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.
Transit. Adolescent B (as adults) : 18-21 yrs,
Detailed Study Protocol Parameters
Study Design Description
This is a prospective cohort to continue follow-up of the subjects who participated in (1)
the IDE premarket study and (2) the continued access arm and metal ion study.
Study Population Description
The study include IDE, CAS and metal ion study subjects. This device is indicated in
skeletally mature patients for reconstruction of the disc from C3-C7 following single-level discectomy for intractable radiculopathy and/or myelopathy. Intractable radiculopathy and/or myelopathy should present with at least one of the following items producing symptomatic nerve root and/or spinal cord compression which is documented by patient history (e.g., pain [neck and/or arm pain], functional deficit, and/or neurological deficit), and radiographic studies (e.g., CT, MRI, x-rays, etc.): 1) herniated disc, and/or 2) osteophyte formation. The PRESTIGE 9 device is implanted via an open anterior approach.
A minimum of 200 patients (minimum of 100 patients each from control and PRESTIGE groups)
at 7-year follow-up
A patient will be considered an overall success if all of the following conditions are
1. Postoperative Neck Disability Index score improvement of at least a 15-point increase from preoperative;
2. Maintenance or improvement in neurological status from preoperative;
3. Functional spinal unit height success;
4. No serious adverse event classified as implant associated or implant/surgical procedure associated; and
5. No additional surgical procedure classified as a "failure".
Followup Visits and Length of Followup
Postoperative data will be collected at 3, 5, and 7 years
Final Study Results
Actual Number of Patients Enrolled
Actual Number of Sites Enrolled
Patient Followup Rate
The sponsor was expected to follow a minimum of 200 patients (minimum of 100 patients
each from control and PRESTIGE groups) through 7-year follow-up, at 31 study sites. The sponsor has followed-up
228 (84.8%) investigational and 199 (80.9%) control patients through year 7. However, the follow-up is lower, when availability of data on Functional Spinal Unit (FSU) if taken into account, n=168 (62.5%) and n=135 (54.9%) for the investigational and control patients, respectively.
Final Safety Findings
In terms of cumulative adverse events n=259 (97.7%) of investigational patients had an adverse event
the study as compared to n= 232 (94.5%) of control patients (pWilcoxon=0.722). For neck the time-to-event analysis, the cumulative rate is 70.2% and 64.7% for the investigational and control groups, respectively, with pWilcoxon = 0.070.
Further, no adverse local tissue reactions (ALTR) were observed in 6 explanted investigational devices. However, four (n=4) explanted devices showed greater than anticipated wear rate (derived from bench studies).
In the metal ion group of the investigational device patients (n=34), the Chromium levels were higher than pre-operative levels, but about 41 fold less than undesired level (7 ng/ml)
Final Effectiveness Findings
The primary end-point for the study was overall success-a composite of safety and effectiveness. Hundred
twenty two (n=122) out of 168 or 72.6% of investigational patients have reached overall success. In comparison, 81 (60%) out of 135 control patients have reached overall success, p (non- inferiority)<0.001. Please refer to the table below for additional information.
Study Strengths and Weaknesses
This study provided much needed information on the Prestige long term (7-years) performance. However, the
findings and interpretation of this study are limited due to the observed high loss to the follow-up. A total of 108 study subjects in the investigational group and 130 in the control group have missing data on the overall success with FSU at 84 months. Additionally, 64 study subjects in the investigational group and 83 in the control group have missing data for overall success without FSU at
84-month. Furthermore, 48 study subjects in the investigational group and 66 in the control group have no 84-month data. The high proportion of loss to follow-up can introduce bias in the rate estimates, possibly due to differences in loss to follow-up between patients with different overall success at 24- months. For example, study subjects who completed the PAS in Prestige group were more likely to have achieved overall success at 24-month; whereas, study subjects in the control group who did not achieve overall success at 24-month were more likely to complete the PAS. This suggests differential loss to the follow-up between treatment groups, which limits the interpretation of the study results. Trends for several of the other study outcomes were similar.
Recommendations for Labeling Changes
Yes: Long term data on the device safety and effectiveness is available and the labeling
should include additional information on the long term device performance; (2) Higher than predicted wear during bench testing was observed in the explanted devices after long-term use.