Long Term Safety And Effectiveness Of Dysport® In Adults With Cervical Dystonia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Long Term Safety And Effectiveness Of Dysport® In Adults With Cervical Dystonia (NCT01753336), a na phase 3 study. The primary outcome is TWSTRS Total Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3..

2. Clinical Question

The trial’s stated purpose was to assess the long-term safety of repeat Dysport® treatment cycles using the 2 mL dilution scheme, and the primary outcome also tracks TWSTRS scores over the cycles. These are related but distinct questions: safety concerns adverse events during treatment, while TWSTRS records the assessed impact of cervical dystonia. Because there is no concurrent comparison group, the study can describe measurements among participants who took part, but its design does not provide a randomized comparison of Dysport® with another treatment or with no treatment.

3. Trial Design

The registry describes a Phase III study; the official title identifies it as a Phase IIIb, prospective, multicentre, open-label extension study. Its purpose was to assess long-term safety and effectiveness of Dysport® using a 2 mL dilution in adults with cervical dystonia. It is identified as an extension of Study 169, and the brief summary describes repeat treatment cycles of Dysport® 500 U using that dilution scheme.

The study is listed as single-group, with allocation recorded as NA and masking as NONE. The arm description names Dysport® and states up to 500 units per vial using 2 mL dilution. Enrollment was 112. The registry lists the study as completed, with a start in 2013-03 and primary completion in 2015-10. These dates describe the registry record and do not supply additional details about how participants entered or continued in the extension.

The primary outcome is TWSTRS total score at Week 4 and Week 12 for treatment cycles 1, 2 and 3. The stated cycle duration is 12 - 16 weeks each. The outcome description says both visit scores and differences from each cycle’s baseline, defined as Day 1 of that cycle, are presented. Secondary outcomes include further TWSTRS assessments and a treatment-response measure. The registry lists six outcome measures and 30 analyses, but the detailed numerical outcome results are not reported in the registry record.

With one treatment group and no masking, the study is descriptive rather than a randomized, blinded comparison. Within-participant measurements over multiple cycles can document the observed course of scores and safety events among those assessed. They do not by themselves separate treatment effects from other explanations for changes over time, such as the natural course of symptoms, expectations, or changes in who remains available for 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: Subjects who completed Study 169 and had no on-going Adverse Events (AEs) or whose Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score between Weeks 4 and 8 was reduced by ≤15% from baseline were invited to participate in this OLE study. 112 of the 134 subjects in Study 169 were enrolled into Study 170 (signed informed consent).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety population included all subjects who received at least 1 dose of study treatment, regardless of the amount of study treatment administered, and who had at least 1 safety record post-treatment or attended a post-treatment visit.

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.

Population: The safety population included all subjects who received at least 1 dose of study treatment, regardless of the amount of study treatment administered, and who had at least 1 safety record post-treatment or attended a post-treatment visit.

6. Primary Endpoint

The registry lists the primary outcome as TWSTRS Total Score at Week 4 and Week 12 for Treatment Cycles 1, 2 and 3., measured over Week 4 and 12 of treatment cycles 1, 2 and 3 (12 - 16 weeks duration each).

The primary outcome is the TWSTRS total score at Week 4 and Week 12 in treatment cycles 1, 2 and 3, along with differences from the baseline for each cycle. The cycle baseline is defined as Day 1. The registry describes the TWSTRS as an assessment of the impact of cervical dystonia, scored by the investigator at baseline and post-treatment visits.

The total combines three separately scored subscales: severity, disability and pain. The total score ranges from 0 to 85, with the registry specifying best to worst in that order. A total score therefore brings several aspects of the condition into one measure, while the subscales retain information about those distinct aspects. The registry also lists separate secondary outcomes for the severity, disability and pain subscales.

Assessments at Week 4 and Week 12 allow the registry to describe scores at two points within each treatment cycle. Reporting differences from Day 1 can describe how each participant’s measured score changed relative to that cycle’s starting value. That change is not, by itself, a comparison with an untreated course or another intervention. The registry record does not report the observed primary scores, changes, variability estimates, or confidence intervals, so the magnitude and precision of the results cannot be assessed from the outcome description alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: the TWSTRS total is a score on a scale, and the registry says it is summarized as a mean with standard deviation. A mean describes the average score in the assessed group; a standard deviation describes how spread out individual scores are around that average. These statistics answer different questions. A mean alone does not show whether participants had similar or widely varying scores, while a standard deviation does not describe the direction of change from baseline.

The registry describes two kinds of primary-outcome summaries: scores at Week 4 and Week 12, and mean differences from the baseline of each treatment cycle. A baseline-referenced difference describes the average change relative to Day 1 within that cycle. It is not a treatment-versus-control effect, because the design has no separate comparator group. The registry does not state whether those differences were calculated from individual participant changes or by another method, nor does it report an adjusted analysis model.

