Neurogenic Intermittent Claudication Evaluation Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neurogenic Intermittent Claudication Evaluation Study (NCT00905359), a randomized phase 4 study. The primary outcome is Mean Percentage Change From Baseline in Physical Function at 1 Year Follow-up Using the Patient Completed Zurich Claudication Questionnaire.

2. Clinical Question

The study concerns a functional questionnaire outcome rather than an isolated imaging measure. The Zurich Claudication Questionnaire captures physical function, symptom severity, and patient satisfaction. Its physical-function domain is based on five questions, with scores ranging from 1 to 4; lower scores represent a better outcome or condition. The primary endpoint, however, is reported as percentage change from baseline in that domain, not simply as the follow-up score.

The interpretation therefore depends on both the direction and the size of change, as well as on the comparison between randomized groups. The posted primary means are negative percentage changes in both arms. Those values describe change from baseline; they do not alone establish whether one procedure met a non-inferiority criterion. The registry record does not report the non-inferiority margin, and the formal reported analysis must be distinguished from an unadjusted recalculation of the posted summaries.

3. Trial Design

The registry describes a multicenter, prospective, randomized controlled clinical trial with a parallel-group model and no masking. It is listed as phase 4 and completed. The stated enrollment is 163. The study began in 2010-01, and primary completion was recorded as 2014-09. These record details describe the trial’s registration and design; they do not establish how many participants contributed to each particular outcome.

Participants were randomized to the Aperius™ PercLID™ System or standalone decompressive surgery. The latter is defined as decompressive surgery without instrumentation or fusion. Randomization is an important design feature because, when appropriately implemented, it supports a comparison between groups that is less vulnerable to systematic differences at baseline than a nonrandomized comparison. The registry does not report the sequence-generation or allocation-concealment procedures.

The study was unmasked. Knowledge of assigned treatment can influence participant reports, care decisions, and outcome assessment, especially for questionnaire-based outcomes. The registry does not report whether any outcome assessors were separately masked. No further design information about masking is available in the registry record.

The primary outcome was mean percentage change from baseline in physical function at 1 year using the patient-completed Zurich Claudication Questionnaire. Its stated analysis population was per protocol: subjects who did not undergo the surgical procedure assigned by randomization were excluded. The primary arm summaries use 72 participants in the Aperius™ arm and 73 in the standalone surgery arm. These outcome-specific numbers should not be treated as the original randomized group sizes; the record does not provide the randomized allocation counts by arm in the material summarized for this outcome.

The trial also listed secondary outcomes across questionnaire domains, pain, quality of life, secondary surgical intervention, serious adverse device effects, and MRI-assessed stenosis. One secondary outcome gives an overall study-period timeframe of up to 24 months. The registry does not report the trial’s original sample-size justification, detailed statistical analysis plan, interim analyses, or the procedures used to manage missing observations.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per-protocol analysis (subjects who were not performed surgical procedure as assigned per randomization were excluded).

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.

Population: Per statistical analysis plan, populations excluded patients who withdrew consent during the study.

6. Primary Endpoint

The registry lists the primary outcome as Mean Percentage Change From Baseline in Physical Function at 1 Year Follow-up Using the Patient Completed Zurich Claudication Questionnaire, measured over 1 year.

The primary endpoint is the mean percentage change from baseline in physical function at 1 year, measured using the patient-completed Zurich Claudication Questionnaire (ZCQ). The ZCQ is described in the registry as a validated instrument specific to lumbar spinal stenosis. It measures three domains: physical function, symptom severity, and post-treatment patient satisfaction. The primary outcome uses the physical-function domain, which is the mean score across five physical-function questions.

The ZCQ physical-function score ranges from 1 to 4, and a lower score represents a better outcome or condition. Reporting percentage change from baseline expresses the change relative to each participant’s starting score, then summarizes the changes as a group mean. The posted endpoint is therefore a continuous measure. Its stated spread is the standard deviation, which describes variability among participant measurements rather than uncertainty in the estimated group mean.

