Curr Urol Rep (2014) 15:380 DOI 10.1007/s11934-013-0380-3
FEMALE UROLOGY (K KOBASHI, SECTION EDITOR)
Implications of the FDA Statement on Transvaginal Placement of Mesh: The Aftermath Michelle E. Koski & Eric S. Rovner
Published online: 3 January 2014 # Springer Science+Business Media New York 2014
Abstract The release of the U.S. Food and Drug Administration (FDA) safety communication on the use of transvaginal mesh (TVM) for pelvic organ prolapse (POP) has resulted in changes in the pelvic reconstruction community. This monograph reviews the implications of the FDA statements over the last 18–24 months. Recent findings show that there have been significant developments in the areas of regulatory mandates, media and medico-legal activity, and statements from surgical societies. In summary, well-publicized communications from the FDA and major medical organizations are defining a change in the use of TVM for POP. Keywords Transvaginal mesh . Pelvic organ prolapse . Food and Drug Administration . Urinary incontinence
Introduction The number of surgeries for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) has increased significantly over the last decade [1]. Transvaginal mesh (TVM) has been used frequently in the correction of POP and SUI. It has been estimated by the U.S. Food and Drug Administration (FDA) that, in 2010, approximately 300,000 women underwent surgical procedures in the United States for POP and approximately 260,000 for SUI. Of these estimates, approximately one out of three POP surgeries used mesh, and three out of four of the mesh POP procedures were done transvaginally. This article is part of the Topical Collection on Female Urology M. E. Koski (*) : E. S. Rovner Department of Urology, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29451, USA e-mail: [email protected] E. S. Rovner e-mail: [email protected]
For SUI surgeries, over 80 % were done transvaginally with mesh [2••]. Such widespread expansion of mesh in female pelvic surgery has led not only to substantial change in practice, but also to well-publicized communications from the FDA and major medical organizations. This monograph will review the implications of the FDA statements over the last 18–24 months.
FDA Regulatory Process and Communications Preformed mesh kits for pelvic surgery were approved as “Class II” devices through the FDA regulatory 510(k) process. From 2002 to 2011, the FDA cleared more than 100 mesh products indicated for SUI and POP [3, 4]. In that era, the FDA classification of surgical mesh products as Class II devices meant that device manufacturers were required to show “substantial equivalence,” as compared with existing products (“predicate devices”), in order to gain approval. Premarketing clinical data regarding efficacy and safety were typically not required to support clearance for mesh products while this pathway was in use [5]. The FDA initially issued a safety communication regarding the use of mesh in pelvic reconstructive surgery in 2008 and opened a database to collect additional information on mesh complications—the Manufacturer and User Facility Device Experience (MAUDE) database. It should be noted that the MAUDE database is a passive surveillance system with several limitations, including the potential for submission of incomplete or inaccurate data, underreporting of events, lack of denominator data, and a lack of report timeliness [6•]. An FDA update was issued in July 2011, detailing their analysis of the MAUDE database [7•]. In the 3-year period between FDA communications, an additional 2,874 mesh-related complications were reported to the database. Although it was acknowledged that device reports typically increase after an
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FDA communication, the emphasis of the subsequent report was that transvaginal mesh complications are “not rare.” In the 2011 report, which focused on TVM POP and did not address TVM for SUI, the FDA performed an independent literature review and concluded that TVM in the apical and posterior compartments does not provide substantial added benefit. Furthermore, this document asserted that although TVM in the anterior compartment may provide anatomic benefit, this does not necessarily result in improved symptomatic results. However, it is important to note that in this document, the FDA did not specifically recommend against the use of mesh for the repair of POP or SUI, nor were there mandatory recalls of any particular mesh or mesh “kit.”
Curr Urol Rep (2014) 15:380
disorders and their surgical repair in partnership with the FDA, the National Institutes of Health, the American College of Obstetricians and Gynecologists (ACOG), and industry— the Pelvic Floor Disorders Registry. Initially, the registry will focus on surgical and nonsurgical treatment of POP. It is designed to monitor patient outcomes for providers and manufacturers, as well as to provide data for the FDA-required postmarket research as part of the reclassification process for POP TVM products. Manufacturers are not required to participate in the AUGS registry; however, those who do not participate are still required to file postmarketing studies with the FDA and must create their own data set for submission.
