Botulinum Toxin as a Novel Treatment for Prevention of Post-Traumatic Elbow Stiffness: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Botulinum Toxin as a Novel Treatment for Prevention of Post-Traumatic Elbow Stiffness (NCT01129583), a randomized na study. The primary outcome is Disabilities of the Arm, Shoulder, and Hand (DASH) Questionnaire.

2. Clinical Question

The central comparison is between two randomized groups following elbow fracture surgery. The registry record describes the study as double blind and placebo controlled, and its design fields list quadruple masking. These descriptions indicate an effort to mask treatment assignment, but the identities of the masked parties and the practical masking procedures are not reported in the registry record.

The question is about a patient-reported measure of upper-limb disability and symptoms at the stated follow-up, rather than a direct measure of stiffness alone. The study summary gives the rationale as reducing postoperative stiffness and improving function. The endpoint therefore addresses a broader functional outcome that includes symptoms, while the listed secondary outcomes include range of motion and an elbow-function score.

3. Trial Design

The registry record describes a randomized, parallel-group study comparing botulinum toxin A with saline. The study is listed as completed, with enrollment of 18 participants. The recorded start is 2003-11 and primary completion is 2009-09. The phase is listed as NA. Columbia University is identified as the sponsor.

The botulinum toxin arm had 9 participants in the posted primary outcome results, as did the saline arm. The intervention descriptions specify 100 U in the biceps and 100 U in the brachialis for each arm, with the active treatment identified as botulinum toxin A and the comparator as saline. The registry’s summary describes injections into muscles surrounding the elbow following surgical treatment of an elbow fracture.

The study is described in its summary as randomized, double blind, and placebo controlled. The registry design fields list quadruple masking and a parallel model. The record does not explain which groups of people were masked, how masking was maintained, or whether treatment assignments were concealed during enrollment. Those operational details are not reported in the registry record.

The primary outcome was the DASH questionnaire score at 1 year post-op. The recorded outcome measure is continuous, expressed on a scale from 0 to 100, and summarized by a mean and standard error for each arm. The registry lists elbow range of motion and the Broberg Morrey Composite Elbow Function Score as secondary outcomes. It reports 3 outcome measures and 3 analyses, but details sufficient to describe all analysis populations or methods are not available in the record.

The study’s design rationale, eligibility criteria, allocation procedure, and sample-size justification are not reported in the registry record. The registry also does not report whether interim analyses were planned or conducted. Consequently, the design can be described from the recorded randomized, masked, parallel comparison, but a fuller assessment of how the trial was planned and conducted is not possible from these details alone.

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.

Before assignment: Of the 59 patients assessed for eligibility, 41 patients were excluded based on the listed inclusion/exclusion criteria.

Overall Study

Reasons for not completing this period:

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 Disabilities of the Arm, Shoulder, and Hand (DASH) Questionnaire, measured over 1 year post-op.

The primary endpoint was the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire score at 1 year post-op. The registry describes the DASH as a measure of physical function and symptoms in people with musculoskeletal disorders of the upper limb. The recorded score is on a scale from 0 to 100, where 0 represents no disability and 100 represents maximum possible disability. Thus, lower scores correspond to less reported disability on this scale.

The disability and symptom component contains 30 items, each scored from 1 to 5. The record also describes optional high-performance sport/music or work items. The stated score is calculated by averaging the relevant item scores, subtracting one, and multiplying by 25. The posted primary results summarize the outcome as a mean with a standard error for each treatment arm.

A patient-reported measure can capture perceived difficulties and symptoms that may not be fully represented by a physical examination. This makes the DASH relevant to a trial concerned with both stiffness and functional recovery. It is not, however, a direct measurement of elbow range of motion, and the registry lists range of motion separately as a secondary outcome. The primary endpoint therefore addresses upper-limb disability and symptoms rather than stiffness in isolation.

The endpoint’s stated follow-up is 1 year post-op. The registry does not report the questionnaire completion rate, the handling of incomplete questionnaires, or whether the posted means include all randomized participants. Those details matter when interpreting a patient-reported outcome because the observed group summaries depend on which assessments were available and included.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each participant’s DASH score lies on a scale from 0 to 100, and the posted arm-level results are expressed as means. For a continuous measure, a mean describes the central value of the observed scores in a group. It does not describe the full shape of the score distribution or how much individual participants differ from one another. The registry reports a standard error alongside each mean, which describes the estimated precision of that group mean rather than the spread of individual scores.

