Efficacy of Functional Electrical Stimulation (FES) in Persons Receiving Botulinum Neurotoxin for Upper Extremity Spasticity: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy of Functional Electrical Stimulation (FES) in Persons Receiving Botulinum Neurotoxin for Upper Extremity Spasticity (NCT00462449), a randomized na study. The primary outcome is Change From Baseline in Arm Function Based on Motor Activities Log (MAL-O).

2. Clinical Question

The clinical question concerns whether adding device-assisted stimulation to repetitive task practice is associated with a different change in arm function than repetitive task practice alone in this study population. Both arms are described in the context of botulinum neurotoxin treatment; the comparison is the addition of FES and associated instruction, not FES versus no therapy.

The primary outcome is the Motor Activities Log observer rating, reported as change from baseline. It focuses on use of the upper extremity in activities of daily living. The registry also lists change in dexterous hand function measured by the Action Research Arm Test and change in self-performance in activities of daily living assessed with the MAL self-report. Results for those secondary outcomes are not reported in the registry record.

3. Trial Design

This was a randomized, parallel-group study with an enrollment of 23. The registry lists masking as double, while the official title describes the study as single blind. The record does not explain this difference or identify which groups were masked. The phase is listed as NA. The study is marked completed.

The two groups were repetitive task practice alone and repetitive task practice with FES. The device intervention is identified as the Ness H200. The record describes FES as electrical stimulation intended to activate muscles, alongside therapist-designed repetitive activities. The study context is people receiving botulinum neurotoxin type A injections for upper extremity spasticity.

The registry lists a primary outcome of change from baseline in arm function based on the observer-rated Motor Activities Log, with a 12-week timeframe. The posted primary results are identified as per protocol. The result groups contain 10 participants for FES plus repetitive task practice and 13 for repetitive task practice alone. These are the counts reported for the primary results; the registry does not report a participant flow account explaining exclusions or losses.

The start is listed as 2007-11 and primary completion as 2010-01. The sponsor is the University of Pittsburgh. The registry record does not report the protocol’s sample-size justification, recruitment targets by arm, allocation concealment methods, or detailed procedures for generating and implementing the randomization sequence. It also does not describe the specific therapy schedule or the amount and timing of device use.

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

Analysis population for the primary outcome, as defined in the registry: Per protocol. Number was determined based on the number of participants enrolled and eligible.

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 From Baseline in Arm Function Based on Motor Activities Log (MAL-O), measured over 12 weeks.

The primary endpoint is change from baseline in arm function measured with the observer-rated Motor Activities Log (MAL-O), assessed at 12 weeks. The registry describes the measure as observer ratings of upper extremity function during activities of daily living. Its scale runs from 0, meaning not used, to 5, meaning normal function; the record says no subscales were used.

Change scores are intended to express how a participant’s measured function differs from the baseline assessment by the specified follow-up. The registry posts a mean change and a 95% confidence interval for each arm. It does not post baseline values, participant-level changes, or a direct between-arm estimate for this endpoint. As a result, the arm-specific means describe the observed changes in the respective per-protocol groups, but do not themselves quantify the randomized treatment contrast.

Observer ratings are used to capture reported performance of the arm in daily activities, rather than only performance on a specific laboratory task. That makes the endpoint relevant to the functional focus of repetitive task practice. The registry does not provide further information about observer training, rating procedures, reliability, or how assessments were kept masked.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The principal statistical summaries are means with 95% confidence intervals for a continuous change score. The outcome is the change from baseline in MAL-O at 12 weeks. The registry identifies the parameter as a mean and the dispersion as a 95% confidence interval; it does not provide a standard deviation or details of the calculation used for the intervals.

What does a confidence interval express?

In general, a confidence interval quantifies the uncertainty associated with an estimate under a specified statistical procedure and its assumptions. It does not describe the spread of individual participant scores, and it is not a guarantee that the true value lies within the particular interval. For this trial, the posted intervals are attached to the mean change within each arm. They do not represent a confidence interval for the difference between arms.

Why is a direct comparison important?

In a randomized parallel-group study, the treatment question is ordinarily expressed as a contrast between the assigned groups. For a continuous endpoint, that could be a difference in mean change, with an interval and an appropriate test if those analyses were specified. The registry says the two-arm comparison values are missing or not estimable. Accordingly, the available arm-specific means cannot replace that contrast. A comparison of whether each arm’s interval includes a particular value would answer a different question from whether the groups differ.