A patient-completed functional measure is relevant to a study of neurogenic intermittent claudication because it records reported difficulty with physical activities. It complements other listed outcomes, including symptom severity, pain, quality of life, patient satisfaction, surgical intervention, and MRI-assessed stenosis. These measures address related but distinct aspects of outcome; change in one should not be taken as a substitute for change in another.

The primary analysis population is per protocol, excluding subjects who did not undergo the procedure assigned by randomization. This population definition matters because excluding participants after randomization can affect the balance created by random assignment. The registry record does not report how missing questionnaire responses were handled or whether additional populations were analyzed.

7. Results Posted in the Registry

• Standalone Decompressive Surgery: mean -37.48 versus -32.31 on control; difference -5.17 (95% CI -14.23 to 3.89), standardized effect d = -0.19; z-test p = 0.264.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Subjects Requiring Secondary Surgical Intervention

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Standalone Decompressive Surgery: 8.0% (6/75) versus 20.8% (16/77) on control; risk difference -12.8 percentage points (95% CI -23.7 to -1.8), risk ratio 0.39 (0.16–0.93); unadjusted two-proportion z-test p = 0.025.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Standalone Decompressive Surgery than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes spanning physical function, symptom severity, patient satisfaction, leg pain, quality of life, secondary surgical intervention, serious adverse device effects, and MRI-assessed spinal canal stenosis. This range covers patient-reported symptoms and function, subsequent procedures, safety, and an imaging measure. These endpoints address different dimensions of the study and should not be expected to move together in a simple way.

The detailed secondary data include a count of subjects requiring secondary surgical intervention over the overall study period, up to 24 months. The posted unadjusted comparison is statistically notable by its reported p-value, but it is one secondary analysis among a broader group of outcomes. Its role is supportive and exploratory in interpretation; it does not replace the primary physical-function endpoint or resolve the registry’s unreported non-inferiority margin.

Unadjusted secondary results carry less weight because multiple outcomes create multiple opportunities for apparently strong findings by chance. The registry does not report a multiplicity adjustment or a prespecified hierarchy for secondary endpoints. Without such information, nominal p-values should not be treated as confirmatory evidence in isolation. The secondary findings can help describe the outcome profile and identify questions for further evaluation, but they do not establish a unified pattern of benefit or harm across all domains.

Nor can a secondary result automatically explain the primary result. For example, a subsequent-procedure outcome is distinct from the questionnaire’s physical-function change, and imaging findings are distinct from patient-reported experience. The registry record does not provide enough information to characterize an overall direction across every secondary endpoint. The appropriate reading is therefore endpoint-specific, with due caution about multiplicity and the different populations, timeframes, and measurement types involved.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Mean Percentage Change From Baseline in Physical Function, Using Patient Completed Zurich Claudication Questionnaire
• Mean Percentage of Change From Baseline in Symptom Severity of the Patient Completed Zurich Claudication Questionnaire
• Patient Satisfaction (PS) Scores of Zurich Claudication Questionnaire
• Mean Percentage Change of Visual Analog Scale (VAS) From Baseline in Leg Pain
• Mean Percentage Changes From Baseline in Quality of Life Using the Patient-completed SF-36 Questionnaire
• Number of Subjects Requiring Secondary Surgical Intervention
• Percentage of Subjects With Serious Adverse Device Effects
• Changes in Stenosis of the Spinal Canal Assessed by Magnetic Resonance Imaging (MRI) at the Follow-up Time Points

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is continuous, and the registry reports a mean and standard deviation for each arm. A mean describes the central value of measurements in a group. The standard deviation describes how dispersed participant-level values are around that mean. It is not the same as a confidence interval: the standard deviation describes variability among observations, while a confidence interval describes uncertainty about an estimated quantity.

What does the mean difference represent?

The unadjusted comparison uses the difference between the two posted arm means. The recalculated estimate is -5.17 for standalone decompressive surgery relative to the Aperius™ arm. The negative sign follows that comparison’s direction; it does not by itself indicate whether the difference is important to patients. The endpoint is percentage change in physical function, and the registry does not report a threshold for a clinically important between-group difference.

