Medtronic CRM Product Performance Report

Introduction

All product performance reports are not created equal. For 26 years, Medtronic has monitored performance via both returned product analysis and multicenter clinical studies.

This Product Performance Report (PPR) presents device survival estimates, advisory summaries, performance notes, and other information pertinent to assessing the performance of Medtronic implantable pulse generators (IPGs), implantable cardioverter defibrillators (ICDs), cardiac resynchronization therapy (CRT) devices, and implantable pacing and defibrillation leads.

This Product Performance Report has been prepared in accordance with International Standard ISO 5841- 2:2000(E).

The survival estimates provided in this report are considered to be representative of worldwide performance.

Survival Estimates
Medtronic Cardiac Rhythm Disease Management (CRDM) uses both returned product analysis and multicenter clinical studies to monitor performance.

Medtronic, like other companies, monitors CRT, ICD, and IPG device performance using returned product analysis. We also monitor CRT, ICD, and IPG device performance using an active multicenter clinical study. Medtronic CRDM is unique in the industry in that we track CRT, ICD, and IPG device survival using both methods.

Returned product analysis is a passive approach to assessing product performance. This approach provides a suitable measure of product performance only when a significant number of explanted products are returned to the manufacturer. Returned product analysis provides a measure of hardware performance, but not necessarily the total clinical performance (e.g., the incidence of complications such as infection, erosion, muscle stimulation, etc. are not estimated).

The survival estimates provided in this report for CRT, ICD, and IPG devices are based on returned product analysis. This approach is suitable because a significant number of explanted generators are returned for analysis.

Lead performance is monitored differently. In contrast to CRT, ICD, and IPG devices, a very small percentage of leads are returned to the manufacturer due to the difficulty of explanting them. For leads, an active clinical study provides more accurate survival estimates compared to estimates based solely on returned product analysis.

Survival estimates for leads are based on clinical observations recorded via Medtronic CRDM’s System Longevity Study. This multicenter clinical study is designed to record clinical observations representative of the total clinical experience. Therefore, the lead survival estimates include both lead hardware failure and lead-related medical complications, and do not differentiate a lead hardware failure from other clinical events such as exit block, perforation, dislodgement, or concurrent pulse generator failure.

The actuarial life table method is applied to the data collected for CRT, ICD, and IPG devices and leads to provide the survival estimates included in this report. A general introduction to understanding this method of survival analysis is given later in this introduction.

ICD Charge Times
Since May 2000, Medtronic has provided important information on charge time performance of ICDs. The information provided in this report shows how ICD charge time can vary during the time a device is implanted. The information is presented in graphical format showing charge time as a function of implant time. The data for charge times are collected from devices enrolled in the System Longevity Study.

Advisory Summaries
This Product Performance Report includes summaries of all advisories applicable to the performance of the products included in the report. An advisory is added to the report when any product affected by the advisory remains in service and at risk of experiencing the behavior described in the advisory. The advisory will remain in the report until Medtronic estimates no product affected by the advisory remains active, or the risk of experiencing the behavior described in the advisory has passed.

For most advisories, the products subject to the advisory retain essentially the same survival probability as the products of the same model(s) not affected by the advisory. For those advisories where the survival probabilities of the affected and non-affected populations do differ significantly, Medtronic will provide separate survival data for each population. The separate survival data will remain in the report until Medtronic estimates no affected product remains in active service.

Performance Notes
This report concludes with a number of Performance Notes developed by Medtronic to provide additional product performance information relevant to follow-up practice and patient management.

Medtronic urges all physicians to return explanted products and to notify Medtronic when a product is no longer in use, regardless of reason for explant or removal from use.

How You Can Help
Medtronic urges all physicians to return explanted products and to notify Medtronic when a product is no longer in use, regardless of the reason for explant or removal from use. The procedures for returning products vary by geographic location.

Mailer kits with prepaid US postage are available for use within the United States to send CRTs, ICDs, IPGs, and leads to Medtronic’s CRDM Returned Product Analysis Lab. These mailers are sized to accommodate the devices and leads from a single patient or clinical event and are designed to meet postal regulations for mailing biohazard materials.

If the product being returned is located outside the United States, please contact your local Medtronic representative for instructions.

Medtronic also requests the return of explanted products from non-clinical sources, such as funeral homes, and will assume responsibility for storage and disposal of the product once received. For return of larger quantities of explanted products than the mailer can accommodate, Medtronic has handling and shipping guidelines available upon request.

Both mailers and guidelines can be requested by contacting the Returned Product Lab. For information on how to contact the Lab, refer to Contact Information.

We continually strive to improve this CRDM Product Performance Report. In keeping with this philosophy, we ask for your suggestions on the content and format of this report, as well as any information you have regarding the performance of Medtronic products. For information on how to comment on this report, see Contact Information.

Overview of Survival Analysis
Medtronic uses the Cutler-Ederer actuarial life table method to estimate the length of time over which devices and leads will perform within performance limits established by Medtronic. This probability to perform within performance limits over time is called the survival probability.

Devices and leads are followed until an event occurs where the device or lead ceases to operate within performance limits. The length of time from implant to the event is recorded for each individual device and lead in the population sample. The population sample for CRT, ICD, and IPG devices is made up of patients whose devices are registered as implanted in the United States. For leads, the population sample is the patients enrolled in our multicenter, international prospective System Longevity Study.

