Safety, Efficacy and Tolerability Study of Paliperidone Extended-Release (ER) in Participants With Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Efficacy and Tolerability Study of Paliperidone Extended-Release (ER) in Participants With Schizophrenia (NCT01662648), a non-randomized phase 3 study. The primary outcome is Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 26.

2. Clinical Question

3. Trial Design

This completed Phase 3 study was an open-label, prospective, non-randomized, single-group trial of paliperidone ER in participants with schizophrenia. The registry reports enrollment of 1117. The study began in 2007-06, and primary completion was in 2008-04. The treatment period described for the intervention was 6 months.

Participants switched from other oral antipsychotics to paliperidone ER. The record distinguishes participants by the main reason for switching: lack of efficacy, or lack of tolerability, compliance or other. Dose was flexible, from 3 to 12 milligram (mg) per day, and was determined at the investigator’s discretion. The record describes these groups for the primary outcome, but does not establish that assignment to the groups was randomized.

There was no masking and no randomized comparator. Consequently, changes within either switching-reason group cannot be interpreted as a treatment effect relative to an untreated or alternative-treatment control group. Differences between the groups, if reported, would also be observational: the group distinction is based on reason for switching, not random allocation. Baseline characteristics, other factors that might differ between groups, and any adjustment for such differences are not reported in the registry record.

The study is marked completed, but completion status does not supply outcome findings. The registry record does not report the primary endpoint estimates, statistical tests, confidence intervals, or analysis results. It also does not report a statistical analysis plan, sample-size justification, or interim-analysis plan. The design and outcome definitions can therefore be described, but the efficacy findings cannot be reconstructed from the registry information.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT) population for efficacy included all the participants who received paliperidone extended-release (ER) at least once and who had at least 1 post baseline efficacy assessment. "N" (number of participants analyzed) signifies the participants evaluable for this measure.

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 Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 26, measured over Baseline and Week 26.

The primary endpoint was change from baseline in total score on the Positive and Negative Syndrome Scale (PANSS) at Week 26. PANSS is a 30-item scale covering symptoms that include delusions, grandiosity, blunted affect, poor attention, and poor impulse control. Each item is rated on a 7-point scale, from 1 (absent) to 7 (extreme psychopathology). The total is the sum of all 30 items and ranges from 30 to 210; higher scores indicate worsening.

A change score expresses how a participant’s measured score at follow-up differs from their baseline score. In general, this can describe the direction and magnitude of change over the study period, while the spread of individual scores indicates how much participants’ changes vary. The registry specifies the primary outcome as a mean with standard deviation, but does not report the group means, standard deviations, or change estimates.

The record presents the endpoint by reason for switching: lack of efficacy and lack of tolerability, compliance or other. These are descriptive groups within a non-randomized study, not randomized treatment arms. The endpoint definition indicates what was intended to be measured; it does not establish the magnitude, precision, or statistical significance of any result. Those findings are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods that can be described from the registry record are limited to the design, endpoint scale, outcome summary type, and stated analysis population. The record identifies a prospective, open-label, non-randomized, single-group study and describes the primary outcome as a mean change in PANSS total score with standard deviation. It does not report the statistical model, test, estimation procedure, or analysis results. The explanations below distinguish these registry entries from general statistical concepts.

What does a mean change describe?

The primary endpoint is change from baseline in PANSS total score at Week 26. In general, a mean change is the average of participants’ individual differences between their follow-up and baseline measurements. It summarizes the group’s average observed trajectory, but does not show whether every participant changed in the same direction. A standard deviation describes the spread of the individual measurements around the mean; it is not the same as the uncertainty in the estimated mean.

The scale’s stated range and scoring direction give context for interpreting a reported change. But the registry does not give the mean change or its standard deviation for either group. These quantities cannot be inferred from the scale description, study duration, or enrollment. No direction or magnitude of change can therefore be stated from the registry record.

What would a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimated quantity under a specified statistical method and its assumptions. A relatively narrow interval indicates more precise estimation than a wide interval, while the interval’s position indicates which values remain compatible with the data and method. A confidence interval is not a guarantee that the true value lies within the particular interval. No confidence interval for the primary outcome is reported in the registry record.

A p-value, in general, measures how compatible observed data are with a stated null hypothesis under the chosen model. It does not measure the size or clinical importance of an effect, and it does not provide the probability that the null hypothesis is true. The registry record reports no primary-outcome p-value or hypothesis test. It also does not state the null hypothesis or testing procedure.

Why does the non-randomized design matter?

In a randomized comparison, random assignment is intended to make treatment groups comparable on average with respect to both measured and unmeasured baseline factors. This study is reported as non-randomized and single-group, with participants described in categories based on their reason for switching. The categories are not randomized controls. Differences in outcomes between these groups, were they reported, could reflect differences in participant characteristics, prior treatment experience, or other factors rather than a causal effect of group membership or treatment.