This recalculation is based on the posted summary statistics and is unadjusted. It is not a reconstruction of an individual-participant analysis, nor does it incorporate covariates or other adjustments. The registry’s sponsor-reported non-inferiority test is a separate result. The two analyses answer related but not identical statistical questions, so their p-values should not be treated as competing versions of the same test.

How does a non-inferiority question differ?

A superiority analysis typically asks whether there is evidence of a difference between groups. A non-inferiority analysis instead asks whether the outcome for one intervention is not unacceptably worse than that for a comparator, according to a margin defined in advance. The margin is central: it sets the largest difference that would still count as acceptable under the study’s criterion. The registry record does not report that margin, so readers cannot assess the reported non-inferiority p-value against the study’s exact decision rule from the available record alone.

The sponsor-reported method is identified as a one-sided t-test for non-inferiority or equivalence, with p = 0.172. A one-sided test evaluates evidence in a specified direction, unlike a two-sided test that considers departures in either direction. The record does not report more detail about the test implementation, assumptions, or any corresponding confidence bound. The unadjusted recalculation instead gives a two-sided comparison based on the posted means and standard deviations.

Why can over-dispersion matter?

In general, over-dispersion means that observed variation is greater than a statistical model assumes. When a model understates variability, standard errors can be too small and confidence intervals too narrow, making evidence appear more precise than it is. The primary endpoint is continuous and the record reports standard deviations, but it does not identify an over-dispersion adjustment or indicate that one was used. The concept is relevant generally; there is no basis in the registry record to claim that over-dispersion affected this analysis.

For a continuous outcome, assumptions about the distribution of measurements and the behavior of the mean can influence a t-based analysis. The registry identifies the sponsor’s test as a t-test, but does not report diagnostic checks, transformations, or robust alternatives. The recalculation is explicitly unadjusted and uses the posted summary values; it cannot verify participant-level distributional assumptions.

What does the analysis population imply?

The primary endpoint is analyzed per protocol. The registry defines that population as subjects who were not excluded for failing to undergo the procedure assigned by randomization; in its wording, subjects who did not undergo the assigned procedure were excluded. In general, a per-protocol analysis focuses on participants who followed the assigned treatment path, while an intention-to-treat analysis retains participants according to their randomized assignment. These approaches can differ if post-randomization exclusions are related to outcomes or participant characteristics.

Randomization supports an unbiased comparison when the randomized groups are retained and analyzed appropriately. Removing participants after randomization can weaken that protection. This does not establish that bias occurred in this trial; it means the reported population definition should be considered when interpreting the estimate. The number and characteristics of excluded participants, an intention-to-treat estimate, and sensitivity analyses are not reported in the registry record.

Why distinguish statistical from clinical meaning?

A p-value describes how compatible data are with a specified statistical null hypothesis under the test assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. A confidence interval adds information about the range of estimates compatible with the data and method. Neither statistic supplies a clinical-importance threshold unless one is defined and reported.

Non-inferiority conclusions also require attention to the choice and justification of the margin, the analysis population, and consistency across analyses. The registry record identifies the study objective and a sponsor-reported one-sided test but does not report the margin or original statistical plan. Therefore, the formal test result can be stated, while a full independent evaluation of the non-inferiority framework is limited by missing design details.

11. Confidence Intervals and Precision

The unadjusted recalculated mean difference is -5.17, with a 95% confidence interval from -14.23 to 3.895. This interval expresses uncertainty about the between-arm mean difference under the recalculation’s assumptions. It extends from a negative value to a positive value and includes zero. Thus, the posted summaries do not pin down the direction of the difference with high precision under this two-sided comparison.

The confidence interval should not be read as a range containing most individual participant outcomes. Individual measurements vary more widely, as reflected by the arm standard deviations of 32.06 and 22.79. The interval instead concerns the estimated difference between group means. Its width reflects sampling uncertainty as well as the variability and sample sizes used in the recalculation.

