Assessment of the Effect of Botulinum Toxin in Extensor Digitorum Brevis Via Strain Gauge and Nerve Conduction Studies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessment of the Effect of Botulinum Toxin in Extensor Digitorum Brevis Via Strain Gauge and Nerve Conduction Studies (NCT00822523), a randomized na study. The primary outcome is Change in Measured Force (Change From Baseline) (Using Strain Gauges) of Dorsiflexion of Digits 2 and 3 ("Force of EDB") After vs. Before Botulinum Toxin Injection Into EDB.

2. Clinical Question

This is a measurement-feasibility question, not simply a question about whether an injection changes muscle force. The registry description identifies force measured with a strain gauge as the primary outcome and describes nerve conduction and surface electromyography as established measurement approaches relevant to the study’s purpose. The record includes a placebo arm as well as two toxin-dose arms, but it does not report primary outcome results or estimates comparing the arms.

The registered outcome assesses force before and after injection at specified visits. Therefore, the intended question includes both whether force can be tracked over time and how the observed force measure relates to other physiological measures. The registry record does not report whether the strain-gauge method proved feasible, how closely its measurements corresponded to the other measures, or whether any changes differed across groups.

3. Trial Design

This was a randomized, parallel-group study with quadruple masking. The registry record lists enrollment of 13 and a completed status. The study start is recorded as 2009-01, with primary completion recorded as 2009-03. The phase is listed as NA. The sponsor was Loma Linda University.

Three arms are described: a single intramuscular injection of botulinum toxin type A, 20 units; a single intramuscular injection of botulinum toxin type A, 2 units; and saline as placebo. The toxin injections were described as going into the EDB muscle of the foot. The placebo description specifies the right EDB. The record does not report how participants were allocated among the three arms, or whether allocation was balanced.

Quadruple masking indicates that the registry record classifies the study as masked across four roles, but the identities of those roles and the practical masking procedures are not reported in the registry record. The method used to generate the random sequence and conceal allocation is also not reported. These details matter for evaluating how allocation and knowledge of treatment could have influenced conduct or measurement, but cannot be inferred from the masking and allocation labels alone.

The primary outcome description specifies force measurement before injection and at Day 1, Day 2, Day 4, Day 14, Day 21, and Month 4. Baseline was defined using the mean of 3 force measurements obtained before injection. The registry also lists secondary outcomes concerning baseline force stability, force change between Day 14 and Day 21, adverse effects, and correlations between changes in compound muscle action potential (CMAP) and surface electromyography (SEMG) measures. The record lists 17 outcome measures and 46 analyses. Full analysis procedures and outcome results are not reported in the registry record.

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 Measured Force (Change From Baseline) (Using Strain Gauges) of Dorsiflexion of Digits 2 and 3 ("Force of EDB") After vs. Before Botulinum Toxin Injection Into EDB, measured over Baseline (3 times) then following single injection of botulinum toxin into EDB with testing at Day 1, Day 2, Day 4, Day 14, Day 21, and Month 4.

The primary endpoint is change from baseline in force measured by strain gauges during dorsiflexion of digits 2 and 3 together. Force is expressed in kg. The registry describes the outcome as a mean, with standard deviation as the dispersion measure. Baseline is the mean of the 3 force measurements taken before injection; subsequent measurements are compared with this baseline.

The measure is intended to quantify force in the EDB, a small foot muscle, following a single injection of botulinum toxin type A or placebo. Measuring force directly can offer a way to track muscle output over time. In this feasibility study, the strain-gauge measure is of interest both as an outcome and as a measurement approach that could be considered alongside nerve conduction studies and SEMG. The registry’s stated rationale is to determine whether temporary weakness induced by a local injection can be measured with a strain gauge in addition to those other approaches.

The scheduled assessments extend from Day 1 through Month 4, allowing the registered endpoint to address measurements at more than one time after injection. The outcome description does not specify a single follow-up visit as the only primary assessment. The registry record does not report the observed force means, standard deviations, changes from baseline, or comparisons among the three groups. It also does not report a threshold defining a meaningful or detectable force change. As a result, the endpoint’s measurement purpose is clear, but its observed performance and the magnitude or precision of any changes cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the force outcome represent?

The primary measure is continuous: force is recorded in kg rather than classified into a set of categories. The registry describes the reported summary as a mean and the dispersion as a standard deviation. In general, a mean describes the central value of a set of measurements, while a standard deviation describes how spread out individual measurements are around that mean. These summaries answer different questions: the mean concerns average force, and the standard deviation concerns variability among the measurements being summarized.

The baseline is defined as the mean of the 3 force values collected before injection. Subsequent measurements are compared with that baseline. In general, using a baseline summary can reduce reliance on a single pre-treatment reading, but it does not by itself establish that measurements are stable or that a follow-up change is caused by treatment. The registry lists stability of baseline measurements as a secondary outcome, but its result is not reported in the registry record.

Why are several follow-up times relevant?