What does the reported t-test assess?

The registry reports a two-sided t-test comparing the botulinum toxin and saline groups. In general, a two-sided test evaluates departures in either direction from a null comparison, rather than testing only whether one specified group is higher or lower. A t-test uses the observed group summaries and assumptions about the data to assess how compatible the results are with the null hypothesis of no difference in group means. The registry does not report further detail about the particular t-test implementation or its assumptions.

The reported p-value is 0.06. In general, a p-value is a measure of compatibility between the observed data and a specified null model, conditional on the analysis assumptions. It is not a measure of effect size, clinical importance, or the chance that the result arose by chance. A result near a conventional threshold should not be converted into a binary claim that there is or is not an effect. Interpretation also depends on the magnitude and precision of the estimate, the study design, outcome relevance, and the limitations of the available record.

Why does a confidence interval matter?

A confidence interval gives a range of values that are compatible with the data and the method used to construct the interval. It can communicate the uncertainty around an estimated treatment contrast more directly than a p-value alone. The registry lists a 95% confidence level for the comparison, but the lower and upper confidence limits are not reported. As a result, the interval cannot be interpreted from the registry record. The reported standard errors apply to each arm’s mean; they are not the missing confidence limits for the difference between arms.

The posted results do not give a recalculated unadjusted comparison because the required values are missing or not estimable for a two-arm comparison of this continuous endpoint. Recalculation from summary statistics would require enough information to reconstruct the comparison and its uncertainty. It would not replace the sponsor’s reported analysis when the registry reports an analysis. The absence of a recalculated estimate means that no independent numerical contrast or interval should be inferred from the arm summaries alone.

What can standard errors tell the reader?

Standard error concerns the uncertainty of an estimated mean, not the variation among participants. In general, standard errors tend to be smaller when estimates are more precise and larger when they are less precise. They should not be interpreted as a range containing most individual scores. Assessing participant-level variability would require a measure such as a standard deviation or access to the individual observations; neither is reported with these primary results.

For continuous outcomes, the t-test’s reliability depends on the data and the assumptions of the chosen test. General considerations include the distribution of scores, the independence of observations, and whether the method handles the pattern of variability appropriately. The registry record does not report diagnostic checks or alternative analyses. With only 9 participants in each arm, the posted summaries offer limited information about distributional shape, outliers, or how sensitive the comparison might be to individual scores. These are interpretive cautions, not evidence that a particular assumption was violated.

What are planning illustrations?

Sample-size illustrations based on an observed effect are planning exercises, not evidence about the study’s actual design or its probability of detecting an effect. General planning calculations depend on assumptions such as the significance level, allocation, statistical model, and the effect size selected for detection. The registry record does not report the trial’s own sample-size justification, so any planning illustration should not be described as the planned sample size or as observed power. Power is a design concept and cannot be recovered as a meaningful post-trial verdict from the observed result alone.

Uncertainty is especially important when the observed effect is used to plan a future study, because an estimate from a small trial may be imprecise. General planning practice can therefore examine a range of plausible effect sizes rather than treating one observed estimate as certain. Any such planning values are hypothetical inputs for future design, not additional findings from this trial.

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("Botulinum Toxin", "Saline")
n   <- c(9, 9)
m   <- c(27, 54)
sp  <- c(11, 8)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  Botulinum Toxin  9  27.000  33.000  1.634  52.366
CARM  Saline  9  54.000  24.000  35.552  72.448

11. Analyses Reported by the Sponsor

The registry reports the sponsor’s own comparison as a two-sided t-test, with p = 0.06. It also reports a mean DASH score of 27.0 with a standard error of 11.0 for botulinum toxin and a mean of 54.0 with a standard error of 8.0 for saline. These are the posted arm summaries and the reported inferential result.

A separate unadjusted recalculation is not available for this continuous two-arm comparison because the necessary comparison values are missing or not estimable in the registry record. The registry does not report a treatment-effect estimate or confidence limits for the t-test. Accordingly, there is no independent recalculated estimate to place alongside the sponsor’s p-value, and no basis for claiming that the sponsor’s result has been contradicted by a recalculation.

