Neoadjuvant Weekly Ixabepilone for High Risk, Clinically Localized Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neoadjuvant Weekly Ixabepilone for High Risk, Clinically Localized Prostate Cancer (NCT00828308), a na phase 2 study. The primary outcome is Prostate-Specific Antigen (PSA) Response.

2. Clinical Question

Statistically, this is a question about the observed frequency of a defined binary outcome in a single group: each participant either had a decreased PSA level at the stated assessment or did not. The record does not report the criteria for classifying a decrease, the PSA values themselves, or the number who met the endpoint. It therefore does not permit an estimate of the response frequency from the registry information alone.

3. Trial Design

The registry describes BrUOG-PROS-221 as a phase II study of neoadjuvant weekly ixabepilone for high-risk, clinically localized prostate cancer. The study is marked completed, with enrollment of 16. The recorded start is 2009-02 and primary completion is 2011-03. These dates identify the study record; they do not establish the timing of individual participants’ assessments or follow-up.

The design is listed as single group, with allocation marked NA and masking marked NONE. Thus, the registry record does not describe random assignment or a masked comparison. It lists ixabepilone at 16 mg/m2 or 20mg/m2, weekly x 3, in 4 week cycles, x 4 cycles. It does not explain how the two doses were assigned, whether dose assignment followed a prespecified rule, or how outcomes were compared between dose levels.

Prostatectomy appears among the interventions, but the record explicitly says it was standard of care and not part of the study. It was described as occurring 2-8 weeks after completion of ixabepilone. This distinction matters when interpreting what the study tested: the listed primary endpoint concerns PSA after ixabepilone, while the surgery is described as care outside the study intervention.

The record lists one outcome measure and no analyses. It does not report the study protocol, the statistical analysis plan, the rationale for the enrollment target, or details of recruitment and participant flow. The single-group design can describe outcomes among enrolled participants if results are reported, but by itself it cannot separate an observed change from other influences or establish a controlled treatment contrast.

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

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 Prostate-Specific Antigen (PSA) Response, measured over after 12 weeks of ixabepilone.

The primary endpoint is the number of participants with a decreased serum prostate-specific antigen (PSA) level after 12 weeks of ixabepilone. It is recorded as a participant count, making the outcome binary at the individual level: a participant either meets the stated decrease criterion or does not. The registry record does not report a PSA threshold, the measurement procedure, or how borderline or unavailable measurements were handled.

PSA is a biomarker associated with prostate disease, so a change in its measured level can be used as an indicator of biological response in a clinical study. That general rationale does not make PSA change equivalent to a clinical outcome, nor does it establish that a particular decrease predicts later outcomes. The endpoint’s interpretation depends on how the decrease was defined and measured, details not reported in the registry record.

The specified assessment is after 12 weeks of ixabepilone. The registry defines what was to be counted but does not give the observed count or the total number included in the endpoint analysis. Consequently, the outcome frequency and its precision cannot be described from this record. The listed endpoint also does not, on its own, provide a comparison with an untreated or standard-care group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods depend on the outcome type, design, and analysis that were actually carried out. The registry record identifies a binary primary endpoint and a single-group study, but lists no analyses. It does not describe a statistical analysis plan, so any explanation of methods below is general rather than a claim about procedures used in this trial.

What does a binary endpoint mean?

For a binary endpoint, each participant is classified into one of two categories. Here, the stated event is a decrease in serum PSA after 12 weeks of ixabepilone. A basic descriptive summary would report the number meeting that definition and the number assessed. A proportion could then describe the frequency among the assessed participants. The registry record gives neither the endpoint count nor the number assessed, so that summary cannot be reconstructed.

Endpoint definition is essential. A decrease might depend on a threshold, the baseline measurement, the timing of samples, and rules for handling repeat or missing measurements. The registry record defines the endpoint in broad terms as a decreased serum PSA level but does not report those operational details. Without them, readers cannot determine exactly how a participant would be classified or whether the same rule was applied consistently.

What would an interval estimate communicate?

In general, a confidence interval expresses the uncertainty around an estimated quantity, such as a response proportion. It is not a range that guarantees the true value lies within it; rather, it describes the behavior of an estimation procedure under repeated sampling assumptions. With a small group, interval estimates can be wide, and the chosen method can matter, especially for a binary outcome near the boundaries of its possible range. No response estimate or interval is reported in the registry record for this endpoint, so no trial-specific precision statement can be made.

Why does the design affect interpretation?

