Study Evaluating the Safety and Efficacy of Fixed-dose Once-daily 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 Study Evaluating the Safety and Efficacy of Fixed-dose Once-daily Oral Aripiprazole in Children and Adolescents With Tourette's Disorder (NCT01727700), a randomized phase 3 study. The primary outcome is Change From Baseline to Week 8 in Yale Global Tic Severity Scale (YGTSS) Total Tic Score (TTS)..

2. Clinical Question

3. Trial Design

The registry describes a Phase 3, randomized, quadruple-masked, parallel-group, placebo-controlled study sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. It is titled as a study of fixed-dose, once-daily oral aripiprazole in children and adolescents with Tourette’s disorder. The study status is completed. The recorded start is 2012-11, and primary completion is 2013-08. The enrollment entry is 133.

There were three treatment arms: aripiprazole low dose, aripiprazole high dose, and placebo. The arm descriptions specify immediate-release once-daily aripiprazole 5 mg or 10 mg for the low-dose arm and 10 mg or 20 mg for the high-dose arm; placebo was matching and once daily. The registry does not explain the dose-selection or dose-adjustment process, so those details should not be inferred from the arm labels.

Randomization is a design feature intended to allocate treatment groups without systematic selection by investigators. Masking is intended to limit the influence of treatment knowledge on care, assessment, or reporting. The record says quadruple masked but does not identify the roles covered by that description. It also does not report the randomization procedure or allocation concealment details.

The primary endpoint was change from baseline to Week 8 in YGTSS Total Tic Score. The registry identifies an intent-to-treat population of all participants randomly assigned to double-blind treatment, while the endpoint record notes that Week 8 data were available for 42 low-dose, 35 high-dose, and 42 placebo participants. These entries describe the reported endpoint data and should not be treated as a complete account of every participant’s follow-up.

The original sample-size justification, planned allocation ratio, and trial-specific power assumptions are not reported in the registry record. Likewise, the record does not give enough detail to reconstruct the full protocol or analysis plan from the design labels alone.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: The trial consisted of a pretreatment phase and a treatment phase. Pretreatment phase consisted of a screening and washout (when applicable) period. This was followed by an 8-week treatment phase starting with the baseline visit (Day 0). Particpants were randomized 1:1:1 to aripiprazole high dose, aripiprazole low dose or placebo.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population: All participants randomly assigned to the double-blind treatment. At Week 8, data were available for 42 participants in the low dose, 35 in the high dose and 42 in the placebo group.

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 to Week 8 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 Yale Global Tic Severity Scale Total Tic Score. The YGTSS is described as a semi-structured clinical interview assessing current tic severity over the past 1 week. It includes a tic inventory and ratings across dimensions of motor and vocal tics, including number, frequency, intensity, complexity, and interference. The ratings are combined into the Total Tic Score, which ranges from 0 to 50 according to the registry description. The instrument also includes an impairment ranking, but that ranking is distinct from the primary Total Tic Score.

A change score expresses how the measured score shifted over the specified interval. Since lower YGTSS scores represent lower tic severity, negative changes indicate a decrease in the measured score. The endpoint is useful for comparing the groups’ average change over the same follow-up period, but it does not describe every participant’s individual course or establish what a particular score change means for an individual.

The registry reports least-squares means, with standard errors, for each group. Least-squares means are model-based group averages; they are not necessarily identical to simple arithmetic averages. The primary comparison is the treatment difference between each aripiprazole group and placebo. The registry gives Week 8 data availability counts for the endpoint, but detailed information about the model specification and missing-data handling is not reported in the registry record.

7. Results Posted in the Registry

• Aripiprazole Low Dose: mean -13.35 versus -7.09 on control; difference -6.26 (95% CI -10.61 to -1.91), standardized effect d = -0.62; z-test p = 0.005.
• Aripiprazole High Dose: mean -16.94 versus -7.09 on control; difference -9.85 (95% CI -14.23 to -5.47), standardized effect d = -1.00; 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.

Change in Clinical Global Impressions Scale-Tourette's Syndrome (CGI-TS) Score at Week 8.

