This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study Comparing the Tolerability of Seroquel IR With Seroquel XR in Patients With Bipolar Depression (NCT00926393), a randomized phase 4 study. The primary outcome is Modified Bond-Lader Visual Analog Scale Score After 50-mg Dose (Day 2).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00926393 |
| Phase | Phase 4 |
| Condition | Bipolar Depression |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 139 |
| Arms in the primary outcome | 2 |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
Patients with bipolar depression who were randomized and received study treatment. The primary modified intent-to-treat analysis set included patients with a baseline Modified Bond-Lader Visual Analog Scale score and a score at least one hour after the 50 mg dose.
Intervention
Quetiapine extended release (XR), with the arm description listing doses of 50, 200 and 300 mg during initial dose escalation.
Comparator
Quetiapine immediate release (IR), with the arm description listing doses of 25, 100, 200 and 300 mg during initial dose escalation.
Primary question
How did the Modified Bond-Lader Visual Analog Scale score one hour after the 50 mg dose on Day 2 compare between the IR and XR groups? The registry record describes the trial purpose as comparing the sedation profile one hour after dose administration. It posts separate arm estimates and confidence intervals, but no formal primary between-arm estimate or test.
This was a comparison of early sedation-scale scores during dose escalation, not a comparison of longer-term symptoms or disease course. The scale places Alert at 0 and Drowsy at 100, with a score of 100 assigned if a patient is sleeping. Thus, a higher score represents greater reported drowsiness on the measure. The registry record identifies 139 participants as enrolled; the primary outcome estimates use 65 participants in the IR group and 69 in the XR group. Reasons for the difference between enrollment and the analysis counts are not reported in the registry record.
3. Trial Design
The registry record describes a completed Phase IV, randomized, parallel-group study sponsored by AstraZeneca. It lists the design as multicenter, double-blind and double-dummy, and categorizes masking as quadruple. Participants were assigned to quetiapine IR or quetiapine XR. The study title and brief description emphasize tolerability during initial dose escalation and sedation one hour after dosing.
The IR arm description lists quetiapine doses of 25, 100, 200 and 300 mg; the XR arm description lists 50, 200 and 300 mg. The primary endpoint is the Modified Bond-Lader Visual Analog Scale score one hour after the 50 mg dose on Day 2. Secondary outcomes include scores after later doses, maximum intensity, time to maximum intensity, area under the scale-time curve, and change in the Simpson-Angus Scale total score. The registry lists 13 outcome measures and 12 posted secondary outcomes.
Enrollment was 139. The registry lists the study as completed, with a start in 2009-06 and primary completion in 2009-08. Details about the randomization sequence, concealment procedures, dose timing beyond the stated endpoint time, treatment duration, and sample-size justification are not reported in the registry record. A planned statistical analysis document and interim-analysis details are also not reported in the registry record. The registry record therefore supports a description of the broad design and outcome structure, but not a reconstruction of all protocol or analysis decisions.
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: Patients must have DSM-IV-TR documented bipolar I or bipolar II, most recent episode depressed, and outpatient status at enrollment . Patients must not have another current, major disorder that is symptomatic or has required treatment within 6 months of enrollment.
Overall Study
| Stage | Quetiapine IR | Quetiapine XR |
|---|---|---|
| STARTED | 69 | 70 |
| COMPLETED | 67 | 67 |
| NOT COMPLETED | 2 | 3 |
Reasons for not completing this period:
| Reason | Quetiapine IR | Quetiapine XR |
|---|---|---|
| Withdrawal by Subject | 1 | 2 |
| Adverse Event | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: The modified intent-to-treat (MITT) analysis data set included all randomized patients who received study treatment, classified according to their randomized treatment and provided the Modified Bond-Lader VAS score at baseline (pre-dose at Day 1 or Day 2) and at least 1 hour after 50 mg dose administration.