Implications for the Public Implications for Manufacturers On the basis of the deliberations from the September 2011 meeting of the Obstetrics and Gynecology Devices Advisory Committee of the FDA (which are now available on the FDA Web site [8]), assessment of the MAUDE data, and their independent literature review, the FDA is considering the recommendation that urogynecologic surgical mesh used for transvaginal repair of POP be reclassified from Class II (lowto moderate-risk devices) to Class III (high-risk devices). Class III devices require premarket and postmarket clinical studies for approval. The FDA announced a new action on January 4, 2012 [3], requiring manufacturers of TVM for POP and of single-incision slings to perform postmarket studies (“522 studies”) on their products. As of February 27, 2012, 95 postmarket study orders had been issued to 34 manufacturers of surgical mesh for POP, and 14 orders were issued to 7 manufacturers of single-incision slings [4]. In the 1.5–2 years allotted for these studies, POP TVM products and singleincision slings will remain available for clinical use [9]. For SUI, the Devices Advisory Committee of the FDA agreed that the currently marketed first-generation slings are safe and effective, with a positive risk:benefit profile [4, 8]. In March of 2013, the FDA updated their Web site to include more information for patients and physicians regarding the use of mesh for SUI [6•]. This information is based on an analysis of the MAUDE database, FDA literature review, and input from the September 2011 Device Advisory Committee. The FDA’s independent literature review confirmed that the safety and efficacy of multi-incision slings is well established in clinical trials up to 1 year [6•]. In the wake of the FDA requirements for postmarket studies, which may prove to be expensive and time consuming, in addition to the burgeoning product liability issues, several TVM manufacturers have voluntarily ceased production, marketing, and sales of their products. Since the summer of 2012, the American Urogynecological Society (AUGS) has been in the process of creating a national registry for pelvic floor
The FDA statement initially led to significant confusion for patients, the public, physicians, and the media. For example, the statement did not mention that complications may occur with traditional nonmesh repairs. The complications cited do occur with traditional repair (with the exception of mesh erosion and exposure), but the exact incidence is unknown. The update issued by the FDA discussed the use of mesh for SUI and POP in the same statement, leading to confusion between the mesh used for POP repair and that used for SUI (this has been clarified in later statements [6•]). This resulted in a cycle of misinformation from the media to the public, which extended to some very well established media outlets [10]. An important medico-legal implication of this period of misinformation is that a substantial portion of the lawsuitdriven media output has not and does not differentiate mesh for SUI from that used for POP, even though the FDA proceedings have not associated the same strength of concern with mesh used for midurethral sling as it has with mesh for POP. Legal ads have a high penetrance into the patient population, with similar findings in two studies in two different geographic areas finding that 60 % of patients aware of TVM are aware through legal advertisements [11, 12]. The Internet is saturated with these sources as well. A perfunctory Google™ search for the term “transvaginal mesh” (as of May 2013) reveals a roughly 10:1 ratio of lawsuit-orientated information to other sources in the first two pages [13].
Medicolegal Implications The first lawsuit against a mesh manufacturer (Bard) resulted in a $5 million verdict to a patient who asserted that alleged design defects led to damage to her colon [14]. $500,000 was awarded to her husband for “loss of consortium.” In this lawsuit, the judgment was paid by the manufacturer, but the implanting physician was found responsible for 40 % of the liability. The patient’s lawyers plan to press forward with
Curr Urol Rep (2014) 15:380
claims against the surgeon at a later trial [14]. The bellwether first trial against Ethicon (the first of over 1,800 cases against the manufacturer pending in New Jersey courts) was settled in February 2013, awarding $11.1 million to the plaintiff. The jury found that Ethicon inadequately warned the surgeon of the Prolift TVM kit’s risks and misrepresented the device to the patient [15]. At present, the majority of the lawsuits against the manufacturers are being processed as multidistrict litigation under a single judge, with trials to be held in West Virginia. As of May 2013, 21,257 cases had been filed in federal court in West Virginia against five manufacturers (C.R. Bard, American Medical Systems, Boston Scientific, Ethicon, and Coloplast) (http://meshmedicaldevicenewsdesk.com/ latest-in-the-litigation-concerning-mesh-and-medicaldevices/mdl-news-21257-cases-filed-in-federal-transvaginalmesh-litigation/). At present, the lawsuits are directed against manufacturers, but it is unclear whether physicians will eventually be named as well. There is legal precedent in older cases that supports physician liability in device cases. Mucowski et al, provide an excellent overview of these liability issues and the role of informed consent [16].
Implications in Organized Medicine In the midst of the flurry of medico-legal news, legal advertisements, and other layman’s media productions, it is important to keep in mind that physicians are still the primary advocates for unbiased scientific information and for their patients’ care. There are several well-written responses to the FDA update issued by professional societies, including the American Urologic Association (AUA) [17, 18], the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) [19••], AUGS [20], ACOG [21], and the Society of Gynecologic Surgeons (SGS) [22]. The AUA has two position statements, addressing POP [17] and SUI [18] separately. Most of the statements are in agreement with the FDA statement regarding surgeon training, proper selection of patients, detailed counseling of the patients about the treatment options and the complications related to mesh use, and the need for postmarket studies to confirm efficacy and safety. In 2012, the International Urogynecological Association (IUGA) published several reports based on their roundtable meeting discussing graft usage. Although the “ideal graft” [23] has not yet been determined, the usage of type I mesh can be optimized with some of these recommendations. Several articles discuss patient selection for TVM [24], optimization of safety with graft use [25], and possible training requirements for physicians [26]. The IUGA recommendations for training considerations focus more on the development of an “added qualification” process, as opposed to the creation of new credentialing guidelines, citing the variability of TVM procedures for POP [26]. In contrast to this approach, in February of
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2013, AUGS issued a document outlining guidelines for privileging and credentialing physicians for sacrocolpopexy [27] (note that the FDA safety communication and literature reviews are not critical of mesh use in sacrocolpopexy [2••]). Other organizations, such as ABU, AUA, ABOG, and SUFU, have chosen not to issue such guidelines for privileging and credentialing. It remains that the optimal mechanism for determining competence and, therefore, privileging/credentialing in surgery remains controversial. As such, privileging remains a local process in each community. As always, patient counseling and informed consent are of paramount importance, and the significance of proper counseling is further emphasized by the current media and medicolegal environment. The FDA notice, IUGA roundtable report, and AUA and SUFU statements all have detailed guidelines for consenting patients for physicians [7•, 17, 18, 25]. Given the paucity of clear and accurate information on the Internet and television [11, 12], one might argue that beyond specific patient counseling, there should be distribution of accurate information on TVM to the general public. For example, one result of the current media output is the potential limitation of the use of TVM by medical malpractice insurers, hospital formularies, and medical insurance companies. Hospitals Insurance Company, a medical malpractice insurer, issued a communication to insured physicians in October 2012, to inform them that they would be excluding coverage for TVM procedures for POP as a result of, among other things, “plaintiffs’ attorneys actively seeking patients to bring lawsuits” (letter from D. Feldman of Hospitals Insurance Company, 10/ 25/2012). In response to these types of measures, AUGS released a position statement against the restriction of surgical options for pelvic floor disorders [28]. This statement outlines key points regarding TVM for POP (Table 1) [28].
