I write today to update my last Presidential Message from April 18, 2019 on the April 16th FDA Announcement ordering both manufacturers of the three surgical mesh products for transvaginal repair of prolapse to stop selling and distributing their products in the U.S. My previous message highlighted several unanswered questions about the FDA Announcement, including why the order was made prior to publication of 3-year data, and why it did not accommodate the use of these devices for patients at high risk of failure from native tissue repairs.
Based on social media, it appears that many of you are concerned about these questions as well. This is reflected in the recent Change.org petition, Ensure Ethical and Balanced FDA Mesh Research. The petition calls on the FDA to;
“protect the ethics and intent of the -522 studies, and to ensure these challenging circumstances result in the best outcome, by reserving final regulatory determinations until the 3 year study period has been reached”…….,
and “also consideration of highly relevant non-522 clinical trials that provide critical insight into these procedures and their importance in women's healthcare.”
The petition has been signed by more than 2,700 people and has engendered further anxiety, such as,
“Due to the FDA decision regarding vaginal mesh placement for pelvic organ prolapse, it is possible that minimally invasive and open procedures, including midurethral sling and sacrocolpopexy will be scrutinized to the same degree.”
In an effort to answer these questions, Shawn Menefee, President Elect, Charles Rardin, Past President, Michelle Zinnert, CEO, and I had a call with 10 members of the FDA Obstetrics and Gynecology Devices Branch. It was an illuminating call that provided answers to these questions, and the goal of this communication is to bring this information to members of our Society.
Why was the announcement made prior to the completion of the 3-year study period for the 522 studies?
Based on the 2011 Obstetrics and Gynecology Panel’s recommendations on safety and efficacy, the FDA issued post-market surveillance study orders (522 studies) for these devices in 2012. Both Boston Scientific and Coloplast initiated 522 studies with 36-month follow up, as required by FDA’s 522 orders. The FDA then reclassified transvaginally placed mesh for pelvic organ prolapse to a Class III device in 2016. As part of this reclassification, the manufacturers that were marketing devices at that time were also required to submit premarket approval (PMA) applications, although the FDA allowed them to use the 522 studies that were underway.
The PMA process is the agency’s most stringent device review pathway, and is a Congressionally mandated process with strict criteria, including the timeline. So the timing of the April 16th FDA order for manufacturers to stop marketing transvaginal mesh prolapse procedures was based on this Congressionally mandated timeline. It required the FDA Obstetrics and Gynecology Branch to make this decision based on the available evidence submitted by the manufacturers at that point. Importantly, based on a variety of reasons, some of these studies were slower in recruitment/enrollment than anticipated and the 36-month data collection was not complete by the time FDA needed to make its decision. Given today’s climate, I recognize the challenge of enrolling participants in studies like the 522 studies, and certainly we hope that the 36-month data for all such patients would be used. This is why the FDA requires the completion of the 522 studies. Incidentally, once 36-month follow up of the 522 studies is complete, then the companies can resubmit these data under the same PMA.
Were relevant non-522 clinical trials considered in making the decision?
The NIH funded 2 PFDN randomized controlled trials, which included transvaginal mesh for prolapse. The SUPeR Trial, that compares the efficacy and safety of native tissue repair with vaginal hysterectomy and suture apical suspension versus uterine conservation with Uphold Lite, for primary repair of uterovaginal prolapse with a minimal follow-up of 36 months. The 36-month results are completed. The ASPIRe Study is a three-arm study that compares the Uphold Lite to sacral colpopexy and native tissue repair in post hysterectomy prolapse. While recruitment was near completion at the time of the FDA Panel, none of the participants had undergone 36-month assessment. The SUPeR data was presented at the February 2019 FDA Panel Meeting. In our conversation with the FDA, they noted that they reviewed all information submitted by industry to support the PMA. They also noted that the ASPIRe Study and similar studies, can apply for an IDE for the transvaginal mesh products. Likewise, new devices are also open to investigation as part of a research trial once an IDE is in place.
Why has the FDA not considered the use of these devices in high-risk populations?
Many FPMRS surgeons reserve the transvaginal mesh prolapse repairs for high-risk patients who have failed a prior native tissue repair, and would like to have the ability to use the devices in this population. However, the FDA evaluates the proposed device in the population for which the device is proposed in the PMA. That is to say that the manufacturer determines the study population. The manufacturers have the possibility to request approval for high-risk populations with adequate supporting data.
Does this now mean that using some form of free-cut mesh for transvaginal use is considered “illegal?”
The FDA does not regulate the practice of medicine. In the course of treatment, providers may offer patients surgical techniques that use cut mesh transvaginally, which in their education, training and experience, may benefit the patient. AUGS encourages providers pursuing this approach to 1) employ a detailed shared-decision-making model and robust consent process and documentation, 2) engage in registry or other data collection process so that we can gather as much reproducible collective experience as is possible.
Does the FDA plan to change its regulatory expectations for the traditional midurethral sling or sacral colpopexy mesh?
The FDA first publicized safety concerns about transvaginal use of mesh for prolapse in 2008, and expressed stronger concerns in 2011. These safety concerns were the basis of issuing 522 orders in 2012 and reclassifying the devices as Class III Devices in 2016. They have consistently made a clear distinction between midurethral slings and sacral colpopexy mesh, and transvaginal mesh for prolapse. Moreover, they have not initiated 522 orders related to traditional midurethral slings or sacral colpopexy mesh, and expressed no future intent to do so.
It is my hope that this information from the FDA will dispel some of the angst generated by the April 16th announcement. To put the announcement in context, it does not preclude future innovation, but defines a clear process for determining safety and efficacy prior to marketing, and that includes the research to establish the safety and efficacy of these specific devices.