Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar (NCT00176202), a randomized phase 3 study. The primary outcome is Young Mania Rating Scale (YMRS).

2. Clinical Question

3. Trial Design

This was a randomized, triple-masked, parallel-group Phase 3 trial, listed as completed. The registry reports enrollment of 65 participants and names the University of Illinois Chicago as sponsor. The study start is listed as 2003-04, and primary completion as 2008-01. The intervention arms were risperidone and divalproex sodium.

In general, randomization is intended to reduce systematic differences between treatment groups at assignment. A parallel-group design assigns participants to a study arm and follows the assigned groups during the trial. Triple masking indicates that the registry classified the study as masked at three levels, but which people or roles were masked, and how masking was maintained, are not reported in the registry record. The allocation sequence, allocation concealment, and the number assigned to each treatment arm are also not reported in the registry record.

The primary outcome description specifies baseline and end-of-study YMRS assessment during a six-week study, with an earlier endpoint if a participant ended the study before six weeks. The record also lists the Child Depression Rating Scale-Revised, Child Mania Rating Scale, and Clinical Global Improvement in Bipolar Disorder Overall as secondary outcomes. The registry does not report the treatment schedule, visit schedule beyond the primary measure's timeframe, or criteria for ending participation early. It does not report details about recruitment locations or whether the trial was conducted at one or more sites.

The randomized design defines the intended comparison, but design labels alone do not establish how the analysis was performed or what the results were. Numerical estimates for the primary endpoint and details of the statistical analysis are not reported in the registry record. The trial's completion status does not by itself indicate the direction, size, or precision of an outcome.

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: Exclusion Criteria: * Children with general medical condition such as head injury, epilepsy, endocrine disorders * Those who are on mood altering medications such as steroids, and those diagnosed with mental retardation are excluded to avoid confounding and contributing factors to mood swings.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Inclusion criteria were a DSM-IV diagnosis of bipolar disorder Type I (mixed or manic episode); 8 to 18 years old; and medication free or currently clinically unstable on medication, justifying termination of the ineffective regimen.

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.

Population: AGE 10 TO 20 YRS GENDER :BOTH

6. Primary Endpoint

The registry lists the primary outcome as Young Mania Rating Scale (YMRS), measured over Six week study with assessment at baseline and end of the study (at the end of 6 weeks or earlier if they ended the study before 6 week end point)..

The primary measure was the Young Mania Rating Scale (YMRS), a clinician-rated measure of manic symptom severity. Its 11 items assess the severity of abnormalities using the participant's report about the previous forty-eight hours and the clinician's behavioral observations during the interview, with greater emphasis on the latter. Four items are graded on a 0 to 8 scale, and the remaining seven items are graded on a 0 to 4 scale. The possible total ranges from zero to 60; the description identifies zero as normal and 60 as severe, and states that a score equal to or above 12 serves as a cutoff point for illness.

The registry describes reporting the mean and standard deviation at week 0 and week 6. A mean conveys the group's average score, while the standard deviation describes how dispersed individual scores are around that average. These summaries can characterize symptom scores at the recorded time points, but by themselves they do not specify a treatment contrast or account for any baseline differences. The record permits an earlier endpoint for participants who ended the study before six weeks; how such observations were incorporated into the primary analysis is not reported in the registry record.

The measure is relevant to the trial's stated question because it quantifies manic symptom severity in the enrolled population. However, the numerical YMRS means, standard deviations, changes, and comparison between arms are not reported in the registry record. The endpoint description therefore explains what was intended to be measured, not what the trial found.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a continuous measure reported as a mean with standard deviation. It specifies YMRS assessment at baseline and at the end of the six-week study, or earlier when a participant ended participation before the six-week endpoint. The registry's outcome description says the mean and standard deviation are shown at week 0 and week 6, but numerical summaries are not reported in the registry record.

What do the mean and standard deviation describe?

In general, the mean is an average of the scores in a group. It provides a measure of the group's central score, but does not show whether participants had similar or widely varying scores. The standard deviation describes the spread of scores around the mean. A larger standard deviation indicates more dispersion among individual scores; a smaller one indicates that scores are more closely clustered around the group average. Neither statistic alone gives the uncertainty in a between-group comparison.

Because the record describes repeated measurement at baseline and follow-up, an interpretation might distinguish scores at each time point from change over time. These are different summaries. A comparison of follow-up means is not necessarily the same as a comparison of change from baseline, and an adjusted analysis could differ from an unadjusted comparison. The registry record does not report whether the primary analysis compared endpoint scores, changes, or another summary, nor whether it adjusted for baseline scores. No specific statistical model or estimation procedure is reported.

How should uncertainty be considered?

In general, an effect estimate describes the size and direction of a comparison, while a confidence interval communicates uncertainty around that estimate under the chosen model. A p-value addresses the data's compatibility with a specified null hypothesis, conditional on the analysis assumptions. These measures answer related but distinct questions. An estimate and its interval are needed to understand both the possible size of a difference and its precision; a p-value alone would not describe clinical importance. The registry record does not report a primary-outcome contrast, confidence interval, or p-value.