Force was scheduled for measurement at Day 1, Day 2, Day 4, Day 14, Day 21, and Month 4 after a single injection, in addition to repeated baseline measurement. Multiple visits allow a study to examine how a measure changes over time rather than focusing only on one follow-up. They also create multiple possible comparisons. In general, interpreting measurements across visits requires knowing which time points were prespecified as key, how repeated observations were handled, and whether all planned measurements were available. Those analysis details and the observed time-specific force values are not reported in the registry record.

Repeated measurements from the same participant are generally related, rather than independent observations. General statistical methods for repeated data account for that dependence when estimating changes or comparing groups over time. The registry record does not identify a model or other procedure used for this purpose, so it is not possible to say how within-participant dependence was handled.

What would precision information add?

In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. Its width conveys precision: a narrower interval indicates a more precise estimate, while a wider interval indicates greater uncertainty. A confidence interval does not show the probability that a particular treatment effect is true. The registry record does not report confidence intervals for the primary force outcome, so the precision of any estimated change or group contrast is unknown.

A p-value, in general, describes how compatible data are with a specified null hypothesis under the assumptions of a statistical test. It does not measure the size or clinical importance of an effect. No primary-outcome p-value or test procedure is reported in the registry record. Therefore, neither statistical significance nor the strength of evidence for a difference can be assessed from the registered outcome description alone.

How should the correlation outcomes be understood?

The listed secondary outcomes include correlations between percent change in CMAP and percent change in SEMG, using different SEMG processing windows and measures. In general, correlation describes the direction and strength of association between two variables; it does not establish that one measure causes a change in the other, nor that the two measures can be used interchangeably. Comparing a strain-gauge measure with nerve conduction and SEMG measures could inform whether these assessments track related changes, but the planned correlations and their results are not reported in the registry record.

Different SEMG windows or summaries may capture different aspects of the recorded signal. General measurement principles suggest that processing choices can affect estimates, so the exact definition and reliability of each measure matter. The record names several processing approaches but does not give the correlation coefficients, uncertainty estimates, or analysis details. No conclusion about agreement or relative performance can be drawn from the outcome titles alone.

What do the planning assumptions mean?

The registry’s sample-size description characterizes planning calculations as illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also says the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the study was designed or completed with a particular level of power. The registry record does not report the underlying observed effect or the numerical planning results in the information available for this analysis. The description does not establish that these assumptions were the trial’s original design assumptions.

In general, a sample-size calculation depends on assumptions about the target effect, variability, type I error, allocation, and analysis. If those assumptions differ from the study’s actual design or data, the calculation may not describe the study’s operating characteristics. The posted planning assumptions should therefore be understood as illustrations, not as a substitute for results, precision estimates, or a documented protocol-based justification.

Overall, the endpoint definitions make the intended measurement schedule and summary type understandable. The statistical procedures used to analyze those measurements, and the resulting estimates and uncertainty, are not reported in the registry record. Explanations of means, dispersion, repeated measurements, correlation, confidence intervals, and p-values above are general statistical context rather than a description of analyses known to have been performed in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures and 46 analyses. These counts indicate that the record encompasses multiple planned or listed measurements and analyses, including force outcomes, safety outcomes, and correlations involving CMAP and SEMG. The record does not report how the analyses relate to one another, which were designated primary or secondary in a statistical analysis plan, or whether any multiplicity adjustment was used.

In general, evaluating many outcomes or time points can increase the chance of finding an apparently notable result by chance if each test is treated independently. Statistical approaches can address multiplicity, but the appropriate approach depends on the questions and analysis plan. No correction procedure, hierarchy among outcomes, or prespecified strategy for interpreting multiple tests is reported in the registry record. Since the primary force results are also not reported, the effect of any multiplicity procedure cannot be assessed.

Missing-data procedures and analysis populations are likewise not reported in the registry record. The record does not state how many participants contributed measurements at each visit, whether any observations were missing, how missing values were handled, or whether analyses followed an intention-to-treat, per-protocol, or other population definition. These details are important for longitudinal outcomes because the available measurements may differ across visits. Without them, it is not possible to determine how complete the outcome data were or how the analysis population was defined.

The registry’s outcome descriptions and study design do not supply the missing analysis details. Any assumptions about adjustment for multiple testing, imputation, exclusions, or handling of incomplete follow-up would be speculative. Those methods are not reported in the registry record.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse effects separately from other adverse effects for each group. It records 0 participants with serious adverse effects among 5 at risk in the 20-unit toxin group, 0 among 4 at risk in the 2-unit toxin group, and 0 among 4 at risk in the placebo group. These are registry counts; they do not describe the nature of any events or establish the completeness of safety follow-up.

For other adverse effects, the record lists 3 participants among 5 at risk in the 20-unit group, 1 among 4 at risk in the 2-unit group, and 0 among 4 at risk in the placebo group. These figures concern participants recorded as affected, not necessarily the total number of separate events. The registry does not provide event terms for these other adverse effects, their timing, severity, duration, or relationship to the injection in the information.