Table 1 Key points from the AUGS position statement on restriction of surgical options for pelvic floor disorders [28] 1. A complete restriction on the use of surgical mesh was not the stated intent of the FDA safety communication. 2. The decision on surgical alternatives should be made by the patient and his or her surgeon. 3. A ban on surgical mesh would prohibit the surgical studies mandated by the FDA and recommended by the NIH, ACOG, and AUGS. 4. In some circumstances, transvaginal mesh for POP may be the most appropriate surgical option. 5. Any restriction of mesh slings for the treatment of stress urinary incontinence is clearly not supported by any professional organization or the FDA. 6. Any restriction of mesh placed abdominally for the treatment of prolapse is clearly not supported by any professional organization or the FDA. 7. Instead of a ban on mesh, the implementation of credentialing guidelines so that mesh procedures are performed by qualified surgeons was recommended.
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Conclusions In summary, the FDA Safety Communication has resulted in a proliferation of information and activity in the world of pelvic reconstruction. Mesh kits should be subject to ongoing highquality Level I research if they are to be used as frequently as they have been in the past decade. Research to date suggests that TVM augmentation in anterior compartment repair leads to improved anatomic outcomes [29, 30•]. Superiority in subjective outcomes, as compared with native tissue repair, has not been established by the current data [31]. However, it must be noted that in the existing randomized control trial data, oftentimes multiple compartments are addressed or other prolapse repairs are included in both study groups. Few of the current studies have more than 1 year of follow-up [29, 30•]. FDA-mandated studies may bridge this gap in our knowledge if they provide for inclusion of realistic anatomic outcomes, uniform subjective outcomes, long-term follow-up, and standardization of the mesh versus nonmesh groups in terms of whether other repairs are performed concomitantly. As such, it is important to realize that although randomized controlled trials generally represent a higher level of evidence, even the best designed trials lack the ability to highlight special cases in which mesh may offer a particularly significant advantage, such as high-grade or recurrent POP after multiple operations. It is important to keep in mind in “the aftermath” of the FDA Safety Communication that the intent of the communication was not to limit options for our patients. Compliance with Ethics Guidelines
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Conflict of Interest Dr. Michelle E. Koski received travel/ accommodations expenses covered or reimbursed by American Medical Systems. Dr. Eric S. Rovner has served as a consultant for American Medical Systems.
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Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
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References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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16. 1.
Drutz HP, Alarab M. Pelvic organ prolapse: demographics and future growth prospects. Int Urogynecol J Pelvic Floor Dysfunct. 2006;17 Suppl 1:S6. 2.•• Urogynecologic Surgical Mesh: Updated on the Safety and Effectiveness of Transvaginal Placement for Pelvic Organ Prolapse. July 2011. Federal Drug Administration. Available at:
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http://www.fda.gov/downloads/MedicalDevices/Safety/ AlertsandNotices/UCM262760.pdf. This document delineates the summary of the MAUDE database reports, the FDA literature review, and the FDA activity in detail and provides a basis for why the FDA Safety Communication was issued. Physicians should be aware of these details. Urogynecologic Surgical Mesh Implants. The US Food and Drug Administration (FDA). 1/4/2012 http://www.fda.gov/MedicalDevices/ ProductsandMedicalProcedures/ImplantsandProsthetics/ UroGynSurgicalMesh/default.htm. Medical Devices—FDA’s Roles and Activities. The US Food and Drug Administation. http://www.fda.gov/MedicalDevices/ ProductsandMedicalProcedures/ImplantsandProsthetics/ UroGynSurgicalMesh/ucm262301.htm. Premarket notification (510k). The US Food and Drug Administration (FDA). 6/18/2009. http://www.fda.gov/medicaldevices/ productsandmedicalprocedures/deviceapprovalsandclearances/ 510kclearances/default.htm. Considerations about Surgical Mesh for SUI. March 2013. The US Food and Drug Administration (FDA). http://www. fda.gov/MedicalDevices/ProductsandMedicalProcedures/ ImplantsandProsthetics/UroGynSurgicalMesh/ucm345219. htm. This Web site helps clarify the differences between the FDA considerations of TVM for POP versus SUI. FDA Safety Communication: UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse. The US Food and Drug Administration (FDA). July 13, 2011 http://www.fda.gov/MedicalDevices/Safety/ AlertsandNotices/ucm262435.htm. Physicians need to be aware of the details of the FDA Safety Communication, with special attention to how it pertains to patient selection and counseling. 