Device Survival Analyses NEUROMODULATION PRODUCT PERFORMANCE

Device performance is expressed in terms of device survival estimates, where ”survival” refers to freedom from a product performance event, not the survival of the patient. These survival probabilities are estimated using the Kaplan-Meier method1. The estimates are intended to illustrate the probability that a device will survive for a given number of years without a product performance related event.

Active surveillance normally begins at the time of implant and continues until a product performance or censoring event occurs. In some cases in the registry, active surveillance of a device starts after the device was implanted, which is called left truncation1. The survival probability of such a device is conditional on survival to the time when the device enters the registry. For the PPR analysis, a statistical method to incorporate data from these retrospectively enrolled devices was applied. Left truncation provides a statistical technique that uses data from existing devices while appropriately adjusting the device survival curves for the time the device was not actively followed in the registry. Thus, in some cases sample sizes may fluctuate from one time interval to the next interval.

Throughout this report, cumulative device survival plots are presented. These figures show the percentage of implanted devices that remain free from product performance-related events at various time points. This survival estimate is a good representation of the probability a device will survive a period of time without a product performance event. For example, a device survival probability of 90% indicates that through the stated follow-up time, the device had a 10% risk of incurring a product performance event since the time of implant.

The survival curves are statistical estimates. As performance experience accumulates, the accuracy of 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 the standard errors, and the log-log method is used to produce the 2-sided 95% confidence bounds2. This can be roughly interpreted as meaning that the true survival of the device will fall somewhere in the interval, with 95% probability. When confidence intervals for device models overlap, estimates of survival from product performance-related events may not be different between models. When confidence intervals do not overlap, estimates of survival from product performance-related events may be different between models. Statistical significance may be further evaluated using the Log-rank test or Wilcoxon test as appropriate.

The device survival curves are presented through all continuous time points where there are at least 20 devices, and are cut off at the last 3-month time point where at least 20 total devices were still being followed. Since the survival estimate can become very imprecise with small sample sizes, a minimum of 20 devices must have at least 12 months of follow-up as of the report cut-off date to present a survival curve in this report. Device survival estimates are presented at the device level, not at the system level which involves the combination of 2 or more devices.

1

Klein, John P., Moeschberger, Melvin L. Survival Analysis Techniques for Censored and Truncated Data, New York: Springer-Verlag New York, Inc., 1997.

2

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