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.
| Characteristic | Unit | Quetiapine IR | Quetiapine XR | Total |
|---|---|---|---|---|
| Participants analysed | 69 | 70 | 139 | |
| Age, Customized: 18-39 | Participants | 28 | 31 | 59 |
| Age, Customized: 40-50 | Participants | 41 | 39 | 80 |
| Sex: Female, Male: Female | Participants | 32 | 34 | 66 |
| Sex: Female, Male: Male | Participants | 37 | 36 | 73 |
6. Primary Endpoint
The registry lists the primary outcome as Modified Bond-Lader Visual Analog Scale Score After 50-mg Dose (Day 2), measured over At 1 hour post-dose, Day 2 (50 mg).
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | units on scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the Modified Bond-Lader Visual Analog Scale score one hour after the 50 mg dose on Day 2, expressed in units on the scale. The instrument uses a 100 mm line with opposing adjectives at its ends: Alert (=0) and Drowsy (=100). The registry specifies that a patient who is sleeping receives a score of 100. The endpoint is therefore a measure of subjective alertness or drowsiness at a defined point after dosing.
Using a defined time after the dose makes the measure relevant to the stated study question about the sedation profile soon after administration. It is a continuous measure: values can take different positions along the alert-to-drowsy scale, rather than only classifying a participant as having or not having an event. The primary outcome is reported as a least-squares mean with a 95% confidence interval for each arm.
The primary analysis population is the modified intent-to-treat set described in the registry. It includes randomized patients who received study treatment and had a baseline score and a score at least one hour after the 50 mg dose. This definition is narrower than simply counting everyone enrolled or randomized. The registry does not report a primary between-arm difference, its confidence interval, or a primary p-value. Consequently, the arm-specific estimates describe the posted results, but do not by themselves supply the formal comparative estimate for the primary question.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
At the primary assessment, the least-squares mean score was 45.02 units for quetiapine IR (95% confidence interval 38.29 to 51.76) and 32.47 units for quetiapine XR (95% confidence interval 25.93 to 39.01). Since higher values on this scale indicate greater drowsiness, the posted arm estimates place the XR mean lower than the IR mean at this assessment. These are arm-specific estimates, not a reported estimate of the between-arm difference.
The confidence intervals describe uncertainty around each arm’s estimated mean. They are not confidence intervals for the difference between treatments. The registry does not post a primary comparison estimate, confidence interval for that comparison, or p-value. It is therefore not possible to characterize the primary result as a statistically significant or statistically non-significant between-arm difference from the posted primary results alone. Nor should a comparison be reconstructed from the separate arm intervals as though that were the registry’s formal analysis.
The secondary outcomes provide comparative estimates for several later assessments. Those comparisons are explicitly unadjusted recalculations from posted summary statistics, rather than sponsor-reported analyses. For the Day 3 score after 100 mg, the XR-minus-IR mean difference is -22.38 units (95% confidence interval -31.5 to -13.25; unadjusted p < 0.001). For the Day 4 score after 200 mg, it is -18.21 units (95% confidence interval -28.34 to -8.071; unadjusted p < 0.001). For the Day 5 score after 300 mg, it is -16.79 units (95% confidence interval -28.71 to -4.862; unadjusted p = 0.006). These estimates are in the same direction, with lower mean scores in the XR arm at each of these assessments.
Those secondary results do not fill the gap in the primary record. They concern later dose assessments, are unadjusted for multiple testing, and are recalculations rather than posted sponsor analyses. No sponsor-reported comparisons are listed for these outcomes. The posted results therefore support a descriptive reading of the arm means and a cautious reading of the recalculated secondary comparisons, while the formal primary between-arm result remains not reported in the registry record.
9. Statistical Methods Explained
The reported continuous outcomes are least-squares means. General explanation: a least-squares mean is an estimated group mean from a statistical model, often adjusted for factors specified in that model. The registry does not describe the model, its covariates, or the estimation details for the primary outcome, so the extent and nature of any adjustment are not reported in the registry record. The label should not be taken as evidence for a particular model specification.
What do the confidence intervals describe?
The primary arm estimates are accompanied by 95% confidence intervals. General explanation: a confidence interval represents uncertainty in an estimate under the assumptions of the analysis. It describes a range of values compatible with the observed data and the method used, rather than a guarantee about an individual participant’s score. The posted intervals apply separately to each arm’s estimated mean. They do not directly quantify uncertainty in the difference between arms. Because a primary contrast and its interval are not posted, the arm intervals cannot substitute for that comparison.
