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.
Julie Unger
Project Manager, Post-Approval Studies Program
Food and Drug Administration
10903 New Hampshire Ave
WO66-4206v
Silver Spring, MD
20993-0002
This study is a 24-week, multi-center, single arm prospective cohort study. All subjects in the
study receive the device.
Study Population Description
The device is indicated for injection into the mid to deep dermis for the correction
of moderate to severe facial wrinkles and folds, such as nasolabial folds. The study population includes Fitzpatrick skin types V, V, and VI.
Sample Size
100 subjects, 9 sites
Data Collection
Endpoints include observed and reported adverse events at each visit and in a subject diary.
Specific safety endpoints include keloid formation and pigmentation change at the site of injection.
Followup Visits and Length of Followup
Treatment visits will be conducted every 14 days until optimal cosmetic correction is obtained. Follow-up
visits will take place at 2, 6, 12, and 24 weeks after the last injection.
Final Study Results
Actual Number of Patients Enrolled
122
Actual Number of Sites Enrolled
9
Patient Followup Rate
96%
Final Safety Findings
Of the 122 patients enrolled, a total of 100 were included in the analysis.
(1) No
keloids were observed at the injection site during the 24-week follow-up.
(2) Ten (10%) subjects experienced 13 occurrences of mild hyperpigmentation, none requiring treatment or medical intervention. The incidence of injection site discoloration is 23 per 100 person years, which is greater than that observed in the pivotal clinical study.
(3) A total of 47 (47%) experienced a total of 95 adverse events. All local adverse events were attributed to the device. From patient diaries, 80% of patients reported some type of injection site reaction, all reactions were mild and the most common reactions were swelling bruising and redness. The most serious adverse events were abcesses or cysts at the site of injection requiring further surgical or medical intervention. Rare adverse events were also reported: disfigurement (6 reports), facial nerve palsy (1 report), impaired vision (1 report), swollen lymph nodes (1 report).
Specific device related events that were higher in the post-approval study than the pivotal study include injection site discoloration (10% vs. 1.4%), induration (5% vs. 0.5%), nodule (4% vs. 1%) and pain (4% vs. 1%).
Final Effectiveness Findings
Not applicable
Study Strengths and Weaknesses
Strengths:
¿The high follow-up rate of 96% for 100 subjects minimizes the potential bias that
might arise due to losses to follow-up. None of the patients who were lost to follow-up discontinued participation due to adverse events. The most often reason for discontinuation cited was person/family reasons.
¿Because the methods of injection, dose and intended use for Hydrelle in this study are similar to the approved use, it was possible to compare the incidence of patient and physician-reported adverse outcomes in the current study with those observed in the pre-market pivotal study.
¿Data collected on volume of injection and number of touch-ups allowed evaluation of trends in association between these variables and the study endpoints.
Weaknesses:
¿Given the small sample size within each site, no conclusions can be drawn about the impact of device dose on the adverse events. The small sample size at each study site also limited the ability to interpret the results of analyses of the association between all adverse events and Fitzpatrick skin type.
¿ There were a significant number of protocol deviations mostly involving observations outside of the study window (61of 107 protocol violations).
Recommendations for Labeling Changes
Yes, to update the AEs for Fitzpatrick skin types IV-VI
