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, multi-center, single-arm study to assess the freedom from ARM at five years.
Study Population Description
The study involves follow-up of the VALOR II cohort. Criteria for being in this study
include: age between 18 and 85; a candidate for elective repair of an aneurysm of the descending thoracic aorta; either a fusiform aneurysm with a maximum diameter of at least 5 cm or at least two times the diameter of the non-aneurysmal thoracic aorta, and/or a saccular aneurysm; aneurysm meets the specified anatomic criteria
Based on the need for a statistical power of 80%, using a one-sided 95% confidence
level, an estimated ARM free rate of 94%, and a performance goal of 83.6%, the sponsor calculates a required sample size of 117 at five years. Assuming a 15% annual attrition rate, that calculates out to an initial sample size of 160, which is the number of patients that will be followed from the IDE study. Those patients were enrolled from 24 sites.
Primary Endpoint The primary endpoint of the study is aneurysm-related mortality at five years, defined as:
from rupture of the fusiform aneurysm or saccular aneurysm/penetrating ulcer or from any procedure intended to treat the fusiform aneurysm or saccular aneurysm/penetrating ulcer. If a death occurred within 30 days of any procedure intended to treat the fusiform aneurysm or saccular aneurysm/penetrating ulcer, then it is presumed to be aneurysm related. . Secondary Endpoints All-cause mortality Aneurysm rupture Conversions to open surgical repair Endoleaks Secondary endovascular procedures Stent graft migration Loss of stent graft patency, defined as loss of continued blood flow through the treated vessel Major adverse events
Followup Visits and Length of Followup
Final Study Results
Actual Number of Patients Enrolled
Actual Number of Sites Enrolled
Patient Followup Rate
Final Safety Findings
The majority of aneurysms at all time periods either decrease in size or show no
change in size from baseline. From one month to 4 years, 6% or less of aneurysms increased in size. At 5 years the percent of aneurysms increased in size is 11%, much smaller than the percent that decreased in size (48%). These results are consistent with results regarding the consequences of increases in aneurysm size: Low abdominal aortic aneurysm (AAA)-related mortality, no surgical conversions to open surgery since the post- approval study (PAS) began, only one aneurysm rupture since the PAS began, and a rate of secondary interventions for any reason of about only 3% per year. They are also consistent with results regarding the causes of increases in aneurysm size: No stent graft migration or loss of stent graft patency, and only approximately a 5% rate of endoleaks per year following the start of the PAS (compared to 13% in the 12 months of the clinical trial).
Final Effectiveness Findings
Five year aneurysm related mortality rate, by KM analysis is 94.8% (with a lower 95%
confidence interval of 91.2%)
Study Strengths and Weaknesses
Strength: Prospective study Device met its performance goal by a large margin (lower bound of 95% confidence
interval) Weakness: No concurrent control group No control for potential confounding variables
Recommendations for Labeling Changes
A change in labeling is recommended to update the results of the PAS.