Holly Kelly Ennis
Bayer's Response to The Bleeding Edge Adds Insult to Injury
Following the release of the powerful documentary The Bleeding Edge, Bayer, the manufacturer of the controversial sterilization device featured in the film, has gone on the attack. Ironically, Bayer's July 27, 2018 press release is filled with many inaccuracies and misinformation, all while protesting that the documentary is misleading. First, Bayer asserts itself as a leader in women's healthcare. This is almost comical given their triple crown birth control failures of Yaz, Mirena and Essure, all of which have been the subject of significant litigation by thousands of women injured by these products.
Bayer next asserts that The Bleeding Edge lacks scientific support, "ignoring the full body of scientific evidence" that shows that Essure's benefits outweighs it risks. By full body of scientific support does Bayer mean the clinical trials which were highly criticized in an October 8, 2015 New England Journal of Medicine article which noted the deficiencies in the original clinical trials and provided:
“The premarketing approval of Essure in 2002 was based on two nonrandomized, nonblinded, prospective studies that lacked a comparator group and enrolled a total of 926 women. The FDA review concluded that 97% of women with bilateral Essure placement could rely on the device. This determination of reliability, however, was not based on an intention-to-treat analysis and considered only women who successfully underwent the procedure and had 3-month hysterosalpingograms showing correct Essure placement and bilateral tubal occlusion (data presented to the FDA described a 14% failure rate for the first attempt at bilateral coil placement). Because of these exclusions, the declared reliability rate was based on only 664 (89%) of the 745 women who underwent an implantation attempt and did not account for 181 enrolled women who subsequently chose not to undergo the procedure (for unstated reasons), did not pass screening tests, or were excluded for not meeting other criteria. Among the 745 women who underwent an attempted Essure procedure, only 632 (85%) were followed up at 1 year for effectiveness outcomes and 682 (92%) for safety outcomes. Just 197 (25%) were followed for effectiveness at 2 years, which further limited the evaluation of adverse events and device safety.”
Although Essure is designed to remain in place for a woman's lifetime, few women in the premarketing studies were followed for more than 1 year — a limitation that precludes conclusions about longer-term risks. Appropriately, FDA approval was conditional on two mandatory post-approval studies to provide 5-year follow-up data on patients in the premarketing approval studies. However, these studies were not made well known: neither one was registered at ClinicalTrials.gov (though that probably wasn't legally required under the FDA Modernization Act) and their results were not disseminated in a timely way.
Additionally, several members of the September 24, 2015 Advisory Panel also questioned the clinical trial protocol, particularly concerning the nature of the nonrandomized, non-blinded prospective study and the lack of data on nickel allergies:
SCHALOCK: It was a question for anybody who will answer it. How do we not have data on nickel allergy when we have a device that's 55% nickel, and 20% of women -- approximate numbers -- are known to be nickel allergic? Why is there no data? How can you put this in your package insert and then have no clue?
SCHALOCK: Well, considering that they listed it as a contraindication themselves. At least from my understanding, if they're listing it, are we just making this up just for fun, or is there data? Do we have data? That's what I want to know.
CHAPPELL: Rick Chappell: I do have a parting comment. Because we are not asked, as part of Question 1 or any other question, to provide FDA with advice under general strategy, but the situation we find ourselves in today absolutely demands it because post-marketing studies behind huge clinical trials, I'd say that post-marketing studies are especially good for detecting rare outcomes. A clinical trial even with a couple of thousand could not detect some rare outcomes. But as Dr. Juran commented today, she showed that many of the medical issues faced by the patients we heard from, as severe as they are, are very common in the general population, pain, et cetera. And so we 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; it was single armed. And I say so-called dismissively because I don't see how a pivotal trial can be a non-randomized, uncontrolled trial. Therefore, I recognize the logistical difficulties, the expense, but therefore, I strongly urge the FDA to abide by its own statement, which it made in 1967, that the gold standard is a randomized clinical trial.
There were also no studies undertaken regarding any adverse or long-term effects of the PET fibers used in the device to create an inflammatory response, which have been the cause of significant harm to the women. Although Bayer claims this type of material has been used in other medical applications, it was not tested for use in the mucosal environment of the fallopian tubes, particularly when combined with the other components of the device, and Bayer has admitted it can trigger an autoimmune response in women.
Bayer next asserts that the movie's focus was told not through science, but through the stories of women. It is unclear how to illustrate how a product has impacted thousands of women without sharing their stories. However, not only women, but physicians are reporting problems with the device. Reports from physicians have nearly doubled following the FDA safety hearing. It is completely disingenuous for Bayer to assert that 99% of the women "reported to have rated comfort of wearing the Essure implants as "good" or "excellent" and 97% of women reporting being "somewhat" to "very satisfied" when the film explicitly showed how clinical trial participants answers were either 'changed' or how their answers were misconstrued to fit Bayer’s (Conceptus’) agenda.