The registry’s record of 10 participants in the FES and repetitive task practice arm and 13 in the repetitive task practice alone arm relates to the primary per-protocol outcome summary. It does not, by itself, explain the analysis model, degrees of freedom, handling of repeated measurements, or whether any covariate adjustment was applied. Those details are not reported in the registry record. The record also does not state whether the primary analysis used a model of follow-up values adjusted for baseline or an analysis of change scores; the outcome is named as change from baseline, but that label does not supply all modeling details.

What does per protocol imply?

In general, a per-protocol analysis evaluates outcomes among participants meeting specified eligibility or adherence criteria, as defined by a study. The registry identifies the primary population as per protocol and says the number was determined from participants enrolled and eligible. It does not state the precise criteria, participant disposition by arm, or whether eligibility decisions were made before or after outcomes were known. This limits assessment of how the analysis population was formed and how it relates to the randomized groups.

How should uncertainty and small groups be considered?

In general, estimates based on fewer observations tend to be less precise than estimates based on more observations, although the degree of uncertainty also depends on outcome variability and the analysis. The two reported group counts are modest, and the confidence intervals show uncertainty around their means. The record does not provide standard deviations, participant-level data, or an adjusted comparison from which to examine the precision of the treatment contrast. It would therefore be inappropriate to reconstruct a between-group test or confidence interval from these summaries.

The registry includes a description of planning illustrations based on the observed effect: two-sided significance level 0.05, equal allocation, and a normal approximation, with the target effect described as a stated fraction of the observed effect. It distinguishes participants per arm for non-time-to-event outcomes. These are described as planning illustrations rather than the trial’s own design justification. The registry does not report the trial’s original sample-size justification, and the illustration assumptions should not be interpreted as evidence of observed power or as proof that the enrolled sample was adequate.

General statistical interpretation also depends on prespecification. A protocol may define the primary analysis, covariates, handling of missing outcomes, and decision threshold in advance. Those details, along with interim analyses and any multiplicity adjustment, are not reported in the registry record. The absence of those details does not establish that a method was or was not used; it means the posted record does not allow readers to verify it.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and two secondary outcomes: change in dexterous hand function measured by the Action Research Arm Test, and change in self-performance in activities of daily living assessed with the MAL self-report. The primary outcome is MAL-O change at 12 weeks. Results for the secondary outcomes are not reported in the registry record. The record indicates three outcome measures overall, but does not provide result summaries for the two listed secondary outcomes.

When a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures can be used to control the interpretation of a family of tests, or outcomes can be designated in advance as primary and secondary. The registry record does not report whether any multiplicity adjustment was planned or applied, or how the secondary outcomes were intended to inform conclusions.

Missing-data handling is also not reported in the registry record. The primary results are per protocol, and the record says the number was determined based on participants enrolled and eligible. It does not give a flow of randomized participants through follow-up, reasons for exclusions, the number with missing primary outcomes, or any method for handling missing observations. It is therefore not possible to determine from the posted results whether all randomized participants contributed to an analysis or whether missingness could have affected the estimates.

The registry record does not report the detailed statistical analysis plan, interim analyses, or whether the reported analysis population and endpoint analyses were prespecified. These omissions prevent a full evaluation of selective reporting and analysis choices. They should be treated as unavailable information, not as evidence that a particular method was omitted in the conduct of the trial.

11. 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% reporting threshold.

The adverse-event record lists zero serious adverse events among 13 participants in the group labelled “Chedoke-McMaster Assessment Hand Impairment 2, 3 - RTP Alone” and zero among 10 in the group labelled “Chedoke-McMaster Assessment Hand Impairment 4-6 RTP + FES.” The registry lists zero other adverse events in each of those groups as well.

These figures describe what is entered in the registry for the listed groups. They do not establish that no adverse events occurred outside the recorded categories or reporting period. The record does not provide the adverse-event collection timeframe, definitions, severity grading, or details of how events were assessed. Death counts are not reported in the registry record.

Zero reported events in groups of these sizes should be interpreted as an absence of events recorded in these entries, not as proof that an intervention has no safety risks. The group labels in the adverse-event record differ from the primary outcome arm titles, although they identify RTP alone and RTP plus FES. The registry does not explain the additional impairment categories in those labels.

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

The posted primary results describe mean changes in observer-rated arm function within the two per-protocol groups at 12 weeks. Each mean is accompanied by a 95% confidence interval. These summaries provide information about the observed arm-specific changes and their precision, but the registry does not provide the direct comparison needed to estimate the incremental difference associated with adding FES.

For that reason, the figures do not establish that the groups had the same outcome, nor do they establish that one group had a better outcome. The missing or non-estimable two-arm comparison leaves the central randomized contrast unresolved in the posted results. The arm-level values alone cannot determine statistical significance or the magnitude of a between-group effect.

