A Trial to Explore the Tolerability, Safety and Efficacy of Paliperidone Extended Release in Patients With Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial to Explore the Tolerability, Safety and Efficacy of Paliperidone Extended Release in Patients With Schizophrenia (NCT01606228), a na phase 3 study. The primary outcome is The Proportion of Patients Improving 20% in Total Positive and Negative Syndrome Scale (PANSS) at Endpoint (Day 90).

2. Clinical Question

3. Trial Design

The registry record describes a prospective, open-label trial listed as PHASE3. Its official title identifies treatment-naïve and newly diagnosed patients with schizophrenia, and its brief summary describes an exploration of tolerability, safety, and efficacy of flexibly dosed paliperidone ER. The record lists one intervention and one group, with an enrollment of 188. It records the study status as completed.

The design is single-group, with no listed comparator and no masking. Allocation is recorded as NA. Consequently, the study can describe outcomes observed among participants receiving paliperidone ER, but it does not provide a randomized estimate of how those outcomes differ from an alternative treatment or from a control group. Changes over time within the treated group may also reflect factors other than treatment, including the natural course of symptoms, concurrent care, measurement variation, or changes in participation.

The primary endpoint uses baseline and Day 90 as its timeframe and is specified for the Per Protocol population. Although the overall enrollment is recorded, the number of participants who entered that analysis population, completed the endpoint assessment, or contributed data at each time point is not reported in the registry record. The registry record also does not report dose schedules, treatment adherence, detailed eligibility criteria, or the handling of participants who discontinued.

Several secondary outcomes are listed, including PANSS, Clinical Global Impression-Severity, and Personal and Social Performance scores at baseline and Day 90, along with patient satisfaction and quality of sleep measures. The record lists 12 outcome measures, but it does not provide analysis estimates for them. No separate control arm or comparative treatment effect is available from this design.

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: There were 188 patients enrolled in the study which were included in the safety analysis set. The main analysis set included only 176 subjects due to 12 protocol violations. Of these 176 patients, only 73 were included in the per-protocol analysis set. For the Clinical Global Impression-Severity scores, data was collected for only 60 patients.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Per Protocol (PP) population

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 The Proportion of Patients Improving 20% in Total Positive and Negative Syndrome Scale (PANSS) at Endpoint (Day 90), measured over Baseline, Day 90.

The primary endpoint is the proportion of patients in the Per Protocol (PP) population who improved 20% in total PANSS score at endpoint, specified as Day 90, relative to baseline. The PANSS is described as a 30-item scale covering symptoms of schizophrenia, including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. Each symptom is rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology), and the total score is the sum of the item scores. The total score range is 30-210; higher scores indicate worsening.

A threshold-based endpoint converts change in a continuous score into a responder classification: participants either meet the stated improvement criterion or do not. Such an endpoint can be straightforward to interpret as a proportion, but it does not show the full distribution of score changes. Participants with different amounts of improvement may fall into the same category, while small differences around the threshold may determine whether a participant is counted as meeting it.

The registry record does not report the observed proportion meeting the criterion, the number assessed at Day 90, a confidence interval, or a statistical test. Therefore, the endpoint definition can be described, but its result and precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a proportion endpoint convey?

In general, a proportion reports the share of an analysis population that meets a defined condition. For this trial, the condition is improvement of 20% in total PANSS score at Day 90, and the designated analysis population is the PP population. To interpret a proportion, readers need both the count meeting the condition and the relevant denominator. The registry record does not report either for this endpoint, so the proportion cannot be reconstructed from the posted information.

In general, a confidence interval expresses uncertainty around an estimate. It is not a guarantee that the true value lies within the interval; rather, it indicates a range of values compatible with the data under the method’s assumptions. A narrow interval generally indicates greater precision than a wide one. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed.

Why does the study design matter?

In general, random assignment to treatment groups helps balance known and unknown participant characteristics across groups, supporting a more credible comparison. This study is recorded as SINGLE GROUP, with allocation NA and masking NONE. There is no concurrent control group against which to estimate a treatment contrast. A change from baseline, if reported, would be a within-group observation rather than a randomized between-group effect. Without a comparator, observed changes cannot by themselves distinguish treatment-associated change from other influences over time.

Open-label means participants and study personnel are not masked to the assigned intervention. In general, lack of masking can affect subjective outcomes through expectations, reporting, clinical management, or assessment. PANSS uses structured ratings, but that does not remove all potential influence from an open-label setting. The registry record does not describe rater training, independent assessment, or procedures intended to limit assessment bias.

What does the endpoint threshold leave out?

In general, turning a continuous score into a responder outcome can make a result easier to communicate as a proportion, but it discards information about the amount of change within each category. Participants just above and just below the threshold are classified differently despite potentially similar score changes. Those with larger changes may be grouped together with those who only meet the threshold. The posted endpoint is therefore one particular summary of PANSS change, not a complete description of score trajectories or score distributions.