• 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 Low Dose: mean 2.12 versus 3.15 on control; difference -1.03 (95% CI -1.60 to -0.46), standardized effect d = -0.78; z-test p = <0.001.
  • Aripiprazole High Dose: mean 2.13 versus 3.15 on control; difference -1.02 (95% CI -1.59 to -0.45), standardized effect d = -0.80; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Aripiprazole Low Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Aripiprazole High Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Mean Change From Baseline to Endpoint (Week 8) in Total YGTSS 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 Low Dose: mean -26.69 versus -13.43 on control; difference -13.26 (95% CI -22.42 to -4.10), standardized effect d = -0.62; z-test p = 0.005.
  • Aripiprazole High Dose: mean -32.80 versus -13.43 on control; difference -19.37 (95% CI -28.60 to -10.14), standardized effect d = -0.94; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Aripiprazole Low Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Aripiprazole High Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Mean Change From Baseline to Endpoint (Week 8) in CGI-TS Severity 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 Low Dose: mean -1.35 versus -0.55 on control; difference -0.80 (95% CI -1.33 to -0.27), standardized effect d = -0.65; z-test p = 0.003.
  • Aripiprazole High Dose: mean -1.47 versus -0.55 on control; difference -0.92 (95% CI -1.45 to -0.39), standardized effect d = -0.78; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Aripiprazole Low Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Aripiprazole High Dose than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary results generally follow the direction of the primary endpoint: the reported group changes and treatment differences for the secondary continuous measures are more negative in the aripiprazole groups than in placebo. The posted comparisons also report small p-values for these measures. In broad terms, this pattern is consistent with the direction of the primary YGTSS Total Tic Score result, but secondary outcomes are supporting context rather than an independent replacement for the primary endpoint.

The secondary outcomes named in the registry include the Clinical Global Impressions Scale-Tourette’s Syndrome score, total YGTSS score, CGI-TS severity score, response rate, and treatment discontinuation rate. The registry lists six outcome measures and five secondary results posted. The continuous secondary summaries include CGI-TS score at Week 8, change in total YGTSS score, and change in CGI-TS severity score. Results for response rate and treatment discontinuation rate are not reported in the registry record, so their direction or magnitude cannot be inferred.

Secondary analyses commonly involve multiple outcomes or comparisons. When many hypotheses are assessed, the chance of seeing at least one nominally small p-value can increase unless the analysis accounts for multiplicity. Whether a correction or hierarchical testing plan was used is not reported in the registry record. Therefore, unadjusted secondary p-values carry less weight than a prespecified primary analysis and should not be read as confirmatory evidence on their own.

The different scales also capture related but non-identical aspects of symptoms and clinical assessment. Agreement in direction can add coherence to the overall pattern, but it does not establish that every endpoint measures the same construct or that their estimates are interchangeable. The posted endpoint-specific results and their uncertainty remain the appropriate basis for describing each measure.

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

• Change in Clinical Global Impressions Scale-Tourette's Syndrome (CGI-TS) Score at Week 8.
• Mean Change From Baseline to Endpoint (Week 8) in Total YGTSS Score
• Mean Change From Baseline to Endpoint (Week 8) in CGI-TS Severity Score
• Response Rate
• Treatment Discontinuation Rate

9. Statistical Interpretation

10. Statistical Methods Explained

Clinical trial results for continuous outcomes often describe each group’s average change and a difference between groups. Here, the continuous outcome is YGTSS Total Tic Score change from baseline to Week 8. The group values are least-squares means, accompanied by standard errors. The treatment difference compares the mean change in an aripiprazole arm with the mean change in placebo. Since the endpoint is a change score, its negative direction indicates a decrease in the scale score; a more negative treatment difference indicates a greater average decrease relative to placebo.

What does a least-squares mean represent?

A least-squares mean is an estimate from a statistical model. In general, model-based means can account for the structure specified in that model and may differ from unadjusted arithmetic averages. The registry gives the least-squares mean parameter and identifies the reported comparison method as Mixed Models Analysis, but the full model specification, included covariates, covariance structure, and estimation details are not reported in the registry record. Those details matter when attempting to reproduce a model-based result.

What does the standard error describe?

A standard error describes the statistical uncertainty in an estimated mean, rather than the spread of individual participants’ scores. Smaller standard errors generally indicate a more precisely estimated mean, while larger standard errors indicate more uncertainty. The reported standard errors are 1.59, 1.61, and 1.55 for the primary endpoint’s low-dose, high-dose, and placebo groups, respectively. They should not be interpreted as standard deviations or as the range of participant-level responses.

How should a confidence interval be read?

A confidence interval gives a range of values reasonably compatible with the data and the method used, under the model’s assumptions. The sponsor-reported primary comparison intervals are 95% confidence intervals. They communicate both the direction and the precision of the estimated treatment differences. A confidence interval is not a probability statement that the true effect lies in the particular interval after the data have been observed, and it does not describe how widely individual outcomes vary.

What does a p-value say?

