Efficacy And Safety Of Dysport In The Treatment Of Upper Limb Spasticity In Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy And Safety Of Dysport In The Treatment Of Upper Limb Spasticity In Children (NCT02106351), a randomized phase 3 study. The primary outcome is Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG.

2. Clinical Question

3. Trial Design

The registry identifies NCT02106351 as a Phase III, randomized, double-blind, parallel-group study. It lists enrollment of 212 and a completed status. The recorded study start is 2014-04 and primary completion is 2017-09-21. The sponsor is Ipsen. The stated purpose was to assess efficacy and safety of multiple Dysport doses in children with cerebral palsy and upper limb spasticity.

The treatment descriptions distinguish three initial dose groups. Group A received Dysport 16 U/kg for Treatments 1, 2, 3 and 4; Group B received 8 U/kg for those treatments. Group C received 2 U/kg for Treatment 1, then 8 or 16 U/kg for Treatments 2, 3 and 4. Doses were given in one upper extremity, called the study limb. The registry record does not report how participants in Group C were assigned between the later dose levels.

The primary measure is the mean change in MAS score in the PTMG from baseline at TC 1, Day 1 to TC 1, Week 6. The analysis population is described as mITT and requires receipt of at least 1 study-treatment injection and MAS assessments at both time points. That population definition is narrower than simply being randomized. The primary-endpoint analysis has 69 participants in the 2 U/kg group, 69 in the 8 U/kg group and 70 in the 16 U/kg group.

The record lists two secondary outcomes: Physician's Global Assessment and Goal Attainment Scale total score at TC 1, Week 6. Details such as the randomization procedure, allocation concealment, who was masked, the original sample-size justification, and the protocol's analysis plan 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.

Before assignment: Subjects had a body weight ≥10 kilograms (kg), increased muscle tone/spasticity in at least 1 upper limb, a modified Ashworth scale (MAS) score ≥2 in the upper limb primary targeted muscle group (PTMG) of the study limb at baseline. Subjects were stratified according to age (2-9 and 10-17 years) and Botulinum Toxin (BTX) naïve or non-naïve status.

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: The mITT population consisted of all randomised subjects who received at least 1 injection of the study treatment and had a MAS score in the PTMG assessed at both baseline (TC 1, Day 1) and at TC 1, Week 6.

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: Baseline characteristics are presented for the safety population, which consisted of all randomised subjects who received at least 1 injection of the study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change From Baseline to TC 1, Week 6 in MAS Score in the TC 1 PTMG, measured over Baseline (TC 1, Day 1) and TC 1, Week 6..

The primary endpoint is mean change from baseline to TC 1, Week 6 in the Modified Ashworth Scale (MAS) score for the PTMG. The registry describes MAS as a graded assessment of upper-limb muscle tone, with grades running from 0, indicating no increase in muscle tone, to 4, indicating rigidity in flexion or extension. The original '+1' grade was recoded to a numeric score, leaving a 0 to 5 score range. Higher scores indicate greater muscle tone.

The endpoint is expressed as a change from baseline. A negative change therefore indicates a decrease in muscle tone, while the comparison between groups asks whether the average change differed by assigned dose group. This is a continuous outcome summarized by its mean and standard deviation. The registry's mITT definition requires a baseline and TC 1, Week 6 assessment, as well as receipt of at least 1 injection. The observed group means describe the analyzed participants; they do not by themselves describe how every randomized participant's score changed.

MAS is used to quantify muscle tone using a structured clinical scale. It should not be treated as a complete measure of a child's overall condition or as a direct measure of function, participation or quality of life. Those broader outcomes are not the primary endpoint described in the registry record.

7. Results Posted in the Registry

• Dysport 8 U/kg: mean -1.90 versus -1.50 on control; difference -0.40 (95% CI -0.75 to -0.05), standardized effect d = -0.38; z-test p = 0.025.
• Dysport 16 U/kg: mean -2.20 versus -1.50 on control; difference -0.70 (95% CI -1.03 to -0.37), standardized effect d = -0.70; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Mean Physician's Global Assessment (PGA) Score at TC 1, Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Dysport 8 U/kg: mean 2.00 versus 1.70 on control; difference 0.30 (95% CI -0.00 to 0.60), standardized effect d = 0.33; z-test p = 0.051.
  • Dysport 16 U/kg: mean 2.00 versus 1.70 on control; difference 0.30 (95% CI -0.00 to 0.60), standardized effect d = 0.33; z-test p = 0.050.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dysport 8 U/kg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dysport 16 U/kg and the control. The interval gives the range of effects that remain compatible with the data.

