Temporal Trends of Urogynecologic Mesh Reports to the U.S. Food and Drug Administration

Abstract

OBJECTIVE:

To compare temporal trends of urogynecologic mesh medical device reports with sentinel U.S. Food and Drug Administration (FDA) notices and to examine all linked reports of patient death.

METHODS:

The Reed Tech Navigator is an online tool used to extract and analyze data in the Manufacturer and User Facility Device Experience database. We used FDA product codes to search for reports of synthetic mesh for stress urinary incontinence (SUI) and pelvic organ prolapse (POP). Reports with “death” listed as a patient event were queried further.

RESULTS:

There were 43,970 medical device reports involving urogynecologic mesh reported to the FDA between August 2000 and January 2019, with most occurring after the 2011 FDA communication (n=43,018, 97.8%). Of these medical device reports, 64.6% (n=28,422) were for SUI products, 27.0% (n=11,876) were for transvaginal POP products, and 8.4% (n=3,672) were for transabdominal POP products. Peak reporting occurred in 2013, which corresponded with the first major plaintiff verdicts and class action vaginal mesh settlement. There were 645 (1.5%) medical device reports of death, with 49.3% (n=318) having no cause of death identified. Only four (0.6%) could be directly attributed to the initial surgery.

CONCLUSION:

Since 2011, urogynecologic mesh has been the focus of thousands of medical device reports annually, although the data submitted are often incomplete. Few reported deaths are directly attributable to mesh products, and the majority lack sufficient information to draw causal conclusions. A high-quality registry is necessary to improve our understanding of the patient effect from urogynecologic mesh products.

Surgical mesh has been used by gynecologists since the 1970s to treat pelvic floor disorders with the goal of improving durability and efficiacy.^1–4 Synthetic mesh products have been U.S. Food and Drug Administration (FDA) approved and available to treat stress urinary incontinence (SUI) since 1996 and pelvic organ prolapse (POP) since 2002. The FDA has reported that about 1 out of 3 of the nearly 300,000 surgeries used to treat POP in 2010 and 80% of the 260,000 procedures to treat SUI used a synthetic mesh product.¹ Complications of urogynecologic mesh can include exposure, pain, or erosion into bowel, bladder or vasculature.^5,6 Rates and types of complication can be influenced by mesh composition (polyester vs polypropylene), pore size, weight, stiffness and surgical technique (transvaginal vs transabdominal).^7–9

The FDA monitors adverse events related to medical devices for all specialties through their publicly available Manufacturer and User Facility Device Experience (MAUDE) database. These medical device reports come from various sources such as manufacturer, physician or patient and vary in quantity and quality of information. Reports to the MAUDE database led the FDA to issue their first Public Health Notification regarding urogynecologic mesh in 2008, which reported complications as “rare.”¹ They issued an updated Safety Communication in 2011, which focused on transvaginal POP mesh. The FDA communication reported transvaginal POP mesh complications as “not rare” and suggested potential future regulatory changes in FDA class status and postmarket monitoring.¹ Importantly, the 2011 FDA communication did not include SUI mesh, which is used for a different indication, or transabdominal POP mesh, which has a different risk profile than transvaginal POP mesh.

After these two communications, the FDA reclassified transvaginal POP mesh from class II to class III, or high-risk, in 2016.¹⁰ Medical devices are grouped by the FDA into one of three classes based on safety and efficacy. Most surgical mesh products are classified as class II, moderate-risk devices.¹ class III devices, such as breast implants and implantable pacemakers, present a “potential unreasonable risk of illness or injury” and represent 10% of all medical devices.¹⁰ This change in status required manufacturers to submit premarket approval applications before any market release of transvaginal POP products. This series of events culminated in the formation of a 2018 advisory panel, which concluded that transvaginal mesh should be superior to native tissue repair at 3 years to support its continued use. The two companies with transvaginal mesh devices completed or were in the process of completing 522 postmarket surveillance studies when, in April 2019, the FDA ordered that all manufacturers suspend distribution of transvaginal POP mesh products immediately stating they had not “demonstrated reasonable assurance of safety and effectiveness.”¹⁰

