A Prospective Open-label Study of Aripiprazole in Fragile X Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Prospective Open-label Study of Aripiprazole in Fragile X Syndrome (NCT00420459), a na phase 2 study. The primary outcome is Aberrant Behavior Checklist.

2. Clinical Question

The study asked whether aripiprazole could be evaluated for effectiveness and tolerability in children and adolescents with Fragile X Syndrome. Its primary measure was the Aberrant Behavior Checklist (ABC), obtained at baseline and Week 12. The ABC measures maladaptive behaviors; the registry record does not report the resulting scores or their change over time.

The clinical question is therefore descriptive in the posted record: it concerns observations during treatment in a single group. Without reported outcome values or a control group, the record cannot quantify an ABC change attributable to treatment or distinguish such a change from other explanations.

3. Trial Design

This was a prospective, open-label, phase 2 study of aripiprazole in Fragile X Syndrome. The registry lists a single-group model, no masking, and allocation as not applicable. It records enrollment of 12 and a completed status. The study began in 2007-04, and primary completion was recorded as 2010-03.

Because there was no comparator group, participants were not assigned between treatment and control arms in a randomized comparison. An open-label design also means masking was absent. These features matter when interpreting outcomes: observations made during the study do not, by themselves, separate treatment-related change from natural variation, changes over time, expectations, or other influences.

The ABC was assessed at baseline and Week 12. The record describes the primary endpoint as a mean on a continuous scale, with standard deviation as its dispersion measure. It also lists the Children's Yale-Brown Obsessive Compulsive Scale, Social Responsiveness Scale, Vineland Adaptive Behavior Scales, and Vineland Maladaptive Behavior Subscales as secondary outcomes.

The registry record does not report the treatment regimen, eligibility criteria, participant characteristics, follow-up beyond the stated assessment time, or reasons for any missing observations. It also does not report a sample-size justification or a detailed statistical analysis plan. Although the study is marked completed, the primary-outcome values and analyses 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.

Overall Study

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 Aberrant Behavior Checklist, measured over Obtained at Baseline and Week 12.

The primary endpoint is the Aberrant Behavior Checklist (ABC), a 58-item measure of maladaptive behaviors described in the record as a measure of drug effects. It was obtained at baseline and Week 12. The registry identifies the endpoint summary as a mean, with standard deviation describing variability.

The ABC has five subscales: Social Withdrawal, Irritability, Inappropriate Speech, Hyperactivity, and Stereotypy. The listed score ranges are 0 to 48 for Social Withdrawal, 0 to 45 for Irritability, 0 to 12 for Inappropriate Speech, 0 to 48 for Hyperactivity, and 0 to 21 for Stereotypy. Items are rated from 0, meaning not at all, to 3, meaning severe. These subscale ranges describe the instrument; they are not study results.

Such a measure can give a structured way to characterize behavior across defined items. A mean describes the group’s average score, while a standard deviation describes how dispersed individual scores are around that average. To interpret change, readers would need the actual scores at each assessment, the number of observations contributing to them, and an appropriate estimate of uncertainty. Those results are not reported in the registry record, so the direction and magnitude of any ABC change cannot be determined from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized as a mean and standard deviation. General statistical explanation: a mean represents the arithmetic average of observed scores, while a standard deviation describes their spread. Neither statistic alone expresses the uncertainty in an estimated treatment effect. An interval estimate, such as a confidence interval, is commonly used to show a range of values compatible with the observed data under the analysis assumptions. No such estimate is reported for the primary outcome in the registry record.

What does a baseline-to-follow-up comparison require?

Because the ABC was obtained at baseline and Week 12, an analysis of change would need to account for the relationship between measurements from the same participant. General statistical explanation: measurements from the same person are often correlated, so treating them as independent observations can misstate uncertainty. A paired analysis uses the within-person relationship; an alternative model may account for repeated observations in another way. The registry record does not report which approach, if any, was used. It also does not provide the scores or the number of participants with measurements at both assessment times.

A mean at each time point and a mean change answer different descriptive questions. A difference between group means does not, without further information, describe the distribution of individual changes. For a paired change estimate, the variability of within-person differences is relevant. The registry record does not report a baseline mean, a Week 12 mean, a change estimate, or the dispersion needed to assess that change.

Why does the single-group design matter?

