Open-label Study to Compare Hospitalization Rates of Schizophrenic Patients Treated With Oral Antipsychotics Versus IM Depot Aripiprazole: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-label Study to Compare Hospitalization Rates of Schizophrenic Patients Treated With Oral Antipsychotics Versus IM Depot Aripiprazole (NCT01432444), a na phase 3 study. The primary outcome is Number of Inpatient Psychiatric Hospitalization for Retrospective Period (Months 4-6) and Prospective Period (Months 4-6)..

2. Clinical Question

The registry describes the study as a comparison of retrospective hospitalization rates during oral antipsychotic treatment with prospective rates during treatment with depot aripiprazole in a naturalistic community setting. The stated primary endpoint focuses on whether participants had inpatient psychiatric hospitalization during the specified periods. It is therefore framed as a binary event outcome, rather than as a comparison of the total number of hospital days.

The question is clinically recognizable but statistically nonrandomized. The same participants’ earlier and later treatment periods form the comparison, yet those periods differ in timing and treatment. Changes in hospitalization could reflect treatment, changes in participants’ circumstances, or other differences between the retrospective and prospective periods. The registry record does not report a primary result, so the direction and precision of the observed comparison cannot be described.

3. Trial Design

This was a completed Phase 3, open-label study sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. The registry lists enrollment of 493 participants, an allocation value of NA, no masking, and a single-group model. The study began in 2011-09 and reached primary completion in 2013-12. The title and summary describe a comparison between oral antipsychotic treatment and aripiprazole IM depot treatment, but the design does not include a randomized, concurrent control arm.

The intervention was aripiprazole IM depot injection, listed at 300 mg or 400 mg. The retrospective period covered months 4-6 while participants were receiving oral standard-of-care antipsychotic treatment. The prospective period covered Phase B months 4-6, identified as Weeks 12 to 24, after switching to depot treatment. Both periods therefore refer to later portions of their respective treatment periods, but one is retrospective and the other prospective.

The primary endpoint analysis used a Phase 3-month completer sample of 336 participants who entered the open-label treatment phase and completed at least 3 months of treatment. The registry also defines an Intent-to-Treat dataset for efficacy analyses as participants who entered Phase B, regardless of whether they received a dose. These descriptions identify different analysis-population concepts; the record does not explain their relationship in enough detail to resolve every population-specific analysis choice.

Secondary outcomes include changes from baseline in PANSS total, positive and negative subscale scores, change in CGI-S, and mean CGI-I by week. The record lists six outcome measures and five analyses. It does not report the detailed analysis plan, the rationale for the sample size, or the rules governing dose selection.

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: 493 participants were enrolled, 325 of which had no history of tolerating oral aripiprazole entered Phase A, all participants completed Phase A combined with remainder of participants to enter Phase B. All outcome measures were assessed in Phase B.

Tolerability/Cross-titration Phase

Reasons for not completing this period:

Treatment Phase

Reasons for not completing this period:

Extension Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The core dataset for all efficacy analyses is the Intent-to-Treat (ITT) dataset which consisted of data from all participants who entered Phase B regardless of receiving a dose in the Open-label Aripiprazole IM Depot Treatment Phase.

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 Inpatient Psychiatric Hospitalization for Retrospective Period (Months 4-6) and Prospective Period (Months 4-6)., measured over Retrospective period Months 4-6; Prospective period Months 4-6.

The primary endpoint concerns inpatient psychiatric hospitalization in two specified periods: retrospective months 4-6 during oral standard-of-care antipsychotic treatment and prospective Phase B months 4-6 after the switch to aripiprazole IM depot. The endpoint description defines the comparison in terms of the proportion of participants with at least one inpatient psychiatric hospitalization. Although the endpoint title uses “number,” the description frames the primary comparison as a participant-level event indicator.

A binary endpoint can summarize whether a participant experienced the event during a defined period. It does not, by itself, distinguish someone with one hospitalization from someone with multiple hospitalizations, nor does it describe length of stay. Those details would require separate outcomes. A rate comparison based on the proportion experiencing hospitalization is intended to make the periods comparable at the participant level, but interpretation still depends on how event ascertainment and missing periods were handled; those details are not reported in the registry record.

