Efficacy & Safety Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy & Safety Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder (NCT01418339), a randomized phase 3 study. The primary outcome is Change From Baseline in Yale Global Tic Severity Scale (YGTSS) - Total Tic Score (TTS).

2. Clinical Question

The registry record describes a trial of once-weekly oral aripiprazole in children and adolescents with Tourette's Disorder. Its central question was whether change in tic severity over the treatment period differed between participants assigned to aripiprazole and those assigned to placebo. The main outcome was change from baseline to Week 8 in the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS).

3. Trial Design

This was a phase 3, randomized, parallel-group, placebo-controlled study. The registry lists quadruple masking and describes the treatment as double-blind. The study status is completed. The recorded enrollment was 135, but that is not the number analyzed for every outcome: the primary analysis reports participants with data available for analysis, and the safety groups have their own denominators.

The intervention was flexible-dose oral aripiprazole, given once weekly for 8 weeks, compared with a matching placebo given on the same schedule. The aripiprazole group began at 52.5 mg on Day 0. The available dose description does not give complete details of later adjustments, so the precise dose received over follow-up is not reported in the registry record. The randomization method and allocation concealment details are not reported in the registry record.

The primary outcome was change from baseline to Week 8 in YGTSS TTS, analyzed using a mixed effect repeated measure model (MMRM). The primary analysis population was described as modified intention-to-treat, excluding participants from two terminated sites and including participants with data available for analyses. The primary endpoint results list 71 participants in the aripiprazole group and 34 in the placebo group. The registry does not report the reasons for missing endpoint data or the detailed handling of missing observations.

Secondary outcomes were change from baseline to Week 8 in the Clinical Global Impressions Scale for Tourette's Syndrome (CGI-TS) score and the Gilles de la Tourette Syndrome Quality of Life Scale (GTS-QOL) total score. The registry also reports safety outcomes. The original sample-size justification, planned enrollment rationale, and detailed statistical 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: The study consisted of a Pretreatment and Treatment Phase. The Pretreatment Phase consisted of a Screening Period, Washout Period (when applicable), and Baseline visit. This was followed by an 8-week Treatment Phase. There was also a Follow-up Period (30 days) for participants who did not roll over into the open-label study 31-10-274 (NCT01416441).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intention-to-Treat (mITT) included all participants randomly assigned to the double-blind treatment, excluding participants from the two sites that were terminated. Overall number of participants analyzed is the number of participants with data available for analyses.

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: Intention-to-Treat (ITT) included all participants randomly assigned to the double-blind treatment.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Yale Global Tic Severity Scale (YGTSS) - Total Tic Score (TTS), measured over Baseline to Week 8.

The primary endpoint was change from baseline to Week 8 in the YGTSS Total Tic Score. The YGTSS is described as a semi-structured clinical interview designed to measure tic severity. It includes a tic inventory and ratings of motor and vocal tics across dimensions that include number, frequency, intensity, complexity, and interference, along with an impairment ranking. The TTS is the sum of motor- and vocal-tic severity scores.

The scale ranges from 0, indicating no symptoms, to 50, indicating severe symptoms. Higher scores represent more severe symptoms. Accordingly, a reduction from baseline is represented by a negative change, and a greater reduction is described in the registry as greater improvement. This direction is important when reading the group estimates: a more negative mean change indicates a larger average decrease in the score.

A continuous score preserves information about the degree of change rather than reducing outcomes to a yes-or-no category. The endpoint is used to quantify symptom severity in a structured way and to compare average changes between randomized groups. The interpretation remains limited to the measure and follow-up period: the score does not by itself establish how participants experienced other aspects of daily life, nor does it establish longer-term outcomes.

The registry reports least-squares means and standard errors for the groups and an MMRM treatment difference. These are model-based estimates, rather than simple unadjusted averages of each participant's change. Details beyond the stated MMRM approach are not reported in the registry record.

7. Results Posted in the Registry

• Aripiprazole: mean -12.34 versus -7.72 on control; difference -4.62 (95% CI -7.58 to -1.66), standardized effect d = -0.63; z-test p = 0.002.

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.

