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 without malfunction or battery depletion.
The survival estimates are determined from the analysis of Medtronic Cardiac Rhythm and Heart Failure (CRHF’s) United States device registration data and US returned product analysis data.
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 CRHF and analyzed in the CRHF Returned Product Analysis laboratory is assigned to one of three categories. The device 1) is functioning 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 survival curves.
Definition of Malfunction
Medtronic CRHF 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 CRHF and found, through analysis, to have performed outside the performance limits established by Medtronic.
Not all malfunctions expose the patient to a loss of therapy. Some malfunctions included in the following survival estimates may not have been detected at all by the physician or the patient. All 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.
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) 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
(b) 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, or
(c) a device is taken out of service without an associated complaint and with evidence the battery reached its elective replacement indicator(s)
Medtronic CRHF 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. The statistical mean value minus three standard deviations is used as the expected longevity for determining if a battery depleted normally. 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.
Acute and Qualifying Observations (for Transcatheter Pacing Systems)
Transcatheter pacing systems (TPS) combine the pacing functions of an IPG with the therapy delivery functions of an implantable lead into a single device implanted inside the heart. TPS is therefore subject to some events previous reserved for leads, such as dislodgement, cardiac perforation, failure to capture and sensing complications.
In the first weeks following implantation, physiologic responses and device performance can vary until long-term stability is attained. Acute (defined as the first month after implant) performance may be subject to a number of factors, including patient-specific anatomy, clinical conditions and/or varying implant conditions/techniques. After a period of time, the implant and the device performance stabilizes.
Information about this clinical experience is summarized in the Acute and Qualifying Observation tables. The source for this information is Medtronic‘s complaint handling system database.
Each Event Report received by Medtronic’s complaint handling system is assigned one or more Reason for Report codes based on the information received. The Reason for Report codes have been grouped into categories. The categories used for this product performance reporting are drawn from the "FDA Guidance for Submission of Research and Marketing Applications for Permanent Pacemaker Leads and for Pacemaker Lead Adapter 510(k) Submissions." The categories are:
1. Cardiac Perforation
3. Failure to Capture
6. Failure to Sense
7. Impedance Abnormal
Events occuring within the first month after implant are summarized in the Acute Observations table. Events occuring after one months are summarized in the Qualifying Observations table. Although multiple acute observations are possible for any given TPS device, only one observation is reported per device. The observation reported is the observation highest on the list. For example, if an Event Report includes observations for both Dislodgement and Failure to Sense, Dislodgement is reported. Similarily for Qualifying Observations, only one is reported.
The event reported to Medtronic may or may not have involved clinical action or product returned to Medtronic. The device may have remained implanted and in service.
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 CRHF maintains in-house expertise and performs its failure analysis using facilities it owns and supports. This capability permits detailed failure analysis.
Statistical Methods for Survival Analysis
Of the several different statistical methods available for survival analysis, the Standard Actuarial Method, with suspensions assumed distributed evenly within the intervals (Cutler-Ederer Method), is used to determine survival estimates for CRT, IPG and ICD devices. 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.
Each graph includes a survival curve where events include malfunctions and normal battery depletions (labelled as "Including Normal Battery Depletion"). 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 (labeled as "Excluding Normal Battery Depletioon"). 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.
For Transveneous Pacing Systems (TPS), a third survival curve is included (labelled as "Including Qualifying Observations"). For this curve, events include malfunctions, normal battery depletions and qualifying observations.
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%.
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 accompanying the survival curves 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 CRHF for analysis, these numbers underestimate the true number of malfunctions and battery depletions. To more accurately estimate the device survival probabilities, the number of malfunctions and battery depletions used to plot each interval of the "Including Normal Battery Depletion" and (for TPS) the "Including Qualifying Observations" 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 comparing data in Medtronic’s Device And Registrant Tracking (DART) system with data from Returned Product Analysis.
The DART system is an important element of Medtronic’s Quality System. The DART system is designed to meet or exceed the US FDA’s device tracking requirements set forth by the Safe Medical Devices Act. In the United States, over 98% of Medtronic’s CRT, ICD, and IPG implants become registered in the DART system.
Because pacemakers do not cure the patient’s underlying health problem, when a pacemaker stops functioning (due to either normal battery replacement or malfunction) it is replaced with a new pacemaker. Therefore, the replacement recorded in the DART system is a good indication that the previous pacemaker experienced either battery depletion or malfunction. The fraction of replaced devices that are subsequently returned can be used to estimate the correction factor for the under reporting of the combination of battery depletion and malfunction.
Note that devices of patients who have expired do not factor into the calculation of the correction. It is possible some proportion of these devices experienced battery depletion or malfunction. Since these are not counted into the correction factor based on the return rate of replaced devices, a correction factor based only on the return rate of replaced devices may still underestimate the true rate of battery depletion and malfunction. However, devices that are replaced because the patient is receiving a system upgrade or are removed because the patient no longer needs it (e.g., due to heart transplant) do contribute to the calculation of the correction factor and therefore impart an opposite bias.
Also note that this method of calculating the correction factor cannot distinguish between devices that are removed due to malfunction and those due to normal battery depletion. It might seem intuitive that devices that unexpectedly malfunction should be much more likely to be returned to the manufacturer than a device with ordinary normal battery depletion. But this has not been conclusively demonstrated. Therefore, this method only provides a correction factor reflecting the combination of battery depletion and malfunction, and , for TPS, qualifying observations.
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 non-device 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.
Medtronic addresses this under reporting to ensure the number of devices in service is not overstated . Regular updates obtained from third party sources such as the Social Security Administration are used to update Medtronic’s DART data about patients who have died but whose deaths had not been reported to Medtronic. In addition, the patient mortality rate derived from our DART 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 DART is significantly different from published rates, an adjustment is applied to correct the difference. The correction factor is also applied to account for devices that were removed and not reported or returned.