Effectiveness and Safety of 3 Fixed Doses (25 mg eq., 100 mg eq., and 150 mg eq.) of Paliperidone Palmitate in Patients With Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness and Safety of 3 Fixed Doses (25 mg eq., 100 mg eq., and 150 mg eq.) of Paliperidone Palmitate in Patients With Schizophrenia (NCT00590577), a randomized phase 3 study. The primary outcome is Change in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 13 or the Last Post-baseline Assessment.

2. Clinical Question

The study was randomized, placebo-controlled, and parallel-group, with a registry listing of quadruple masking. Its brief description characterizes the study as comparing three fixed doses with placebo over a total of 13 weeks of treatment. The posted primary outcome is a continuous score change, rather than a binary response or a time-to-event outcome. The central statistical question is therefore about the mean difference in score change between each dose group and placebo, with uncertainty around those estimates.

3. Trial Design

The registry describes a randomized, phase 3, parallel-group study with quadruple masking and placebo control. Its official title also describes the study as double-blind. The record lists total enrollment of 652 and status as completed. The recorded start was 2007-03, and primary completion was 2008-03. The study evaluated paliperidone palmitate at 25 mg eq., 100 mg eq., and 150 mg eq. against placebo in participants with schizophrenia.

The intervention descriptions identify intramuscular injections. In the 25 mg eq. group, the schedule was a 150 mg eq. dose on Day 1, followed by 25 mg eq. doses on Days 8, 36, and 64. In the 100 mg eq. group, the schedule was a 150 mg eq. dose on Day 1, followed by 100 mg eq. doses on Days 8, 36, and 64. The 150 mg eq. group received 150 mg eq. on Days 1, 8, 36, and 64. The placebo group received placebo on those days. The brief summary describes the initial loading dose as given in the deltoid muscle and subsequent injections as either deltoid or gluteal.

The primary outcome was assessed from baseline to Week 13 or the last post-baseline assessment, which the record identifies as the end of the double-blind treatment period or an earlier final assessment for participants who left the study early. Outcome-specific arm counts were 155 for 25 mg eq., 161 for 100 mg eq., 160 for 150 mg eq., and 160 for placebo. These are the counts listed for the primary outcome, not the total enrollment figure. The registry record does not report the original sample-size justification or further details of the randomization procedure.

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: Before assignment to treatment groups, patients stopped taking disallowed medications. At the same time, patients who had not previously taken paliperidone extended release (ER) or risperidone or had previously taken it but were not currently taking another antipsychotic took paliperidone ER 6 mg/day for 4 to 6 days to assess tolerance to the drug.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The primary outcome measure used the intent-to-treat analysis set, which consisted of all enrolled subjects who got at least 1 dose of paliperidone palmitate and had both a baseline and at least 1 post-baseline efficacy measurement during the study. For imputation of missing time points, last observation carried forward (LOCF) was used.

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 in Positive and Negative Syndrome Scale (PANSS) Total Score From Baseline to Week 13 or the Last Post-baseline Assessment, measured over Baseline to 13 weeks or the last post-baseline assessment.

The primary endpoint is change in the Positive and Negative Syndrome Scale (PANSS) total score between baseline and Week 13, or the last post-baseline assessment if a participant left the study early. PANSS is a continuous measure of the severity of psychotic symptoms associated with schizophrenia. The registry describes its scale as ranging from 30, best, to 210, worst. Because the outcome is change from baseline, negative mean changes indicate that the measured score decreased over the assessment period.

A continuous score retains information about the amount of change, rather than reducing each participant’s outcome to a yes-or-no category. Comparing group means can therefore describe the average change in each randomized group and the average contrast between a dose group and placebo. The posted results also report standard deviations, which describe how dispersed individual scores were around each group’s mean. These are useful for understanding that an average change does not describe every participant’s course.

The registry states that the primary outcome used an intent-to-treat analysis set consisting of enrolled participants who received at least one dose and had a baseline and at least one post-baseline efficacy measurement. The stated assessment window allows the final outcome to come from Week 13 or an earlier last post-baseline assessment. The registry record does not fully report the missing-time-point imputation procedure. The primary endpoint consequently describes the recorded change within that stated analysis set and assessment window; it should not be interpreted as a measure of outcomes outside them.

