Study of Aripiprazole to Treat Children and Adolescents With Autism: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Aripiprazole to Treat Children and Adolescents With Autism (NCT00619190), a non-randomized phase 2 study. The primary outcome is Change From Baseline in Aberrant Behavior Checklist-Irritability at 12 Weeks.

2. Clinical Question

3. Trial Design

This was a Phase 2, parallel-group study with non-randomized allocation and no masking. The registry record lists the study as completed and reports enrollment of 30 participants. The sponsor was the University of North Carolina, Chapel Hill. The recorded study start was 2006-01, and primary completion was 2012-06.

One group received open-label, flexibly dosed aripiprazole, with doses described as ranging from 1mg to 30mg. The other group was a no-medication control consisting of children whose parents did not want them to take medication for autism over the year following enrollment. The groups therefore reflect different treatment choices rather than randomly assigned alternatives. In general, non-random assignment can leave differences between groups that complicate interpretation of comparisons. The registry record does not report methods for adjusting for such differences.

The primary outcome was change from baseline to 12 weeks in the ABC Irritability subscale. The study description also refers to acute and long-term effects, while listed secondary outcomes include the Clinical Global Impressions Scale - Severity Score and change from baseline in the ABC Lethargy/Social Withdrawal subscale at 12 weeks. The registry record lists 3 outcome measures, but 0 analyses. It does not report numerical results for the primary endpoint or describe an analysis plan for these outcomes.

The primary-outcome population description says that 20 of 21 participants in the aripiprazole group were analyzed because one participant dropped out before 12 weeks and the data were unavailable. The record does not give a corresponding primary-outcome analysis count for the no-medication group. It also does not report the allocation procedure beyond identifying the study as non-randomized, or describe a masking procedure; masking is recorded as none.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Only 20 out of 21 total participants were analyzed in the aripriprazole group because one participant dropped out before 12 weeks and so the data was not available.

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 in Aberrant Behavior Checklist-Irritability at 12 Weeks, measured over Baseline to 12 weeks.

The primary endpoint was change from baseline to 12 weeks in the Aberrant Behavior Checklist Irritability subscale, expressed in units on a scale. The ABC is described as a caregiver-rated questionnaire about a child’s problem behaviors over the past week relative to typically developing children of the same age. The overall checklist uses ratings from 0, meaning not at all a problem, to 3, meaning a problem is severe in degree. Raters are instructed to consider both severity and frequency.

The irritability subscale contains 15 items, with a minimum score of 0 for no irritability problems and a maximum of 45 when all irritability items are rated severe. Higher scores indicate worse symptoms. The registry description says a rating of 18 or more on this subscale is considered clinically significant. This provides context for interpreting a score level, but it does not itself define how a change between two time points should be judged.

Using change from baseline focuses the outcome on how a participant’s score differs from their starting score during the specified period. The caregiver rating provides a structured way to represent observed behaviors, while the fixed 12-week timeframe makes the endpoint time-specific. In general, a scale score is a measurement rather than a direct count of events, and its meaning depends on the instrument, the rating process, and the analysis used. The registry record does not report the mean change, standard deviation, or other numerical primary-outcome results. Therefore, the magnitude and precision of change cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: the endpoint is change on the ABC Irritability subscale, expressed in units on a scale. The registry record specifies a mean as the summary measure and standard deviation as the dispersion measure. These summaries answer different questions. In general, a mean describes the group’s average value, while a standard deviation describes how widely individual values vary around that average. Neither summary alone gives the uncertainty of a group comparison.

What does a change score represent?

A change score compares a participant’s follow-up value with their baseline value. Here, the timeframe is baseline to 12 weeks. A group mean change would describe the average change for participants included in that group’s analysis. A comparison of group mean changes would then describe a difference between those averages, if such an estimate were reported. The registry record gives the endpoint definition but does not report the mean changes or a between-group estimate.

Change scores can be useful because they express movement relative to the starting measurement. In general, interpretation still depends on the scale’s properties, the starting values, the pattern of missing observations, and the analysis population. A change score does not by itself account for differences between groups at baseline. In a non-randomized study, those differences may be especially relevant because allocation did not occur at random. The registry record does not report a statistical adjustment strategy or baseline outcome summaries for assessing those issues.

What does the standard deviation tell the reader?

A standard deviation describes variability in individual measurements around a group mean. It is not a confidence interval and does not directly indicate how precisely a mean or a between-group contrast has been estimated. In general, the precision of an estimate also depends on the number of observations and the analysis method. The registry record specifies standard deviation as the dispersion measure for the primary outcome but does not report a numerical value for it.

A confidence interval, if reported, would give a range of values compatible with the data and the statistical method at its stated confidence level. Its width is informative about precision: a narrower interval indicates greater precision than a wider interval under the same interpretation. No confidence interval for the primary endpoint is reported in the registry record. Nor is a p-value reported. Neither omission can be filled by interpreting enrollment counts or the endpoint definition.

Why does allocation matter?