Precision is not the same as clinical importance. The registry record does not report a minimum clinically important difference for the physical-function endpoint. It also does not report the non-inferiority margin. Consequently, the interval cannot be judged against a recorded clinical threshold or the formal non-inferiority boundary. The interval’s inclusion of zero is relevant to a conventional two-sided difference test, but does not by itself resolve a one-sided non-inferiority question.

The sponsor-reported one-sided non-inferiority test gives p = 0.172. A p-value does not show the range of plausible effect sizes, and the record does not include the corresponding confidence bound or margin. The recalculated interval and the sponsor-reported test should therefore be kept distinct when assessing precision. Both are based on the same trial context, but they answer different formulations of the statistical question and the registry does not provide enough detail to reconcile their decision criteria fully.

The outcome is per protocol, so the precision pertains to the reported analysis population, not necessarily to all randomized participants. Information about missing observations, exclusions beyond the stated definition, or additional analyses that might assess robustness is not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrative sample-size calculations based on the observed effect, not the original trial design. For the continuous primary outcome and the binary secondary outcome, the figures are participants per arm. They are not total event counts. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column indicates the number of participants per arm that the calculation estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions, if that effect were real. The 90% power column describes the corresponding planning target for a 90% chance. These are design concepts, not guarantees about what a future study would find. The reported planning examples use 100%, 75%, and 50% of the observed effect.

The rows describe planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. A smaller target effect is harder to distinguish from random variation, so it generally requires more participants to achieve the same planned power. The calculations are based on the observed effect, which is itself uncertain; they should not be treated as proof that a future study will reproduce that estimate.

These figures are not observed power. Observed power calculated from an effect estimate does not add useful information beyond the estimate and its uncertainty. The planning values are best read as conditional illustrations of how sample-size requirements change when the assumed effect size changes, not as a retrospective verdict on the trial’s adequacy.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -5.170; pooled standard deviation σ = 27.782.
2. n = 2 × (1.96 + 0.842)² × 27.782² / -5.170² = 453.3, rounded up to 454 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -5.16999999999999                      # observed difference in means
sigma <- 27.7819369299626                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(905359)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 454 (80% power), 607 (90% power)
 75% of observed effect: n per arm = 806 (80% power), 1,079 (90% power)
 50% of observed effect: n per arm = 1,814 (80% power), 2,428 (90% power)
power.t.test: 454.3 
Simulated power at n = 454 per arm: 0.792 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a one-sided t-test for non-inferiority or equivalence, with p = 0.172. That is the analysis explicitly recorded for the primary endpoint. The registry does not report the non-inferiority margin, the detailed test specification, or the associated confidence bound, limiting independent assessment of the formal decision criterion.

The unadjusted recalculation uses the posted arm means and standard deviations to estimate a mean difference of -5.17, with a 95% confidence interval from -14.23 to 3.895 and an unadjusted p-value of 0.264. It is not a reproduction of the sponsor’s one-sided non-inferiority test. It applies a different comparison to summary statistics and does not include details that may have informed the sponsor’s formal analysis.

The two results should therefore be read alongside one another, not substituted for one another. The recalculation offers a transparent, simple comparison of the posted summaries; it does not supersede the registry’s reported analysis or demonstrate whether the study met its intended non-inferiority criterion. The record does not indicate a discrepancy between the posted summaries and the reported analysis. Without the margin and full analysis details, the sponsor-reported p-value cannot on its own convey how close the estimate was to the non-inferiority boundary or how that boundary was selected.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and 14 posted secondary outcomes. The primary outcome is the one-year percentage change in physical function, while the secondary list covers multiple questionnaire domains, pain, quality of life, further surgery, adverse effects, and MRI assessment. Evaluating many outcomes raises a multiplicity issue: even when there is no true effect, testing many hypotheses can increase the chance that at least one result appears statistically unusual by chance.