For the three posted secondary scale outcomes, the registry gives least-squares means and standard errors by arm. A standard error describes the estimated precision of a mean; it is not the spread of individual scores. The secondary comparisons include estimated mean differences and confidence intervals. Their p-values are marked unadjusted. General explanation: a p-value evaluates the compatibility of the data with a specified null hypothesis under a particular analysis; it does not quantify the size or clinical importance of an effect. An unadjusted p-value does not account for the possibility of chance findings when many outcomes or comparisons are considered.
How should the recalculated comparisons be read?
The secondary comparison estimates are recalculated, unadjusted estimates from the posted summary statistics. They are not identified as results from a sponsor-reported analysis, and no reported analyses are listed for these outcomes. The estimates are expressed as XR minus IR, so negative values correspond to a lower estimated mean in the XR arm. Their confidence intervals and unadjusted p-values should be read as exploratory descriptions of the posted summary data, not as evidence that a prespecified analysis plan was followed. The registry does not report a multiplicity adjustment or the broader statistical plan.
The recalculations also use an approximate pooled standard deviation derived from the standard errors, as indicated for these comparisons. General explanation: a standard deviation describes participant-level variability, whereas a standard error describes uncertainty in a group mean. Converting between them requires assumptions about the analysis and sample size. Where a pooled standard deviation is approximate, standardized effect-size and planning calculations based on it inherit that approximation. These recalculations do not replace the original trial analysis.
What do the planning illustrations mean?
The planning illustrations use the observed secondary effect as a reference and show participant counts per arm for specified power targets and fractions of that effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. General explanation: power is the probability that a planned analysis will detect an effect of a specified size under the assumptions of the calculation. Because the effect sizes are anchored to observed results, the illustrations are sensitivity examples, not the trial’s original sample-size justification and not observed power. The sample-size justification for this trial is not reported in the registry record. The illustrations should not be read as evidence that the trial was designed around those calculations.
General explanation: over-dispersion occurs when observed variability is greater than a model’s assumptions allow. In such cases, standard errors can be too small if the extra variability is ignored, leading to confidence intervals that are too narrow and p-values that may overstate evidence. The registry information does not establish whether over-dispersion is relevant to these scale outcomes or whether any adjustment was used; such methods are not reported in the registry record. More generally, the outcome summary does not state how the analysis handled repeated measurements, missing scores, or departures from model assumptions.
What can be concluded from the posted methods information?
The primary analysis population is defined, and the endpoint timing and scale are described. However, the registry does not report a full analysis plan, model specification, handling of missing data, primary contrast, or multiplicity strategy. These omissions limit assessment of whether the analyses match the intended protocol and how robust the estimates are to alternative analytic choices. General statistical interpretation should therefore distinguish the reported arm estimates from the recalculated secondary contrasts and from any unreported sponsor analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies one primary endpoint and lists 12 posted secondary outcomes. It does not report whether any adjustment for multiple comparisons was planned or applied, whether a hierarchy among secondary endpoints was specified, or whether any outcomes were designated as exploratory. Multiplicity methods and the planned statistical analysis are not reported in the registry record. This matters because interpreting many tests as if each were the sole planned test can make isolated unadjusted p-values appear more decisive than they are.
The listed secondary comparison p-values are unadjusted recalculations. No sponsor-reported analyses are listed for them. The primary outcome has separate arm estimates and confidence intervals but no posted contrast or p-value. The record does not state whether a primary test was performed but omitted from the posted results, or whether a different analysis was used. The sample-size justification, target effect, and intended power are not reported in the registry record. The posted planning illustrations are based on observed effects and explicitly do not represent the trial’s own design calculations.
The primary analysis population is defined as randomized patients who received treatment and had a baseline score and an eligible post-dose score. This is a modified intent-to-treat definition, rather than an analysis of every randomized participant regardless of outcome availability. The registry does not report how many randomized participants lacked an eligible score, why scores were missing, or how missing data were handled. It also does not describe sensitivity analyses for missing outcomes.
