Post Approval Study Protocol for the Two Level Simplify® Cervical Artificial Disc

• Simplify Disc (Device): The Simplify Disc is a cervical artificial disc manufactured from polyether ether ketone (PEEK) endplates and a mobile, zirconia-toughened alumina ceramic core.

Primary outcomes

• Clinical Composite Success [Data through 24 months gathered in IDE (NCT03123549; start date 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-op. Comparison data from historical controls up to 60 months post-op is also reported]: Individual success for Simplify Disc was defined as follows: * Neck Disability Index (NDI) score improvement of at least 15 points from pre-operative; * Maintenance or improvement in neurological status; * No serious adverse event classified as implant associated or implant/surgical procedure associated; and * No additional surgical procedure classified as a "failure."

Secondary outcomes

• Clinically Significant Improvement in One or More Radicular Symptoms or Myelopathy [Data through 24 months gathered in IDE (NCT03123549; start date 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-op. Comparison data from historical controls up to 60 months post-op is also reported]: An arm pain questionnaire was used to measure radicular symptoms and compare to baseline symptoms in the IDE study. Changes of at least 2 points on a 10-point scale were regarded as clinically significant (0=no pain; 10=worst pain)
• Health Survey; 36-Item Short Form Survey (SF-36) - Physical Component Score (PCS) Maintenance or Improvement [Data through 24 months gathered in IDE (NCT03123549; start date 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-op. Comparison data from historical controls up to 60 months post-op is also reported]: The PCS is a sub-score of the SF-36. The SF-36 is a multipurpose survey with 36 questions. The questions were combined, scored, and weighted to create two scores that provide glimpses into mental and physical functioning and overall health-related quality-of-life. Higher scores indicate better outcomes. Scores range from 0-50. Maintenance or improvement was defined as PCS(Postop) - PCS(Preop) ≥0.
• Health Survey; 36-Item Short Form Survey (SF-36) - Mental Component Score (MCS) Maintenance or Improvement [Data through 24 months gathered in IDE (NCT03123549; start date 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-op. Comparison data from historical controls up to 60 months post-op is also reported]: The MCS is a sub-score of the SF-36. The SF-36 is a multipurpose survey with 36 questions. The questions were combined, scored, and weighted to create two scores that provide glimpses into mental and physical functioning and overall health-related quality-of-life. Higher scores indicate better outcomes. Scores range from 0-50. Maintenance or improvement was defined as PCS(Postop) - PCS(Preop) ≥0.
• Dysphagia Handicap Index (DHI Scale) [Data through 24 months gathered in IDE (NCT03123549 with start date of 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-operative.]: Dysphagia Handicap Index score for the Simplify Disc subjects at 60 months. A higher score is indicative of a less desirable outcome. It is scored 0-100. Data was not collected on DHI in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design.
• Patient Satisfaction [Data through 24 months gathered in IDE (NCT03123549; start date 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-op. Comparison data from historical controls up to 60 months post-op is also reported]: Patient satisfaction was assessed by survey based on the response to the statement "I am satisfied with the results of my surgery" at 60 months. Answer options ranged from definitely true to definitely false.
• Physician's Perception [Data through 24 months gathered in IDE (NCT03123549; start date 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-op. Comparison data from historical controls up to 60 months post-op is also reported]: Results at 60 months were categorized by the physician's perception of the subject's condition (excellent, good, fair, or poor).
• Change in Average Disc Height (Superior Index Level) [Data through 24 months gathered in IDE (NCT03123549 with start date of 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-operative.]: Average disc height (superior index level) at 60 months was compared to the baseline measurement in the IDE study and the change was calculated. Measurements were scored by an independent core lab. Average disc height was calculated as the simple average of the anterior and posterior disc heights. Data was not collected on average disc height in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design.
• Change in Average Disc Height (Inferior Index Level) [Data through 24 months gathered in IDE (NCT03123549 with start date of 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-operative.]: Average disc height (inferior index level) at 60 months was compared to the baseline measurement in the IDE study and the change was calculated. Measurements were scored by an independent core lab. Average disc height was calculated as the simple average of the anterior and posterior disc heights. Data was not collected on average disc height in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design.
• Adjacent Level Deterioration - Superior Adjacent Level [Data through 24 months gathered in IDE (NCT03123549 with start date of 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-operative.]: Outcome reports the number and percentage of subjects with adjacent level disc degeneration (ALDD) above the index level based on X-ray images. Degeneration was graded as none (no degenerative changes), doubtful (Minimal osteophytosis only), minimal (Definite osteophytosis with some sclerosis of anterior part of vertebral plates), moderate (Marked osteophytosis and sclerosis of vertebral plates with slight narrowing of disk space), or severe (Large osteophytes, marked sclerosis of vertebral plates, and marked narrowing of disk space). Assessments were made by an independent core lab. Data was not collected on adjacent level deterioration in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design.
• Adjacent Level Deterioration - Inferior Adjacent Level [Data through 24 months gathered in IDE (NCT03123549 with start date of 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-operative.]: Outcome reports the number and percentage of subjects with adjacent level disc degeneration (ALDD) below the index level based on X-ray images. Degeneration was graded as none (no degenerative changes), doubtful (Minimal osteophytosis only), minimal (Definite osteophytosis with some sclerosis of anterior part of vertebral plates), moderate (Marked osteophytosis and sclerosis of vertebral plates with slight narrowing of disk space), or severe (Large osteophytes, marked sclerosis of vertebral plates, and marked narrowing of disk space). Assessments were made by an independent core lab. Data was not collected on adjacent level deterioration in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design.
• Displacement or Migration of the Device [Data through 24 months gathered in IDE (NCT03123549; start date 4/1/17). This PAS (start date 8/1/21) followed the same patient cohort through 60 months post-op. Comparison data from historical controls up to 60 months post-op is also reported]: Displacement or migration of the device at 60 months was be compared to immediate post-op data collected in the IDE study. This was be graded by the radiographic core lab. Migration was considered "present" if changes of >3mm were noted. The superior index level and inferior index level was assessed separately.

