SGA-induced Metabolic Syndrome in Bipolar Youth: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for SGA-induced Metabolic Syndrome in Bipolar Youth (NCT01858948), a randomized phase 3 study. The primary outcome is Body Mass Index (BMI).

2. Clinical Question

The statistical question is whether the recorded mean BMI at the endpoint differs between randomized groups, and how precisely any such difference can be estimated. The registry presents a mean and standard deviation for each arm, but the comparison is marked as missing or not estimable for a two-arm continuous endpoint. It therefore does not report an effect estimate, confidence interval, or p-value for the primary comparison.

The study hypothesis concerned whether long-chain omega-3 fatty acid supplementation would attenuate adverse cardiometabolic effects associated with second-generation antipsychotic exposure. BMI is one measure relevant to that question, but the posted endpoint summaries alone do not establish whether a treatment-related difference occurred. The registry also lists manic symptom severity as a secondary outcome, without a posted analysis for it.

3. Trial Design

The registry classifies this as a Phase 3, randomized, quadruple-masked, parallel-group trial. Its status is completed. Enrollment was 19. The recorded start was 2013-07, and the primary completion was 2018-04.

The stated population was first-episode adolescent manic patients treated with open-label quetiapine. They were randomized to adjunctive fish oil or placebo for 24 weeks. The two arm descriptions are Quetiapine plus Omega and Quetiapine plus Placebo. The registry also lists quetiapine fumarate, omega, and placebo as interventions.

The omega arm description specifies EPA+DHA supplements at a fixed dose of 3.0 g/day, consisting of EPA 2.0 g and DHA 1.0 g, taken as 5 capsules/d for 24 weeks. The placebo arm description identifies corn oil and says the placebo supplements were similar in shape and color. Further details about the placebo regimen are not reported in the registry record.

Randomization and masking describe important features of the design, but the registry record does not give the allocation sequence method, concealment procedures, or which roles were included in quadruple masking. It also does not report how participants were assigned when enrollment occurred or what procedures were used to preserve masking. Those details should not be inferred from the design labels alone.

The parallel-group structure means the randomized groups were followed as separate arms rather than as a crossover in which participants switched treatments. The primary endpoint was BMI at 24 weeks. The registry identifies manic symptom severity as a secondary outcome, but does not report its results or an analysis. No further information about follow-up schedules, adherence, or treatment discontinuation is 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.

Before assignment: All patients received 6-week open-label quetiapine prior to entering the trial.

Overall Study

Analysis population for the primary outcome, as defined in the registry: First-episode adolescent manic patients treated with open-label quetiapine were randomized to adjunctive treatment with fish oil or placebo for 24-weeks.

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 Body Mass Index (BMI), measured over 24 weeks.

The primary endpoint is body mass index (BMI), reported as a mean in kg/m^2 at 24 weeks. BMI is calculated from weight in kilograms divided by height in meters squared. It is a continuous measure: its numerical value can vary across a range rather than placing each participant in only one category. The registry states that greater decreases in BMI are a better outcome.

The record also gives BMI categories: underweight is <18.5, normal weight is 18.5-24.9, overweight is 25-29.9, and obesity is BMI of 30 or greater. These categories offer a way to describe BMI values in relation to conventional ranges, but the posted primary results are means and standard deviations rather than counts in each category. The registry does not report category-specific results.

BMI is used as a measure related to body fat, but it is not a direct measure of body composition. In this trial, it is relevant to the stated interest in cardiometabolic effects during second-generation antipsychotic exposure. A group mean describes the average BMI in an arm; it does not show every participant’s value, the distribution of values, or the number of participants whose BMI increased or decreased.

The 24-week arm summaries are 24.4 kg/m^2 with a standard deviation of 4.7 for Quetiapine plus Omega, and 26.3 kg/m^2 with a standard deviation of 7.4 for Quetiapine plus Placebo. These are descriptive endpoint summaries. The registry does not report an estimable statistical comparison between them, so they should not be interpreted as a quantified treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean summarize?

A mean is the arithmetic average of the observed values in a group. For this trial, each reported mean summarizes BMI at 24 weeks within one randomized arm. A mean gives a compact description of the center of the observed values, but it does not show the full distribution. Different collections of participant values can have the same mean, and a mean can be influenced by unusually high or low observations.

