Accelerated Immunization to Induce Cytomegalovirus Immunity in Stem Cell Donors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Accelerated Immunization to Induce Cytomegalovirus Immunity in Stem Cell Donors (NCT00353977), a na phase 2 study. The primary outcome is Cellular Immune Response in Vaccine Recipients.

2. Clinical Question

The clinical rationale is the possibility of CMV reactivation in people with weakened immune systems, including transplant recipients. The study aimed to boost immunity in donors, with the stated intention of helping prevent reactivation in recipients. That rationale describes the intended purpose; it is not evidence that recipient outcomes were measured or improved in this trial.

The available record is most informative about the study’s structure and what it chose to measure. It identifies the intervention, endpoint timeframe, and a limited set of adverse-event counts. It does not provide the result needed to quantify the primary immune response, nor does it report a comparison that could separate a vaccine effect from other influences.

3. Trial Design

This was a completed phase 2 pilot trial of an accelerated ALVAC-pp65 immunization schedule. The registry records an enrollment of 38 and classifies the study as single-group, with allocation listed as not applicable and masking listed as none. Participants were assigned to the vaccinated group; no concurrent control arm is described. The record identifies the intervention as ALVAC-CMV (vCP260).

The study’s purpose was to evaluate whether the schedule could generate CMV-specific immunity in seronegative transplant donors and healthy volunteers and augment existing immunity in seropositive transplant donors. The primary outcome was described as cellular immune response in vaccine recipients, with a Day 45 timeframe. The record also gives a population description listing 11 CMV-seropositive subjects and 3 seronegative subjects. It does not explain how these subjects relate to the enrollment figure, or specify which participants contributed to the primary endpoint analysis.

Because there is no concurrent comparator, the design can describe what was recorded among vaccinated participants but cannot provide a randomized estimate of the difference between vaccination and a control condition. The absence of masking is also part of the design context: the record does not indicate that participants or investigators were masked to the intervention. It does not report whether outcome assessment was masked.

The registry describes the study as a pilot. A detailed protocol, recruitment flow, dose schedule, follow-up beyond the primary timeframe, and rationale for the enrollment target are not reported in the registry record. Nor is a statistical analysis plan reported. These omissions limit what can be inferred about how the study was intended to handle eligibility, follow-up, endpoint assessment, and analysis. The design should therefore be read as a small, single-group investigation of an immune-response question, rather than as a randomized comparison of clinical outcomes.

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

Analysis population for the primary outcome, as defined in the registry: 11 subjects were CMV seropositive and 3 subjects were seronegative.

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 Cellular Immune Response in Vaccine Recipients, measured over Day 45.

The primary endpoint is titled “Cellular Immune Response in Vaccine Recipients” and has a Day 45 timeframe. The record classifies it as a count of participants with an event. Its description frames the endpoint around two aims: generating CMV-specific immunity in seronegative transplant donors and healthy volunteers, and augmenting CMV-specific immunity in seropositive transplant donors.

Cellular immune responses are relevant to the study’s stated rationale because the intervention was intended to stimulate CMV-specific immunity. An endpoint focused on immune response can assess whether the vaccination schedule is associated with the targeted biological response, rather than directly measuring whether CMV reactivates in transplant recipients. The registry does not state that recipient reactivation or other recipient clinical outcomes were primary endpoints.

The record does not define the threshold or assay used to classify a participant as having a response, provide a numerical response count, or report a result estimate. Although the endpoint is described as a number of participants, the outcome value itself is not reported in the registry record. The record also does not state whether the same response definition was applied to seropositive and seronegative participants or how results were summarized across those groups.

Without a response definition and observed result, the endpoint’s measurement properties and magnitude cannot be evaluated from this record. The stated biological aim and timeframe explain what the trial set out to assess, but they do not establish how many participants responded or how precisely any response rate was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary outcome as a binary count: participants with an event. In general, a binary outcome places each participant into a response category, such as response or no response, according to a defined rule. A count of participants in one category can be useful for describing an outcome, but interpreting it requires the number assessed and the rule used to assign the category. The registry record does not report the cellular response rule, the primary endpoint count, or its analysis denominator.