In addition to recent FDA actions, there has been an increase in liability claims regarding urogynecologic mesh used for POP and SUI since 2000.¹¹ A 1% sampling of the Bloomberg Law Database showed 63.3% of urogynecologic mesh claims involved SUI mesh products, 13.3% involved POP mesh and the remaining claims involved both. Importantly, they demonstrated a nearly exponential increase in cases filed from 2011 to 2013 with 730 claims filed in 2011 and 34,017 claims filed in 2013.¹¹ This is supported by publicly available corporation data showing a significant increase in claims pending between 2011 and 2014.¹²

Despite public mesh concerns, the number of women in the United States who will require and seek surgical management for POP and SUI is expected to increase by 35% between 2010 and 2030.¹³ A better understanding of medical device reporting, including available information and how this has been used by the FDA and legal sources, is needed to inform patient counseling. Our primary aim is to report temporal trends of urogynecologic mesh reports to the FDA MAUDE database relative to sentinel FDA notifications with a secondary aim to examine patient reports of death included in urogynecologic mesh reports.

METHODS

The FDA MAUDE database was searched using the Reed Tech Navigator for Medical Devices.¹⁴ This is an online tool that pulls directly from FDA databases to provide information regarding regulatory and safety data for medical devices. U.S. Food and Drug Administration product codes were employed to search for all reports of synthetic urogynecologic mesh used for the treatment of SUI (product codes OTN and PAH) or POP (product codes FTL and OTO) between August 2000 and January 2019. Both the primary investigator (J.C.S.) and co-investigator (A.M.A.) searched the database independently to ensure all reports were identified. Duplicate reports were excluded. The total number of unique medical device reports were recorded for each SUI and POP product currently and formerly on the market. Reporting source (manufacturer, voluntary, user facility or distributor) and event category (death, injury, malfunction or other) were recorded along with the number of medical device reports by month and year. Categorical variables were compared between groups using chi-squared test. Institutional Review Board approval was not indicated because all data were from the publicly available FDA MAUDE database and not institutionally based.

Reports with “death” listed as an event category were queried further. Categorization of cause of death by organ system was done by the principal investigator (J.C.S.) with adjudication by co-investigator (A.M.A.) for all reports with an ambiguous cause of death. “No cause of death” was recorded when explicitly stated in the report or if no cause of death was given.

RESULTS

There were 43,970 medical device reports for synthetic urogynecologic mesh products reported to the FDA MAUDE database. Patient demographics and surgical characteristics such as age, comorbidities and surgical complications are not documented. Only 0.4% (n=161) of the medical device reports occurred before the 2008 Public Health Notification, 1.8% (n=791) occurred between the 2008 and 2011 FDA announcements, and 97.8% (n=43,018) occurred after the 2011 Public Health Notification (Fig. 1). Peak reporting occurred in 2013. Of these medical device reports, 64.6% (n=28,422) were for SUI products, 27.0% (n=11,876) were for transvaginal POP products, and 8.4% (n=3,672) were for transabdominal POP products. There were medical device reports for 18 distinct SUI products, with 10 products currently on the market as of the writing of this manuscript (Table 1). These currently available products account for 70.1% of all SUI medical device reports (n=20,146) and 45.8% of total medical device reports. The highest number of SUI medical device reports (n=11,518, 40.5%) were from Gynecare Obturator midurethral sling. The highest number of reports for retropubic slings came from Gynecare TVT Secur (n=6,178, 21.7%) and Gynecare TVT (including TVT Exact, n=5,696, 20.0%). Currently available transabdominal POP products account for 36.8% of transabdominal POP medical device reports (n=1,350) and 3.1% of total medical device reports; there are currently no commercially available transvaginal POP products. More than half (53.3%, n=6,334) of all medical device reports for transvaginal POP products involve Gynecare Prolift.

Fig. 1.