Sex: All

Inclusion Criteria:

\- All subjects enrolled in the two level Simplify Disc IDE study are considered for this long-term follow-up study.

Exclusion Criteria:

* Subjects who were not implanted with the Simplify Disc during the IDE study
* Subjects who had a secondary surgical intervention at the index level during the IDE study
* Subjects who were withdrawn or withdrew consent to participate in the IDE study
* Subjects who do not consent to participate in long-term follow-up post-approval study

Participant flow

Outcome results

• Clinical Composite Success (Primary), Count of participants, Participants: Simplify Disc 127; ACDF: Historical ACDF control data 84
• Clinically Significant Improvement in One or More Radicular Symptoms or Myelopathy (Secondary), Count of participants, Participants: Simplify Disc 125; ACDF: Historical ACDF control data 90
• Health Survey; 36-Item Short Form Survey (SF-36) - Physical Component Score (PCS) Maintenance or Improvement (Secondary), Count of participants, Participants: Simplify Disc 122; ACDF: Historical ACDF control data 86
• Health Survey; 36-Item Short Form Survey (SF-36) - Mental Component Score (MCS) Maintenance or Improvement (Secondary), Count of participants, Participants: Simplify Disc 110; ACDF: Historical ACDF control data 80
• Dysphagia Handicap Index (DHI Scale) (Secondary), Mean, score on a scale: Simplify Disc 7.1 +/- 11.6
• Patient Satisfaction (Secondary), Count of participants, Participants: Simplify Disc 116; ACDF: Historical ACDF control data 77
• Physician's Perception (Secondary), Count of participants, Participants: Simplify Disc 126; ACDF: Historical ACDF control data 57
• Change in Average Disc Height (Superior Index Level) (Secondary), Mean, mm: Simplify Disc 1.10 +/- 0.84
• Change in Average Disc Height (Inferior Index Level) (Secondary), Mean, mm: Simplify Disc 0.81 +/- 0.94
• Adjacent Level Deterioration - Superior Adjacent Level (Secondary), Count of participants, Participants: Simplify Disc 70
• Adjacent Level Deterioration - Inferior Adjacent Level (Secondary), Count of participants, Participants: Simplify Disc 81
• Displacement or Migration of the Device (Secondary), Count of participants, Participants: Simplify Disc 0; ACDF: Historical ACDF control data 0

Adverse events

Time frame: Data presented includes adverse events (AEs) collected under both the parent IDE study (G150206) and this Post Approval Study (PAS) for patients who enrolled in this PAS. Data collected from the time of surgery through 24 months was gathered in the IDE (NCT03123549; start date 4/1/17) and data for the same patient cohort from 24 months through 60 months post-op was gather under this PAS (start date 8/1/21). Comparison data from historical controls through 60 months post-op is also reported

Serious adverse events by term

Other adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2021-06-14)

• Kyle Malone, Study director, Globus Medical