A single-group study can estimate a descriptive outcome frequency when the outcome data are available. A randomized comparison addresses a different question: whether outcomes differ between assigned groups, subject to the design and analysis assumptions. This record lists a single-group model, allocation as NA, and no masking. It therefore does not document a randomized control comparison. Comparing an outcome with an external benchmark would require a specified benchmark and assumptions about comparability; neither is reported in the registry record.

The record mentions two ixabepilone dose levels, but does not explain their assignment or provide dose-specific results. It is therefore not possible to determine whether participants at the different doses formed planned comparison groups, whether dose was escalated or selected by another rule, or whether any dose comparison was performed. The mere listing of two doses is not evidence of a comparative analysis.

How should planning calculations be distinguished from results?

General sample-size calculations ask how many participants might be needed to detect a specified effect under chosen assumptions. The registry’s stated planning illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a fraction of the observed effect. The record does not identify these assumptions as the trial’s own design justification. Such calculations are planning illustrations, not observed power, and do not supply a missing trial result.

The two-arm assumptions also differ from the recorded single-group model. They may be useful for illustrating a hypothetical future comparison, but they should not be read as the allocation or analysis actually used in this study. The registry record does not report the trial’s sample-size justification, target effect, or any interim analysis. These details cannot be inferred from enrollment or phase alone.

What can be concluded from the posted analysis information?

The record lists one outcome measure and zero analyses. This means it describes the endpoint but does not give an analysis result for it. It does not report a statistical test, an adjusted model, a confidence interval, or a method for handling potential covariates. Nor does it identify a prespecified primary analysis population. Statistical significance, effect size, and precision are consequently unavailable for the primary outcome.

For a binary endpoint, the count and denominator are both needed to understand the observed frequency; an inferential estimate also depends on the method and assumptions. The denominator may differ from total enrollment if some participants lack an assessment, but whether that occurred is not reported in the registry record. It would be inappropriate to substitute enrollment for an endpoint denominator without a reported analysis population or completion count.

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("Ixabepilone")
n      <- c(16)
events <- c(14)
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  Ixabepilone  16  14  87.5  61.7  98.4  64.0  96.5  63.6  96.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure, the number of participants with decreased serum PSA after 12 weeks of ixabepilone, and lists no analyses. It does not describe a multiplicity strategy, such as adjustment for testing multiple outcomes or comparisons, and it does not report a testing hierarchy. With no analysis results listed, there is no basis for evaluating how multiple statistical tests may have affected any reported inference. The absence of a reported adjustment is not evidence that no such procedure was used; the procedure is not reported in the registry record.

Missing-data handling is also not described. The record gives enrollment of 16 but does not state how many participants had an evaluable PSA assessment, whether any endpoint measurements were missing, or how missing observations were handled. In general, a missing outcome can affect both the denominator and interpretation of a response frequency. Complete-case analysis, imputation, or another approach would each require details that are not reported in the registry record.

The analysis population is not specified. The record does not say whether all enrolled participants, only those who started ixabepilone, or another defined group contributed to the primary endpoint. It also does not report participant flow, treatment discontinuations, or protocol deviations. Therefore, enrollment cannot be assumed to equal the endpoint analysis population.

These omissions matter because the endpoint count, denominator, and analysis population are needed to interpret the primary outcome. No assumptions about missingness, multiplicity, or analysis-set membership should be substituted for the absent registry information.

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: pneumonia (3) with normal anc, post infuection bronchitis (3), wheezing (3) (6.2%).

The registry reports 16 participants at risk for other adverse events and 16 affected. That indicates that the record counted all 16 in the at-risk group as having at least one event in this broader category. It separately lists 16 at risk for serious adverse events and 1 affected. These are participant-level summaries in the registry record; they do not describe the duration, severity beyond the serious classification, or clinical course of each event.

The serious-event term entry reads “pneumonia (3) with normal ANC, post infuection bronchitis (3), wheezing (3)” and is paired with 6.2%. The registry record does not clarify the precise denominator or how the terms and parenthetical counts relate to the participant-level serious-event count. The term entry should therefore be read as a registry listing, not as a basis for reconstructing unique participants or event totals.

Deaths are listed as null, so the registry record does not report a death count. A null entry should not be interpreted as confirmation that no deaths occurred. These safety summaries do not establish comparative risk because the study is single group and no control comparison is recorded.

