Sequential Vaccinations in Prostate Cancer Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sequential Vaccinations in Prostate Cancer Patients (NCT00060528), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants With an Immune Response.

2. Clinical Question

This is an immunologic-outcome question, not a direct test of tumor control or survival. The registry also lists PSA-specific T-cell change by ELISPOT assay as a secondary objective and says objective anti-tumor responses were to be documented. Those aims provide context, but the posted primary result is a count of participants meeting the immune-response definition. The record does not report inferential analyses comparing the groups or establish whether any observed differences are distinguishable from chance variation.

3. Trial Design

The study is identified as a Phase I/II pilot study with randomized allocation, no masking, and a parallel design. The registry reports enrollment of 32 participants and a completed status. The recorded study start was 2003-05-22, and the primary completion date was 2006-03-07. The sponsor was the National Cancer Institute.

The four posted groups were No GM, Rec-hGM, rF-GM (10^7pfu), and rF-GM (10^8). The No GM group received no GM-CSF. The Rec-hGM description specifies recombinant human GM-CSF (Sargramostim) at 100mcg/day on days 1-4 following each vaccine, given subcutaneously at the vaccine site. The two rF-GM descriptions specify recombinant fowlpox GM-CSF on day one at the listed dose, also given subcutaneously at the vaccine site. The study title and intervention descriptions identify PROSTVAC-F/TRICOM and PROSTVAC-V/TRICOM as the sequential vaccination approaches under study.

The primary outcome counts are reported for 8 participants in No GM, 6 in Rec-hGM, 7 in rF-GM (10^7pfu), and 8 in rF-GM (10^8). The safety denominators differ for Rec-hGM: the registry lists 9 participants at risk for adverse events in that group. The reason for this difference is not reported in the registry record. A sample-size justification, allocation procedure, details of sequence generation, and masking rationale are not reported in the registry record. The word “pilot” identifies the study’s stated character, but does not by itself reveal how its enrollment target was selected.

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 Number of Participants With an Immune Response, measured over 48 months.

The primary endpoint is the number of participants with an immune response. The registry defines a response as an enhanced PSA-specific T-cell immune response at least twofold after vaccination compared with the pre-vaccination response. Peripheral blood mononuclear cells were collected by apheresis before vaccination and after approximately three months of therapy. The record lists a timeframe of 48 months, but it does not explain how that timeframe relates to the described blood-collection schedule.

This endpoint is a binary participant-level outcome: each participant either meets the response definition or does not. Immune assays can provide evidence of a biological response to vaccination, which is relevant to the study’s primary immunologic objective. However, an immune response is not the same outcome as a change in tumor burden, an objective anti-tumor response, or survival. Those outcomes are listed separately among the secondary measures.

The reported results are counts: 2 participants in No GM, 4 in Rec-hGM, 4 in rF-GM (10^7pfu), and 3 in rF-GM (10^8) had an immune response. Counts indicate how many participants met the definition in each group; they do not, on their own, express the uncertainty around a group’s response rate or establish a treatment-group difference. The registry does not report confidence intervals or a statistical comparison for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary because the registry classifies participants according to whether they meet the defined immune-response threshold. A participant meeting the threshold is counted as having an immune response; otherwise, the participant is not included in that response count. Reporting the number with the outcome alongside the group size makes the observed data interpretable without requiring a model. It does not, by itself, measure uncertainty or test a treatment contrast.

What can a count tell us?

A count answers how many observed participants met the response definition in a group. A denominator is needed to understand the count relative to the number assessed. Here, the primary endpoint counts are reported with group sizes: 2 of 8 for No GM, 4 of 6 for Rec-hGM, 4 of 7 for rF-GM (10^7pfu), and 3 of 8 for rF-GM (10^8). The underlying response percentages are not stated in the registry result. No additional percentage or contrast is calculated in this interpretation.

General statistical explanation: a proportion is an estimate of the probability of an event in a population. Its precision depends in part on how many observations contribute to it and on the observed event pattern. A confidence interval is a range of values compatible with the data under a specified statistical method; it communicates uncertainty around an estimate. The registry does not report confidence intervals for the immune-response results, so the precision of the group estimates is not quantified in the posted result.

How should group differences be assessed?

Because the study has multiple parallel groups, a treatment comparison would need to specify which groups are being contrasted and how the binary outcome is analyzed. Possible methods for binary outcomes include comparing proportions or fitting a regression model, but the registry record does not report which method, if any, was used for inferential comparisons. It also does not report effect estimates, p-values, or confidence intervals for group contrasts. The descriptive counts therefore do not establish statistical evidence of a difference.

General statistical explanation: random allocation can help make groups comparable in expectation, but it does not guarantee that small groups will have similar characteristics. Random variation can create apparent differences even when underlying effects are alike. An analysis plan ordinarily specifies the primary contrast, the treatment of missing measurements, and the model or test used. Those details are not reported in the registry record for this study.

What does the sample-size illustration mean?

The planning illustration is not the trial’s original design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated planning quantity is the total number of events; for other outcomes, it is participants per arm. These are planning assumptions, not observed trial results, and an illustrative sample size is not observed power. The record does not report the trial’s own sample-size justification or show that the illustration governed enrollment.