A p-value measures how compatible the observed data are with a specified null hypothesis under the analysis assumptions. A small p-value indicates that data as extreme as those observed would be less compatible with that null model. It does not measure the probability that the null hypothesis is true, the probability that the result is due to chance, or the clinical importance of the estimated difference. The sponsor-reported primary p-values are 0.002 and < 0.001 for the low-dose and high-dose comparisons, respectively.

Why do the recalculated results differ in precision?

The recalculated estimates are simple unadjusted comparisons using posted group summary statistics. The pooled standard deviations used for those comparisons are approximate, inferred from the reported standard errors. That approach cannot reproduce all features of a mixed model, including any model adjustments or assumptions that are not captured by the summary statistics. Accordingly, recalculated confidence intervals and p-values differ from the sponsor’s reported results even though the estimated treatment differences match at the precision shown. They serve as a transparent summary-statistic check, not as an alternative version of the trial’s full analysis.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. It is especially relevant to count outcomes when a simple count model assumes less variability than the data contain. Greater variability can make uncertainty estimates too narrow if it is not addressed. The primary endpoint in this trial is a continuous scale score, so count-model over-dispersion is not the central issue for the primary comparison. The registry record does not report whether over-dispersion was assessed for any other outcome.

These statistical concepts explain how to read the estimates; they do not establish that the model assumptions were met. The registry record does not report diagnostic checks or enough details to assess the model specification independently.

11. Confidence Intervals and Precision

The primary treatment-difference estimates are accompanied by 95% confidence intervals from the sponsor-reported Mixed Models Analysis. For low-dose aripiprazole versus placebo, the estimate is -6.26 and the interval runs from -10.18 to -2.34. For high-dose aripiprazole versus placebo, the estimate is -9.85 and the interval runs from -13.84 to -5.86. Both reported intervals lie on the negative side of zero, consistent with a more negative mean change in the aripiprazole group than in placebo under the reported model.

Precision concerns how narrowly an estimate is determined. A confidence interval gives a range of values compatible with the observed data and analysis assumptions; narrower intervals indicate greater precision than wider intervals. The intervals do not show the spread of individual participant outcomes, and they do not guarantee that the true effect lies within the reported range. Their interpretation depends on the model and its assumptions, whose full details are not reported in the registry record.

The recalculated unadjusted intervals are wider than the sponsor-reported intervals for both primary comparisons: -10.61 to -1.908 for low-dose aripiprazole and -14.23 to -5.47 for high-dose aripiprazole. These were derived from summary statistics using an approximate pooled standard deviation, so the differences in interval width should not be read as a direct test of which analysis is correct. The sponsor-reported mixed-model estimates and intervals describe the trial’s own posted analysis; the recalculated intervals are supplementary approximations.

The reported interval endpoints and p-values indicate statistical uncertainty, not clinical importance. The registry record does not provide a clinically meaningful threshold for the YGTSS treatment difference. The available Week 8 counts are 42, 35, and 42 across the low-dose, high-dose, and placebo groups, respectively; the record does not give sufficient missing-data details to determine how data availability may affect precision.

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 sample-size figures are planning illustrations based on the observed effect in the trial, not the original design calculations. For these continuous outcomes, the entries are participants per arm, not total participants across arms or total events. The planning assumptions are 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 80% power column gives the estimated participants per arm for a hypothetical study to have an 80% chance of detecting the chosen effect under those assumptions, if that effect is the true one and the planning model applies. The 90% power column gives the corresponding per-arm illustration for 90% power. These are design calculations; they do not say how likely the observed trial result was to be true or how likely the trial was to detect its actual effect.

Rows for planning at 100% of the observed effect use the observed estimate as the target. Rows for 75% and 50% use smaller fractions of that estimate. A smaller effect is harder to distinguish from random variation, so the illustration requires more participants per arm as the target effect gets smaller. This is not observed power.

These calculations do not reconstruct the trial’s original planning. The original sample-size assumptions and justification are not reported in the registry record. The illustrations rely on observed effects, which may be unstable estimates, and their assumptions may not match the trial’s actual model, allocation, missingness, or multiplicity procedures. Use the values as conditional planning scenarios rather than as evidence that the completed study was designed or powered in a particular way.

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 = -6.260; pooled standard deviation σ = 10.176.
2. n = 2 × (1.96 + 0.842)² × 10.176² / -6.260² = 41.5, rounded up to 42 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 <- -6.26                      # observed difference in means
sigma <- 10.1755884350734                     # 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(1727700)
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 = 42 (80% power), 56 (90% power)
 75% of observed effect: n per arm = 74 (80% power), 99 (90% power)
 50% of observed effect: n per arm = 166 (80% power), 223 (90% power)
power.t.test: 42.5 
Simulated power at n = 42 per arm: 0.796 (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’s reported primary analyses use Mixed Models Analysis. For the low-dose comparison, the sponsor reports a treatment difference of -6.26, a 95% confidence interval from -10.18 to -2.34, and p = 0.002. For the high-dose comparison, it reports -9.85, a 95% confidence interval from -13.84 to -5.86, and p < 0.001.