Change From Baseline in Clinical Global Impressions Scale for Tourette's Syndrome (CGI-TS) Score

• 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 errors.
• Result:
  • Aripiprazole: mean 2.29 versus 2.81 on control; difference -0.52 (95% CI -0.93 to -0.11), standardized effect d = -0.52; z-test p = 0.012.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Aripiprazole than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change From Baseline in Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL) Total Score

• 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 errors.
• Result:
  • Aripiprazole: mean 10.04 versus 12.04 on control; difference -2.00 (95% CI -8.23 to 4.23), standardized effect d = -0.13; z-test p = 0.529.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Aripiprazole and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes extend the assessment beyond the primary tic-severity score, covering clinical global impressions and quality of life. The results do not form a uniformly conclusive pattern: the registry-reported CGI-TS comparison has a confidence interval that excludes no difference, while the GTS-QOL interval includes no difference. This contrast cautions against treating the secondary outcomes as a single consistent body of evidence.

These measures address different constructs from the YGTSS TTS. A secondary finding can complement the primary result by describing another dimension of the trial, but it does not directly replicate the primary endpoint. Nor does an association on a secondary scale establish that the primary finding translates into a broader change in daily functioning or quality of life.

The registry records superiority analyses for the secondary comparisons but does not report a multiplicity adjustment, a testing hierarchy, or a prespecified strategy for interpreting the set of endpoints. When several outcomes are tested, the chance of at least one apparently notable result can increase if the tests are treated as independent opportunities for significance. This is a general statistical concern, not a claim about the actual probability of findings in this trial. Without a reported adjustment or analysis plan, the secondary p-values carry less inferential weight than a result protected by a clear prespecified testing strategy.

The appropriate overall reading is therefore supportive and cautious: the secondary findings add information about measured outcomes, but they do not establish a broad, consistent effect across all domains. The registry does not report thresholds for clinically meaningful changes on these secondary measures, so statistical evidence alone cannot establish the importance of the observed differences to participants.

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

• Change From Baseline in Clinical Global Impressions Scale for Tourette's Syndrome (CGI-TS) Score
• Change From Baseline in Gilles de la Tourette Syndrome - Quality of Life Scale (GTS-QOL) Total Score

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it records a score and its change over time. The registry reports least-squares means, standard errors, and an MMRM treatment difference. A least-squares mean is a model-based estimate of the group mean after accounting for the structure of the statistical model. It can differ from a raw arithmetic mean. A standard error describes the estimated uncertainty in a mean estimate; it is not the spread of individual participant scores.

What does the MMRM contribute?

A mixed effect repeated measure model is designed for outcomes measured repeatedly over time. In general, such a model can use the pattern of available repeated observations and account for the fact that measurements from the same participant are related. This can be useful when evaluating changes across visits, rather than treating each observation as independent. The registry says MMRM was performed, but details such as the covariance structure, fixed effects, visit-by-treatment terms, and missing-data assumptions are not reported in the registry record. Those details therefore cannot be assessed from the record.

The reported primary contrast is a treatment difference, with a 95% confidence interval and a p-value. The estimate is negative, consistent with a larger decrease in TTS in the aripiprazole group under the score's direction. The confidence interval describes a range of values compatible with the data and model at the stated confidence level; it does not give the probability that the true effect is inside that particular interval. The p-value measures how unusual data at least as incompatible with a no-difference hypothesis would be under the null model and its assumptions. It is not the probability that the null hypothesis is true, nor is it a measure of clinical importance.

How does the recalculation differ?

The recalculated comparison is an unadjusted calculation from the posted group summaries. It uses the group estimates and standard errors to approximate a between-group difference and its uncertainty. The pooled standard deviation used for standardized effect calculations is marked as approximate because it is derived from standard errors rather than directly reported participant-level variation. This recalculation does not reproduce the MMRM or its use of repeated measurements. It is a check based on summary statistics, not a second trial analysis.

The recalculated primary mean difference is -4.62, compared with the reported MMRM treatment difference of -4.63. Their confidence intervals are also close. The registry marks no discrepancy. These estimates can be compared as a consistency check, but the MMRM result remains the trial's reported analysis. The recalculation does not account for any model features that cannot be reconstructed from the summaries.

Why does over-dispersion matter in general?

In general, a model that assumes less variability than the data actually contain can understate uncertainty and make confidence intervals too narrow. Over-dispersion refers to variation greater than a model's assumed level. Allowing for appropriate variation matters because standard errors and significance tests depend on the uncertainty model. The primary endpoint is analyzed with MMRM, not a count model, and the registry does not report a model-based over-dispersion assessment. This general concept should not be read as a claim that over-dispersion occurred in this trial.

