Post-Approval Study Protocol for the Simplify Cervical Artificial Disc: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Post-Approval Study Protocol for the Simplify Cervical Artificial Disc (NCT04630626), a non-randomized na study. The primary outcome is Number of Participants With Clinical Composite Success, Parent IDE Study + Post Approval Study (PAS).

2. Clinical Question

The question is about an extended-follow-up cohort and a historical reference, rather than a randomized test of two treatments. The record lists Simplify Disc and ACDF as interventions and describes historical ACDF data as the control. However, the design is marked non-randomized, and the record explicitly cautions against treating the arms as a like-for-like comparison. Differences between the groups could therefore reflect differences in their source data or other features, not only the device or procedure.

The study record is marked completed. It describes the aim as demonstrating five-year long-term safety and efficacy, while the primary outcome timeframe is expressed as the IDE study's 24 months plus the post-approval study's 36 months. Those periods are stated to total 60 months. The actual primary outcome findings, and the results for the listed secondary outcomes, are not reported in the registry record.

3. Trial Design

This is a completed, non-randomized post-approval study of extended follow-up among IDE participants treated with the Simplify Cervical Artificial Disc. The registry classifies the model as single group, allocation as non-randomized, and masking as none. The study is described as having been conducted under IDE G140154. Its listed enrollment is 145; that is a registry enrollment figure, not a count of participants with reported primary outcome data.

The study dates listed in the record are a start date of 2021-01-01 and a primary completion date of 2023-04-23. Its stated purpose is to assess long-term safety and efficacy in subjects enrolled in the non-randomized Simplify Disc IDE study. The primary outcome timeframe combines the IDE study's 24 months with the post-approval study's 36 months, expressed as 60 months total.

The record also includes a Historical ACDF Control arm, described as historical ACDF data from a similar protocol used as control. That does not make this a randomized or contemporaneous comparison. The record specifically notes that the arms are not a like-for-like control comparison. The historical information can offer context, but differences between the data sources may limit direct interpretation of contrasts.

No further allocation procedure, masking procedure, protocol-level sample-size justification, or statistical analysis plan is reported in the registry record. The registry lists 10 outcome measures and 0 analyses. It names secondary outcomes concerning neurological status, visual-analog-scale symptoms, disc height, adjacent-level disc deterioration, device displacement or migration, treatment satisfaction, and SF-12 status. The registry record does not report results for these outcomes. The distinction between a registered outcome and a reported analysis matters: naming an outcome does not show how many participants contributed data, how missing measurements were handled, or what estimates were observed.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Clinical Composite Success, Parent IDE Study + Post Approval Study (PAS), measured over IDE study 24 months + PAS 36 months = 60 months total.

The primary endpoint is a count of participants with clinical composite success, assessed over the stated 60-month timeframe. The definition combines three conditions. A participant must have improvement on the Neck Disability Index (NDI) of at least 15 percentage points compared with baseline in the Simplify Disc IDE study, have no device failure by month 60, and have no subsequent surgical procedure at the index level by month 60. The listed procedures include revision, removal, reoperation, or supplemental fixation.

Because this is a composite, success depends on satisfying the full definition, not just improving on the NDI. The components address a patient-reported disability measure, device failure, and further index-level surgery. Combining them gives a single endpoint that encompasses different aspects of the study's stated clinical-success concept. It also means that a composite result alone would not show which component most often determined whether participants met the definition.

The primary outcome is specified for Simplify Disc and the historical ACDF control. The registry record does not report the number meeting the composite definition, component-specific results, or an estimate comparing groups. It also does not report the number assessed for this endpoint or the handling of missing component data. Accordingly, the endpoint can be described from its definition, but its observed frequency and precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help explain what an outcome estimate can and cannot show. In this record, the primary endpoint is a count of participants meeting a defined composite. No estimate for that endpoint is reported in the registry record, so there is no primary result whose magnitude or precision can be interpreted. The following concepts are general explanations, not claims about analyses performed in this study.

