Study Comparing Short Term Efficacy of Dysport and Dysport NG to Placebo, and to Assess Efficacy and Safety of Dysport NG of Subjects With Cervical Dystonia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Comparing Short Term Efficacy of Dysport and Dysport NG to Placebo, and to Assess Efficacy and Safety of Dysport NG of Subjects With Cervical Dystonia (NCT01261611), a randomized phase 3 study. The primary outcome is Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score Following First Treatment Cycle.

2. Clinical Question

3. Trial Design

This was a Phase III, randomized, parallel-group trial with quadruple masking and an open-label phase. It compared two formulations of botulinum toxin type A, Dysport NG and Dysport, with placebo. The registry record describes short-term comparisons following the first treatment cycle and assessment of Dysport NG following repeated treatments. The study status is completed. It reports enrollment of 382; the number analyzed for each outcome can differ from enrollment and is reported alongside the outcome estimates.

For the primary endpoint, the analysis population was the Intent to Treat population, defined in the registry record as randomized subjects who received at least one study-treatment injection, regardless of the amount administered. Subjects were analyzed according to their randomized assignment. The primary results are least-squares mean changes with 95% confidence intervals. The record also reports ANCOVA tests for Dysport NG versus placebo and Dysport versus placebo, and a least-squares mean difference for Dysport NG versus Dysport.

The treatment descriptions report 500U of Dysport NG on day 1 of the first and second treatment cycles, with different dose options described for later cycles. The Dysport description gives 500U on day 1 of the first cycle, while placebo is described as 1mL on day 1 of the first cycle. The complete Dysport NG schedule is not reported in the registry record. The record does not report further detail on randomization procedures, allocation concealment, the duration or conduct of the open-label phase, or the sample-size justification. These design details should not be inferred from the study title or the treatment descriptions.

The first-cycle primary assessment was at Week 4, against baseline. The registry record lists additional secondary outcomes involving TWSTRS subscales and total score, subject-reported visual analogue scores, and treatment response. Results for all listed secondary outcomes are not reported in the registry record. The available results therefore support discussion of the posted primary outcome and the secondary responder outcome, not a complete account of every planned or listed assessment.

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: 382 subjects screened, 369 randomised due to 13 screen failures.

Treatment Cycle 1

Reasons for not completing this period:

Treatment Cycle 2

Reasons for not completing this period:

Treatment Cycle 3

Reasons for not completing this period:

Treatment Cycle 4

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis based on number (n) of subjects in the Intent to Treat (ITT) population (all randomised subjects who received at least one injection of study treatment regardless of the amount of study treatment administered). The ITT population was analysed using subjects as randomised. Missing data were not imputed.

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 Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score Following First Treatment Cycle, measured over Baseline and Week 4.

The primary endpoint was change from baseline in TWSTRS Total Score following the first treatment cycle, assessed at baseline and Week 4. TWSTRS measures cervical dystonia through three components: Severity, Disability and Pain. Its total ranges from 0 to a maximum of 85, with higher scores denoting worse outcome. A negative change from baseline represents improvement in symptoms. The total score combines the three component scores, giving a broad measure of symptom burden rather than focusing only on pain, disability or severity.

The endpoint is useful for comparing average change across randomized groups because it captures several clinically relevant dimensions of cervical dystonia in one measure. The registry record reports least-squares means and 95% confidence intervals for the group changes. These are adjusted model estimates, not simple raw averages; the registry record identifies ANCOVA for the reported active-treatment versus placebo tests, but further details of the primary model are not reported in the registry record. A confidence interval conveys uncertainty around an estimate under the model, rather than a range containing a known proportion of individual participants' outcomes.

The score’s direction matters when reading the results: a more negative change indicates a larger average reduction in TWSTRS Total Score from baseline. That interpretation describes the scale, not a judgment about whether a change is meaningful to an individual subject. A threshold for clinical importance is not reported in the registry record, so statistical change alone cannot establish the importance of the difference to patients.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: each subject has a numerical change in TWSTRS Total Score, and the reported group results are least-squares means. A least-squares mean is a model-based estimate of the group mean after accounting for terms included in the analysis. This can differ from a raw average. The registry record identifies ANCOVA for the two reported comparisons with placebo, but the covariates and full model specification are not reported in the registry record. No additional adjustment should be assumed.

What does a confidence interval convey?