7. Results Posted in the Registry

• Paliperidone Palmitate 25 mg eq.: mean -8.00 versus -2.90 on control; difference -5.10 (95% CI -9.43 to -0.77), standardized effect d = -0.26; z-test p = 0.021.
• Paliperidone Palmitate 100 mg eq.: mean -11.60 versus -2.90 on control; difference -8.70 (95% CI -12.74 to -4.66), standardized effect d = -0.47; z-test p = <0.001.
• Paliperidone Palmitate 150 mg eq.: mean -13.20 versus -2.90 on control; difference -10.30 (95% CI -14.44 to -6.16), standardized effect d = -0.55; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change in Personal and Social Performance Scale (PSP) Score From Baseline to Week 13 or the Last Post-baseline Assessment.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Paliperidone Palmitate 25 mg eq.: mean 2.90 versus 1.70 on control; difference 1.20 (95% CI -2.21 to 4.61), standardized effect d = 0.08; z-test p = 0.491.
  • Paliperidone Palmitate 100 mg eq.: mean 6.10 versus 1.70 on control; difference 4.40 (95% CI 1.20 to 7.60), standardized effect d = 0.30; z-test p = 0.007.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Paliperidone Palmitate 25 mg eq. and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Paliperidone Palmitate 100 mg eq. than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry identifies change in Personal and Social Performance Scale (PSP) score and change in Clinical Global Impression-Severity (CGI-S) score as secondary outcomes. The posted PSP means have positive changes in each group, with larger mean changes in the active-dose groups than in placebo. Sponsor analyses are reported for the 100 mg eq. and 150 mg eq. PSP comparisons, while the record does not include a sponsor analysis for the 25 mg eq. PSP comparison. Numeric CGI-S results are not reported in the registry record.

At a broad level, the posted PSP pattern is directionally consistent with the primary outcome in that the reported active-group mean changes differ from placebo in the favorable direction of the respective scales. This does not make PSP interchangeable with PANSS: the measures assess different constructs, and their scales and interpretation differ. Nor does a similar pattern across outcomes independently confirm the primary result, especially when the endpoints and analyses are related within the same trial.

Secondary results carry less weight when they are unadjusted for the number of outcomes or comparisons examined. The registry record does not report whether a multiplicity procedure was used or establish a hierarchy for the secondary outcomes. Without that information, a nominally small p-value should be treated as exploratory rather than as definitive confirmation. The absence of posted CGI-S results also means that no conclusion about that listed secondary measure can be drawn from the registry record. The secondary outcomes can add context, but they do not replace the primary endpoint or resolve its limitations.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change in Personal and Social Performance Scale (PSP) Score From Baseline to Week 13 or the Last Post-baseline Assessment.
• Change in Clinical Global Impression-Severity (CGI-S) Scores From Baseline to Week 13 or the Last Post-baseline Assessment

9. Statistical Interpretation

10. Statistical Methods Explained

The primary measure is continuous, so the registry reports each group’s mean change and standard deviation. A mean describes the average observed change in that group. A standard deviation describes how widely individual observed changes are spread around that average. The mean is not a prediction for a particular participant, and the standard deviation is not the uncertainty in the mean itself. The latter is reflected in the uncertainty interval for a group comparison.

What does the sponsor’s ANCOVA estimate?

The sponsor reports an analysis of covariance, or ANCOVA, and gives differences in least-squares means. In general, ANCOVA estimates adjusted group means and their contrast while accounting for covariates included in the model. The registry record identifies the method and the least-squares mean contrast, but does not report the full model specification or the covariates used. It is therefore possible to describe the reported adjusted comparison, but not to reconstruct all of its modeling choices from the registry record.

The sponsor’s reported contrast compares each dose group with placebo. A negative contrast is in the direction of a greater decrease in PANSS score for the dose group, given the posted group ordering and score direction. The sponsor reports a 95% confidence interval and p-value for each contrast. These are results of the sponsor’s analysis, not the same calculation as a direct comparison of the posted group means.

What is recalculated from the posted summary statistics?

The unadjusted recalculations compare group means using the posted means, standard deviations, and outcome-specific sample sizes. They do not adjust for baseline score or other covariates. The recalculated mean difference is the dose-group mean change minus the placebo mean change. Its confidence interval describes uncertainty in that unadjusted contrast under the calculation’s assumptions. The associated p-value is unadjusted as well. It is useful as a transparent check based on the summary statistics, but it does not replace the sponsor’s prespecified or model-based analysis. Because the registry record flags a discrepancy, the sponsor’s own analysis takes precedence.

Confidence intervals are ranges of values compatible with the data and the statistical procedure at the stated confidence level. They indicate both the estimated direction and the precision of an estimate. A narrower interval indicates greater precision than a wider interval, while an interval spanning zero does not rule out either direction of the contrast at that confidence level. A p-value describes how compatible the observed data are with a specified null hypothesis under the analysis assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect.

Why do dispersion and model assumptions matter?

