Study of Aripiprazole in the Treatment of Serious Behavioral Problems in Children and Adolescents With Autistic Disorder (AD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Aripiprazole in the Treatment of Serious Behavioral Problems in Children and Adolescents With Autistic Disorder (AD) (NCT00365859), a non-randomized phase 3 study. The primary outcome is Number of Participants With Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (AEs), Deaths, AEs Leading to Discontinuation, Extra Pyramidal Syndrome (EPS)-Related AEs.

2. Clinical Question

3. Trial Design

This was a phase 3, multicenter, open-label study with a single-group model and non-randomized allocation. Its official title describes a 52-week study of the safety and tolerability of flexibly dosed aripiprazole. The registry lists a start date of 2006-09-01 and primary completion date of 2009-06-01, and records the study as completed.

The groups were De Novo, Roll Over Aripiprazole, and Roll Over Placebo. De novo participants had not taken part in the named earlier protocols. The rollover groups had completed participation in those protocols while receiving aripiprazole or placebo, respectively, and continued to meet eligibility criteria. In the current study, the groups received open-label aripiprazole. Thus, the rollover labels describe prior study treatment, not randomized treatment assignments within this study.

The registry reports enrollment of 330. The posted safety results give group-specific numbers at risk: 86 for De Novo, 174 for Roll Over Aripiprazole, and 70 for Roll Over Placebo. These entries should not be treated as evidence of random allocation or as like-for-like control groups. Prior treatment history, selection into rollover, and the open-label design distinguish the groups in ways that limit direct comparisons.

The primary endpoint covered safety events from screening through Week 52 for serious adverse events, and from Week 0 through Week 52 for adverse events. The record lists several Week 52 symptom outcomes as secondary measures. It does not report the study's statistical analysis plan, sample-size justification, or a randomized efficacy comparison.

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: 109 participants were enrolled in the De Novo arm, 70 in the Rollover Placebo arm, and 174 in the Rollover Aripiprazole arm. 23 participants in the De Novo arm were considered "baseline failures," and did not enter the treatment phase.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety Population

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 Number of Participants With Serious Adverse Events (SAEs), Treatment-Emergent Adverse Events (AEs), Deaths, AEs Leading to Discontinuation, Extra Pyramidal Syndrome (EPS)-Related AEs, measured over From Screening (up to 42 days prior to treatment start) through Week 52 (end of study) for SAEs; from Week 0 (Baseline) through Week 52 (End of Study) for AEs.

The primary endpoint is a set of participant counts for safety events: serious adverse events, treatment-emergent adverse events, deaths, adverse events leading to study discontinuation, and EPS-related adverse events. An adverse event is defined in the registry as a new untoward medical occurrence or worsening of a pre-existing medical condition. The registry defines a serious adverse event by consequences such as death, life threat, inpatient hospitalization or prolonged hospitalization, persistent or significant disability, cancer, congenital anomaly or birth defect, drug dependency or abuse, or another important medical event.

Counting participants with events is a direct way to describe how many people in the safety population were recorded as having specified events during the observation period. It is relevant to a study whose stated purpose is long-term safety and tolerability. Such counts describe what was recorded in the enrolled groups; without a randomized comparator, they do not isolate the effect of treatment from other explanations for events.

The registry provides counts for serious and other adverse events by group, but it does not provide numerical results for every component named in the primary endpoint. Death counts are not reported in the registry record. Nor are counts for adverse events leading to discontinuation or EPS-related events separately reported in the available results. The endpoint therefore has broader scope than the numerical safety results that are posted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary safety outcome, the basic descriptive result is the number of participants recorded with the event, alongside the number at risk. The registry reports such counts for serious and other adverse events in each group. These summaries show how many participants were recorded in each category during the stated observation window. They do not, by themselves, describe event timing, recurrence, severity beyond the event classification, or causal attribution.

Different safety summaries answer different questions. A participant count indicates whether a participant had an event, but it does not count repeated events separately. An event rate would require a defined event count and exposure-time denominator. The registry results presented in the record are participant counts, not person-time rates. Comparisons of raw counts between groups are especially difficult when group sizes differ, and the non-randomized design further prevents interpreting those contrasts as treatment effects.

