Spinal Cord Stimulation to Augment Activity Based Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Spinal Cord Stimulation to Augment Activity Based Therapy (NCT03240601), a randomized na study. The primary outcome is Change in Walking Function - 10m Walk Walking Speed (m/s).

2. Clinical Question

The clinical question is whether adding active stimulation during locomotor training is associated with a different change in walking speed than training with subthreshold stimulation. The study also listed secondary outcomes concerning walking function, spasticity, and stimulation tolerability. These include the 2-minute walk, ankle clonus drop test, muscle co-contraction during voluntary activation, and the Spinal Cord Assessment Tool for Spastic Reflexes test.

The comparison is between two study conditions, not between stimulation and no locomotor training. Both arm descriptions include physical therapist-directed locomotor training and transcutaneous spinal cord stimulation. The registry record does not report enough detail to infer how the treatment conditions were implemented beyond their descriptions, or to establish which participants contributed data to each posted outcome.

3. Trial Design

The registry record describes a randomized, triple-masked, parallel-group trial. The listed enrollment is 18, and the study status is completed. The listed study dates run from 2017-07-01 to primary completion on 2019-09-11. The phase is recorded as NA.

The two arms are named Active and Subthreshold. Both descriptions specify standard physical therapist-directed locomotor training alongside transcutaneous spinal cord stimulation. The Active description says stimulation was increased to a level that produces tingling throughout the lower extremity. The Subthreshold description says intensity was briefly raised to the lowest level detected by the participant and then ramped down. The full arm descriptions are not reported in the registry record.

Random allocation means assignment was intended to use a chance-based process, while a parallel model assigns participants to an arm rather than having each participant receive both conditions. The registry record labels masking as triple but does not identify which groups of people were masked or describe how masking was maintained. The randomization procedure, allocation concealment, and any stratification factors are not reported in the registry record.

The primary outcome is change in walking speed on the 10-meter walk test during the intervention phase, from Week 2 to Week 4. The posted arm results include the number contributing, the mean change, and its standard deviation. The record also lists secondary outcomes for walking function, several measures of spasticity, and tolerability. It does not report posted numerical results for those secondary outcomes in the registry record for this analysis.

The sponsor is Shepherd Center, Atlanta GA. The record does not report the protocol details, rationale for the enrollment target, or a statistical analysis plan. The status and dates establish the registry-recorded study timeline, but do not by themselves explain how participants were recruited, followed, or included in each analysis.

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 Change in Walking Function - 10m Walk Walking Speed (m/s), measured over Change in 10m Walk Speed (m/s) during the Intervention Phase (Week 2 test to Week 4 test).

The primary endpoint is change in walking speed on the 10-meter walk test, expressed in meters per second. The registry record describes a test in which participants walk over a sensor-containing mat and wear motion-tracking sensors. Participants could use their usual assistive devices, such as braces, a walker, or forearm crutches; the record also notes that gait kinematics were assessed.

The endpoint is defined as change from the Week 2 test to the Week 4 test during the intervention phase. A change score represents how the measured value shifted between the two stated assessments. The registry record reports the mean change and standard deviation for each arm. It does not describe the exact sign convention for change, so interpretation should stay with the stated outcome values rather than presume how increases or decreases were encoded.

Walking speed is a direct measure of performance on the specified walking task. In general, using a defined test and time interval makes the outcome interpretable as a change over the intervention phase, rather than as a single measurement at one visit. The registry record also identifies walking function and spasticity as study interests, but the primary endpoint is specifically the 10-meter walk speed change. It should not be treated as a complete measure of walking ability, daily function, or quality of life.

The posted results give a mean change of 0.16 m/s for Active and 0.06 m/s for Subthreshold. The accompanying standard deviations describe variability among observations within each arm. These summaries alone do not indicate the precision of the between-arm comparison or establish that a difference is statistically distinguishable from chance.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean change summarize?

The primary endpoint is a continuous measure: change in walking speed, measured in meters per second. A mean is the arithmetic average of the observations included in an arm's summary. Here, the registry record gives a mean change for each arm. In general, a mean offers a compact description of the center of observed values, but it can conceal variation between participants and does not show the shape of the data distribution.

The endpoint is a change score between the Week 2 and Week 4 tests during the intervention phase. Change scores focus on within-participant movement between assessments and then summarize those changes by arm. The record does not report individual values, the exact calculation convention, or whether an adjusted model was used. No assumption about those details should be made.

How should the standard deviations be read?

The posted standard deviations are 0.13 for Active and 0.08 for Subthreshold. A standard deviation describes how spread out observed values are around their mean. It is not the standard error, which concerns the precision of an estimated mean, and it is not a confidence interval. The standard deviations alone cannot determine the uncertainty of the difference between arm means.