The standard deviation describes how dispersed observed values are around their group mean. A larger standard deviation indicates greater spread among the recorded values. It does not quantify how precisely the mean estimates a population value, and it is not the uncertainty interval for a between-group treatment effect. In the registry, the reported arm standard deviations are 4.7 for Quetiapine plus Omega and 7.4 for Quetiapine plus Placebo.

How is a randomized comparison usually interpreted?

In general, randomization is intended to make treatment groups comparable at assignment, on average, with respect to measured and unmeasured characteristics. A statistical comparison then estimates the outcome contrast between the assigned groups. The result depends on the endpoint definition, the analysis population, how missing observations are handled, and whether the comparison is adjusted for other variables. The registry record identifies randomization but does not report the analysis method or an estimable comparison for BMI.

A confidence interval is a range of values compatible with the data and the statistical model at a stated confidence level. Its width conveys precision: a narrower interval indicates a more precise estimate under the model, while a wider interval indicates greater uncertainty. A confidence interval would help readers judge which magnitudes of between-arm difference remain plausible. No confidence interval for the BMI comparison is reported in the registry record.

A p-value, when calculated under a specified statistical model, measures how surprising data at least as extreme as those observed would be if a stated null hypothesis were true. It does not give the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry does not report a p-value for the primary BMI comparison. Without the comparison estimate and its uncertainty, the arm means should not be used as a substitute for inferential analysis.

What does the record’s missing comparison mean?

The registry marks the two-arm continuous endpoint comparison as having values missing or not estimable. It also records zero analyses. This is a limitation of the posted statistical result: the available record supplies arm summaries but not a calculated contrast between them. It does not establish why that comparison could not be estimated, and reasons such as a particular model failure or a prespecified analysis decision are not reported in the registry record.

Because no comparison is posted, there is no registry-reported estimate to characterize as adjusted or unadjusted, and there is no basis for describing a statistical test or model as the trial’s chosen approach. In general, continuous outcomes may be analyzed with methods that compare group means, with adjustment for baseline values or other prespecified factors where appropriate. Which method was used or intended in this trial is not reported in the registry record. Any description of such methods is general, not a claim about the trial’s analysis plan.

What role do sample-size calculations play?

In general, a sample-size calculation is a planning exercise. It asks how many participants may be needed to detect a specified effect under assumptions about variability, allocation, significance level, and power. It does not describe the observed evidence after a trial has been conducted, and a planning number is not observed power. The registry record does not report the trial’s own sample-size justification or design assumptions.

The planning illustrations associated with these results use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Their target effect is defined as a stated fraction of the observed effect. Such illustrations are conditional on those assumptions and should be read as hypothetical planning scenarios, not as the trial’s original design rationale. The record does not report the original sample-size justification, and the posted primary comparison is not estimable, so the illustrations cannot replace an inferential result from this trial.

More generally, sample-size planning depends on the target effect and assumed variability. Over-dispersion means that the outcome varies more than a simple statistical model expects; when present, it can make standard errors too small and intervals too narrow if the model does not account for it. This is a general statistical consideration, not a reported feature of the BMI data in this trial. The registry does not identify an over-dispersion assessment or report a model for the endpoint.

For a continuous outcome, the interpretation also depends on whether the analysis concerns endpoint values or change from baseline. The registry names BMI at 24 weeks as the primary measure and posts arm means at that time. It does not report baseline BMI summaries or say that the posted result is a change score. It also does not describe covariate adjustment, imputation, sensitivity analyses, or an analysis population. These absent details limit reproducibility and make it inappropriate to attribute a particular statistical procedure to the trial.