Adverse events by date and U.S. Food and Drug Administration (FDA) advisory reports.

Sassani. Urogynecologic Mesh Reports to the FDA. Obstet Gynecol 2020.

Table 1.

Medical Device Reports by Product Name

SUI Products	n=28,422	Transvaginal POP Products	n=11,876	Transabdominal POP Products	n=3,672
Currently available		No longer available		Currently available
Gynecare Obturator	11,518 (40.5)	Gynecare Prolift	6,334 (53.3)	Restorelle	1,157 (31.5)
Gynecare TVT	5,029 (17.7)	Uphold Lite	2,072 (17.4)	Upsylon	224 (6.1)
Advantage Fit Blue	1,052 (3.7)	Prolene Soft	1,170 (9.9)	Artisyn	31 (0.8)
Gynecare TVT Exact	667 (2.3)	Avaulta	1,115 (9.4)	No longer available
Solyx	543 (1.9)	Perigee	723 (6.1)	Gynecare Gynemesh	2,056 (56.0)
Desara	431 (1.5)	Surgisis	431 (3.6)	Alyte	126 (3.4)
Gynecare TVT Abbrevo	429 (1.5)	Exair	26 (0.2)	Novasilk	45 (1.2)
Altis	343 (1.2)	Ascend	5 (<0.1)	IntePro Y	33 (0.9)
Supris	86 (0.3)
Aris	48 (0.1)
No longer available
Gynecare TVT Secur	6,178 (15.4)
Align	814 (2.9)
Monarc	813 (2.9)
Blue SUI Sling	238 (0.8)
Ajust	156 (0.5)
T-sling	42 (0.1)
Desara Mini	22 (<0.1)
Uretex	13 (<0.1)

SUI stress urinary incontinence, POP pelvic organ prolapse.

Data are n (%).

Information in medical device reports was often incomplete with dates of procedure and event, details of medical or surgical complications and outcome data lacking. The majority of medical device reports were reported by the manufacturer (99.0%, Table 2). Injuries were the most commonly reported event (96.5%), followed by malfunction (1.2%) and death (1.3%). Reporter source was most likely to be the manufacturer (P<.001) and event type most likely to be injury for each type of mesh product (P<.001).

Table 2.

Medical Device Reports by Product Type

	SUI (n=28,422)	Transvaginal POP (n=11,876)	Transabdominal POP (n=3,672)	P
Source				<.001
Manufacturer	28,058 (98.8)	11,823 (99.6)	3,655 (99.6)
Voluntary	95 (0.3)	25 (0.2)	15 (0.4)
User	69 (0.2)	28 (0.2)	2 (<0.0)
Distributor	197 (0.7)	0 (0.0)	0 (0.0)
Event				<.001
Injury	27,622 (97.2)	10,791 (94.3)	3,615 (98.5)
Malfunction	417 (1.5)	462 (4.0)	37 (1.0)
Death	364 (1.3)	189 (1.7)	16 (0.5)
Other	17 (<0.1)	3 (<0.0)	0 (0.0)

SUI stress urinary incontinence, POP pelvic organ prolapse.

Data are n (%) unless otherwise specified.

There were 645 (1.5%) medical device reports of “death,” with 49.3% (n=318) of these having no cause of death identified. The most common cause of death by category was cardiovascular (n=102, 15.8%) followed by malignancy (n=94, 14.6%, Table 3). Only four (0.6%) deaths could be directly attributed to the initial surgery. These included two intraoperative vascular injuries and two cases of necrotizing fasciitis in the immediate postoperative period. One vascular injury occurred during SUI trocar placement when the femoral artery was lacerated, though details describing how or where along the femoral artery are lacking. The other vascular injury occurred during placement of a transvaginal POP mesh at the time of trocar placement through the sacrospinous ligament. This report states, “the bleeding occurred due to the puncture needle before mesh was placed into the patient.” Additionally, a woman undergoing midurethral sling placement was admitted postoperatively in a moribund state and subsequently underwent leg amputation during management of necrotizing fasciitis. The medical device report notes infection affecting “the obturator externus, abductor compartment, hamstrings, sartorius muscle, lateral aspect of quadriceps, sciatic nerve, and the gastrocnemius soleus muscle group.” The last reported death was from a prolonged postoperative course after transvaginal POP mesh placement that was attributed to “necrotizing perineal infection” with ultimate cause of death listed as ventilation acquired pneumonia and septic shock.

