Aripiprazole Open-Label, Safety and Tolerability Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Aripiprazole Open-Label, Safety and Tolerability Study (NCT00102518), a na phase 3 study. The primary outcome is Percentage of Subjects Experiencing SAEs.

2. Clinical Question

The study’s stated purpose was to assess long-term safety and tolerability in the named pediatric populations. The endpoint description gives a timeframe of baseline and Week 23 and describes summaries of serious adverse events by system organ class, preferred term, and severity. The registry also lists changes in PANSS total score and Young Mania Rating Scale total score as secondary outcomes. Results for those changes are not reported in the registry record.

Because the study has no randomized comparator, its central question is descriptive: what serious adverse events were recorded among enrolled subjects? A single-group safety description can document events observed during follow-up, but it cannot separate treatment-associated events from events that might have occurred for other reasons. The endpoint therefore needs to be read as a summary of reported safety experience, not as a causal comparison.

3. Trial Design

This is a Phase 3, open-label, single-group study of oral aripiprazole. The record lists allocation as not applicable and masking as none. Enrollment was 325. The study status is completed; the registry lists a start of 2004-09 and primary completion of 2007-02. The official title describes flexible dosing in the treatment of adolescent patients with schizophrenia and child and adolescent patients with bipolar I disorder, manic or mixed episode, with or without psychotic features.

The arm description identifies the participants as subjects from studies NCT00102063 and NCT00110461. It says all subjects had either completed or withdrawn from the double-blind extension phase of those studies. This background is relevant to understanding who entered the single-group study, but the registry record does not describe a concurrent comparator in the present study. The participants’ earlier study phases do not turn this record into a randomized comparison.

The primary endpoint is the percentage of subjects experiencing serious adverse events, with the stated timeframe of baseline and Week 23. The endpoint description says incidences are summarized by system organ class, by system organ class and MedDRA preferred term, and by system organ class, preferred term, and severity. The registry also lists changes in PANSS total score and Young Mania Rating Scale total score as secondary outcomes, but their estimates and analyses are not reported in the registry record.

Open-label, single-group studies are suited to describing events and changes recorded during treatment, but they provide limited grounds for attributing those observations to treatment. Without a concurrent control group, differences in patient characteristics, the course of the conditions, background care, and other influences cannot be assessed through a randomized contrast. The registry record does not report the protocol’s detailed dosing schedules, adherence summaries, or procedures for follow-up beyond the endpoint timeframe.

The record does not report a statistical analysis plan or a prospective sample-size justification. Its listed planning assumptions concern an illustration based on an observed effect and a hypothetical two-arm allocation, rather than the single-group design recorded for this study. Those assumptions should not be mistaken for evidence that the study was designed or powered for a two-arm 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: All participants had previously completed NCT00102063 (OPDC 31-03-239, adolescents with schizophrenia) or had withdrawn from the double-blind extension phase of NCT00110461 (OPDC 31-03-240, children and adolescents with bipolar 1 disorder), both clinical studies of aripiprazole.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All enrolled subjects.

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 Percentage of Subjects Experiencing SAEs, measured over Baseline and Week 23.

The primary endpoint is the percentage of subjects experiencing serious adverse events. It is a binary participant-level outcome: a participant is counted according to whether a serious adverse event was recorded during the endpoint’s stated timeframe, rather than according to the number of events alone. The registry identifies all enrolled subjects as the endpoint population and gives baseline and Week 23 as the timeframe.

Such an endpoint is used to describe serious safety events during study follow-up. Reporting the proportion of participants affected can make the frequency of an event category easier to understand than a list of event narratives alone. The registry’s description also calls for event summaries by system organ class, preferred term, and severity, which provide clinical classifications of the reported events.

The endpoint does not, by itself, show that the study drug caused an event. In a single-group, open-label study, the observed frequency has no randomized control rate against which to compare it. The endpoint also does not summarize every aspect of safety: it focuses on serious adverse events, while other adverse events are listed separately in the posted results.

