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 Compare the Effect on Cognitive Functioning of Two Formulations of Seroquel, Seroquel XR and IR in Patients With Stable Schizophrenia (NCT01213836), a randomized phase 4 study. The primary outcome is Mean for Attentional Standardised Composite Score Based on Performance Scores From the CogState Test Battery Domains Detection (Speed of Processing)and Identification (Attention/Vigilance).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01213836 |
| Phase | Phase 4 |
| Condition | Schizophrenia |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Quadruple |
| Enrollment | 75 |
| Arms in the primary outcome | n/a |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
Patients with stable schizophrenia, described as stabilized on a single antipsychotic medication. The primary endpoint population was the per protocol set: a subset of the full analysis set whose members fulfilled all inclusion criteria, none of the exclusion criteria, complied with the study medication dosing scheme, followed study restrictions, and completed the study without a protocol violation. The registry record does not give the number of participants in this endpoint population.
Intervention
Quetiapine fumarate extended release, identified as Seroquel XR, dosed once daily in the evening. Patients assigned to this sequence received the XR formulation in the first treatment period and crossed over to the immediate-release formulation in the next period.
Comparator
Quetiapine fumarate immediate release, identified as Seroquel IR, dosed twice daily. Patients assigned to the reverse sequence received IR first and then crossed over to XR. Matching placebos for both formulations were also listed, consistent with the double-dummy design.
Primary question
How did the mean attentional standardized composite score, based on CogState detection and identification performance, compare across the treatment periods? The score represents processing speed and attention or vigilance, with higher scores indicating better performance. The registry record does not report numerical primary endpoint results, so the direction and precision of any treatment contrast cannot be assessed from this record.
3. Trial Design
This was a Phase IV, prospective, randomized crossover study in patients with stable schizophrenia. The registry lists 75 participants enrolled and a completed status. The study start is recorded as 2010-11, with primary completion in 2011-08. Its brief description gives an overall study duration of 20 -32 days.
Participants were randomized to one of two treatment sequences: Seroquel XR followed by Seroquel IR, or Seroquel IR followed by Seroquel XR. Each treatment period is described as lasting 10-16 days. Thus, the design compares the formulations within a participant across successive periods rather than assigning each participant to remain on only one formulation throughout the study. A crossover can make within-participant comparisons useful because each participant contributes measurements under both treatments. However, the interpretation depends on appropriate handling of repeated measurements and potential period or sequence effects; the registry record does not report how those issues were analyzed.
The official title describes the study as double-blind and double-dummy, while the registry masking classification is quadruple. Matching placebos for XR and IR are listed. The record does not describe the identities of the masked parties or give details about how masking was maintained.
The primary cognitive measure was collected at baseline and at three visits in each treatment period. The period descriptions specify a 5-day (maximum 8 day) testing period, with the last test day not earlier than after 10 days of randomized treatment or crossover treatment, respectively. The record does not give further operational details about visit spacing, treatment adherence, or washout between periods. These details should not be inferred from the crossover label.
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: Screening (0 days to 14 days before enrolment), enrolment at Visit 1 (14 days to 3 days prior to randomisation), randomisation at Visit 2 after confirmation of eligibility. 75 patients were screened/enrolled. Of these, 9 were not randomised; 2 patients due to own decision to discontinue and 7 patients due to eligibility criteria not fulfilled.
Period 1, First Intervention
| Stage | First Seroquel XR Then Seroquel IR | First Seroquel IR Then Seroquel XR |
|---|---|---|
| STARTED | 34 | 32 |
| COMPLETED | 31 | 29 |
| NOT COMPLETED | 3 | 3 |
Reasons for not completing this period:
| Reason | First Seroquel XR Then Seroquel IR | First Seroquel IR Then Seroquel XR |
|---|---|---|
| Adverse Event | 2 | 1 |
| Protocol Violation | 0 | 1 |
| Withdrawal by Subject | 1 | 1 |
Period 2, Second Intervention
| Stage | First Seroquel XR Then Seroquel IR | First Seroquel IR Then Seroquel XR |
|---|---|---|
| STARTED | 31 | 29 |
| COMPLETED | 31 | 29 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: The per protocol set (PPS) is a subset of the FAS consisting of patients who fulfilled all inclusion criteria but none of the exclusion criteria, complied with study medication dosing scheme, did not violate any of the study restrictions and completed the study without protocol violation.
