Method for Estimating CRT, ICD, and IPG Device Performance

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.

The performance of CRT, ICD, and IPG devices is expressed in terms of device survival estimates, where “survival” refers to the function of the device, not the survival of the patient. These survival estimates are intended to illustrate the probability that a device will survive for a given number of years with neither malfunction nor battery depletion.

The survival estimates are determined from the analysis of Medtronic CRDM’s United States device registration data and US returned product analysis data. These data are presented graphically and numerically.

Because this analysis is based on returned product analysis, the performance data does not reflect any device-related medical complications such as erosion, infection, muscle stimulation, or muscle inhibition.

Categorization of Depleted and Malfunctioning Devices for Survival Analysis
For survival estimation, every device returned to Medtronic CRDM and analyzed in the CRDM Returned Product Analysis laboratory is assigned to one of three categories. The device 1) has functioned normally, 2) has reached normal battery depletion, or 3) has malfunctioned. This categorization is combined with data from our device registry for the total number of implants and the implant durations to create the survival curves presented on the following pages.

Definition of Malfunction

Medtronic CRDM considers a device as having malfunctioned whenever the analysis shows that any parameter was outside the performance limits established by Medtronic while implanted and in service. To be considered a malfunction or battery depletion, the device must have been returned to Medtronic and analyzed.

Devices damaged after explant, damaged due to failure to heed warnings or contraindications in the labeling, or damaged due to interaction with other implanted devices (including leads) are not considered device malfunctions.

A device subject to a safety advisory is not considered to have malfunctioned unless it has been returned to Medtronic CRDM and found, through analysis, to actually have performed outside the performance limits established by Medtronic.

Not all malfunctions expose the patient to a loss of pacing or defibrillation therapy. Some malfunctions included in the following survival estimates may not have been detected at all by the physician or the patient. These malfunctions, however, are included in the survival estimates and provide important feedback to our product development organization.

To provide insight into the nature of malfunctions, each malfunction is categorized as Malfunction with Compromised Therapy Function or Malfunction without Compromised Therapy Function. A summary of these malfunctions is presented for the most recently market-released models.

For this report, Normal Battery Depletion, Malfunction with Compromised Therapy Function, and Malfunction without Compromised Therapy Function are defined as follows:

Normal Battery Depletion – The condition when:

a device is returned with no associated complaint and the device has reached its elective replacement indicator(s) with implant time that meets or exceeds the nominal (50 percentile) predicted longevity at default (labeled) settings, or
a device is returned and the device has reached its elective replacement indicator(s) with implant time exceeding 80% of the expected longevity calculated using the available device setting information.

Medtronic CRDM establishes expected longevity by statistically characterizing the power consumed by the device and the power available from the device battery. This characterization is applied to a number of parameter configurations to derive a statistical mean longevity value and standard deviation for each parameter configuration. The statistical mean value minus three standard deviations is used as the expected longevity for determining if a battery depleted normally.

The Standard Actuarial Method is used to estimate IPG and ICD survival. This product performance report has been prepared in accordance with International Standard ISO 5841-2:2000(E).

For reference purposes, the following pages include estimated longevities for each model. The actual longevity achieved for any device while implanted will depend on the actual programmed parameters and patient factors, and may differ significantly from these estimates.

Malfunction with Compromised Therapy Function
The condition when a device is found to have malfunctioned in a manner that compromised pacing or defibrillation therapy (including complete loss or partial degradation), while implanted and in service, as confirmed by returned product analysis.

Examples: Sudden loss of battery voltage; accelerated current drain such that low battery was not detected before loss of therapy; sudden malfunction during defibrillation therapy resulting in aborted delivery of therapy, intermittent malfunction where therapy is compromised while in the malfunction state.

Malfunction without Compromised Therapy Function
The condition when a device is found to have malfunctioned in a manner that did not compromise pacing or defibrillation therapy, while implanted and in service, as confirmed by returned product analysis.

Examples: Error affecting diagnostic functions, telemetry function, data storage; malfunction of a component that causes battery to lose power quickly enough to cause premature battery depletion, but slowly enough that the condition is detected through normal follow-up before therapy is lost; mechanical problems with connector header that do not affect therapy.

Expanded Malfunction Detail
The malfunctions are further divided into categories that identify the subject area of the malfunction. The malfunctions are divided into the following subject areas:

Electrical Component – Findings linked to electrical components such as integrated circuits, resistors, capacitors, diodes, etc.

Electrical Interconnect – Findings linked to the connections between electrical components such as wires, solder joints, wire bonds, etc.

Battery – Findings linked to the battery and its components

Software/Firmware – Findings linked to software or firmware function

Possible Early Battery Depletion – Findings where the actual reported implant time is less than 80% of the expected longevity calculated using the available device setting information with no device malfunction observed. There may not be sufficient device setting information to determine conclusively if battery depletion was normal or premature in the absence of a specific root cause finding. However, returned devices meeting the above criteria are conservatively classified as Possible Early Battery Depletion malfunctions.

