Evaluate the Efficacy and Safety of Quetiapine Fumarate (SEROQUEL) Extended Release as Monotherapy in the Treatment of Patients With Bipolar Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluate the Efficacy and Safety of Quetiapine Fumarate (SEROQUEL) Extended Release as Monotherapy in the Treatment of Patients With Bipolar Depression (NCT01256177), a randomized phase 3 study. The primary outcome is Change From Baseline (Visit 2) to End of Study (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score.

2. Clinical Question

The central statistical question is about the average change in a symptom-rating score over the stated period, rather than a comparison of the proportion meeting a response or remission threshold. MADRS is the primary measure; the record also lists secondary measures addressing response, remission, other symptom scales, global clinical impressions, suicidal ideation, and treatment-emergent mania.

The trial enrolled 361 participants. That total is not the same as the number contributing to the primary endpoint at Week 8: the registry record identifies 100 participants in the placebo group and 114 in the quetiapine XR group for that assessment. These endpoint counts describe the stated analysis population at that visit, but do not explain why other enrolled participants are not represented in those counts.

The question is comparative and specific to this trial’s participants, intervention, comparator, and Week 8 endpoint. The record does not provide results that would establish the direction, size, or precision of any treatment difference. It therefore supports describing the planned comparison, but not drawing a conclusion about the observed primary outcome.

3. Trial Design

This was a Phase 3, randomized, double-blind, placebo-controlled study with a parallel-group model. The registry title describes a multicenter study of quetiapine fumarate extended release as monotherapy for bipolar depression. AstraZeneca is listed as the sponsor. The record marks the study as completed, with a start of 2010-12 and primary completion of 2012-11.

The listed interventions were quetiapine fumarate extended release and placebo. The study objective was to evaluate the efficacy of once-daily quetiapine XR monotherapy compared with placebo for depressive symptoms in patients with Bipolar I and Bipolar II Disorder. The arm descriptions in the registry record are blank, so further arm-level operational details are not reported in the registry record.

There were 361 participants enrolled. The primary endpoint is described as change from baseline, identified as Visit 2, to Week 8 in MADRS total score. Its analysis population is identified as the Full Analysis Set. The record states that the number of participants at Week 8 was 100 for placebo and 114 for quetiapine XR. It does not describe the precise criteria used to define the Full Analysis Set or explain the difference between enrollment and Week 8 counts.

Randomization and double masking can help limit systematic differences between groups and influence on outcome assessment, in general. The registry record does not report how the random sequence was generated, whether allocation was concealed, who was masked, or whether masking was assessed. Details such as the treatment duration beyond the Week 8 primary timeframe, visit schedule, dosing procedures, and adherence are not reported in the registry record.

The record lists nine outcome measures and 14 analyses. It does not identify a complete analysis plan, so the relationship between those analyses and the outcomes cannot be reconstructed from the registry entry alone. The posted record therefore establishes the broad design and endpoint, while leaving important implementation and analysis details unspecified.

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: 361 patients were enrolled in the study of which 296 patients were randomized and 65 patients were not randomized. Reasons for patients not being randomized are (22 due to eligiblity criteria not fullfilled, 40 due to subject decision, 3 due to others).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (Number of participants at Week 8: Placebo=100; Quetiapine XR=114)

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: Full Analysis Set (FAS) Of the 148 patients randomized to each group, 1 in each group did not receive treatament. In addition, there were 15 patients (7 placebo; 8 quetiapine XR) for which no MADRS data were collected. All 17 patients are included in the Reason Not Completed Section above.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline (Visit 2) to End of Study (Week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score, measured over Baseline to Week 8.

The primary endpoint is change from baseline to Week 8 in total score on the Montgomery-Asberg Depression Rating Scale (MADRS). The scale ranges from 0 to 60, with higher scores indicating more severe symptoms. Change is defined as the Week 8 total score minus the baseline score. Under this convention, a negative change indicates a lower score at Week 8 than at baseline, while a positive change indicates a higher score.