What does a count measure?

A count records how many participants meet an outcome definition. For this endpoint, the count would refer to participants who satisfy all three composite-success criteria. A count alone does not show the share of an analysis group unless the corresponding denominator is also specified. The registry record lists an enrollment figure, but enrollment should not automatically be treated as the denominator for every endpoint: some participants may not have outcome data, and the record does not report endpoint-specific denominators.

For a binary outcome, analysts often report the count alongside the number assessed and a proportion. A confidence interval can describe the statistical uncertainty around an estimated proportion. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. Neither an estimate nor its interval establishes that an observed association is causal. Here, the registry record does not report an interval or a primary endpoint estimate.

How should a composite be understood?

A composite endpoint combines multiple criteria into one outcome. It can represent several dimensions of clinical success in a single definition, but the combined result can obscure differences among components. In this study, success requires NDI improvement, no device failure, and no subsequent index-level surgical procedure by month 60. A participant who does not meet any one criterion does not meet the full composite definition. If results were available, separate component counts would help explain which criteria were most influential. Such component results are not reported in the registry record.

The definition also specifies a change relative to baseline for the NDI component. A baseline comparison is meaningful only with a clear baseline measure and follow-up data. The registry gives the criterion but does not report the observed NDI changes, endpoint denominators, or missing-data rules. Therefore, it is not possible to assess the data completeness behind the composite from the record.

What does non-randomized allocation imply?

Random allocation is one way to make comparison groups similar, on average, with respect to factors that could affect outcomes. In a non-randomized study, group membership is not assigned by random allocation. Differences between groups can reflect the intervention, but can also reflect differences in who entered each group, the source of the data, follow-up, or other measured and unmeasured characteristics.

This consideration is especially relevant because the ACDF arm is described as historical data from a similar protocol. The record explicitly cautions that the arms are not a like-for-like control comparison. Even a numerical difference between group outcomes, if reported, would require careful interpretation and would not alone identify a causal effect. The registry record does not report adjustment methods or enough details to assess comparability.

How do uncertainty and significance differ?

In general, a confidence interval describes a range of estimates compatible with the data and a specified statistical procedure. A significance test addresses a particular null hypothesis under stated assumptions. A p-value is not the probability that a treatment works, nor does it measure the size or clinical importance of an effect. Neither a confidence interval nor a p-value can substitute for examining the estimate, the study design, and the data quality. No primary endpoint confidence interval or test result is reported in the registry record.

What can sample-size planning show?

In general, a sample-size calculation describes the information a future study might need under stated assumptions; it does not describe the result observed in a completed study. The registry record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, a normal approximation, and planning at a stated fraction of the observed effect. It specifies that non-time-to-event illustrations are expressed as participants per arm, while time-to-event illustrations give total events. These assumptions are described as a planning illustration, not the trial's own design, and any resulting sample-size values would be planning quantities, not observed power.

The record does not report the trial's own sample-size justification or its analysis plan. The existence of a planning illustration cannot fill those gaps. Nor should a calculated sample size be interpreted as evidence that a study had adequate power after completion: observed power is not a substitute for estimates and uncertainty intervals.

Why does over-dispersion matter?

In general, over-dispersion occurs when count data vary more than a statistical model assumes. If an analysis assumes less variability than is present, its standard errors and confidence intervals may be too small, which can make evidence appear more precise than it is. Choosing a model that reflects the data's variability can improve inference. The registry record does not identify a count model or report an over-dispersion assessment, and the primary outcome is described as a participant count rather than an event-rate model. This general concept should not be mistaken for a method documented in the study.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Simplify Disc", "Historical ACDF Control")
n      <- c(123, 63)
events <- c(117, 40)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Simplify Disc  123  117  95.1  89.7  98.2  89.8  97.7  89.8  97.7
ARM  Historical ACDF Control  63  40  63.5  50.4  75.3  51.1  74.3  51.1  74.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 10 outcome measures and 0 analyses. It names one primary composite-success outcome and several secondary outcomes, including neurological status, symptom ratings, disc height, adjacent-level disc deterioration, device displacement or migration, treatment satisfaction, and SF-12 status. Listing multiple outcomes raises a general statistical issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase if each is assessed without adjustment. In general, a prespecified approach to multiplicity can help readers interpret a collection of tests.