The key statistical distinction is between descriptive arm summaries and an inferential treatment comparison. The posted means and standard deviations describe the recorded endpoint data. A comparison estimate, accompanied by uncertainty, would address how much the arms differed under an analysis model. Since that estimate is not reported as estimable, the results support descriptive reading only. They do not establish the magnitude, precision, or statistical significance of a treatment 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("Quitiapine Plus Omega", "Quetiapine Plus Placebo")
n   <- c(9, 10)
m   <- c(24.4, 26.3)
sp  <- c(4.7, 7.4)
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  Quitiapine Plus Omega  9  24.400  4.700  20.787  28.013
CARM  Quetiapine Plus Placebo  10  26.300  7.400  21.006  31.594

11. Multiplicity, Missing Data and Analysis Populations

The registry lists Body Mass Index as the primary outcome and Manic Symptom Severity as a secondary outcome. It also records 3 outcome measures and zero analyses. The results include arm summaries for BMI, but the two-arm continuous comparison is marked as missing or not estimable. No analysis of the secondary outcome is posted.

When a study evaluates multiple outcomes or multiple comparisons, multiplicity can increase the chance of a false-positive finding if results are interpreted without an appropriate strategy. A prespecified hierarchy, adjustment procedure, or other multiplicity approach can clarify how confirmatory conclusions are protected. The registry record does not report a multiplicity plan, so no particular procedure or control of the overall error rate can be attributed to this trial.

The record does not report the number of participants with missing BMI observations, the reasons for missingness, or how missing measurements were handled. It does not describe imputation, complete-case analysis, or sensitivity analyses. The arm sizes associated with the posted BMI summaries are 9 and 10, but those figures alone do not identify the analysis population or explain whether any randomized participants lacked endpoint data.

The registry record also does not report whether the analysis followed intention-to-treat, per-protocol, or another population definition. It does not describe exclusions after randomization, treatment adherence, or handling of treatment discontinuation. These are important because analysis choices and missing outcomes can affect the meaning of a randomized comparison. In the absence of this information, the arm summaries should be treated as descriptive and the missing comparison should not be reconstructed by assumption.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

For Quetiapine plus Omega, the registry records 9 participants at risk for serious adverse events and 0 affected. It records 9 participants at risk for other adverse events and 0 affected, with 0 deaths. For Quetiapine plus Placebo, 10 participants are recorded at risk for serious adverse events and 0 affected; 10 are recorded at risk for other adverse events and 0 affected, with 0 deaths.

These figures describe the safety counts entered in the registry for the listed groups. A count of zero means that no events of the corresponding recorded category are reported among the participants counted at risk. It does not prove that an event is impossible, nor does it establish that the groups have equivalent safety profiles. With these group sizes, the counts provide limited information about uncommon events.

The record lists no top serious adverse event terms. It does not provide further detail in the registry record about event definitions, collection procedures, exposure time, or the relationship of any event to treatment. The zero counts should therefore be read as registry-reported counts, not as a guarantee that no safety concern can occur or as a comparative safety analysis.

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

The posted results show 24-week mean BMI values of 24.4 kg/m^2 for Quetiapine plus Omega and 26.3 kg/m^2 for Quetiapine plus Placebo. The corresponding standard deviations are 4.7 and 7.4. These summaries describe the observed values recorded for the two arms; they do not provide a quantified treatment contrast.

The registry does not report an estimable comparison for the primary continuous outcome. It therefore does not establish the direction or magnitude of a treatment effect with statistical uncertainty, and no p-value is reported. The descriptive ordering of the two means should not be turned into a claim that one assigned regimen caused a difference. The record does not provide baseline BMI values, so the endpoint means should not be described as changes from baseline.

The stated research hypothesis concerned attenuation of adverse cardiometabolic effects associated with second-generation antipsychotic exposure. BMI is one endpoint relevant to that question, but it does not by itself represent every cardiometabolic outcome. The registry identifies manic symptom severity as a secondary outcome, but no analysis for it is posted. The available outcome information consequently does not resolve the broader hypothesis.

The randomized, quadruple-masked, parallel design is relevant context for how the study was structured, but a design label does not replace the missing comparison result. The enrollment was 19, and the posted BMI summaries include 9 and 10 participants in the respective arms. The record does not explain whether all randomized participants contributed endpoint data or how missing values were handled. These uncertainties limit interpretation of the summaries.

In general, a clinical result is most informative when it includes an effect estimate and a measure of precision, alongside clear definitions of the analysis population and missing-data approach. Those elements are not reported for the primary comparison in the registry record. The evidence that can be described is therefore narrow: arm-specific BMI summaries and recorded adverse-event counts. It does not support a conclusion that omega supplementation works or does not work, or a conclusion about the treatment’s overall clinical value.

