Effectiveness of Quetiapine XR on the Control of Symptoms of Manic Phase of Bipolar Disorder.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of Quetiapine XR on the Control of Symptoms of Manic Phase of Bipolar Disorder. (NCT00521365), a non-randomized phase 4 study. The primary outcome is Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to End of Treatment (Day 21).

2. Clinical Question

The registry also describes quality of life and productivity loss as study interests, and lists secondary outcomes covering YMRS, Clinical Global Impression, and EQ5D measures. Those aims do not alter the central design limitation: without a concurrent control group, any baseline-to-follow-up change cannot by itself distinguish a treatment-associated change from other influences over time.

3. Trial Design

This was a Phase IV study with a single-group, non-randomized design and no masking. The registry lists 88 participants as enrolled and marks the study as completed. The intervention was quetiapine 600 mg, described in the study summary as extended release at 600 mg per day. The summary allows treatment either as monotherapy or in combination with other therapy; details about any combined treatments are not reported in the registry record.

The principal outcome was change in YMRS total score from baseline to end of treatment, specified as Day 21. The population for that outcome was modified intention to treat, defined in the record by receipt of at least one dose and an evaluable baseline YMRS assessment. The endpoint description refers to the final visit or last observation carried forward (LOCF). The record does not give a participant flow showing how many enrolled patients met this analysis definition or contributed follow-up measurements.

Because all participants received the study intervention and there was no control group, this design estimates within-group change rather than a comparative treatment effect. Non-randomized allocation also means there is no randomized basis for balancing influences on outcomes between treatment groups. Masking was absent, so participants and study personnel were not described as blinded to treatment assignment.

The registry names 14 outcome measures and lists secondary outcomes for symptom ratings, clinical impression, and quality of life. The analysis entries are not reported in the registry record. Details such as the protocol’s statistical analysis plan, eligibility criteria beyond the primary population definition, treatment adherence, concomitant care, and sample-size justification are not reported in the registry record. These omissions limit assessment of how the planned design was implemented and how the posted outcome data were analyzed.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intention to treat patients (88). Patients who had taken at least one dose of study drug and had at least one evaluable Young Mania Rating Scale at baseline.

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 Change in the Young Mania Rating Scale (YMRS) Total Score From Baseline to End of Treatment (Day 21), measured over Baseline and 3 weeks.

The primary endpoint is the mean change in total score on the Young Mania Rating Scale from baseline to the end of treatment, identified as Day 21. The registry describes the score as ranging from 0 to 60. Its 11 items use scales ranging from 0 to 4 for 7 items and from 0 to 8 for 4 items; 0 indicates normal, while 4 or 8 indicates the most abnormal rating for an item. The total score combines ratings across the items to represent the level of manic symptoms.

A change score describes how a participant’s measurement differs from baseline at follow-up. The mean change summarizes the average change in the specified analysis population; the standard deviation describes variation in individual change scores around that average. The registry identifies the endpoint as a mean with standard deviation, but it does not report the numerical mean change or standard deviation. It also does not report a confidence interval or a statistical test for this primary result.

A symptom scale can provide a structured way to track change, but the endpoint is not itself a comparison with an untreated or alternative-treatment group. Since the study had a single group, the baseline-to-end change describes the participants’ course during the study period. It does not isolate the effect of quetiapine from other reasons scores could change. The endpoint description allows the final visit or LOCF, but the record does not report how many endpoint values came from each source.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a mean change in a continuous score, with standard deviation. General explanation: a mean is a measure of the center of observed values, while a standard deviation describes how spread out individual values are around that mean. These are descriptive summaries. By themselves, they do not show how uncertain the estimated mean is; a confidence interval is commonly used to express that uncertainty. The registry record does not report a confidence interval for this endpoint.

What does a change score represent?

A change score is calculated by comparing a follow-up measurement with the same participant’s baseline measurement. A group mean change then averages those individual changes. This can be useful for describing how scores moved over the observation period. Interpretation depends on what is included in the analysis population and how missing follow-up values are handled. The record describes the primary population as modified intention to treat and states that the endpoint could use the final visit or LOCF. It does not report the number of participants with observed follow-up or the number whose endpoint depended on LOCF.

General explanation: the standard deviation of participant-level change is not the same quantity as the standard error of the mean. The standard deviation describes variation among participants; the standard error concerns precision of the group mean and depends on the amount of information available. A confidence interval for a mean is typically built from an estimate and its uncertainty. Since the registry record reports neither the numerical mean change nor the standard deviation, these summaries cannot be examined for the primary outcome.

What can a single-group design estimate?

This study’s single-group design can describe changes observed among participants who received the intervention. A controlled trial can additionally compare outcomes between groups, which helps account for changes that might occur without the intervention. General explanation: random allocation supports comparability of groups on average, including factors that may not have been measured. Here, allocation is listed as non-randomized and there is no separate comparator. Thus, a within-group difference from baseline would not establish what would have happened to the same participants over the same period under another treatment or without the study intervention.

