Holly Kelly Ennis
FDA Sets Guidelines for Essure Post-Market Study
On September 24, 2015, the FDA held a 12 hour emotionally charged hearing to evaluate the risks and benefits of the Essure Sterilization device after receiving complaints from thousands of women who have been harmed by the device. Five months later, on February 29, 2016, the FDA finally rendered its decisions concerning Essure and among other requirements, ordered Bayer to conduct yet another post market surveillance study to obtain more data regarding Essure’s benefits and risks. In a letter dated February 29, 2016 from the FDA to Bayer, it ordered Bayer to conduct post market surveillance to evaluate the following:
1. What are the rates of Essure System (device) removal in routine clinical practice in the U.S.? What are the reasons for women to undergo device removal? What are the baseline patient and procedural characteristics that may be associated with higher likelihood of device removal? What are the outcomes associated with device removal (e.g., resolution of symptoms) and at what time point following device removal are these outcomes observed?
2. What gynecologic surgical procedures are being used to remove the device or any portion of the device, and what are the rates for each of these surgical procedures in routine clinical practice? How does the surgical procedure chosen for device removals vary based on location of the device, time since device placement, and patient medical history?
3. What are the rates of uterine and/or tubal perforation (symptomatic or asymptomatic), device migration, and device expulsion in routine clinical practice? What are the clinical sequelae, and interventions required, for these events? How do the migration rates compare to rates of clip or ring migration experienced after bilateral tubal ligation?
4. What are the rates of symptoms of allergic/hypersensitivity reactions and autoimmune-like reactions in women with the device, compared to rates in women who receive bilateral tubal ligation (as an interval procedure) in routine clinical practice? How are the
allergic/hypersensitivity reactions and autoimmune-like reactions characterized in terms of symptomology (including single and/or multiple concurrent events) and timing since device placement? What are the baseline and post-procedural characteristics that may be associated with higher risk of developing allergic/hypersensitivity reactions or autoimmune-like reactions? How do these symptom complexes respond to therapy, including device removal?
5. What are the rates of patient reported outcomes such as abnormal uterine bleeding (AUB) in routine clinical practice through three years post device placement, compared to women who receive bilateral tubal ligation (as an interval procedure)? What are the baseline patient and procedural characteristics that may be associated with higher risk of AUB? How is AUB experienced post device placement, characterized in terms of onset, frequency, interventions received, reasons for AUB (such as malposition or perforation of the insert), and severity measured by impact on activities of daily living?
6. What are the rates of patient reported outcomes such as chronic pelvic pain in routine clinical practice through three years post device placement, compared to women who receive bilateral tubal ligation (as an interval procedure)? What are the baseline patient and procedural characteristics that may be associated with higher risk of chronic pelvic pain? How is chronic pelvic pain experienced post device placement associated with chronic pain conditions experienced before device placement? How is chronic pelvic pain experienced post device placement, characterized in terms of onset, frequency, interventions received, reasons for pain (such as malposition or perforation of the insert), and severity measured by impact on activities of daily living?
7. What are the risk factors or underlying reasons for failure to complete the three steps of the Essure System method (placement, confirmation, reliance), specifically failure to receive confirmation testing? How are factors such as health insurance coverage, age, parity, difficulty/length of procedure, and other patient characteristics related to the likelihood of confirmation test compliance?
The FDA recommended that Bayer develop a study which includes:
1. Prospective enrollment of a minimum of 1,200 women in each of two arms (for a total of 2,400 subjects): hysteroscopic sterilization with the Essure System and laparoscopic bilateral tubal ligation.
2. Follow-up of patients for a minimum of three years. The schedule of follow-up visits should include data collection at baseline (pre-placement), immediately post-placement, soon after placement (e.g., 1 week), at confirmation testing, and over the follow-up period.
3. Prospective data collection on:
a. Baseline Patient Characteristics: patient demographics, anthropometric characteristics (height, weight, body mass index), relevant gynecological history (including pregnancies, and gynecological procedures such as endometrial ablation), history of vaginal bleeding including menses and AUB, medication use, family history of autoimmune disease, history of allergies/hypersensitivities, history of chronic pain conditions, history of permanent implants (including body tattoos with metallic colorants), and baseline laboratory testing including inflammatory and autoimmune markers and allergy testing before sterilization;
b. Essure System Practitioner Characteristics: experience with the Essure System as measured by number of Essure System placements, date of successful completion of
Essure System training program including number of proctored cases performed,
c. Tubal Ligation Procedural Characteristics: for women who receive bilateral tubal ligation, what type of procedure was performed (e.g., use of electrocoagulation, clips, rings, etc.);
d. Essure System Procedural Characteristics: for women who receive the Essure System, characteristics of the procedure including length, physician assessment of procedural difficulty, reasons for procedural difficulty or complications (such as poor visualization, anatomical irregularities or tubal spasm), number of attempts, concomitant procedures, post-placement insert location, patient symptoms including pelvic pain soon after placement (e.g., 1 week post-placement), and confirmation test results;
e. Surgical Procedures for Removal of Essure System: methods of device removal (e.g., hysterectomy, salpingectomy, hysteroscopic device removal, laparoscopic device
removal); complications and outcomes of device removal (e.g., symptom resolution);
plan for analysis of explanted devices and surrounding tissue; laboratory testing including
inflammatory and autoimmune markers and allergy testing at time of removal and at a
later time point after removal;
f. Adverse Events: e.g., intra-operational and post-operational complications, infection, allergic/hypersensitivity reactions, development of autoimmune-like symptoms, uterine or tubal perforation, device migration, device expulsion;
g. Immunological testing: laboratory testing including inflammatory and autoimmune markers and allergy testing, pre- and post-implant in a subset of patients;
h. Quality of Life post-sterilization: measured by patient reported outcomes, including chronic pelvic pain and AUB;
i. Other Gynecological Events post-sterilization: pregnancy including pregnancy outcomes, gynecological procedures such as endometrial ablation and the indication for the procedure, any other relevant gynecological events;
j. Compliance with Steps of the Essure System method: reasons for non-compliance, including factors such as health insurance coverage, age, gravidity/parity, and difficulty/length of Essure System placement procedure.
4. Geographically distributed clinical sites that include large medical centers as well as small health care facilities and office-only practices, to ensure that the data will be representative of routine clinical practice in the U.S.
5. Practitioners with varying levels of experience with Essure System placement, including some physicians that are newly trained in order to be representative of real-world experience.
It was also suggested that Bayer work with other entities experienced in such data gathering including the FDA, Centers for Disease Control (CDC), Patient Centered Outcomes Research Institute (PCORI), National Institute of Health (NIH), American Congress of Obstetricians and Gynecologists (ACOG), and patient advocacy groups (shout out to Essure Problems Group) following in the model of the Collaborative Review of Sterilization (CREST) study in which long term data is collected on multiple sterilization procedures.
The FDA is requiring a fairly comprehensive study of the device, albeit the device should be removed from the market while the study is pending. If not for the tireless efforts of the Essure Problems Group, this study would never have been ordered or required. The Group will continue its fight to have the device removed from the market, and to demand that adequate warnings and a patient decision checklist be implemented as soon as possible.
For questions concerning the post surveillance study or any other Essure related inquiries, contact attorney Holly Ennis at 1-800-856-6405 or visit us online at www.Ennislaw.com.