FDA & Transvaginal Mesh: What Happened? What s Next?

Transcription

1 FDA & Transvaginal Mesh: What Happened? What s Next? Matthew D. Barber, MD MHS Professor & Vice Chair for Clinical Research Obstetrics Gynecology & Women s Health Institute

2 Disclosures I receive no grants, honoraria or other funding from industry.

3 Objectives To briefly discuss the US FDA regulatory process for medical device approval To review the FDA actions on Graft/Mesh for pelvic organ prolapse and stress urinary incontinence To discuss the impact on current clinical practice with specific emphasis on: Informed Consent Surgeon Credentialing

4 Presentation Title l August 22, 2012 l 4

5 Mesh Timeline First sling kit Protagen (Boston Sci) TVT (Ethicon) First marketed POP kit - IVS Tunneler First POP Mesh - Gynemesh Apogee/Perigee (AMS) introduced Prolift (Ethicon) introduced Non-trocar kits (Elevate, Uphold) Presentation Title l August 22, 2012 l 5

6 POP Repair Surgeries - US Market 2010* 300,000 women *industry source

7 POP Mesh Sales 2010* Total 121,260 *US Markets for Soft Tissue Repair 2010, Millennium Research Group, Inc. All rights reserved. Reproduction, distribution, transmission or publication is prohibited. Reprinted with permission.

8 HOW ARE MEDICAL DEVICES CLEARED IN THE U.S.? Presentation Title l August 22, 2012 l 8

9 Phases of Drug Development

10 FDA Medical Device Regulation Class Regulation Examples Approval Process I General Controls Bandages, Gloves, Surgical instruments II III General and Special Controls Premarket Approval (PMA) Catheters, wheel chairs, infusion pumps, L/S trocars Mesh? Cardiac pacemakers, Interstim, Transurethral bulking agents Labeling, Good manufacturing practices 510(k) PMA study

11 FDA 510 (k) Does not require evidence of clinical safety or efficacy Unlike medications, no phase I, II, or III studies required FDA clearance for many 510 devices (k) approval does requires not evidence necessarily of substantial equivalence to an already approved device indicate safety or efficacy! Same technological characteristics Same intended use Predicate Devices on the market prior to May 28, 1976 or previously cleared Example: Surgical Mesh for Hernia

12 Littman & Culligan, 2009

13 Class III Devices that require Premarket (PMA) studies Urethral Bulking Agents (Coaptite, Durasphere, etc) Tubal ligation devices (Filshie clip, Essure, etc) Without Grandfather Clause there is no doubt Transvaginal Mesh would require Pre-market Studies Endometrial ablation devices Sacral Nerve Stimulation (Interstim)

14 Transvaginal Mesh: Timeline Perigee (AMS) Prolift (Ethicon) Elevate (AMS) UpHold (Bost Sci) Introduced in US First Study Feb 2012 May 2012 First RCT ??

15 Cochrane Review Ogah et al, 2009 Mid-urethral Slings Over 500 articles, 40+ RCTs Similar efficacy to traditional slings but with shorter OR time and less voiding dysfunction and de novo urgency. Similar efficacy to Burch/MMK but with fewer postop complications, less voiding dysfunction, shorter OR time, shorter hospital stay but more bladder perforations Similar efficacy for TVT and TOT but different safety profiles 10+ year data suggest efficacy is durable Definitive Standard of Care

16 FDA timeline 2006 AE signals, safety problems FDA initial review of MAUDE, received over 1,000 reports from nine surgical mesh manufacturers 2008 FDA issues Public Health Notice regarding adverse events associated with surgical mesh when used for repair for SUI and POP

17 FDA 2008 PHN Alert about complications associated with transvaginal placement of surgical mesh to treat Pelvic Organ Prolapse (POP) and Stress Urinary Incontinence (SUI) Although rare, these complications can have serious consequences Recommendations- specialized training, watch for AEs, provide written copy of the patient labeling, inform patients about the potential for serious complications, mesh is permanent, watch for complications Reporting Adverse Events to FDA- requires hospitals and other user facilities to report deaths and serious injuries, report directly to MedWatch

18 Serious complications associated with surgical mesh for transvaginal repair of POP are not rare. Transvaginally placed mesh in POP repair does not conclusively improve clinical outcomes over traditional non-mesh repair.

19 Conclusions from FDA Literature Review Vaginal repair with mesh is main concern serious AEs are not rare effectiveness not superior to traditional repair (possible exception for anterior repair) little known about long term implications safety and effectiveness in question Sacrocolpopexy less concerning lower rates of mesh complications excellent anatomic outcomes low re-surgery rates for recurrent prolapse safety and effectiveness demonstrated in literature

20 Top 10 Adverse Events for POP Reports Rank Adverse Events # of MDRs Percentile Rate 1 Erosion % 2 Pain % 3 Infection % 4 Bleeding % 5 Dyspareunia % 6 Organ Perforation % 7 Urinary Problems % 8 Neuro-muscular problems % 9 Vaginal scarring (41)/ Shrinkage (2) % 10 Recurrence, Prolapse % Total number of adverse events is larger than total number of MDR reports because the majority reported more than one adverse event

21 Transvaginal Mesh for Prolapse 70% decline in sales since July 2011 Over 400 lawsuits nationwide against manufacturers January 2012 FDA issues 522 orders requiring post-marketing surveillance studies for all manufacturers of transvaginal mesh for POP Several companies withdrawing from the market Others investing multi-millions of dollars in research to meet FDA requirements

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23 The FDA waited a decade to ask mesh makers for safety studies.