The endpoint is used to address whether hospitalization occurrence differed between the retrospective oral-treatment period and the prospective depot-treatment period. It is important to separate that research question from a causal treatment effect: the record describes a single-group, open-label comparison across time, not randomized allocation to concurrent treatments. No primary event proportions, treatment contrast, confidence interval, or significance test are reported in the registry record. Consequently, the endpoint definition can be explained, but the estimated difference and its precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary outcome: whether a participant had inpatient psychiatric hospitalization in each of the specified treatment periods. For a binary endpoint, an analysis commonly summarizes the fraction of participants who experience the event and compares those summaries across groups or periods. The registry states that its comparison concerns the proportion of patients with hospitalization, but it does not report the statistical test, model, effect measure, or uncertainty method used. No particular analysis technique should therefore be attributed to the investigators.

The study’s structure affects which methods would be appropriate. The oral-treatment period is retrospective, whereas the depot-treatment period is prospective, and both periods concern the same general participant cohort. If individual-level paired observations are available for both periods, the dependence between a participant’s observations may matter. Treating such data as independent groups can misrepresent uncertainty. The registry record does not state whether the analysis accounted for within-participant pairing, nor does it explain how participants without complete information for both periods were handled.

For a binary outcome, the estimated event proportion is only one part of the statistical account. A contrast could be expressed in different ways, and each measure answers a somewhat different question. The registry record does not identify which contrast was used or provide the underlying event counts. Without those details, it is not possible to reconstruct the reported analysis or judge its precision. No recalculated estimate is available in the registry record.

A confidence interval is a general statistical tool for expressing uncertainty around an estimated quantity. A narrower interval indicates greater precision under the assumptions of the method; a wider interval indicates less precision. It is not a guarantee that the true value lies within the interval, and it does not address biases created by a nonrandomized design. The registry record does not report a confidence interval for the primary endpoint.

A p-value, as a general concept, describes how surprising data at least as incompatible with a specified null hypothesis would be if that hypothesis and the analysis assumptions held. It does not measure the probability that a treatment works, and it does not quantify clinical importance. No primary p-value is reported in the registry record. Statistical significance, if reported elsewhere, would need to be interpreted alongside the effect estimate, its uncertainty, the design, and the endpoint’s clinical meaning.

Hospitalization counts can also be analyzed as event counts or rates, but that is not automatically the same as the stated binary endpoint. Count models may require attention to over-dispersion, a condition in which event counts vary more than a chosen model expects. That is a general modeling consideration, not evidence that this study used a count model or encountered over-dispersion. The endpoint description specifies a proportion of participants with hospitalization; the registry record does not report a separate analysis of recurrent admission counts or person-time rates.

The record’s sample-size assumptions describe a planning illustration based on the observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such a planning illustration is distinct from the trial’s single-group, historical-versus-prospective design. It is not a report of the trial’s original design calculation, and its assumed two-arm allocation does not mean that the study randomized participants between arms. Planning sample sizes are hypothetical design quantities, not observed power. The registry record does not report the trial’s own sample-size justification.

General interpretation of a planning calculation also depends on its assumptions. A calculation tied to an observed effect does not establish that the effect is unbiased, clinically important, or reproducible. Changing the target effect or other assumptions changes the planning question. The registry record does not provide a basis to treat the illustration as a prospective design decision or as a measure of the study’s ability to detect its actual effect.

Finally, analysis populations and endpoint definitions should be read together. The primary endpoint description names a 3-month completer sample of 336, while the efficacy-population description identifies an ITT dataset of Phase B entrants regardless of dose receipt. The registry does not state whether the primary outcome was also analyzed in the ITT population, how the two period-specific records were assembled, or whether sensitivity analyses were conducted. These missing method details constrain any independent assessment of the primary comparison.