The secondary outcomes are also continuous measures and are reported with MMRM treatment differences. The registry gives separate results for CGI-TS and GTS-QOL. It does not report whether the secondary analyses were prespecified in a hierarchy, whether testing was adjusted for multiplicity, or what role they had in the trial's confirmatory inference. Without those details, their p-values are best treated as exploratory or supportive rather than as independent confirmation of the primary result.

Analysis populations also affect interpretation. The primary outcome description defines a modified intention-to-treat population and specifies exclusions related to two terminated sites. It further states that the number analyzed is the number with data available. This is not identical to an analysis of every randomized participant regardless of data availability. The detailed missing-data approach, participant flow by visit, and sensitivity analyses are not reported in the registry record, so the robustness of the result to missing observations cannot be evaluated fully.

11. Confidence Intervals and Precision

The sponsor-reported primary treatment difference is -4.63, with a 95% confidence interval from -7.62 to -1.63. The interval gives a range of effect estimates compatible with the observed data and the MMRM assumptions at the stated confidence level. Every value in the interval is negative, which supports a between-group difference in the direction of a larger decrease in TTS for aripiprazole relative to placebo. The interval also shows that the exact size of the difference remains uncertain; the point estimate alone should not be read as exact.

The recalculated interval, from -7.584 to -1.656, has a similar direction and extent. Its precision is based on approximate reconstruction from the posted summary statistics and is not the same as the model-based uncertainty reported by the trial. The sponsor's reported interval should be used when describing the trial's own analysis.

A confidence interval is not a guarantee that the true effect lies within its endpoints, and it does not describe the range of individual participant responses. It quantifies uncertainty around a group-level estimate under the analysis assumptions. A narrow interval indicates more precision than a broad interval, but precision does not determine whether an effect is important to patients. Clinical importance requires interpretation beyond statistical significance, and a threshold for meaningful change is not reported in the registry record.

For the primary estimate, the interval excludes zero, while the GTS-QOL secondary interval spans zero. This difference in interval position is relevant to whether each comparison is statistically distinguishable from no difference under its analysis, but it does not itself settle the relative importance of the measures or resolve multiplicity concerns. The registry does not report confidence intervals for individual participant outcomes or a prediction interval for future settings.

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 figures are participants per arm, not total events. They are illustrations based on the observed effect, not the trial's original design calculation. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. The original trial's own sample-size assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm that the planning calculation indicates would give an 80% chance of detecting the chosen effect under those assumptions, if that effect were the true effect. The 90% power column describes the corresponding number per arm for a 90% chance. These are planning probabilities under a hypothetical effect and model, not guarantees for a future study. They are not observed power.

The rows using 100%, 75%, and 50% of the observed effect illustrate how the planning requirement changes when the effect targeted for detection changes. A smaller effect is harder to distinguish from random variation and therefore requires more participants for the same nominal power and significance level. The curve represents this planning relationship; it should be read as a sensitivity illustration, not as a reconstruction of the trial's protocol or an assertion about what the original investigators planned.

The observed group sizes were unequal, whereas the planning illustration assumes equal allocation. That difference is another reason to treat the figures as hypothetical planning guidance rather than a direct account of the trial's design. The registry record does not report whether the original design used a different allocation target, allowance for attrition, or other assumptions.

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 = -4.620; pooled standard deviation σ = 7.338.
2. n = 2 × (1.96 + 0.842)² × 7.338² / -4.620² = 39.6, rounded up to 40 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 <- -4.62                      # observed difference in means
sigma <- 7.33805204171995                     # 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(1418339)
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 = 40 (80% power), 54 (90% power)
 75% of observed effect: n per arm = 71 (80% power), 95 (90% power)
 50% of observed effect: n per arm = 159 (80% power), 213 (90% power)
power.t.test: 40.6 
Simulated power at n = 40 per arm: 0.801 (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 registry reports the primary analysis as an MMRM treatment difference of -4.63, with a 95% confidence interval from -7.62 to -1.63 and p=0.003. This is the sponsor's reported analysis and should anchor interpretation of the trial result.

