Cognitive-Behavioral Therapy in Veterans With Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cognitive-Behavioral Therapy in Veterans With Schizophrenia (NCT00688259), a randomized na study. The primary outcome is Changes in Positive Schizophrenia Symptoms.

2. Clinical Question

3. Trial Design

NCT00688259 is recorded as a completed, randomized, single-masked, parallel-group study. It enrolled 122 participants and compared two forms of individual psychotherapy: Cognitive Behavioral Therapy for Psychosis (CBTp) and Supportive Therapy (ST). The condition labels are schizophrenia and schizoaffective disorder. The registry identifies the phase as NA. The sponsor is the VA Office of Research and Development.

The study summary describes symptomatic Veteran outpatients receiving treatment for approximately 6 months. CBTp was weekly, individual, and manualized; the available description refers to setting personal goals and evaluating beliefs and experiences that might interfere with those goals. ST was also weekly and manualized, and aimed to support a therapeutic alliance and a safe setting for discussion. More complete eligibility criteria, the allocation procedure, the masking role, and details of treatment delivery are not reported in the registry record.

Outcome data were collected at baseline, post-treatment, and at a 6-month post-treatment follow-up, according to the study summary. The primary endpoint, however, is specified as change from pre-treatment to the end of treatment, approximately 6 months post-randomization. The listed secondary outcomes include changes in distress from schizophrenia symptoms, while the record lists 6 outcome measures and 6 analyses. The exact definitions and results for the other outcomes are not included in the available record.

The study is marked completed. Its recorded start is 2009-04 and its primary completion is 2014-09. Those dates describe the registry record and do not establish when results were analyzed or posted. The registry record does not report the randomization ratio, the number assigned to each treatment arm, or participant flow through follow-up.

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: 122 individuals consented for study; 34 did not meet study criteria after more careful screening during baseline phase or withdrew before baseline assessments were completed; Remaining 88 were randomized.

Overall Study

Reasons for not completing this period:

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 Changes in Positive Schizophrenia Symptoms, measured over Pre-treatment to end of treatment, approximately 6 months post-randomization.

The primary endpoint is change in positive schizophrenia symptoms from pre-treatment to the end of treatment, approximately 6 months post-randomization. The registry describes the outcome as the mean positive-symptom interview rating on the Brief Psychiatric Rating Scale. Scores range from 1-7, with higher scores indicating greater symptoms. The listed analysis parameter is a least-squares mean, and the stated dispersion measure is the standard error.

Symptom ratings provide a continuous measure: they can reflect variation in symptom severity rather than only classifying a participant as having or not having a symptom. A change endpoint is intended to describe how ratings differ between the start and end of the specified treatment period. The score direction matters when interpreting any estimate: a higher score corresponds to greater symptoms, but the registry record does not provide the observed change in either arm.

In general, a least-squares mean is a model-based mean estimate, often adjusted for factors included in the analysis model. Which factors were included, how the model was specified, and whether the estimate was adjusted for baseline scores are not reported in the registry record. A standard error describes the sampling uncertainty of an estimate; it is not the same as the spread of individual participants’ scores. No arm-level endpoint estimates, standard errors, confidence intervals, or between-group test results are reported in the posted record, so the magnitude and precision of the primary comparison cannot be assessed from it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, single-masked, parallel-group design and describes a primary endpoint analyzed as a least-squares mean with standard error. These details describe the design and the type of summary planned or recorded; they do not reveal the full statistical analysis plan. The model specification, covariates, handling of repeated observations, and primary hypothesis are not reported in the registry record. The statistical concepts below are general explanations rather than claims about analyses used in this trial.

What does randomization contribute?

In general, randomization assigns participants to treatment groups using a chance-based process. Its purpose is to reduce systematic differences between groups at assignment, so that a between-group comparison can be interpreted more fairly. Random allocation does not guarantee that groups are identical, especially in a finite study, and it does not by itself address missing outcomes, treatment adherence, or bias after assignment. The record does not describe the sequence-generation method, concealment of assignment, or allocation ratio. Thus, the randomized designation is known, but the operational details cannot be assessed from the registry record.

What does a parallel-group comparison mean?

In a parallel-group design, participants are assigned to one treatment group and outcomes are compared across groups. Here the two named treatments are CBTp and ST. A comparison of change can be expressed through each group’s estimated change and a contrast between those changes, but the record does not report those estimates or the contrast. The primary endpoint is specified over the period from pre-treatment to the end of treatment. The summary also mentions a later follow-up, but the primary endpoint’s stated timeframe is the end-of-treatment assessment.

What is a least-squares mean?

In general, a least-squares mean is an estimate derived from a statistical model. It may adjust for variables included in that model and can differ from a simple arithmetic average. The label alone does not identify which variables were used, how repeated measures were modeled, or whether the estimate corresponds to a particular analysis population. The registry lists the least-squares mean as the endpoint parameter, but its model details are not reported in the registry record. Without those details and the numerical estimates, a reader cannot reproduce or fully evaluate the analysis.

How should a standard error be read?

