In January 2005, the oversight responsibility of the Post-Approval Studies Program was transferred to the Division of Epidemiology (DEPI) of the Office of Surveillance and Biometrics (OSB)/Center for Devices and Radiological Health (CDRH).
The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a premarket approval (PMA) application, protocol development product (PDP) application, or humanitarian device exemption (HDE) application. The program helps ensure that well-designed post-approval studies (PAS) are conducted effectively and efficiently and in the least burdensome manner.
CDRH has established an automated, internal tracking system that efficiently identifies the reporting status of active PAS studies ordered since January 1, 2005 based on study timelines incorporated in study protocols and agreed upon by the CDRH and applicants. This system represents CDRH's effort to ensure that all PAS commitments are fulfilled in a timely manner.
In addition, CDRH launched this publicly available webpage to keep all stakeholders informed of the progress of each PAS. The webpage displays general information regarding each PAS, as well as the overall study status (based on protocol-driven timelines and the adequacy of the data) and the applicant's reporting status for each submission due.
This is a prospective study cohort to continue the follow-up of premarket cohort to evaluate
the long term safety and effectiveness
Study Population Description
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. Study includes women who received the device while undergoing reconstruction or revision between 1998 and November 17, 2006 are being followed through their 5th post-surgery year and evaluated at 1, 3, and 5 years to assess satisfaction and occurrence of local complications.
Between study start in 1998 and device approval in November 2006, there were 43,384 reconstruction
patients and 38,653 revision patients enrolled
Primary objectives are to evaluated and estimate the rates of local complications (for example, capsular
contracture, pain, implant rupture, seromas, and hematomas), and reoperations, and other longer term outcomes (connective tissue diseases, rheumatological signs and symptoms, neurological diseases, neurological signs and symptoms, specific health problems in the children born to women receiving Allergan Natrelle silicone gel filled breast implants, miscarriages and stillbirths, problems with lactation, cancer, and suicide through scheduled follow up visits. Other objectives include estimating the rate of rupture with mammography, potential interference of breast implant with timing of breast cancer diagnosis, and compliance with the recommended schedule for MRI screening for implant rupture.
Followup Visits and Length of Followup
There are 3 scheduled follow up visits at 1, 3 and 5 years. Length of follow up is 5 years.
Final Study Results
Actual Number of Patients Enrolled
A total of 84, 329 patients were enrolled in the study; 45,055 in the reconstruction
cohort and 39,274 in the revision cohort
Actual Number of Sites Enrolled
Patient Followup Rate
Reconstruction cohort: 54.3% at Year 1, 29.8% at Year 3, 17.8% at Year 5 Revision cohort:
47.9% at Year 1, 26.1% at Year 3, 15.7% at Year 5
Final Safety Findings
The most commonly observed complications in the reconstruction and revision cohorts were capsular contracture, asymmetry,
implant palpability/visibility, implant malposition and wrinkling. The cumulative 5-year risk rate for these complications in reconstruction and revision were as follows, respectively; capsular contracture (15.0%, 21.5%), asymmetry (11.1%, 10.6%), implant palpability/visibility (7.1%, 11.5%), implant malposition (6.5%, 7.1%) and wrinkling (5.6%, 8.9%).
The rate of any reoperation at 5 years post-implantation was 34.4% in the reconstruction cohort and 30.1% in the revision cohort.
The most common reasons by cohort for reoperation were: capsular contracture (30.9%), cosmetic (30.9%), infection (5.1%) in the reconstruction cohort capsular contracture (44.3%), cosmetic (33.6%), and infection (4.8%) in the revision cohort.
The incidence of implant removal with replacement at 5 years post-implantation was 18.6% in the reconstruction cohort and in the revision cohort. The incidence of implant removal without replacement at 5 years post-implantation was 5.1% in the reconstruction cohort and 4.3% in the revision cohort.
The Kaplan-Meier cumulative rupture rates at 5 years were 1.3% in the reconstruction cohort and 1.5% in the revision cohort.
Final Effectiveness Findings
For the reconstruction cohort, on a 1 (definitely dissatisfied) to 5 (definitely satisfied) scale, the
average satisfaction level for patients and physicians was 4.3-4.4 at each follow-up timepoint. For the revision cohort, the average satisfaction level for patients and physicians was 4.4-4.5 at each follow-up timepoint.
Study Strengths and 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 follow-up rates of the reconstruction cohort at 1, 3 and 5 years were 54.3%, 29.8%, 17.8%, respectively. The follow-up rates were slightly lower in the revision cohort, i.e., 47.9% at Year 1, 26.1% at Year 3, 15.7% at Year 5. The poor patient compliance provides limited meaningful interpretation of the available safety results.
Recommendations for Labeling Changes
No. The Adjunct Study was designed to address the public health needs of reconstruction and
revision patients before device approval. The follow-up rates of the reconstruction cohort and revision cohort were low for the duration of the study. Therefore, there is lack of valuable safety data from the study due to poor patient compliance.