Mean Goal Attainment Scale (GAS) Total Score at TC 1, Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Dysport 8 U/kg: mean 52.60 versus 51.30 on control; difference 1.30 (95% CI -2.09 to 4.69), standardized effect d = 0.13; z-test p = 0.452.
  • Dysport 16 U/kg: mean 52.00 versus 51.30 on control; difference 0.70 (95% CI -2.55 to 3.95), standardized effect d = 0.07; z-test p = 0.673.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dysport 8 U/kg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Dysport 16 U/kg and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists Physician's Global Assessment and Goal Attainment Scale total score as secondary outcomes at TC 1, Week 6. Across these measures, the numerical group summaries show small differences between the 2 U/kg group and the higher-dose groups relative to the variation reported within groups. The sponsor's analyses do not report a statistically clear separation for either secondary outcome. The posted comparisons therefore do not provide a consistent pattern of secondary evidence that strengthens the primary finding.

These measures address different aspects of assessment from the primary MAS change endpoint. Their estimates should not be treated as interchangeable with muscle-tone change, and a result on one outcome does not automatically confirm or negate a result on another. The overall pattern is best understood as a primary endpoint with sponsor-reported superiority analyses, alongside secondary outcomes whose reported analyses do not show a clear between-group difference.

Secondary results generally carry less inferential weight when many outcomes or comparisons may have been examined without a reported multiplicity plan. Testing several outcomes increases the opportunity for apparently notable findings to arise by chance. The registry record does not report whether a prespecified hierarchy, adjustment procedure or other multiplicity strategy was used. The posted secondary p-values and estimates should consequently be read as supportive or exploratory evidence rather than as standalone confirmation.

The registry does not report a full protocol-based interpretation of how these secondary outcomes were prioritized relative to the primary endpoint. Their estimates still describe the posted results, but uncertainty and multiplicity mean they should be considered in context rather than used to make a broad claim about every domain of outcome.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Mean Physician's Global Assessment (PGA) Score at TC 1, Week 6
• Mean Goal Attainment Scale (GAS) Total Score at TC 1, Week 6

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean change compare?

The primary outcome is continuous: each participant has a MAS score at baseline and at TC 1, Week 6, and the outcome is the change between those assessments. The reported group means summarize average change. Comparing mean changes asks whether the average score shift differs between dose groups. It does not imply that every participant's score changed by the group average. Standard deviations describe spread among individual values, rather than uncertainty in the estimated group mean.

General explanation: a mean difference is the first group mean minus the reference group mean under the stated comparison. A negative estimate in this endpoint means the higher-dose group had a more negative average change than the 2 U/kg group. The clinical interpretation still depends on the scale, population and importance of a score difference; a statistical contrast does not determine that importance on its own.

What is the recalculated comparison?

The recalculated comparisons are simple, unadjusted contrasts derived from the posted means and standard deviations. They summarize the difference between the 2 U/kg group and each higher-dose group without adjustment for other variables. The associated confidence intervals and p-values are likewise unadjusted. These recalculations are useful for understanding the scale and uncertainty of the posted summaries, but they are not a substitute for the sponsor's model-based analysis.

The sponsor reports ANCOVA for the primary endpoint, with back-transformed least-squares mean differences, and labels the comparisons as superiority analyses. ANCOVA is a regression-based approach that can compare group outcomes while accounting for covariates specified in the model. The covariates, model details and handling of the repeated treatment sequence are not reported in the registry record. The sponsor's p-values therefore represent its reported analysis, whereas the simple recalculation is a distinct analysis based only on posted summary statistics.

What do standard deviations and confidence intervals convey?

General explanation: a standard deviation describes how dispersed participant outcomes are around a group mean. It is not the same as a standard error, which describes the precision of an estimated mean. A confidence interval gives a range of values compatible with the data and the method used to calculate it. Wider intervals indicate less precision; intervals that include zero are compatible with no mean difference as well as differences in either direction, under the interval's assumptions.

For the primary recalculations, the interval for the 8 U/kg contrast excludes zero, and the interval for the 16 U/kg contrast also excludes zero. The primary-endpoint sponsor results report p-values but no confidence-interval limits in the registry record. The record does not provide the full ANCOVA model information needed to reconstruct those adjusted intervals.

Why can the analysis method matter?

