Study Evaluating the Clinical Benefit of SEROQUEL XR in Subjects With Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating the Clinical Benefit of SEROQUEL XR in Subjects With Schizophrenia (NCT00640601), a non-randomized phase 3 study. The primary outcome is Percentage of Subjects With Improved Clinical Benefit From Assessment of Clinical Global Impression-Clinical Benefit (CGI-CB) Scale From Baseline to Week 24 or End of Study.

2. Clinical Question

3. Trial Design

This was a Phase 3, multicentre, open-label, prospective, long-term study of quetiapine fumarate extended-release in subjects with schizophrenia. The record identifies AstraZeneca as the sponsor and marks the study as completed. The recorded start is 2008-03, and primary completion is 2010-07. Enrollment is listed as 331.

The design is non-randomized, has no masking, and uses a single group. Participants were not assigned through randomization to separate treatment arms, and the record does not list a concurrent control group. This matters for interpretation: observed changes over time can be described for the study group, but the design alone cannot distinguish a treatment-associated change from changes related to the natural course of illness, other care, expectations, or measurement circumstances. These are general considerations for uncontrolled studies, not claims about what occurred in this study.

The intervention is listed as quetiapine fumarate extended-release. The precise dose, titration schedule, permitted concomitant treatments, and adherence details are not reported in the registry record. The study is described as prospective and long-term, but those labels do not establish how often participants attended visits or how complete follow-up was.

The primary endpoint is framed around baseline to 24 weeks or the end of the study. The analysis population is described as the intention-to-treat population, defined in the record as participants who received at least one dose, with n=295. The registry also lists 11 outcome measures and 0 analyses. That distinction is important: outcome measures identify planned or recorded measures, while the absence of listed analyses and numerical primary results leaves the actual endpoint findings unavailable in the record.

The record does not report the protocol’s sample-size justification, the planned statistical analysis, interim analyses, or details of how missing outcome measurements were handled. Those elements should not be inferred from the study’s phase, duration, or enrollment.

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 had to fulfill criteria for schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and their current antipsychotic treatment had to be considered inadequate because of insufficient efficacy, poor tolerance, and/or non acceptability of dosing regimen.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The intention to treat (ITT) population (i.e., all subjects who received at least one dose of the study medication) comprised the population for the analysis (n=295)

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 Percentage of Subjects With Improved Clinical Benefit From Assessment of Clinical Global Impression-Clinical Benefit (CGI-CB) Scale From Baseline to Week 24 or End of Study, measured over Baseline to 24 weeks (or end of study).

The primary endpoint is titled as the percentage of participants with improved clinical benefit from baseline to Week 24 or the end of the study. Its stated measure is the Clinical Global Impression-Clinical Benefit (CGI-CB) scale. The record describes the scale as an investigator’s global weighted impression of efficacy and interference from adverse events. It ranges from 1 to 10, with lower scores described as better. A score of 1 is characterized as marked therapeutic effect with no burden of adverse events; a score of 10 signifies that adverse-event burden outweighs therapeutic effect, or that there is no therapeutic effect with high adverse-event burden.

The record says a change score for each subject is calculated by subtracting the baseline score from the visit score. This kind of change measure can summarize whether a participant’s score moved from their own starting value, rather than describing only a follow-up score. The registry’s endpoint title, however, refers to the percentage of participants improved, while its analysis description identifies the parameter as a mean and describes a proportional change in CGI-CB score. These descriptions do not fully clarify whether the reported primary summary would be a participant-level percentage, a mean change, or both. The exact operational definition and threshold for “improved” are not reported in the registry record.

The endpoint is intended to combine a global view of perceived benefit and adverse-event burden. It is an investigator-rated measure, not a direct measure of a single symptom or an objective biological measure. No numerical primary estimate or confidence interval is reported in the registry record, so the amount and precision of any observed change cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how observations are summarized and how uncertainty is represented. The registry record describes a primary endpoint parameterized as a mean with a 95% confidence interval, while the endpoint title refers to a percentage of participants improved. It gives no numerical estimate or interval limits. The distinction between the endpoint’s wording and its stated parameter matters because a percentage and a mean change answer different questions. A percentage describes the share meeting a defined improvement criterion; a mean summarizes values across participants. The criterion for improvement and the precise primary summary are not reported in the registry record.