The recalculated comparisons use the posted group summary statistics and are unadjusted. Their difference estimates are -6.26 and -9.85, matching the sponsor’s treatment-difference estimates at the displayed precision. Their confidence intervals and p-values differ: the recalculated results use approximate pooled standard deviations inferred from reported standard errors and do not reproduce the mixed-model analysis. They are useful as a separate summary-statistic check, but should not be substituted for the sponsor’s analysis when reporting the trial’s own inferential results.

The registry marks no discrepancy between the recalculated and reported estimates. That does not make the methods identical: the agreement in the point estimates coexists with differences in uncertainty estimates and p-values. The full mixed-model specification is not reported in the registry record, so the recalculation cannot be used to reconstruct or verify every detail of the sponsor’s model.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary endpoint, change from baseline to Week 8 in YGTSS Total Tic Score, and lists secondary outcomes that include clinical global impression scores, total YGTSS score, response rate, and treatment discontinuation rate. It also records 14 analyses. Having multiple outcomes and comparisons raises a multiplicity question: repeated statistical testing can increase the chance of one or more small p-values even if no true differences exist for some comparisons.

The registry record does not report whether the trial used a multiplicity adjustment, a hierarchical testing procedure, or another prespecified approach to control the overall error rate. It does not report the order in which endpoints were tested or whether some comparisons were designated exploratory. Consequently, the primary endpoint should be distinguished from secondary results, and unadjusted secondary p-values should be interpreted cautiously. The original statistical analysis plan and the detailed rationale for the number of analyses are not reported in the registry record.

The primary outcome description defines the intent-to-treat population as all participants randomly assigned to double-blind treatment. It also states that Week 8 data were available for 42 participants in the low-dose arm, 35 in the high-dose arm, and 42 in placebo. The registry does not provide a complete participant-flow account in the registry record recorded for this analysis, nor does it explain why outcome data were not available for everyone in the intent-to-treat population.

Missing data can affect both the estimated treatment difference and its precision. The effect depends on why observations are missing and how the analysis handles them. The registry record does not report the missing-data assumptions, imputation method, sensitivity analyses, or whether the mixed model used all available repeated measurements. It would therefore be inappropriate to assume that missingness was harmless or that a particular method was used.

The record names a Mixed Models Analysis for the primary comparisons but does not supply its complete specification. It also does not report interim analyses, stopping rules, protocol deviations, or sensitivity analyses. These omissions limit an independent assessment of how analysis choices and missing observations may have influenced the posted estimates.

16. 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 non-serious adverse event terms

The registry reports serious adverse event counts among participants at risk by arm. The serious adverse event count is 0 in the low-dose aripiprazole group, with 44 at risk; 0 in the high-dose group, with 45 at risk; and 0 in the placebo group, with 44 at risk. These figures mean that no serious adverse events are recorded as affecting participants in the posted group summaries. They do not establish that no adverse events of any kind occurred.

The record separately reports other adverse events affecting 21 participants in the low-dose group, 29 in the high-dose group, and 8 in placebo, with the corresponding at-risk counts stated above. Those counts are not serious adverse event counts and should not be conflated with them. The registry’s serious adverse event terms list is empty.

Deaths are not shown as numeric counts in the registry record, so death counts are not reported in the registry record. The summaries do not give event types for the other adverse events here, severity, timing, duration, attribution, or participant-level detail. Counts by arm alone do not establish comparative safety, causation, or the clinical importance of events. They should be read as registry-reported event summaries, not as a complete safety assessment.

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

The posted primary results show more negative average change in YGTSS Total Tic Score in both aripiprazole groups than in placebo over baseline to Week 8. The sponsor-reported mixed-model treatment differences are negative, and their 95% confidence intervals lie below zero. This describes the estimated difference in group mean change under the reported analysis; it is not a statement that every participant’s score decreased or that every participant experienced the same degree of change.

The estimates do not, by themselves, establish the clinical importance of the differences. The registry describes the YGTSS and its scoring but does not report a threshold for a clinically meaningful treatment difference. Statistical evidence and clinical importance are related but distinct questions. A small p-value does not tell how valuable a difference is to patients, and a confidence interval does not describe an individual participant’s likely response.