A confidence interval describes the precision of an estimated effect under a statistical model and its assumptions. A narrower interval indicates greater precision than a wider interval. For the group-level primary estimates, the posted 95% confidence intervals show uncertainty around each least-squares mean change. For the direct Dysport NG–Dysport comparison, the interval extends from -0.819 to 3.883 around the estimate of 1.532. Because the interval crosses zero, it is compatible with no difference as well as with values on either side of zero. This is not proof that the groups are identical; it indicates that the reported interval does not exclude zero.

Confidence intervals are not intervals containing 95% of individual outcomes. They also do not account for every possible source of uncertainty, such as model misspecification, missing outcome data or selective reporting. They quantify sampling uncertainty as represented by the stated analysis. For the two active-versus-placebo primary comparisons, the registry reports p-values but no contrast estimates or confidence intervals. The separate confidence intervals around each group’s estimated change are not a substitute for a confidence interval for a between-group contrast.

How should the p-values be read?

A p-value describes how incompatible the observed data are with a specified null hypothesis, assuming the statistical model and its assumptions apply. The registry reports p < 0.001 for each active formulation versus placebo. This is evidence against the corresponding null hypothesis of no difference under the reported ANCOVA analyses. It does not give the probability that the null hypothesis is true, the probability that the result occurred by chance, or the size of the treatment difference. The registry does not report the full ANCOVA model or adjusted contrasts for these comparisons, so the test results cannot be independently reconstructed from the posted group means alone.

The direct active-treatment comparison is framed differently. Its posted least-squares mean difference has a 95% confidence interval that includes zero, while no p-value is reported for that comparison. The record describes the analysis as a non-inferiority or equivalence legacy analysis. Non-inferiority is not established merely because a confidence interval includes zero or because a conventional difference test is not significant. It requires a prespecified margin and a rule for judging the interval against that margin. Those details are not reported in the registry record.

What does the responder re-calculation add?

The secondary responder measure is binary: subjects either meet the response definition or do not. The posted recalculated comparisons express the absolute difference in response proportions between each active group and placebo. For Dysport NG, the risk difference is 0.25, with a 95% confidence interval from 0.115 to 0.385 and an unadjusted p-value of 0.001. For Dysport, the risk difference is 0.350, with a 95% confidence interval from 0.216 to 0.484 and p <0.001. These are simple unadjusted re-calculations from posted summary counts, not the sponsor’s adjusted analysis. The relative risk and odds ratio are also recalculated measures, but they do not replace the absolute difference in proportions when considering the magnitude on the probability scale.

These re-calculations use the posted responder counts and group sizes. They do not account for covariates, and the confidence intervals and p-values depend on the methods used for the re-calculation. The registry record does not report an adjusted analysis for this secondary endpoint. The calculations should be regarded as descriptive support for interpreting the posted data, not as confirmation of a prespecified sponsor analysis.

Why do planning illustrations need caution?

The sample-size illustrations use the observed responder effect as a planning reference and display hypothetical participants per arm for specified power levels and fractions of that observed effect. They are not observed power and do not establish what sample size the trial was designed to have. The registry describes the illustration assumptions as a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation. Sample-size calculations based on an observed effect can be optimistic because that effect is itself uncertain. Planning for a smaller fraction of an observed effect illustrates how required enrollment depends on the effect one seeks to detect; it does not establish that the smaller effect is clinically important.

The registry record does not report the trial’s own sample-size justification, any interim analyses, or the complete statistical analysis plan. It also does not report details needed to assess all model assumptions or missing-data procedures. These omissions limit how fully the posted tests and estimates can be audited.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary ANCOVA tests against placebo: p < 0.001 for Dysport NG versus placebo and p < 0.001 for Dysport versus placebo. It also reports a Dysport NG–Dysport least-squares mean difference of 1.532, with a 95% confidence interval from -0.819 to 3.883, in an analysis labeled as non-inferiority or equivalence. The registry record does not report the non-inferiority margin, a decision rule, or a p-value for this comparison. The reported difference and interval therefore cannot, by themselves, establish that a non-inferiority criterion was satisfied.

The responder calculations are separate unadjusted re-calculations from posted summary counts. They are not a replacement for the sponsor’s own analyses and should not be presented as adjusted trial findings. The recalculated confidence intervals and p-values give a way to assess the posted responder proportions using a simple two-group comparison, but they do not reproduce the primary ANCOVA model. The primary group estimates are least-squares means, and the sponsor-reported placebo comparisons are ANCOVA tests; raw summary results and recalculated binary comparisons answer related but not identical questions.