What does a single-group design estimate?

A single-group study records outcomes among participants who receive the intervention. It can describe the observed experience of that group, assuming outcomes and follow-up are adequately documented. Without a concurrent control group, it does not directly estimate how outcomes would differ under another intervention or under no intervention. Participants can differ from people who were not enrolled, and outcomes can also reflect natural variation, measurement procedures, or events occurring over time. Randomized allocation is often used to make groups comparable on average; this trial is not recorded as randomized and has no like-for-like control group.

Accordingly, any immune-response observations from this study would need to be interpreted as observations in vaccinated participants, not as a randomized treatment contrast. The registry does not report a comparison with an unvaccinated group, an alternative schedule, or another vaccine. The study’s single-group structure is not a flaw that can be repaired by statistical adjustment alone: without comparator data, the direct comparative effect is not identified by the design.

What would an estimate and confidence interval mean?

In general, a point estimate summarizes the observed outcome in the participants analyzed. A confidence interval expresses the statistical uncertainty around an estimate under the assumptions of the method used. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. Neither an estimate nor its interval can be recovered from the registry’s endpoint title or from enrollment alone. The registry record does not report a primary response estimate or confidence interval, so precision cannot be assessed for that outcome.

A confidence interval would also not remove limitations in the design. It describes sampling uncertainty under a statistical model; it does not account automatically for bias from participant selection, missing outcomes, an unclear response definition, or lack of a concurrent control. A precise estimate of an outcome in a single group would still not provide a randomized comparison with another condition.

What do the safety counts convey?

The registry reports event counts and the number at risk for the vaccinated group. In general, a count describes how many events or participants with events were recorded, while the at-risk number indicates the group size used for that safety measure. The record reports 0 serious adverse events among 38 at risk and 14 other adverse events among 38 at risk. These categories should not be combined: they describe different event classifications. The registry does not provide event terms for the serious adverse-event category or details identifying the other events.

These counts do not show event timing, severity within the other-event category, relatedness to vaccination, or a comparison with background event experience. The registry record also does not explain the safety follow-up period. Therefore, the reported counts are descriptive, and they cannot by themselves establish a causal relationship or comparative safety profile.

How should planning calculations be read?

General sample-size calculations are planning illustrations: they ask how much information a future study might need to detect an assumed effect under stated statistical conditions. They are not evidence about what the completed trial observed, and they are not observed power. The planning assumptions described for this record use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of an observed effect. Those assumptions describe a hypothetical two-arm calculation, whereas the trial itself is recorded as single-group with no randomized comparator. The planning exercise should not be mistaken for the trial’s design or for an analysis of its primary endpoint.

In general, a planning calculation depends on choices such as the outcome, the effect considered meaningful, the variability or event frequency, the significance level, and the desired power. If an assumed effect is smaller, more participants may be needed to detect it under otherwise similar assumptions; this is a general statistical relationship, not a result reported for this trial. The registry does not report the trial’s own sample-size justification, so the planning illustration cannot establish whether the enrollment target was chosen for a particular power or precision goal.

What statistical analyses are documented?

The registry record reports no statistical analyses for the primary outcome. It does not provide a model, a hypothesis test, an adjusted estimate, a confidence interval, or subgroup analysis results. The count-based endpoint classification indicates the general form of the measure but does not tell readers which statistical method was used. In the absence of a reported result and method, no inferential conclusion can be reconstructed from the endpoint description.

For a binary outcome, general analysis options may include reporting the observed count and denominator, estimating a response proportion with an interval, or fitting a model when the design and data justify one. The suitable method depends on the response definition, the number assessed, missingness, and whether comparisons are intended. Those details are not reported in the registry record. No new estimate should be inferred from the enrollment figure or subgroup descriptions.