The record reports that 20 of 325 subjects were affected in the serious-event category. No confidence interval, p-value, or adjusted estimate for this endpoint is reported in the registry record. The raw count can describe what was recorded in this group, but without uncertainty estimates or a comparator it does not quantify a treatment-related increase or decrease in risk.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on matching the method to the study question and design. This study is recorded as open-label and single-group, so its principal numerical results describe the enrolled participants rather than a randomized difference between groups. General statistical principles can help explain what the reported counts do and do not convey, but they cannot replace analyses that are not reported in the registry record.

What does a participant-level event count describe?

A binary adverse-event endpoint classifies each participant according to whether the event occurred during the defined observation period. A count of affected participants is therefore different from a count of total event episodes: a participant with repeated episodes may still contribute once to a participant-level measure, depending on the endpoint definition. The primary endpoint is described as the percentage of subjects experiencing serious adverse events, and the population is all enrolled subjects. The record lists 20 affected subjects and 325 at risk for that category.

A proportion is a descriptive summary of the observed group. It can be useful for communicating how frequently an outcome was recorded, but it depends on the population and observation process. If follow-up duration varies, or if some participants leave early, a simple proportion may not capture differences in time under observation. The registry record does not report participant-level follow-up duration, event timing, or a time-to-event analysis for this endpoint. The stated timeframe is baseline and Week 23.

Why is a control group important for causal interpretation?

Randomized comparison helps distinguish an outcome associated with treatment assignment from outcomes that might reflect the underlying condition, background care, participant characteristics, or chance variation. This record lists no allocation and no masking and identifies a single-group model. Consequently, the serious-event count does not provide a risk difference or other randomized treatment contrast. Comparing these results informally with figures from a different study would also require caution because populations, follow-up, event definitions, and ascertainment may differ.

Open-label observation can be useful for recording events in the circumstances of a study, but knowledge of treatment may influence reporting or assessment. The record does not describe specific procedures used to reduce or evaluate this possibility. Nor does the registry record provide an external control group. The event data should therefore be read as descriptive observations rather than estimates of causal effect.

What would uncertainty measures add?

A confidence interval is a statistical range that conveys uncertainty around an estimate under a specified analysis and its assumptions. It does not resolve bias from an uncontrolled design, but it can show how imprecise a sample estimate may be. A p-value evaluates data against a stated statistical hypothesis under a model; it is not a measure of clinical importance and does not prove causation. Neither a confidence interval nor a p-value for the primary endpoint is reported in the registry record. No new inferential estimate can be recovered from the registry summaries without performing a recalculation, and no recalculated result is reported.

For binary outcomes, uncertainty can be affected by the number of participants and by how frequently the event occurs. Rare events are particularly difficult to estimate precisely from a limited group, and individual events can have a substantial influence on the observed pattern. General statistical interpretation should distinguish the observed count from the unknown frequency in a broader population. The record does not report a confidence interval that would quantify uncertainty for these event summaries.

How should event categories be understood?

The registry’s primary endpoint refers to serious adverse events and describes classification by system organ class, MedDRA preferred term, and severity. Classification systems organize event reports into categories; they do not by themselves establish cause. The posted results give selected serious-event terms with percentages, while the broader detailed classification results are not reported in the registry record. Terms such as schizophrenia, bipolar disorder, or psychotic disorder also require care in interpretation because the study population includes people with those conditions. A listed event term is a registry classification, not an adjudication of treatment causality.

The record separately lists 230 affected participants in the other adverse-event category. The meaning of that category should not be expanded beyond the information reported. Without additional definitions, it should not automatically be relabeled as a specific severity class or taken to mean that the events were clinically unimportant. The primary endpoint remains the serious adverse-event measure.

What does the planning illustration mean?

The registry describes planning assumptions based on an observed effect, a stated fraction of that effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It labels this a planning illustration rather than the trial’s own design. The actual study is single-group, with no randomized allocation, so a hypothetical two-arm planning framework does not describe the design used to produce the posted safety counts. No prospective sample-size justification is reported in the registry record.

Sample-size calculations are conditional on assumptions about the target effect, variability or event frequency, significance level, and allocation. They describe planning under those assumptions; they are not measures of the probability that a completed study found a true effect. In particular, a planning illustration cannot be interpreted as observed power. The registry record does not provide a numerical planning result in the information reported for this analysis, and no planning value should be treated as an observed study finding.