The PANSS description gives the scale composition, scoring range, rating anchors, and direction of higher scores. These details help explain what the endpoint represents. The record does not provide the baseline and endpoint score distributions, individual changes, or the observed responder count. No conclusion about the extent of score improvement can be derived from the endpoint definition alone.

What can be said about analysis choices?

The registry record identifies the PP population for the primary endpoint, but does not report the analysis set definition, exclusions, statistical test, model, covariate adjustment, or confidence-interval method. It also does not report how missing Day 90 assessments were handled. These choices matter because analysis populations and missing-data methods can change both the estimate and its uncertainty. The phrase PP alone does not reveal which participants were included or how protocol deviations were treated.

In general, a statistical test evaluates whether data are compatible with a stated null hypothesis under specified assumptions. A p-value is not the probability that a treatment has no effect, nor is it a measure of clinical importance. No test result or p-value for the primary endpoint is reported in the registry record. The absence of a posted test does not establish either a positive or a negative result.

How should planning illustrations be understood?

In general, a sample-size calculation asks how many participants would be needed under assumptions about an effect, variability, allocation, significance level, and desired power. The planning assumptions associated with this trial describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. These are planning illustrations, not the trial’s observed power and not evidence that the trial was designed around those assumptions.

The study itself is a single-group trial, whereas the stated planning assumptions describe equal allocation between two arms. They should not be mistaken for the actual design. The registry record does not report the trial’s sample-size justification or confirm that these assumptions were used in planning the study. The observed effect referenced in the planning assumptions is not reported as an endpoint estimate in the registry record, and no calculated planning sample-size values are available in the registry record.

In general, planning illustrations based on a fraction of an observed effect show how required sample size can depend on the assumed effect magnitude. They do not establish that an effect is real, and they do not change the uncertainty of the trial’s observed estimate. Since no primary endpoint estimate is reported, the planning illustrations cannot substitute for an efficacy analysis or provide a basis for judging the precision of an unreported result.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Paliperidone Extended-release (ER)")
n      <- c(73)
events <- c(71)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Paliperidone Extended-release (ER)  73  71  97.3  90.5  99.7  90.5  99.2  90.6  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures, including the primary PANSS responder endpoint and secondary measures involving PANSS, Clinical Global Impression-Severity, Personal and Social Performance, patient satisfaction, and quality of sleep. When a study evaluates multiple outcomes or multiple time points, the chance of at least one apparently notable result can increase if each is tested separately. In general, statistical plans may address this through a prespecified hierarchy, adjusted thresholds, or other multiplicity procedures. The registry record does not report whether any such procedure was planned or used.

The record lists 0 analyses. It therefore does not report primary or secondary outcome estimates, inferential tests, or analysis details for the listed measures. The primary endpoint’s analysis population is identified as PP, but the number analyzed and the participant-level rules defining that population are not reported in the registry record. It is also not reported whether other populations were analyzed.

Missing-data handling is not reported in the registry record. The record does not state how participants without Day 90 PANSS scores were handled, whether their missingness was examined, or whether any sensitivity analyses were performed. In general, missing outcomes can affect an estimate if participants with missing data differ systematically from those with observed data. The possible direction or size of such an influence cannot be assessed without participant flow, reasons for missingness, and analysis details.

The registry record also does not report interim analyses, a prespecified statistical analysis plan, or a sample-size justification. These omissions leave uncertainty about the intended inferential framework and whether the posted outcome definitions align with a complete analysis plan.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: schizophrenia (1.1%), schizophrenia paranoid type (0.5%), arrhythmia (0.5%), ventricular extrasystoles (0.5%), akathisia (0.5%).

For the Paliperidone Extended-release (ER) group, the registry record lists 188 participants at risk for serious adverse events, with 4 affected. It also lists 188 at risk in the other adverse-event category, with 43 affected. These counts describe the posted safety categories for this single group. They are not comparisons against another treatment, because the study has no listed control group.

The serious-event terms with reported percentages are Schizophrenia (1.1%), Schizophrenia paranoid type (0.5%), Arrhythmia (0.5%), Ventricular Extrasystoles (0.5%), and Akathisia (0.5%). These term-level percentages should be read as registry listings, not as proof that paliperidone ER caused the events. The record does not provide details on timing, event duration, clinical adjudication, or participant-level overlap among terms. The registry record does not report deaths; that is not the same as confirming that no deaths occurred.

In general, adverse-event counts are descriptive safety information. A causal comparison requires an appropriate comparator and details about event ascertainment and follow-up. Because the record reports one group, these figures do not establish whether the frequency of an event is higher or lower than it would have been without treatment.

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

The registry record defines a study of flexibly dosed paliperidone ER in patients with schizophrenia and specifies a primary endpoint based on improvement in PANSS total score by Day 90. It also records enrollment of 188 and reports safety counts for the single treatment group. These registry entries describe the study and its posted safety information, but they do not supply an efficacy estimate.