The p-value should be interpreted as the result of the sponsor’s reported test, not as a measure of the size or clinical importance of the difference between the group means. The lower observed mean in the botulinum toxin group describes the direction of the posted group summaries, while the p-value reflects the test result under its assumptions. The missing interval and analysis details limit how precisely the treatment contrast can be understood from the registry record.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and 3 analyses. The primary endpoint is the DASH score at 1 year post-op. Elbow range of motion and the Broberg Morrey Composite Elbow Function Score are listed as secondary outcomes. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a plan specifying which analyses were confirmatory. It is therefore not possible to determine whether the reported p-value was interpreted within a prespecified family of comparisons or how the secondary outcomes were incorporated into the study’s inference.

In general, testing multiple outcomes or making multiple comparisons can increase the chance of obtaining at least one apparently notable result under a set of null hypotheses. Methods to address this can include adjusting the testing procedure or defining an outcome hierarchy in advance. Whether either approach was used in this trial is not reported in the registry record. The primary result should not be treated as adjusted for multiplicity unless that is documented.

The registry provides arm-level primary outcome summaries for 9 participants in each group, but does not describe the analysis population. It is not reported whether these were all randomized participants, participants with an available 1 year post-op questionnaire, or a different analysis set. The record also does not state whether analyses followed an intention-to-treat principle or whether any participants were excluded after randomization.

Missing outcome data and the methods used to handle them are not reported in the registry record. The number of missing DASH assessments, reasons for missingness, and any imputation or sensitivity analysis are also not reported. These details are important because a comparison based only on participants with observed scores can be affected if availability of outcome data is related to treatment assignment or participant outcomes. This general concern does not establish that missing data occurred or biased the result; the registry simply does not give the information needed to assess it.

The record does not report interim analyses, stopping rules, or whether the analysis plan was finalized before outcome data were examined. It also does not provide sufficient detail to assess how protocol deviations or other post-randomization events were handled. These gaps leave uncertainty about the analysis process and the robustness of the reported result.

13. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (11.1%).

The adverse-event record lists 9 participants at risk for serious adverse events in each arm. It records 1 participant affected in the botulinum toxin group and 0 in the saline group. The record also lists 1 participant affected by other adverse events in each arm. These counts describe what is posted for the small groups; they do not establish whether an event was caused by the assigned injection.

The serious adverse-event terminology includes Death among the top serious terms, with 11.1% listed. The group-level adverse-event information separately shows deaths as null for both arms. The record does not explain the relationship between this term and the group-level death fields, so they should not be reconciled by assumption. The timing, circumstances, and treatment relatedness of the serious event are not reported in the registry record.

With 9 participants per arm, counts provide limited information about uncommon harms or differences in safety between groups. In general, a small trial cannot reliably characterize the full range or frequency of adverse events. The registry does not report detailed event descriptions, severity grades, seriousness criteria, or the investigators’ assessment of causality. These posted figures should be read as limited safety reporting rather than a complete safety profile.

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

The posted primary results show a mean DASH score of 27.0 in the botulinum toxin group and 54.0 in the saline group at 1 year post-op. The DASH scale is described so that lower scores represent less disability. The registry’s two-sided t-test reports p = 0.06. Taken together, these figures describe a lower observed mean in the botulinum toxin arm and a test result that does not meet the conventional 0.05 threshold.

These findings do not establish that the treatments are equivalent. A non-significant p-value is not evidence that two groups have the same outcomes, and the registry does not report an equivalence or non-inferiority analysis. Nor does the result prove that an underlying difference exists. The record lacks a reported treatment-effect estimate and confidence interval, so the range of effects compatible with the data cannot be assessed directly.

The results also do not establish that any observed difference was caused by the intervention. Randomization is intended to support a fair comparison, but assessment still depends on the conduct of the study, completeness of follow-up, analysis choices, and uncertainty in the estimates. Details about allocation procedures, missing outcomes, and analysis populations are not reported in the registry record.

The primary outcome measures upper-limb disability and symptoms, not elbow stiffness alone. The study summary identifies prevention of postoperative stiffness and improvement in function as its rationale, and the registry lists elbow range of motion and an elbow-function score as secondary outcomes. Their results are not presented in the primary outcome details available in the record, so the DASH result cannot stand in for those separate outcomes.