In general, randomization helps make groups comparable on average with respect to both measured and unmeasured characteristics. Here, allocation was non-randomized, and group membership reflects whether participants were new to the study or had completed a prior protocol on placebo or aripiprazole. The groups are therefore not interchangeable controls. Open-label treatment also means participants and study personnel were not masked to treatment in this study, as recorded in the registry. These design features matter when interpreting subjective symptom measures and the reporting or classification of adverse events.

The primary endpoint is a collection of safety-event categories rather than a single continuous measurement. Serious adverse events have a registry definition based on specified consequences or important medical events. Treatment-emergent adverse events are described over the interval from Week 0 through Week 52, while the serious-event interval also begins at screening, up to 42 days before treatment start. The registry lists deaths, discontinuations, and EPS-related events in the endpoint title, but does not provide their separate numerical results in the posted data.

The secondary outcomes include mean changes from baseline in CGI severity and several ABC scores, CGI improvement, and change in CY-BOCS score at Week 52. The outcome titles specify endpoint values with LOCF. In general, last observation carried forward uses a participant's last available measurement in place of a later missing measurement. This can retain participants with incomplete follow-up in an endpoint analysis, but it relies on assumptions about what the unobserved later measurement would have been. The registry record does not report how much data were missing, how LOCF was implemented for each measure, or whether any alternative missing-data analyses were conducted.

Multiplicity arises when several outcomes or comparisons are examined: the chance of at least one apparently notable result can increase if each is tested without accounting for the family of analyses. The registry lists multiple secondary outcomes but does not report a multiplicity procedure or an analysis plan. No inference about statistical significance should be made from outcome names alone. The record reports zero registry analyses, so inferential estimates and tests are not listed.

Sample-size planning is distinct from analysis of observed trial data. The record's planning assumptions describe illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. Such planning values are not observed power. The record also states that time-to-event illustrations use total events, while other illustrations use participants per arm. These assumptions do not establish the design rationale for this single-group, non-randomized study, and its sample-size justification is not reported in the registry record.

Overall, the statistical information available supports descriptive reading of the posted safety counts. It does not support a randomized comparison, a causal estimate, or a precise estimate of symptom change. The sponsor's own analysis would take precedence if a recalculated result conflicted with it; the registry record does not list an analysis result to compare with a recalculation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes at Week 52, including CGI, ABC, and CY-BOCS measures. It does not report a multiplicity strategy or explain whether any outcome was designated as a principal secondary analysis. When multiple outcomes are examined, multiplicity matters because interpreting each result independently can make chance findings more likely across the set. Without a stated procedure and reported estimates, the listed outcomes should be read as planned or recorded measures, not as evidence of confirmed differences.

The outcome titles specify LOCF for the Week 52 endpoint measures. In general, LOCF replaces a missing later assessment with the participant's last observed assessment. This approach makes assumptions about the course of the outcome after the last observation. The registry record does not report the amount or pattern of missing outcome data, the details of the LOCF implementation, or sensitivity analyses using other missing-data approaches. Missing-data handling for the primary safety outcome is not reported in the registry record.

The primary outcome identifies the Safety Population, but the registry does not describe further analysis-population rules or give participant flow by outcome. Its posted safety counts are descriptive. The record lists no registry analyses, confidence intervals, or hypothesis tests, and does not report an analysis plan. Accordingly, the precision and inferential status of the listed symptom outcomes cannot be assessed from the registry record.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: convulsion (1.4%), aggression (1.2%), suicidal ideation (1.2%), skin infection (1.2%), impulsive behaviour (0.6%).

For serious adverse events, the registry reports 3 participants among 86 at risk in De Novo, 5 among 174 at risk in Roll Over Aripiprazole, and 1 among 70 at risk in Roll Over Placebo. For other adverse events, it reports 73 among 86, 136 among 174, and 61 among 70, respectively. These are participant counts within the groups, not counts of every event occurrence.

The serious-event terms listed include CONVULSION, AGGRESSION, SUICIDAL IDEATION, SKIN INFECTION, IMPULSIVE BEHAVIOUR, and CHOLECYSTITIS, with the percentages reported in the registry. The record does not report death counts. It also does not separately provide numerical counts for every category named in the primary endpoint, including events leading to discontinuation and EPS-related events.

These data describe events recorded during the stated periods; they do not establish causation. The groups were not randomized controls, and their differing prior-treatment histories limit direct comparison. The counts should therefore be read as descriptive safety information, not as evidence that one group had a greater or lesser treatment effect.