For the primary measure, the arm analysis counts are 65 for IR and 69 for XR, while the registry lists 139 enrolled. Safety counts use 69 in the IR group and 70 in the XR group. These are different analysis counts; reasons for the differences are not reported in the registry record. The record also does not describe whether any participants were excluded after randomization, how protocol deviations were handled, or whether analysis populations differed across secondary outcomes. These omissions constrain evaluation of selection and missing-data risks.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Quetiapine IR | 0 | 69 | 0.0% |
| Quetiapine XR | 3 | 70 | 4.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Quetiapine IR | 33 of 69 |
| Quetiapine XR | 29 of 70 |
Most frequent serious adverse event terms
| Event term | Organ system | Quetiapine IR | Quetiapine XR |
|---|---|---|---|
| Convulsion | Nervous system disorders | 0 of 69 | 1 of 70 |
| Depression | Psychiatric disorders | 0 of 69 | 1 of 70 |
| Suicide Attempt | Psychiatric disorders | 0 of 69 | 1 of 70 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Quetiapine IR | Quetiapine XR |
|---|---|---|---|
| Dry Mouth | Gastrointestinal disorders | 9 of 69 | 15 of 70 |
| Increased Appetite | Metabolism and nutrition disorders | 11 of 69 | 11 of 70 |
| Dizziness | Nervous system disorders | 11 of 69 | 4 of 70 |
| Headache | Nervous system disorders | 8 of 69 | 4 of 70 |
| Somnolence | Nervous system disorders | 5 of 69 | 7 of 70 |
| Fatigue | General disorders | 3 of 69 | 6 of 70 |
| Sedation | Nervous system disorders | 4 of 69 | 5 of 70 |
| Tachycardia | Cardiac disorders | 6 of 69 | 3 of 70 |
| Akathisia | Nervous system disorders | 4 of 69 | 1 of 70 |
| Nausea | Gastrointestinal disorders | 1 of 69 | 4 of 70 |
Serious events with the highest arm-level rate: convulsion (1.4%), depression (1.4%), suicide attempt (1.4%).
The registry lists serious adverse events for 69 participants at risk in the IR group and 70 in the XR group. It records 0 serious adverse events in the IR group and 3 in the XR group. The most frequently listed serious-event terms are Convulsion, Depression and Suicide Attempt, each reported as 1.4%. The record does not supply death counts; deaths are not reported in the registry record.
The registry also records other adverse events for 69 participants at risk in the IR group and 70 in the XR group, with 33 and 29 affected, respectively. These counts should be read as the registry’s event-group summaries, not as a complete description of each participant’s experience. The record does not provide detailed event-level timing, severity, duration, relationship to treatment, or a full account of how events were collected.
Safety counts are descriptive. Without additional detail about event definitions, exposure, follow-up, and analysis, they do not establish comparative risk or explain why events occurred. The listed serious-event terms and percentages should not be interpreted as evidence of causation. No medical conclusion about either formulation follows from these counts alone.
12. What the Result Does, and Does Not, Mean
The posted primary results describe estimated sedation-scale means at one defined time during early dose escalation. The XR mean is lower than the IR mean at that assessment, on a scale where higher values indicate greater drowsiness. The registry does not report the formal primary contrast, its uncertainty, or a p-value. The estimates therefore answer part of the descriptive question but do not provide the complete comparative result needed to characterize the primary analysis statistically.
The later posted secondary comparisons also have lower XR means, with negative recalculated XR-minus-IR differences. They are unadjusted and are not sponsor-reported comparisons. Their direction is consistent with the primary arm estimates, but they concern different assessment days and do not repair the missing primary contrast. No adjustment for testing multiple outcomes is reported, so the secondary p-values should not be treated as definitive evidence.
General explanation: statistical evidence and clinical importance are distinct. A numerical difference can be estimated precisely or imprecisely, and its practical meaning depends on context, measurement properties, and prespecified interpretation criteria. The registry record does not provide a threshold for a clinically important difference on this scale. The posted results therefore do not establish whether any observed mean difference is clinically meaningful.
These findings concern scale scores at specified post-dose assessments during initial titration. They do not establish effects on longer-term bipolar depression symptoms, functioning, quality of life, or other outcomes not assessed in the reported endpoint results. Nor do the safety summaries establish causal effects or comparative safety. The interpretation should remain limited to the measures, time points, and analysis information recorded in the registry.