The simple recalculation from group-level summaries gives a mean difference of -4.62, a 95% confidence interval from -7.584 to -1.656, and p=0.002. These results are close to the reported MMRM estimates in direction and magnitude. The record does not flag a discrepancy. Similarity is reassuring as a consistency check, but the recalculation is not a reproduction of the repeated-measures model: it relies on summary statistics and cannot recover details of the underlying model or participant-level data.

The reported MMRM analysis and the recalculation answer related but not identical computational questions. The former is the analysis recorded for the trial; the latter is an unadjusted approximation based on posted summaries. The recalculation should not replace the sponsor's analysis or be treated as an independent replication. Its role is to provide a transparent comparison of the posted group summaries with the reported treatment contrast.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and two secondary outcomes. It does not report a multiplicity adjustment, a hierarchical testing sequence, or a rule for controlling the overall type I error across outcomes. Testing several outcomes without adjustment can increase the chance that at least one result appears statistically significant by chance. This general concern is why secondary results usually receive less weight when the statistical plan for multiple testing is not available.

The primary endpoint was analyzed with MMRM. The registry describes the analysis population as modified intention-to-treat: participants randomly assigned to double-blind treatment were included, except participants from two sites that were terminated. It also says the number analyzed is the number of participants with data available for analyses. This definition makes clear that the primary analysis was not simply every randomized participant under all circumstances.

The available record does not report the number of missing endpoint observations by group or visit, reasons for missingness, how the MMRM handled missing measurements, or sensitivity analyses under alternative missing-data assumptions. It also does not report whether there was an interim analysis, whether any stopping rules were used, or the detailed statistical analysis plan. These points are not reported in the registry record and should not be inferred from the completed status or the posted outcome analysis.

Missing data matter because the observed participants may differ from those without outcome measurements. A model can make use of available repeated observations, but the validity of its estimate depends in part on assumptions about why data are missing and how that missingness relates to observed and unobserved outcomes. Without fuller information, the direction and size of any potential bias cannot be determined from the registry results alone.

The record also does not provide enough detail to evaluate whether exclusions related to the terminated sites were decided before outcomes were reviewed or how those exclusions affected the analysis. This is not evidence of inappropriate handling; it is a limit on what can be assessed from the registered information.

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: dystonia (2.2%), hyperthermia (1.1%), alanine aminotransferase increased (1.1%), aspartate aminotransferase increased (1.1%), blood creatine phosphokinase increased (1.1%).

The safety summaries use denominators different from the primary efficacy analysis. Serious adverse events were reported for 3 participants among 90 at risk in the aripiprazole group and 0 among 45 at risk in the placebo group. Other adverse events were reported for 38 among 90 and 8 among 45, respectively. Deaths were reported as 0 in both groups. These are event summaries for the stated safety populations, not the primary analysis population.

The listed serious-event terms include dystonia at 2.2%, and hyperthermia, increased alanine aminotransferase, increased aspartate aminotransferase, increased blood creatine phosphokinase, and prolonged electrocardiogram QT at 1.1% each. These term-level percentages describe the registry's listed serious-event terms; they should not be interpreted as a complete account of event severity, timing, recurrence, or causal relationship.

Safety counts are descriptive and do not by themselves establish that an event was caused by treatment or that differences between groups are reliable. The registry record does not provide enough detail to assess exposure-adjusted event rates, event duration, or the clinical circumstances of each event. These figures describe what was recorded during the trial, not a prediction for an individual.

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

The primary result indicates that the trial's MMRM estimate of average change in YGTSS TTS favored a larger decrease in the aripiprazole group than in the placebo group over the recorded interval from baseline to Week 8. The reported confidence interval excludes zero, and the reported p-value is consistent with a statistically distinguishable group difference under the model and analysis assumptions.

This result does not mean that every participant had a decrease, that each participant benefited to the same extent, or that the average difference is necessarily meaningful to every patient or family. Group averages do not show the full distribution of individual responses. The registry does not report a threshold for a clinically meaningful change in TTS, so statistical evidence should not be equated automatically with clinical importance.

The finding is specific to the population, treatment schedule, comparator, endpoint, analysis population, and follow-up period described in the record. The outcome concerns tic severity as measured by the YGTSS TTS. It does not by itself establish effects on all symptoms, functioning, quality of life, or outcomes beyond Week 8. The secondary outcomes provide additional measured information but do not make the evidence uniform across domains.