The registry record does not report a multiplicity adjustment, a prespecified hierarchy of outcomes, or a procedure for controlling the overall type I error rate across secondary analyses. Thus, unadjusted secondary p-values should be interpreted cautiously and should not be treated as if they were each the sole confirmatory test. The record also does not report whether all listed outcomes were analyzed according to a detailed prespecified analysis plan.

The primary endpoint’s population is described as per protocol, excluding subjects who did not undergo the assigned procedure. The record does not report an intention-to-treat analysis for the primary outcome, a sensitivity analysis comparing populations, or the number and characteristics of participants excluded from the per-protocol analysis. These omissions limit assessment of how the analysis population may affect the estimated treatment contrast.

Missing-data procedures are not reported in the registry record. It is not stated how incomplete questionnaire responses, loss to follow-up, or unavailable measurements were handled, whether imputation was used, or what assumptions would underlie any such method. The number of missing observations by arm and outcome is also not reported in the information summarized for these results. Without those details, the potential influence of missingness cannot be assessed.

The registry does not report interim analyses, stopping rules, the original statistical analysis plan, or the original sample-size justification. This absence does not show that such procedures were absent in the trial; it means they are not reported in the registry record. These limitations matter when distinguishing confirmatory conclusions from descriptive or exploratory findings.

16. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0.0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: spinal claudication (7.8%), osteoarthritis (6.5%), lumbar spinal stenosis (5.2%), extradural haematoma (2.7%), lumbar vertebral fracture (2.6%).

The serious adverse event summaries report 26 affected participants among 77 at risk in the Aperius™ PercLID™ System group and 25 among 75 at risk in the standalone decompressive surgery group. These are the posted counts and denominators; they are not newly calculated rates. The registry lists serious-event terms including spinal claudication, osteoarthritis, lumbar spinal stenosis, extradural haematoma, lumbar vertebral fracture, and pain in extremity, with the corresponding percentages recorded in the safety results.

The listed serious-event terms are not assigned to a specific arm in the record summarized for these results. They should therefore be read as reported terms and percentages, not as evidence that a particular term occurred more often in one group. The registry also reports other adverse events, with 53 affected among 77 at risk in the Aperius™ group and 57 among 75 at risk in the surgery group; those figures describe the other-event category and should not be conflated with serious events.

Deaths are not reported in the registry record. These summaries describe reported events during the trial and do not, by themselves, establish causation or provide a complete comparison of safety. The record does not supply enough detail to assess event timing, recurrent events, seriousness criteria, or participant-level overlap between event categories.

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

The posted primary data describe mean percentage changes in physical function from baseline at 1 year in two randomized groups. Both arm means are negative, and the unadjusted recalculation estimates a mean difference of -5.17 with a 95% confidence interval from -14.23 to 3.895. The uncertainty interval includes zero, so the recalculation does not establish a conventional two-sided difference between the means.

The study’s stated objective was to evaluate whether the Aperius™ PercLID™ System was safe and non-inferior to standalone decompressive surgery. A non-inferiority conclusion depends on a prespecified margin and the formal analysis used to compare the observed estimate with that margin. The registry reports a one-sided non-inferiority or equivalence t-test with p = 0.172, but the margin and corresponding confidence bound are not reported in the registry record. The available data therefore do not permit a complete independent assessment of the non-inferiority decision rule.

These results do not mean that the interventions are identical. A nonsignificant two-sided result does not demonstrate equivalence, and a non-inferiority objective cannot be settled by treating a conventional difference test as interchangeable with a non-inferiority test. The interpretation also depends on the per-protocol population, which excludes subjects who did not undergo the procedure assigned by randomization.

The outcome concerns self-reported physical function, not every aspect of the condition. The registry also lists symptoms, satisfaction, pain, quality of life, secondary surgery, adverse effects, and MRI outcomes. Findings from one domain cannot be assumed to describe the others. Secondary results require additional caution because multiplicity handling is not reported.

The registry record supports a description of the trial design, endpoint, arm summaries, and reported statistical test. It does not provide the full analysis plan, non-inferiority margin, missing-data procedures, or a clinical-importance threshold. The data should not be used as medical advice or as a stand-alone basis for an individual treatment decision.

