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U.S. Department of Health and Human Services

Post-Approval Studies (PAS)

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The FDA has the authority to require sponsors to perform a post-approval study (or studies) at the time of approval of a premarket approval (PMA), humanitarian device exemption (HDE), or product development protocol (PDP) application. Post-approval studies can provide patients, health care professionals, the device industry, the FDA and other stakeholders information on the continued safety and effectiveness (or continued probable benefit, in the case of an HDE) approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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OSB Lead-Large PAS


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General
Application Number P030053 / PAS001
Current Plan Approved 10/01/2014
Study Name OSB Lead-Large PAS
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 Design Description The Large post-approval study is a 10-year cohort study to address specific issues for which the Core Study was not designed to fully answer, as well as to provide a long-term real-world assessment of study endpoints
Study Population Description 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.
Sample Size 41,900 MemoryGel and 1,000 saline patients
Data Collection 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.
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
Final Study Results
Interim Safety Information 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.
Number of Patients 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.

Number of Sites 2,342
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.

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.

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.

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.

Label Changes Due to very low follow-up rate, labeling changes are not recommended.


OSB Lead-Large PAS Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
Large PAS 3 month report 02/16/2007 02/16/2007 On Time
Large PAS 6 month report 05/18/2007 05/18/2007 On Time
Large PAS Semi-annual Report 05/18/2007 05/18/2007 On Time
Large PAS 9 month report 08/17/2007 08/17/2007 On Time
Large PAS 1 year report 11/17/2007 11/16/2007 On Time
Large PAS 15 month report 02/16/2008 02/15/2008 On Time
Large PAS 18 month report 05/17/2008 05/16/2008 On Time
Large PAS 21 month report 08/16/2008 08/18/2008 Overdue/Received
Large PAS 2 year report 11/16/2008 11/10/2008 On Time
Large PAS 27 month report 02/15/2009 02/17/2009 Overdue/Received
Large PAS 30 month report 05/17/2009 05/18/2009 Overdue/Received
Large PAS 33 month report 08/16/2009 08/14/2009 On Time
Large PAS 3 year report 11/16/2009 11/16/2009 On Time
Large PAS 39 month report 02/15/2010 02/12/2010 On Time
Large PAS 42 month report 05/17/2010 05/17/2010 On Time
Large PAS 45 month report 08/16/2010 08/16/2010 On Time
Large PAS 4 year report 11/16/2010 11/16/2010 On Time
Large PAS 51 month report 02/15/2011 02/15/2011 On Time
Large PAS 54 month report 05/18/2011 05/18/2011 On Time
Large PAS 57 month report 08/16/2011 08/16/2011 On Time
Large PAS 5 year report 11/16/2011 11/17/2011 On Time
Large PAS 63 month report 02/15/2012 02/15/2012 On Time
Large PAS 66 month report 05/16/2012 05/15/2012 On Time
Large PAS 6 year report 11/15/2012 11/07/2012 On Time
Large PAS 7 year report 11/15/2013 11/12/2013 On Time
Large PAS 8 year report 11/15/2014 11/13/2014 On Time
final report 05/31/2015 05/28/2015 On Time


Contact Us

Julie Unger
Project Manager, Post-Approval Studies Program
Food and Drug Administration
10903 New Hampshire Ave
WO66-4206v Silver Spring, MD
20993-0002

Phone: (301) 796-6134
Fax: (301) 847-8140
julie.unger@fda.hhs.gov

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