The confidence interval communicates uncertainty around the estimated group difference, while the p-value addresses compatibility with a no-difference hypothesis under stated statistical assumptions. Neither quantity measures the chance that the treatment will produce a particular outcome for an individual. The safety summaries likewise describe recorded events in the trial groups and cannot determine causation for an individual event.

In statistical terms, the posted primary analysis supports a group-level difference in change on the specified scale. It does not, on its own, settle questions about broader benefits, longer-term outcomes, clinical importance, or applicability to people outside the trial population. Those questions require evidence beyond the endpoint estimate and its statistical uncertainty.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should be read through its endpoint, analysis population, model, and uncertainty together. The primary scale has a clear direction: higher TTS means more severe symptoms, while a more negative change represents a larger decrease. That direction makes the sign of the treatment difference interpretable rather than merely numerical.

The record also makes a useful distinction between the reported model-based analysis and a simple recalculation from group summaries. Their close estimates offer a consistency check, while the MMRM result remains the trial's own analysis. The recalculation cannot reconstruct repeated-measures modeling details or substitute for participant-level data.

Different analysis denominators matter. The primary efficacy population and the safety groups have different reported counts, reflecting different analysis contexts. Treating enrollment, efficacy analysis, and safety denominators as interchangeable would obscure who contributed to each result.

The secondary outcomes show why multiplicity and outcome scope matter. Statistical findings across outcomes are not automatically equivalent, particularly when an adjustment strategy is not reported. A primary endpoint can show a comparatively clear estimate while secondary measures offer a less uniform pattern. This calls for a calibrated interpretation rather than a single all-purpose conclusion.

Finally, confidence intervals help convey the uncertainty around the average difference, but precision is not the same as clinical importance. Reading the effect estimate alongside the scale's meaning, the study's follow-up, and limitations in the registry's analysis details is central to sound biostatistical interpretation.

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.

The registry record leaves important design and analysis details unreported. It does not give complete eligibility criteria, the randomization procedure, allocation concealment details, the full dose-adjustment schedule, or the original sample-size justification. The description of the aripiprazole starting dose is available, but later dosing specifics are not reported in the registry record.

The primary analysis excludes participants from two terminated sites and is limited to participants with available data. The record does not explain the site terminations, report missing outcome data by group, or provide sensitivity analyses for missingness. It is therefore not possible to judge from the registry alone how strongly the findings depend on the exclusions or missing-data assumptions.

The MMRM is identified, but the registry does not report its detailed specification, including covariance structure, model terms, or assumption checks. The recalculated summaries use an approximate standard deviation and cannot reproduce the model. The reported results also do not provide individual participant data or the distribution of responses, limiting assessment of heterogeneity.

The registry does not report adjustment for multiple secondary outcomes or a hierarchy for their interpretation. Nor does it provide a clinical-importance threshold for the primary or secondary measures. Safety information is presented as counts and listed terms; details needed to assess exposure duration, timing, recurrence, and attribution are not available in the record.

Follow-up for the primary outcome is baseline to Week 8. Longer-term outcomes and broader applicability beyond the recorded population and treatment schedule are not established by these results. These limitations identify what cannot be assessed from the registry information; they do not negate the estimates that are reported.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy & Safety Study of Once-weekly Oral Aripiprazole in Children and Adolescents With Tourette's Disorder — NCT01418339.
• Registry record last updated 2021-10-07; status last verified 2021-09.
• Results first posted 2021-10-07.
• 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

The registry record describes a completed, randomized, parallel, placebo-controlled phase 3 study of once-weekly oral aripiprazole in children and adolescents with Tourette's Disorder. It lists quadruple masking and describes an 8-week treatment period. The primary outcome was change from baseline to Week 8 in YGTSS Total Tic Score, analyzed using MMRM in a modified intention-to-treat population.

The reported primary treatment difference was -4.63, with a 95% confidence interval from -7.62 to -1.63 and p=0.003. A simple unadjusted recalculation from posted group summaries was similar. Secondary outcomes covered CGI-TS and GTS-QOL; their overall statistical pattern was not uniform. Safety summaries report serious and other adverse events using separate safety denominators, with no deaths recorded in either group.

Multiplicity handling, detailed missing-data methods, and the original sample-size rationale are not reported in the registry record. Interpretation is therefore strongest for the posted primary comparison and should remain specific to its endpoint, analysis population, and follow-up.