What does a standard deviation say?

General statistical explanation: a standard deviation expresses the dispersion of observed values around their mean, in the same units as the measurement. It is not a confidence interval and does not show how precisely the mean has been estimated. The precision of a mean estimate depends on the amount of information available and the variability in the measurements. The registry record does not report primary-outcome standard deviations or confidence intervals, so that precision cannot be judged for these TWSTRS results.

Why do repeated measurements matter?

General statistical explanation: measurements from the same person over time are related, rather than independent observations. An analysis that uses several visits should account for that within-person relationship if it is making an inferential claim across visits. The record names assessments at Week 4 and Week 12 in three cycles, but does not report a repeated-measures model, covariance structure, or other method for handling the relationship among visits. It is therefore not possible to identify the inferential method used from the registry record.

What can a confidence interval add?

General statistical explanation: a confidence interval gives a range of values compatible with the data and the assumptions of the analysis, and communicates uncertainty around an estimate. It is useful alongside a mean difference because a point estimate alone does not show how precisely that difference is known. No primary-outcome confidence intervals are reported in the registry record. Without the estimates and their uncertainty, neither the size of a score change nor its precision can be evaluated.

How should planning calculations be understood?

General statistical explanation: a sample-size calculation asks how many participants might be needed to detect a specified effect under stated assumptions. It is a planning exercise, not evidence that a study had a particular probability of detecting an effect after it was completed. The planning assumptions associated with the posted results use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. For non-time-to-event outcomes, the stated planning convention is participants per arm for a specified power level; time-to-event calculations use a total number of events.

These assumptions describe an illustrative two-arm calculation, not the single-group extension design listed in the registry. The original sample-size justification and the study’s own power calculation are not reported in the registry record. The observed primary outcome estimates are also not reported, so any planning output based on an observed effect should not be interpreted as an independent confirmation of the study’s findings. No planning illustration is observed power.

What analysis details remain unknown?

The registry lists six outcome measures and 30 analyses, but the number of listed analyses does not identify the statistical model or its assumptions. The record does not report whether estimates were adjusted for covariates, how distributions were checked, whether any sensitivity analyses were performed, or what inferential tests were used for the continuous outcomes. It also does not report how repeated measurements, missing observations, or departures from model assumptions were handled. General statistical practice would consider whether the analysis method suits the scale, repeated observations, and available data; the registry entries do not establish which choices were made.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome includes more than one visit and more than one treatment cycle, and the registry also lists secondary outcomes for TWSTRS total and subscale measures as well as treatment response. Examining several outcomes or time points creates a multiplicity issue: when many statistical tests are considered, the chance of at least one apparently notable result can increase. General statistical explanation: a prespecified testing hierarchy or an adjustment for multiple comparisons can help control that issue, depending on the study’s goals.

The multiplicity strategy, if any, is not reported in the registry record. It is also not reported whether the primary outcome was treated as one overall test or as separate comparisons across visits and cycles, or whether secondary outcomes were confirmatory or exploratory. Without that information and the numerical analyses, the results cannot be placed within a known family of tests or interpreted using a stated multiplicity procedure.

Missing-data handling is not reported in the registry record. The definition of the safety population requires at least one dose and post-treatment safety information, but that does not specify the population used for the primary outcome. The record does not state how many participants had TWSTRS data at each visit, whether all available observations were analyzed, how missing scores were handled, or whether sensitivity analyses addressed missingness. The reasons for missing measurements are also not reported.

Interim analyses and stopping rules are not reported in the registry record. Nor are the primary-outcome analysis population, the statistical analysis plan, or a sample-size justification. These absences limit interpretation of the analysis choices; they do not establish that a particular procedure was or was not used outside what the registry record describes.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: osteoarthritis (1.8%), colitis ischaemic (0.9%), cholecystitis (0.9%), appendicitis (0.9%), thoracic vertebral fracture (0.9%).

The listed Dysport® group has 112 participants at risk for the serious-adverse-event summary, with 7 affected. For the other-adverse-event summary, 112 were at risk and 70 were affected. These are participant counts in the registry record, not estimates of how many events occurred in total. The record lists serious adverse-event terms including Osteoarthritis (1.8%), Colitis ischaemic (0.9%), Cholecystitis (0.9%), Appendicitis (0.9%), Thoracic vertebral fracture (0.9%), and Transient ischaemic attack (0.9%).

The terms and percentages describe what was recorded; they do not establish that Dysport® caused the events. No separate comparison group is listed, so these counts cannot be compared with an untreated or alternative-treatment group within this study. The registry record does not report an attribution assessment or provide further detail about event timing, recurrence, or severity beyond the serious-event classification.

The death count is not reported in the registry record. A missing death count should not be interpreted as a count of zero. The adverse-event figures are therefore best read as descriptive safety summaries for the listed group, with the stated denominator and without a causal comparison.