What does a confidence interval communicate?

General statistical explanation: a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater statistical precision, while a wider interval indicates less precision. An interval is not a guarantee that the true value lies within its limits, and it does not by itself indicate whether a result is clinically important. Here, the registry identifies a 95% confidence interval as the dispersion measure, but does not report the interval or the estimate it would accompany. Precision and the range of values compatible with the posted primary result therefore cannot be assessed.

How should a change score be understood?

General statistical explanation: a change score compares a follow-up measure with a participant’s baseline measure. The registry says the CGI-CB change score is calculated by subtracting baseline from the visit score. Because lower CGI-CB scores are described as better, a negative score change would correspond to a lower visit score than baseline, if the calculation follows that stated subtraction. This is an explanation of the scale direction and arithmetic definition, not a report that such a change occurred. The registry does not provide individual scores, a group change estimate, or a result for the primary endpoint.

Change scores can be summarized in different ways. A mean change uses the values of participants in the analysis, while a percentage improved requires a specified rule for classifying each participant. These summaries may tell different stories, particularly when participants’ changes vary. The record’s description uses both the language of percentage improved and the parameter “mean”; the exact statistical estimand and improvement rule are not reported in the registry record. Readers should not treat those terms as interchangeable.

What does the single-group design allow?

General statistical explanation: a single-group before-and-after analysis can describe the observed change among participants with measurements at the relevant time points. It cannot, on its own, estimate what would have happened to the same participants under a different treatment or without the study intervention. Randomized concurrent comparisons are one way to address that counterfactual question, but this trial is listed as non-randomized and single-group. Therefore, even if a change estimate were available, it would be a within-group description rather than a randomized treatment contrast.

Open-label conduct is another design feature relevant to interpretation. General statistical explanation: when treatment and assessment are unmasked, expectations and knowledge of treatment may influence reporting, clinical judgments, or participant behavior. That possibility does not show that bias occurred in this study. The registry lists no masking and does not report whether outcome-rating procedures or other safeguards were used.

What do the planning illustrations represent?

General statistical explanation: a sample-size calculation can estimate how many participants per arm would be required under specified assumptions to detect a chosen effect with a chosen power and significance level. The registry’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers a stated fraction of the observed effect. The record also distinguishes total-event planning for time-to-event outcomes from participants per arm for other outcomes. These are planning assumptions, not evidence that the original study was designed or powered in that way.

The study itself is single-group, whereas the stated illustration assumes two arms with equal allocation. The illustration therefore should not be read as the trial’s actual design calculation. The protocol’s own sample-size justification is not reported in the registry record. Any such illustration is conditional on an effect estimate and assumptions; it does not show that the trial had a particular probability of detecting an effect. Observed power is not a substitute for an effect estimate and its confidence interval, and the registry reports no primary summary statistics from which to assess that result.

Finally, analysis choices about populations, missing values, and multiplicity affect how results should be interpreted. The record defines the primary population as participants who received at least one dose, but it does not state the model, estimation method, or missing-data procedure. Nor does it describe a multiplicity strategy for the listed outcomes. In the absence of those details and numerical analyses, readers can explain the general statistical issues but cannot reconstruct the study’s analysis or verify its reported endpoint findings.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary CGI-CB measure and secondary measures covering clinical benefit, symptom scales, global severity and improvement, and social and occupational functioning. It lists 0 analyses and gives no numerical result for the primary endpoint. A list of several outcomes raises a general multiplicity issue: when many outcomes or comparisons are examined, the chance of at least one apparently notable result can increase. Statistical plans may address that issue by defining a primary outcome, limiting confirmatory tests, or adjusting interpretation. Which approach was used in this study is not reported in the registry record.