No masking is listed. General explanation: masking can reduce the influence of knowledge of treatment assignment on participant reports, clinical ratings, and decisions about care. Its absence does not automatically invalidate a measurement, but it is relevant when outcomes involve ratings or judgments. YMRS and Clinical Global Impression outcomes involve symptom assessment, and the registry record does not describe procedures used to limit rating or expectation effects.

How should the YMRS measurement be read?

The YMRS is a composite symptom score. The registry describes 11 items, with 7 items scored from 0 to 4 and 4 items scored from 0 to 8; the total possible score is 0 to 60. The record defines 0 as normal and 4 or 8 as the most abnormal rating for an item. General explanation: a scale total condenses multiple item ratings into a single summary, making change easier to describe, but the total does not show which particular symptoms changed. No item-level outcomes are reported in the registry record.

The primary outcome is labeled as change from baseline to end of treatment, with a timeframe of baseline and 3 weeks and a named endpoint at Day 21. The record’s description specifies final visit or LOCF. It does not report whether there were different follow-up times among participants, how the final visit was identified, or whether the analysis followed a prespecified scoring rule for incomplete questionnaires.

What is missing from the inferential analysis?

The registry contains no analysis entries. General explanation: an inferential analysis may use a statistical model or test to quantify uncertainty or assess a specified hypothesis. The choice depends on the design, the outcome distribution, the measurement schedule, and the intended estimand. The registry record does not report the statistical model, test, confidence interval method, or hypothesis test for the primary endpoint. It is therefore not possible to assess whether assumptions were checked or whether the analysis accounted for repeated measurements or other design features.

The study record includes an assumption statement for a planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect defined as a stated fraction of the observed effect. Those are planning assumptions, not a description of this single-group study’s observed analysis. The record does not report numerical planning outputs. Planning sample sizes are illustrations under assumptions and are not observed power or evidence about the precision of this study’s result.

General explanation: when data are more variable than a model assumes, standard errors and confidence intervals can be misleading unless the analysis accounts for that extra variability. This is called over-dispersion in settings where a model expects less variation than the data show. The posted record does not identify an over-dispersed outcome model or provide enough analysis detail to assess whether this issue applied. Since the primary endpoint is a continuous score, the registry’s mean and standard deviation description does not itself indicate an over-dispersion adjustment.

Overall, the available methodological details define the scale, endpoint, and population criteria, but do not document the statistical procedures needed to reproduce or fully evaluate an inferential result. The registry record does not report the protocol-level analysis plan, handling of all missing observations, or any analysis results for the primary or secondary outcomes.

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("Quetiapine 600 mg")
n   <- c(88)
m   <- c(-20.72)
sp  <- c(10.2)
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  Quetiapine 600 mg  88  -20.720  10.200  -22.881  -18.559

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures and names several secondary outcomes: YMRS change at additional visits, YMRS response and remission, Clinical Global Impression measures, and EQ5D index and visual analogue scale changes. The study summary also describes quality of life and productivity loss as areas of interest. The registry record does not report numerical results for these outcomes or analysis entries.

General explanation: when a study examines multiple outcomes or multiple time points, the chance of at least one apparently unusual result can increase if each result is assessed separately. A prespecified hierarchy, adjustment method, or clear distinction between primary and exploratory outcomes can help readers understand how results were interpreted. The registry record identifies a primary outcome, but does not report a multiplicity strategy, a hierarchy for secondary outcomes, or whether any adjustment was used. Those details are not reported in the registry record.

The primary outcome population requires at least one dose and an evaluable baseline YMRS assessment. This is the record’s modified intention-to-treat definition. The endpoint description permits the final visit or LOCF. General explanation: missing-data methods make assumptions about outcomes that were not observed, and different assumptions can lead to different estimates. LOCF carries a participant’s last observed value forward to a later assessment; its suitability depends on the setting and the pattern and reasons for missingness. The record does not report how many observations were missing, how many values were carried forward, or the reasons for missing follow-up.

The record also does not report a comparison between results using observed follow-up values and results under another missing-data approach. Nor does it provide a participant flow by analysis population. As a result, the extent to which the primary analysis reflects all enrolled participants cannot be determined from the registry record. The absence of these details limits evaluation of both multiplicity and missing-data sensitivity.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: mania increased (1.1%).

The registry lists one group, Quetiapine 600 mg, with 88 participants at risk for serious adverse events and 1 affected participant. The listed top serious adverse event term is “Mania Increased,” reported as 1.1%. The record also lists 88 participants at risk for other adverse events and 30 affected participants. These figures describe counts in the study group; they do not establish that the intervention caused the events.

General explanation: a serious adverse event is classified by seriousness criteria, which are distinct from how severe a symptom may feel. The registry’s serious-event count should therefore not be read as a count of all adverse events or as a measure of overall symptom severity. The record does not report event-level timing, duration, outcome, or an assessment of causal relationship for the listed serious event. Deaths are not reported in the registry record.

These safety counts come from an uncontrolled study. There is no comparator group in the registry record against which to assess whether event counts differed under another treatment or without study treatment. The counts are descriptive and should be read within that design context.