In general, a confidence interval gives a range of effect values that are compatible with the data under the specified statistical model and confidence procedure. Its width reflects precision. No confidence interval for the between-arm comparison is reported in the registry record. A p-value would address a different question, under a specified null hypothesis and test procedure; no p-value for the primary comparison is reported either.

What does a randomized comparison require?

Random allocation is intended to make assigned groups comparable, on average, with respect to measured and unmeasured characteristics. A treatment-effect analysis generally compares outcomes between randomized groups, with the chosen method reflecting the endpoint, study design, and analysis population. The registry record identifies randomization and a parallel model, but it does not describe the random sequence, allocation concealment, model, covariate adjustment, or testing procedure.

The available primary data are arm-level summaries, not participant-level observations. A recalculated comparison from summary statistics would be an unadjusted calculation and could not reproduce an adjusted sponsor analysis if one existed. There is no sponsor inferential analysis reported in the registry record to take precedence. The posted means should consequently be read as descriptive results, not as a substitute for an unreported analysis.

What do planning illustrations mean?

The record's planning assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed trial outcomes and not observed power. The registry record does not report the trial's own sample-size justification or provide the numerical planning estimates in the registry record for this analysis.

In general, a sample-size calculation estimates the amount of information that a future design might need under specified assumptions. Its result depends on the target effect, outcome variability, error-rate choices, allocation, and statistical model. Using an effect observed in a small trial for planning can be uncertain because that estimate itself is subject to sampling variation. A planning figure should not be interpreted as evidence that a completed trial had a particular probability of detecting an effect.

Why can variability affect an analysis?

In general, over-dispersion means that observed variability is greater than a model expects. When that happens, model-based uncertainty can be understated if the model does not account for the extra variation. The primary endpoint is continuous and the registry record reports standard deviations, but it does not report an over-dispersion assessment or a model. The concept is therefore general context, not a claim about this trial's data.

Other design and data features also matter. The registry record does not report an analysis population definition, handling of missing outcomes, or sensitivity analyses. Without those details and an inferential comparison, readers cannot assess how the reported summaries relate to the planned analysis or how sensitive conclusions might be to alternate reasonable methods.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Subthreshold", "Active")
n   <- c(8, 8)
m   <- c(0.06, 0.16)
sp  <- c(0.08, 0.13)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Subthreshold  8  0.060  0.080  -0.007  0.127
CARM  Active  8  0.160  0.130  0.051  0.269

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the 10-meter walk speed change as the primary outcome and identifies secondary outcomes covering the 2-minute walk, ankle clonus drop test, muscle co-contraction during voluntary activation, the Spinal Cord Assessment Tool for Spastic Reflexes test, and stimulation tolerability. It does not report a multiplicity procedure, such as how interpretation of statistical tests across multiple outcomes was to be controlled. Nor does it report inferential results for the secondary outcomes in the registry record for this analysis.

In general, when multiple outcomes or repeated tests are examined, the chance of at least one apparently notable result can increase. A prespecified hierarchy or adjustment can help clarify how evidence across outcomes should be interpreted. Since the registry record does not report such a plan, no claim can be made about whether or how multiplicity was addressed.

Missing-data handling is not reported in the registry record. The primary outcome summaries list 8 observations in each arm, while the safety summaries list 9 at risk in each arm; the reason for these different counts is not reported. The record does not say whether primary outcome data were unavailable, excluded, or handled by a particular imputation or modeling method. No missingness mechanism should be inferred from the counts alone.

The record also does not report the analysis population, such as whether results followed the randomized assignment regardless of adherence, or whether a different population was used. It does not describe protocol deviations, exclusions, or sensitivity analyses. These omissions limit assessment of how the posted summaries were produced and whether missing data or analysis choices could affect interpretation.

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 1% reporting threshold.

The registry record reports safety counts separately for the Subthreshold and Active arms. For each arm, 9 participants are listed as at risk for serious adverse events, and 0 are listed as affected. The record also lists 9 at risk and 0 affected for other adverse events in each arm. Deaths are recorded as 0 in each arm, and no top serious adverse-event terms are listed.

These are counts as recorded, not a complete account of the type, timing, severity, or relatedness of every event. The registry record does not provide event narratives or further detail on monitoring. Zero affected in the posted counts means no events in those categories are recorded as affecting participants in these summaries; it does not establish that risk is absent or that every possible event was ruled out.

The safety counts use a different at-risk count from the primary-outcome summaries, which list 8 observations per arm. The reason for this distinction is not reported in the registry record. Safety figures should be read within their own reported context and not used to infer the number contributing to the primary endpoint or the completeness of outcome follow-up.