Random allocation is designed, in general, to distribute measured and unmeasured participant characteristics across groups by chance. This study is recorded as non-randomized. The control group consisted of children whose parents did not want them to take medication for autism over the year following enrollment, while the intervention group received open-label aripiprazole. Group membership therefore followed a choice described in the registry rather than random assignment.

When groups form through different choices, they may differ in prognostic characteristics as well as treatment exposure. A simple comparison would not necessarily separate an intervention-associated difference from other differences between the groups. This is a general limitation of non-randomized comparisons, not a claim that any specific imbalance occurred in this study. The registry record does not report a statistical plan or adjustment method that would clarify how such differences were handled.

The study was also unmasked. In general, when participants and caregivers know which intervention is being received, expectations or awareness may influence subjective ratings. That consideration is pertinent to a caregiver-rated behavior scale, but the registry record does not establish that any particular rating was affected. It does not report masking procedures or an approach to assess the effect of awareness on outcome measurement.

How should planning calculations be read?

The stated planning assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. In general, a sample-size calculation asks how many participants would be needed under specified assumptions to detect a target effect with a chosen power. The answer depends on the assumed effect, variability, allocation, significance level, and statistical method.

These planning illustrations are not a description of the trial’s actual assignment or enrollment. The trial enrolled 30 participants, with 21 in the aripiprazole group and 9 in the no-medication group, so its observed group sizes were not equal. A planning scenario with equal allocation is an assumption for calculation, not evidence that the trial used equal allocation. Sample-size illustrations are not observed power and cannot replace a confidence interval or a reported outcome estimate.

The registry record does not report a trial-specific sample-size justification, the assumptions used in the original design, or a statistical analysis plan. It also lists 0 analyses. Consequently, it does not establish whether the posted planning assumptions were part of the original protocol or how analyses were prespecified. The endpoint’s numerical results remain unreported, so readers cannot assess whether the trial’s estimates were precise or how they compare with a target effect.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Open Aripipraprazole", "no Medication Control")
n   <- c(20, 9)
m   <- c(7.6, -0.6)
sp  <- c(9.7, 0.5)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Open Aripipraprazole  20  7.600  9.700  3.060  12.140
CARM  no Medication Control  9  -0.600  0.500  -0.984  -0.216

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 3 outcome measures: the primary ABC Irritability change outcome, the Clinical Global Impressions Scale - Severity Score, and the ABC Lethargy/Social Withdrawal subscale change outcome. It lists 0 analyses, and numerical results for these outcomes are not reported in the registry record. The record does not report a multiplicity strategy, such as how interpretation would account for testing more than one outcome or multiple analyses. It is therefore not possible to determine from the registry record which comparisons, if any, were prespecified as confirmatory or how repeated testing was handled.

For the primary outcome, the registry states that 20 of 21 participants in the aripiprazole group were analyzed. One participant dropped out before 12 weeks, and the data were unavailable. That is a specific missing observation described for that group and endpoint. The registry record does not report the corresponding primary-outcome analysis population for the no-medication control group, the number of missing observations for secondary outcomes, or the reasons for any other missing data.

The record does not describe how missing data were handled, whether any imputation was used, or whether analyses included all enrolled participants or only participants with available outcome data. These methods matter in general because the assumptions used to handle missing observations can affect estimates, particularly when missingness is related to the outcome. No missing-data sensitivity analysis is reported in the registry record.

The registry record also does not report a statistical analysis plan, analysis populations, or a prespecified hierarchy among outcomes. Without those details and without numerical outcome results, the consistency of the analyses with any planned approach cannot be assessed. The one reported dropout should not be treated as evidence that missing data had no effect; its impact is not reported.

12. 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 4% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for both groups. In the open aripiprazole group, 0 serious adverse events were reported among 21 participants at risk. In the no-medication control group, 0 serious adverse events were reported among 9 participants at risk. The registry record lists no serious adverse event terms.

The record also lists other adverse events: 19 among 21 participants at risk in the open aripiprazole group and 5 among 9 participants at risk in the no-medication control group. These are event counts as recorded; the registry information does not describe the event types in this summary. Deaths are not reported in the registry record.

These figures describe reported events in the groups, not a randomized comparison of safety. The study was non-randomized, and group sizes differed. In general, adverse-event counts should be interpreted in light of how events were defined, collected, and followed, as well as the size and comparability of the groups. Those details are not reported in the registry record. The counts alone do not establish that the groups had equivalent safety profiles or that an event was caused by the intervention.

Zero serious adverse events in the registry listing means none were reported for the specified participants at risk in these groups. It does not show that the risk of a serious event is zero. The registry record does not report additional detail that would allow a more complete assessment of event timing, severity beyond the listed categories, or attribution.

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

The registry record establishes that a completed, open-label, non-randomized study examined aripiprazole in children and adolescents with autism spectrum disorders. It identifies a primary measure, change in caregiver-rated ABC Irritability score from baseline to 12 weeks, and describes the intervention and no-medication control groups. It also reports enrollment and the primary-outcome analysis count for the aripiprazole group.

