|
|
| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P030053 / PAS003 |
| Date Original Protocol Accepted |
11/17/2006
|
| Date Current Protocol Accepted |
11/17/2006
|
| Study Name |
Informed Decision Process
|
| Device Name |
MEMORYGEL SILICONE GEL -FILLED BREAST IMPLANTS
|
| General Study Protocol Parameters |
| Study Design |
Other Study Design
|
| Data Source |
New Data Collection
|
| Comparison Group |
No Control
|
| Analysis Type |
Descriptive
|
| Study Population |
Adolescent: 13-18 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
The Informed Decision Process study is a random survey of physicians on an annual basis to determine the success of the informed decision process provided to woman who is seeking breast implants surgery
|
| Study Population |
Each year, a random selection of 50 physicians are targeted for a survey to determine the success of the patient informed consent process.
|
| Sample Size |
A total of 50 physicians surveyed each year
|
| Key Study Endpoints |
Survey is administered to 50 physicians and asks questions on the level of understanding a patient has after consulting the Allergan patient planner.
|
| Follow-up Visits and Length of Follow-up |
There are no follow up visits in this study
|
| Interim or Final Data Summary |
| Interim Results |
There is no interim device safety Information from this study
|
| Actual Number of Patients Enrolled |
The Informed Decision Process consisted of yearly surveys. Each year a different sample was selected for the survey. These are the results for 2011 annual report.
54 surveys were returned. Per the condition of approval, the sponsor did administer the survey to a random selection of 50 physicians.
|
| Actual Number of Sites Enrolled |
N/A
|
| Patient Follow-up Rate |
N/A
|
| Final Safety Findings |
N/A
|
| Final Effect Findings |
The majority of respondents (94.2%) said the Informed Decision Brochure was of value in helping patients to understand the risks and benefits of implant surgery.
|
| Study Strengths & Weaknesses |
The sample of physicians was chosen randomly, which is a strength of the study.
However, the observational, cross-sectional design of the study does not allow for any hypothesis testing. The results are descriptional only.
|
| Recommendations for Labeling Changes |
Mentor has no current plans to change the Informed Decision Process based on the survey results.
|
| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P030053 / PAS004 |
| Date Original Protocol Accepted |
11/17/2006
|
| Date Current Protocol Accepted |
11/17/2006
|
| Study Name |
Adjunct Study
|
| Device Name |
MEMORYGEL SILICONE GEL -FILLED BREAST IMPLANTS
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
No Control
|
| Analysis Type |
Analytical
|
| Study Population |
Adolescent: 13-18 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
The Adjunct study is a 5-year study, in which patients will be followed at 1, 3, and 5 years postoperatively to assess satisfaction and occurrence of local complications.
|
| Study Population |
The study population is as per device indication. This device is indicated for breast augmentation for women at least 22 years old and for breast reconstruction for women of any age. Breast Augmentation includes primary breast augmentation to increase the breast size, as well as revision surgery to correct or improve the results of a primary breast augmentation surgery. Breast reconstruction includes primary reconstruction to replace breast tissue that has been removed due to cancer or trauma or that has failed to develop properly due to a severe breast abnormality. Breast reconstruction also includes revision surgery to correct or improve the results of a primary breast reconstruction surgery.
|
| Sample Size |
number of study sites: 2,958; 12,811 reconstruction patients were implanted with 23,090 implants
|
| Key Study Endpoints |
Safety endpoints include clinical complications such as infection, seroma, implant rupture and capsular contracture at 1 ,3, 5 years of follow-up and rheumatologic/immunologic symptoms and connective tissue disorders at 3, 5 years of follow-up
|
| Follow-up Visits and Length of Follow-up |
3 follow-up visits during 5 years of study (1, 3, 5 years post-implantation)
|
| Interim or Final Data Summary |
| Interim Results |
A total of 136,609 patients implanted with MemoryGel breast implants for reconstruction and revision-reconstruction were enrolled in the Adjunct study. The overall patient follow-up rates at 1, 3 and 5 years were 35.7%, 24.0% and 16.0% respectively.
|
| Actual Number of Patients Enrolled |
147,585
|
| Actual Number of Sites Enrolled |
4,684
|
| Patient Follow-up Rate |
44.0% at 1 year, 24.7% at 3 years, 13.8% at 5 years
|
| Final Safety Findings |
The 3 most commonly reported complications using the Kaplan-Meier cumulative incidence estimates at
5 years were: asymmetry (18.6%), wrinkling (9.9%), and Capsular Contracture, Baker III/IV (8.3%) in the Reconstruction Cohort; asymmetry (23.7%), wrinkling (14.3%), and Capsular Contracture, Baker III/IV (11.7%) in the Revision-Reconstruction Cohort; wrinkling (12.3%), asymmetry (11.4%), and Capsular Contracture, Baker III/IV (9.2%) in the Revision- Augmentation Cohort.