2011 Meeting Materials of the Obstetrics and Gynecology Devices Panel. FDA. 10/7/2011 http://www.fda.gov/ AdvisoryCommittees/CommitteesMeetingMaterials/ MedicalDevices/MedicalDevicesAdvisoryCommittee/ ObstetricsandGynecologyDevices/ucm262488.htm. 24-hr Summary—OB/GYN Devices Panel. September 8–9, 2011. The US Food and Drug Administration. http://www.fda.gov/ downloads/AdvisoryCommittees/CommitteesMeetingMaterials/ MedicalDevices/MedicalDevicesAdvisoryCommittee/ ObstetricsandGynecologyDevices/UCM271769.pdf. Meier B. F.D.A. Orders surgical mesh makers to study risks. The New York Times; 2012. Chamberlain J, Rosoff J, Kaufman MR, et al. The media and patient perception of transvaginal mesh. Abstract presented at American Urologic Association, San Diego May 2013 Brown L, Fenner DE, Berger MB, et al. Defining patient knowledge and perceptions of vaginal mesh surgery. Oral Poster presented at SGS 2013, Charleston SC, April 8–10 2013. Google Search, search term “Transvaginal Mesh,” May 2, 2013 Feeley J. Bard, Doctor ordered to pay $5.5 million over implant. July 25 2012. http://www.bloomberg.com/news/2012-07-24/bardmust-pay-5-5-million-over-vaginal-mesh-implants.html. Moylan T. Jury Awards $7.76 Million in Punitive Damages in New Jersey’s 1st Pelvic Mesh Trial. Lexis Nexis Communities. February 28, 2013. http://www.lexisnexis.com/community/ litigationresourcecenter/blogs/litigationblog/archive/2013/02/ 28/jury-awards-7-76-million-in-punitive-damages-in-newjersey-s-1st-pelvic-mesh-trial.aspx. Mucowski SJ, Jurnalov C, et al. Use of vaginal mesh in the face of recent FDA warnings and litigation. Am J Obstet Gynecol. 2010;203:103. American Urologic Association (AUA) position statement on the use of vaginal mesh for repair of pelvic organ prolapse. 2012. http:// www.auanet.org/content/aua-policies/position-statements/pelvicorgan-prolapse.cfm.
Curr Urol Rep (2014) 15:380 18.
19.••
20. 21.
22.
23.
24.
American Urologic Association (AUA) position statement on the use of vaginal mesh for the surgical treatment of stress urinary incontinence. 2012 http://www.auanet.org/content/aua-policies/ position-statements/stress-urinary-incontinence.cfm. Society for Female Urology and Urodynamics (SUFU) Response: FDA Safety Communication: UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse (July 2011). http://www.sufuorg.com/pdf/ SUFU%20FDA%20response%207%2018%2011.pdf. This document outlines the current stance of leadership in female urology on the use of TVM and the FDA Safety Communication. The American Urogynecologic Society (AUGS) response: FDA Safety Communication, 2011 http://www.augs.org/p/cm/ld/fid=163. The American College of Obstetricians and Gynecologists (ACOG). Committee Opinion. Vaginal Placement of Synthetic Mesh for Pelvic Organ Prolapse. 2011 http://www.acog.org/ Resources_And_Publications/Committee_Opinions/Committee_ on_Gynecologic_Practice/Vaginal_Placement_of_Synthetic_ Mesh_for_Pelvic_Organ_Prolapse. The Society of Gynecologic Surgeons (SGS) Executive Committee Statement Regarding the FDA Communication: surgical placement of mesh to repair pelvic organ prolapse imposes risks. http://www. sgsonline.org/sgsinc/sgsmeetings/pdf/SGS_Statement.pdf. Shveiky D, Hants Y. Biomaterials in obstetrics and gynecology. P161. In: Biomaterials science: an integrated clincial and engineering approach. Boca Raton: CRC Press; 2012. Davila GW, Baessler K, Cosson M, et al. Selection of patients in whom vaginal graft use may be appropriate. Consensus of the 2nd
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25.
26.
27.
28. 29.
30.•
31.
IUGA grafts roundtable: optimizing safety and appropriateness of graft use in transvaginal pelvic reconstructive surgery. Int Urogynecol J. 2012;23(supp 1):7. Miller D, Milani AL, Sutherland SE, et al. Informed surgical consent for a mesh/graft-augmented vaginal repair of pelvic organ prolapse. Consensus of the 2nd IUGA grafts roundtable: optimizing safety and appropriateness of graft use in transvaginal pelvic reconstructive surgery. Int Urogynecol J. 2012;23(supp 1):33. Winters JC, Jacquetin B, Castro R. Credentialing for transvaginal mesh placement—a case for “added qualification” in competency. Consensus of the 2nd IUGA grafts roundtable: optimizing safety and appropriateness of graft use in transvaginal pelvic reconstructive surgery. Int Urogynecol J. 2012;23(supp 1):27. Visco AG. AUGS releases guidelines of privileging and credentialling physicians for sacrocolpopexy for POP. http://www.augs.org/p/ bl/et/blogid=6&blogaid=156. American Urogynecologic Association. Guidelines and Statements. http://www.augs.org/p/cm/ld/fid=202. Koski ME, Rovner ES. The use of mesh for pelvic organ prolapse and stress urinary incontinence. AUA Update Series, Lesson 19. June 2013. Keys T, Campeau L, Badlani G. Synthetic mesh in the surgical repair of pelvic organ prolapse: current status and future directions. Urology. 2012;80:237. This article provides an overview of the basis of use of TVM and future directions. Lee U, Wolff EM, Kobashi KC. Native tissue repairs in anterior vaginal prolapse surgery: examining definitions of surgical success in the mesh era. Curr Opin Urol. 2012;22:265.