The record identifies the trial as randomized and parallel-group, but does not report the analysis model, any covariates, the handling of repeated observations, or whether the analysis followed randomized assignment. Randomization describes how treatment assignment was intended to occur; it does not reveal which analysis was ultimately used. Allocation concealment, the randomization sequence, and analysis-population definitions are not reported in the registry record.

What does the planning illustration represent?

The registry's sample-size assumptions describe a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The intended effect to detect is described as a stated fraction of the observed effect. Such calculations are planning illustrations, not the trial's own design justification and not observed power. The registry record does not report the trial's sample-size justification or the numerical participant counts for the planning illustrations. It also does not report which effect estimate or outcome was used to define the observed effect.

In general, sample-size planning asks how many participants would be needed under specified assumptions to detect a chosen effect with a chosen power. These calculations depend on assumptions about the effect, variability, significance level, allocation, and analysis. They do not establish that a trial was adequately powered after the fact. In particular, observed power calculated from an observed result is not a substitute for reporting the estimate and its uncertainty. The posted enrollment of 65 is the trial enrollment figure, whereas any planning illustration is a separate calculation and should not be read as the number actually analyzed.

Over-dispersion is a general concern when observed variability is greater than the model assumes. If a model understates variability, its uncertainty estimates may be too narrow and its tests may appear more decisive than warranted. The registry record does not identify an over-dispersion issue or describe a model for the continuous YMRS outcome, so it is not possible to say whether this concern arose in this trial. More generally, the appropriateness of a statistical method depends on its assumptions and the data structure, which cannot be evaluated from the design labels alone.

How do multiple outcomes affect interpretation?

The record lists four outcome measures, including the YMRS and three secondary measures, and reports eight analyses. In general, conducting multiple analyses can increase the chance that at least one result appears unusual by chance if each is considered separately. Methods for addressing multiplicity can include prespecifying a primary comparison or adjusting the criteria used for inference. The registry record does not report whether any multiplicity approach was planned or used. The eight analyses are not described in sufficient detail to identify their relationship to the outcome measures, time points, or analysis populations.

The methods information therefore supports a limited statistical account: the primary measure is continuous, the registry describes means and standard deviations at baseline and follow-up, and the design is randomized and parallel-group. It does not provide the numerical outcomes or enough analysis detail to reproduce or assess the primary comparison. Any stronger claim about estimation, adjustment, missing-data handling, or statistical significance would go beyond what is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures: the YMRS primary outcome and the Child Depression Rating Scale-Revised, Child Mania Rating Scale, and Clinical Global Improvement in Bipolar Disorder Overall as secondary outcomes. It also reports eight analyses. The record does not describe how the analyses map to the outcome measures or time points, which comparisons were prespecified, or whether any multiplicity adjustment was planned or applied. In general, multiplicity matters because repeated testing can make isolated nominal results harder to interpret as confirmatory evidence. Without the analysis plan or results, the role of multiplicity in this trial cannot be evaluated.

Missing-data procedures are not reported in the registry record. The primary outcome timeframe allows an assessment at the end of the six-week study or earlier if a participant ended the study before that point. The record does not state how early endpoint measurements were treated, how missing follow-up scores were handled, or whether imputation or another method was used. The number of participants with observed primary outcome data at each time point is also not reported.

The analysis populations are not defined in the registry record. It is not reported whether analyses included all randomized participants, only participants who received treatment, or only those with available outcome data. The enrollment figure alone does not establish the number analyzed for any outcome. These gaps prevent assessment of attrition, the influence of missing observations, and whether the analysis preserved the intended randomized comparison.

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 adverse-event record lists zero serious adverse events among 32 participants at risk in the risperidone group and zero among 33 participants at risk in the Depakote or divalproex sodium group. These are the serious-event counts and corresponding at-risk group sizes recorded for the listed arms. The registry does not list any serious adverse-event terms.

The record separately lists other adverse events: 8 among 32 participants at risk in the risperidone group and 10 among 33 at risk in the divalproex sodium group. The listing does not provide descriptions of those other events in the information. The death fields are not populated with numerical values, so death figures are not reported in the registry record.

These counts should be read as event reporting within the groups and period covered by the registry entry. Zero recorded serious events does not establish that serious events were impossible or that the treatments have no risk. The record does not provide further details about event definitions, collection procedures, duration of safety follow-up, or statistical comparisons. The counts also do not supply evidence about the primary YMRS outcome, whose numerical results are not reported in the registry record.

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

The registry record establishes that a randomized, triple-masked, parallel-group Phase 3 trial compared risperidone with divalproex sodium in pediatric bipolar disorder. It identifies the YMRS as the primary measure and describes baseline and end-of-study assessment during a six-week study, with earlier assessment for participants who ended the study before that endpoint. These details clarify the question the trial set out to address and the measure selected for it.