The most common reasons by cohort for removal were: capsular contracture (36.4%), infection
(13.2%), and patient request for size and implant change (10.5%) in the Reconstruction Cohort;
capsular contracture (37.4%), leakage/rupture/ deflation (12.2%), and infection (11.5%) in the Revision-Reconstruction Cohort; capsular contracture (36.1%), leakage/rupture/ deflation (16.1%), and patient request for size and implant change (10.3%) in the Revision-Augmentation Cohort.
The Kaplan-Meier cumulative rupture rates at 5 years were: 1.8% in the Reconstruction Cohort; 3.6%
in the Revision-Reconstruction Cohort; 3.5% in the Revision-Augmentation Cohort.
Bilateral implantation, white, infra-mammary surgical approach and sub-glandular surgical approach showed a higher risk of rupture, and reconstruction, smooth surface implant, high profile implant, high education and sub-muscular surgical placement showed a lower risk of rupture.
Rheumatoid arthritis was the most common patient-reported rheumatic disease at 0.6%. Fibromyalgia and Raynaud's phenomenon were the most commonly reported rheumatic syndromes at 0.8% and 0.5% respectively.
|
| Final Effect Findings |
N/A
|
| Study Strengths & Weaknesses |
A large number of patients were enrolled in the adjunct study. However, the study was originally
designed to address the public health needs of reconstruction and revision patients before device approval and to gather safety data regarding short-term post-implant complications under a limited clinical protocol without follow-up goals. The overall patient follow-up rates at 1, 3 and 5 years in this final report were only 44.0%, 24.7% and 13.8% respectively. The poor patient compliance significantly limited meaningful interpretation of the available safety results.
|
| Recommendations for Labeling Changes |
No
|
| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P030053 / PAS005 |
| Date Original Protocol Accepted |
11/17/2006
|
| Date Current Protocol Accepted |
11/17/2006
|
| Study Name |
Core
|
| Device Name |
MEMORYGEL SILICONE GEL -FILLED BREAST IMPLANTS
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
No Control
|
| Analysis Type |
Analytical
|
| Study Population |
Adolescent: 13-18 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
The Core study is a 10-year prospective, open-label, multi-center cohort study to evaluate the safety and effectiveness of MemoryGel breast implants
|
| Study Population |
The study populaiton is as per device indication. This device is indicated for breast augmentation for women at least 22 years old and for breast reconstruction for women of any age. Breast Augmentation includes primary breast augmentation to increase the breast size, as well as revision surgery to correct or improve the results of a primary breast augmentation surgery. Breast reconstruction includes primary reconstruction to replace breast tissue that has been removed due to cancer or trauma or that has failed to develop properly due to a severe breast abnormality. Breast reconstruction also includes revision surgery to correct or improve the results of a primary breast reconstruction surgery.
|
| Sample Size |
1000 patients at up to 40 sites
|
| Key Study Endpoints |
Safety endpoints include point prevalence on a per patient and per device basis of rates of occurrence of all adverse events and time to occurrence of the complication; Effectiveness endpoints include patient satisfaction measured by validated quality of life questionnaires and change in breast size measured by both bra and cup size and the chest/bust circumference.
|
| Follow-up Visits and Length of Follow-up |
11 follow-up visits (6 months and annually 1-10 years after surgery) during 10 years of study
|
| Interim or Final Data Summary |
| Interim Results |
A total of 1,008 female patients (including 552 Augmentation, 145 Revision-Augmentation, 251 Reconstruction, and 60 Revision-Reconstruction patients) were enrolled in the Core study. The overall follow-up rate was 64.4% at 7 years. The top 3 7-year Kaplan-Meier cumulative incidence rates of complications were any operation (19.3%), Baker III, IV capsular contracture (10.3%) and ecxplantation with or without replacement (7.2%) for augmentation patients; any operation (36.9 Baker III, IV capsular contracture (23.3%) and ecxplantation with or without replacement (20.1%) for revision-augmentation patients; any operation (36.8%), ecxplantation with or without replacement (19.8%) and Baker III, IV capsular contracture (14.0%) for reconstruction patients; any operation (38.9 Baker III, IV capsular contracture (29.4%) and ecxplantation with or without replacement (26.0%) for revision-reconstruction patients.
|
| Actual Number of Patients Enrolled |
1,008
|
| Actual Number of Sites Enrolled |
48
|
| Patient Follow-up Rate |
62% at 10 years
|
| Final Safety Findings |
For the Primary Augmentation cohort, the 10-year Kaplan-Meier estimated cumulative incidence rates for the key complications at the patient level were: capsular contracture III/IV, 12.1%; infection, 1.6%;
explantation with or without replacement, 11.6%; explantation with replacement with study device, 7.4%;
and any reoperation, 25.5%. The most frequently reported primary reasons for reoperation were capsular contracture II/III/IV (25.4% of reoperations) and breast mass (10.6% of reoperations).