The endpoint is analyzed as a continuous measure, with the primary parameter identified as a least-squares mean and dispersion described using a standard error. A mean change uses information across the score distribution rather than reducing each participant to a response category. This can retain gradations in change that would be lost if the outcome were represented only as meeting or not meeting a threshold.

In general, a symptom-rating scale is useful for evaluating change when the same measure is collected at baseline and follow-up. The baseline-to-Week 8 comparison frames the outcome over the stated period, and using a common scale allows the two randomized groups to be compared. The registry record does not report the specific model used to obtain the least-squares means, how baseline score was incorporated, or how missing Week 8 scores were handled.

The record names this endpoint and describes its scale, timeframe, population, and summary measure, but it does not report the actual arm-level means, treatment contrast, standard error, or confidence interval. Consequently, the endpoint’s definition is clear enough to interpret, but the observed magnitude and precision of the comparison are not available in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a continuous outcome: MADRS total score change from baseline to Week 8. Continuous outcomes retain the amount of change in the score, rather than grouping participants into categories. The primary result is identified as a least-squares mean, with standard error as the measure of dispersion around that estimate. The record does not give the numerical estimates, so the statistical methods can be described only at the level of the stated summary approach.

What does a least-squares mean represent?

In general, a least-squares mean is an estimated average derived from a statistical model. Depending on the model, it may account for specified variables or repeated measurements. It is not necessarily identical to the raw arithmetic average. The registry record does not identify the model, its covariates, or whether any repeated measurements were included. It is therefore not possible to determine what adjustment, if any, was applied or to reproduce the estimate from the registry description.

The endpoint definition is Week 8 score minus baseline score. In general, estimating change can focus attention on how the score shifts over the assessment period. When groups are randomized, a between-group comparison can assess whether the average change differs between assigned groups, subject to the analysis assumptions and the quality of outcome data. The registry record does not report the primary between-group contrast or its test result.

How should the standard error be read?

In general, a standard error describes the sampling precision of an estimated quantity. It is distinct from a standard deviation, which describes variability among individual observations. A smaller standard error generally indicates a more precisely estimated mean, while a larger one indicates greater uncertainty. For a treatment comparison, uncertainty is best interpreted alongside the contrast and a confidence interval. The record gives no primary standard error or confidence interval, so precision cannot be evaluated from the posted results.

A confidence interval, in general, gives a range of values that is compatible with the data and the statistical model at a stated confidence level. It can communicate both the direction and plausible magnitude of an estimated effect. A p-value addresses compatibility of the observed data with a null hypothesis under model assumptions, but does not by itself express the size or clinical importance of an effect. The registry record reports neither a primary confidence interval nor a primary p-value.

Why can over-dispersion matter?

General statistical context: over-dispersion occurs when observed variability is greater than a model assumes. It is especially relevant for outcomes modeled as counts or proportions, where a simple distributional model can understate uncertainty if observations vary more than expected. The primary endpoint in this study is described as a continuous score, and no model information is available to determine whether over-dispersion was relevant or assessed. No claim about its presence or impact can be made for this trial from the registry record.

The listed secondary outcomes include categorical measures, such as response and remission, as well as continuous score changes and clinical global assessments. General statistical practice may use different models for continuous, binary, ordinal, or event outcomes. The registry record does not identify which methods were used for these secondary outcomes. It also does not provide the detailed definitions and analysis populations for every listed outcome beyond the descriptions in the outcome titles.

What does the planning illustration represent?

The record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. Such figures are planning illustrations, not observed trial outcomes and not a measure of the probability that the trial found a real effect. Because the primary observed effect is not reported in the registry record, the assumptions alone do not establish what effect size underlies any illustration.

In general, a planning calculation estimates the sample size associated with chosen assumptions about an effect, error rate, allocation, and statistical method. It does not show that those assumptions were used when the trial was designed. The registry record does not report the trial’s own sample-size justification, target power, or protocol calculations. No design rationale should be inferred from an illustrative calculation.