General statistical explanation: a sample-size calculation depends on the anticipated effect, variability or event frequency, significance criterion, desired power, and design assumptions. If an effect is smaller than the one used as a planning target, a larger study may be needed to detect it with comparable power. The illustration’s assumptions should therefore not be mistaken for a prespecified protocol plan, particularly when the record does not report that plan.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model underestimates variability, its uncertainty estimates can be too narrow and its tests can be too optimistic. This concept can matter for count outcomes or clustered and repeated observations. The primary endpoint is reported as participant counts for a binary outcome, and the registry does not report a model or an over-dispersion assessment. No conclusion about over-dispersion can be drawn from the posted results.

The record reports 0 analysis results and gives descriptive participant counts for the primary endpoint. It does not report whether the analysis was adjusted, whether the outcome was assessed at a prespecified time for every participant, or how repeated immune measurements were handled beyond the definition’s pre- and post-vaccination collection description. There are no posted recalculated comparisons to distinguish from a sponsor analysis. Accordingly, the statistical interpretation remains descriptive: the reported counts document observed responses, while inferential uncertainty and comparative effects are not reported in the registry record.

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("No GM", "Rec-hGM", "rF-GM (10^7pfu),", "rF-GM (10^8)")
n      <- c(8, 6, 7, 8)
events <- c(2, 4, 4, 3)
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  No GM  8  2  25.0  3.2  65.1  7.1  59.1  7.5  60.0
ARM  Rec-hGM  6  4  66.7  22.3  95.7  30.0  90.3  29.0  90.1
ARM  rF-GM (10^7pfu),  7  4  57.1  18.4  90.1  25.0  84.2  24.5  84.3
ARM  rF-GM (10^8)  8  3  37.5  8.5  75.5  13.7  69.4  13.7  70.1

11. Multiplicity, Missing Data and Analysis Populations

The study has several treatment groups and multiple stated outcomes. The primary objective concerns immune response, while secondary measures include a PSA decrease of at least 30%, objective response, overall survival, and adverse events. When several outcomes or group comparisons are examined, multiplicity can increase the chance of finding an apparently unusual result by chance. General statistical practice may address this through a prespecified hierarchy or an adjustment procedure, but such an approach is not reported in the registry record.

The record reports no analysis results for the posted measures beyond the primary endpoint counts. It does not describe which pairwise or overall comparisons were planned, whether any adjustment for multiple comparisons was used, or whether analyses were exploratory. Without that information, the immune-response counts cannot be treated as the result of a specified confirmatory comparison among the GM-CSF groups.

Missing-data handling and analysis populations are also not reported in the registry record. The primary outcome lists group sizes of 8, 6, 7, and 8, whereas the safety denominators list 9 for Rec-hGM and the same group sizes as the primary outcome for the other groups. The reason for the Rec-hGM denominator difference is not reported. The record does not say whether participants without an evaluable immune assessment were excluded, whether any missing values were imputed, or whether the primary analysis followed an intention-to-treat population. These omissions limit assessment of whether the endpoint counts represent all randomized participants or only those with an available assessment.

General statistical explanation: an intention-to-treat analysis generally retains participants in their assigned groups, whereas an evaluable-participant analysis may include only those with outcome data. The choice can affect interpretation when outcome availability differs among groups. The registry record does not identify which population definition was used.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: myalgia (muscle pain) (25.0%), bone pain (22.2%), anorexia (14.3%), dehydration (14.3%), supraventricular arrhythmias (supraventricular tachycardia (svt)/atrial fibrillation/flutter) (12.5%).

The serious-adverse-event results are reported as affected participants among those listed at risk: 1 of 8 for No GM, 3 of 9 for Rec-hGM, 2 of 7 for rF-GM (10^7pfu), and 3 of 8 for rF-GM (10^8). The registry lists 0 deaths in each group. These figures describe the recorded safety counts; they do not establish that the groups have different underlying risks. The groups are small, and no confidence intervals or comparative statistical analyses are reported.

The registry separately reports other adverse events affecting all participants listed at risk in each group: 8 of 8, 9 of 9, 7 of 7, and 8 of 8, respectively. Serious and other adverse-event categories are distinct in the record and should not be combined into a single count. The reason for the larger Rec-hGM safety denominator relative to its primary-outcome group size is not reported in the registry record.

Myalgia (muscle pain) is listed at 25.0%, bone pain at 22.2%, anorexia at 14.3%, dehydration at 14.3%, supraventricular arrhythmias at 12.5%, and hemoglobin at 12.5% among the top serious-event terms. The record does not specify the denominator for these percentages or clarify whether terms represent participants or event occurrences. They should therefore be read as reported term frequencies, not as comparable group-specific risks.

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

The results establish that immune responses meeting the registry’s at-least-twofold definition were recorded in each of the four groups. The counts are 2 in No GM, 4 in Rec-hGM, 4 in rF-GM (10^7pfu), and 3 in rF-GM (10^8). The record also reports the group sizes used for those primary-outcome results. These data give a descriptive account of the observed endpoint in this pilot study.