In general, adjustment methods can account for measured covariates under specific assumptions, but they cannot automatically remove all confounding, particularly from factors that were not measured or were inadequately captured. The registry record does not report adjusted analyses, covariates, or a model for comparing the switching-reason groups. It is therefore not possible to assess whether or how any potential confounding was addressed.

How should the outcome population be understood?

The record defines the efficacy intent-to-treat population as participants who received paliperidone ER at least once and had at least one post-baseline efficacy assessment. It also states that the “N” for a measure means the number of participants evaluable for that measure. This definition makes the availability of post-baseline assessment part of the stated efficacy population. The record does not report the number analyzed for the primary endpoint or the number missing a Week 26 assessment.

In general, excluding participants without an available post-baseline measurement can affect an estimate if the likelihood of having an assessment is related to the outcome. Methods for handling missing data require assumptions about why measurements are missing and may yield different estimates. The registry does not report imputation, sensitivity analyses, or other missing-data procedures, so their use cannot be assumed.

What does dispersion tell us?

For a continuous outcome, a standard deviation describes variation among observed scores or changes. General statistical models sometimes account for over-dispersion when the observed variation is greater than a model would otherwise expect. That concept is not a reported analysis feature of this study: the endpoint is a continuous score summarized by a mean and standard deviation, and the registry does not report a model or an over-dispersion assessment.

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and effect sizes defined as stated fractions of the observed effect. These assumptions are not the trial’s own design justification, and the record does not report the calculated planning values in the information available for interpretation. Such illustrations are planning quantities, not observed power and not evidence that the study was designed around those assumptions.

In summary, the record supports a methodological description but not a reconstruction of the analysis. The statistical test, model, confidence intervals, multiplicity strategy, handling of missing data, and any interim analyses are not reported in the registry record. Without outcome estimates and analysis details, neither the size nor the precision of the primary endpoint result can be assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary PANSS total-score change at Week 26 and several secondary outcomes. These include the proportion with at least 20 percent improvement in PANSS total score, changes in PANSS positive and negative subscale scores, CGI-S, PSP, sleep quality, and daytime drowsiness, and categories of patient satisfaction. The record states that there are 9 outcome measures, but does not report analyses for them.

When a study evaluates multiple outcomes or multiple statistical hypotheses, the chance of at least one apparently noteworthy finding can increase. In general, a multiplicity strategy may define a hierarchy, adjust significance thresholds, or specify which outcomes are confirmatory and which are exploratory. The registry record does not report a multiplicity plan, testing hierarchy, or adjustment. It also does not report whether any secondary outcomes were analyzed.

The efficacy population is described as participants who received paliperidone ER at least once and had at least one post-baseline efficacy assessment. The number analyzed for the primary endpoint is not reported in the registry record. The record does not state how missing Week 26 measurements were handled, whether participants who discontinued treatment were followed for outcomes, or whether any imputation or sensitivity analysis was conducted.

In general, missing outcome data can affect interpretation if participants with unavailable measurements differ systematically from those with observed measurements. The direction and size of any such effect depend on the missingness pattern and assumptions used in analysis. Those details cannot be assessed because the registry record does not report them. The statistical analysis plan, sample-size justification, and interim analyses 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.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: schizophrenia (2.3%), psychotic disorder (1.4%), extrapyramidal disorder (0.5%), agitation (0.4%), aggression (0.3%).

The safety record separates participants by their reason for switching. In the lack-of-efficacy group, 35 participants were reported with serious adverse events among 512 at risk, and 208 with other adverse events among 512 at risk. In the lack-of-tolerability, compliance or other group, 29 were reported with serious adverse events among 587 at risk, and 239 with other adverse events among 587 at risk. These are descriptive counts in groups that were not randomized treatment comparisons.

The listed serious adverse-event terms and percentages are schizophrenia, 2.3%; psychotic disorder, 1.4%; extrapyramidal disorder, 0.5%; agitation, 0.4%; aggression, 0.3%; and vomiting, 0.3%. The registry record does not give additional detail about event timing, severity beyond the serious-event classification, or how events were attributed to treatment.

In general, an adverse event recorded during a study is not necessarily caused by the study treatment. Without a randomized comparator, these counts cannot establish whether the event frequency differs from another treatment or from what would otherwise have occurred. The deaths field has no reported count in the registry record; this should not be interpreted as evidence that no deaths occurred.

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

The record establishes the setting and design of a study of flexible-dose paliperidone ER in participants with schizophrenia who switched from other oral antipsychotics. It specifies a primary outcome, change from baseline in PANSS total score at Week 26, and describes the scale and the intended efficacy population. It also reports serious and other adverse-event counts for two groups defined by reason for switching.