More broadly, the registry identifies 14 analyses but does not describe the statistical analysis plan. The model specification, handling of missing data, analysis-set definitions, multiplicity strategy, and treatment of protocol deviations are not reported in the registry record. These details are needed to understand how the estimates were generated and how strongly they support an interpretation. The methods described in the record establish the outcome type and reported summary measure, but not the full analysis procedure.

10. Multiplicity, Missing Data and Analysis Populations

The record lists nine outcome measures and 14 analyses, but does not report a multiplicity strategy. Multiplicity arises when several outcomes, time points, contrasts, or analyses are evaluated. In general, assessing many comparisons without an appropriate plan can increase the chance of finding an apparently notable result by chance. The number of listed analyses alone does not reveal which tests were intended as primary, whether tests were organized hierarchically, or how any error rate was controlled.

The primary outcome is identified as change in MADRS total score from baseline to Week 8. The registry record does not report a full statistical analysis plan, the planned treatment contrast, or whether the primary test was adjusted for other comparisons. The secondary outcomes cover multiple domains, including response, remission, symptom scores, global impressions, suicidal ideation, and mania. Their presence does not establish that all were tested as confirmatory endpoints.

Missing-data handling is also not reported in the registry record. The Full Analysis Set is named for the primary endpoint, and the record gives Week 8 counts of 100 for placebo and 114 for quetiapine XR. It does not define that analysis population, report baseline availability, explain why Week 8 counts differ from the enrollment total of 361, or state how incomplete observations were handled. Methods for missing values can affect estimates when participants with observed outcomes differ from those without them.

The registry also does not report sensitivity analyses that might assess how conclusions change under different assumptions about unavailable outcomes. Without those details, it is not possible to assess whether the analysis accounted for missingness in a way that is robust to plausible alternatives. These are limits in the information recorded, not evidence that a particular method was or was not used.

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: peritonitis (0.7%), bipolar i disorder (0.7%), intentional self-injury (0.7%).

The serious adverse event figures are reported for 147 participants at risk in each group. The placebo group had 3 participants with serious adverse events, and the quetiapine XR group had 0. These are participant counts in the registry record; they are not, by themselves, a complete account of event timing, duration, severity, relatedness, or recurrence.

The record also reports other adverse events for 43 participants in the placebo group and 81 in the quetiapine XR group, with 147 participants at risk in each group. These figures are separate from the serious adverse event counts and should not be treated as interchangeable categories. The registry record does not provide details about event definitions, exposure time, statistical comparisons, or whether events were judged related to treatment.

Three serious-event terms are listed among the most frequent: peritonitis, bipolar I disorder, and intentional self-injury, each reported as 0.7%. The entry does not identify the group attribution for those terms in this listing. Deaths are not reported in the registry record.

In general, adverse-event counts describe events observed and recorded in the trial, but do not alone establish causality or quantify risk over differing exposure periods. These figures should be read as registry safety summaries, not as proof of a treatment effect on safety.

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

The registry record establishes that this was a randomized, double-blind, placebo-controlled Phase 3 study with a primary endpoint of MADRS total score change from baseline to Week 8. It identifies the intervention, comparator, analysis population label, score range, and Week 8 counts. Those details allow a reader to understand what comparison was intended and what the primary measure represents.

However, the registry record does not report the primary outcome means, treatment contrast, standard error, confidence interval, or p-value. It therefore does not show the observed magnitude, direction, or precision of the primary comparison. The absence of those results from this record is not evidence that there was no difference; it means the comparison cannot be characterized from the registry information available.

Nor can the entry establish clinical importance. A score difference, even if reported, would need to be interpreted with its uncertainty, the measurement context, and a relevant threshold for meaningful change. No such threshold is reported in the registry record. The scale’s direction is described: higher scores indicate more severe symptoms, and change is Week 8 minus baseline. This defines how a result would be read, but does not supply the result.

The secondary outcome list and safety counts provide additional context, but do not substitute for the primary outcome analysis. The secondary outcome results are not reported in the registry record. Safety counts are descriptive and do not by themselves establish causation or comparative safety. Important information on missing data, multiplicity, and model specification is also absent.