General explanation: adjustment can change an estimate or its precision when covariates are related to the outcome. A model can also use assumptions about outcome distributions, relationships among variables and missing observations. If an outcome is skewed, has outliers, or does not fit model assumptions, a mean-based analysis may not capture every feature of its distribution. For a continuous score, it is useful to consider the group summaries alongside model-based estimates and uncertainty.

The MAS outcome is described as a graded scale recoded to a 0 to 5 numeric range and analyzed as a mean. The registry does not report a distributional assessment, a sensitivity analysis, a model diagnostic, or an alternative analysis of the ordinal score. That absence does not show that these methods were or were not used elsewhere; the relevant detail is not reported in the registry record.

How should p-values be read?

General explanation: a p-value describes how surprising data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the analysis assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The sponsor's primary p-values are from its ANCOVA comparisons; the recalculated p-values are unadjusted and arise from a simpler comparison.

The registry describes two sponsor primary comparisons against the 2 U/kg group. It does not report whether a multiplicity procedure was applied across these comparisons or across the wider set of outcomes. Without that information, the p-values should be interpreted as reported, with caution about the number of tests and the analysis plan.

What do the planning illustrations represent?

The sample-size illustrations use the observed effect as their starting point and show participant requirements under specified hypothetical assumptions. They are not a reconstruction of the trial's original design. General explanation: planning calculations translate an assumed effect size, variability, allocation and significance threshold into an approximate sample requirement for a chosen probability of detecting that effect. The resulting estimate depends on those assumptions and is not a guarantee that a future study will detect an effect.

11. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimated group difference. The recalculated primary comparison for 8 U/kg has a mean difference of -0.4, with an interval extending from below zero to a value close to zero; its unadjusted p-value is 0.025. The interval for 16 U/kg is centered on a more negative contrast, and its limits remain below zero; the unadjusted p-value is <0.001. These intervals describe the unadjusted comparisons, not the sponsor's ANCOVA estimates.

The sponsor-reported primary analyses give differences of -0.4 and -0.7, but confidence-interval limits are not reported in the registry record. A p-value alone cannot show the full range of effects compatible with a model. The registry also does not report a clinical threshold for interpreting whether a particular MAS difference is important to patients or caregivers. Statistical evidence against a null difference and clinical importance are related but separate questions.

The group standard deviations for primary MAS change are 1.1, 1.0 and 0.9 for the 2 U/kg, 8 U/kg and 16 U/kg groups, respectively. Standard deviations describe outcome variability, not the uncertainty in the estimated mean difference. The recalculated intervals combine the group summaries under the unadjusted comparison method. Differences between such intervals and model-based intervals can arise because the methods and assumptions differ.

General explanation: a confidence interval is not a range that contains a fixed proportion of individual participant outcomes. It expresses uncertainty about an estimated parameter under a specified method. A narrow interval indicates greater precision than a wide one, but neither width nor exclusion of zero alone establishes clinical relevance. The primary endpoint intervals provide a view of statistical precision for the unadjusted contrasts; missing sponsor interval limits and absent information on clinical thresholds constrain further interpretation.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations are participant counts per arm for the continuous outcomes in this study; they are not total event counts. They are based on a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as the stated fraction of the observed effect. The original design assumptions and sample-size justification for the trial are not reported in the registry record.

The 80% power column means the illustrated number of participants per arm for a design with an 80% chance of detecting the assumed effect under those planning assumptions, if that effect and the other assumptions hold. The 90% power column uses a higher target chance of detection and therefore generally requires more participants per arm. These are planning illustrations, not observed power.

Rows for planning at 100% of the observed effect use the full observed contrast as the hypothetical target. Rows for planning at 75% or 50% of the observed effect consider smaller target differences. Smaller effects are harder to distinguish from random variation when variability and other assumptions are held fixed, so the planning figures rise as the target effect becomes smaller. This relationship is a feature of the planning calculation, not evidence that a smaller effect will occur in a future study.

The 8 U/kg and 16 U/kg comparisons have separate planning figures because their observed contrasts differ. The illustrations do not account for details that are not stated in the planning assumptions, such as loss to follow-up or multiplicity adjustment. They should be read as conditional design examples rather than as evidence about the trial's actual power, adequacy of its original enrollment target or outcome certainty.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.400; pooled standard deviation σ = 1.051.
2. n = 2 × (1.96 + 0.842)² × 1.051² / -0.400² = 108.4, rounded up to 109 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.4                      # observed difference in means
sigma <- 1.05118980208143                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(2106351)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 109 (80% power), 146 (90% power)
 75% of observed effect: n per arm = 193 (80% power), 259 (90% power)
 50% of observed effect: n per arm = 434 (80% power), 581 (90% power)
power.t.test: 109.4 
Simulated power at n = 109 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor's primary analysis uses ANCOVA and reports back-transformed least-squares mean differences against the Dysport 2 U/kg group. For 8 U/kg, the reported difference is -0.4 with p = 0.012; for 16 U/kg, it is -0.7 with p < 0.001. Both comparisons are labeled superiority analyses. The registry does not report confidence-interval limits for these primary analyses.