The primary endpoint result is not reported in the registry record. Without the number of participants meeting the 20% improvement criterion, the denominator analyzed, and an uncertainty estimate, the frequency and precision of that outcome cannot be evaluated. The listed secondary outcomes likewise have no posted analysis estimates. The absence of reported results should not be interpreted as evidence that the endpoint was or was not met.

The design also sets a limit on what the study can establish. A prospective, open-label, single-group study can describe observations among participants receiving the intervention, but it cannot estimate a randomized contrast with a control group. Even a reported within-group improvement would not, by itself, show what would have happened under another treatment or without the intervention. The registry record does not provide a comparator, masking, or a reported analysis that resolves this limitation.

The safety counts are informative as descriptive observations in the enrolled group, but they do not determine whether events were caused by treatment. No event comparison group is listed, and the registry record lacks detail about event timing, adjudication, and follow-up. The serious-event terms and percentages should therefore be understood as reported event categories rather than causal findings.

Overall, the posted record allows readers to understand the endpoint definition, broad design, enrollment, and some safety counts. It does not support a conclusion about treatment efficacy, comparative benefit, or comparative risk. Those judgments require outcome estimates and methods that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a clearly defined outcome and a reported outcome result. The primary endpoint is described with a scale, threshold, timeframe, and analysis population. That definition helps clarify what investigators intended to measure. Yet without the observed proportion and its uncertainty, the endpoint cannot answer how often participants met the criterion or how precisely that frequency was estimated.

The design also illustrates why study structure shapes interpretation. A single-group study can document participant outcomes during treatment, but it lacks the concurrent comparator needed for a randomized treatment contrast. The open-label design adds the possibility that expectations or assessment processes influence outcomes. These are design limitations, not defects that can be corrected by simply applying a more elaborate statistical test to the same data.

The record makes visible another important distinction: safety counts and efficacy results are different kinds of information. Counts of participants with reported adverse events can describe what was recorded in a treated group, but do not establish a causal relationship or comparative risk. Likewise, a planned responder definition is not evidence that participants did or did not respond.

Finally, the record lists multiple outcome measures but no analyses. This underscores why readers need more than endpoint names: analysis populations, missing-data handling, multiplicity choices, effect estimates, and uncertainty all contribute to interpretation. The available information supports a careful description of the design and safety listings, while leaving the central efficacy question unanswered in the registry record.

15. 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.

Several limitations are specific to the information recorded for this trial. First, the primary outcome is defined, but its observed result is not reported in the registry record. The number meeting the 20% improvement criterion, the analyzed denominator, and a confidence interval are unavailable. Consequently, neither the magnitude nor precision of the primary endpoint can be assessed.

Second, the trial is a single-group, open-label study with no listed comparator. The findings cannot provide a randomized comparison with another treatment or a control condition. Any within-group change, if it were reported, could not be attributed solely to the intervention based on this design alone.

Third, the primary analysis population is identified as PP, but the registry record does not define its membership or report its size. Participant flow, completion at Day 90, adherence, protocol deviations, and reasons for missing assessments are not reported. These omissions make it difficult to judge whether the analysis population represents all enrolled participants or whether missing outcome data could influence interpretation.

Fourth, although 12 outcome measures are listed, the record lists 0 analyses. Statistical methods, multiplicity handling, interim analyses, and a sample-size justification are not reported in the registry record. The record’s planning assumptions do not establish the study’s own design rationale, and the actual primary effect needed to interpret effect-based planning is not reported.

Finally, the safety data provide counts and selected serious-event terms, but limited context on timing, event assessment, participant overlap, or follow-up. Deaths are not reported in the registry record. These gaps restrict both efficacy interpretation and the ability to make comparative safety judgments.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Trial to Explore the Tolerability, Safety and Efficacy of Paliperidone Extended Release in Patients With Schizophrenia — NCT01606228.
• Registry record last updated 2012-10-22; status last verified 2012-09.
• Results first posted 2012-10-22.
• 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.

19. Record Summary

The registry record describes a completed, prospective, open-label trial listed as PHASE3 of flexibly dosed paliperidone ER in patients with schizophrenia. It records a SINGLE GROUP model, allocation NA, masking NONE, and enrollment of 188. The primary endpoint is the proportion of the PP population improving 20% in total PANSS score at Day 90.

The record lists 12 outcome measures and 0 analyses. It does not report the primary endpoint result, a confidence interval, or a statistical test. For the treatment group, 4 of 188 participants are listed as affected by serious adverse events and 43 of 188 in the other adverse-event category. Selected serious-event terms and percentages are reported, but deaths are not reported in the registry record.

Because there is no control group and no posted efficacy analysis, the record supports a description of the study design and listed safety observations, not a comparative treatment-effect conclusion.