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("Alvac pp65 Vaccine")
n      <- c(14)
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  Alvac pp65 Vaccine  14  14  100.0  76.8  100.0  78.5  100.0  78.2  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary outcome measure, but does not report a statistical analysis for it. It does not describe a prespecified testing hierarchy, a family of secondary hypotheses, or an adjustment for multiple comparisons. The number of analyses recorded is zero. This does not establish whether additional analyses were planned or conducted outside the posted record; their status is not reported in the registry record.

Multiplicity arises when several hypotheses or outcomes are tested and the chance of a false-positive finding across the collection of tests becomes a concern. In general, a prespecified strategy can define which outcomes are confirmatory and how multiple tests are handled. No such strategy is reported, so the record does not support an assessment of multiplicity control. Because no primary endpoint result or p-value is reported, there is also no inferential result to interpret in light of multiplicity.

Missing-data handling is not reported in the registry record. It is not stated how many participants had an endpoint measurement at Day 45, how incomplete measurements were treated, or whether participants who did not complete follow-up were included in an analysis. The record also does not specify an intention-to-treat population, a per-protocol population, or another analysis population. The enrollment figure and the population description do not, by themselves, establish who was included in the primary endpoint analysis.

In general, missing outcome data can affect interpretation if the people with measurements differ systematically from those without them. The direction and magnitude of any such effect depend on why data are missing and on the analysis method. Since the registry does not report completeness or handling, the impact of missing data cannot be assessed. The record also does not give a protocol-level analysis plan, so it is not possible to determine from the registry whether outcomes were analyzed as originally planned.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

For the vaccinated group, the registry reports 0 serious adverse events among 38 at risk. It separately reports 14 other adverse events among 38 at risk. These are descriptive counts from the single-group safety record. They should not be treated as a comparison between vaccination and another treatment or no treatment.

The record does not list serious adverse-event terms, and the serious-event term list is empty. It also does not identify the types of other adverse events in the information reported. The counts therefore do not show what events occurred, when they occurred, how severe the other events were, or whether investigators considered them related to vaccination. A count of zero recorded serious adverse events is not evidence that no risk exists; it states what the registry reports for this group during the recorded safety assessment.

The number at risk gives context for the count, but interpretation also depends on follow-up duration and completeness. The safety follow-up period and handling of missing safety information are not reported in the registry record. Without a comparator and fuller event detail, these figures cannot establish a relative safety profile or support a causal conclusion.

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

The registry record establishes that a completed phase 2 pilot evaluated an accelerated ALVAC-pp65 schedule in a single vaccinated group. It identifies the intended immune-response question and a Day 45 primary timeframe. It also reports the safety counts for serious and other adverse events. These details describe the study’s aims and recorded observations, but the primary numerical result is not reported.

The result does not show how many participants developed or augmented CMV-specific cellular immunity, because the registry does not report the endpoint count, denominator, or response definition. It also does not quantify the precision of an immune-response estimate. The number enrolled is not a substitute for the number assessed for the primary endpoint, and the registry does not state which participants were included in an endpoint analysis.

The study does not provide a randomized comparison. Therefore, the record cannot establish whether the observed immune response, if measured, differed from what would have occurred without vaccination or under another schedule. The stated intention to boost donor immunity and help prevent recipient CMV reactivation is a rationale, not a demonstrated recipient outcome. The registry does not report a recipient outcome that would allow that intended downstream effect to be assessed.

The safety counts are limited to the vaccinated group and do not establish comparative risk. The absence of a serious adverse-event count in the posted record should not be read as proof that serious harms are impossible, nor do the other adverse-event counts identify event types or causality. Follow-up duration is not reported.