For the Revision-Augmentation cohort, the rates were: capsular contracture III/IV, 24.4%; infection,
1.4%; explantation with or without replacement, 24.1%; explantation with replacement with study device,
13.6%; and any reoperation, 43.6%. The most frequently reported primary reason for reoperation was capsular contracture II/III/IV (30.4% of reoperations).
For the Primary Reconstruction cohort, the rates were: capsular contracture III/IV, 20.5%; infection,
6.2%; explantation with or without replacement, 33.4%; explantation with replacement with study device,
19.8%; and any reoperation, 49.0%. The most frequently reported primary reasons for reoperation were asymmetry (16.6% of reoperations), capsular contracture II/III/IV (14.0% of reoperations), rupture (12.7% of reoperations), and breast mass (10.8% of reoperations).
For the Revision-Reconstruction cohort, the rates were: capsular contracture III/IV, 36.9%; infection, 0%;
explantation with or without replacement, 37.8%; explantation with replacement with study device,
24.8%; and any reoperation, 50.7%. The most frequently reported primary reasons for reoperation were capsular contracture II/III/IV (23.4% of reoperations) and breast mass (12.8% of reoperations).
Overall, the most frequently reported reasons for explantation through 10 years were size change, capsular contracture II/III/IV, and rupture. Based on the MRI cohort, the overall Kaplan-Meier estimated cumulative rupture rates at 10 years were 27.9% and 18.5% for patients and implants, respectively
|
| Final Effect Findings |
The overall mean changes in circumferential chest size were positive and statistically significant. The overall mean bra cup size increase from baseline across all follow-up visits was 1.8 cup sizes and was statistically significant. At the 10-year follow-up visit, overall 97.6% of patients indicated they would make the same decision to have breast implant surgery.
|
| Study Strengths & Weaknesses |
One of the study strengths is that the study is a prospective, multicenter study that provides long term data up to 10 years on the safety and effectiveness of the device. The weaknesses of the study were the lack of
a comparison group and lack of statistical power to detect rare events due to the small sample size.
|
| Recommendations for Labeling Changes |
The labeling will be updated based on the 10-year safety and effectiveness results reported in the Core
PAS final report.
|
| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P030053 / PAS006 |
| Date Original Protocol Accepted |
11/17/2006
|
| Date Current Protocol Accepted |
11/17/2006
|
| Study Name |
Focus Group
|
| Device Name |
MEMORYGEL SILICONE GEL -FILLED BREAST IMPLANTS
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
No Control
|
| Analysis Type |
Descriptive
|
| Study Population |
Adolescent: 13-18 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
The Focus Group study is a one time study designed to evaluate how easily patients understand the information in the informed decision brochure about the risks associated with the use of slicone breast implants. A total of 35 women participated in one of four group interviewers for the study. Two discussion groups were conducted for women considering breast implants for augmentation and two group interviews were conducted with women considering breast implantssfor reconstruction. Each group was composed of eight to ten women. A trained female moderator led the discussion groups, which were each abouat 2 hours long. Respondents received a $150 honorarium in return for their time. Group interviewrs were conducted in a professional resaraevh facilities that alloesd for observation and audio recording.
|
| Study Population |
The study population is as per device indication. This device is indicated for breast augmentation for women at least 22 years old and for breast reconstruction for women of any age. Breast Augmentation includes primary breast augmentation to increase the breast size, as well as revision surgery to correct or improve the results of a primary breast augmentation surgery. Breast reconstruction includes primary reconstruction to replace breast tissue that has been removed due to cancer or trauma or that has failed to develop properly due to a severe breast abnormality. Breast reconstruction also includes revision surgery to correct or improve the results of a primary breast reconstruction surgery.
|
| Sample Size |
35 women in one of each of 4 groups. Two were held in Dallas, Texas and two in San Francisco, California. These sites were selected based on the volume of breast implant surgeries condcuted in these areas.
|
| Key Study Endpoints |
The study used two methods of data collection: discussion groups and a self-administered survey-- to capture both group level and individual level data. A female moderator led each discussion group using a discussion guide prepared in advance by the contracted research firm with the assitance of Mentor Corporation. Two versions of the brochure were tested, one designed for augmentation patients and one designe for reconstruction patients. Endpoints included respondents' reactions to the overall layout oand format of the brochures, content ordering, and iollustrations and tables.. Data were collected on respondents' comprehesnion and perceived relevance of the content. Throughout the discussion, data were gathered on respondents' suggestions for improvements.
|
| Follow-up Visits and Length of Follow-up |
No Follow-up required
|
| Interim or Final Data Summary |
| Interim Results |
Study is completed. See Final Results
|
| Actual Number of Patients Enrolled |
35 women distributed over 4 groups.