General statistical explanation: random assignment to a comparator can help balance known and unknown influences between groups. In a single-group study, there is no concurrent randomized control estimate. Any measured change across time can be affected by the course of the condition, other care, measurement variability, or expectations, as well as by the intervention. This limitation is separate from whether a within-person statistical test is chosen. A test of change in a single group cannot create the missing randomized contrast.

The record lists an open-label design and no masking. General statistical explanation: masking can reduce some influences of knowledge about treatment assignment on behavior, reporting, and assessment. The record does not describe additional procedures to limit those influences. It does not report how the ABC was administered, who completed it, or whether assessment procedures were standardized beyond the instrument description.

What can the planning illustration establish?

The sample-size assumptions describe a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is based on fractions of an observed effect, with non-time-to-event quantities expressed as participants per arm. Those assumptions describe a hypothetical planning framework, not this study’s single-group design. The registry record does not report a trial-specific sample-size justification. A planning illustration is not observed power and is not evidence that the study had adequate precision. The primary-outcome estimates needed to evaluate the illustration are not reported in the registry record.

General statistical explanation: planning calculations depend on a target effect, variability, the chosen error rate, and design assumptions. If the assumptions differ from the actual design or the true outcome variability, the resulting planning quantities may not describe the study’s ability to estimate its outcome. Since the registry record does not include the ABC results or their uncertainty, the planning illustration cannot fill that evidentiary gap.

What is reported about analysis and uncertainty?

The registry records zero analyses. No model, test, adjustment, confidence interval, or p-value for the ABC is reported in the registry record. It is therefore not possible to determine whether the outcome was analyzed as a change score, as repeated measurements, or by another method. Nor can the analysis population, handling of incomplete observations, or any model assumptions be assessed.

General statistical explanation: over-dispersion matters when observed variability exceeds what a chosen model assumes; ignoring it can make standard errors too small and intervals too narrow. This is a general consideration, not a claim that over-dispersion occurred in this study. The posted record does not give outcome distributions or model diagnostics with which to assess it.

For continuous outcomes, precision depends on both variability and the amount of usable information. A reported mean without its contributing observation count and an uncertainty estimate may be difficult to interpret. Here, even the endpoint means are absent. The most reliable statistical conclusion is therefore that the registry identifies the measurement plan but does not report the primary-outcome analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures, including the ABC primary measure and four named secondary outcomes: the Children's Yale-Brown Obsessive Compulsive Scale, Social Responsiveness Scale, Vineland Adaptive Behavior Scales, and Vineland Maladaptive Behavior Subscales. It records zero analyses. Results for the primary and secondary outcomes are not reported in the registry record.

Multiplicity is the issue that arises when several outcomes or statistical tests are examined. General statistical explanation: as the number of tests increases, the chance of at least one apparently unusual result can increase if no adjustment or prespecified interpretation strategy is used. The registry record does not report whether any multiplicity adjustment, outcome hierarchy, or prespecified testing strategy was used. It is not possible to determine how secondary results would have been interpreted relative to the primary outcome.

Missing-data methods are also not reported in the registry record. The record does not give the number of participants with ABC measurements at baseline or Week 12, identify any missing observations, state reasons for missingness, or describe imputation or other handling. The enrollment count alone does not establish how many observations contributed to an outcome analysis.

The analysis population is not reported in the registry record. It is not stated whether analyses included all enrolled participants, only participants with follow-up measurements, or another defined group. These omissions prevent assessment of how incomplete data and outcome selection may affect interpretation. The record’s completed status does not resolve those uncertainties.

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 non-serious adverse event terms

The registry reports serious adverse events for the Aripiprazole group: 0 of 12 participants at risk were affected. It reports other adverse events for 12 of 12 participants at risk. These are separate registry categories; the counts should not be added together because the record does not establish that they represent mutually exclusive participants or events.

The specific serious adverse-event terms are not reported in the registry record. The death count is not reported in the registry record. The record does not give details of the other adverse events, their severity, timing, duration, or relationship to treatment. Therefore, the count for other adverse events does not identify what events occurred or how consequential they were.

General statistical explanation: an observed count is descriptive, and its interpretation depends on event definitions, follow-up, ascertainment, and the amount of information available. A count from a single-group study does not by itself establish whether an event was caused by the intervention. These safety figures should be read as registry-reported counts, not as a comparative estimate of risk.