The simple recalculations from the posted group means and standard deviations give differences of -0.4 and -0.7, with unadjusted p-values 0.025 and <0.001, respectively. The similarity in the displayed point estimates indicates that the direction and approximate scale of the sponsor estimates align with the summary-statistic contrasts. The p-values differ because the sponsor's ANCOVA and the unadjusted recalculations are not the same analysis; the registry does not report enough model detail to explain the precise difference.

The sponsor's own analysis takes precedence as the trial's reported inferential analysis. The recalculations provide context, not a correction or replacement. Since the discrepancy flag is false, no discrepancy between the posted summaries and the recalculated primary contrasts is identified in the record. Limits on interpretation remain: model covariates, analysis assumptions, multiplicity handling and adjusted confidence intervals are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The registry reports sponsor analyses for the primary endpoint against two dose groups and lists two secondary outcomes. It does not report whether the analysis plan adjusted for multiple comparisons, whether a testing hierarchy was specified, or how the secondary outcomes were intended to contribute to formal conclusions. When multiple outcomes or contrasts are tested, the chance of at least one apparently notable result can increase. General explanation: multiplicity procedures control or account for this issue, but their choice depends on the planned family of tests and the intended interpretation. Without a reported plan, the posted p-values should be read as individual results rather than assumed to have family-wise error control.

The primary analysis population is described as mITT: randomized participants who received at least 1 injection and had both baseline and TC 1, Week 6 MAS assessments. That definition excludes participants without the required endpoint measurements from this particular analysis. The registry record does not report how missing observations were handled, whether imputation was used, or what sensitivity analyses assessed the effect of missing data. It also does not report the full numbers randomized and analyzed by treatment sequence for every outcome.

Requiring observed values at both endpoint time points can affect which participants contribute to the mean change estimate. General explanation: if missingness is related to outcomes or treatment, a complete-observation analysis may not represent the randomized groups in the same way as an analysis that accounts for all randomized participants. The registry record does not supply enough detail to determine whether missingness was balanced or to assess its likely influence.

Random allocation and double masking are recorded, but methods of randomization, concealment and masking are not reported. The protocol's statistical analysis plan, interim analyses, model covariates, and sensitivity analyses are also not reported in the registry record. These omissions limit assessment of prespecification and robustness; they do not establish that these procedures were absent from the trial.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: vomiting (4.5%), cerebrovascular accident (4.5%), headache (4.5%), abdominal pain (4.5%), electrocardiogram st segment elevation (4.5%).

The registry reports serious adverse event counts separately by treatment cycle and dose group, with an at-risk denominator for each listed group. For TC1, the counts with serious adverse events are 4 of 70 for Dysport 2 U/kg, 2 of 70 for 8 U/kg and 2 of 70 for 16 U/kg. The later treatment-cycle entries list 6 of 88 and 1 of 90 for TC 2, 3 of 49 and 2 of 58 for TC 3, and 2 of 22 and 1 of 33 for TC 4, for the 8 U/kg and 16 U/kg entries respectively. These are cycle-specific records and should not be combined into a single participant total.

The registry lists deaths as 0 for each reported treatment group. Serious adverse event terms include vomiting, cerebrovascular accident, headache, abdominal pain, electrocardiogram ST segment elevation and dehydration, each reported at 4.5%. The record does not provide enough detail to infer causality or compare event risk across doses. Counts should be interpreted with their listed denominators and treatment-cycle context; they do not, alone, establish whether a treatment caused an event or characterize all safety outcomes.

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

The primary endpoint results describe mean MAS change from baseline to TC 1, Week 6 in the defined mITT population. Each dose group had a negative mean change, and the higher-dose group averages were more negative than the 2 U/kg group average. The sponsor's ANCOVA comparisons are reported as superiority analyses, with p-values 0.012 and < 0.001. These findings concern the measured muscle-tone score and the specified analysis; they are not a complete account of each participant's response.

The results do not establish that every child experienced a decrease, that dose groups differed in daily function, or that a score difference was important to children and families. The registry does not report a minimally important MAS difference or outcomes sufficient to answer those broader questions. Nor should the results be generalized beyond the studied population, doses, treatment schedule and assessment time without additional evidence.