Table 3.

Cause of Death

Cause of Death	n=645
No cause of death	318 (49.3)
Cardiovascular	102 (15.8)
Malignancy	94 (14.6)
Pulmonary	44 (6.8)
Sepsis or infection	41 (6.4)
Overdose or trauma	17 (2.6)
Neurologic	12 (1.9)
Other*	17 (2.6)

Data are n (%).

^*Other category includes renal, gastrointestinal, and nonspecified hemorrhage.

DISCUSSION

Medical Device Reports for synthetic urogynecologic mesh to the FDA MAUDE database have dramatically risen in the past 10 years. We found that peak reporting occurred in 2013, with thousands of reports filed each month. Unfortunately, the data submitted were often incomplete, making this information insufficient from which to draw conclusions or develop policy. Although 1.5% of all medical device reports reported “death,” a very small proportion of these could be attributed to the incident mesh procedure based on available data.

Urogynecologic mesh reports to the FDA increased after the 2011 FDA communication but did not exhibit a sharp upward trend until early 2013. This increase followed the first two major plaintiff verdicts against transvaginal mesh manufacturers, which awarded close to $15 million in damages.¹² Large class action settlements followed, which further spurred claims and an increasingly litigious environment regarding mesh.¹² The media coverage of mesh litigation and legal advertisements directly affects our patients’ perceptions of urogynecologic mesh products. In a study of 99 female urology patients, 33% reported advertisements as the most influential source on their opinions regarding transvaginal POP and SUI products, compared with 23% who listed a medical professional in that role.¹⁵ In another survey of 77 new urogynecology patients, Dessie et al¹⁶ found that one third (33.8%) of patients surveyed had a negative impression of transvaginal mesh and almost half (48.1%) received their information from the media with another quarter (24.7%) obtaining information from the internet.

The 2019 FDA order to suspend distribution of transvaginal POP mesh follows the actions of other countries, such as Australia and the United Kingdom, which have banned transvaginal POP mesh within the past few years.¹⁷ Moreover, declining utilization of urogynecologic mesh products after the FDA notifications has been reported worldwide.^18,19 The 2019 mesh order explicitly states that based on currently available evidence, the risk-benefit profile of SUI and transabdominal POP mesh is favorable.¹⁰ Despite this assertion, many patients have limited or incorrect knowledge regarding types of mesh available and their safety profile.^16,20 Many resort to the internet, which does not always provide a reliable source of information. Our data do not include specifics regarding the event precipitating the report to the medical device reports, except for some reports with “death” listed as an outcome. Of those with “death” listed, the majority were either unrelated to the mesh products themselves or seem clinically distinct. Further information is needed regarding all listed events, which would aid in patient counseling.

Given the confusion surrounding publicly available mesh information, numerous professional societies have attempted to clarify the role and safety of mesh products, specifically for SUI. The American Urological Association published a position statement on the use of vaginal mesh for SUI and felt “that any restriction of the use of synthetic polypropylene mesh suburethral slings would be a disservice to women who choose surgical correction of SUI.”²¹ The American Urogynecologic Society (AUGS) and the Society for Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction published a joint statement emphasizing the safety and effectiveness of polypropylene midurethral slings.²² This position paper was supported by the American College of Obstetricians and Gynecologists, the Society of Gynecologic Surgeons, and other professional organizations. All organizations support the FDA recommendations regarding informed consent and adequate health care provider training both for procedural tasks and recognition and management of complications.^21,22