|
| Actual Number of Sites Enrolled |
2 (San Francisco and Dallas)
|
| Patient Follow-up Rate |
not applicable
|
| Final Safety Findings |
No safety findings. Key findings reported by sponsor are summarized here. Overall reaction to both versions of brochures tested was positive. Group discusions and self-administered survey indicate that solid understanding of the information in brochures. Respondents all agreed that brochure was more comprehensive than anything else they had seen. Respondents had difficulty understanding particular points in the brochure. Misost respondents interpreted the informtion on MRIs for the detection of silent ruptures to mean that MRIs were recommended as replacements for mammography. Many respondents perceived that silicone breast implnats are fragile and prone to rupture. Many were alarmed by this and teh combination of the fact that most ruptures are silent. A few respondents concluded that the true purpose of the brochure was to protect Mentor, rather than inform patietns about breast implant surgery. Respondents reported taht most of the information did not help them weigh the relative importance of risks and complications associated with breast implants. Brochure fell short of provideing infiormation on the benefits of breast implants and did not acknowledge the deeply personal benefits of body image and self-esteem, especially for women who lose their breast to cancer.
|
| Study Strengths & Weaknesses |
Discussion groups are useful for exploring attitudes, knowledge and beliefs. Readers should be cautious in intrepreting the data and in making generalizations about the target population as a whole. Given the qualitative nature of the data, they suggest general tendencies but can not be considered definitive. The study is limited by its small sample size and the selection of a non-probablistic sample.
|
| Recommendations for Labeling Changes |
Add information clearly describing differences between restoration, replacement, reconstruction, and revision early in the main body of the brochure. add informtion on Organize information on potential complications based onteh likelihood of occurrence and calling attention to the relative importance of each possible outcome. Provide more information about benefits. provie more qualitative information (personal testimony, caes histories) to help women make more informed decisions. Include more illustrations, visual white space, color and bolding. mke illustrations, larger, darker, ,orerealistinc and more clearly labelled.
|
| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P030053 / PAS009 |
| Date Original Protocol Accepted |
01/16/2015
|
| Date Current Protocol Accepted |
08/28/2020
|
| Study Name |
Re-Op Phase
|
| Device Name |
MEMORYGEL SILICONE GEL -FILLED BREAST IMPLANTS
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
No Control
|
| Analysis Type |
Descriptive
|
| Detailed Study Protocol Parameters |
| Study Objectives |
On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant anaplastic large cell lymphoma (BI-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75).
This Re-Op study requirement was designed as part of the re-design of the LARGE PAS for the MemoryGel® breast implants. In this Re-Op Phase of the study, data will be collected when the subjects with MemoryGel® breast implants have secondary surgical procedures/re-operations. This Re-Op Phase will serve as a bridge between the Large PAS and NBIR.
|
| Study Population |
Women with MemoryGel breast implants who were enrolled in the Large PAS.
|
| Sample Size |
41,900
|
| Key Study Endpoints |
Implant removal and reoperation rates; Reasons for reoperation.
|
| Follow-up Visits and Length of Follow-up |
The follow쳌]up data will be collected when the participant requires a secondary procedure/reoperation.
|
| General |
| Study Status |
Ongoing |
Application Number /
Requirement Number |
P030053 / PAS008 |
| Date Original Protocol Accepted |
10/01/2014
|
| Date Current Protocol Accepted |
03/08/2022
|
| Study Name |
MemoryGel and Shape Glow Study
|
| Device Name |
MEMORYGEL SILICONE GEL -FILLED BREAST IMPLANTS
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
Concurrent Control
|
| Analysis Type |
Analytical
|
| Study Population |
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant anaplastic large cell lymphoma (BI-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75).
The MemoryGel and Shape Glow Study was designed as part of the re-design of the LARGE PAS. This is a smaller cohort study (10 years follow-up) designed to address safety outcomes (i.e., including local complications, less rare connective tissue diseases, rheumatologic and neurologic signs and symptoms, breast cancer, lung cancer and suicide), reproduction and pregnancy outcomes, lactation problems, effects on mammography, effects on patient satisfaction with breasts and psychosocial wellbeing, and silicone subject compliance with magnetic resonance imaging (MRI) recommendations.
This restructured PAS, once completed as designed, would satisfy the post-approval requirements for both the MemoryGel® (P030053) and Memory Shape (P060028) silicone breast implants. In addition, information gained from the NBIR will help strengthen the general understanding of implantation rates and certain risks associated with breast implants.
|
| Study Population |
Women who receive Mentor’s MemoryGel and MemoryShape breast implants for the purpose of primary or revisional breast augmentation and primary or revisional breast construction. Additionally, women who undergo aesthetic surgery (for example liposuction, rhinoplasty, brow lift, autoplasty, rhytidectomy, mentoplasty/genioplasty, otoplasty, or blepharoplasty) will be enrolled as concurrent controls.
|
| Sample Size |
The study will enroll 2,518 women who receive Memory Gel and MemoryShape Breast Implants for augmentation, reconstruction, augmentation revision, or reconstruction revision. The study will also enroll 300 women undergoing aesthetic surgery who will serve as concurrent control group.
