FDA panel reaffirms safety, efficacy of silicone implants – and looks to the future

By Lori Shoaf

09/15/2011 at 10:00AM

The Food and Drug Administration's (FDA) General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee conducted a hearing on Aug. 30-31 in Gaithersburg, Md., to evaluate the progress of long-term post-approval studies (PAS) mandated when silicone gel-filled breast implants were approved by the Agency to return to market in 2006.

The hearing included a review of data targeting performance and long-term safety of breast implants and suggestions for improving future studies.

The panel heard a range of perspectives on the device from patients, women's health and consumer groups and medical professionals - including ASPS and ASAPS representatives.

While implant opponents continued to raise concerns about the availability of silicone breast implants, FDA personnel who spoke at the hearing pointed to the Agency's May 2011 white paper "Update on the Safety of Silicone Gel-Filled Breast Implants" to affirm the safety and effectiveness of the device. The white paper noted that data and scientific literature reveal no correlation between silicone breast implants and connective tissue disease.

"ASPS has always taken a stand for patient safety," ASPS President Phil Haeck, MD, told the panel. "We want the best for our patients, and we've been a leader in pursuing outcomes data that support therapeutic decision-making by our members."

Additional testimony by representatives of breast implant manufacturers Allergan Inc. and Mentor/Johnson & Johnson focused on current data, adverse events, follow-up rates for the current PAS, methods to improve patient follow-up and potential changes to current and future studies - including new methods of data collection.

ASPS testimony

In addition to Dr. Haeck, ASPS members Steven Bonawitz, MD; Andrea Pusic, MD (who helped create the BREAST-Q®); and ASPS/PSF Board Vice President of Health Policy and Advocacy Robert X. Murphy Jr., MD, testified before the panel. The ASPS leaders provided several recommendations in their testimony that would improve the post-approval studies and potentially changelabeling for the device, including:

• The literature does not support the use of MRI as a screening tool for asymptomatic patients, particularly given the cost/benefit equation and the potential detrimental effects of false positives. In addition, the MRI requirement appears to be a detriment to maintaining enrollment of patients in the study.
• ASPS continues to support investigation of alternatives for implant rupture screening.
• A key limitation in current studies is the reliance on prospective data collected from U.S. patients; therefore, ASPS recommends that data should be gathered from existing sources inside and outside the United States to fill gaps. Specifically, the FDA should consider data sources such as the Australian, British, Canadian and Danish registries, among others, as supplemental data to achieve end points, as these registries are older and have more data than the PAS. When combined with data already collected, these alternative data sources could enhance post-approval data without the costly need to pursue women lost to follow-up.
• ASPS supports changes to the studies that make it less burdensome for enrolled patients and physicians to comply. For example, Allergan now allows patients to fill out the questionnaire online and by telephone. Additionally, Mentor has modified its study website for easier access and use. The Society supports any further changes that make it less burdensome for patients to complete appropriate follow-up.
• ASPS believes the FDA should carefully consider and prioritize the clinical questions they want answered in future PAS with an eye toward reducing burden and improving compliance for patients and surgeons.
• Post-market surveillance through case reports, registries and other databases, such as the ASPS Tracking Operations and Outcomes in Plastic Surgery (TOPS) - a HIPAA compliant, confidential national database of more than 1 million plastic surgery procedures - and the narrowly focused ALCL registry currently under development, are also critical adjuncts to the post-approval studies.

"The TOPS registry can serve as a valuable resource and tool for broadly collecting procedural-specific and longitudinal outcomes data related to breast implant procedures," Dr. Murphy told the panel. "TOPS data fields could easily be expanded to facilitate and formalize data collection for the purpose of developing a national breast implant registry. These efforts can inform and supplement global data collection to enhance the post-approval studies and breast safety."

Dr. Pusic told the panel that accumulating data beyond the current PASwill increase the knowledge base. "We believe additional data from outside the existing construct may be needed to supplement these studies," she said.

"New initiatives can be employed such as data mining from existing international resources to answer questions," she added. "Clearly, there's a need to improve the studies to achieve the endpoints."
ASPS representatives also discussed the need to foster further innovation relative to breast implants, as well as the high levels of satisfaction among plastic surgery patients with silicone breast implants - a position reaffirmed by the FDA white paper.

FDA panel reactions and recommendations

The FDA hearings also yielded a number of highlights and recommendations. During the public portion of the silicone-gel breast implant proceedings, the panel:

• Discussed the 35 percent of women in the PAS who are lost in follow-up, and noted that it seemed to be an appropriate assumption due to the many follow-up and enrollment challenges the companies and clinicians face. However, when discussing both current and future post-approval study designs, the panel had many ideas to increase follow-up compliance.
• Recommended that the questionnaires be web-based and revised to be more understandable for enrollees, as the current paper questionnaire is too lengthy and tedious. The panel noted that confidentiality is important to patients, and it recommended emphasizing to enrollees that they're assisting research that targets women's health.
• Noted that consideration should be given to providing incentives for physicians and patients to improve follow-up rates.
• Discussed study methodology and the potential for obtaining better data with fewer patients or conducting multiple studies to address different data end points, rather than a single large study.
• Reached a consensus that it was necessary to assess failure rates in terms of long-term effectiveness, and agreed that 15 years was a reasonable expectation for the life of breast implant devices.
• Discussed the use of registries that may collect a larger amount of data and can capture rare occurrences. The panel also noted that pooling registry data from various databases could help identify rare endpoints, and that smaller cohort studies could capture more common endpoints.
• Indicated that a breast implant registry of all patients could provide answers to many long-term questions – particularly those related to possible association with rare adverse events.
• Debated current scientific data on the approved product labeling recommendations for MRI screening for silent rupture, and questioned the efficacy of this recommendation given the cost to patients and potential for false positives.
• Heard concerns by some of its members that high-resolution ultrasound may be a reasonable technology option in the future, particularly for detecting ruptures on the front surface of the implant, while MRI can detect ruptures of the entire breast implant-including the back wall.
• Noted that future studies for newer breast implants that utilize the same technology as those already approved should be combined with implants already marketed to answer any additional data endpoints. This type of data pooling would allow for comparisons to be made.
• Felt that a post-approval registry should be created to capture all breast implant data.

The panel also emphasized the importance of participation by third-party stakeholders - for example, professional societies like ASPS - to improve current and future post-approval studies.

What happens next

The FDA is reviewing the data and presentations as well as the panel recommendations. The Agency plans to engage the stakeholder community on changes to post-approval studies and the improvement of data collection. ASPS will continue its longstanding dialogue with the FDA regarding these studies and the safety of silicone implants.

Additionally, ASPS has signed a Collaborative Research and Development Agreement with the FDA to establish a registry to study the possible association between anaphylactic large cell lymphoma (ALCL) and breast implants. Discussions are underway to establish a work plan and timeline, and solicit subject matter experts. The Society anticipates that it will take six to 12 months to set up the registry and finalize a work plan.

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Silicone-gel breast implant timeline and FDA

• 2006: Silicone gel-filled breast implants are approved for market with substantial post-approval studies (PAS)
• 2007 - present: ASPS members are urged to participate in PAS; the Society continues to engage FDA on areas of concern
• June 2011: FDA releases its white paper analyzing PAS and reaffirming safety and effectiveness of silicone breast implants
• August 2011: FDA holds panel hearing to examine post-approval stuies improvements; ASPS representatives testify at the panel hearing – and the Society pledges to continue its engagement with the FDA on improved data collection