18. Why This Trial Matters Statistically

This trial illustrates why the label attached to a statistical question matters. A superiority comparison asks whether the data support a difference, while non-inferiority asks whether an intervention is not worse than a comparator by more than a prespecified acceptable amount. The same observed group summaries can be considered under either framework, but the decision rules are not interchangeable. The non-inferiority margin is essential to interpreting the study’s stated objective, yet it is not reported in the registry record.

The result also demonstrates the importance of distinguishing a sponsor-reported test from a recalculation based on summary statistics. The registry’s one-sided non-inferiority or equivalence test and the unadjusted two-sided recalculation address different statistical formulations. Stating both transparently helps readers avoid treating a single p-value as a complete account of the evidence.

The per-protocol primary analysis is another important design feature to consider. Randomization helps create comparable groups, but excluding participants who did not undergo the assigned procedure can change the composition of the groups analyzed. Reporting the analysis population is therefore central to understanding what comparison the estimate represents.

Finally, the trial’s outcomes span patient-reported function, symptoms, safety, further surgery, and imaging. Such a broad set can provide a richer view of study results, but it also raises questions about multiplicity, prespecification, and how to weigh secondary findings. The registry record does not report enough detail to answer all of those questions. These issues make the study useful for illustrating how design, analysis population, endpoint choice, and reporting completeness jointly shape statistical interpretation.

19. 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.

The primary outcome is analyzed in a per-protocol population that excludes subjects who did not undergo the procedure assigned by randomization. The registry does not report the number or characteristics of excluded participants, an intention-to-treat result, or sensitivity analyses. This limits assessment of whether the reported estimate is robust to the analysis population.

The trial was unmasked, and the primary endpoint was patient-completed. Participants’ knowledge of assignment may influence reporting or expectations in general, although the registry record does not establish that this occurred. It does not report whether outcome assessors were separately masked or describe procedures intended to limit assessment bias.

The record reports the sponsor’s one-sided non-inferiority or equivalence test but does not report the non-inferiority margin, its justification, the associated confidence bound, or the full analysis plan. The clinical-importance threshold for the physical-function measure is also not reported. These omissions prevent a full independent appraisal of how the formal result relates to an acceptable difference.

Missing-data handling is not reported. The registry does not describe the number of missing measurements, how incomplete questionnaire data were treated, whether imputation was used, or whether sensitivity analyses examined alternative assumptions. The trial’s original sample-size justification and interim analysis procedures are also not reported in the registry record.

The study lists multiple secondary outcomes, but multiplicity adjustment and a hierarchy of secondary tests are not reported. Consequently, secondary statistical findings should be viewed cautiously. The results also include different timeframes and types of measurement, so they do not form a single interchangeable outcome. These are reporting limitations; they do not establish that the methods were absent from the trial’s full documentation.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Neurogenic Intermittent Claudication Evaluation Study — NCT00905359.
• Registry record last updated 2017-02-10; status last verified 2016-12.
• Results first posted 2016-07-29.
• 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.

23. Record Summary

NCT00905359 is a completed, randomized, parallel-group, unmasked phase 4 trial of the Aperius™ PercLID™ System versus standalone decompressive surgery for degenerative lumbar spinal stenosis with neurogenic intermittent claudication. The registered enrollment is 163. The study began in 2010-01, with primary completion in 2014-09.

The primary endpoint was mean percentage change from baseline in Zurich Claudication Questionnaire physical function at 1 year. The reported primary population was per protocol. The registry gives a one-sided sponsor-reported non-inferiority or equivalence t-test with p = 0.172. An unadjusted recalculation from posted summaries estimates a mean difference of -5.17, with a 95% confidence interval from -14.23 to 3.895 and an unadjusted p-value of 0.264.

The registry lists secondary outcomes across function, symptoms, satisfaction, pain, quality of life, further surgery, adverse effects, and MRI assessment. Important details—including the non-inferiority margin, missing-data procedures, multiplicity approach, and original sample-size justification—are not reported in the registry record.