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

The registry record establishes that a prospective, open-label, single-group study of aripiprazole in Fragile X Syndrome was completed. It specifies the ABC as the primary measure, identifies baseline and Week 12 assessments, and describes the instrument’s subscales and score ranges. It also reports the listed serious and other adverse-event counts.

It does not report the ABC scores, their change, the variability of those results, or an uncertainty estimate. It therefore does not show the direction or magnitude of any primary-outcome change. Statistical significance and clinical importance cannot be judged from the record. These are different questions: a statistical analysis addresses compatibility with a model or null hypothesis, while clinical importance concerns the relevance of a change in context. Neither can be evaluated without reported outcome results and suitable interpretation criteria.

The single-group, open-label design is not a randomized comparison. General statistical explanation: even a clearly measured change within a group cannot on its own establish that the intervention caused the change, because time trends and other influences are not controlled by a randomized comparator. The record does not report procedures that would address those alternative explanations.

The safety counts are also limited. They do not include event descriptions or a comparison group, and the death count is not reported in the registry record. Accordingly, they describe what the registry records, not a comparative safety profile or a causal conclusion.

The most defensible reading is narrow: the record documents the study framework and selected safety counts but does not provide the outcome analyses needed to answer its primary effectiveness question. The absence of reported analyses is not evidence that the outcome was unchanged, nor is it evidence that the intervention had a particular effect.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a defined measurement plan and an interpretable result. The record names a primary behavioral measure, specifies baseline and Week 12 assessment, and identifies how the score is summarized. Those details help readers understand what the investigators intended to measure.

At the same time, the design is a single-group, open-label study. That design can describe observations over time, but it does not supply a randomized control contrast. General statistical explanation: separating change associated with treatment from other changes is a central reason controlled comparisons are useful. The study’s design must therefore be considered alongside any outcome estimate; in this record, the estimate itself is not reported.

The record also shows why reporting uncertainty and analysis details matters. Means and standard deviations are identified as the summary approach, but the actual values, analysis methods, missing-data handling, and analysis population are not reported in the registry record. Without them, readers cannot assess the size or precision of the primary result, or determine how incomplete observations were handled.

The safety counts provide a limited descriptive account, but event terms and the death count are not reported in the registry record. The registry’s completed status and the presence of a defined endpoint do not replace outcome reporting. The statistical lesson is that design, measurement, analysis, and transparent reporting all contribute to what can be concluded; none alone supplies information absent from the others.

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.

Several limitations are specific to the information recorded for this study. The single-group design has no randomized comparator, and the open-label design includes no masking. As a result, any within-group change, if measured, would not by itself distinguish an intervention-associated change from time trends, other influences, or assessment effects.

The registry record does not report the primary ABC means at baseline or Week 12, the change estimate, standard deviations for the observed results, or confidence intervals. It also records zero analyses. The primary question therefore cannot be answered from the posted outcome information, and the precision of any change cannot be evaluated.

Eligibility criteria, participant characteristics, treatment regimen details, and the number of participants with outcome data at each assessment are not reported in the registry record. Missing-data procedures and the analysis population are also not reported. These omissions limit assessment of who contributed to outcome summaries and how representative those summaries would be of enrolled participants.

The record names secondary outcomes but does not report their results or describe an approach to multiplicity. It does not report a trial-specific sample-size justification or a detailed analysis plan. Finally, safety reporting is limited: serious-event terms and the death count are not reported in the registry record, and details of other adverse events are absent. These constraints restrict interpretation to the study design and the counts explicitly recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Prospective Open-label Study of Aripiprazole in Fragile X Syndrome — NCT00420459.
• Registry record last updated 2017-04-18; status last verified 2017-03.
• Results first posted 2017-04-18.
• 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

NCT00420459 is a completed phase 2, prospective, open-label, single-group study of aripiprazole in Fragile X Syndrome. The registry lists enrollment of 12, a start date of 2007-04, and primary completion in 2010-03. The primary outcome is the mean ABC score, assessed at baseline and Week 12.

The record lists four secondary outcomes and six outcome measures overall, but records zero analyses. Primary and secondary outcome results, analysis methods, missing-data handling, and analysis populations are not reported in the registry record. Safety reporting lists 0 of 12 affected by serious adverse events and 12 of 12 affected by other adverse events. Serious-event terms and the death count are not reported in the registry record.

The posted record documents the design and outcome measurement plan but does not provide the results needed to estimate or interpret ABC change.