The study was conducted in children and adolescents with Tourette’s disorder and compared two aripiprazole dose arms with matching placebo. The results should not be generalized automatically to other populations, conditions, dose regimens, follow-up periods, or clinical settings. The registry record focuses the primary endpoint on Week 8 and does not establish longer-term outcomes.

The record also leaves important analytic details unreported, including the full model specification, missing-data handling, and multiplicity strategy. The results can be described accurately as registry-reported group estimates and comparisons, while acknowledging that these details limit independent evaluation. The safety counts are likewise descriptive and do not resolve the overall balance of benefits and harms.

In short, the posted evidence is about group-level change on a particular scale during a defined interval. It does not establish individual outcomes, long-term effects, comparative safety in full, or a treatment recommendation. The interpretation should remain tied to the trial population, endpoint, time frame, and analysis actually recorded.

18. Why This Trial Matters Statistically

This trial illustrates why a registry result should be read at several levels. The group means describe change in a continuous score, treatment differences express the contrast with placebo, confidence intervals convey estimation uncertainty, and p-values address compatibility with a null hypothesis under an analysis model. These quantities answer related but distinct questions. None alone conveys the full clinical meaning of a treatment comparison.

The posted results also show why it is important to distinguish an analysis reported by the trial sponsor from a simple recalculation using group summaries. Here, the treatment-difference estimates match at the displayed precision, while the recalculated intervals and p-values differ from the reported mixed-model results. The method used affects uncertainty estimates, and summary-statistic checks cannot recreate model details that are not available in the registry record.

Secondary results add context but come with a multiplicity concern when many endpoints and analyses are considered. Without a reported testing strategy, secondary p-values should not be treated as though each were the single primary test. Likewise, the Week 8 outcome counts and absent missing-data details matter for judging how much confidence to place in estimates derived from available observations.

Finally, a completed randomized and masked trial can still leave uncertainties in a registry summary. Original planning assumptions, model details, analysis-population handling, and some safety details are not reported in the registry record. Identifying those limits is part of sound statistical interpretation: it separates what the recorded results establish from what remains unknown and prevents numerical results from being overstated.

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 provides a concise description of the trial but not a complete protocol or statistical analysis plan. It does not report the original sample-size justification, full randomization procedure, allocation concealment, or which specific roles were covered by quadruple masking. The arm descriptions identify dose options but do not explain how participants received or moved among those dose levels.

For the primary analysis, the record names Mixed Models Analysis but does not report the model specification, covariates, covariance structure, or diagnostic checks. It also does not describe missing-data assumptions or sensitivity analyses. Although the intent-to-treat population is defined as all participants randomly assigned to treatment, the endpoint entry gives Week 8 availability counts rather than a full participant-flow explanation.

The registry does not report whether multiplicity was controlled across the listed outcomes and analyses. This limits the confirmatory interpretation of secondary results, particularly their p-values. Results for the named response-rate and treatment-discontinuation outcomes are not reported in the registry record.

Safety summaries are limited to group counts. Serious adverse event terms are not listed, and death counts are not reported in the registry record. The available summaries do not provide event descriptions, timing, severity, attribution, or enough detail to assess the full safety profile.

Finally, the primary assessment is at Week 8. The record does not establish durability beyond that endpoint. A registry summary also cannot by itself resolve whether the scale difference represents a clinically meaningful change, because a meaningful-difference threshold is not reported. These limits constrain interpretation without negating the estimates that are posted.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study Evaluating the Safety and Efficacy of Fixed-dose Once-daily Oral Aripiprazole in Children and Adolescents With Tourette's Disorder — NCT01727700.
• Registry record last updated 2015-02-13; status last verified 2015-02.
• Results first posted 2015-02-13.
• 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

NCT01727700 is a completed Phase 3 randomized, quadruple-masked, parallel-group study comparing once-daily aripiprazole with matching placebo in children and adolescents with Tourette’s disorder. The registry records enrollment of 133 and identifies change from baseline to Week 8 in YGTSS Total Tic Score as the primary endpoint.

The sponsor-reported Mixed Models Analysis gives treatment differences of -6.26 for low-dose aripiprazole versus placebo and -9.85 for high-dose aripiprazole versus placebo, with 95% confidence intervals from -10.18 to -2.34 and from -13.84 to -5.86, respectively. Secondary results generally show a similar direction across the posted continuous measures, but multiplicity handling is not reported.

Week 8 data were available for 42 low-dose, 35 high-dose, and 42 placebo participants. The full model, missing-data handling, original planning assumptions, and death counts are not reported in the registry record. The posted estimates therefore support a description of the recorded group comparisons, with the stated limits on precision, clinical interpretation, and completeness.