Multiplicity concerns arise when many outcomes or comparisons are tested. Multiple testing can increase the chance of at least one apparently notable result if tests are interpreted without adjustment. The record lists multiple outcomes and event summaries but reports zero analyses. It does not report a multiplicity procedure, a prespecified testing hierarchy, or inferential results for the listed outcomes. The number of outcome measures alone does not establish what tests were performed or how they were handled.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("NCT00102063 and NCT00110461 Subjects")
n      <- c(325)
events <- c(20)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  NCT00102063 and NCT00110461 Subjects  325  20  6.2  3.8  9.3  4.0  9.3  4.0  9.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the serious adverse-event endpoint as primary and gives changes in PANSS total score and Young Mania Rating Scale total score as secondary outcomes. It reports zero analyses. Numerical results and inferential tests for the secondary outcomes are not reported in the registry record. No adjustment for multiplicity, testing hierarchy, or other strategy for handling multiple outcomes is reported in the registry record.

Multiplicity matters when several hypotheses are tested because interpreting each result in isolation can make chance findings more likely across the set. A prespecified strategy can clarify which outcomes are confirmatory and how evidence should be judged. The record does not report whether such a strategy was specified. The listed outcomes should therefore be understood as registered measures, not as evidence that statistical tests were conducted or that any outcome met a particular threshold.

Missing-data methods are not reported in the registry record. The endpoint population is described as all enrolled subjects, and the primary endpoint timeframe is baseline and Week 23, but the record does not state how missing endpoint information, withdrawal, incomplete follow-up, or participants with no recorded event were handled. The reported at-risk count is 325 for each adverse-event category, but it does not by itself establish complete observation for every participant.

The registry also does not report an analysis population definition beyond the primary endpoint’s description of all enrolled subjects. It is not possible to determine from the record whether an intention-to-treat, safety, or other analysis set was used for particular outcomes. These omissions limit assessment of how the results were constructed and how much missing information could affect their interpretation.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: schizophrenia (1.2%), aggression (0.9%), bipolar disorder (0.9%), psychotic disorder (0.6%), bronchitis acute (0.3%).

The serious adverse-event results list 20 affected subjects among 325 at risk. Separately, the other adverse-event category lists 230 affected subjects among 325 at risk. These counts describe participants recorded in the registry’s categories; they are not a randomized comparison and do not establish that treatment caused an event. The registry does not report deaths for this group, so the death value should not be read as zero.

The selected serious-event terms are schizophrenia, 1.2%; aggression, 0.9%; bipolar disorder, 0.9%; psychotic disorder, 0.6%; bronchitis acute, 0.3%; and hepatitis A, 0.3%. These are event-term percentages reported by the registry. They are not comparative risks, and no uncertainty intervals are reported for them. The record’s endpoint description refers to additional summaries by system organ class, preferred term, and severity; those detailed results are not reported in the registry record.

Event terms indicate how reports were classified, not whether the event was caused by aripiprazole. The study includes participants with schizophrenia and bipolar disorder, so condition-related terms should be interpreted in the context of the enrolled population and the registry’s classifications. The reported counts also do not describe event timing or duration. They are safety observations from a single-group study, not evidence of comparative safety.

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

The registry records serious adverse events in this enrolled group and lists selected serious-event terms with percentages. Those observations can contribute to a descriptive account of safety during the study. The record also reports a separate count for other adverse events. These are the results that can be stated directly from the posted data.

The counts do not show what would have happened to comparable participants under a different treatment or without aripiprazole. There is no concurrent control group, and the study is open-label. Accordingly, the findings do not establish that aripiprazole caused the reported events, prevented events, or changed their frequency. They also cannot be used to estimate a comparative treatment effect from this record alone.

The results do not establish statistical significance or precision for the primary endpoint. No confidence interval, p-value, or adjusted estimate is reported in the registry record. A count in a study group is an observation, not a complete description of the range of plausible event frequencies in a broader population. The record also does not report event timing, participant-level exposure duration, or missing-data methods, all of which can affect interpretation of safety summaries.