The registry discrepancy flag is false, so there is no recorded discrepancy requiring the sponsor’s own analysis to take precedence over a recalculation. Even without a flagged discrepancy, the sponsor-reported model-based analysis remains the relevant record of the trial’s prespecified analysis to the extent its methods are documented. Since the complete statistical plan and important model details are not reported in the registry record, the posted results cannot independently establish every aspect of that analysis.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes in addition to the primary TWSTRS Total Score endpoint. Testing multiple endpoints creates a multiplicity issue: even if every null hypothesis were true, conducting many tests can increase the chance that at least one result appears statistically significant. A prespecified testing hierarchy, adjustment procedure or other strategy can address this concern, but the multiplicity plan is not reported in the registry record. The secondary responder p-values are unadjusted re-calculations, so they should not be interpreted as multiplicity-controlled evidence.

The primary analysis population is described as the Intent to Treat population, including randomized subjects who received at least one injection and analyzed as randomized. This is not the same as an analysis of every randomized subject regardless of treatment receipt. The endpoint estimates report group-specific analysis counts, but the registry record does not explain all reasons for differences between enrollment and those counts.

The primary population description says missing data were, but the registry text is incomplete at that point. The missing-data handling method is therefore not reported in the registry record. Without that information, it is not possible to assess whether missing outcomes were imputed, excluded, or handled using another approach, or to evaluate the assumptions that method would require. The extent and pattern of missing primary outcome data are also not reported in the registry record.

The record does not report whether interim analyses were performed, or the complete statistical analysis plan, sample-size justification, covariates used in the ANCOVA, or the full decision rule for the non-inferiority or equivalence analysis. These gaps matter because they limit assessment of prespecification, model adequacy, multiplicity control and the interpretation of the direct active-treatment comparison. They do not invalidate the posted estimates, but they constrain the strength and scope of conclusions that can be drawn from the registry results alone.

12. 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: gastritis haemorrhagic (1.8%), gastrooesphageal reflux disease (1.8%), lung adenocarcinoma (0.6%), malignant pleural effusion (0.6%), pericardial effusion malignant (0.6%).

The safety record gives serious and other adverse event counts for treatment groups, including Dysport NG dose groups, Dysport and placebo. For example, the serious adverse event count is 16 among 363 at risk in the Dysport NG, 500U group, while the other adverse event count is 59 among 363 at risk in that group. For Dysport, the record lists 3 serious events among 156 at risk and 15 other events among 156 at risk. For placebo, it lists 0 serious events among 55 at risk and 1 other event among 55 at risk. These are counts in the registry’s stated groups, not estimates of causal risk attributable to treatment.

The safety groups span treatment doses and repeated treatment exposure, so they should not be treated as if they were necessarily the same populations or follow-up conditions as the primary first-cycle efficacy groups. The registry record does not report the full safety analysis methods or follow-up time associated with each safety count. It also does not report a numerical death count; deaths are not reported in the registry record.

The serious-event terms listed include gastritis haemorrhagic and gastrooesphageal reflux disease, each reported as 1.8%, as well as several terms reported as 0.6%. These percentages should be read as registry-reported figures; the record does not provide enough context to infer the underlying denominators or compare rates across groups. Counts and terms alone cannot establish whether an event was caused by treatment, and uncommon events may be difficult to characterize in a trial of this size.

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

The primary outcome results describe average TWSTRS Total Score change at Week 4 following the first treatment cycle. The active groups had negative least-squares mean changes, as did the placebo group. The registry reports ANCOVA evidence of a difference between each active formulation and placebo. These findings describe the recorded group-level results under the analyses reported; they do not show how every participant responded, and they do not determine the cause of a change for an individual.

The direct comparison between Dysport NG and Dysport has an estimated difference of 1.532 and a 95% confidence interval from -0.819 to 3.883. Since the interval includes zero, it does not rule out no difference. The registry record labels the analysis as non-inferiority or equivalence, but the margin and decision criteria are not reported. A claim of non-inferiority or equivalence cannot be made from the interval alone without those criteria.

The responder findings provide a second, binary measure, with unadjusted comparisons recalculated from posted counts. They are consistent with a higher response percentage in the active groups than placebo, but they are secondary, unadjusted results and must be considered in light of the multiple outcomes listed. The registry record does not report complete results for all secondary outcomes, and the definition of responder is not reported in the registry record.

The results do not establish the size of a clinically meaningful benefit because a threshold for meaningful TWSTRS change is not reported in the registry record. Nor do first-cycle Week 4 data establish the effect of repeated treatment or long-term outcomes. The study included repeated-treatment and longer-term assessment of Dysport NG, but corresponding outcome results are not reported in the registry record. Safety counts are descriptive and do not alone establish causal attribution or comparative safety.