13. Why This Trial Matters Statistically
This trial is statistically instructive because it has a clearly described continuous primary endpoint but only arm-specific primary estimates in the registry. A reader can interpret the direction and uncertainty of each group mean, yet cannot recover the formal primary treatment contrast from those values without making additional assumptions or doing a new calculation. Keeping arm estimates separate from a comparison estimate is important: the latter directly addresses the randomized contrast, while the former describe each group individually.
The record also illustrates why the label “least-squares mean” is not enough to understand an analysis. The model, covariates, missing-data approach, and planned contrast are not reported. Without those details, it is difficult to judge the estimand, reproduce the analysis, or assess whether the posted results follow the prespecified plan. Transparency about analysis choices is especially valuable for repeated outcomes collected across dose days.
The secondary comparisons show another common interpretive issue. Their estimates are recalculated from summary statistics and their p-values are unadjusted, while the registry lists multiple secondary outcomes. The calculations can help readers understand the scale and direction of the posted results, but they are not a replacement for sponsor analyses or a multiplicity plan. The planning illustrations likewise show how assumed effect sizes influence hypothetical sample requirements; they are not evidence of the trial’s design rationale or observed power.
Finally, analysis counts differ across primary and safety summaries, and the registry does not explain why. Clear reporting of participant flow, missing outcomes, analysis populations, and event definitions would make it easier to assess completeness. The statistical lesson is not that the results point in a particular clinical direction, but that estimates need their analysis context and a direct comparison to support a defensible interpretation.
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 primary limitation for interpretation is that no formal primary between-arm estimate, confidence interval for the contrast, or p-value is posted. Separate least-squares means and their confidence intervals do not directly provide the uncertainty around the treatment difference. The registry record also does not report the model used to obtain the least-squares means, any covariates, or the planned analysis contrast.
The statistical analysis plan, sample-size justification, multiplicity strategy, and interim-analysis details are not reported in the registry record. The record does not explain the missing or incomplete primary outcome data, the handling of such data, or the differences between the enrolled count and the outcome and safety analysis counts. The modified intent-to-treat population requires a baseline measure and an eligible post-dose measure; the record does not state how many participants failed to meet those criteria or why.
The secondary comparisons are unadjusted recalculations from posted summary statistics, not sponsor-reported analyses. They use approximate variability estimates, and the registry does not provide a multiplicity plan. Results across different dose days and outcome definitions may not be directly comparable. Although the record lists additional secondary outcomes, it does not post a formal analysis for every listed measure.
The safety summary gives counts and selected serious-event terms but does not report detailed exposure, event timing, severity, treatment relationship, or full event-level information. Death counts are not reported in the registry record. The endpoint is an early post-dose scale score; the registry results do not establish how these measurements relate to later clinical outcomes. These reporting gaps limit reproducibility and the strength of conclusions that can be drawn from the posted summaries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study Comparing the Tolerability of Seroquel IR With Seroquel XR in Patients With Bipolar Depression — NCT00926393.
- Registry record last updated 2011-05-11; status last verified 2011-05.
- Results first posted 2011-03-31.
- 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.
Continue through the Clinical Biostats statistical pathway
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18. Record Summary
NCT00926393 is a completed Phase IV randomized parallel-group study of quetiapine IR versus quetiapine XR in patients with bipolar depression. The study title describes a multicenter, double-blind, double-dummy comparison during initial dose escalation, and the registry categorizes masking as quadruple. Enrollment was 139.
The primary endpoint was the Modified Bond-Lader Visual Analog Scale score one hour after the 50 mg dose on Day 2. The registry posts arm-specific least-squares means and 95% confidence intervals, but no primary between-arm comparison. Three later Bond-Lader comparisons are available as unadjusted recalculations; sponsor-reported comparisons are not listed. The analysis plan, missing-data methods, multiplicity strategy, and sample-size justification are not reported in the registry record.
Safety summaries list serious and other adverse-event counts by group, along with selected serious-event terms. The record does not report death counts or detailed event-level analyses. The results support descriptive interpretation of the posted estimates, with important limits on formal comparative inference.