Finally, the trial enrolled 18 participants. The small size limits the precision and breadth of conclusions that can be drawn from the posted summaries, particularly about variation between patients and uncommon safety events. The result is a comparison in a small randomized study, not a definitive estimate of the effect across all people undergoing surgery for an elbow fracture.

15. Why This Trial Matters Statistically

This trial is statistically instructive because it pairs a randomized comparison with a patient-reported continuous outcome and a small enrollment. The two arm means point in different directions from the null in a descriptive sense, while the reported p-value is 0.06. This illustrates why interpretation should consider both the observed summaries and their uncertainty, rather than reducing a result to a threshold label.

The DASH score measures disability and symptoms across the upper limb, while the study rationale concerns postoperative elbow stiffness and function. Considering the outcome’s construct is important: a measure can be relevant to the broader functional question without directly measuring the physical attribute named in the trial rationale. The registry lists elbow range of motion and an elbow-function score separately, highlighting that different outcomes may capture different aspects of recovery.

The record also illustrates the limits of summary reporting. Means and standard errors do not reveal the distribution of participant scores, and the lack of a reported confidence interval prevents direct inspection of uncertainty around the treatment contrast. Missing details about analysis populations, missing outcomes, and multiplicity further constrain what can be concluded from a reported p-value.

Finally, planning calculations based on observed effects should be kept separate from a trial’s original design. The registry does not report its sample-size justification. Any planning illustration based on an observed estimate is hypothetical and should not be mistaken for evidence that the study was adequately or inadequately powered. Keeping design, analysis, and interpretation distinct helps prevent a small trial’s numerical result from carrying more certainty than the record supports.

16. 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 trial’s enrollment was 18, with 9 participants in each arm in the posted primary outcome results. This small sample limits the precision with which group differences can be estimated and the ability to assess variation across participants. The registry reports standard errors but not standard deviations or participant-level data, limiting assessment of the spread and shape of the scores.

The primary comparison is reported with a p-value but without a treatment-effect estimate or confidence limits. The registry record therefore does not permit direct assessment of the size and precision of the between-arm contrast. The available arm means describe the observed groups, but do not supply the missing interval estimate.

Details about eligibility criteria, allocation concealment, the masking procedure, and the identities of masked parties are not reported in the registry record. The record’s summary calls the study double blind, while its design field lists quadruple masking; the practical meaning of these descriptions is not explained. The record also does not provide enough information to assess adherence to the assigned injection or other protocol deviations.

Information about missing data, outcome completion, and the analysis population is not reported. The registry does not specify whether all randomized participants contributed to the primary analysis or describe any method for handling incomplete questionnaires. It also does not report whether multiplicity was addressed, whether an analysis plan was prespecified, or whether interim analyses occurred.

Finally, although the registry lists elbow range of motion and the Broberg Morrey Composite Elbow Function Score as secondary outcomes, their results are not included in the primary outcome details. The serious adverse-event record is limited and does not describe event timing, relatedness, or the context of the listed serious term. These limitations restrict conclusions about functional outcomes beyond DASH and about safety.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Botulinum Toxin as a Novel Treatment for Prevention of Post-Traumatic Elbow Stiffness — NCT01129583.
• Registry record last updated 2015-03-27; status last verified 2015-03.
• Results first posted 2011-05-02.
• 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.

20. Record Summary

NCT01129583 is a completed randomized, parallel-group study sponsored by Columbia University. It compared intraoperative botulinum toxin A with saline following surgical treatment of an elbow fracture. Enrollment was 18, and the posted primary outcome results include 9 participants per arm.

The primary endpoint was the DASH questionnaire score at 1 year post-op, on a scale from 0 to 100, with lower scores representing less disability. The posted means were 27.0 for botulinum toxin and 54.0 for saline, with standard errors of 11.0 and 8.0, respectively. The reported two-sided t-test had p = 0.06. A treatment-effect confidence interval is not reported in the registry record.

Elbow range of motion and the Broberg Morrey Composite Elbow Function Score are listed as secondary outcomes. Further information about missing data, analysis populations, multiplicity, and the sample-size justification is not reported in the registry record.