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

This study’s record documents an open-label, single-group extension design in adults with cervical dystonia, with repeat Dysport® treatment and planned assessment of TWSTRS total score across three treatment cycles. The outcome definition identifies the scale, its subscales and direction, the visit timing, and the cycle baseline. Those details clarify what the study sought to measure.

The record does not include the numerical primary-outcome results. It therefore does not establish the average TWSTRS scores, the direction or size of changes from baseline, the amount of variation among participants, or the precision of any estimate. Statements about improvement, worsening, stability, or a clinically important change would require results and interpretation criteria that are not reported in the registry record.

Even if numerical changes were available, a single-group extension would describe what happened among participants in the study, rather than establish what would have happened to comparable participants without the study treatment. The absence of randomization and a concurrent comparator limits causal interpretation. Open-label status means treatment was not masked, and the record does not describe methods used to address possible influences of treatment awareness on assessment.

The safety counts add descriptive information: 7 participants were affected by serious adverse events and 70 by other adverse events among 112 at risk in each listed summary. These figures do not show whether an event was caused by treatment, and the death count is not reported. The registry record also does not provide the statistical plan, missing-data approach, multiplicity strategy, or primary-outcome analysis population. The study can therefore be understood from its design and outcome definitions, but the registry information does not support a complete assessment of efficacy estimates, uncertainty, or causal safety conclusions.

13. Why This Trial Matters Statistically

The study illustrates a common statistical distinction between describing repeated observations and estimating a comparative treatment effect. The registry specifies TWSTRS assessments at Week 4 and Week 12 over three cycles, and changes from a Day 1 baseline within each cycle. Such measurements can characterize scores over time among participants who were assessed. Because the design is single-group, however, those within-group patterns are not equivalent to a randomized comparison against another course of care.

The extension design also makes clarity about the analysis population important. The registry gives a safety-population definition but does not report the number of participants contributing primary scores at each visit or how missing data were treated. For outcomes measured repeatedly, the relationship between a participant’s observations and the availability of data across visits affect how estimates should be interpreted. Those analysis details are not reported in the registry record.

Safety reporting offers a related lesson. Counts of participants affected by adverse events are useful descriptive information, but without a concurrent comparator they do not establish excess risk or treatment causation. The listed serious-event terms and percentages should be read as registry-recorded summaries rather than comparative evidence.

Finally, the record illustrates why outcome definitions and outcome results must be distinguished. It describes the TWSTRS scale, timing, and intended summaries, but does not report the numerical primary results. A detailed outcome definition helps readers understand what was to be measured; it cannot substitute for estimates, measures of uncertainty, or a complete statistical analysis plan.

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 central limitation for interpreting the primary outcome is that the registry record does not report the numerical TWSTRS results. Means, standard deviations, baseline differences, confidence intervals, and visit-specific participant counts are not reported. The scale and assessment schedule are described, but the outcome magnitude and precision cannot be assessed.

The single-group design has no concurrent comparator and is not randomized. Consequently, observed changes from each cycle’s Day 1 baseline cannot be separated from other changes over time using this design alone. The study is open-label, and the registry does not report whether assessment procedures addressed the potential influence of treatment awareness.

The study is an extension of Study 169, but the registry record does not report the details needed to characterize entry into the extension or the relationship between participation in the earlier study and the extension analysis population. The safety population is defined, but the primary-outcome population and participant retention at each assessment are not reported.

Important analysis details are also not reported: the statistical model, handling of within-participant repeated measurements, missing-data method, multiplicity strategy, interim analyses, and statistical analysis plan. The original sample-size justification is not reported. The adverse-event summaries are descriptive and have no concurrent control group; the death count is not reported. These limitations constrain both outcome interpretation and assessment of the analyses, without establishing that any unreported method was or was not used.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Long Term Safety And Effectiveness Of Dysport® In Adults With Cervical Dystonia — NCT01753336.
• Registry record last updated 2019-08-07; status last verified 2019-07.
• Results first posted 2017-05-04.
• 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

NCT01753336 is a completed Phase III registry study, described in its official title as a prospective, multicentre, open-label extension of Study 169. It enrolled 112 adults with cervical dystonia for repeat Dysport® treatment using a 2 mL dilution scheme. The study is listed as single-group, with no masking.

The primary outcome is TWSTRS total score at Week 4 and Week 12 in treatment cycles 1, 2 and 3, including differences from each cycle’s Day 1 baseline. The TWSTRS total ranges from 0 to 85, with best to worst. Numerical primary-outcome results and key analysis details are not reported in the registry record.

For the listed Dysport® group, 7 participants were affected by serious adverse events and 70 by other adverse events, with 112 at risk in each summary. The death count is not reported. The single-group, open-label design and missing outcome and analysis details limit comparative and causal interpretation.