10. Multiplicity, Missing Data and Analysis Populations

The record lists several efficacy outcomes: PANSS total score, PANSS positive and negative subscale scores, CGI-S, and CGI-I by week, in addition to the hospitalization endpoint. It reports six outcome measures and five analyses, but those counts do not specify which outcomes were tested together, which analyses were designated primary or secondary in the analysis plan, or whether any multiplicity adjustment was used. The statistical analysis plan and multiplicity procedure are not reported in the registry record.

Multiplicity is a general concern when several outcomes, time points, or comparisons are examined. Conducting many statistical tests can increase the chance of finding an apparently notable result by chance. Adjustment procedures can address some forms of this concern, but their relevance depends on the prespecified testing strategy. Without the analysis plan and results, it is not possible to determine whether multiplicity affected interpretation in this study.

Missing-data methods are also not reported in the registry record. The primary analysis is described as using participants who entered the open-label phase and completed at least 3 months of treatment, while the broader efficacy dataset includes Phase B entrants regardless of whether they received a dose. The record does not explain how missing hospitalization information, incomplete periods, withdrawal, or other unavailable measurements were handled. It also does not report sensitivity analyses assessing the consequences of missing data.

The population definitions should not be treated as interchangeable. The 336-person primary endpoint sample is described by treatment completion, whereas the ITT definition is based on entering Phase B. The record does not report how many participants in each population contributed to each endpoint-specific analysis. This limits the ability to assess whether exclusions or missing observations could have influenced the findings.

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: schizophrenia, paranoid type (3.2%), schizophrenia (3.1%), psychotic disorder (1.9%), suicidal ideation (1.4%), convulsion (0.9%).

The registry lists adverse-event information separately for the open-label Aripiprazole IM Depot Treatment Phase (Phase B) and the Extension Phase (Phase C). For Phase B, 431 participants were at risk for serious adverse events and 61 were recorded as affected; 431 were at risk for other adverse events and 60 were recorded as affected. For Phase C, 192 participants were at risk for serious adverse events and 19 were recorded as affected; 192 were at risk for other adverse events and 24 were recorded as affected. These are phase-specific counts and should not be combined as if they came from one common follow-up group.

The record lists selected serious adverse-event terms with percentages: schizophrenia, paranoid type, 3.2%; schizophrenia, 3.1%; psychotic disorder, 1.9%; suicidal ideation, 1.4%; convulsion, 0.9%; and suicide attempt, 0.7%. These terms describe reported serious events; they do not establish that treatment caused them. The registry does not report death counts, so deaths are not reported in the registry record.

Event counts depend on the number at risk and the duration and completeness of observation. These figures are descriptive, not a randomized safety comparison against oral treatment. The registry record does not provide a matched control group or enough detail to infer comparative risk from these counts alone.

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

The study addresses a practical comparison between retrospective hospitalization experience during oral antipsychotic treatment and prospective experience after a switch to aripiprazole IM depot in a naturalistic community setting. Its stated endpoint is participant-level inpatient psychiatric hospitalization during specified portions of those periods. That question is distinct from whether the treatment caused any observed change.

The record does not report the primary endpoint result. It therefore cannot establish whether the proportion of participants hospitalized was higher or lower in either period, how large a difference may have been, or how precisely it was estimated. The listed objective, endpoint definition, and study completion status do not supply those missing results. Nor do the listed secondary measures establish changes in symptom scores or clinical global ratings.

The single-group, open-label design is central to what the comparison can mean. The earlier oral-treatment period is retrospective and the depot-treatment period is prospective, so factors other than treatment may vary across time. A difference, if reported, could reflect changes in participants’ circumstances, clinical practice, event recording, or treatment as well as any treatment-related effect. Without random allocation and appropriate analysis details, causal attribution is limited.

The registry does offer design and population details that help frame the evidence: enrollment was 493, while the primary endpoint analysis used 336 participants who completed at least 3 months of open-label treatment. The separate ITT definition includes Phase B entrants regardless of dose receipt, but the primary endpoint’s handling of missing information is not reported. These details matter because findings from a completer population may not represent all enrolled participants.

