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U.S. Department of Health and Human Services

Post-Approval Studies (PAS) Database

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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) of approved medical devices. This database allows you to search Post-Approval Study information by applicant or device information.

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BIFS (Large PAS)

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Study Status Redesigned/Replaced Study
Application Number /
Requirement Number
P020056 / PAS001
Date Original Protocol Accepted 11/17/2006
Date Current Protocol Accepted 08/03/2015
Study Name BIFS (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 Transit. Adolescent B (as adults) : 18-21 yrs, Adult: >21
Interim or Final Data Summary
Actual Number of Patients Enrolled * NOTE: The PAS001 (BIFS Large PAS) were revised and replaced with two ongoing PASs, i.e. PAS007 (Re-Op Phase, i.e. the NBIR arm selected for Re-Op study), and PAS008 (Natrelle and 410 combined cohort).
The evaluable subjects by indications are summarized in table below:
Subjects by Indication 39,069 Silicone 14,487 Saline
augmentation 28,365 (72.6%) 13,379 (92.4%)
revision augmentation 5,662(14.5%) 896 (6.2%)
reconstruction 4,386(11.2%) 171 (1.2%)
revision reconstruction 656(1.7%) 41 (0.3%)
Actual Number of Sites Enrolled 873
Patient Follow-up Rate The follow-up rates from year 1 to 8 are 70.2%, 74.8%, 74.4%, 69.4%, 60.5%, 55.1%, 50.8%, and 63.2% for Silicone cohort, and 46.1%, 53.8%, 60.9%, 58.6%, 52.9%, 46.0%, 42.0%, and 50.0% for Saline cohort, respectively. . Follow-up rate is calculated as [actual observed subjects/(yearly cohort - completed study without data in visit window)].
Final Safety Findings Deaths
There were 367 deaths (311 silicone and 56 saline) reported, which represents 0.7% of the analyzed population with a calculated event rate of 25 per 10,000 subject years. The most common cause of death was breast cancer (0.2%). Less than 0.1% of subjects in each cohort committed suicide. None of the deaths were related to the implant.
Very rare adverse events
All collected data (including any data on events occurring through Year 7) encompassing a total of > 157,000 observed subject years. For augmentation, reconstruction, and revision-augmentation cohorts, no event rate was twice as high in silicone subjects compared to national norms. Higher standard incidence ratios (SIRs) were observed in the revision-reconstruction cohort for scleroderma, Sjogren’s syndrome, and dermatomyositis/polymyositis.
Rare target adverse events
All collected data (including any data on events occurring through Year 7) encompassing a total of > 157,000 observed silicone subject years and > 14,000 observed saline subject years. No adverse event demonstrated an increased risk (adjusted risk ratios) associated with the NATRELLE Silicone-filled Breast Implants compared to saline breast implants since all the 90% confidence interval included 1.0.
Local complications
The Year 5 Kaplan Meier rates for local complications as well as rates of reoperation and implant removal with and without replacement are compared with Allergan’s Core study. In the Augmentation, Reconstruction, and Revision-Augmentation cohorts, no rate was higher in the BIFS study compared to the Core Study. Higher local complication rates were observed in the Revision-Reconstruction cohort that had smaller sample sizes (699 in BIFS study and 15 in Core study). The Kaplan-Meier estimated cumulative incidence rates at 5 years for less frequent, but severe complications were infection (0.3%-1.9%), rupture (1.4%-2.6%), removal without replacement (1.1%-2.4%). Rheumatologic Signs & Symptoms
There was no clear pattern to reports of rheumatologic signs and symptoms, although there were ~500 possible events in silicone vs less than 5 events occur in saline, and some symptoms occurred more frequently in the silicone cohort compared to the saline cohort, even after an age-adjusted analysis.
Final Effect Findings A total of 12,758 (32.6%) Silicone subjects and 1,393 (9.6%) saline subjects completed the year 4 questionnaire. On the 100-point BREAST-Q scale, median satisfaction with breasts was 33.3 for both the Silicone and Saline cohorts at baseline and improved to 94.4 in both cohorts at year 1. At year 4, the median satisfaction with breasts decreased slightly to 88.9 for both cohorts.
The medians of psychosocial well-being scores were 66.7 for Silicone and 58.3 for Saline at baseline and improved to 97.2 for each cohort at year 1. At year 4, psychosocial well-being scores were 91.7 for Silicone and 88.9 for saline.
Study Strengths & Weaknesses Strength:
This is a large cohort study.
The follow-up rates are low (~40-60% from years 5-8) and the percentages of censoring/missing data are high (94% saline and 54% Silicone at year 1). Missing data and/or loss to follow-up introduce study bias and limit the interpretation of the study results.
Recommendations for Labeling Changes Due to very low follow-up rates after 5 years post-implant, labeling changes are not recommended

BIFS (Large PAS) Reporting Schedule

Reporting Schedule
Date Due
FDA Receipt
Applicant's Reporting Status
Large PAS 3 month report 02/16/2007 03/09/2007 Overdue/Received
Large PAS 6 month report 05/18/2007 05/16/2007 On Time
Large PAS 9 month report 08/17/2007 08/16/2007 On Time
Large PAS 1 year report 11/17/2007 11/13/2007 On Time
Large PAS 15 month report 02/16/2008 02/12/2008 On Time
Large PAS 18 month report 05/17/2008 05/08/2008 On Time
Large PAS 21 month report 08/16/2008 08/13/2008 On Time
Protocol Deviations report 10/24/2008 10/24/2008 On Time
Large PAS 2 year report 11/16/2008 11/12/2008 On Time
Large PAS 27 month report 02/15/2009 02/13/2009 On Time
Large PAS 30 month report 05/17/2009 05/15/2009 On Time
Large PAS 33 month report 08/16/2009 08/14/2009 On Time
Large PAS 3 year report 11/16/2009 11/10/2009 On Time
Large PAS 39 month report 02/15/2010 02/12/2010 On Time
Large PAS 42 month report 05/17/2010 05/13/2010 On Time
Large PAS 45 month report 08/16/2010 08/11/2010 On Time
Large PAS 4 year report 11/16/2010 11/12/2010 On Time
Large PAS 51 month report 02/15/2011 02/11/2011 On Time
Large PAS 54 month report 05/17/2011 05/12/2011 On Time
Large PAS 57 month report 08/16/2011 08/15/2011 On Time
Large PAS 5 year report 11/16/2011 11/17/2011 Overdue/Received
Large PAS 63 month report 02/15/2012 02/10/2012 On Time
Large PAS 66 month report 05/16/2012 05/14/2012 On Time
Large PAS 69 month report 08/15/2012 08/09/2012 On Time
Large PAS 6 year report 11/19/2012 11/27/2012 On Time
Large PAS 7 year report 11/15/2013 11/14/2013 On Time
Large PAS 8 year report 11/15/2014 11/06/2014 On Time
Large PAS 9 year report-final 11/15/2015 11/13/2015 On Time

Contact Us

Mandated Studies Program
Food and Drug Administration
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
Email: MandatedStudiesPrograms@fda.hhs.gov

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