Those details do not provide the primary efficacy result. The registry record does not report group-specific PANSS changes, standard deviations, confidence intervals, p-values, or participant counts analyzed for that endpoint. It is therefore not possible to say from this record whether the average score changed, how large any change was, how variable the changes were, or how precisely an effect was estimated.

The two switching-reason groups do not form a randomized treatment comparison. Even if their outcomes had been reported, a difference between them would not by itself establish that one switching reason, prior treatment experience, or paliperidone caused the difference. The record does not report adjustments that might address group differences, and adjustment would in any case depend on measured information and assumptions.

The safety counts describe events recorded in the study groups. They do not show a causal relationship between paliperidone and an event, and they do not offer a direct comparison with another treatment. The deaths count is not reported in the registry record.

Accordingly, the record can be used to understand the trial’s design and the outcomes it intended to assess, as well as the safety categories recorded. It cannot support a conclusion about the magnitude or statistical significance of the primary endpoint, comparative efficacy, or a causal treatment effect. Those claims would require outcome results and analysis details not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why a registry record’s design description and outcome definitions should be distinguished from its results. The primary endpoint is defined in detail: a Week 26 change in PANSS total score, with a stated scale range, item structure, and score direction. These details make clear what the investigators intended to measure, but they do not reveal what the participants’ scores did.

The non-randomized, single-group design also matters for interpretation. Participants were categorized by their main reason for switching from another oral antipsychotic, rather than assigned randomly to competing treatments. The categories may be useful for describing the study population, but they do not create a like-for-like control comparison. This is an important distinction whenever group-level outcomes are read as evidence about treatment effects.

The record also separates the stated efficacy population from the total enrollment. It defines efficacy participants as those who received paliperidone ER at least once and had at least one post-baseline efficacy assessment, and says that the analyzed number is measure-specific. Because the endpoint-specific number is not reported, the extent of available outcome data cannot be judged from the record.

Finally, the safety information illustrates the difference between recording adverse events and establishing causation. Event counts and listed terms describe what was recorded, but a non-randomized comparison without a control group cannot establish whether treatment caused an event or changed its frequency relative to another option. The trial is therefore statistically informative as a description of design, measurement, and recorded safety categories, while its posted record leaves the primary efficacy estimate and its uncertainty unreported.

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 efficacy is that the registry record does not report the primary endpoint results. No group-specific PANSS change, standard deviation, confidence interval, p-value, or endpoint analysis count is reported. The direction, magnitude, and precision of the primary outcome therefore cannot be evaluated.

The study is non-randomized, open-label, and described as single-group. The two reported categories reflect reasons for switching, not randomized assignment to treatment strategies. There is no like-for-like control comparison in the registry record. Group differences could be associated with participant characteristics or other factors; baseline comparisons and adjusted analyses are not reported.

The record describes an efficacy population requiring at least one post-baseline assessment, but does not give the number included in the primary analysis or explain how missing observations were handled. The frequency and pattern of missing outcomes, treatment discontinuation, imputation, and sensitivity analyses are not reported in the registry record. The endpoint-specific completeness of follow-up therefore cannot be assessed.

Although multiple secondary outcomes are listed, analyses and a multiplicity strategy are not reported. The statistical model, hypothesis tests, confidence-interval methods, sample-size justification, and interim analyses are also not reported in the registry record. These omissions prevent an assessment of the analysis choices and the strength of statistical evidence.

The safety information is descriptive and lacks a randomized comparator. The record lists event counts and selected serious-event terms, but does not provide enough context to infer causality or compare the event experience with another treatment. A deaths count is not reported in the registry record. These limitations apply to interpretation of the record and do not establish what may or may not have been analyzed elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety, Efficacy and Tolerability Study of Paliperidone Extended-Release (ER) in Participants With Schizophrenia — NCT01662648.
• Registry record last updated 2014-05-05; status last verified 2014-04.
• Results first posted 2014-03-26.
• 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

This completed Phase 3 study evaluated flexibly dosed oral paliperidone ER in participants with schizophrenia who switched from other oral antipsychotics. It was prospective, open-label, non-randomized, and single-group, with enrollment of 1117. The registered primary outcome was change from baseline in PANSS total score at Week 26, summarized as a mean and standard deviation. Participants were described by reason for switching: lack of efficacy, or lack of tolerability, compliance or other.

The registry record does not report primary outcome estimates, statistical tests, confidence intervals, or the number analyzed for the primary endpoint. It lists secondary outcomes and reports descriptive adverse-event counts and selected serious-event terms. These safety figures are not a randomized comparison and do not establish causation. The analysis plan, missing-data methods, multiplicity approach, sample-size justification, and interim analyses are not reported in the registry record.