The registry record does not report whether multiplicity was addressed, which outcomes were included in any inferential testing, or whether a hierarchy of outcomes was used. It does not report primary or secondary analysis results in the analyses listing. Therefore, no claim about adjusted or unadjusted testing can be made from the registry record. The presence of multiple registered outcomes does not itself establish that all were tested or that a particular correction was required or applied.

Missing-data handling is also not reported in the registry record. The record does not describe imputation, complete-case analysis, rules for defining endpoint availability, or sensitivity analyses for missing outcomes. These details matter because the endpoint requires information about several criteria through month 60. Without the number assessed for each criterion and the approach to incomplete records, the potential influence of missing data cannot be evaluated.

Analysis-population definitions are not reported in the registry record. The enrollment figure should not be assumed to equal the population used for each outcome analysis. The record also does not state whether results were based on all enrolled participants, participants with available follow-up, or another defined population. These omissions limit assessment of both the outcome estimates and the degree to which the analysis followed a prespecified plan.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: adjacent segment degeneration (4.5%), gastrointestinal complications (3.8%), infection - not at surgical site (2.8%), cancer (2.8%), trauma (2.3%).

The registry record lists serious adverse-event counts for both groups. For Simplify Disc, 25 participants are listed as affected among 132 at risk; for Historical ACDF Control, 17 are listed as affected among 106 at risk. The record also lists other adverse events affecting 105 among 132 at risk for Simplify Disc and 72 among 106 at risk for Historical ACDF Control. Deaths are listed as 1 and 0, respectively. These are the registry's group counts; they should not be read as a randomized comparison or as proof of a difference caused by treatment.

The record lists serious adverse-event terms with percentages, including Adjacent Segment Degeneration at 4.5%, Gastrointestinal Complications at 3.8%, Infection - Not At Surgical Site at 2.8%, Cancer at 2.8%, Trauma at 2.3%, and Pain (Narcotic Given) at 1.9%. The denominator and method used for these percentages are not reported in the registry record. The list does not establish that these terms account for all serious events.

Counts provide a direct description of recorded events, but interpretation also depends on how events were defined, the period covered, ascertainment, exposure time, and participant follow-up. The record does not report those details for these safety counts. Because the comparator is historical and the registry cautions that the arms are not like-for-like, crude counts should not be used to infer comparative risk. The listed safety data are descriptive and do not replace the unreported primary outcome results.

13. What the Result Does, and Does Not, Mean

The registry record documents a completed study designed to extend follow-up of IDE participants treated with the Simplify Disc. It specifies a composite clinical-success definition and a total timeframe of 60 months. It also gives counts for serious adverse events, other adverse events, and deaths in the Simplify Disc and historical ACDF groups. These registry entries describe the study's structure and some safety reporting; they do not provide a reported primary efficacy result.

The primary endpoint asks whether participants met all of the listed conditions: the specified NDI improvement from baseline, no device failure by month 60, and no subsequent index-level surgical procedure by month 60. The registry record does not report how many met those conditions. Without that result, it is not possible to describe the observed frequency of composite success, compare it with the historical group, or assess statistical precision.

Even if a group contrast were available, the non-randomized design and historical comparator would limit causal interpretation. The record explicitly says the arms are not a like-for-like control comparison. A difference could be related to factors beyond the device or procedure, and the registry record does not report adjustment methods that would address such differences. The safety counts also remain descriptive and do not establish equivalence or a causal safety effect.

In general, a completed registry status means the study is marked completed in the record; it does not mean that all results have been posted or that every outcome has been analyzed in a way visible in the record. The outcome listing and safety counts should therefore be distinguished from a full results report. Missing information on endpoint denominators, missing-data handling, analysis populations, and statistical methods also limits evaluation of the evidence.