Bayer claims the film provides no balance on the important topic of Essure removal. It is outrageous to imply that women are unnecessarily encouraging major surgeries. The fact that women are willing to undergo major surgeries because they are desperate to rid themselves of a device, which is literally killing them speaks volumes. No woman “wants” to undergo a hysterectomy or salpingectomy and surgeons do not perform unnecessary surgeries. Often, hysterectomies are required because the device, which is supposed to remain in place for a lifetime according to Bayer, has migrated and imbedded into the uterus making a hysterectomy an unfortunate necessity. Additionally Essure’s Instructions for Use regarding removal has been repeatedly modified and there was no real removal protocol until thousands of women had already undergone removal procedures. The Instructions for Use in physicians' offices today still have grossly inadequate and controversial removal instructions.
Interestingly, Bayer asserts that the film failed to disclose the alleged conflicts of interests of several individuals who spoke out against the Essure device. However, Bayer ignores the fact that the Essure device has been replete with conflicts since its conception. For example, when Essure was going through the original premarket approval process it was significantly helped by Cindy Domecus.
Essure received an “expedited approval” due to relationships between Conceptus and FDA, which created a conflict of interest. Cindy Domecus served as Senior Vice-President of Clinical Research/Regulatory Affairs at Conceptus from May 1944- December 2003, owned stock in the Corporation and was heavily involved in the development of Essure. Ms. Domecus also served on the Obstetrics and Gynecology Device Panel of the Medical Device Advisory Committee from March 1995-January 2001. Much of Essure’s clinical studies were performed while Ms. Domecus was serving both Conceptus and the FDA. Not surprisingly, Essure received a “fast track approval” from the FDA and was granted, “expedited review status.” We have been very appreciative of the Agency’s input throughout the course of the Essure product development and of their willingness to consider the least burdensome and most expeditious route to PMA filing,” said Ms. Domecus. Clearly having your Vice President of Clinical Research serve on the FDA Advisory Panel reviewing your device makes the process more “expeditious” and “less burdensome.”
However, it appears that an accelerated approval time line was critical to the bottom line and existence of Conceptus, which was in significant financial trouble at the time. On June 4, 2002, Conceptus filed paperwork with the Securities and Exchange Commission (SEC) prior to offering 4,000,000 shares of Conceptus stock for sale. In the prospectus, Conceptus noted that it had a limited history of operation and had incurred significant operating losses since inception. The SEC filing also stated, “Essure is our only product and we are wholly dependent on it. Essure may be unsuccessful, which would harm our business and force us to curtail or cease operations. We will need FDA approval before commercializing Essure in the U.S and clinical trials of Essure for that purpose are still ongoing.”
Another conflict existed when Conceptus was well aware of a nickel allergy component but elected to do what was best for their bottom line as opposed in the best interested of their patients. Essure was originally approved with the following warnings:
CONTRAINDICATIONS: Known hypersensitivity to nickel confirmed by skin test (see Warnings section below for patients with suspected hypersensitivity to nickel).
WARNINGS: Patients with suspected hypersensitivity to nickel should undergo a skin test to assess hypersensitivity prior to an Essure placement procedure.
However, when it became financially inconvenient to have the contraindication, Conceptus applied for and the FDA agreed to have this contraindication simply removed from the product labeling, and a warning implemented instead. The FDA was just as complicit in this egregious conduct as was Conceptus, which based its action on greed in order to gain an edge over its only competitor at the time. "This FDA label decision will further strengthen our competitive advantage and leadership in the permanent birth control market, and we are pleased that we were able to secure it," said Mark Sieczkarek, president and chief executive officer of Conceptus. "The upgraded label change significantly diminishes the biggest competitive selling point of our competitor's hysteroscopic sterilization product against Essure, which was the nickel hypersensitivity contraindication. We will be aggressively marketing this IFU change to the OB/GYN community, and especially to those physician accounts that are trialing the competitor's product primarily because of potential nickel allergy in patients," said Mr. Sieczkarek
Many physicians who have authored articles and ran clinical studies regarding Essure are actually highly paid spokespersons for Bayer. Cindy Basinski, who was recently the subject of a CNN report allegedly received over $150,000 in compensation from Bayer. The CNN analysis of federal data, shows that from August 2013-December 2017, Bayer paid 11,850 doctors $2.5 million related to a controversial birth control for consulting fees and similar services. It is inconceivable to believe that none of these physicians had any conflicts of interests when highly recommending Essure as the best option for their patients. The conflicts of interests surrounding this device are many and varied.
Finally, Bayer claims it is removing the device from the market due to declining sales. However, the FDA has rendered some tough unprecedented requirements for future sales of the device, making it nearly impossible for Bayer to comply and still sell the device to unsuspecting women. Additionally and more importantly, the tenecity of thousands of women from the Essure Problems Group has revealed the true destructive nature of the product. Bayer is correct that the risk-benefit profile of Essure has not changed. It is still the same dangerous device that has significantly harmed tens of thousands of women and it is high time the device is removed from the market. However, the sad truth is that unscrupulous doctors will now scramble to unload their remaining inventories and push this device on unsuspecting women to the bitter end. Bayer should step up and do the right thing and purchase all of the outstanding inventory of this product to prevent any future harm.