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.
CSR FAS: 94% (377/401), ITT: 93.8% (378/403) at 3 years LLR FAS: 95.2% 99 (104), ITT:
95.3% (101/106) at 3 years
Final Safety Findings
Core Size Registry (FAS population) endpoint rates observed through 3 years
All Death (Cardiac, vascular, non-cardiovascular) 3.1%
TV-MI - Q-wave and non Q-wave per protocol 2.6% (10/390) per ARC 6.2% (24/390)
Non-target vessel MI (Q-wave, Non Q-wave) per protocol 0.8% (3/390) per ARC 0.8% (3/390) Clinically indicated-TLR 5.4% (21/390) Clinically indicated Target Vessel Revascularization 9.5% (37/390) All TLR (Clinically indicated and non-Clinically indicated) 5.6% (22/390) All TVR (Clinically indicated and non-Clinically indicated) 10.0% (39/390) All Coronary Revascularization (TVR and non-TVR) 14.9% (58/390)
Target Lesion failure (cardiac death, target vessel MI and CI-TLR) per protocol 8.5% (33/390) per ARC 10.8% (42/390) DMR (All death, all MI and all revascularization) per protocol 19.0% (74/390 per ARC 20.5% (80/390)
MACE (Cardiac death, all MI and CI-TLR) per protocol 9.0% (35/390) per ARC 12.6% (49/390)
Cardiac death or All MI per protocol 3.8% (15/390) per ARC 8.7% (34/390)
Stent thrombosis, Overall per protocol 1.0% (4/390) per ARC 0.8% (3/380)
Long Lesion Registry (FAS) endpoint rates observed through 3 years
All Death (Cardiac, vascular, non-cardiovascular) 2.9% (3/104)
TV-MI - Q-wave and non Q-wave per protocol 4.8% (5/104) per ARC 10.6% (11/104)
Non-target vessel MI (Q-wave, Non Q-wave) per protocol 1.9% (2/104) per ARC 1.9% (2/104) Clinically indicated-TLR 4.8% (5/104) Clinically indicated Target Vessel Revascularization 7.7% (8/104) All TLR (Clinically indicated and non-Clinically indicated) 4.8% (5/104) All TVR (Clinically indicated and non-Clinically indicated) 7.7% (8/104) All Coronary Revascularization (TVR and non-TVR) 14.4% (15/104) Target Lesion failure (cardiac death, target vessel MI and CI-TLR) per protocol 9.6% (10/104) per ARC 14.4% (15/104)
DMR (All death, all MI and all revascularization) per protocol 20.2% (21/104) per ARC 25.0% (26/104)
MACE (Cardiac death, all MI and CI-TLR) per protocol 10.6% (11/104) per ARC 15.4% (16/104)
Cardiac death or All MI- per protocol 5.8% (6/104) per ARC 11.5% (12/104)
Stent thrombosis, Overall per protocol 0.0% (0/99) per ARC 0.0% (0/99)
Final Effectiveness Findings
No separate effectiveness findings were reported.
Study Strengths and Weaknesses
Strength: The study achieved a follow-up rate greater than 90% at 3 years.
Weakness: No formal
statistics were performed to compare the clinical outcomes in SPIRIT PRIME Core Size Registry versus pooled SPIRIT II, III and IV or SPIRIT PRIME Long lesion Registry versus SPIRIT IV overlapping cohort analyses.
Recommendations for Labeling Changes
Labeling change is recommended to reflect the long term data from the post-approval study. The
labeling change should include a new section on the label showing a summary of the post- approval study methods (including study objectives, design, population, number of enrolled sites/subjects, key endpoints, follow -up visits etc.), results and study strengths and limitations.
XIENCE PRIME and XIENCE PRIME LL Everolimus Elut