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

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Long-Term Study


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General
Study Status Completed
Application Number P060023 / PAS001
Date Current Protocol Accepted 05/12/2009
Study Name Long-Term Study
General Study Protocol Parameters
Study Design Randomized Clinical Trial
Data Source New Data Collection
Comparison Group Concurrent Control
Analysis Type Analytical
Study Population Transit. Adolescent B (as adults) : 18-21 yrs, Adult: >21
Detailed Study Protocol Parameters
Study Design Description This is a prospective cohort study that involves continued follow-up of the premarket cohort. The goal of this post-approval study is to assess longer-term performance of the BRYAN Cervical Disc in the treatment of patients with cervical degenerative disc disease. The primary consideration of longer-term performance will be overall success, a composite variable comprised of key safety and effectiveness parameters. The overall success rate for the BRYAN disc treatment will be compared to that of a concurrent fusion control group. Study success will be based on showing non-inferiority for the BRYAN device group overall success rate at ten years following surgery. The secondary objective of the study is to assess superiority, if non-inferiority can be established.
Study Population Description Study population is as per device indication. 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. The BRYAN device is implanted via an open anterior approach.
Sample Size Postoperative data will be collected at 5, 7, and 10 years on a minimum of 200 eligible patients (minimum of 100 patients each from control and BRYAN groups)
Data Collection The primary outcome variable, overall success, is defined below. A patient will be considered an overall success if all of the following conditions are met:
Follow-up Visits and Length of Follow-up Data will be collected at 60 months (5 years), 84 months (7 years), and 120 months (10 years) postoperative to determine the long-term safety and effectiveness of the device.
Interim or Final Data Summary
Interim Safety Information As of the latest 12-month PAS interim report, 356 IDE subjects have been enrolled into PAS. Of them, 83% (160/193) Bryan Disc patients and 75% (119/159) control achieved success at 60-month follow-up.
Actual Number of Patients Enrolled 463 randomized subjects were enrolled in the IDE. The number of subjects participating in the PAS (60 months) was 206 investigational subjects and 167 control subjects.
Actual Number of Sites Enrolled 17
Patient Follow-up Rate 63.1% (130/206) Investigational group; 62.3% (104/167) Control group.
Final Safety Findings The cumulative rate of subjects who reported any Grade 3 or 4 adverse event up to 120 months was 68.6% in the investigational group and 73.0% in the control group. At 120 months, the rate of implant- or implant/surgical procedure-associated adverse events was 19.1% in the investigational group and 7.3% in the control group. The rate of implant- or implant/ surgical procedure-associated Grade 3 or 4 adverse events was 4.1% in the investigational group and 4.9% in the control group. In all categories of spinal events (overall, procedure-related, device-related), events were numerically greater in the investigational group than the control group, deemed clinically significant

(though not statistically significant). Data on neurologic outcomes is incomplete in that relatedness to the device and procedure could not be determined and should be interpreted accordingly. The rate of secondary surgeries at the index level was 6.7% in the investigational group and 11.5% in the control group (not statistically significant).

Final Effect Findings Based on the data available, the study met its primary objective d with non-inferiority of the investigational treatment over the control treatment in overall success rate for the primary composite endpoint at 120 months (81.3% investigational vs 66.3% control.) The study also met its secondary objective of superiority of the Bryan device over the control for the primary endpoint.

Non-inferiority of the investigational treatment compared to the control was also reported in secondary effectiveness endpoints, including NDI success, neck pain success, arm pain success, SF-36 PCS and MCS success, and gait success status at 120 months following surgery. NDI success rate in the investigational group was superior to that in the control group.

At 120 months following surgery, the radiographic success rate in the investigational group was 80.0%, while the fusion success rate in the control group was 97.2%. In the investigational group, 80.0% of subjects had angular motion maintained (more than 4°). The Functional Spinal Unit (FSU) success and subsidence success rates at all postoperative follow-up time points were 100.0% for both investigational and control groups, indicating there were no subjects having a surgical intervention due to FSU height loss or subsidence in either group. At 120 months, 7.4% (9/122) investigational subjects had Grade III HO, and 6.6% (8/122) had Grade IV HO. The incidence of HO increased and worsened over time with resultant loss of motion. Bryan implant migration was observed in two investigational subjects (one at 60 months and another at 120 months).

Study Strengths & Weaknesses This long term (10-year) extended follow-up study was able to meet the study objectives, demonstrating both non-inferiority and superiority in the primary success outcome (a composite endpoint of safety and effectiveness) for the Bryan device compared to anterior cervical discectomy and fusion (ACDF). However, the study is limited to IDE study subjects, though patients, physicians, and clinical sites who utilize the device in the postmarket environment may differ significantly from the relatively select patients, physicians, and clinical sites that participated in the premarket trial; therefore, the study may not be representative of real-world use.

Though there were no significant differences in AE rates between the groups, categorization of Adverse events is suboptimal in that all systemic AEs were considered non-device or non-procedure related, which may or may not be the case, and should be interpreted accordingly. Data on neurologic outcomes is incomplete in that relatedness to the device and procedure could not be determined and should be interpreted accordingly. Further, because fusion outcomes on subjects undergoing removal SSSI were not captured, the study does not permit a conclusion regarding possible deleterious effect of fusion after device removal (i.e., the possibility of incomplete or delayed fusion is not known).

Overall, though missing data imputed in worst case sensitivity analyses withheld the claim of non-inferiority, there is a selection bias concern due to the high percentage of patients lost to follow-up and the ongoing (through 10 year) consent process. Accordingly, the final risk to benefit conclusions should be interpreted with caution.

Recommendations for Labeling Changes The labeling should be updated to include the long-term follow-up data generated in this Post-Approval study.


Long-Term Study Schedule

Report Schedule
Report
Date Due
FDA Receipt
Date
Applicant's Reporting Status
6 month report 11/10/2009 11/10/2009 On Time
1 year report 05/12/2010 06/28/2010 Overdue/Received
18 month report 11/10/2010 11/10/2010 On Time
2 year report 06/10/2011 06/10/2011 On Time
3 year report 05/11/2012 05/09/2012 On Time
4 year report 05/11/2013 05/08/2013 On Time
5 year report 06/10/2014 06/10/2014 On Time
6 year report 05/11/2015 05/05/2015 On Time
Final Report 09/30/2016 09/16/2016 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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