Essure FDA Warnings: Will A Recall Be Issued?

Essure FDA Warnings: Will A Recall Be Issued?2016-11-29T09:19:11+00:00

doctor examining Essure patientEssure is a relatively new method of female sterilization advertised by its manufacturer Bayer as a safe, “surgery-free” alternative to tubal ligation, which was previously one of the only permanent birth control approaches readily available to women. Released in 2002, Essure is currently used for family planning by an estimated 750,000 women worldwide.

Though the FDA granted Essure the Pre-Market Approval (PMA) necessary for the manufacture and sale of the “high-risk” device in 2002, an influx of distressing patient complaints has the agency taking a second look. In response to thousands of reports from patients suffering severe adverse effects of the device as well as a citizen’s petition calling for a retraction of Essure’s PMA, the FDA launched a comprehensive investigation on Essure’s efficacy rates, possible side effects, and complications in 2015.

The FDA is slated to share its findings and decisions on possible regulatory changes resulting from this investigation by the end of February 2016. Could official Essure FDA warnings or even a recall be on the agenda?

How Was Essure Approved In The First Place?

Essure consists of a pair of coil-shaped metal “micro-inserts” that act as permanent contraception by causing the development of  tissue barriers that close off the fallopian tubes. Because it’s a device that must be implanted inside a woman’s body in order to function, it fits within the FDA’s Class III for medical devices—the highest-risk category.

Normally, Class III devices cannot be released for public use without going through a strict pre-market approval review process, which often requires the manufacturer to run a number of stringent safety tests, clinical trials, and other studies to help demonstrate efficacy and a reasonable level of safety. However, because Essure was presented as a “first-of-a-kind” device, the FDA accelerated its approval with an “Investigational Device Exemption” and allowed the manufacturer to submit less-than-rigorous data, such as results from uncontrolled, non-randomized clinical trials.

Rather than granting outright approval, FDA offered conditional Pre-Market Approval (CPMA) for Essure if its manufacturer agreed to follow a set of special regulations, including prompt reporting of any adverse effects and / or injuries discovered.  The FDA also required a comprehensive 5-year post-market study which:

  • Compares 2 sets of Essure patients – one group that doesn’t exclusively rely on Essure for contraception, and one group that does
  • Must include and examine pregnancies and other outcomes, adverse events, and “histological explant data following any extirpative surgeries”
  • Must be submitted to the FDA through annual reports until the 5 years is up

Because correctly placing both coils on the first attempt is crucial to the functioning of the Essure system, the FDA asked for another post-approval study regarding the success of newly-trained physicians with the implantation procedure. This study had to cover:

  • Rates of successful implantation of both coils
  • Identification of predictive factors of failure at the first implantation attempt

These post-market studies had supposedly been successfully completed by 2015, but researchers and consumer advocates question the soundness of the data. And though these studies, along with the early manufacturer-sponsored clinical trials, suggest high patient satisfaction and near-zero complication rates, complaints to the FDA from women all over the nation tell a different story.

Thousands Of Complaints In 2 Years

From Essure’s approval on November 4, 2002 up until May 31, 2015, the FDA received a total of 5093 adverse event reports concerning the device, but only 943 were filed in the first 11 years. The FDA found cause for alarm in the sheer volume of reports received after October 2013 — 4150 complaints in just 2 years.  What’s more, most of the reports are made voluntarily by patients and physicians (adverse event reports are required of manufacturers). If reporting had been compulsory, it’s likely that an even larger number of complaints would have been submitted to the FDA. Today, the total amount of Essure-related adverse reports has reached over 10,000.

Commonly-Cited Problems

The reports describe a variety of adverse physical symptoms that patients believe to be caused by Essure implants:

  • Pain, especially in the abdominal or pelvic region (3353 reports)
  • Unusually heavy or irregular periods (1408)
  • Headaches (1383)
  • Fatigue (996)
  • Unexplained weight changes (936)

In addition to these troubling symptoms, some patients faced serious Essure complications directly caused by specific characteristics of the device, procedural errors, or malfunctioning:

  • Patient incompatibility with device, including nickel allergies (941)
  • Device migration (482)
  • Device differing from expectations (301)
  • Breaking of device (259)
  • Incorrect placement of device (133)

Most reports included more than one of the symptoms or problems listed above.  