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 | First Seroquel XR Then Seroquel IR | First Seroquel IR Then Seroquel XR | Total |
|---|---|---|---|---|
| Participants analysed | 34 | 32 | 66 | |
| Age Continuous: between 18 and 29 years | participants | 6 | 3 | 9 |
| Age Continuous: Between 30 and 50 years | participants | 26 | 28 | 54 |
| Age Continuous: >50 years | participants | 2 | 0 | 2 |
| Age Continuous | years | 38.6 (SD 8.2) | 37.0 (SD 5.2) | 37.8 (SD 6.9) |
| Gender: Female | participants | 11 | 9 | 20 |
| Gender: Male | participants | 23 | 22 | 45 |
| Region of Enrollment: Spain | participants | 1 | 1 | 2 |
| Region of Enrollment: Denmark | participants | 1 | 1 | 2 |
| Region of Enrollment: Austria | participants | 1 | 2 | 3 |
| Region of Enrollment: Germany | participants | 18 | 10 | 28 |
| Region of Enrollment: Italy | participants | 13 | 18 | 31 |
6. Primary Endpoint
The registry lists the primary outcome as Mean for Attentional Standardised Composite Score Based on Performance Scores From the CogState Test Battery Domains Detection (Speed of Processing)and Identification (Attention/Vigilance), measured over Period 1 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period. Period 2 at 3 visits,(post 1),(post 2),(post 3), in a 5-day (maximum 8 day) period..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | standardised units |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was the mean attentional standardized composite score derived from performance in the CogState detection and identification domains. Detection represents speed of processing, while identification represents attention or vigilance. The registry describes the endpoint as a standardized speed-of-performance score and states that higher values indicate better performance. Its stated range is minus infinity to plus infinity.
A composite can combine related task results into a single measure intended to reflect a broader cognitive domain. Standardization places performance on a common scale for combining or comparing measures; it does not, by itself, establish what size of score difference would be important to participants or clinicians. The record does not report a threshold for meaningful change.
Measurements were scheduled at baseline and at three visits during each treatment period. Repeated measurements can describe how scores vary over time as well as how they compare between treatments, but the registry record does not report which visit or time-point summary was used for a primary treatment contrast. It also does not report the primary endpoint mean, standard deviation, treatment difference, confidence interval, or p-value. Consequently, the endpoint definition explains what was intended to be measured, but this record does not establish the observed comparative result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a cognitive endpoint and a crossover comparison, but it does not provide numerical results for the primary outcome. In particular, no primary endpoint means, treatment contrast, standard deviation, confidence interval, or p-value are reported in the registry record. The record also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. Therefore, the available information does not support a conclusion about the size, direction, or statistical precision of a treatment difference in attentional performance.
The endpoint description does clarify how a score should be read: higher standardized composite scores correspond to better performance on the combined detection and identification measure. That direction is not itself a result. Without observed scores or a defined treatment contrast, it cannot establish which formulation produced higher performance, whether any difference was small or large, or how uncertain an estimate would be.
The study enrolled 75 participants, but this is not necessarily the number contributing to the primary endpoint analysis. The endpoint population is described as the per protocol set, and the record does not report its size. Safety denominators are 63 for Seroquel XR and 62 for Seroquel IR; those counts should not be substituted for the primary endpoint sample size, because the registry does not identify them as the endpoint analysis population.