General statistical explanation: greater variation among participant outcomes makes a group mean less precise when sample sizes are otherwise comparable. Standard deviations therefore matter to the uncertainty around a difference in means. The recalculations use the posted group standard deviations rather than an assumed common value; their pooled standard deviations are calculation inputs, not additional trial outcomes. General statistical explanation: if a continuous outcome has substantially more variability than a model assumes, standard errors and confidence intervals can be poorly calibrated. The registry does not report a dispersion assessment or diagnostics that would establish whether any such issue arose in this trial.

The outcome is measured at a stated endpoint window, but the registry description permits Week 13 or the last post-baseline assessment. This means the reported change may use different follow-up durations for participants who left early. The primary analysis population requires at least one post-baseline efficacy measurement, so the listed group counts pertain to that outcome analysis rather than all enrolled participants. The record begins to refer to a last-observation approach when discussing imputation, but the full imputation procedure is not reported in the registry record. A reader cannot assess from the registry alone exactly how missing time points were handled or how sensitive the primary result is to alternative assumptions.

How should the power illustrations be understood?

The planning illustrations use the observed effect as a reference and calculate participant requirements under stated assumptions. General statistical explanation: power is the probability that a statistical procedure will reject a null hypothesis under a specified effect and set of assumptions. The illustration is prospective arithmetic applied to an observed effect, not a measure of the probability that this completed trial detected its effect. Smaller target effects require more participants when other planning assumptions are held constant. The original trial’s sample-size justification and design assumptions are not reported in the registry record, so the illustrations should not be mistaken for the trial’s original design calculation.

For the primary outcome, the registry reports three dose-versus-placebo comparisons and additional secondary outcomes. Whenever multiple hypotheses are considered, the chance of at least one false-positive result can increase if each test is assessed without adjustment. General statistical explanation: multiplicity procedures can control that overall error rate, but they may also affect the interpretation of confidence intervals and p-values. The registry record does not report a multiplicity adjustment or a hierarchy for interpreting the outcome tests. Accordingly, the posted p-values should be understood as reported, not assumed to be multiplicity-adjusted.

11. Confidence Intervals and Precision

The sponsor’s ANCOVA results include 95% confidence intervals for the primary comparisons. For 25 mg eq., the reported difference in least-squares means was -5.1, with a 95% confidence interval from -9.01 to -1.10. For 100 mg eq., the estimate was -8.7, with a 95% confidence interval from -12.62 to -4.78. For 150 mg eq., the estimate was -9.8, with a 95% confidence interval from -13.71 to -5.85. Each interval lies below zero, but the intervals also show a range of plausible values for the average contrast rather than a single exact effect.

The intervals for the sponsor’s three comparisons overlap. Overlap alone is not a formal test of whether the dose groups differ from one another. The reported analyses compare each active group with placebo; a direct active-dose contrast is not reported in the registry record. The primary estimates should not be used to claim a statistically established difference among the three doses.

Unadjusted recalculations based on the group summary statistics produce somewhat different intervals, particularly for the 150 mg eq. comparison. Those recalculations are not a substitute for the sponsor’s ANCOVA, and the registry flags a discrepancy. The sponsor’s reported analysis takes precedence when interpreting the trial’s inferential results. Both sets of intervals are estimates subject to their respective assumptions, not guarantees that the true contrast lies within a particular range.

In general, an interval’s width reflects precision: narrower intervals indicate less uncertainty under the calculation, while wider intervals indicate more. The registry’s reported intervals quantify uncertainty around mean contrasts, not the spread of individual responses. Standard deviations describe that spread. Neither an interval that excludes zero nor a small p-value establishes the practical importance of a difference. The registry record does not report a threshold for a clinically important PANSS difference, so clinical importance cannot be determined from these confidence intervals alone.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are expressed as participants per arm, not total events. This is a continuous-outcome comparison, so the entries describe the planned number of participants in each of two equally allocated arms. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For each comparison, the target effect is set to a stated fraction of the observed effect: 100%, 75%, or 50%.

The 80% power column gives the number of participants per arm that the illustration estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions. The 90% power column gives the corresponding per-arm number for a 90% chance. These are planning quantities, not observed outcomes. The figures are based on the observed effect in this trial and are intended to show how requirements change under alternative effect-size assumptions. They are not the original trial’s sample-size justification; that justification is not reported in the registry record.

Smaller effects need more participants to distinguish them from random variation at the stated significance level and power. Thus, the entries for a smaller fraction of the observed effect are larger than those for the full observed effect. This is an illustration of the relationship between effect size, sample size, and statistical power under the assumptions named above, not a recommendation about the appropriate size of a future study.