FEMALE UROLOGY (K KOBASHI, SECTION EDITOR)
Implications of the FDA Statement on Transvaginal Placement of Mesh: The Aftermath Michelle E. Koski & Eric S. Rovner
Published online: 3 January 2014 # Springer Science+Business Media New York 2014
Abstract The release of the U.S. Food and Drug Administration (FDA) safety communication on the use of transvaginal mesh (TVM) for pelvic organ prolapse (POP) has resulted in changes in the pelvic reconstruction community. This monograph reviews the implications of the FDA statements over the last 18–24 months. Recent findings show that there have been significant developments in the areas of regulatory mandates, media and medico-legal activity, and statements from surgical societies. In summary, well-publicized communications from the FDA and major medical organizations are defining a change in the use of TVM for POP. Keywords Transvaginal mesh . Pelvic organ prolapse . Food and Drug Administration . Urinary incontinence
Introduction The number of surgeries for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) has increased significantly over the last decade [1]. Transvaginal mesh (TVM) has been used frequently in the correction of POP and SUI. It has been estimated by the U.S. Food and Drug Administration (FDA) that, in 2010, approximately 300,000 women underwent surgical procedures in the United States for POP and approximately 260,000 for SUI. Of these estimates, approximately one out of three POP surgeries used mesh, and three out of four of the mesh POP procedures were done transvaginally. This article is part of the Topical Collection on Female Urology M. E. Koski (*) : E. S. Rovner Department of Urology, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29451, USA e-mail: [email protected] E. S. Rovner e-mail: [email protected]
For SUI surgeries, over 80 % were done transvaginally with mesh [2••]. Such widespread expansion of mesh in female pelvic surgery has led not only to substantial change in practice, but also to well-publicized communications from the FDA and major medical organizations. This monograph will review the implications of the FDA statements over the last 18–24 months.
FDA Regulatory Process and Communications Preformed mesh kits for pelvic surgery were approved as “Class II” devices through the FDA regulatory 510(k) process. From 2002 to 2011, the FDA cleared more than 100 mesh products indicated for SUI and POP [3, 4]. In that era, the FDA classification of surgical mesh products as Class II devices meant that device manufacturers were required to show “substantial equivalence,” as compared with existing products (“predicate devices”), in order to gain approval. Premarketing clinical data regarding efficacy and safety were typically not required to support clearance for mesh products while this pathway was in use [5]. The FDA initially issued a safety communication regarding the use of mesh in pelvic reconstructive surgery in 2008 and opened a database to collect additional information on mesh complications—the Manufacturer and User Facility Device Experience (MAUDE) database. It should be noted that the MAUDE database is a passive surveillance system with several limitations, including the potential for submission of incomplete or inaccurate data, underreporting of events, lack of denominator data, and a lack of report timeliness [6•]. An FDA update was issued in July 2011, detailing their analysis of the MAUDE database [7•]. In the 3-year period between FDA communications, an additional 2,874 mesh-related complications were reported to the database. Although it was acknowledged that device reports typically increase after an
380, Page 2 of 5
FDA communication, the emphasis of the subsequent report was that transvaginal mesh complications are “not rare.” In the 2011 report, which focused on TVM POP and did not address TVM for SUI, the FDA performed an independent literature review and concluded that TVM in the apical and posterior compartments does not provide substantial added benefit. Furthermore, this document asserted that although TVM in the anterior compartment may provide anatomic benefit, this does not necessarily result in improved symptomatic results. However, it is important to note that in this document, the FDA did not specifically recommend against the use of mesh for the repair of POP or SUI, nor were there mandatory recalls of any particular mesh or mesh “kit.”
Curr Urol Rep (2014) 15:380
disorders and their surgical repair in partnership with the FDA, the National Institutes of Health, the American College of Obstetricians and Gynecologists (ACOG), and industry— the Pelvic Floor Disorders Registry. Initially, the registry will focus on surgical and nonsurgical treatment of POP. It is designed to monitor patient outcomes for providers and manufacturers, as well as to provide data for the FDA-required postmarket research as part of the reclassification process for POP TVM products. Manufacturers are not required to participate in the AUGS registry; however, those who do not participate are still required to file postmarketing studies with the FDA and must create their own data set for submission.