Deaths are not reported in the registry record. The safety counts should be read as descriptive observations from a small study, not as estimates that establish comparative safety. The record does not report a statistical comparison of adverse effects between groups.

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

The registered design addresses a useful measurement question: whether force in the EDB can be tracked with a strain gauge after a local injection, and how that measure relates to nerve conduction and SEMG assessments. The outcome schedule and measurement definitions show how the study intended to investigate the question. The registry record does not report the force results or the correlation results, so it does not establish whether the strain gauge detected a change or how its measurements related to the other methods.

Nor does the record establish a comparative effect of the two toxin doses versus saline. Although the study was randomized and included three arms, group-level outcome estimates and their uncertainty are not reported. No conclusion about the direction, magnitude, or precision of any between-group difference can be drawn from the design description alone. The record also does not report whether the measurement procedure was practical, repeatable, or acceptable to participants.

The study’s stated purpose was feasibility, and the registered secondary outcomes include baseline stability and correlations between measurement methods. These are relevant to evaluating a measurement approach, but their results are not reported in the registry record. The absence of those results should not be interpreted as evidence that the measures were uninformative or that no changes occurred.

More generally, a registered endpoint tells readers what investigators intended to assess; it does not substitute for observed data. Statistical interpretation requires estimates, uncertainty, analysis details, and context. Without the primary outcome results and supporting methods, the record permits an account of the question and design, but not an effectiveness or measurement-performance conclusion. No medical decision can be based on the design description alone.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it centers on measurement, not only on a treatment contrast. A strain gauge was used to quantify force from a small foot muscle, while the registered purpose also involved established nerve conduction and SEMG measures. The study therefore raises a general methodological question: can a direct force measure provide useful information alongside physiological measurements?

Repeated readings before injection and assessments across several post-injection visits create an opportunity to examine both baseline stability and change over time. This structure highlights why endpoint definition matters. A single follow-up value, an average change across visits, and a trajectory over time answer different questions. The registry record gives a schedule but does not report which analytic summary was used to draw conclusions.

The planned correlations also illustrate a distinction important in measurement research. Association between two measures can be informative, but correlation alone does not show agreement or interchangeability. A thorough assessment generally needs clearly defined measurement procedures, estimates of variability, and uncertainty around relationships between measures. The registry lists related outcomes, but those estimates are not reported in the registry record.

Finally, the record shows why design details and results need to be considered together. Randomization, masking, a placebo arm, and multiple dose groups describe features of the planned comparison, while outcome data and analysis methods would be needed to assess what the study found. The posted information makes the feasibility question visible but does not provide the results needed to judge the measurement approach.

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.

Several trial-specific limitations of interpretation follow from information not reported in the registry record. Participant eligibility criteria, baseline characteristics, allocation procedures, and the identities of the masked roles are not described. Although the study is classified as randomized and quadruple-masked, those labels alone do not show how randomization or masking was implemented.

The registry does not report the primary force values or the results of the listed secondary outcomes. It is therefore not possible to assess the size or precision of any changes, the stability of baseline force, or the relationships between strain-gauge, CMAP, and SEMG measures. The record also does not describe the statistical model, handling of repeated observations, analysis populations, or missing-data procedures. These omissions limit evaluation of both the estimates and the risk of bias in their analysis.

Enrollment is listed as 13, but the distribution of participants across arms and the number contributing data at each visit are not reported. The recorded safety counts show that the arm-specific numbers at risk were small, limiting what descriptive counts alone can establish about uncommon events. Follow-up completion and the details of adverse-event ascertainment are not reported in the registry record.

Finally, the study’s stated purpose is feasibility and the record includes multiple measurement and analysis outcomes. Without the results, prespecified analysis hierarchy, and multiplicity procedures, it is not possible to determine which findings were most informative or how uncertainty across the various outcomes was addressed. These limitations concern what can be concluded from the registry record, not proof that the study procedures or results were inadequate.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Assessment of the Effect of Botulinum Toxin in Extensor Digitorum Brevis Via Strain Gauge and Nerve Conduction Studies — NCT00822523.
• Registry record last updated 2018-09-05; status last verified 2018-08.
• Results first posted 2016-08-31.
• 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

The registry describes a completed, randomized, quadruple-masked, parallel-group feasibility study sponsored by Loma Linda University. Enrollment is listed as 13. The study compared single injections of botulinum toxin type A at 20 units or 2 units with saline placebo in an assessment of EDB force.

The primary outcome was change from baseline in force during dorsiflexion of digits 2 and 3, measured with a strain gauge in kg. Baseline was defined as the mean of 3 pre-injection readings, with planned post-injection testing at Day 1, Day 2, Day 4, Day 14, Day 21, and Month 4. The stated purpose was to assess strain-gauge feasibility alongside nerve conduction and SEMG measures.

Primary and secondary outcome results, analysis details, and missing-data procedures are not reported in the registry record. The record lists no serious adverse effects in any group and reports other adverse effects in the toxin groups, with none recorded for placebo.