GAITHERSBURG, Md. -- Several safety and efficacy factors should be considered when evaluating transvaginal surgical mesh for treating pelvic organ prolapse (POP), an FDA advisory panel recommended.
The Obstetrics and Gynecology Devices Panel, which convened here Tuesday, made specific recommendations to the FDA for evaluating postmarketing data on the three surgical mesh devices that remain on the market today -- Boston Scientific's Uphold LITE and Xenform and Coloplast's Restorelle DirectFix Anterior.
For years, safety concerns have dogged anterior-placed mesh in the vaginal compartment, which were reclassified as high-risk class III devices in January 2016. Thousands of adverse events and serious injuries, including several deaths, have been reported to the FDA in relation to the devices. Now the agency is considering what to do with data from ongoing postmarket surveillance studies of these remaining devices, and sought the committee's advice.
Following a full day of manufacturer presentations, patient testimonials, and statements from professional societies -- including the American College of Obstetricians and Gynecologists, the American Urogynecologic Society, and the Society of Gynecologic Surgeons -- the panel deliberated for several hours. Of top concern included how to evaluate safety and efficacy, particularly when comparing these therapy options to native tissue repair, another method of POP treatment.
Most panel members said studies comparing the two types of repair must show superior efficacy of the surgical mesh in order to justify its higher risks, and superiority should be demonstrated at 12 months, 24 months, and 36 months post-op.
"I do think that it needs to have superiority because there are very specific complications associated with mesh, so I don't know what the purpose would be of finding an equivalently bad process that might also have higher levels of complications," commented panel member Donna Mazloomdoost, MD, of the National Institutes of Child Health and Human Development in Bethesda, Maryland, who added that superior efficacy lasting only 12 months is "not sufficient because the whole purpose of using the mesh is durability, and to me 12 months is not durability."
Two panel members voted against requiring superiority, saying non-inferiority was sufficient.
"If we're looking at a group that already maybe has fewer options or because they've had more prolapse surgery or they've had other medical problems... maybe the non-inferiority is a reasonable standard because you're already treating a patient population that has fewer options and at least they're doing as well, or if not a little bit better," said Daniel Morgan, MD, of the University of Michigan in Ann Arbor.
Objective Versus Subjective Efficacy
Looking even closer at surgical outcomes, the panel discussed whether anatomic or objective outcomes, as well as subjective patient-reported outcomes should both be incorporated when assessing efficacy of surgical mesh compared with native tissue repair. The panel was in agreement that both outcomes must be considered when determining efficacy, but more weight should be given to subjective outcomes.
"If you had a score of 100, then 75% of that score should be subjective and 25% objective. So they should be looked at together but not weighted the same," commented panel chair Keith Isaacson, MD, of Newton-Wellesley Hospital in Massachusetts.
The panel went on to recommend that a validated questionnaire be used to blindly obtain this data both before -- in order to have baseline comparison data -- and after surgery.
When the committee turned to device safety, members discussed the FDA's previously compiled list of known adverse events that should be tracked, which included:
- Pelvic pain
- Erosion/exposure of mesh
- De novo voiding dysfunction (i.e. incontinence)
- Vaginal shortening
- Atypical vaginal discharge
- Neuromuscular problems
- Vaginal scarring
- De novo vaginal bleeding
- Fistula formation
Members said this was a "comprehensive list" but suggested adding intraoperative complications, such as hemorrhage. However, the panel agreed that pain was generally the most important adverse event to consider, particularly in regard to its impact on quality of life. The panel also recommended these adverse events be evaluated for at least 36 months post-operatively.
One question to the patient that the group recommended be included in a long-term follow-up study was: "Would you do this procedure again?"
"[This question] could be incredibly valuable as a tool to assess quality of life," suggested Isaacson.
Other Study Considerations
While discussing other research questions to consider beyond safety and efficacy, the panel touched on several potentially confounding variables for the FDA to bear in mind when evaluating the post-market data. One of these included the hot topic of the surgeon's level of training, which all panel members strongly felt could affect safety and efficacy outcomes for mesh versus native tissue repair. As a result, the groups recommended that studies gather data on the performing physician's volume of surgery cases and level of training.
Characteristics of the patient population should also be collected, members said, including comorbidities such as obesity or connective tissue disease that can influence outcomes. Baseline characteristics of the two surgery groups should be as similar as possible to eliminate these as confounding factors.
The FDA is not required to follow advisory panels' recommendations but it usually does.
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Transvaginal Mesh Complications and Side Effects. The panel was in agreement that both outcomes must be considered when determining efficacy, but more weight should be given to subjective outcomes. Food and Drug Administration (FDA) for the treatment of vulvovaginal atrophy (m/fda-approves-monalisa- and-work, and html). Sponsors are strongly encouraged to evaluate OTC contraceptive products towards this use. Conversely, Michael Carome, director of Public Citizen's health research group, was unmoved by FDA's push for greater clinical trials, calling transvaginal mesh products the "poster child example of whats wrong with FDA oversight of medical devices." "Our views on these.