Implications for the Public Implications for Manufacturers On the basis of the deliberations from the September 2011 meeting of the Obstetrics and Gynecology Devices Advisory Committee of the FDA (which are now available on the FDA Web site [8]), assessment of the MAUDE data, and their independent literature review, the FDA is considering the recommendation that urogynecologic surgical mesh used for transvaginal repair of POP be reclassified from Class II (lowto moderate-risk devices) to Class III (high-risk devices). Class III devices require premarket and postmarket clinical studies for approval. The FDA announced a new action on January 4, 2012 [3], requiring manufacturers of TVM for POP and of single-incision slings to perform postmarket studies (“522 studies”) on their products. As of February 27, 2012, 95 postmarket study orders had been issued to 34 manufacturers of surgical mesh for POP, and 14 orders were issued to 7 manufacturers of single-incision slings [4]. In the 1.5–2 years allotted for these studies, POP TVM products and singleincision slings will remain available for clinical use [9]. For SUI, the Devices Advisory Committee of the FDA agreed that the currently marketed first-generation slings are safe and effective, with a positive risk:benefit profile [4, 8]. In March of 2013, the FDA updated their Web site to include more information for patients and physicians regarding the use of mesh for SUI [6•]. This information is based on an analysis of the MAUDE database, FDA literature review, and input from the September 2011 Device Advisory Committee. The FDA’s independent literature review confirmed that the safety and efficacy of multi-incision slings is well established in clinical trials up to 1 year [6•]. In the wake of the FDA requirements for postmarket studies, which may prove to be expensive and time consuming, in addition to the burgeoning product liability issues, several TVM manufacturers have voluntarily ceased production, marketing, and sales of their products. Since the summer of 2012, the American Urogynecological Society (AUGS) has been in the process of creating a national registry for pelvic floor
The FDA statement initially led to significant confusion for patients, the public, physicians, and the media. For example, the statement did not mention that complications may occur with traditional nonmesh repairs. The complications cited do occur with traditional repair (with the exception of mesh erosion and exposure), but the exact incidence is unknown. The update issued by the FDA discussed the use of mesh for SUI and POP in the same statement, leading to confusion between the mesh used for POP repair and that used for SUI (this has been clarified in later statements [6•]). This resulted in a cycle of misinformation from the media to the public, which extended to some very well established media outlets [10]. An important medico-legal implication of this period of misinformation is that a substantial portion of the lawsuitdriven media output has not and does not differentiate mesh for SUI from that used for POP, even though the FDA proceedings have not associated the same strength of concern with mesh used for midurethral sling as it has with mesh for POP. Legal ads have a high penetrance into the patient population, with similar findings in two studies in two different geographic areas finding that 60 % of patients aware of TVM are aware through legal advertisements [11, 12]. The Internet is saturated with these sources as well. A perfunctory Google™ search for the term “transvaginal mesh” (as of May 2013) reveals a roughly 10:1 ratio of lawsuit-orientated information to other sources in the first two pages [13].
Medicolegal Implications The first lawsuit against a mesh manufacturer (Bard) resulted in a $5 million verdict to a patient who asserted that alleged design defects led to damage to her colon [14]. $500,000 was awarded to her husband for “loss of consortium.” In this lawsuit, the judgment was paid by the manufacturer, but the implanting physician was found responsible for 40 % of the liability. The patient’s lawyers plan to press forward with
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claims against the surgeon at a later trial [14]. The bellwether first trial against Ethicon (the first of over 1,800 cases against the manufacturer pending in New Jersey courts) was settled in February 2013, awarding $11.1 million to the plaintiff. The jury found that Ethicon inadequately warned the surgeon of the Prolift TVM kit’s risks and misrepresented the device to the patient [15]. At present, the majority of the lawsuits against the manufacturers are being processed as multidistrict litigation under a single judge, with trials to be held in West Virginia. As of May 2013, 21,257 cases had been filed in federal court in West Virginia against five manufacturers (C.R. Bard, American Medical Systems, Boston Scientific, Ethicon, and Coloplast) (http://meshmedicaldevicenewsdesk.com/ latest-in-the-litigation-concerning-mesh-and-medicaldevices/mdl-news-21257-cases-filed-in-federal-transvaginalmesh-litigation/). At present, the lawsuits are directed against manufacturers, but it is unclear whether physicians will eventually be named as well. There is legal precedent in older cases that supports physician liability in device cases. Mucowski et al, provide an excellent overview of these liability issues and the role of informed consent [16].
Implications in Organized Medicine In the midst of the flurry of medico-legal news, legal advertisements, and other layman’s media productions, it is important to keep in mind that physicians are still the primary advocates for unbiased scientific information and for their patients’ care. There are several well-written responses to the FDA update issued by professional societies, including the American Urologic Association (AUA) [17, 18], the Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction (SUFU) [19••], AUGS [20], ACOG [21], and the Society of Gynecologic Surgeons (SGS) [22]. The AUA has two position statements, addressing POP [17] and SUI [18] separately. Most of the statements are in agreement with the FDA statement regarding surgeon training, proper selection of patients, detailed counseling of the patients about the treatment options and the complications related to mesh use, and the need for postmarket studies to confirm efficacy and safety. In 2012, the International Urogynecological Association (IUGA) published several reports based on their roundtable meeting discussing graft usage. Although the “ideal graft” [23] has not yet been determined, the usage of type I mesh can be optimized with some of these recommendations. Several articles discuss patient selection for TVM [24], optimization of safety with graft use [25], and possible training requirements for physicians [26]. The IUGA recommendations for training considerations focus more on the development of an “added qualification” process, as opposed to the creation of new credentialing guidelines, citing the variability of TVM procedures for POP [26]. In contrast to this approach, in February of
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2013, AUGS issued a document outlining guidelines for privileging and credentialing physicians for sacrocolpopexy [27] (note that the FDA safety communication and literature reviews are not critical of mesh use in sacrocolpopexy [2••]). Other organizations, such as ABU, AUA, ABOG, and SUFU, have chosen not to issue such guidelines for privileging and credentialing. It remains that the optimal mechanism for determining competence and, therefore, privileging/credentialing in surgery remains controversial. As such, privileging remains a local process in each community. As always, patient counseling and informed consent are of paramount importance, and the significance of proper counseling is further emphasized by the current media and medicolegal environment. The FDA notice, IUGA roundtable report, and AUA and SUFU statements all have detailed guidelines for consenting patients for physicians [7•, 17, 18, 25]. Given the paucity of clear and accurate information on the Internet and television [11, 12], one might argue that beyond specific patient counseling, there should be distribution of accurate information on TVM to the general public. For example, one result of the current media output is the potential limitation of the use of TVM by medical malpractice insurers, hospital formularies, and medical insurance companies. Hospitals Insurance Company, a medical malpractice insurer, issued a communication to insured physicians in October 2012, to inform them that they would be excluding coverage for TVM procedures for POP as a result of, among other things, “plaintiffs’ attorneys actively seeking patients to bring lawsuits” (letter from D. Feldman of Hospitals Insurance Company, 10/ 25/2012). In response to these types of measures, AUGS released a position statement against the restriction of surgical options for pelvic floor disorders [28]. This statement outlines key points regarding TVM for POP (Table 1) [28].