The registry reports no serious adverse events among 63 participants at risk in the Seroquel XR group and none among 62 at risk in the Seroquel IR group. It separately reports four other adverse events in each group. These counts describe the posted safety categories; they do not provide a comparative estimate of cognitive performance or establish the completeness of adverse-event ascertainment. Death counts are not reported in the registry record.
Secondary outcomes were listed, including treatment satisfaction, cognitive domains, sedation measures, dropouts, and plasma concentration ratios. Listing an outcome does not mean its result is available. The record does not report analyses for these outcomes. The posted information therefore supports a description of the planned comparison and selected safety counts, but not a quantitative assessment of the primary cognitive effect or its uncertainty.
9. Statistical Methods Explained
What does a crossover design compare?
In a crossover study, participants receive treatments in a sequence, so measurements under one treatment can be compared with measurements from the same participant under another. This can reduce the influence of stable differences between participants because each person serves as their own reference. It does not remove all sources of uncertainty. Scores may change over time, treatment periods may differ, and effects from an earlier period could potentially influence a later one. These are general methodological considerations, not claims that such effects occurred in this trial.
This study randomized participants to XR-then-IR or IR-then-XR sequences. The record specifies treatment periods of 10-16 days but does not report a washout period or the statistical handling of period, sequence, or possible carryover effects. The crossover design therefore describes how treatments were ordered; it does not by itself show that the analysis accounted for every feature of the design.
What does the mean and standard deviation describe?
The primary endpoint is a continuous score. A mean describes the average observed score for a defined group or treatment condition. A standard deviation describes how dispersed individual scores are around that mean. It is not the same as a confidence interval: a standard deviation describes participant-level variability, while a confidence interval expresses uncertainty around an estimated quantity. No primary means or standard deviations are reported in the registry record, so those quantities cannot be interpreted for this comparison.
Because the endpoint was measured repeatedly, an analysis may need to account for correlation among observations from the same participant. General statistical methods for repeated measurements do this in different ways, and the choice can affect estimates and uncertainty. The registry record does not report the model, covariance structure, or other details of the primary analysis. No particular method should be attributed to the investigators on the basis of the endpoint description alone.
What would a confidence interval add?
In general, a confidence interval gives a range of values compatible with an estimate under the assumptions of the analysis. It helps distinguish the estimated magnitude from its uncertainty. A narrow interval indicates greater precision than a wide interval, but neither width nor location can be judged without the interval itself. The registry record does not report a confidence interval for the primary treatment comparison.
A p-value, when reported, addresses how incompatible the observed data are with a specified null model, under the assumptions used. It does not quantify the size or practical importance of a difference. A p-value is also not a substitute for the estimate and its confidence interval. No primary p-value is reported in this registry record.
How should the sample-size illustrations be read?
The sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. Such illustrations answer a hypothetical planning question: how many participants per arm would be needed under those assumptions to detect a specified effect with a chosen power. They are not the trial's observed sample size, and they are not observed power.
These assumptions do not establish the original protocol's sample-size justification. The registry record does not report that justification. Nor does a planning illustration establish that the trial was designed around the same effect or assumptions. Since the primary outcome includes several categories or time points and is not reduced to one comparison in the registry analysis, a single comparison should not be inferred from a planning value. The record does not provide a numerical primary effect estimate to interpret alongside such planning assumptions.
Why does over-dispersion matter in general?
Over-dispersion means that observed variability is greater than a model assumes. When a model underestimates variability, its standard errors may be too small and its confidence intervals too narrow. Appropriate modeling can account for extra variability when the data and endpoint require it. The primary endpoint in this study is continuous, and the registry record does not report an over-dispersion assessment or a model. This general concept should not be taken as evidence that over-dispersion occurred.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint was assessed at baseline and at multiple visits across both treatment periods. The registry record notes that the primary outcome has several categories or time points and was not reduced to one comparison. When several outcomes, visits, or contrasts are examined, the chance of at least one apparently unusual result can increase. General approaches to multiplicity include pre-specifying a primary contrast or adjusting inference across a defined family of comparisons. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or which time-point contrast would govern the primary conclusion.