The study was designed to have 80% power to be able to detect as statistically significant a relative risk of 2.0 for adverse events that occur,
without implants with a frequency of 5.0 per 10,000 person-years, based on a one-sided test conducted at level of significance of 0.05. Based on these specifications, it was determined that approximately 20,328 person-year, a total of at least 2,518 breast implants patients would be required. Patient are to be followed for 10 years. For purposes of sample size calculationns, assuming a follow-up rate of 65% at 10 years and a linear loss to follow-up, there would be an average of 8, 075 person-years per patient. Thus, in order to obtain the 20,328 person-years, a total of 2,518
breast implants patients would be required.
|
| Key Study Endpoints |
Safety Endpoints to be evaluated are as follows:
Local complications, connective tissue diseases, rheumatologic and neurologic signs and symptoms, cancer, suicide, and lactation complications
and magnetic resonance imaging (MRI) compliance and results.
Effectiveness BREAST-Q will be assessed in a subset of breast implant patients, approximately 500 patients, by responses to questions addressing their perceived quality-of-life and satisfaction with their breast implants.
|
| Follow-up Visits and Length of Follow-up |
Patients will be followed for 10 years. MemoryGel and Memory Shape Breast Implant patients will be evaluated by the investigator at baseline and years 1, 5, and 10, and will complete questionnaires at baseline and annually for 10 years. A concurrent control group of women undergoing other aesthetic surgery (patients are referred to as Control participants) will complete questionnaires at baseline and annually for 10 years.
|
| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
3,611 total subjects
|
| Actual Number of Sites Enrolled |
62
|
| Patient Follow-up Rate |
The 2 year follow-up rates are:
82.6% - MemoryGel cohort
90.6% - MemoryShape Prospective cohort
83.3% - MemoryShape Retrospective cohort
76.7% - Control cohort
|
| General |
| Study Status |
Other |
Application Number /
Requirement Number |
P030053 / PAS002 |
| Date Original Protocol Accepted |
11/17/2006
|
| Date Current Protocol Accepted |
11/17/2006
|
| Study Name |
Device Failure Study
|
| Device Name |
MEMORYGEL SILICONE GEL -FILLED BREAST IMPLANTS
|
| General Study Protocol Parameters |
| Study Design |
Bench/Lab Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
No Control
|
| Analysis Type |
Descriptive
|
| Study Population |
Adolescent: 13-18 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
The Device failure study is still ongoing. The data is submitted to the FDA in PMA Annual Reports.
|
| Study Population |
All explanted devices are to be returned to Mentor and analyzed and tested
|
| Sample Size |
All returned devices are analyzed.
|
| Key Study Endpoints |
An analysis was performed on the following categories to identify specific trends correlating to device failures: device type, size, clinical variables, visual observations, in-vivo time, surgical approach, device placement, incision size, pocket irrigation usage. Explanted devices underwent the following physical testing to assess the physical characteristics of the explanted devices: tension set, joint strength, ultimate elongation, gel cohesion.
|
| Follow-up Visits and Length of Follow-up |
There is no patient follow-up in this study
|
| General |
| Study Status |
Redesigned/Replaced Study |
Application Number /
Requirement Number |
P030053 / PAS001 |
| Date Original Protocol Accepted |
11/17/2006
|
| Date Current Protocol Accepted |
10/01/2014
|
| Study Name |
Large PAS
|
| Device Name |
MEMORYGEL SILICONE GEL -FILLED BREAST IMPLANTS
|
| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
|
| Data Source |
New Data Collection
|
| Comparison Group |
Concurrent & Historical Control
|
| Analysis Type |
Analytical
|
| Study Population |
Adolescent: 13-18 yrs,
Transit. Adolescent B (as adults) : 18-21 yrs,
Adult: >21
|
| Detailed Study Protocol Parameters |
| Study Objectives |
On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee (link) met
to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant anaplastic large cell lymphoma (BI-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75).
The Large PAS for the MemoryGel® Silicone Breast Implant was an observational prospective cohort study (10 years of follow-up), originally designed to address very rare adverse events with the target enrollment goal of 41,900 MemoryGel® and 1,000 saline patients. Mentor® met patient enrollment goals, but the study was limited by low follow-up rates. The Large PAS was re-designed (listed as Revised/Replaced on the PAS webpage) with: a re-operation data collection phase (Re-op Phase), a smaller cohort study, and a case-control studies requirement. The smaller cohort study and Re-Op Phase are ongoing and the description of study objectives and designs can be found in the PAS webpage under OSB Lead-MemoryGel and Shape Glow Study and OSB Lead-Re-Op Phase. The case-control study requirements originally were designed to study the following endpoints: rare connective tissue diseases, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma. The PAS case-control study requirements were put-on hold while the systematic literature review was conducted. The systematic literature review demonstrated insufficient evidence of association between silicone gel-filled breast implants and lymphoma, brain cancer, cervical cancer, rare connective tissue diseases (CTDs), or rare neurological events. Therefore, the PAS case-control studies were terminated because using case-control studies to evaluate these rare adverse events among patients with silicone breast implants would not provide additional value.
