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.
This analysis plan is created to leverage data that is already available as part of
the Medtronic CareLink remote management system. An RV LIA trigger requires 2 of 3 components to be satisfied within 60 days: abrupt pace sense impedance change, frequent extremely short R-R intervals, and rapid non-sustained VT episodes. The save-to-disk file associated with each of these alert (RV LIA or impedance nominal threshold) triggers, and any associated data from DRS and/or GCHS, will be reviewed by the lead failure adjudication committee to determine the cause of the RV LIA alert or impedance nominal threshold crossing.
Study Population Description
This is a retrospective analysis of existing data from CareLink. Among the large number of
patients and clinics that use CareLink to manage their devices, there are some that have already been implanted with a combination of an RV LIA enabled device and an RV defibrillation lead not manufactured by Medtronic. There are three Medtronic sources of information that will be used to support this analysis:
¿X Data Warehousing and Analytics Services (DWAS)
¿X Device Registration System (DRS)
¿X Global Complaint Handling System (GCHS)
The DWAS, DRS and GCHS databases will be queried as follows to obtain all necessary data. All Medtronic devices that were connected to non-Medtronic RV defibrillation leads and had the RV LIA algorithm active prior to the data cutoff will be queried. The cutoff date will be set to a date on or after October 4, 2013
As there are no hypotheses being tested for this analysis, there are no powered sample
size estimates. However, two requirements were identified to determine the sample size and timing of the analysis. First was to ensure the amount of lead follow-up is at least the size of the PMA analysis (11,052 RV LIA years of follow up across both St. Jude and Boston Scientific leads) and secondly the analysis will occur after PMA approval. Current estimates are that the RV LIA years of follow-up since the PMA cut off of October 4, 2011 has already been exceeded with approximately 14,500 years of RV LIA enabled follow-up. Therefore, assuming event rates remain the same as in the PMA cohort, it is expected at 77 additional lead events will be included in this study which is 28% more than the 60 true lead events observed across both manufacturers in the PMA analysis. The data cut off for analysis will be the first day after PMA approval in which the RV LIA enabled years of follow-up is greater than 11,050 years of follow-up.
There are three Medtronic sources of information that will be used to support this analysis:
Warehousing and Analytics Services (DWAS)
? Device Registration System (DRS)
? Global Complaint Handling System (GCHS)
The DWAS, DRS and GCHS databases will be queried as follows to obtain all necessary data. All Medtronic devices that were connected to non-Medtronic RV defibrillation leads and had the RV LIA algorithm active prior to the data cutoff will be queried. The cutoff date will be set to a date on or after October 4, 2013.
To summarize the number of lead failure events associated with RV LIA triggers and impedance nominal threshold crossings. This objective will be evaluated separately for each lead manufacturer (i.e. St. Jude Medical Riata/Durata leads and Boston Scientific Endotak leads).
To summarize the number of other detected events associated with RV LIA triggers and impedance nominal threshold crossings. This objective will be evaluated separately for each lead manufacturer (i.e. St. Jude Medical Riata/Durata leads and Boston Scientific Endotak leads).
Followup Visits and Length of Followup
No follow-up visits and length of follow-up
Final Study Results
Actual Number of Patients Enrolled
Actual Number of Sites Enrolled
Patient Followup Rate
Final Safety Findings
Final Effectiveness Findings
The incidence of right ventricular (RV) Lead Integrity Alert (LIA) trigger or impedance nominal threshold
during the post-approval period was low in St. Jude Medical (STJ) Riata/Durata leads and Boston Scientific (BSX) Endotak leads (0.725% per device year in STJ leads and 1.23% per device year in BSX leads). The majority of identified triggers classified as lead failure events (LFEs) or other detected events (ODE) were detected by only the RVLIA criterion in both STJ and BSX leads. These findings were consistent with events identified during the original analysis supporting the PMA labeling language for RV LIA use with Non- Medtronic leads.
Study Strengths and Weaknesses
Strength: Large sample size;
Weakness: Retrospective data analysis. Lack of data presented to support advance warning
of RV LIA
relative to lead failure events. No data available on the positive predictive value or negative predictive value.
Recommendations for Labeling Changes
LIA in Non-MDT Leads Surveillance Update Analysis