In general, an estimate and its uncertainty are needed to judge the scale and precision of a statistical result. Since those primary-result details are not reported in the registry record, no conclusion about the observed hospitalization comparison can be drawn from this record alone.

13. Why This Trial Matters Statistically

This trial is statistically instructive because its title describes a treatment comparison, while its registry design is single-group and open-label. The comparison is between a retrospective oral-treatment period and a prospective depot-treatment period, rather than between randomized groups followed concurrently. Recognizing that distinction prevents a temporal association from being read as a clean estimate of a treatment effect.

The endpoint also illustrates why operational definitions matter. The title refers to the number of hospitalizations, while the endpoint description defines the primary comparison as the proportion of participants with at least one inpatient psychiatric hospitalization. A participant-level event indicator does not capture the same information as total admissions or time spent in hospital. Clear interpretation depends on knowing which measure was analyzed.

Population definitions are another important feature. The primary endpoint description identifies a 3-month completer sample of 336 participants, while the efficacy-population definition includes participants who entered Phase B regardless of dose receipt. These definitions represent different inclusion rules. If the analysis population is not clearly linked to each result, readers may not know who contributed to the estimate or how exclusions affected it.

Finally, the registry record shows the limits of interpreting a completed study when the primary numerical result and its uncertainty are not reported. Design details can clarify the intended question, but they cannot replace the estimate, confidence interval, or statistical analysis description needed to assess an observed result. The study is a useful example of keeping the endpoint, design, population, and reported evidence distinct.

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 comparison is not randomized: allocation is listed as NA, masking is none, and the model is single group. The retrospective oral-treatment period and prospective depot-treatment period may differ in ways beyond the treatment received. The registry does not report an approach that can separate treatment effects from other time-related or contextual differences.

The primary outcome result is not reported in the registry record. There are no period-specific hospitalization proportions, estimated contrast, confidence interval, or p-value. This prevents assessment of the observed direction, magnitude, and precision of the primary comparison.

The primary endpoint population is described as 336 participants who entered the open-label treatment phase and completed at least 3 months. Enrollment was 493. The record does not explain the reasons for noninclusion in the primary sample or report the endpoint result in the broader ITT dataset. Missing-data procedures and sensitivity analyses are not reported.

The endpoint description refers to the proportion of participants with hospitalization, although the title uses “number.” The record does not clarify whether recurrent admissions or hospitalization duration were separately evaluated. Details of event ascertainment across retrospective and prospective periods are also not reported, limiting assessment of comparability.

The registry does not report the statistical analysis plan, the method used for the primary comparison, multiplicity handling, or the trial’s sample-size justification. Safety counts are phase-specific and lack a randomized comparison against oral treatment. Death counts are not reported in the registry record. These limitations mean the registry description supports a clear account of the study question and design, but not a full evaluation of efficacy or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open-label Study to Compare Hospitalization Rates of Schizophrenic Patients Treated With Oral Antipsychotics Versus IM Depot Aripiprazole — NCT01432444.
• Registry record last updated 2015-05-07; status last verified 2015-04.
• Results first posted 2015-03-27.
• 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

NCT01432444 is a completed Phase 3, open-label, single-group study sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. It enrolled 493 participants with schizophrenia. The study compared retrospective hospitalization experience during oral standard-of-care antipsychotic treatment with prospective experience after switching to aripiprazole IM depot, listed as 300 mg or 400 mg.

The primary endpoint concerns the proportion of participants with inpatient psychiatric hospitalization in retrospective months 4-6 and prospective Phase B months 4-6. Its primary analysis population is described as 336 participants who completed at least 3 months of open-label treatment. The registry separately defines an ITT efficacy dataset based on entering Phase B, regardless of dose receipt.

Secondary outcomes include PANSS and CGI measures. The registry lists adverse-event counts for Phase B and Phase C. It does not report the primary hospitalization result, its uncertainty, the detailed statistical plan, missing-data handling, or multiplicity procedures.