Those design details do not answer how much the endpoint changed. The registry record does not report a mean change, standard deviation, comparison estimate, confidence interval, or p-value for the primary outcome. As a result, it does not show the direction, size, or precision of the primary outcome result. The listed secondary outcome names likewise do not establish their numerical results.

Even if numerical differences were available, the allocation design would matter to interpretation. The groups were not randomly assigned: the control group was made up of children whose parents did not want them to take medication for autism over the year following enrollment. In general, a difference between such groups may reflect factors beyond the intervention. The registry record does not report adjustment methods that would help assess this possibility.

The ABC description gives a structured definition of the endpoint and indicates that higher irritability scores represent worse symptoms. Its clinical-significance threshold is a score level, not a reported change or a comparison result. Without the outcome estimates, that scale context cannot be used to judge what occurred during the study.

The adverse-event listing reports 0 serious adverse events in each group and reports other adverse events in both groups. These counts describe the registry’s event reporting; they do not demonstrate that the groups are equivalent or establish causation. The registry record also does not report deaths.

In general, a trial’s result is best understood by considering its estimate, uncertainty, analysis population, missing data, and design. Here, the primary numerical result and several analytic details are not reported in the registry record. The study description can therefore clarify what was examined, but it cannot support a quantified conclusion about the primary endpoint’s effect or its precision.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why a clearly named endpoint is not enough to interpret a trial. The registry record defines a specific continuous outcome, identifies its timeframe, and describes the scale’s direction and range. Yet it does not report the numerical endpoint results. Without an estimate and an uncertainty measure, readers cannot judge the magnitude or precision of the outcome, even when enrollment and analysis counts are available.

The study also illustrates the interpretive distinction between randomized and non-randomized comparisons. The no-medication group was based on parents’ decision not to use medication for autism over the year following enrollment. This creates a comparison between groups formed through different choices, rather than a randomized allocation. In general, such designs require careful attention to group differences and analysis assumptions. The registry record does not report an adjustment strategy.

Missing outcome data are another relevant feature. The primary-outcome description specifies that one participant in the aripiprazole group dropped out before 12 weeks and was not analyzed because data were unavailable. That fact makes the analysis population important, but the record does not give comparable analysis-population detail for the control group or describe a missing-data method.

Finally, the study lists multiple outcome measures but no analyses. This highlights the importance of reporting which outcomes were analyzed, how they were analyzed, and how uncertainty and multiple outcomes were handled. The record identifies the clinical question and measurement framework, but the absence of numerical results and methodological detail limits statistical interpretation. These limitations are about what can be concluded from the registry record, not a claim about what may have been reported elsewhere.

15. Limitations

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

The central limitation for interpreting results from this registry record is that it does not report numerical primary-outcome results. Mean change, standard deviation, a between-group estimate, a confidence interval, and a p-value are not reported in the registry record. The record also lists 0 analyses. This prevents assessment of effect direction, magnitude, and precision.

The study was non-randomized and open-label. The intervention group received flexible-dose aripiprazole, described as 1mg to 30mg, while the control group comprised children whose parents did not want them to take medication for autism over the year following enrollment. The groups may therefore differ in ways related to group selection, though the registry record does not report specific imbalances. Masking was recorded as none, which is relevant in general when outcomes are based on caregiver ratings.

The primary-outcome population description reports that 20 of 21 aripiprazole participants were analyzed, because one participant dropped out before 12 weeks and outcome data were unavailable. The record does not describe how missing data were handled, provide a corresponding analysis count for the control group, or report sensitivity analyses. It also does not report analysis populations for the listed secondary outcomes.

Other details needed for fuller statistical assessment are not reported in the registry record: a statistical analysis plan, a trial-specific sample-size justification, an adjustment strategy for group differences, and a multiplicity approach. The record lists 3 outcome measures but 0 analyses. The listed safety counts also lack further detail about event definitions, timing, and attribution. These reporting gaps limit what can be concluded from the registry record, without establishing what information might be available outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Aripiprazole to Treat Children and Adolescents With Autism — NCT00619190.
• Registry record last updated 2014-03-26; status last verified 2014-02.
• Results first posted 2014-03-26.
• 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.

19. Record Summary

NCT00619190 is a completed Phase 2, parallel-group, open-label, non-randomized study sponsored by the University of North Carolina, Chapel Hill. The registry record reports 30 participants enrolled. The study compared open-label, flexibly dosed aripiprazole with a no-medication control group whose parents did not want medication for autism over the year following enrollment.

The primary endpoint was change from baseline to 12 weeks in the ABC Irritability subscale. The registry record describes the scale and reports that 20 of 21 participants in the aripiprazole group were analyzed because one dropped out before 12 weeks and data were unavailable. Numerical primary and secondary outcome results are not reported in the registry record, which lists 0 analyses. The serious adverse event listing reports 0 events in each group; other adverse events are also listed for both groups.