Overall, the record supports a cautious description of a pilot study’s design and a limited safety summary. It does not support a numerical conclusion about primary immune response, a comparative treatment-effect estimate, or a conclusion about prevention of CMV reactivation in transplant recipients. These are limits of what the registry record reports, not evidence for or against the biological rationale.

14. Why This Trial Matters Statistically

This trial raises statistical issues that are common in early studies of biological responses. A pilot may focus on whether an intervention can generate a measurable response and whether the planned assessment is feasible. Interpreting such a study depends on clear outcome definitions, complete measurements, and an appropriate description of who was assessed. The registry record gives the endpoint title and timeframe but not the response rule or numerical result, leaving those central interpretive details unavailable.

The single-group structure also matters. A response observed after vaccination can be described, but without a concurrent comparison it cannot be cleanly separated from changes that might occur for other reasons. This distinction is fundamental: an observed outcome in a treated group and an estimated effect relative to a comparator are different statistical quantities. The record identifies no randomized control comparison, so it should not be read as one.

The distinction between immune response and clinical outcome is also important. The trial’s primary question concerns cellular immunity among donors and healthy volunteers, while the stated motivation includes reducing the possibility of reactivation in transplant recipients. A biological measure can be relevant to that aim without directly demonstrating a recipient benefit. The registry does not report recipient outcomes.

Finally, numerical reporting determines whether readers can assess uncertainty. Counts, denominators, response definitions, and intervals each contribute different information. The available registry record reports some safety counts, but no primary response result, analysis method, or precision measure. The absence of these elements limits interpretation regardless of the trial’s rationale. Statistically, the clearest conclusion is about the evidence available in the record: it describes the question and design, but does not quantify the primary endpoint or establish a comparative effect.

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 trial-specific limitations constrain interpretation. First, the study is recorded as single-group, with no randomized control arm and no masking. The vaccinated group therefore cannot serve as a controlled estimate of what would have happened under another condition. The registry does not report outcome-assessor masking.

Second, the primary endpoint is not reported numerically. The record names cellular immune response and gives Day 45 as the timeframe, but does not define the response threshold or describe the measurement method. Without the endpoint result, denominator, and definition, readers cannot assess the frequency or precision of response.

Third, the population description is incomplete for interpreting the endpoint. It lists 11 seropositive and 3 seronegative subjects, while the overall enrollment is 38. The record does not explain how these descriptions relate to each other, whether all enrolled participants contributed endpoint data, or how healthy volunteers were represented in the analysis. This should not be resolved by assuming an unreported analysis population.

Fourth, statistical methods, missing-data handling, and the analysis population are not reported in the registry record. No inferential result is provided. The record also does not report the trial’s own sample-size justification. The described planning assumptions concern an illustrative two-arm calculation and do not alter the single-group design.

Finally, safety information is limited to group-level counts. Event descriptions, relatedness, timing, follow-up duration, and comparative safety data are not reported. These limitations apply to the registry information available and do not establish what may or may not have been documented elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Accelerated Immunization to Induce Cytomegalovirus Immunity in Stem Cell Donors — NCT00353977.
• Registry record last updated 2014-07-08; status last verified 2014-06.
• Results first posted 2014-07-08.
• 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 describes a completed phase 2 pilot of an accelerated ALVAC-pp65 schedule, also identified as ALVAC-CMV (vCP260). The study enrolled 38 participants and used a single-group, unmasked design. Its primary question concerned cellular immune response at Day 45 in relation to generating or augmenting CMV-specific immunity.

The record does not report a numerical result for the primary endpoint, its response definition, or a statistical analysis. It lists 11 seropositive and 3 seronegative subjects in the endpoint population description, without explaining their relation to the overall enrollment or the analysis population.

For safety, the vaccinated group had 0 serious adverse events among 38 at risk and 14 other adverse events among 38 at risk. Event details and comparative safety data are not reported. The registry therefore documents the trial’s design and limited safety counts, but does not provide a quantitative primary immune-response result or a controlled treatment-effect estimate.