcare providers about. The agency also included pioglitazone in its warnings, but usage of that drug, which received far less media attention, didn’t drop precipitously after the FDA released its black box warning. A study published in the Journal of Managed Care & Specialty Pharmacy actually observed an increase in the use of pioglitazone, likely because doctors were switching their patients from the more-popular rosiglitazone to its competitor, which was perceived, inaccurately, as less dangerous.

In short, a black box warning alone will not ensure that dangerous drugs or medical devices don’t reach patients. There is evidence that some doctors will not even have a conversation about the boxed warning with their patients. Hence the “patient decision checklist.”

Essure Patient Decision Checklist

Along with the black box warning, FDA recommends that device manufacturers include a patient decision checklist, underscoring significant risk and benefit information, in their packaging for Essure-like medical devices. The checklist is meant to be discussed and completed by every patient and every physician considering hysteroscopic sterilization implants.

The following “key items” should be included:

  • the sterilization procedure is permanent and, in some cases, irreversible
  • there are alternative contraception methods available, along with a section on their own safety and effectiveness
  • contraindications, situations in which the device should not be used
  • steps that must be followed before the implant can be relied upon as adequate contraception and a reiteration of the importance of following steps
  • effectiveness information, including data on the risks of an unintended pregnancy and ectopic pregnancy
  • a statement that no birth control device is 100% effective
  • safety risk information detailing significant and / or common adverse events, including patient-reported outcomes
  • clinical trial information detailing long-term adverse events reported in clinical trials or via device-use experience
  • discussion of the signs, symptoms or events that could represent implant-related complications
  • device material information, including any risks that may be posed by the implant’s materials
  • implant removal information, including details on why someone would have the device removed, along with the techniques necessary to remove the implant and potential outcomes

Each “topic grouping,” the FDA says, should be followed by a “line for the patient to initial her acknowledgment and understanding” of the information. At the end of the checklist will be a section where both patients and physicians can sign off, acknowledging that they have read and understood the information and had satisfactory opportunity to discuss the procedure’s implications.

As Michael Mezher at the Regulatory Affairs Professional Society notes, the new patient decision checklist does not include reference to the “black box” warning. In this omission, the FDA has rejected the requests of several public health organizations, including Planned Parenthood.

Is FDA’s New Black Box Warning Required?

Not quite. Manufacturers are not bound to the specific language outlined by the FDA. The FDA’s new guidelines are “nonbinding.” They are “recommendations,” rather than requirements. In fact, the agency’s new Essure guidance is prefaced with a lengthy disclaimer, notifying manufacturers that guidance documents “do not establish legally enforceable responsibilities.” Rather than defining a contour of the law, these guidances are intended to “describe FDA’s current thinking on a topic and should be viewed only as recommendations.”

So long as manufacturers abide by existing statutes and regulations, they are within their limits to take an “alternative approach,” although alternatives should first be approved by the FDA. If, however, a manufacturer chose to disregard the FDA’s guidelines, it’s likely that they could be held liable for “misbranding” the product, ie allowing it to be sold with “false or misleading” labeling. In this context, “false or misleading” includes labeling that does not provide adequate warnings.