At Least 9 Deaths Recorded

A total of 9 deaths connected to Essure were revealed from the reports.  4 of these were adult deaths attributed to:

  1. An infection contracted after the implantation procedure
  2. A uterine perforation during device placement
  3. An air embolism suffered during Essure removal surgery
  4. Suicide that may have been related to suffering / loss from Essure

The other 5 death reports involved fetal deaths from women who became pregnant despite having Essure implants.

“Essure Problems” Group Presents Citizen Petition To FDA

Thousands of women who found themselves afflicted with debilitating adverse symptoms after Essure implantation had no one to turn to for help or support. They describe going from doctor to doctor in search of one who could figure out what was wrong, or even just to find a physician who would take their complaints seriously. Many doctors were unfamiliar with Essure itself, much less the possible adverse effects that could occur, especially since Bayer training and advertising material portrays it as a simple, “worry-free” device.

Essure patient using laptopSo in 2011, when a New York resident named Angie Firmalino started the “Essure Problems” Facebook group in order to warn her friends and family of the device that caused her years of excruciating pain and heavy bleeding, the group grew steadily to over 25,500 members (by Jan. 2016) as women from all over the country banded together to help each through the pain, suffering and uncertainty.

Always working to raise awareness for Essure victims, Firmalino and other group administrators have made numerous public appearances, including a speech before Bayer shareholders in Germany, and even aided in organized a citizen’s petition alleging that Bayer violated the terms of Essure’s FDA approval agreement and should therefore be pulled from the market.

The FDA’s Investigation

In response to public outcry over Essure and the citizen petition, the FDA made an announcement in September 2015  that it was planning to thoroughly investigate the safety and effectiveness of Essure. In addition to reviewing relevant literature, the agency also held a public panel meeting and opened a docket (open from July 22 to October 24, 2015) for the public to share any comments, reports, and grievances regarding the device.

Pressing Issues Revealed In Panel Meeting

The Obstetrics and Gynecology Devices Panel of the FDA’s Medical Devices Committee, a group of respected researchers, medical professionals, and other health care industry experts, was assembled to discuss Essure on September 24, 2015. The panel meeting was open to the public and consisted of an Essure background presentation from the FDA, an Open Public Hearing during which audience members were invited to speak and present to the panel, and a closing discussion that included specific recommendations from the panel members. 

Victims Shared Tragic Stories, Called For Ban

During the Open Hearing session, many women who’d experienced life-altering adverse effects from Essure stepped forward to speak. Almost 20 patients presented their stories, including members and administrators from the online “Essure Problems” community who had traveled at their own expense in order to have their voices heard:

  • Angie Firmalino. After receiving Essure in 2009 and suffering 2 years of severe joint aches, pelvic pain, and bleeding, an ultrasound revealed that the Essure coils had migrated, fragmented, and became embedded in her uterus. In order to remove the broken pieces, Firmalino underwent several surgeries, including a hysterectomy. No one had told her that migration, perforation, or adhesion could occur, and she says that if she had “any idea of the possible consequences of Essure,” she would not have chosen the device.  Though Bayer now lists migration and perforation as possible adverse events on Essure’s label, Firmalino still feels that impact of such effects is “ruthlessly downplayed.”
  • Kim Hudak. In 2000, she participated in an early Essure clinical trial. Shortly after implantation, she developed adverse symptoms such as fatigue, painful periods, migraines, and joint pain, including a sharp, persistent pain in her right hip. Though these symptoms were severe enough to keep her from working a full-time schedule, she feels that the Bayer-employed researchers strongly “lead” her to give Essure high ratings in clinical trial questionnaires. For example, when rating comfort level for the device, Hudak says, “I was told specifically that if I can’t definitely feel that coil inside of me, I should rate it as excellent.”
  • Sharilyn Ervin. Shortly after undergoing Essure implantation, Ervin experienced bleeding, cramps, and migraines severe enough that she went to the ER, but no one was able to diagnose her or help alleviate her symptoms. Suffering at home, her unexplained condition worsened to the point where she lost bowel control and needed a caretaker at all times. She ended up hospitalized for 17 weeks, and although many specialists were called in to attempt a diagnosis, doctors still could not pinpoint what had gone wrong.