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

The study contributes a registry record of long-term, open-label aripiprazole exposure and descriptive safety-event counts in children and adolescents with autistic disorder. It documents serious adverse events and other adverse events by the three study groups, as well as a list of serious-event terms and their reported percentages. This is the scope of the numerical safety evidence available in the posted results.

The record does not establish that aripiprazole caused any particular event, nor does it provide a randomized comparison against placebo or another treatment. Although one rollover group had received placebo in an earlier protocol, participants in this study were assigned open-label aripiprazole. The prior-protocol labels do not create a concurrent placebo control. Differences in counts across the groups therefore cannot be interpreted as causal treatment differences.

The record also lists behavioral and symptom outcomes at Week 52, but their numerical results are not reported in the registry record. It is not possible from the posted results to quantify change in CGI, ABC, or CY-BOCS measures or assess the precision of such change. The record does not provide confidence intervals, hypothesis tests, or a reported statistical analysis plan.

Thus, the posted information supports a descriptive account of recorded events and the study's design. It does not establish comparative safety, quantify treatment benefit, or settle whether the treatment is appropriate for an individual. It also does not provide enough outcome data to assess the stated symptom measures statistically.

13. Why This Trial Matters Statistically

This trial is statistically notable because its long-term safety question is addressed in an open-label, non-randomized design. Such a design can document events during treatment and follow participants over time, but it cannot provide the same basis for causal comparison as a randomized control trial. The distinction is especially important because the groups reflect prior study participation and prior treatment rather than randomized assignment in this study.

The rollover structure also illustrates why group labels need careful interpretation. A group previously assigned placebo is not a placebo arm in the current study when its participants receive open-label aripiprazole. Prior exposure and eligibility to continue from an earlier protocol may be associated with differences between groups, so their observed counts should not be read as if participants had been assigned to comparable arms under the same conditions.

Separating descriptive counts from inferential claims is central to reading the record. The safety counts provide information about events recorded in the study, while the missing numerical results for listed symptom outcomes limit assessment of those measures. No registry analyses are listed, and the analysis plan and multiplicity approach are not reported. Statistical significance, precision, and causal effect therefore cannot be evaluated from the registry record.

The stated planning illustrations are also distinct from evidence about this trial's design or observed performance. They use specified assumptions and are planning exercises, not observed power. In general, keeping design, descriptive findings, and planning calculations conceptually separate helps prevent overinterpretation of a registry result.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The non-randomized allocation, absence of masking, and single-group model limit causal interpretation. All groups received open-label aripiprazole in this study, and the rollover groups were defined by earlier treatment histories. The record explicitly cautions that the groups are not a like-for-like control comparison. Any differences in their safety counts could reflect group composition or prior study experience rather than a treatment contrast.

The available numerical results do not cover every component of the primary endpoint. Death counts are not reported in the registry record, and separate counts for discontinuation-related or EPS-related adverse events are not available in the posted results. The record also does not report numerical results for the listed Week 52 symptom measures, despite naming them as secondary outcomes.

Further details needed to evaluate precision and potential bias are not reported in the registry record. These include confidence intervals, inferential tests, the statistical analysis plan, multiplicity handling, participant flow for each outcome, and the extent and pattern of missing outcome data. Although LOCF appears in the secondary-outcome titles, its implementation and sensitivity analyses are not described. These limitations restrict interpretation to the descriptive information actually posted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Aripiprazole in the Treatment of Serious Behavioral Problems in Children and Adolescents With Autistic Disorder (AD) — NCT00365859.
• Registry record last updated 2026-08-04; status last verified 2026-07.
• Results first posted 2010-01-25.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes NCT00365859, a completed phase 3, 52-week, open-label, multicenter study of flexibly dosed aripiprazole in children and adolescents with autistic disorder. Allocation was non-randomized, the model was single group, and enrollment was 330. De novo and rollover groups all received open-label aripiprazole; rollover labels refer to treatment in earlier protocols.

The primary outcome concerned counts of participants with safety events. The posted results include group-specific counts for serious and other adverse events, plus selected serious-event terms. Death counts are not reported in the registry record. Multiple Week 52 symptom outcomes are listed, but their numerical results, along with registry analyses and the statistical analysis plan, are not reported. The available evidence is therefore descriptive and does not support a randomized treatment comparison.