This study highlights the flaws of the MAUDE database as a basis for making medical and policy decisions, including a lack of comprehensive information regarding each report, an absence of contextual information such as the number of products placed, and the temporal association with major media and courtroom events. The MAUDE database is a central repository for medical device reports from all specialties, which subjects them to comparable limitations in reporting. In fact, similar limitations have been identified by studies looking at vascular, cardiac and urologic medical devices.^23–25 The FDA estimates around 100,000 prolapse mesh products and 200,000 incontinence mesh products were placed in 2010 alone, which is helpful to keep in mind when viewing the total number of medical device reports over a nearly 20-year period.¹ User facilities are required to report any device associated death to both the manufacturer and FDA within 10 days.²⁶ The information provided in the MAUDE database sometimes includes “death” as a patient event; however, as noted above, these are rarely able to be attributed to the initial surgery or product. Nearly half of all reports had no cause of death listed and the majority of remainders were either medically implausible (ie, death from pancreatic cancer after SUI mesh placement), unrelated (ie, gunshot wound after POP mesh placement), or did not contain enough information to make any causal conclusion. This limited reporting system has led AUGS to conceptualize and develop a national registry meant to track POP treatment outcomes and complications.²⁷

In 2015, AUGS began the national Pelvic Floor Disorders Registry with the goal to closely monitor the outcomes of surgically and nonsurgically managed POP.²⁷ The Pelvic Floor Disorders Registry is supported by grants and industry sponsors. They specifically aim to look at effectiveness, safety and quality of life associated with native tissue and mesh augmented repairs. Information is submitted to the Pelvic Floor Disorders Registry by research staff and health care providers at participating centers. This is in contrast to the FDA MAUDE database where reports contain disparate amounts of unverified information submitted by patients, health care providers, user facilities and manufacturers.^1,26,28 Although the Pelvic Floor Disorders Registry contains a nationally represented sample, it is not all-inclusive of POP management within the United States, nor does it contain information about women who required SUI management exclusively. Excluding these groups of patients will affect the comprehensiveness and utility of the information available. Additionally, data collected are from predominantly large academic centers, which may affect generalizability to a national sample. However, this source of publicly available, high quality information represents the first step towards an inclusive patient registry that can be used to monitor safety and efficacy data with the goal of improving patient outcomes and satisfaction.

Limitations of this study are related to available data. Reports to the FDA MAUDE database are sporadic and require effort by both mandatory (device manufacturers) and voluntary (patient and health care provider) reporters.¹ The vast majority of medical device reports reported are from the manufacturer (99.0%) with no available information regarding how they came to be aware of the perceived event. Our finding of manufacturers as the primary reporting source is consistent with a 2019 review of nearly eight million medical device reports across all specialties that showed 96.6% originated from the manufacturer.²⁹ Additionally, Sandberg et al²⁸ have previously noted that the FDA MAUDE database has data-entry flaws, likely a result of their multiple reporting sources and lack of identifiable patient information. They noted this results in unidentified duplicates with some reports representing multiple patients. To counteract this, the Reed Tech Navigator identifies and separates duplicate reports, which likely explains the difference between the 2,874 medical device reports from 2008 to 2011 reported in the 2011 FDA Communication, compared with 791 unique reports identified during this period in the current study. This discrepancy may also relate to misfiling under incorrect product codes or inclusion of other related devices such as trocars used to place mesh. As the Reed Tech Navigator pulls reports directly from the MAUDE database, it is likely that these data represent a true trend regarding the increase in reports relating to FDA notifications and media-covered litigation.

The number of women who will seek surgical management for POP and SUI is growing,¹³ and we need an accurate way to track urogynecologic mesh utilization and complications. Reports to the FDA MAUDE database are useful as an initial warning system for trends in Medical Device Reports but are insufficient in scope and information to be used for policy making going forward. AUGS Pelvic Floor Disorders Registry is a step in the right direction. Information obtained from high-quality patient registries will help guide regulatory bodies and manufacturers, as well as allow health care providers to offer accurate information to their patients for shared decision making.