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

The posted results describe mean changes in 10-meter walking speed during the intervention phase: 0.16 m/s in the Active arm and 0.06 m/s in the Subthreshold arm. They also report the standard deviation and the number contributing to each arm summary. These results characterize the recorded change scores in this trial.

The means do not establish that stimulation caused a difference between arms. Randomization is an important design feature, but a causal interpretation also depends on sound implementation, outcome availability, and an appropriate analysis. The registry record does not report a confidence interval or inferential test for the primary comparison, or explain the difference between the primary outcome counts and safety counts. Thus the precision of the arm contrast cannot be assessed from the posted summaries alone.

The result also does not establish whether any observed change is important to participants or reflects a meaningful change in daily walking. The registry record does not provide a threshold for interpreting the size of a change, nor does it report the full range of individual outcomes. The primary measure is a walking-speed test; it is not equivalent to all aspects of mobility, spasticity, function, or quality of life.

The study's listed secondary outcomes indicate broader research interests, but their numerical results are not reported in the registry record. Safety summaries show zero affected in the posted serious and other adverse-event counts for both arms, but these summaries are not proof that an intervention is risk-free.

Accordingly, the result supports a descriptive statement about the reported arm means, not a definitive judgment about efficacy, safety, or generalizability. The registry record does not report enough information about participant characteristics, analysis methods, missing data, or precision to extend the interpretation beyond the recorded summaries.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a randomized design and a fully interpretable treatment-effect estimate. Randomization, triple masking, and a parallel model describe important aspects of the design. Yet the posted primary outcome consists of arm-level means, standard deviations, and contributing counts. Without a reported contrast and its uncertainty, readers cannot judge the precision of the comparison from the registry record.

The endpoint is a change score over a defined interval, which makes the time frame explicit. The arm summaries also show why reporting variability matters: a mean alone gives no sense of how dispersed individual changes may be. Standard deviations add context, but do not replace an interval estimate for the difference between arms.

The differing counts across outcome and safety summaries underscore the value of transparent reporting of analysis populations and missing-data methods. The registry record does not explain the counts, so readers cannot identify their cause. Likewise, the listed secondary outcomes raise the need for a clear multiplicity plan when interpreting a family of outcomes. That plan is not reported.

These features matter for clinical researchers and biostatisticians because design labels and numerical outcomes answer different questions. Design information describes how the study was organized; inferential reporting explains what the data support and how uncertain the estimate is. Clear reporting of both helps readers distinguish observed patterns from reliable estimates and avoid overstating evidence.

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 trial-specific details needed for a fuller assessment are not reported in the registry record. The participant characteristics relevant to interpreting walking speed are not described in the primary-outcome information. The randomization procedure, allocation concealment, and the identities of those masked are also not reported. The arm descriptions are incomplete in the record, which limits detailed reconstruction of the stimulation conditions.

The primary summaries list 8 observations in each arm, while safety summaries list 9 at risk in each arm. The record does not explain the difference or report the reason for missing primary outcome observations, if any. It does not define an analysis population or describe how incomplete data were handled. This makes it difficult to assess possible selection or missing-data effects.

No confidence interval, p-value, or sponsor-reported inferential comparison is reported for the primary endpoint. The analysis model, covariate adjustment, and statistical testing procedure are not described. The record also does not report a multiplicity plan despite listing secondary outcomes, nor numerical results for those outcomes in the registry record for this analysis.

The registry record does not report a sample-size justification or numerical planning estimates in the registry entries. The primary endpoint captures walking speed on a specified test, but the record does not provide a threshold for interpreting the importance of change. The limited safety counts do not describe event details or establish absence of risk. These limitations restrict interpretation to the posted summaries and reported design features.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Spinal Cord Stimulation to Augment Activity Based Therapy — NCT03240601.
• Registry record last updated 2022-01-25; status last verified 2021-12.
• Results first posted 2022-01-25.
• 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

NCT03240601 is a completed randomized, triple-masked, parallel-group study sponsored by Shepherd Center, Atlanta GA. The listed enrollment is 18. The registry dates are 2017-07-01 for study start and 2019-09-11 for primary completion.

The trial compares Active and Subthreshold transcutaneous spinal cord stimulation during locomotor training. The primary outcome is change in 10-meter walk speed from the Week 2 test to the Week 4 test during the intervention phase. Posted mean changes are 0.16 m/s for Active and 0.06 m/s for Subthreshold, with standard deviations of 0.13 and 0.08; the primary summaries list 8 observations per arm.

The registry record lists additional walking, spasticity, and tolerability outcomes. It reports 0 affected for serious and other adverse-event categories in each arm, with 9 at risk per arm. Inferential results, missing-data methods, and the statistical analysis plan are not reported in the registry record.