These calculations are not observed power. Observed power would attempt to describe the probability of detecting an effect using the completed study’s observed result, a practice that is not a substitute for examining the estimate and its confidence interval. The planning figures instead pose hypothetical targets and show the per-arm sample size associated with them under the listed assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -5.100; pooled standard deviation σ = 19.578.
2. n = 2 × (1.96 + 0.842)² × 19.578² / -5.100² = 231.3, rounded up to 232 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -5.1                      # observed difference in means
sigma <- 19.5775029328631                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(590577)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 232 (80% power), 310 (90% power)
 75% of observed effect: n per arm = 412 (80% power), 551 (90% power)
 50% of observed effect: n per arm = 926 (80% power), 1,239 (90% power)
power.t.test: 232.3 
Simulated power at n = 232 per arm: 0.798 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports sponsor analyses using ANCOVA and differences in least-squares means. Those estimates are adjusted model-based comparisons of each paliperidone group with placebo. The unadjusted recalculations use only the posted group means, standard deviations, and sample sizes. They do not reproduce the sponsor’s adjustment, so agreement or disagreement between the two is not a like-for-like test of the sponsor’s model.

For the 25 mg eq. and 100 mg eq. comparisons, the recalculated mean differences match the sponsor’s reported point estimates as posted, though the recalculated confidence limits differ from the sponsor’s limits. For 150 mg eq., the recalculated point estimate is -10.3, compared with the sponsor’s reported -9.8. The registry flags a discrepancy. That flag means the sponsor’s own analysis takes precedence for the trial’s principal inferential interpretation; the simple recalculation is best viewed as a check on the posted summary data, not a replacement result.

The registry record does not provide enough information to reconstruct the ANCOVA model fully, including its covariates and other detailed specifications. The sponsor’s results can therefore be reported as the registry presents them, but the precise source of the difference between adjusted and unadjusted estimates cannot be determined from the record. The reported p-values and intervals should not be combined with recalculated quantities as if they arose from a single analysis.

15. Multiplicity, Missing Data and Analysis Populations

The primary outcome has three reported comparisons with placebo, and the registry also lists secondary outcomes. Testing multiple comparisons creates a multiplicity issue: if each is judged using an unadjusted threshold, the chance of at least one false-positive result across the set can be greater than for a single test. General statistical explanation: prespecified procedures such as a testing hierarchy or an adjustment to significance levels can address this issue, but interpretation depends on what was planned and implemented.

The registry record does not report a multiplicity adjustment, a formal hierarchy among primary and secondary outcomes, or whether the listed comparisons were treated as confirmatory or exploratory. The posted p-values should therefore be described as the values reported for the individual analyses, without assuming that they control an overall error rate. This is especially relevant to secondary outcomes, where multiple measures and group contrasts may be considered.

The primary analysis population is described as enrolled participants who received at least one dose and had both baseline and at least one post-baseline efficacy measurement. The outcome window is Week 13 or the last post-baseline assessment for participants who left early. This definition makes clear that the analysis does not simply include every enrolled participant. The registry description begins to refer to a last-observation approach for imputing missing time points, but the full procedure is not reported in the registry record. The handling of missing outcomes, including its assumptions and sensitivity analyses, is therefore not clear from the posted description.

The record also does not report whether interim analyses were planned or performed, or provide a complete statistical analysis plan. No interim-analysis procedure or original sample-size rationale should be inferred. These absences limit assessment of the full analysis framework, including how outcome timing, incomplete follow-up, multiplicity, and any planned decision rules were managed.

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

The posted results show that mean PANSS total score decreased in each randomized group over the outcome assessment period. In the sponsor’s ANCOVA comparisons, each paliperidone dose group had a more negative estimated mean change than placebo, and all three reported 95% confidence intervals were below zero. These estimates describe average differences for the trial’s stated analysis population and assessment window.

They do not show that every participant experienced a decrease, that the group averages predict an individual participant’s outcome, or that the observed differences are necessarily important to patients. The registry record does not report a threshold for a clinically important PANSS difference. A statistical comparison and a clinical judgment are distinct: an estimate can be statistically distinguishable from zero without establishing the value of that difference in a particular care context.

The findings also do not establish that one active dose is superior to another. The posted sponsor analyses compare each dose with placebo, and the registry does not report a direct comparison among the active doses or a formal dose-response test. An ordering of group means is descriptive; it is not, by itself, evidence that the differences between those means are statistically reliable.