In general, a standard error describes the statistical uncertainty in an estimated quantity across repeated samples under the assumptions of the method. It is not the standard deviation of individual participants’ measurements. A smaller standard error generally indicates greater precision for the estimate, while a larger standard error indicates less precision. A standard error can contribute to a confidence interval or test, but the registry record does not report numerical standard errors for the primary endpoint. No precision assessment can therefore be made for the treatment comparison.

What does the scale direction tell the reader?

The primary measure is an interview rating on the Brief Psychiatric Rating Scale, with values from 1-7 and higher values indicating greater symptoms. In general, a scale’s direction helps interpret an estimate: the sign and value of a change must be read in relation to whether higher scores indicate more or less of the measured attribute. The record names the scale and direction but does not report score distributions, baseline values, changes, or an estimated contrast. The scale range alone does not indicate the observed effect.

How do sample-size illustrations differ from observed results?

The registry record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. In general, such illustrations explore how sample size would vary under stated assumptions. They are not observed outcomes and are not evidence that a planned power level was achieved. The record does not include numerical sample-size illustration results or a trial-specific sample-size justification. It also does not report whether the original design used the same assumptions. Any illustration should be distinguished from the actual enrollment of 122 and from the unreported number analyzed for the primary endpoint.

Why does over-dispersion matter in some analyses?

In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. If it is ignored, uncertainty estimates and tests can be misleading. This is a general consideration for analyses whose outcomes and models make over-dispersion relevant; the registry identifies the primary endpoint as continuous and does not report an over-dispersion assessment or a model to which such an adjustment could be applied. It would not be appropriate to infer that over-dispersion was present or that a correction was used.

What is needed to evaluate the analysis?

A full statistical assessment would ordinarily consider the estimand, analysis population, model, covariates, missing-data assumptions, multiplicity strategy, and sensitivity analyses, alongside the effect estimate and its uncertainty. The registry record does not report these details for the primary endpoint. It lists 6 outcome measures and 6 analyses, but does not identify the complete analysis plan or explain how results across outcomes were handled. These omissions limit assessment of robustness and of the degree to which the posted endpoint result, if available elsewhere, would reflect a prespecified analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures and 6 analyses. It names changes in positive schizophrenia symptoms as the primary outcome and lists changes in distress from schizophrenia symptoms among secondary outcomes, with that secondary description repeated. The registry does not report a multiplicity adjustment, a hierarchy of secondary outcomes, or the family of hypotheses to which any adjustment might apply. It is therefore not possible to determine how the chance of false-positive findings across multiple analyses was addressed.

In general, multiplicity refers to the increased risk of finding at least one apparently notable result when many outcomes, time points, subgroups, or statistical tests are examined. A prespecified testing strategy can define which comparisons are confirmatory and how uncertainty should be interpreted across them. The number of listed outcomes and analyses indicates that multiple analyses were recorded, but does not by itself establish which analyses were planned, exploratory, or adjusted. Those distinctions are not reported in the registry record.

The study summary describes outcome collection at baseline, post-treatment, and 6 months post-treatment. The primary endpoint timeframe is pre-treatment to end of treatment, approximately 6 months post-randomization. The registry does not state how the later follow-up was incorporated into analyses or whether every outcome was assessed at each time point. Results by time point are not reported.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not give participant flow, the number with observed primary outcomes, reasons for missingness, or whether the analysis followed assignment regardless of treatment received. In general, incomplete outcomes can affect both the amount of information and the validity of estimates, depending on why data are missing and how the analysis handles them. Without these details, the effect of missing data and the population represented by any primary estimate cannot be assessed.

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

Serious events with the highest arm-level rate: hospitalization due to psychiatric symptom exacerbation (13.6%), hospitalization for cardiac problems (6.8%), hospitalization for substance use (6.8%), surgeries (4.5%), hospitalization for cellulitis (2.3%).

The serious adverse event record lists 44 participants at risk in each group. It records serious adverse events affecting 11 participants in the CBTp group and 12 participants in the ST group. The record also lists 44 at risk for other adverse events in each group, with 0 affected in each group. These are the posted group counts; they do not describe the number of events per participant, event timing, or a statistical comparison.

The listed serious-event terms include hospitalization due to psychiatric symptom exacerbation (13.6%), hospitalization for cardiac problems (6.8%), hospitalization for substance use (6.8%), surgeries (4.5%), hospitalization for cellulitis (2.3%), and hospitalization for fainting (2.3%). The registry does not explain the denominator used for these term-specific percentages or whether categories overlap. They should therefore be read as the percentages recorded for the listed terms, not assumed to represent mutually exclusive groups or the proportion of all events.

The deaths field is null, so deaths are not reported in the registry record. No information is given on event relatedness, severity grading beyond serious-event classification, or adjudication. The counts alone do not establish that treatment caused an event, and they do not support a comparative safety conclusion without fuller context and analysis.

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

The record establishes that a randomized study compared CBTp with ST in symptomatic Veteran outpatients diagnosed with schizophrenia or schizoaffective disorder. It identifies the main symptom endpoint, the instrument and score direction, and the intended end-of-treatment timeframe. It also records serious adverse event counts for the two groups. These registry entries describe the trial and its reporting, but they are not enough to determine the comparative treatment result.