The primary outcome title refers to improvement through Week 24 or the end of study. The record does not explain how participants who ended follow-up before that time were treated in the analysis, whether the end-of-study visit substituted for Week 24, or how repeated visits were handled. The actual follow-up schedule is not reported in the registry record.

The primary population is defined as all participants who received at least one dose, and is reported as n=295. This definition does not establish that every participant in that population had an evaluable baseline and follow-up CGI-CB measure. The amount and pattern of missing endpoint data, reasons for missingness, and methods for handling missing values are not reported in the registry record. General statistical explanation: missing-data methods rely on assumptions about why values are absent; different assumptions can lead to different estimates. Without the analysis details, those assumptions cannot be assessed.

The record does not report whether the statistical plan was prespecified, whether interim analyses occurred, or whether any adjustment for multiple testing was made. Those details should not be inferred from the endpoint list or study phase. Because numerical analyses are absent, there are no reported p-values or confidence intervals to interpret for the primary or secondary measures.

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: psychotic disorder (2.7%), schizophrenia (2.7%), delusional perception (1.0%), suicidal ideation (1.0%), suicide attempt (1.0%).

The registry’s safety listing identifies the Seroquel XR group with 295 participants at risk. It records 33 participants in the serious adverse-event category and 224 in the other adverse-event category. The separate at-risk value for the latter category is null, and the number of deaths is also null. A null entry should not be interpreted as zero; the relevant information is not reported in the registry record.

The serious adverse-event terms listed with percentages are Psychotic Disorder, 2.7%; Schizophrenia, 2.7%; Delusional Perception, 1.0%; Suicidal Ideation, 1.0%; Suicide Attempt, 1.0%; and Acute psychosis, 0.7%. These entries describe terms in the registry’s safety listing. The record does not provide event counts for each term, explain whether participants could contribute to more than one term, or give further detail about how the percentages were derived.

These safety entries are descriptive, not a comparison with another treatment. The study has a single group, and the record does not report a control-group safety denominator. The listed events also do not by themselves establish causation. Attribution, timing, severity details beyond the serious-event category, and the criteria used to judge relatedness are not reported in the registry record.

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

The registry record establishes that a completed Phase 3 study examined quetiapine fumarate extended-release in subjects with schizophrenia using an open-label, prospective, single-group design. It defines a primary clinical-benefit measure based on the CGI-CB scale, describes a baseline-to-follow-up change score, and identifies a dose-based analysis population of n=295. It also provides a limited set of safety entries.

What the record does not establish is the size or direction of the primary outcome. It gives no percentage improved, mean change, confidence-interval limits, or numerical analyses for the primary endpoint. The 95% confidence interval is identified as the intended dispersion measure, but its values are not reported in the registry record. The endpoint description is also not fully consistent in its use of a percentage of participants and a mean parameter. Without a numerical result and a clearly specified improvement definition, the clinical-benefit finding cannot be quantified.

Even a complete within-group estimate would need to be interpreted in light of the design. General statistical explanation: observing a change after treatment begins does not by itself establish that treatment caused that change. In a single-group study, there is no concurrent randomized group to provide a direct comparison under the same follow-up conditions. Open-label assessment is another consideration, though the registry record does not establish that it affected ratings in this study.

The adverse-event entries describe reports in the treated group; they do not establish that the intervention caused the events, and they do not provide a controlled estimate of comparative safety. Missing information about event definitions, participant follow-up, and the deaths entry further limits interpretation.

Accordingly, the posted record is useful for identifying the study’s design and intended measurement framework, but it does not supply the primary efficacy result needed to quantify the observed clinical-benefit outcome. Neither benefit nor lack of benefit can be concluded from an endpoint definition without the endpoint findings. The registry record also does not provide enough information to reconstruct the analysis or evaluate the impact of missing data and multiplicity.