The results are limited to the trial’s randomized groups, outcome definition, and observed follow-up. The primary analysis set required at least one dose and at least one post-baseline efficacy measurement, and some final assessments could occur before Week 13. Missing-data procedures and multiplicity handling are not fully reported. The registry record also does not provide enough detail to evaluate all model assumptions or reconstruct the adjusted analysis. These limits should accompany any description of the estimates.

Nothing in these statistical results alone determines an individual treatment decision. They describe group-level outcomes and uncertainty in a clinical trial record; they do not establish what will happen for a particular person or settle questions beyond the measured outcomes and reported follow-up.

17. Why This Trial Matters Statistically

This study is statistically informative because it compares several fixed doses with a concurrent placebo group using randomization and a continuous symptom-severity outcome. A randomized comparison can help separate group differences associated with assigned treatment from some sources of confounding, while the placebo group gives a reference for changes that occurred during the same study period. The posted mean changes and confidence intervals make both the size and uncertainty of the group contrasts visible.

The results also illustrate why different analyses of the same trial need to be distinguished. The sponsor’s ANCOVA estimates are adjusted least-squares mean contrasts; recalculations from posted summary statistics are unadjusted comparisons. Their differences are not simply a matter of rounding, and the registry flags a discrepancy. Clear separation of these analyses prevents an unadjusted reconstruction from being mistaken for the trial’s reported model-based result.

Several doses create a further statistical question: pairwise results against placebo do not automatically establish differences among doses or a dose-response pattern. Multiple outcomes and comparisons also make multiplicity relevant. The registry’s limited reporting of analysis details shows why a reader needs more than estimates and p-values to evaluate the full inferential strategy.

The trial also demonstrates the role of precision. Confidence intervals communicate uncertainty around average contrasts, whereas standard deviations describe variation among participant outcomes. Sample-size illustrations can show how hypothetical planning requirements change with target effect size, but they do not recover the trial’s original design rationale or indicate observed power. Together, these distinctions support a more careful reading of registry results: statistical significance, precision, analysis choices, multiplicity, and clinical importance are related but separate questions.

18. 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 registry record does not provide a complete account of the statistical plan. It does not report the original sample-size justification, the full ANCOVA model specification, a multiplicity procedure, or whether interim analyses were planned or conducted. These gaps limit independent assessment of how the analyses were chosen and how the reported inferences should be interpreted across outcomes and comparisons.

Missing-data handling is another limitation in the posted description. The primary outcome allows Week 13 or the last post-baseline assessment, and the analysis set requires a baseline and at least one post-baseline measurement. The description begins to refer to a last-observation approach for imputation, but the full procedure is not reported in the registry record. Sensitivity analyses addressing alternative missing-data assumptions are not reported in the registry record.

The reported sponsor analysis and the unadjusted recalculation are not identical analyses. The discrepancy flag and the different 150 mg eq. point estimates underscore that the recalculation cannot substitute for the sponsor’s ANCOVA. The registry record does not give enough model detail to explain the difference fully. The sponsor’s analysis takes precedence, while the recalculations should be understood as simple comparisons of posted summaries.

Secondary outcome reporting is incomplete: the registry lists CGI-S as a secondary measure but does not report its numeric results, and it does not report a sponsor analysis for the 25 mg eq. PSP comparison. The safety information also has limits. Counts of participants affected by serious and other adverse events are listed, but the numbers at risk are not reported in the registry record; death counts are not reported in the registry record. The record therefore does not support calculation of event rates or a complete comparative safety assessment from these entries alone.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Effectiveness and Safety of 3 Fixed Doses (25 mg eq., 100 mg eq., and 150 mg eq.) of Paliperidone Palmitate in Patients With Schizophrenia — NCT00590577.
• Registry record last updated 2014-06-04; status last verified 2014-05.
• Results first posted 2009-10-05.
• 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.

22. Record Summary

This completed phase 3 study randomized participants with schizophrenia to paliperidone palmitate at 25 mg eq., 100 mg eq., or 150 mg eq., or to placebo. Total enrollment was 652. The primary outcome was change in PANSS total score from baseline to Week 13 or the last post-baseline assessment.

The sponsor reported ANCOVA comparisons of each dose with placebo. All three reported primary confidence intervals were below zero. The simple unadjusted recalculations differ from some sponsor results, and the registry flags a discrepancy; the sponsor’s own analyses take precedence. The registry also lists PSP and CGI-S as secondary outcomes, but numeric CGI-S results are not reported in the registry record.

Important details remain unreported, including the original sample-size justification, complete missing-data procedure, multiplicity handling, and full ANCOVA specification. Safety entries list affected-participant counts without numbers at risk. These limitations define how far the posted results can be interpreted.