What the record does not establish is the result of the primary comparison. Numerical group scores, changes, an effect estimate, uncertainty interval, and inferential test are not reported in the registry record. Therefore, the stated objective cannot be treated as a finding, and neither equality nor a difference between the treatments can be inferred from the trial design or completion status. The secondary outcomes are named, but their numerical results are not reported either.

In general, statistical evidence and clinical meaning are not interchangeable. An estimate can be small or large, and its uncertainty can be narrow or wide; those features need to be considered together. A statistical test alone would not establish whether an observed difference matters in practice. For this record, neither the magnitude nor precision of the primary comparison is available, so that distinction cannot be evaluated.

The listed adverse-event counts provide a limited description of events recorded in the two arms. They do not establish comparative safety across all possible outcomes, and the absence of listed serious events does not show that risk is absent. The record does not provide death counts or detailed descriptions of the other adverse events.

Accordingly, the most defensible reading is that the registry documents a completed comparative trial and its planned measures, but does not report enough outcome or analysis information to characterize the efficacy result. This distinction matters: a trial's question, design, and measured outcomes are not substitutes for the numerical estimates needed to interpret its findings.

13. Why This Trial Matters Statistically

This trial is statistically notable for posing an explicit comparative question between two active medication arms and registering a continuous symptom measure as its primary outcome. Randomization and parallel-group assignment describe a framework for comparing groups, while the YMRS provides a defined scale for characterizing manic symptom severity. The record also identifies several secondary measures addressing depression symptoms, mania symptoms, and global clinical improvement.

The statistical value of that framework depends on transparent reporting of the estimates and methods. Here, the registry record reports the design, enrollment, outcome definitions, and adverse-event counts, but does not report numerical results for the primary outcome. It also lists eight analyses without describing their relation to outcomes or time points. This illustrates why a registered objective and a completed-trial status cannot replace reported estimates, uncertainty, and analysis details when assessing evidence.

General statistical interpretation requires attention to the size of an estimate, its precision, and the assumptions behind the analysis. For a repeated continuous measure, choices about whether to compare follow-up scores or changes, whether to adjust for baseline, and how to handle missing observations can affect interpretation. The registry record does not report those choices, so an independent reader cannot assess their appropriateness from the record alone.

The record's safety counts also illustrate the need to distinguish observed event counts from broad conclusions about risk. Counts are informative within their reporting scope, but without fuller outcome definitions, follow-up information, and comparisons, they cannot answer every safety question. In this case, the numerical primary-outcome result remains unavailable in the registry record, limiting the statistical conclusions that can be drawn from the trial entry.

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 main limitation for interpreting this trial from the registry record is the absence of numerical primary-outcome results. The YMRS is described, and its planned assessment times are specified, but group means, standard deviations, changes, and a between-arm estimate are not reported. The record therefore does not support assessment of effect size or precision. Numerical results for the listed secondary outcomes are also not reported.

The primary endpoint is described at baseline and week 6, with an earlier endpoint if participants ended the study before six weeks. The record does not report how many participants contributed data at each assessment or how early endpoints were analyzed. It does not give participant flow, attrition information, missing-data methods, or analysis-population definitions. These omissions make it difficult to judge how the reported enrollment relates to the outcome analyses.

The record identifies randomization and triple masking but does not describe the sequence-generation method, allocation concealment, who was masked, or how masking was maintained. It does not report treatment doses, treatment delivery, adherence, or details of concomitant care. The statistical model, baseline adjustment, handling of repeated measures, and multiplicity approach are also not reported. These are limitations of the information available in the registry entry, not evidence that a particular method was or was not used.

The adverse-event listing includes group counts but does not give event descriptions for the other adverse events, additional collection details, or numerical death figures. The record also does not report a sample-size justification. Although planning assumptions are described as an illustration, the numerical planning results are not reported in the registry record. Taken together, the available entry is sufficient to identify the study question and design, but limited for independently evaluating its efficacy analysis, precision, and completeness of safety reporting.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar — NCT00176202.
• Registry record last updated 2015-11-05; status last verified 2015-11.
• Results first posted 2015-11-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a completed, randomized, triple-masked, parallel-group Phase 3 trial sponsored by the University of Illinois Chicago, with enrollment of 65. It compares risperidone and divalproex sodium in young people aged 8 to 18 years with bipolar disorder Type I in a mixed or manic episode, under the stated eligibility conditions.

The primary outcome is the Young Mania Rating Scale, with baseline and end-of-study assessment during a six-week study or earlier for participants who ended the study before that endpoint. Three secondary measures are listed: the Child Depression Rating Scale-Revised, Child Mania Rating Scale, and Clinical Global Improvement in Bipolar Disorder Overall. Numerical primary and secondary outcome results, analysis details, missing-data procedures, and analysis populations are not reported in the registry record.

The adverse-event entry lists zero serious events in each arm, along with counts of other adverse events. Death figures are not reported in the registry record. The available information defines the trial's intended comparison and measures but does not permit interpretation of the primary treatment effect.