In addition to recounting their tragic personal experience with the device, the “Essure Problems” admins described seeing countless examples of re-operations, pregnancies, perforations, and other complications from user postings, gave statistics on complication rates culled from group surveys, and emphatically asked that the FDA ban Essure to prevent more women from falling victim to the pain and suffering they’d endured.

Metal Experts Say Ailments Are Caused By Manufacturing Defects

Also during the Public Hearing, two speakers with expertise in the metal finishing industry proposed possible explanations for Essure side effects relating to metal sensitivity:

Ryszard Rokicki. Rokicki is an independent metal finishing researcher who specializes in improving the biocompatibility of medical devices, particular those formulated from stainless steel, nickel, and cobalt. He believes that many Essure side effects stem from “intermetallic inclusions” (impurities that may form during the manufacturing process) on the nitinol surface of the device’s outer coils.  Properly-finished nitinol doesn’t pose a hazard, but nitinol with inclusions can cause “catastrophic” leaching of nickel onto surrounding tissue.  

Though nitinol is also used in other implantable devices such as stents (heart valves), it’s less likely to cause issues in those applications due to differences in implantation site. Stents are constantly exposed to blood flow, so any leached nickel is washed away and eventually excreted in the urine.  But Essure implants are in permanent contact with fallopian tube tissue, allowing the leached nickel to pool and accumulate.

According to Rokicki, Essure could be made safe if coils afflicted with surface inclusions could be detected and discarded before device assembly.  He says this could be achieved with simple, inexpensive chemical testing that’s “100% effective,” which would be a large improvement over the visual inspection testing that is currently used in the nitinol manufacturing for Essure.

Mark Bell.  licensed metallurgical engineer, Bell presented various Essure unit photos to show examples of pre-existing “latent manufacturing processing defects” that he believes many devices on the market could contain and that may be at the root of some cases of device migration and fragmentation. Such defects include cracks, unpolished surfaces, and crimping, which he says could weaken the coils and cause them to “fail and break in service.”

Bell’s recommendation to the FDA is to pull Essure from the market until more research on manufacturing defects has been completed.

Physicians Speak Out

Several medical doctors voiced harsh criticism of Essure during the Open Hearing:

  • Dr. Julio Novoa.  Dr Novoa spoke about the stark contrast between clinical trial results and real-world patient surveys / reports, and declared that “the FDA’s reliance on company-sponsored clinical data is by its very nature flawed.” He believes that adverse events are “grossly under-reported,” as data from Essure Problems surveys reveal more than 500 unplanned pregnancies and an average of 100 cases per month in which hysterectomy and / or fallopian tube removal surgeries are required.  Additionally, he says that Essure implantation is “absolutely and unequivocally a surgical procedure,” noting that hospitals, state medical boards, and health insurance companies categorize the procedure as surgical. He considers Bayer’s advertising of Essure as nonsurgical as “not only misleading but unethical and potentially criminally deceptive.”
  • Dr. Charles Monteith.  A former NC state medical director of Planned Parenthood, Dr. Monteith now specializes in female sterilization reversal and has performed over 200 Essure removal surgeries. He’s highly disapproving of how difficult and unreliable Essure insertion can be, confessing that in his experience, he was “never sure
    [the device] was going to work when [he] sat down to insert it.” He points out that even the pivotal trial data indicate this difficulty, since 1 in 10 times doctors failed at successful implantation on the first try. He also decries the fact that because the majority of gynecologists are not familiar with proper removal, women are often forced to undergo hysterectomy, a procedure that most gynecological surgeons are trained in.
  • Dr. Amy Reed.  An anesthesiologist famous for campaigning against dangerous medical devices with her husband Dr. Hooman Noorchashm, Dr. Reed asserted that the very concept behind Essure coils is “immunologically flawed.”  Having both an M.D. and Ph.D. in immunology, she sees the problems commonly suffered by Essure patients as “classic symptoms of immune symptoms run awry” and believes they result from the inflammatory response that the device was designed to elicit.