The findings also apply to the reported analysis population, which was per protocol, rather than necessarily to all randomized participants. The registry does not describe exclusions, losses to follow-up, or missing-data procedures. Results for the listed secondary outcomes are likewise not reported in the registry record. These gaps limit how comprehensively the outcome evidence can be interpreted.

The study question is specific: repetitive task practice with FES versus repetitive task practice alone in the context of botulinum neurotoxin treatment for upper extremity spasticity. The registry record does not establish how the results generalize beyond that population, intervention, outcome, and 12-week timeframe. These statistical summaries are not individualized predictions and do not offer medical advice.

In general, evidence about an intervention is stronger when a prespecified between-group estimate, its uncertainty, the analysis population, and missing-data handling are all available. Here, arm-specific means and intervals are posted, but the direct comparison and several analysis details are not. The appropriate reading is therefore descriptive and limited to the summaries recorded.

13. Why This Trial Matters Statistically

This study is statistically notable because its primary outcome is a functional measure tied to daily activities, while the intervention comparison isolates the addition of device-based FES to repetitive task practice. The randomized parallel-group design is suited to comparing those assigned approaches, but the registry’s posted primary results are arm-specific rather than a direct estimate of the randomized contrast.

That distinction is important for readers of clinical trial results. Two group means with separate confidence intervals can describe each group, but the treatment question concerns the difference between groups. Without a reported contrast and its uncertainty, the numerical summaries do not establish whether the observed changes differ beyond what could be expected from sampling variability. The registry explicitly indicates that the two-arm continuous comparison is missing or not estimable.

The record also illustrates why analysis populations and outcome reporting matter. The primary result is per protocol, the registry lists secondary outcomes without their results, and details of missing-data handling and analysis procedures are not reported. These issues affect the completeness and interpretability of the evidence, independently of the direction of the arm-specific means.

For biostatisticians and clinical researchers, the entry is a reminder to distinguish a within-arm change from a between-arm effect, and to distinguish planning illustrations from the trial’s original sample-size rationale. It also underscores the value of reporting the prespecified analysis, participant flow, and results for all registered outcomes. The posted record supports a bounded account of what was measured and summarized, but not a complete evaluation of the comparative treatment effect.

14. 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 most immediate limitation is that the registry does not post an estimable two-arm comparison for the continuous primary endpoint. Although each arm has a mean change and a 95% confidence interval, there is no reported between-arm estimate, confidence interval, or p-value. The principal comparative question therefore cannot be answered from the posted primary results.

The primary analysis is per protocol, but the record does not state the criteria for inclusion in that population or provide participant flow and reasons for any exclusions. The counts reported for the primary summaries are 10 and 13. Missing-outcome counts and missing-data methods are not reported in the registry record, so the effect of incomplete follow-up cannot be assessed.

Only the primary outcome summaries are posted. The Action Research Arm Test and MAL self-report are listed as secondary outcomes, but their results are not reported in the registry record. The record does not describe adjustment for multiple outcomes or provide a detailed statistical analysis plan, including model specification, baseline adjustment, or interim analyses.

The registry lists masking as double, whereas the official title calls the study single blind; the record does not clarify this difference or describe who was masked. It also does not provide detailed information about randomization implementation, the therapy schedule, device-use procedures, or observer-rating procedures. The adverse-event entries report zero serious and other adverse events in the listed groups, but the collection timeframe and death counts are not reported in the registry record.

Finally, the outcome is assessed at 12 weeks, and the posted summaries do not describe longer-term outcomes. The record’s planning-illustration assumptions are not the same as a reported justification for the trial’s enrolled sample size. Together, these limitations constrain interpretation of precision, comparative effect, safety reporting, and generalizability.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy of Functional Electrical Stimulation (FES) in Persons Receiving Botulinum Neurotoxin for Upper Extremity Spasticity — NCT00462449.
• Registry record last updated 2014-06-20; status last verified 2014-06.
• Results first posted 2014-06-20.
• 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.

18. Record Summary

NCT00462449 is a completed randomized parallel-group study sponsored by the University of Pittsburgh, with enrollment of 23. It compares repetitive task practice alone with repetitive task practice plus FES through the Ness H200 in the context of botulinum neurotoxin treatment for upper extremity spasticity. The registry lists masking as double; the official title describes the study as single blind.

The primary outcome is per-protocol change from baseline in observer-rated MAL-O arm function at 12 weeks. The posted mean changes are 1.52 units for FES plus repetitive task practice and 1.79 units for repetitive task practice alone, with separate 95% confidence intervals. A two-arm comparison is not reported as estimable. Secondary outcome results and details of missing-data handling and the statistical analysis plan are not reported in the registry record.