The FDA continues to monitor these rare adverse events using other postmarket surveillance tools and real-world data (e.g. NBIR, PROFILE, MDRs)
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| Study Population |
Study Population consists of women who receive MemoryGel and saline breast implants for augmentation, revision-augmentation, reconstruction and revision-reconstruction . This device is indicated for breast augmentation for women at least 22 years old and for breast reconstruction for women of any age. Breast Augmentation includes primary breast augmentation to increase the breast size, as well as revision surgery to correct or improve the results of a primary breast augmentation surgery. Breast reconstruction includes primary reconstruction to replace breast tissue that has been removed due to cancer or trauma or that has failed to develop properly due to a severe breast abnormality. Breast reconstruction also includes revision surgery to correct or improve the results of a primary breast reconstruction surgery.
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| Sample Size |
41,900 MemoryGel and 1,000 saline patients
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| Key Study Endpoints |
Baseline data will be collected from the study subjects using patient self-administered questionnaire during the visit for preoperative evaluation. For MemoryGel patients, information on local complications including reasons for re-operation with or without removal of breast implants and reasons for removal, results of MRI evaluations, and results of rheumatologic or neurological evaluations will be collected during scheduled follow-up and on an interim/unscheduled basis, as needed.
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| Follow-up Visits and Length of Follow-up |
3 surgeon visits (1, 4-6 and 9-10 years post-implantation) and 10 annual follow-up questionnaire completed by participants during 10 years of study
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| Interim or Final Data Summary |
| Interim Results |
A total of 42,928 female patients (41,911 MemoryGel, 1,017 saline) were enrolled. Through May 1, 2010, the Year 1 follow-up rate of surgeon visit for MemoryGel participants was 22.8%; the Year 1, 2, 3 follow-up rates of patient questionnaire were 21.4%, 24.3%, 23.0% for MemoryGel and 5.9%, 7.3% , 16.7% for saline participants respectively. The follow-up rates were too low to provide meaningful safety information at this time.
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| Actual Number of Patients Enrolled |
A total of 41,452 MemoryGel participants were enrolled in the study.
Enrollment by indication was: 26,173 primary augmentation participants, 8382 revision-augmentation participants, 5023 primary reconstruction participants, 1761 revision-reconstruction participants, and 113 participants with missing indication information.
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| Actual Number of Sites Enrolled |
2,342
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| Patient Follow-up Rate |
At year 7, the overall follow-up rate was 20.1%.
Follow-up rate by indication was: 19.2% primary augmentation group, 17.6% revision-augmentation group, 27.9% primary reconstruction group, 22.7% revision-reconstruction group, and 22% missing indication group.
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| Final Safety Findings |
Participant Reported Complications and Reoperations
For MemoryGel participants in the primary augmentation cohort, the cumulative incidence rate at 7 years of participant reported key local complications/reoperations was estimated to be 35.9% for any complication or reoperation, 3.3% for breast infection, 19.6% for breast pain related to implants, 8.7% for capsular contracture Baker Grade II, 7.2% for capsular contracture Baker Grades III/IV, 0.7% for MRI confirmed rupture, 8.2% for suspected rupture, 6.2% for implant removal, and 11.7% for reoperation.
For MemoryGel participants in the revision-augmentation cohort, the cumulative incidence rate at 7 years of participant reported key local complications/reoperations was estimated to be 50.8% for any complication or reoperation, 4.0% for breast infection, 25.0% for breast pain related to implants, 20.2% for capsular contracture Baker Grade II, 18.0% for capsular contracture Baker Grades III/IV, 2.8% for MRI confirmed rupture, 14.2% for suspected rupture, 12.5% for implant removal, and 18.9% for reoperation.
For MemoryGel participants in the primary reconstruction cohort, the cumulative incidence rate at 7 years of participant reported key local complications/reoperations was estimated to be 53.4% for any complication or reoperation, 6.3% for breast infection, 29.6% for breast pain related to implants, 12.3% for capsular contracture Baker Grade II, 12.7% for capsular contracture Baker Grades III/IV, 2.2% for MRI confirmed rupture, 12.5% for suspected rupture, 15.9% for implant removal, and 24.7% for reoperation.
For MemoryGel participants in the revision-reconstruction cohort, the cumulative incidence rate at 7 years of participant reported key local complications/reoperations was estimated to be 58.5% for any complication or reoperation, 5.9% for breast infection, 27.8% for breast pain related to implants, 16.1% for capsular contracture Baker Grade II, 18.3% for capsular contracture Baker Grades III/IV, 2.6% for MRI confirmed rupture, 15.6% for suspected rupture, 17.4% for implant removal, and 26.6% for reoperation.