The primary outcome estimates and their uncertainty are not reported in the registry record. Consequently, the record does not show whether either group’s positive symptom rating changed, how large any change was, or whether the groups differed. It does not support a conclusion that one treatment was superior, equivalent, or inferior. Absence of a reported estimate is not evidence that there was no difference; it means the comparative result cannot be evaluated from this record.

Nor does the record establish whether a difference, if reported elsewhere, would be important to participants. Statistical evidence and clinical importance are separate considerations. In general, an estimate describes the size and direction of a measured effect, while its uncertainty indicates how precisely it is estimated. Interpreting importance also requires relevant clinical context and an appropriate threshold, neither of which is reported for the primary outcome in this record.

The enrollment count of 122 should not be mistaken for the primary analysis size. The safety groups each list 44 participants at risk, but the record does not explain how those safety denominators relate to total enrollment or provide the number contributing primary endpoint data. It also does not report the analysis population, missing-data handling, or participant flow. The available counts therefore cannot establish whether outcome data were complete or representative of all randomized participants.

The serious adverse event figures are descriptive and should be kept separate from the symptom endpoint. They do not establish causation, and the record does not provide enough detail to evaluate event timing or attribution. Overall, this registry record conveys the study question, design features, and selected safety counts, while leaving the primary comparative result and important analysis details unreported.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it places two manualized psychotherapy approaches in a randomized, parallel-group comparison and identifies a continuous symptom measure as the primary endpoint. The record specifies the scale direction and the treatment-period contrast, which are necessary context for understanding what a numerical result would mean. It also records that symptoms, functioning, and distress were among the outcomes of interest.

At the same time, the record illustrates why design information and outcome evidence must be distinguished. Knowing that a study was randomized and completed does not reveal the estimated treatment contrast, its precision, or the population contributing data. With no primary endpoint estimates or uncertainty measures reported, the central comparative statistical question remains unanswered in this record.

The listed least-squares mean and standard error signal the kind of summary and uncertainty measure associated with the primary endpoint, but the model and values are absent. This matters because estimates depend on the analysis specification, while their precision depends on both the data and the method. Without those details, readers cannot assess whether the approach accounted for baseline scores, repeated assessments, or other factors.

The record also lists multiple outcomes and analyses without stating how multiplicity was handled. That makes the distinction between a primary endpoint and other outcome findings particularly important when interpreting results if they are reported elsewhere. Finally, the differences between overall enrollment and the recorded safety denominators emphasize the need for participant flow and analysis-population information. Taken together, the record is useful for defining the study’s question and design, but it is not a complete statistical account of the trial’s results.

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 principal limitation of this registry record for interpreting the trial is the absence of numerical primary-endpoint results. There are no arm-level least-squares means, standard errors, between-group estimate, confidence interval, or p-value. The record therefore does not permit evaluation of effect direction, size, or precision. Although the endpoint definition and score direction are stated, they cannot establish what participants experienced during treatment.

Important design and analysis details are also not reported in the registry record. These include the allocation ratio and procedure, the role of single masking, the primary analysis population, model specification, covariates, handling of repeated observations, and missing-data methods. The record does not give participant flow or the number with end-of-treatment outcome data. The enrollment of 122 and the safety denominators of 44 per group cannot be reconciled from the information recorded.

The study summary refers to assessments at baseline, post-treatment, and 6 months post-treatment, while the primary endpoint is specified through the end of treatment. Numerical follow-up findings and methods for analyzing those assessments are not reported. The registry lists 6 outcome measures and 6 analyses but does not provide a multiplicity strategy. The repeated secondary-outcome label also leaves the exact set of distinct secondary outcomes unclear.

The CBTp description ends mid-sentence, so the full intervention description is not reported in the registry record. Detailed eligibility criteria, participant characteristics, treatment adherence, and co-interventions are likewise not included in the registry record recorded. Serious adverse event terms are listed with percentages, but their denominators, overlap, timing, and attribution are not explained; deaths are not reported in the registry record. These limitations restrict interpretation of both the comparative symptom outcome and the safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cognitive-Behavioral Therapy in Veterans With Schizophrenia — NCT00688259.
• Registry record last updated 2025-04-09; status last verified 2025-03.
• Results first posted 2017-12-14.
• 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

NCT00688259 is a completed randomized, single-masked, parallel-group study sponsored by the VA Office of Research and Development. It enrolled 122 Veteran outpatients with schizophrenia or schizoaffective disorder and compared approximately 6 months of weekly individual CBTp with weekly individual ST.

The primary endpoint was change in positive schizophrenia symptoms from pre-treatment to the end of treatment, approximately 6 months post-randomization. It used a Brief Psychiatric Rating Scale interview rating ranging from 1-7, with higher scores indicating greater symptoms. The registry identifies a least-squares mean and standard error but does not report the primary estimates or comparative result.

Serious adverse events affected 11 participants in the CBTp group and 12 in the ST group, with 44 at risk listed in each group. Further analysis details, participant flow, and primary outcome results are not reported in the registry record.