The record supports describing the study aim, follow-up horizon, endpoint definition, design, and listed safety counts. It does not support a conclusion that the Simplify Disc is effective or ineffective, nor does it establish a comparative advantage or disadvantage relative to ACDF. Those conclusions would require results and methods not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically important to interpret because it combines extended follow-up with a historical control. Long-term follow-up can address outcomes that are defined over a prolonged period, including device failure and subsequent surgery through month 60. At the same time, longer follow-up makes the definition of the analysis population, outcome availability, and handling of incomplete follow-up important. Those details are not reported in the registry record.

The primary endpoint is a composite, bringing together a patient-reported disability criterion and two criteria concerning device failure and later surgery. A composite can give a compact summary across multiple dimensions, but its meaning depends on each component and on the rule that all criteria must be met. Component-level results would be useful for interpreting any overall count, but are not reported in the registry record.

The historical comparison also highlights the difference between a numerical contrast and a causal estimate. Because allocation is non-randomized and the control is historical, group differences may reflect how the groups or data were assembled. The record itself cautions that the arms are not a like-for-like control comparison. This limits how directly the groups can be contrasted, regardless of whether a test result were available.

Finally, the registry lists outcomes but does not report analyses for them. The absence of posted primary results, uncertainty estimates, missing-data procedures, and analysis-population definitions leaves major statistical questions unanswered. Recognizing those gaps is essential: a clearly defined endpoint is not the same as a reported outcome, and a completed study record is not by itself evidence of a particular result.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to the information reported for this study. First, the primary composite-success outcome is defined, but its observed count is not reported in the registry record. There is consequently no reported estimate or uncertainty interval for the main clinical question. The record also does not give component-specific results, so readers cannot distinguish the contribution of NDI improvement, device failure, or additional index-level surgery.

Second, the comparison is non-randomized and uses historical ACDF data from a similar protocol. The registry explicitly cautions that the arms are not a like-for-like control comparison. The record does not report details sufficient to assess group comparability or adjustment for potential differences. The historical group therefore cannot be treated as equivalent to a concurrent randomized control.

Third, enrollment is reported, but endpoint-specific denominators and analysis-population definitions are not. The registry record does not explain how missing outcome data were handled, how follow-up completeness was assessed, or whether sensitivity analyses were performed. This is particularly relevant to a composite outcome requiring information through month 60.

Fourth, although 10 outcome measures are listed, the analyses listing contains 0 analyses. The registry record does not report the statistical analysis plan, multiplicity procedures, or results for the listed secondary outcomes. It also does not report the protocol's sample-size justification. The planning illustration described in the record is not the trial's own design and does not provide an observed efficacy result.

Finally, safety counts are presented without further reported detail on event definitions, ascertainment, time coverage, or the denominator for the listed serious-event percentages. These omissions constrain interpretation of both the clinical outcome and the safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Post-Approval Study Protocol for the Simplify Cervical Artificial Disc — NCT04630626.
• Registry record last updated 2026-01-08; status last verified 2025-12.
• Results first posted 2024-05-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This registry record describes NCT04630626, a completed post-approval study of extended follow-up for IDE participants treated with the Simplify Cervical Artificial Disc. The stated study aim is long-term safety and efficacy assessment. The registry lists enrollment of 145, a non-randomized allocation, no masking, and a single-group model, while also listing a historical ACDF control based on data from a similar protocol.

The primary endpoint is the number of participants with clinical composite success over the IDE study and post-approval follow-up, stated as 60 months total. Success requires the specified NDI improvement, no device failure by month 60, and no subsequent index-level surgical procedure by month 60. The registry record does not report primary endpoint results or analyses.

The record lists 10 outcome measures and 0 analyses, and gives descriptive adverse-event counts for the two groups. It cautions that the arms are not a like-for-like control comparison. Important statistical details, including missing-data handling, analysis populations, and the analysis plan, are not reported in the registry record.