Statistical significance is not the same as clinical importance. The sponsor's p-values characterize evidence under its model and assumptions, while the recalculated intervals describe uncertainty under unadjusted comparisons. The registry does not report adjusted confidence intervals for the sponsor analyses, model details, multiplicity handling or missing-data sensitivity analyses. These limits matter when assessing how robust or precise the finding is.

Safety counts are listed across treatment cycles, but the registry's event counts alone do not establish causation or provide a complete comparison of safety. The appropriate interpretation is limited: the record reports the named outcomes, group summaries and analyses, while important design and analysis details are not reported in the registry record. The results should be understood as evidence about these endpoints and comparisons, not as a universal statement about treatment effects.

18. Why This Trial Matters Statistically

This study illustrates why statistical interpretation needs more than a single p-value. The primary outcome is a change score on a graded clinical scale, and its direction matters: negative values indicate a decrease in muscle tone. Mean differences put the contrasts on the scale of the endpoint, while standard deviations and confidence intervals help distinguish average differences from participant-level variability and estimation uncertainty.

It also shows the distinction between a sponsor's adjusted model and a simple recalculation from posted summaries. The reported ANCOVA and the unadjusted comparisons have similar displayed point estimates, but they use different methods and produce different p-values. Keeping those analyses separate avoids treating a recalculation as the trial's prespecified or authoritative analysis. The sponsor's analysis is the reported trial analysis; the summary-statistic calculation is contextual.

The registry contains both primary and secondary outcomes, and the secondary findings do not provide a consistent clear separation between groups. Without a reported multiplicity plan, multiple p-values should not be read as if each stood alone with identical evidential weight. The record also defines an mITT population using treatment receipt and endpoint availability, making missing-data handling and analysis-population details important to interpretation.

Finally, the study's planning illustrations make explicit that sample-size needs depend on the effect assumed and the desired power. They are not observed power and do not reveal the original design rationale. The case therefore highlights the value of reporting protocol assumptions, model details, confidence intervals and missing-data methods alongside point estimates and p-values.

19. 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 limitations specific to this record constrain interpretation. The primary endpoint is an MAS score change assessed at TC 1, Week 6, and the record does not report a clinical threshold for judging the importance of a given score difference. MAS is a measure of muscle tone; the primary result should not be extended to functional abilities or broader quality-of-life outcomes that are not reported as primary endpoints.

The analysis population requires both baseline and follow-up MAS measurements and receipt of at least 1 injection. The registry does not report missing-data methods, sensitivity analyses, or a full accounting of excluded participants for the primary analysis. Therefore, the extent to which the analyzed set represents all randomized participants cannot be assessed from the registry record alone.

The sponsor reports ANCOVA, but the model covariates and other specifications are not reported. Confidence-interval limits are also not reported for the sponsor's primary analyses. The simple unadjusted recalculations provide intervals, but they cannot resolve uncertainty about the adjusted model. No multiplicity strategy is described despite multiple dose comparisons and secondary outcomes.

Group C's description includes an initial 2 U/kg treatment followed by 8 or 16 U/kg for later treatments, but the record does not report the allocation details for those later treatments. Safety entries are organized by treatment cycle and include varying at-risk denominators; they should not be treated as a single cumulative participant-level comparison. Randomization and double masking are recorded, but their implementation is not described. The trial's original sample-size assumptions, interim analyses and statistical plan are not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy And Safety Of Dysport In The Treatment Of Upper Limb Spasticity In Children — NCT02106351.
• Registry record last updated 2022-09-28; status last verified 2022-09.
• Results first posted 2019-12-24.
• 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.

23. Record Summary

NCT02106351 is a completed, randomized, double-blind, parallel-group Phase III study sponsored by Ipsen, with enrollment listed as 212. It assessed multiple Dysport doses in children with cerebral palsy and upper limb spasticity. The primary endpoint was mean change in PTMG MAS score from baseline to TC 1, Week 6, with negative change indicating decreased muscle tone.

Mean change was -1.5 for the 2 U/kg group, -1.9 for 8 U/kg and -2.2 for 16 U/kg. Sponsor ANCOVA analyses reported differences of -0.4 and -0.7 against 2 U/kg, with p-values 0.012 and < 0.001. Two secondary outcomes were listed, without a clear separation in the sponsor-reported analyses. Interpretation is limited by unreported details on multiplicity, missing data, model specification and the original design assumptions.