24 Response to Updated PHN FDA Convened the Obstetrics-Gynecology Devices Panel of the Medical Device Advisory Committee, on September 8-9, Institutes of Medicine: Made recommendations to the FDA on the 510k process for approval of class II medical devices. Would require an Act of Congress to change device regulation U.S. Congress debating a law that would keep system essentially intact and ratify an agreement between FDA and industry to get devices to market faster.

25 UPDATE 01/04/2012: Based on assessment of Medical Device Reports (adverse event reports) submitted to the FDA, evaluation of the published literature, and the September 2011 Obstetrics-Gynecology Devices Panel meeting, the FDA is considering the recommendation that urogynecologic surgical mesh used for transvaginal repair of pelvic organ prolapse (POP) be reclassified from Class II to Class III.

26 Mandating postmarket surveillance studies ( 522 studies ) by manufacturers of urogynecologic surgical mesh devices. On January 03, 2012, the FDA issued: 88 post-market study orders to 33 manufacturers of urogynecologic surgical mesh for POP; 11 postmarket study orders to seven manufacturers of single-incision mini-slings for SUI.

27 What the FDA has not done: Removed any products from the U.S. market Changed the regulatory pathway for: Midurethral slings Mesh/Devices for Sacrocolpopexy

28 Surgeons performing transvaginal placement of mesh for POP should undergo training specific to each device and have experience with reconstructive surgical procedures and a thorough understanding of pelvic anatomy. Transvaginal placement of mesh for POP should be reserved for high-risk individuals in whom the benefits of mesh placement may justify the risk, such as individuals with recurrent prolapse (particularly of the anterior compartment) or with medical comorbidities that precluded more invasive and lengthier open and endoscopic procedures.

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31 FDA Recommended Questions for Patients to Ask Surgeons Are you planning to use mesh in my surgery? Why do you think I am a good candidate for mesh? Why are you choosing surgical mesh for my repair? What are the alternatives to transvaginal surgical mesh repair for POP, including non-surgical options? What are the pros and cons of surgical mesh in my particular case? How likely is it my repair could be successfully performed without mesh? Will my partner be able to feel the surgical mesh during intercourse? What if the surgical mesh erodes?

32 FDA Recommended Questions for Patients to Ask Surgeons If you plan to use mesh, how often have you implanted this particular product? What results have your other patients had with this product? What can I expect to feel after surgery and for how long? Which specific side effects should I report to you after surgery? What if the mesh surgery doesn t correct my problem?

33 FDA Recommended Questions for Patients to Ask Surgeons If I develop a complication, will you treat it or will I be referred to a specialist experienced with surgical mesh complications? If I have a complication related to the surgical mesh, how likely is it that the surgical mesh could be removed and what could be the consequences? If you plan to use surgical mesh, is there patient information that comes with the product Informed Consent Checklist

34 Presentation Title l August 22, 2012 l 34 Female Pelvic Med Reconstru Surg 2012; 18:

35 TV Mesh Credentialing Guidelines Surgeons not yet using Mesh for POP Document General Knowledge of Female Pelvic Reconstructive Surgery Fellowship or documentation of appropriate CME Document Specific Knowledge of the Procedure Training in Fellowship or Proctored Cases Experience in treating Pelvic Floor Disorders Fellowship or at least 50% of surgical practice is PFD including at least 30 POP cases/year Current privileges in non-mesh repairs Annual Internal Audit

36 TV Mesh Credentialing Guidelines Surgeons currently using Mesh for POP Continuing Medical Education in female pelvic reconstructive surgery documented annually A minimum of 30 surgical cases annually for pelvic organ prolapse (any route, with or without mesh) Document and maintain privileges in non-mesh vaginal repair of POP Annual Internal Audit Prior to adoption of new technology or device: Demonstrate specific knowledge of device Proctored cases

37 What s Next? All current products stay on market (unless company decides to pull them) Industry to perform 522 postmarket surveillance studies (Start 2013; 3 year follow-up) AUGS in collaboration w/ industry, FDA and others is developing a national PFD registry 5 companies will be performing 522 studies in registry AUGS plans credentialing guidelines for sacrocolpopexy and fundamentals of pelvic reconstructive surgery educational curriculum FDA continues to monitor and will make decision about changing classification of TVM from Class II to Class III

38 Ultimate goals To promote safe and effective are for women with PFD To encourage innovation while maintaining patient safety To maintain a broad range of treatment options to meet the varying needs of our patients

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