The record lists secondary outcomes covering treatment satisfaction, cognitive performance domains, sedation, dropouts, and plasma concentrations. It does not report their analysis results or state how multiplicity across these outcomes was handled. The number of analyses is recorded as 0; this does not provide a statistical plan or explain whether analyses were conducted outside the registry record.
The primary endpoint population is the per protocol set, defined as a subset of the full analysis set meeting specified eligibility, adherence, restriction, completion, and protocol-compliance conditions. The record does not report the size of either set, how participants with missing visits were handled, or whether exclusions from the per protocol set were made before or after outcome review. Missing-data assumptions, imputation methods, and sensitivity analyses are not reported in the registry record.
For a repeated-measures crossover analysis, missing observations can affect the information available from each participant and the assumptions required for estimation. General methods may use incomplete records under stated assumptions, but the appropriate approach depends on the analysis plan and missingness pattern. Neither the missingness pattern nor the analysis method is described in the registry record. Interim analyses and stopping rules are also not reported in the registry record.
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 |
|---|---|---|---|
| Seroquel XR | 0 | 63 | 0.0% |
| Seroquel IR | 0 | 62 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Seroquel XR | 4 of 63 |
| Seroquel IR | 4 of 62 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Seroquel XR | Seroquel IR |
|---|---|---|---|
| somnolence | Nervous system disorders | 1 of 63 | 2 of 62 |
| neutropenia | Blood and lymphatic system disorders | 0 of 63 | 1 of 62 |
| tachycardia | Cardiac disorders | 0 of 63 | 1 of 62 |
| vertigo | Ear and labyrinth disorders | 1 of 63 | 0 of 62 |
| fatigue | General disorders | 0 of 63 | 1 of 62 |
| heart rate increase | Investigations | 0 of 63 | 1 of 62 |
| dizziness | Nervous system disorders | 0 of 63 | 1 of 62 |
| sedation | Nervous system disorders | 1 of 63 | 0 of 62 |
| delusion | Psychiatric disorders | 0 of 63 | 1 of 62 |
| psychotic disorder | Psychiatric disorders | 1 of 63 | 0 of 62 |
The registry reports serious adverse events separately from other adverse events. In the Seroquel XR group, 0 of 63 participants at risk were recorded as affected by a serious adverse event. In the Seroquel IR group, 0 of 62 participants at risk were recorded as affected by a serious adverse event. The registry lists four other adverse events in each group. These are counts in the posted categories; they should not be combined or reclassified as serious events.
A zero count means that no affected participants were recorded in that category for the listed group and denominator. It does not establish that the underlying risk is zero, and the counts alone do not quantify the uncertainty around risk. No serious adverse event terms are listed. Death counts are not reported in the registry record.
The groups arise from a crossover study, and the registry does not explain whether safety counts represent unique participants, treatment-period exposure, or another counting convention. The denominators differ between groups, and the reason is not reported in the registry record. These safety figures do not establish a comparative safety effect, and they do not answer the primary question about cognitive performance.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, masked crossover study was conducted to compare quetiapine extended release and immediate release on a standardized attentional composite in patients with stable schizophrenia. It describes the endpoint, treatment sequences, repeated assessment schedule, and a per protocol population definition. It also posts selected adverse-event counts. These details allow the intended comparison and the limits of the available record to be understood.
The record does not report numerical results for the primary cognitive endpoint. Without treatment means or a treatment contrast, it is not possible to determine the direction or magnitude of the observed difference. Without a confidence interval, the precision of an estimate cannot be assessed. Without a reported primary analysis or p-value, statistical evidence for a specific contrast cannot be evaluated. The record therefore does not show that one formulation produced better or worse cognitive performance.
The absence of a result in the registry record is not evidence that no analysis was conducted or that the formulations had identical outcomes. It means that the relevant numerical result and analysis details are not reported in the registry record. The same distinction applies to the listed secondary outcomes: their presence in the record does not show that a result was posted.