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

The registry record documents a completed Phase IV study of quetiapine extended release 600 mg per day in patients with mania associated with bipolar disorder. It reports enrollment of 88 participants and describes a primary endpoint based on mean YMRS change from baseline to Day 21. It also specifies the YMRS scoring structure and a modified intention-to-treat population definition. These details explain what the study intended to measure and who could contribute to the primary analysis.

The record does not report the numerical primary endpoint result. Therefore, it does not show the size or direction of mean YMRS change, the variability of participant changes, or the precision of an estimate. No numerical efficacy conclusion can be drawn from the primary endpoint information in this record. The secondary outcomes are named, but their numerical results are not reported in the registry record either.

Even if a baseline-to-follow-up change estimate were available, this single-group, non-randomized, unmasked design would not establish that the change was caused by quetiapine. Changes over time can have multiple explanations, and the study has no concurrent comparator to help distinguish them. The registry does not report details about the use of additional therapy, so the role of combined treatment cannot be evaluated from the record.

The safety figures are descriptive counts for the treated group: 1 participant with a serious adverse event, with “Mania Increased” listed at 1.1%, and 30 participants with other adverse events. Without a control group or fuller event detail, these counts do not determine comparative risk or causation.

Accordingly, the record is informative about the design, intended outcome, population definition, and reported event counts, but it does not provide the numerical outcome evidence required to assess the observed symptom change. It should not be treated as evidence of a comparative effect, and the missing result should not be replaced with an assumption about what the analysis might have found.

14. Why This Trial Matters Statistically

This study illustrates why design and reporting details matter when interpreting a clinical outcome. A single-group study can document what happened to participants during treatment and follow-up, but a within-group change does not answer the comparative question of how outcomes would differ under another treatment or no study treatment. Non-randomized allocation and absence of masking add further reasons to be cautious about causal interpretation.

It also illustrates the difference between defining an endpoint and reporting its result. The record gives a clear description of the YMRS total score, its scoring range, the baseline-to-Day 21 change, and the intended summary as a mean with standard deviation. Yet it does not report the numerical change or its variability. Without those values, readers cannot assess magnitude, precision, or the distribution of participant outcomes. A detailed measurement description cannot substitute for the outcome estimate itself.

The modified intention-to-treat definition and reference to LOCF are important because analysis populations and missing-data procedures influence what a result represents. The record does not report follow-up completeness, the amount of LOCF use, or sensitivity analyses. These omissions make it difficult to assess how robust a potential estimate would be to missing observations.

The record further lists multiple symptom, clinical impression, and quality-of-life outcomes without reporting analysis entries or a multiplicity plan. This underscores the value of transparent prespecification and reporting: readers need to know which outcomes were primary, how secondary results were handled, and how uncertainty was quantified. Here, the central statistical lesson is that the registry gives substantial context about the intended study question, while leaving the primary numerical result and key analysis details unreported.

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 main limitation for interpreting the posted evidence is that the registry record does not report a numerical result for the primary YMRS endpoint. It also does not report the standard deviation, confidence interval, or p-value for that endpoint. The direction, magnitude, and precision of mean change therefore cannot be assessed from the record.

The study design has no concurrent control group, uses non-randomized allocation, and is unmasked. A change over time cannot be attributed uniquely to the study intervention on the basis of this design. The study summary permits monotherapy or combined therapy, but the registry does not report which participants received additional therapy or how such treatment was handled analytically.

The registry record does not report participant flow, follow-up completion, the number with observed end-of-treatment YMRS scores, or the extent of LOCF use. The modified intention-to-treat definition is described, but the record does not report whether all 88 participants contributed to the primary outcome analysis. Details of the protocol, statistical analysis plan, sample-size justification, or any interim analyses are not reported in the registry record.

Although 14 outcome measures are listed, numerical results and analysis entries are not reported. The registry also does not report a multiplicity approach or sensitivity analyses for missing data. Safety reporting includes group counts and a listed serious-event term, but not detailed event timing, outcomes, or causal assessments. These limitations apply to interpretation of the registry record and do not establish what may or may not appear in other study materials.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effectiveness of Quetiapine XR on the Control of Symptoms of Manic Phase of Bipolar Disorder. — NCT00521365.
• Registry record last updated 2012-07-17; status last verified 2012-03.
• Results first posted 2012-07-17.
• 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

This completed Phase IV study used a non-randomized, unmasked, single-group design and enrolled 88 participants. The intervention was quetiapine 600 mg, described as extended release at 600 mg per day, for mania associated with bipolar disorder. The primary outcome was mean change in YMRS total score from baseline to Day 21, in a modified intention-to-treat population defined by at least one dose and an evaluable baseline assessment.

The registry record does not report the numerical primary outcome result, its standard deviation, or an inferential analysis. Secondary outcomes are listed but numerical analyses are not reported. Safety entries include 1 participant with a serious adverse event and 30 participants with other adverse events; “Mania Increased” is listed as a serious-event term at 1.1%. With no comparator group, the study describes a treated group rather than a comparative treatment effect.