The doctors chided the FDA for approving Essure based on data that was likely heavily influenced by Bayer and asked the agency to demonstrate its concern for the well-being of American women  by reconsidering its decision.

Was Essure’s Approval Based On Poor Or Limited Data?

After the Open Hearing, the panel members discussed specific issues and gave several recommendations to the FDA.

One major issue discussed among the panel was the quality of research regarding Essure, including the clinical trials submitted for Pre-Market Approval.  The FDA itself stated in a summary of the panel meeting: “Although relatively low rates [of adverse events] were reported in many of these publications, significant limitations must be taken into account when reviewing the data….”  Some flawed or limited characteristics of the data Bayer provided to the FDA include:

  1. No Control Group.  All of the 3 clinical trials conducted by Bayer — the Phase I, Phase II, and Pivotal trials– were single-arm studies, which means that they lacked a control group to compare against, severely limiting any interpretation of the results. Numerous postmarket studies used by Bayer as evidence of low complication and high efficacy rates harbor this design flaw as well.
  2. Limited Follow-Up Of Study Participants.  Especially for a device intended as a permanent birth control solution, long-term follow-up is crucial in assessing the risk-benefit profile. Yet although 1 of the 3 original clinical trials is ongoing and the other 2 attempted follow up with study participants for 5 years, follow-up for many participants was not obtained.
  3. Heavy Reliance On Retrospective Studies.  Unlike prospective studies, in which researchers create a plan to study an outcome of interest, assemble an appropriate pool of study participants, and gather baseline data before any study participants develop the outcome of interest (for instance, a particular health condition),  retrospective studies are conducted “after the fact” using already-available data that may have been recorded for non-research reasons.  Some examples of such data would be medical charts and records, patient or physician surveys, and telephone interviews.  Retrospective studies are often criticized because they are more prone to bias than prospective studies — it’s easier for researchers to “cherry pick” data.
  4. Homogenous Or Too-Small Study Populations.  To get an accurate picture of how a medical device will perform in the general population, it’s important for studies to examine as large and diverse a subject pool as possible.  But some studies provided by Bayer only included data from a single institution. Also, there were some instances in which a study culled data from the same institution as another included study, causing considerable overlap in patient populations between multiple investigations.

Some panel members were convinced that if the manufacturer had stepped up to meet the research “gold standard” by conducting randomized, controlled clinical trials for the PMA, Essure’s adverse effects could have been discovered much sooner and countless injuries might have been prevented.

In the words of Dr. Rick Chappell from the University of Wisconsin: “[W]e find ourselves in a situation, 13 years after this device was approved by the FDA, of asking ourselves about pain and bleeding irregularities and other very common outcomes. And we are doing so because this was approved on the basis of a so-called pivotal trial which was not randomized, not controlled.”

Other Criticisms From The Panel:

  • Lack Of Removal Options.
  • Limited Consideration Of Metal Allergies.

Safety Review In Progress – FDA Warnings May Result

The FDA declares the Essure investigation a “high-priority issue for the Agency” and posted in an update that it was in the process of reviewing information from the panel meeting, public docket, and any additional medical literature and adverse event reports published or received since the meeting.

Did Bayer Violate Essure’s Pre-Market Approval Agreement?

In order to maintain the FDA stamp of approval for a Class III medical device, the manufacturer must strictly follow the terms set out by the FDA in the original PMA.

As we will see, some researchers have examined the preliminary data furnished to the FDA by Bayer and found it lacking, and allegations have been made that the manufacturer violated the pre-market approval and therefore should be taken off the market.