They do not establish that one GM-CSF approach produces a greater immune response than another. The registry reports no comparative effect estimates, confidence intervals, or hypothesis tests for the primary endpoint. Because the groups are small and unequal in size, raw counts alone are not a sufficient basis for judging the magnitude or precision of a between-group difference. No conclusion about the probability of a response in a broader population can be established from these counts alone.

An immune response is a laboratory-based outcome in this study. It is not equivalent to a reduction in PSA, an objective tumor response, or longer overall survival. Those outcomes are listed as secondary measures, but their results are not reported in the registry record. The immune-response counts therefore do not establish clinical benefit, lack of clinical benefit, or the effect of vaccination on any of those outcomes.

The safety record describes serious-event counts and other adverse-event counts, along with selected serious-event terms. It lists no deaths in the reported groups. These figures are descriptive; without definitions, fuller event details, and comparative analyses, they do not support a definitive safety comparison among the groups.

The record also does not explain the discrepancy between the Rec-hGM primary-outcome group size and safety denominator. It does not report missing-data methods, analysis populations, multiplicity handling, or the statistical plan. These gaps limit reproducibility and make it difficult to know exactly which participants contributed to each result. The most supportable reading is therefore narrow: the registry records the stated immune-response and safety counts, while the precision and comparative meaning of those counts remain unquantified.

14. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early clinical research: a biologically relevant endpoint can be reported as simple participant counts, yet those counts may not answer whether treatment groups differ in a reliable way. The primary endpoint is directly connected to the study’s immunologic objective, and its definition uses a pre- and post-vaccination comparison for each participant. That makes the endpoint interpretable as an immune-response measure, while keeping it distinct from tumor response and survival.

The registry also highlights why denominators matter. The primary-outcome counts use group sizes of 8, 6, 7, and 8, while the safety record lists 9 participants at risk in Rec-hGM. Without an explanation of that difference, readers cannot confidently assume that the primary and safety results refer to the same participant populations. Transparent reporting of outcome availability and analysis populations is important even when the number of participants is modest.

Finally, the record separates descriptive observations from statistical inference. The outcome counts are available, but comparative estimates and their uncertainty are not reported. A planning illustration based on stated assumptions cannot fill that gap or stand in for an original sample-size justification. Nor does it constitute observed power. This distinction matters when interpreting pilot studies: their counts can inform understanding of what was observed, but the absence of inferential results constrains claims about group differences.

The study is therefore useful as an example of how endpoint definition, denominators, uncertainty, and analysis transparency shape interpretation. The registry’s immunologic result is a count-based description, not a complete statistical comparison of vaccination strategies.

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 primary result is reported as counts without confidence intervals, p-values, or effect estimates comparing groups. This prevents evaluation of the precision of the observed group results and of the statistical evidence for between-group differences. The group sizes are small, and the endpoint group sizes are unequal, which makes raw count comparisons especially limited.

The registry does not report the original sample-size justification, a statistical analysis plan, or the planned primary contrast. It does not state how randomization was generated or concealed, or how missing outcome measurements were handled. The status is randomized and unmasked, but additional details about allocation and conduct are not reported in the registry record.

The Rec-hGM primary-outcome group size is 6, while the corresponding safety denominator is 9. The other listed safety denominators match their primary-outcome group sizes. The registry does not explain this difference, identify the analysis populations, or say whether some participants lacked an evaluable immune response. That uncertainty limits direct alignment of efficacy and safety summaries.

The endpoint description states that blood samples were collected before vaccination and after approximately three months of therapy, while the listed timeframe is 48 months. The relationship between those timing statements is not explained. The registry also does not report the results of the listed secondary outcomes, including PSA decrease, objective response, and overall survival, so they cannot be used to contextualize the immunologic finding.

Selected serious-event terms are given with percentages, but their denominators and whether they count participants or events are not specified. The record also does not report a multiplicity strategy for the multiple groups and outcomes. These limitations make the posted results descriptive rather than a fully interpretable comparative analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sequential Vaccinations in Prostate Cancer Patients — NCT00060528.
• Registry record last updated 2017-10-26; status last verified 2017-09.
• Results first posted 2012-02-23.
• 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

NCT00060528 is a completed randomized, unmasked Phase I/II pilot study of sequential vaccinations in men with prostate cancer. The registry reports enrollment of 32 participants, a start date of 2003-05-22, and primary completion on 2006-03-07. The study examined vaccine regimens involving PROSTVAC-F/TRICOM and PROSTVAC-V/TRICOM with different GM-CSF approaches.

The primary endpoint was the number of participants with an at-least-twofold enhanced PSA-specific T-cell immune response. The posted counts were 2 of 8 for No GM, 4 of 6 for Rec-hGM, 4 of 7 for rF-GM (10^7pfu), and 3 of 8 for rF-GM (10^8). No inferential analysis results are reported. Safety summaries list serious adverse events, other adverse events, selected serious-event terms, and 0 deaths in each group. Missing-data methods, analysis populations, multiplicity handling, and the reason for the differing Rec-hGM safety denominator are not reported in the registry record.