Reasons for Reoperation
Among MemoryGel participants the Kaplan-Meier estimated cumulative incidences through seven years following implantation of participant reported reoperation are 11.7% for primary augmentation participants, 18.9% for revision-augmentation participants, 24.7% for primary reconstruction participants, and 26.6% for revision-reconstruction participants.
Among primary augmentation participants, the two most frequent reasons for reoperation (at the procedure level) were capsular contracture Baker Grades II/III/IV (26.8% of procedures) and patient requested size change (21.0%).
Among revision-augmentation participants, the two most frequent reasons for reoperation were capsular contracture Baker Grades II/III/IV and patient requested size change (31.1% and 19.9% of procedures, respectively).
Among primary reconstruction participants, the two most frequent reasons for reoperation were asymmetry (22.1%) and capsular contracture Baker Grades II/III/IV (20.0%).
Among revision-reconstruction participants, the two most frequent reasons for reoperation were asymmetry and capsular contracture Baker Grades II/III/IV (24.4% and 21.4%, respectively).
Reasons for Explantation
In the two augmentation cohorts, the most frequent reason for explantation during the seven years after implantation was patient requested size change (58.9% and 44.8% of procedures among participants in the primary augmentation and revision-augmentation cohorts, respectively). In the two reconstruction cohorts, the most frequent reason for explantation was asymmetry (26.4% and 31.2% of procedures among participants in the primary reconstruction and revision-reconstruction cohorts, respectively).
Due to word limits, the safety results are continued in the effectiveness section below.
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| Final Effect Findings |
There were no study objectives related to effectiveness. The information that follows is a continuation of safety findings.
Types of Additional Procedures
Among MemoryGel participants having reoperations during the seven years after implantaton, the most frequent type of procedure in each cohort and overall was implant removal with or without replacement with any device (48.9% of procedures overall). Also frequent in each of the cohorts were capsulectomy (12.3% of procedures overall), pocket adjustment (8.2% of procedures overall), and open capsulotomy (7.5% of procedures overall).
Connective Tissue Disease and Fibromyalgia
Among all MemoryGel participants, there were a total of 349 new cases of rheumatoid arthritis (incidence rate per 10,000 person-years of 32.2), 46 new cases of scleroderma (incidence rate = 4.2), 66 new cases of SLE (incidence rate = 6.0), 62 new cases of Sjögren?s disease (incidence rate = 5.7), 204 new cases of other CTDs (incidence rate = 18.8), and 307 new cases of fibromyalgia (incidence rate = 28.4).
Cancer
Overall, 532 MemoryGel participants without a history of cancer at baseline experienced newly diagnosed cases of cancer. There were 116 participants with newly diagnosed cases of breast cancer, 5 with lung cancer, 3 with brain cancer, and 408 with other types of cancer, including 65 with melanoma. The incidence rates (per 10,000 person-years) were 63.8, 13.9, 0.6, 0.4, and 48.9 for all types of cancer, breast cancer, lung cancer, brain cancer, and other cancers, respectively. The incidence rate (per 10,000 person-years) was 7.8 for melanoma.
Neurological Disease
There were a total of 394 new cases of neurological disease among MemoryGel participants. There were 47 new cases of multiple sclerosis, 17 of myositis, and 332 of other types of neurological diseases. The incidence rates (per 10,000 person-years) were 35.8, 4.3, 1.5, and 30.7 for all types of neurological diseases, multiple sclerosis, myositis, and other neurological diseases, respectively. The most
common ?other neurological diseases? included epilepsy, headache, peripheral neuropathy, stroke, trigeminal neuralgia, and tumor.
Rheumatological and Neurological Signs and Symptoms
Overall, the estimates of mean post-baseline prevalence for MemoryGel participants were highest for persistent non-traumatic joint pain (estimate = 12.9%) and persistent sleep disorders at night (estimate = 25.8%).
Reproduction and Offspring
Overall, a total of 3133 post-operative pregnancies have been reported among MemoryGel participants. Among them, there were a total of 501 miscarriages or stillbirths (16.0%), with 416 miscarriages (13.3%) and 85 stillbirths (2.7%). Overall, a total of 1710 offspring have been reported among MemoryGel participants. Among these, there were 234 premature births (13.7%), 155 low birth weight babies (9.1%), and 194 babies that required neonatal intensive care (11.3%). There were no reported births of children with cleft lip, neural tube defect, or pyloric stenosis. There was one reported birth of cleft palate and one of esophageal deformity. There were 25 reported births (1.5% of births) with other birth defects or congenital malformations.
Suicide
There have been a total of 173 known deaths among the MemoryGel participants. There have been 5 known suicides among these 173 deaths.