Accordingly, the study design and intended statistical question can be described, while the primary result and its implications remain undetermined from this registry record. A completed status is a study-status designation, not a statistical finding.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a clearly specified endpoint and a fully interpretable result. The registry record defines a continuous primary measure, its direction, timeframe, summary parameter, dispersion measure, and analysis population label. These elements are necessary for understanding what a trial intends to estimate.

At the same time, an endpoint definition does not answer the comparative question. Interpretation requires the group estimates or treatment contrast and an indication of their uncertainty. Without these, readers cannot tell whether the observed mean changes differed, in which direction, by how much, or with what precision. The record’s lack of primary results makes that boundary especially clear.

The difference between total enrollment and the Week 8 endpoint counts also highlights why analysis populations and missing-data methods matter. The record reports 361 enrolled participants and Week 8 counts of 100 for placebo and 114 for quetiapine XR, but does not explain how the analysis set was defined or how unobserved outcomes were treated. Such information is important when assessing what population an estimate represents.

The set of listed secondary outcomes raises a further general issue: conclusions based on multiple outcomes require clear reporting of which comparisons were prespecified and how multiplicity was handled. The registry lists nine outcome measures and 14 analyses, but does not report those procedures. This does not establish that the study lacked a plan; it limits what can be assessed from the registry entry.

Overall, the record allows scrutiny of design features and endpoint definitions, while illustrating that statistical conclusions depend on transparent reporting of estimates, uncertainty, analysis choices, and missing-data procedures. Those results and details are not reported in the registry record.

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.

A key limitation for interpreting this trial from the registry record is that the primary outcome results are not reported. No arm-level least-squares means, between-group estimate, standard error, confidence interval, or p-value is available. As a result, the size, direction, and precision of the primary comparison cannot be described.

The record identifies the Full Analysis Set but does not define its membership or explain how participants entered or left the analysis. It gives Week 8 counts of 100 for placebo and 114 for quetiapine XR, while total enrollment was 361. The reasons for the difference are not reported in the registry record. The handling of missing baseline or follow-up values and any sensitivity analyses are also not reported.

The exact statistical model is unspecified. Although the primary parameter is a least-squares mean and dispersion is described as a standard error, the model terms, baseline adjustment, covariance assumptions, and method for estimating uncertainty are not reported in the registry record. Consequently, the estimate cannot be independently reconstructed or checked against the stated analysis description.

The record lists multiple secondary outcomes and 14 analyses, but does not report the analysis hierarchy or multiplicity procedures. It also does not provide secondary outcome results. The study objective describes once-daily monotherapy, but the registry arm descriptions are blank, and further details about dosing implementation, adherence, and exposure are not reported in the registry record.

Finally, the safety summary provides participant counts, but not event-level context, exposure-adjusted comparisons, or attribution details for the listed serious-event terms. Deaths are not reported in the registry record. These limitations concern what can be assessed from the registry information; they do not establish what procedures or results may appear in other records.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluate the Efficacy and Safety of Quetiapine Fumarate (SEROQUEL) Extended Release as Monotherapy in the Treatment of Patients With Bipolar Depression — NCT01256177.
• Registry record last updated 2016-04-15; status last verified 2016-03.
• Results first posted 2016-02-03.
• 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

NCT01256177 is a completed Phase 3 randomized, double-blind, parallel-group, placebo-controlled study sponsored by AstraZeneca. It enrolled 361 participants and evaluated quetiapine fumarate extended release monotherapy against placebo for bipolar depression. The registry lists a study start of 2010-12 and primary completion of 2012-11.

The primary endpoint was change from baseline to Week 8 in MADRS total score, analyzed in a population identified as the Full Analysis Set. The record reports Week 8 participant counts of 100 for placebo and 114 for quetiapine XR, and describes least-squares means with standard errors. The numerical primary results and detailed statistical plan are not reported in the registry record.

Secondary outcomes include response and remission measures, symptom and global-impression scores, suicidal ideation, and treatment-emergent mania. The record also reports serious and other adverse-event counts. It does not report secondary outcome results, explain missing-data handling, or specify multiplicity procedures.