Table 1 Key points from the AUGS position statement on restriction of surgical options for pelvic floor disorders [28] 1. A complete restriction on the use of surgical mesh was not the stated intent of the FDA safety communication. 2. The decision on surgical alternatives should be made by the patient and his or her surgeon. 3. A ban on surgical mesh would prohibit the surgical studies mandated by the FDA and recommended by the NIH, ACOG, and AUGS. 4. In some circumstances, transvaginal mesh for POP may be the most appropriate surgical option. 5. Any restriction of mesh slings for the treatment of stress urinary incontinence is clearly not supported by any professional organization or the FDA. 6. Any restriction of mesh placed abdominally for the treatment of prolapse is clearly not supported by any professional organization or the FDA. 7. Instead of a ban on mesh, the implementation of credentialing guidelines so that mesh procedures are performed by qualified surgeons was recommended.
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Conclusions In summary, the FDA Safety Communication has resulted in a proliferation of information and activity in the world of pelvic reconstruction. Mesh kits should be subject to ongoing highquality Level I research if they are to be used as frequently as they have been in the past decade. Research to date suggests that TVM augmentation in anterior compartment repair leads to improved anatomic outcomes [29, 30•]. Superiority in subjective outcomes, as compared with native tissue repair, has not been established by the current data [31]. However, it must be noted that in the existing randomized control trial data, oftentimes multiple compartments are addressed or other prolapse repairs are included in both study groups. Few of the current studies have more than 1 year of follow-up [29, 30•]. FDA-mandated studies may bridge this gap in our knowledge if they provide for inclusion of realistic anatomic outcomes, uniform subjective outcomes, long-term follow-up, and standardization of the mesh versus nonmesh groups in terms of whether other repairs are performed concomitantly. As such, it is important to realize that although randomized controlled trials generally represent a higher level of evidence, even the best designed trials lack the ability to highlight special cases in which mesh may offer a particularly significant advantage, such as high-grade or recurrent POP after multiple operations. It is important to keep in mind in “the aftermath” of the FDA Safety Communication that the intent of the communication was not to limit options for our patients. Compliance with Ethics Guidelines
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Conflict of Interest Dr. Michelle E. Koski received travel/ accommodations expenses covered or reimbursed by American Medical Systems. Dr. Eric S. Rovner has served as a consultant for American Medical Systems.
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Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
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References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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Drutz HP, Alarab M. Pelvic organ prolapse: demographics and future growth prospects. Int Urogynecol J Pelvic Floor Dysfunct. 2006;17 Suppl 1:S6. 2.•• Urogynecologic Surgical Mesh: Updated on the Safety and Effectiveness of Transvaginal Placement for Pelvic Organ Prolapse. July 2011. Federal Drug Administration. Available at:
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http://www.fda.gov/downloads/MedicalDevices/Safety/ AlertsandNotices/UCM262760.pdf. This document delineates the summary of the MAUDE database reports, the FDA literature review, and the FDA activity in detail and provides a basis for why the FDA Safety Communication was issued. Physicians should be aware of these details. Urogynecologic Surgical Mesh Implants. The US Food and Drug Administration (FDA). 1/4/2012 http://www.fda.gov/MedicalDevices/ ProductsandMedicalProcedures/ImplantsandProsthetics/ UroGynSurgicalMesh/default.htm. Medical Devices—FDA’s Roles and Activities. The US Food and Drug Administation. http://www.fda.gov/MedicalDevices/ ProductsandMedicalProcedures/ImplantsandProsthetics/ UroGynSurgicalMesh/ucm262301.htm. Premarket notification (510k). The US Food and Drug Administration (FDA). 6/18/2009. http://www.fda.gov/medicaldevices/ productsandmedicalprocedures/deviceapprovalsandclearances/ 510kclearances/default.htm. Considerations about Surgical Mesh for SUI. March 2013. The US Food and Drug Administration (FDA). http://www. fda.gov/MedicalDevices/ProductsandMedicalProcedures/ ImplantsandProsthetics/UroGynSurgicalMesh/ucm345219. htm. This Web site helps clarify the differences between the FDA considerations of TVM for POP versus SUI. FDA Safety Communication: UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse. The US Food and Drug Administration (FDA). July 13, 2011 http://www.fda.gov/MedicalDevices/Safety/ AlertsandNotices/ucm262435.htm. Physicians need to be aware of the details of the FDA Safety Communication, with special attention to how it pertains to patient selection and counseling. 