14. Why This Trial Matters Statistically

This trial illustrates the difference between reporting outcome summaries and reporting a treatment comparison. Means and standard deviations are useful descriptions, but they do not show how uncertain a difference between randomized groups may be. Without an estimable contrast and its uncertainty, readers cannot assess the precision of the primary comparison from the registry record.

The distinction matters particularly in a small trial. Enrollment was 19, and the BMI summaries are based on 9 participants in Quetiapine plus Omega and 10 in Quetiapine plus Placebo. Individual observations can have considerable influence on group summaries when groups are small. The posted standard deviations describe spread, but do not tell readers how much an estimated between-group effect would vary across repeated samples.

The record also shows why a completed trial status and posted endpoint values do not ensure that all planned analyses are available. The primary outcome has summary values, but the two-arm comparison is marked as missing or not estimable, and the registry records zero analyses. The reason is not reported. Clear reporting of the analysis method, analysis population, missing-data handling, and uncertainty would help readers understand what the result can support.

Sample-size planning is another distinct statistical task. Planning calculations rely on assumptions and are not a substitute for observed estimates or evidence of treatment effects. The record does not give the trial’s own sample-size justification. Keeping planning illustrations separate from trial results prevents hypothetical design quantities from being mistaken for observed findings.

For clinical research readers, this record is a useful example of cautious interpretation: randomized design and descriptive outcomes are relevant, while the missing inferential comparison places a firm limit on conclusions. Reporting the limitations transparently is as important as reporting the endpoint summaries.

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 primary limitation for interpretation is that the registry does not report an estimable two-arm comparison for BMI. Although mean and standard deviation values are posted for both arms, there is no reported treatment-effect estimate, confidence interval, or p-value. The registry marks the continuous comparison as missing or not estimable, and the reason is not reported in the registry record.

The enrollment was 19, with BMI summaries for 9 participants in the omega arm and 10 in the placebo arm. These small arm summaries may be sensitive to individual observations, and the registry does not give confidence intervals or participant-level distributions. It is not possible to assess the precision of a group contrast from the posted means and standard deviations alone.

The registry identifies BMI at 24 weeks as the primary endpoint, but does not report baseline BMI summaries or whether an adjusted analysis was intended. The posted values therefore cannot be interpreted as within-person change. The record also does not report the statistical model, analysis population, missing-data methods, adherence, or treatment discontinuations. Those omissions limit assessment of potential bias and reproducibility.

The registry lists manic symptom severity as a secondary outcome, but no analysis is posted. It records 3 outcome measures and zero analyses, and no multiplicity plan is reported. The posted BMI endpoint is also only one measure relevant to the study’s cardiometabolic hypothesis; the available record does not provide a complete assessment of that broader question.

Finally, the registry’s completed status and safety counts do not fill these evidence gaps. Zero adverse events in the recorded categories are limited observations in the listed groups, not proof that events cannot occur. The record does not provide further safety-collection details or a comparative safety analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: SGA-induced Metabolic Syndrome in Bipolar Youth — NCT01858948.
• Registry record last updated 2022-11-25; status last verified 2022-11.
• Results first posted 2022-11-25.
• 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

NCT01858948, titled SGA-induced Metabolic Syndrome in Bipolar Youth, is recorded as a completed Phase 3 randomized, quadruple-masked, parallel-group trial sponsored by the University of Cincinnati. Enrollment was 19. The registry describes first-episode adolescent manic patients treated with open-label quetiapine and randomized to adjunctive omega-3 supplementation or placebo.

The primary endpoint was BMI in kg/m^2 at 24 weeks. The posted arm summaries are a mean of 24.4 with standard deviation 4.7 for Quetiapine plus Omega, and a mean of 26.3 with standard deviation 7.4 for Quetiapine plus Placebo. The registry does not report an estimable two-arm comparison. It lists Manic Symptom Severity as a secondary outcome, with no analysis posted.

Safety records show 0 serious adverse events, 0 other adverse events, and 0 deaths in each arm. These are registry counts for the participants recorded at risk, not a comprehensive comparative safety conclusion. Analysis methods, missing-data handling, and the trial’s own sample-size justification are not reported in the registry record.