Event Classification NEUROMODULATION PRODUCT PERFORMANCE

Events currently collected in the registry include all events that appear or worsen during the registry and are a result of:

  • Implanted or external components, Implant or modification procedure, or Infusion or stimulation therapy.
  • Information on all deaths is also collected regardless of their relatedness to the device, implant procedure, and/or therapy.

In early versions of the protocol for infusion and spinal cord stimulation systems, an event was reportable only if it required a surgical intervention, led to therapy abandonment, or resulted in death. This event threshold was expanded for infusion and spinal cord stimulation systems in April 2010 in order to capture additional adverse event data.

Additionally, since the protocol expansion, the seriousness (per ISO 14155-1) of adverse events has been assessed and reported by the registry investigators.

For centers participating in the PSR protocol of the registry, specific therapy relevant events are also collected and include:

  • Negative changes in behavior from baseline for deep brain stimulation, New or worsening depression from baseline for deep brain stimulation, and
  • New or worsened suicidal ideation from baseline, attempted suicide or completed suicide for deep brain stimulation.

By design, not all adverse events experienced by patients during participation were reported in the registry because the registry is primarily focused on understanding the long term reliability and performance of Medtronic implanted systems.

All events reported in the registry are coded using version 21.0 of the Medical Dictionary for Regulatory Activities (MedDRA) and combined by related terms. Medtronic own coding system for events related to implanted neuromodulation systems, which do not exist in the MedDRA dictionary, was integrated with the MedDRA dictionary.

Registry Definitions

In the registry, the events are defined as follows (see Figure 2.1 for the procedure to detemine the event types):

  • Adverse Event any death or undesirable experience (associated with signs, symptoms, illnesses, or other medical events) occurring to the patient that appears or worsens during the clinical study and is possibly related to the device, procedure, and/or therapy.
  • Device Event: an issue with any of the implantable or external system components.
  • Therapy Relevant Event: a specific event type for deep brain stimulation therapies which are collected regardless of relatedness to the device, procedure, or therapy.

Product Performance and Non-product Performance Categorization

For analysis purposes, events collected were collapsed into two categories: product performance events and non-product performance events. All events were reviewed by Medtronic to determine if they were product performance-related (product performance events are events that are possibly due to a device-related issue). A non-product performance related event was any undesirable experience (associated with signs, symptoms, illnesses, or other medical events) occurring to the patient, and that appears or worsens during the clinical study, that possibly resulted from or was related to the implant procedure, or modification between implant and procedure, therapy, or delivery of therapy, and cannot be classified as product performance-related.

Consistency and Accuracy

Consistency and accuracy of event reporting is monitored at four levels: through logic checks built into the study database as center personnel enter information; through review of each event by the study team as it is received by Medtronic; review by the Medical Advisor when necessary; and through routine monitoring at each center per Medtronic standard operating procedures. Monitoring is accomplished through a risk-based approach that aligns with the current FDA guidance on monitoring. Through this approach not every data field is monitored but an emphasis is placed on data related to the primary objective (e.g., events). Clarification and subsequent adjudication of events may be required for, but is not limited to, the following reasons:

  • Inconsistency with the protocols,
  • Inconsistency with the instructions provided to the centers through training materials,
  • Incomplete or inaccurate event description that makes a reported event reason, event reason detail, and the clinical data appear inadequate or inconsistent,
  • Medtronic Customer Support and Vigilance Complaint management requirement for additional information, or
  • Center personnel initiated corrections or additions.