2011 Meeting Materials of the Obstetrics and Gynecology Devices Panel. FDA. 10/7/2011 http://www.fda.gov/ AdvisoryCommittees/CommitteesMeetingMaterials/ MedicalDevices/MedicalDevicesAdvisoryCommittee/ ObstetricsandGynecologyDevices/ucm262488.htm. 24-hr Summary—OB/GYN Devices Panel. September 8–9, 2011. The US Food and Drug Administration. http://www.fda.gov/ downloads/AdvisoryCommittees/CommitteesMeetingMaterials/ MedicalDevices/MedicalDevicesAdvisoryCommittee/ ObstetricsandGynecologyDevices/UCM271769.pdf. Meier B. F.D.A. Orders surgical mesh makers to study risks. The New York Times; 2012. Chamberlain J, Rosoff J, Kaufman MR, et al. The media and patient perception of transvaginal mesh. Abstract presented at American Urologic Association, San Diego May 2013 Brown L, Fenner DE, Berger MB, et al. Defining patient knowledge and perceptions of vaginal mesh surgery. Oral Poster presented at SGS 2013, Charleston SC, April 8–10 2013. Google Search, search term “Transvaginal Mesh,” May 2, 2013 Feeley J. Bard, Doctor ordered to pay $5.5 million over implant. July 25 2012. http://www.bloomberg.com/news/2012-07-24/bardmust-pay-5-5-million-over-vaginal-mesh-implants.html. Moylan T. Jury Awards $7.76 Million in Punitive Damages in New Jersey’s 1st Pelvic Mesh Trial. Lexis Nexis Communities. February 28, 2013. http://www.lexisnexis.com/community/ litigationresourcecenter/blogs/litigationblog/archive/2013/02/ 28/jury-awards-7-76-million-in-punitive-damages-in-newjersey-s-1st-pelvic-mesh-trial.aspx. Mucowski SJ, Jurnalov C, et al. Use of vaginal mesh in the face of recent FDA warnings and litigation. Am J Obstet Gynecol. 2010;203:103. American Urologic Association (AUA) position statement on the use of vaginal mesh for repair of pelvic organ prolapse. 2012. http:// www.auanet.org/content/aua-policies/position-statements/pelvicorgan-prolapse.cfm.
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American Urologic Association (AUA) position statement on the use of vaginal mesh for the surgical treatment of stress urinary incontinence. 2012 http://www.auanet.org/content/aua-policies/ position-statements/stress-urinary-incontinence.cfm. Society for Female Urology and Urodynamics (SUFU) Response: FDA Safety Communication: UPDATE on Serious Complications Associated with Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse (July 2011). http://www.sufuorg.com/pdf/ SUFU%20FDA%20response%207%2018%2011.pdf. This document outlines the current stance of leadership in female urology on the use of TVM and the FDA Safety Communication. The American Urogynecologic Society (AUGS) response: FDA Safety Communication, 2011 http://www.augs.org/p/cm/ld/fid=163. The American College of Obstetricians and Gynecologists (ACOG). Committee Opinion. Vaginal Placement of Synthetic Mesh for Pelvic Organ Prolapse. 2011 http://www.acog.org/ Resources_And_Publications/Committee_Opinions/Committee_ on_Gynecologic_Practice/Vaginal_Placement_of_Synthetic_ Mesh_for_Pelvic_Organ_Prolapse. The Society of Gynecologic Surgeons (SGS) Executive Committee Statement Regarding the FDA Communication: surgical placement of mesh to repair pelvic organ prolapse imposes risks. http://www. sgsonline.org/sgsinc/sgsmeetings/pdf/SGS_Statement.pdf. Shveiky D, Hants Y. Biomaterials in obstetrics and gynecology. P161. In: Biomaterials science: an integrated clincial and engineering approach. Boca Raton: CRC Press; 2012. Davila GW, Baessler K, Cosson M, et al. Selection of patients in whom vaginal graft use may be appropriate. Consensus of the 2nd
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IUGA grafts roundtable: optimizing safety and appropriateness of graft use in transvaginal pelvic reconstructive surgery. Int Urogynecol J. 2012;23(supp 1):7. Miller D, Milani AL, Sutherland SE, et al. Informed surgical consent for a mesh/graft-augmented vaginal repair of pelvic organ prolapse. Consensus of the 2nd IUGA grafts roundtable: optimizing safety and appropriateness of graft use in transvaginal pelvic reconstructive surgery. Int Urogynecol J. 2012;23(supp 1):33. Winters JC, Jacquetin B, Castro R. Credentialing for transvaginal mesh placement—a case for “added qualification” in competency. Consensus of the 2nd IUGA grafts roundtable: optimizing safety and appropriateness of graft use in transvaginal pelvic reconstructive surgery. Int Urogynecol J. 2012;23(supp 1):27. Visco AG. AUGS releases guidelines of privileging and credentialling physicians for sacrocolpopexy for POP. http://www.augs.org/p/ bl/et/blogid=6&blogaid=156. American Urogynecologic Association. Guidelines and Statements. http://www.augs.org/p/cm/ld/fid=202. Koski ME, Rovner ES. The use of mesh for pelvic organ prolapse and stress urinary incontinence. AUA Update Series, Lesson 19. June 2013. Keys T, Campeau L, Badlani G. Synthetic mesh in the surgical repair of pelvic organ prolapse: current status and future directions. Urology. 2012;80:237. This article provides an overview of the basis of use of TVM and future directions. Lee U, Wolff EM, Kobashi KC. Native tissue repairs in anterior vaginal prolapse surgery: examining definitions of surgical success in the mesh era. Curr Opin Urol. 2012;22:265.