Other – Findings related to other components such as insulators, grommets, setscrews, and packaging, and findings where analysis is inconclusive

Returned Product Analysis Process
Analysis of returned product is performed according to written procedures. These procedures determine the minimum analysis required. The analysis required varies depending on the type of device, age of the device, the associated information received with the device, actual experience with models of similar design, and other factors. Additional analysis is performed as necessary to investigate a performance concern from a customer, or to collect specific reliability data.

When a device is returned with a performance concern from a customer, the general analysis process includes a preliminary analysis of the device in its as-received condition, followed by an automated functional test using test equipment equivalent to the equipment used in manufacturing.

When a malfunction is identified, failure analysis is performed to provide the detailed information necessary to investigate possible causes and actions. Medtronic CRDM maintains in-house expertise and performs its failure analysis using facilities it owns and supports. This capability permits detailed failure analysis.

Medtronic CRDM adjusts all-cause survival estimates to account for underreporting. While this lowers our all-cause survival estimates, we feel it gives a more accurate perspective on real performance.

Statistical Methods for Survival Analysis
Of the several different statistical methods available for survival analysis, the Standard Actuarial Method, with suspensions assumed distributed across the intervals (Cutler-Ederer Method), is used to determine estimates of IPG and ICD survival. This method is commonly used by medical researchers and clinicians.

Implant times are calculated from the implant date to the earlier of the explant date or the cutoff date of the report. From this data an estimate of the probability of device survival is calculated at each monthly interval.

On the following pages, each graph includes a survival curve where events include malfunctions and normal battery depletions. This survival curve is a good representation of the probability a device will survive a period of time without malfunction and without battery depletion. For example, if a device survival probability is 95% after 5 years of service, then the device has a 5% chance of being removed due to battery depletion or malfunction in the first 5 years following implant.

In addition, a second curve is included to show survival excluding normal battery depletion. This curve is a good representation of the probability for a device to survive without malfunction. This curve includes only malfunctions as events and excludes normal battery depletion.

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 CRT, ICD, and IPG devices. The survival charts in the Product Performance Report show the effective sample size for each year interval where we have experience. When the effective sample size reaches 100, 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 one-month intervals.

The data in the tables are rounded to the nearest tenth of one percent. Occasionally, a graph may show 100% survival, but have one or more malfunctions or battery depletions. This occurs because, even with the malfunctions or battery depletions, the data rounds to 100%.

The survival curves are statistical estimates. As performance experience accumulates, the estimation improves. Confidence intervals are provided as a way to indicate the degree of certainty of the estimates. Greenwood’s formula is used to calculate corresponding 95% confidence intervals for the standard errors, and the complementary log-log method is used to produce the confidence bounds.

Sample Size and How the Population and Population Samples Are Defined
The population sample from which the survival estimates are derived is comprised of the devices registered as implanted in the United States as of the report cutoff date. The number of registered implants, as well as an estimate of the number that remain in active service, is listed for each model. To be included in the population, the device must have been registered with Medtronic’s registration system and implanted for at least one day.

This sample based on US implants is considered to be representative of the worldwide population, and therefore the survival estimates shown in this report should be representative of the performance worldwide of these models.

A CRT, ICD, or IPG model or model family will be included in this report when it has accumulated at least 10,000 implant months and will remain in the report as long as at least 500 devices remain active.

Methods Used to Adjust for Underreporting of Malfunction and Battery Depletion
The tables on the following pages show the actual number of malfunctions and battery depletions recorded by the analysis lab for US registered devices. Since not all devices are returned to Medtronic CRDM for analysis, these numbers underestimate the true number of malfunctions and battery depletions. To more accurately estimate the all-cause device survival probabilities, the number of malfunctions and battery depletions used to plot each interval of the all-cause survival curves is adjusted (multiplied) by a factor that is based on an estimate of the magnitude of underreporting. The magnitude of underreporting is estimated by analyzing experience in clinical studies (including the System Longevity Study) and the device registration system.

However, at this time, no adjustment for underreporting is applied to the malfunction-free survival curve because a method for estimating malfunction-only underreporting has not been developed.

Adjustments to Registered Implants to Compensate for Unreported Devices Removed from Service
Devices are at times removed from service for reasons other than device malfunction or battery depletion. Examples are devices removed from service due to nondevice related patient mortality and devices removed due to changes in the patient’s medical condition. Because an accurate estimate of device survival depends on an accurate estimate of the number of devices in service, it is important not to overstate the number of devices in service.

To ensure the number of devices in service is not overstated, the patient mortality rate derived from our device registration system is monitored and compared to published mortality rates for comparable patient populations. If, during calculation of the survival curves, the patient mortality indicated by the data in our device registration is significantly different from published rates, an adjustment is applied to correct the difference.