Statistical significance, precision, clinical importance and generalizability are distinct considerations. The p-values address compatibility with null hypotheses under specified analyses; intervals express uncertainty around estimates; neither determines whether the magnitude matters to patients or whether results apply to people outside the studied population. Those judgments require information beyond the posted numerical results.

14. Why This Trial Matters Statistically

This trial is statistically informative because it reports both a continuous primary endpoint and a binary responder outcome, and it includes placebo and active-treatment comparisons. The TWSTRS Total Score provides an average change measure across severity, disability and pain, while the responder classification offers a different summary of outcome. Considering different measures can help assess whether the broad pattern depends on how response is defined, while keeping their distinct interpretations clear.

The active-versus-placebo primary tests are reported as ANCOVA analyses, whereas the active-versus-active result is reported as a least-squares mean difference with a confidence interval. This distinction illustrates why the method and estimand matter: separate group changes are not the same as a treatment contrast, and a p-value alone does not describe the magnitude or precision of a contrast. The direct comparison also illustrates why a label such as non-inferiority requires a documented margin and decision rule.

The responder re-calculations make explicit the uncertainty around simple unadjusted contrasts derived from posted counts. They are useful for understanding the scale and precision of that secondary comparison, but they do not reproduce an adjusted analysis or control for examining many endpoints. The planning illustrations further demonstrate that hypothetical sample-size needs depend on the effect one aims to detect; they are not observed power and do not reveal the original design justification.

Finally, this record highlights the importance of transparent reporting. The absence of a complete missing-data description, multiplicity plan, non-inferiority margin and full analysis specification limits independent assessment. The available results can be interpreted carefully, but fuller methods and secondary outcome reporting would be needed for a more complete evaluation of the trial’s statistical 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.

The registry description of missing-data handling is incomplete: it begins to discuss missing data but does not give the method. The amount and pattern of missing primary outcome data are also not reported in the registry record. This prevents assessment of whether missingness could have affected the estimated changes or whether the analysis depended on assumptions about unobserved outcomes.

The primary results include least-squares mean estimates and confidence intervals, but the registry record does not give full ANCOVA specifications, including the covariates and model details. The sponsor’s placebo-comparison p-values are reported without corresponding adjusted contrast estimates or confidence intervals. As a result, readers cannot assess the magnitude and precision of those adjusted comparisons directly from the reported tests.

The direct Dysport NG–Dysport analysis is described as non-inferiority or equivalence, but the margin, rationale and decision rule are not reported in the registry record. Without those elements, the result cannot support a formal conclusion of non-inferiority or equivalence. The complete statistical analysis plan and the trial’s sample-size justification are also not reported.

Several secondary outcomes are listed, but complete numerical results are not reported in the registry record. The multiplicity strategy is not reported, and the posted responder calculations are unadjusted. The response definition is not reported, limiting interpretation of what qualifies as a responder. The full Dysport NG dosing schedule is not available in the arm description, which is truncated, and details of the open-label phase and long-term outcome results are not reported.

Safety counts cover multiple dose groups and treatment exposure, while the record does not provide all context needed to compare risk consistently across groups. The reported terms and counts cannot establish causation. These limitations are specific to the information recorded and do not show that the underlying trial necessarily lacked additional analyses or documentation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study Comparing Short Term Efficacy of Dysport and Dysport NG to Placebo, and to Assess Efficacy and Safety of Dysport NG of Subjects With Cervical Dystonia — NCT01261611.
• Registry record last updated 2022-09-28; status last verified 2022-09.
• Results first posted 2019-09-24.
• 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

NCT01261611 is a completed Phase III randomized, parallel-group study of Dysport NG, Dysport and placebo in subjects with cervical dystonia. The trial used quadruple masking and included an open-label phase. The primary endpoint was change from baseline in TWSTRS Total Score at Week 4 after the first treatment cycle.

The posted primary group estimates are least-squares mean changes with 95% confidence intervals. The registry reports ANCOVA p < 0.001 for each active formulation versus placebo. The Dysport NG–Dysport difference is 1.532, with a 95% confidence interval from -0.819 to 3.883; the non-inferiority margin is not reported in the registry record. A secondary responder outcome has posted percentages and unadjusted recalculated comparisons against placebo.

The registry lists additional secondary outcomes and safety information, but complete results for all secondary outcomes, missing-data methods, multiplicity handling, the full statistical plan and longer-term efficacy results are not reported in the registry record. Interpretation is therefore limited to the posted results and the methods described.