13. Why This Trial Matters Statistically

This study illustrates why design and reporting details matter alongside an endpoint name. The primary measure aims to combine an investigator’s global impression of efficacy with interference from adverse events. That may capture a broad clinical judgment, but interpretation depends on the rating scale, its direction, the definition of improvement, and the statistical summary. The record describes a 1-to-10 scale with lower scores better and gives a change-score formula, yet its title refers to the percentage improved while its parameter is described as a mean. This ambiguity affects what a reader would understand the target result to represent.

The study also highlights the distinction between a treatment group’s observed course and a comparative treatment effect. A prospective follow-up can document measurements over time, but a single-group, non-randomized design does not supply a concurrent control contrast. That distinction remains important regardless of how familiar or clinically interpretable the outcome measure may be.

For biostatisticians and clinical researchers, the analysis population illustrates another reporting issue. The record states enrollment of 331 and defines an intention-to-treat population of n=295 as everyone receiving at least one dose. Those descriptions do not answer how many participants contributed to the endpoint or how missing measurements were handled. Participant flow and outcome availability are needed to understand the path from enrollment to an estimate.

Finally, this record demonstrates that an endpoint definition is not a result. Although it identifies the intended confidence-interval format and lists several secondary measures, it reports 0 analyses and no numerical primary result. Statistical interpretation requires estimates and their uncertainty, as well as enough methods detail to understand how they were produced. Without those elements, the responsible conclusion is limited to describing the design, measurement plan, and recorded safety entries rather than making a quantitative claim about clinical benefit.

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 this specific registry record is the absence of numerical primary-outcome findings. The record identifies the intended time frame and confidence-interval format but does not give an estimate, interval limits, or the number of participants with endpoint data. It also lists 0 analyses. As a result, the direction, magnitude, and precision of the primary outcome cannot be evaluated.

The endpoint wording leaves an interpretive uncertainty. The title refers to the percentage of participants with improved clinical benefit, while the parameter is listed as a mean and the description refers to proportional change. The registry record does not specify the threshold for classifying a participant as improved or fully explain how the mean relates to that percentage. The scale’s direction and change-score calculation are described, but these details do not resolve the ambiguity.

The single-group, non-randomized, open-label design limits comparative interpretation. It does not offer a randomized control group, and the registry does not report masking. These design features mean that any within-group change, if reported, would not by itself identify a causal treatment effect. This is a general limitation of the design, not evidence that a particular bias occurred.

The record does not report the protocol’s sample-size justification, detailed statistical plan, interim analyses, missing-data procedures, participant flow, adherence, dosing details, or the number contributing to each outcome. It also does not report how multiple outcomes were handled. These omissions prevent assessment of important analytical assumptions and the completeness of outcome reporting.

Safety interpretation is also restricted: the other-event at-risk value and deaths entry are null, and the serious-event terms are listed with percentages but without term-specific counts or further event context. The record does not permit a controlled safety comparison or causal attribution.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Evaluating the Clinical Benefit of SEROQUEL XR in Subjects With Schizophrenia — NCT00640601.
• Registry record last updated 2012-06-25; status last verified 2012-06.
• Results first posted 2012-06-22.
• 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

The registry record describes NCT00640601, a completed Phase 3, multicentre, prospective, open-label, non-randomized, single-group study of quetiapine fumarate extended-release in subjects with schizophrenia. AstraZeneca is listed as sponsor. The recorded start is 2008-03, primary completion is 2010-07, and enrollment is 331.

The primary endpoint concerns clinical benefit on the CGI-CB scale from baseline to Week 24 or the end of study. The record defines the analysis population as participants receiving at least one dose, with n=295, and identifies a 95% confidence interval as the dispersion measure. It lists 11 outcome measures and 0 analyses. No numerical primary endpoint result is reported in the registry record.

The safety listing records 33 participants in the serious adverse-event category and 224 in the other adverse-event category for Seroquel XR. The other-category at-risk value and deaths entry are null. Serious-event terms are listed with percentages. The record does not provide a concurrent control group or enough analysis detail to support a comparative treatment-effect interpretation.