The zero serious adverse event counts are limited to the listed groups and denominators. They do not prove that serious events are impossible or establish a safety difference between treatments. Likewise, the other adverse-event counts are descriptive and do not resolve the cognitive endpoint question.
Accordingly, the defensible reading is narrow: the record describes a trial designed to compare the two formulations using repeated cognitive testing and reports selected safety counts, but does not provide enough primary outcome data to quantify or interpret the treatment comparison. Any broader conclusion would require results and analysis information not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable for its crossover structure and repeated cognitive measurements. The design places both formulations within each participant's sequence, making the within-participant comparison central to interpretation. That feature can be efficient when measurements from the same person are related, but it also makes period, sequence, and possible carryover considerations relevant. The registry record describes the sequence but does not report how those considerations were handled analytically.
The endpoint combines standardized performance from detection and identification tasks, and the record defines the direction of scoring. That gives the reader useful measurement context. At the same time, the endpoint is assessed at multiple visits in each period, and the registry does not identify a single reported contrast. This makes clarity about the prespecified estimand, time point, and multiplicity approach especially important for interpreting a treatment comparison.
The record also distinguishes an enrolled total from a per protocol endpoint population and from safety denominators. Those populations should not be treated as interchangeable. The per protocol definition makes clear that eligibility, adherence, restrictions, completion, and protocol compliance mattered for inclusion, but the population size and participant flow are not reported.
Most importantly, the registry record does not report the primary outcome estimates or the statistical analysis details needed to assess their precision. The trial's design can be described, but the central cognitive comparison cannot be quantified from the available record. This is a statistical reporting limitation, not evidence for a particular treatment effect.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting the trial is that the registry record does not report numerical primary endpoint results. It gives no treatment-specific means, contrast, standard deviations, confidence interval, or p-value. The primary outcome includes several categories or time points and was not reduced to one comparison, leaving the target comparison unclear in the posted record.
Analytical details needed to understand a crossover comparison are not reported in the registry record. These include the model used for repeated observations, handling of period and sequence, treatment of possible carryover, and the definition of the primary contrast. The record also does not report a washout period. These omissions do not demonstrate that the study lacked such procedures; they mean they cannot be assessed from this record.
The endpoint population is defined, but its size and relationship to the 75 enrolled participants are not reported. The registry does not describe participant flow, missing observations, reasons for exclusion, or how missing data were handled. The safety denominators are 63 for XR and 62 for IR, but the record does not explain how these denominators relate to enrollment or the primary endpoint population.
The record lists secondary outcomes but does not report their results or a multiplicity plan. It does not report the original sample-size justification, interim analyses, or a statistical analysis plan. The posted serious adverse event counts are zero in each listed group, but the counting convention and exposure basis are not described, and death counts are not reported in the registry record. Together, these limitations restrict assessment of the effect estimate, its uncertainty, analysis robustness, and safety context.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Compare the Effect on Cognitive Functioning of Two Formulations of Seroquel, Seroquel XR and IR in Patients With Stable Schizophrenia — NCT01213836.
- Registry record last updated 2012-07-27; status last verified 2012-05.
- Results first posted 2012-07-27.
- 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.
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18. Record Summary
This completed Phase IV randomized, quadruple-masked crossover study enrolled 75 patients with stable schizophrenia. Participants received Seroquel XR and Seroquel IR in opposite treatment sequences, with each period described as lasting 10-16 days. The primary endpoint was a standardized attentional composite from CogState detection and identification performance, measured at baseline and repeatedly during both periods; higher scores indicate better performance.
The endpoint population was defined as the per protocol set, but its size is not reported. Numerical results and analysis details for the primary endpoint are not reported in the registry record. The posted safety counts record 0 serious adverse events among 63 participants at risk for XR and 0 among 62 for IR; four other adverse events are listed in each group. Death counts are not reported in the registry record.