The secondary outcomes listed are changes in PANSS total score and Young Mania Rating Scale total score. Their results are not reported in the registry record, so no conclusion about symptom change can be drawn from the information recorded. The study’s safety endpoint is not a substitute for those efficacy-related measures.

Finally, selected event terms should not be confused with a complete listing of all events or with a causal assessment. The endpoint description indicates classifications by system organ class, preferred term, and severity, but detailed results are not reported in the registry record. The posted data support a descriptive reading of recorded events among enrolled participants; they do not support broader conclusions about treatment benefit, comparative risk, or causation.

14. Why This Trial Matters Statistically

This study illustrates a central statistical distinction: describing events in a treated group is not the same as estimating a treatment effect. The registry records an open-label, single-group design, and the primary endpoint is the percentage of subjects with serious adverse events. Such a design can document what was recorded during follow-up, but without a concurrent comparator it cannot isolate the contribution of treatment from other influences.

The distinction is especially important for safety outcomes. Serious events may arise from the underlying conditions, other aspects of care, or factors unrelated to treatment. A participant-level event count is informative as a description of the study experience, while causal interpretation requires a comparison strategy and clear assumptions. The record does not provide a randomized contrast or an adjusted estimate.

The record also illustrates why endpoint definitions and analysis details matter. The primary endpoint specifies a population and a timeframe, and the description identifies classification dimensions for event summaries. Yet missing-data handling, detailed event timing, analysis populations beyond all enrolled subjects, and inferential methods are not reported in the registry record. Without those details, readers should avoid assuming how incomplete follow-up or event classification was handled.

Finally, the planning assumptions described for a hypothetical two-arm illustration are not interchangeable with the actual single-group study design. Planning calculations do not constitute observed evidence or demonstrate observed power. Keeping planning, descriptive results, and causal inference separate is essential for an accurate reading of this study’s statistical record.

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 principal limitation is the absence of a concurrent control group. With a single group and no allocation, the reported event counts cannot estimate a comparative treatment effect or distinguish treatment-related events from events associated with the conditions or other influences. Open-label conduct may also affect event reporting or assessment; specific safeguards or assessments of that possibility are not reported in the registry record.

The registry provides counts for serious and other adverse events and percentages for selected serious-event terms, but no confidence intervals or p-values. The detailed summaries described by system organ class, preferred term, and severity are not reported in the registry record. The value for deaths is also not reported in the registry record and should not be treated as an absence of deaths.

Follow-up and data-handling details are limited. The endpoint timeframe is baseline and Week 23, but event timing, participant-level observation duration, withdrawal effects, missing-data methods, and handling of incomplete follow-up are not reported in the registry record. The primary population is described as all enrolled subjects, but other analysis population definitions are not reported.

The registry lists secondary changes in PANSS and Young Mania Rating Scale total scores, but their numerical results and analyses are not reported. It also reports zero analyses, with no multiplicity procedure or detailed statistical analysis plan reported. These gaps limit evaluation of outcome testing and uncertainty. Finally, the study population and its prior-study context are described, but this record alone does not establish how broadly the observed event experience applies beyond the enrolled participants.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Aripiprazole Open-Label, Safety and Tolerability Study — NCT00102518.
• Registry record last updated 2012-08-31; status last verified 2012-07.
• Results first posted 2012-08-31.
• 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

NCT00102518 is a completed Phase 3, open-label, single-group study of oral aripiprazole, with enrollment of 325. The registry lists a study start of 2004-09 and primary completion of 2007-02. Its stated purpose was long-term safety and tolerability assessment in adolescent patients with schizophrenia and child and adolescent patients with bipolar I disorder, manic or mixed episode.

The primary endpoint is the percentage of subjects experiencing serious adverse events, with baseline and Week 23 as the stated timeframe and all enrolled subjects as the population. The posted results list 20 affected subjects among 325 at risk for serious adverse events and 230 among 325 for other adverse events. Selected serious-event terms and percentages are also listed. The record reports zero analyses; secondary outcome results, inferential estimates, missing-data methods, and the death value are not reported in the registry record.

The single-group results are descriptive. They do not provide a randomized comparison or establish treatment causality.