Anaplastic Large Cell Lymphoma
There has been one confirmed case of Anaplastic Large Cell Lymphoma (ALCL) in a Large PAS participant.
MRI Compliance and Rupture
At years 1, 2, 3, 4, 5, 6, and 7, only 3.4%, 4.7%, 5.2%, 5.5%, 4.9%, 4.5%, and 4.4%, respectively, of MemoryGel participants reported having had an MRI since completing their last questionnaire. Overall, of the 2051 MemoryGel participants with an MRI, there were 132 participants (6.4%) with rupture.
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| Study Strengths & Weaknesses |
Overall, there are a total of 255,541 person-years of follow-up among MemoryGel participants. However, results are difficult to interpret due to the very low follow-up rate. Loss to follow-up can introduce study bias and limits the interpretation of the study results, as those that remain in the study may not be comparable to those that were lost. FDA and the sponsor have agreed to replace the original LARGE study requirement with a new study design to fulfill the condition of approval.
It should also be noted that not all reported cases of CTD or neurological diseases were confirmed as board-certified diagnosed cases. Therefore, the current cases reported in this study (self-reported by participants as diagnosed by a board-certified specialist, rheumatologist or neurologist) may not represent the actual rate.
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| Recommendations for Labeling Changes |
Due to very low follow-up rate, labeling changes are not recommended.
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| General |
| Study Status |
Terminated |
Application Number /
Requirement Number |
P030053 / PAS007 |
| Date Original Protocol Accepted |
04/18/2014
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| Date Current Protocol Accepted |
04/18/2014
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| Study Name |
Breast Implant Case Control Studies
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| Device Name |
MEMORYGEL SILICONE GEL -FILLED BREAST IMPLANTS
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| General Study Protocol Parameters |
| Study Design |
Case Control Study
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| Data Source |
New Data Collection
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| Comparison Group |
Concurrent & Historical Control
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| Analysis Type |
Analytical
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| Study Population |
Adult: >21
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| Detailed Study Protocol Parameters |
| Study Objectives |
On August 30th -31st, 2011, the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee link met to discuss updates on the postmarket experience of silicone gel-filled breast implants and to make recommendations on issues related to the monitoring of silicone gel-filled breast implants. The Advisory Panel recommended more efficient approaches to assessing the performance of silicone gel-filled breast implants than continuing new enrollment in the large prospective studies. Their recommendations included conducting a systematic literature review and re-designing the Large Post-Approval Studies (PAS) to have more efficient methodologies to assess rare outcomes. In response, FDA entered a collaboration with the American Society of Plastic Surgeons (ASPS), the Plastic Surgeons Foundation (PSF), breast implant manufacturers and patient advocate groups, to establish the National Breast Implant Registry (NBIR) and the PROFILE Registry (established to collect data on potential cases of breast-implant associated anaplastic large cell lymphoma (BIA-ALCL)). Tufts University was tasked with conducting a systematic literature review to look at rare endpoints (listed below) and silicone gel-filled breast implants. Details on the literature review methodology and findings can be found here (Balk EM, et al., Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review. Ann Intern Med. 2016. 2;164(3):164-75).
The case-control study requirements originally were designed to study the following endpoints: rare connective tissue diseases, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma. The PAS case-control study requirements were put on-hold while the systematic literature review was conducted. The systematic literature review showed insufficient evidence of association between silicone gel-filled breast implants and lymphoma, brain cancer, cervical cancer, rare connective tissue diseases (CTDs), or rare neurological events. Therefore, the PAS case-control studies were terminated because using case-control studies to evaluate these rare adverse events among patients with silicone breast implants would not provide additional value.
The FDA continues to monitor for these rare adverse events using other postmarket surveillance tools and real-world data (e.g. MDRs MDRs, NBIR, PROFILE).
|
| Study Population |
Women in Denmark, Germany, and the United Kingdom with the studied rare diseases (i.e., rare CTDs, rare neurological diseases, brain cancer, cervical/vulvar cancer and lymphoma) as cases and women without any of the 5 studied rare diseases from the same countries as controls.
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| Sample Size |
For each of the 5 case]control studies, 1,150 cases of women diagnosed with studied rare disease identified from the specialized medical centers and cancer registries in Denmark, Germany and the UK will be enrolled. A total of
5,000 females identified from the same neighborhood as cases without any of the 5 rare disease outcomes will be enrolled as a control group to the 5 case groups.
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| Key Study Endpoints |
Data will be collected by using questionnaires as well as electronic information provided by the cancer registries/tumor centers. The same questionnaires will be used for cases and controls. The participating women will fill in the questionnaires on potential confounders (e.g., life] style related covariates) and exposure to breast implants. Similar questionnaires have been successfully used in previous case]control studies with self]administered questionnaires.
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| Follow-up Visits and Length of Follow-up |
N/A
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