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

The record establishes that a phase II, single-group study of neoadjuvant ixabepilone was registered for high-risk, clinically localized prostate cancer, with enrollment of 16 and a primary endpoint defined as decreased serum PSA after 12 weeks. It also reports participant-level adverse-event summaries. These details describe the study’s structure and the information entered in the registry.

The record does not report the primary endpoint count, the number assessed, PSA measurements, or an analysis. It therefore does not show how often the stated PSA response occurred or how precisely that frequency could be estimated. No efficacy conclusion can be drawn from the endpoint definition alone. Likewise, the status marked completed does not supply an outcome result.

Even if a response frequency were available, a single-group observation would describe participants in that group rather than establish a causal contrast with another treatment or with no study drug. The record does not document randomization, a comparator group, or a masked assessment. The surgery mentioned in the treatment description is identified as standard of care and not part of the study, so it should not be mistaken for a randomized comparator or an experimental study intervention.

The reported safety counts indicate that the registry recorded at least one other adverse event for each participant in the at-risk group, and a serious adverse event for one participant in its at-risk group. Those figures are descriptive, with no control group for comparison. The serious-event terms and the death field require caution because the record does not fully clarify the term-level counts and lists deaths as null.

Overall, the registry record supports a description of the planned question and limited safety information, but not a quantified PSA-response result or a controlled estimate of treatment effect. Missing outcome and analysis details remain material to interpretation.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between an endpoint definition and an endpoint result. A registry can identify what investigators intended to measure, including the timing and event definition, without reporting the observations needed to estimate the outcome. Here, PSA response is clearly named as the primary measure, but the response count and its analysis are absent.

The single-group design also clarifies why design information must accompany outcome summaries. A response count, if reported, could describe the study group, but a treatment contrast requires an appropriate comparator and an analysis that reflects the design. The listing of two ixabepilone doses does not establish a dose comparison, because assignment and dose-specific analyses are not described.

The record is also a reminder that total enrollment, endpoint denominator, and safety denominators answer different questions. Enrollment is 16, while the registry separately reports the numbers at risk for adverse-event categories. It does not identify the number assessed for the primary PSA endpoint. Keeping these quantities distinct avoids treating the enrollment count as an endpoint denominator without evidence.

Finally, registry completeness influences what can be learned from a trial record. Missing analysis methods, missing-data rules, and the absent primary outcome result limit assessment of precision, potential bias, and reproducibility. These are not merely technical details: they determine which statistical conclusions are supported and which remain unavailable.

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.

The registry record does not report the primary PSA-response count, the number with an evaluable assessment, or any analysis of the primary outcome. This prevents calculation or interpretation of the observed response frequency and its precision. It also does not report PSA values, the threshold defining a decrease, or the measurement and classification procedures.

The study is listed as single group, with allocation NA and masking NONE. The registry does not identify a concurrent comparator or describe random assignment. The presence of two ixabepilone dose levels is not accompanied by information about dose assignment or dose-specific results, so a dose contrast cannot be evaluated from the record.

Enrollment is reported as 16, but participant flow and the primary analysis population are not described. Missing endpoint data, discontinuations, protocol deviations, and handling of missing observations are not reported in the registry record. The statistical analysis plan, sample-size justification, interim analyses, and multiplicity procedures are also not reported.

Safety reporting is limited to the listed at-risk and affected counts and a serious-event term entry. The record does not clarify how the terms and parenthetical counts relate to unique participants, and deaths are listed as null. The registry also describes prostatectomy as standard of care and not part of the study, which limits interpretation of the intervention to the ixabepilone regimen and the stated PSA endpoint rather than a study-controlled surgical comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Neoadjuvant Weekly Ixabepilone for High Risk, Clinically Localized Prostate Cancer — NCT00828308.
• Registry record last updated 2022-03-08; status last verified 2022-02.
• Results first posted 2013-11-01.
• 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

NCT00828308 is a completed phase II, single-group study titled “Neoadjuvant Weekly Ixabepilone for High Risk, Clinically Localized Prostate Cancer.” The registry records enrollment of 16, a start of 2009-02, and primary completion in 2011-03. It lists ixabepilone at 16 mg/m2 or 20mg/m2, weekly x 3, in 4 week cycles, x 4 cycles.

The primary endpoint is the number of participants with decreased serum PSA after 12 weeks of ixabepilone. The endpoint result and analyses are not reported in the registry record. Prostatectomy is described as standard of care and not part of the study. Safety entries report 16 of 16 affected for other adverse events and 1 of 16 for serious adverse events; deaths are listed as null.