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U.S. Department of Health and Human Services

522 Postmarket Surveillance Studies

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Study Status Completed
522 Number / Requirement Number PS130046 / PSS001
Date Current Plan Accepted 02/10/2017
Root Document Number P000039 
General Study Protocol Parameters
Study Design Case Control Study
Data Source Other Data Source
Comparison Group Historical Control
Analysis Type Analytical
Study Population Infant: 29 days-2 yrs, Child: 2-12 yrs, Adolescent: 13-18 yrs, Transit. Adolescent B (as adults) : 18-21 yrs, Adult: >21
Detailed Study Protocol Parameters
Study Design Description The manufacturer used data from a published study to fulfill the postmarket surveillance (522) order (McElhinney et al. Circulation.2016;133:1738-1746). The study was a matched case-control study conducted to evaluate relative risk factors for cardiac erosion after ASD closure with an Amplatzer Septal Occluder (cases).

Study Population Description Cases: all erosions events reported to St. Jude Medical after ASD closure with an Amplatzer Septal Occluder reported through 2014. These erosion events were identified through product surveillance complaints, the prospective post-approval study (PAS), and monitoring of the MAUDE database and the published literature.

Controls: Subjects were selected from the post-approval study (P000039/PAS1).
Sample Size 125 cases and 250 controls matched by age and gender

Data Collection Primary endpoint: Cardiac erosion

An Erosion Board determined whether the event is likely to be attributable to erosion and adjudicates on certain technical, anatomic, and other aspects of the case.

Follow-up Visits and Length of Follow-up Retrospective data collection of erosion cases.

Prospective data collection of PAS controls.

Interim or Final Data Summary
Actual Number of Patients Enrolled 125 cases and 250 controls matched by age and gender. Of these cases, 59 were from the US (47%). Controls were selected from the Amplatzer US Post-Approval Study (P000039, https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma_pas.cfm?t_ id=89977&c_id=168).
Actual Number of Sites Enrolled Cases were identified through product surveillance complaints, the prospective PAS, and monitoring of the MAUDE database and the published literature.

Controls: The Amplatzer US Post-Approval Study (P000039) enrolled 50 US sites.

Patient Followup Rate Not applicable for a case-control study
Final Safety Findings A total of 125 erosions were reported between 2002 and 2014. The median duration from implant to erosion was 14 days, but was >1 year in 16 patients. Nine patients (all age =17 years) who died were more likely to have an oversized device, and to have erosion into the aorta, than survivors. Aortic or superior vena cava rim deficiencies were more common in cases than in controls. In addition, larger balloon- sized atrial septal defect (ASD) diameter, Amplatzer septal occluder device size, and device size–ASD diameter difference, and smaller weight:device size ratio were associated with erosion.

The risk factors associated with erosion identified in multivariable analysis were:

• deficiency of the aortic or superior vena cava rims,

• balloon size diameter >5 mm larger than static ASD diameter, and

• low patient weight to device size ratio.

Final Effectiveness Findings Not applicable
Study Strengths and Weaknesses One strength of the study is that it used all the clinical and imaging data from all the erosion cases the sponsor had available between 2002 and 2014. This is a strength given that cardiac erosion is a rare event. Another strength is the selection of controls subjects from a prospective post-approval study (P000039). The study data confirmed the association between aortic rim deficiency and cardiac erosion. It also identified additional risk factors for cardiac erosion: deficiency of the superior vena cava rim, a balloon size diameter device >5 mm larger than static ASD diameter, and low patient weight to: device size ratio. Limitations of the study include missing data on clinical variables for cases (such as location of the erosion, ASD details) and echocardiographic variables for both cases and controls (such as short-axis aortic rim thin information) which potentially affected the statistical power of the study to detect additional risk factors. In addition, half of the cases were implanted in an earlier time-period than the controls. This introduced bias but the authors did not identified differences in the characteristics of the erosion patients during the 2 time periods.
Recommendations for Labeling Changes The manufacturer was asked to submit a labeling update to include the results from the McElhinney et al. case-control study (Circulation.2016;133:1738-1746).


Report Schedule
Date Due
FDA Receipt
Applicant's Reporting Status
6 month report 12/19/2014 12/19/2014 On Time
1 yr report 06/20/2015 06/18/2015 On Time
18 month report 12/19/2015 12/16/2015 On Time
2 yr report 06/19/2016 07/07/2016 On Time
final report 11/10/2017 11/14/2017 On Time

  • The 522 Postmarket Surveillance Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated under section 522 of the Federal Food, Drug and Cosmetic Act. The program helps ensure that well-designed 522 postmarket surveillance (PS) studies are conducted effectively and efficiently and in the least burdensome manner.
  • In May 2008, the oversight responsibility of the 522 Postmarket Surveillance 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). DEPI continues to build the 522 program.
  • CDRH has established an automated internal tracking system that efficiently identifies the reporting status of active 522 PS studies 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 522 PS 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 522 PS study. The webpage displays general information regarding each study, as well as the overall study status (based on protocol-driven timelines and adequacy of the data) and the applicant's reporting status for each submission due.


Contact Information

Cheryl Reynolds
Project Manager, 522 Postmarket Surveillance (PS) Studies Program
Food and Drug Administration
10903 New Hampshire Ave
Silver Spring, MD 20993-0002

Phone: (301) 796-6068
Fax: (301) 847-8140