For IPGs and ICDs, the events can be normal battery depletion or a device malfunction. For leads, the events are complications as defined for the study.

The actuarial life table method allows Medtronic to account for devices and leads removed from service for reasons unrelated to performance. Devices and leads removed for these reasons are said to be suspended. Examples include devices and leads:

For each suspension, the device or lead has performed within performance limits for a period of time, after which its performance is unknown.

An Example
The following example describes the survival analysis method used to establish the survival probability estimates for Medtronic CRDM devices and leads. The example is intended to provide an overview of the analysis process. The definitions of malfunctions and complications, and other details specific to calculating device and lead survival estimates, are provided in the articles Method for Estimating CRT, ICD, and IPG Device Performance (page 9) and Method for Estimating Lead Performance (page 80).

This simple example describes the survival analysis method used to establish the survival probability estimates for Medtronic CRDM devices and leads.

Figure 1

Implant times for devices of 16 patients. Gray bars with an orange X indicate devices removed from service due to an event. Blue bars indicate suspended devices.

Figure 1 - Implant times for devices of 16 patients.

Figure 1 illustrates 16 patients who have implanted devices. The first patient’s device (serial number BH004134) operated within performance limits for 32 months. At that time an event occurred. The fourth patient’s device (serial number BH008926) did not have an event but is suspended, perhaps because it was still in service at the time of the analysis. This patient had 66 months of implant experience. In this example, Figure 1 shows that seven of the 16 devices suffered events, and nine are suspended.

The first step in the life table method is to divide the implant time into intervals of a specific length. This example will use 12-month intervals.

The number of devices entered, suspended, and removed due to an event are counted and summarized, as shown in Table 1. For the first two intervals, all 16 devices survived and none were removed. In the interval (24-36 months), device BH004134 was removed due to an event. Therefore the table entries show that 16 entered the interval, none were suspended, and one was removed due to an event.

For the interval from 36-48 months, only 15 devices entered the interval and one was removed for an event. The remaining intervals are examined and the data entered in columns A, B, and C in like manner. The rest of the columns are filled in using calculations on the data in columns A, B, and C.

The Effective Sample Size (D) is the number of devices with full opportunity to experience a qualifying event in the interval. This is computed by subtracting one half the number suspended in the interval from the number that entered the interval. This calculation more accurately reflects the number of devices that could have experienced a qualifying event than simply using the number that entered the interval. Using the number of devices that enter an interval overestimates the sample size because the suspended devices do not complete the interval. Ignoring the suspended devices underestimates the sample size because suspended devices are not credited with their full service time. Using one half the number of suspended devices effectively splits the difference.

The next column in the table is the Proportion with Event (E). This is the proportion of devices that had an event in the interval. It is calculated by dividing the Number of Events (C) by the Effective Sample Size (D). The number can be interpreted as the estimated rate at which events occur in the time interval.

The Interval Survival Probability (F) is the estimate of probability of surviving to the end of the interval assuming the device was working at the beginning of the interval. It is calculated as 1 minus the Proportion With Event (E). This number can be interpreted as the estimated rate at which events do not occur in the time interval.

The Cumulative Survival Probabilities (G) from the last column of the life table can be plotted versus time intervals in the first column to give a survival curve. Figure 2 shows the survival curve for the data shown in Table 1.

Life Table for Figure 1
Definitions:

Definitions chart for Life Table for Figure 1

Cumulative Survival Probability (G) is the estimate of the unconditional probability of surviving to the end of the interval. It is computed by multiplying the Interval Survival Probability (F) by the previous interval’s Cumulative Survival Probability. The probability of surviving to 132 months in the example is estimated for the table to be 0.341, or 34.1%.

The Cumulative Survival Probabilities (G) of the life table can be plotted versus time intervals in the first column to give a survival curve. Figure 2 shows the survival curve for the data in Table 1.

Figure 2 Survival Curve for Data Given in Table 1

Confidence Intervals
Since survival curves are based on a sample of the device and lead population, they are only estimates of survival. The larger the effective sample size, the more confident the estimate. A confidence interval can be calculated to assess the confidence in an estimate. In the Product Performance Report, Medtronic provides a 95% confidence interval. This can be interpreted as meaning that 95% of the time, the true survival of the device will fall somewhere in the interval.

Survival Curves in the Product Performance Report
Since the survival estimate can become very imprecise with small effective sample sizes, Medtronic truncates the survival curve when the effective sample size is less than 100 for CRTs, ICDs, and IPGs, and when the number entered is less than 50 for leads. The survival charts in the Product Performance Report show the effective sample size for each year interval where Medtronic has experience. When the effective sample size reaches 100 for CRTs, ICDs, and IPGs or when the number entered reaches 50 for leads, the next data point is added to the survival curve.

Although the report provides tabular data in one-year intervals, the curves are actually computed and plotted using 1-month intervals (for CRT, ICD, and IPG devices) or 3-month intervals (for leads).

A number of references are available for additional information on survival analysis using the Cutler- Ederer life table method.1

1 Lee, Elisa T.(2003) Statistical Methods for Survival Data Analysis – 3rd Edition (Wiley Series in Probability and Statistics).