T Cell Responses to Varicella Zoster Virus (VZV) Vaccine SLVP020: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for T Cell Responses to Varicella Zoster Virus (VZV) Vaccine SLVP020 (NCT01911065), a non-randomized phase 4 study. The primary outcome is Number of Participants Who Received Zostavax Immunization or Had Natural Exposure to VZV.

2. Clinical Question

3. Trial Design

This is a Phase 4, non-randomized, parallel study sponsored by Stanford University. The registry lists an enrollment of 54 and a completed status. The recorded start was 2010-09, and primary completion was 2011-12. These dates describe the registry record; they do not supply details about when individual participants were assessed or when analyses were conducted.

The two arms represent different groups rather than alternative treatments allocated under a like-for-like comparison. Participants over 50 years were assigned to the Zostavax™ vaccine group. Participants aged 40–49 with naturally acquired VZV immunity received no intervention, with the stated objective of examining age and inherited factors in VZV-specific immune response. Allocation was non-randomized, masking was none, and the model was parallel.

Because age and intervention status differ between arms, a contrast between them cannot isolate a vaccine effect. The comparison may reflect differences associated with age, prior infection, or other characteristics, as well as the presence or absence of vaccination. The registry record does not report procedures for balancing or adjusting for such differences.

The primary outcome is recorded as a participant count covering immunization or natural VZV exposure during Day 0 to Day 35. The record lists three outcome measures, but does not provide primary endpoint results or analysis details. It also does not report a randomized allocation procedure, masking, a protocol rationale for the enrollment, or an analysis plan.

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 Who Received Zostavax Immunization or Had Natural Exposure to VZV, measured over Day 0 to Day 35.

The primary endpoint is titled as the number of participants who received Zostavax immunization or had natural exposure to VZV. Its timeframe is Day 0 to Day 35, and its unit is participants. In this record, the measure is a count, not a stated measure of the magnitude, quality, or persistence of a T-cell response.

Participant counts can describe how many people in a defined group met an event or exposure definition. Such a measure can be useful for documenting who received the study intervention or had the specified exposure during the stated period. It does not, by itself, show whether an immune response was strong, whether it was associated with clinical protection, or how responses differed between people.

The registry does not provide a fuller endpoint definition, a participant-level result, a group-specific result for this primary measure, or a statistical comparison. The broader study description focuses on immune signatures associated with effective or poor responses, but the primary endpoint title alone does not specify how those signatures were measured or classified. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count describe?

The primary endpoint is expressed as a count of participants, with the unit listed as participants and the timeframe listed as Day 0 to Day 35. A count records how many people meet a stated event or exposure condition. It is different from a continuous measurement, such as a laboratory concentration, and different from a time-to-event measure, which uses the timing of an event. The registry title combines receipt of immunization and natural exposure to VZV. The record does not give a more detailed operational definition of that endpoint or provide its observed group counts.

For a count to be interpretable, its event definition and population at risk need to be clear. The adverse-event information includes group-specific at-risk counts and affected-participant counts. The primary endpoint entry does not include corresponding results. The record therefore does not allow a reader to assess the primary event frequency or compare it across groups. No rate, risk difference, relative effect, or uncertainty interval should be inferred from the endpoint title alone.

Why does the design matter for comparisons?

In a randomized comparison, assignment is intended to make treatment groups comparable, on average, with respect to factors that may affect outcomes. This study is explicitly non-randomized. Its parallel arms also have different age ranges and different intervention status: the vaccine arm received Zostavax™, while the natural-immunity arm received no intervention. The arm descriptions additionally distinguish vaccination from a prior history of chicken pox and natural VZV immunity.

As a general statistical principle, when groups differ in factors that may be related to the outcome, a group contrast can reflect those differences as well as the intervention. This is a concern for interpretation, not a claim that any particular factor changed an outcome in this study. The registry record does not report an adjustment strategy, matching procedure, or other method for addressing differences between arms. The absence of masking is also recorded, but the record does not describe how outcome assessment was conducted.

What can an analysis estimate?

For binary outcomes, analyses commonly compare the proportion of participants with an event between groups. For counts, methods depend on what is counted, the amount of variation, and whether the count represents events or people with an event. These are general statistical options, not methods documented for this study. The registry labels the primary outcome as a participant count and provides no analysis results. It would therefore be inappropriate to attribute a particular model or effect measure to the investigators.

A confidence interval is a general way to express uncertainty around an estimate. It gives a range of values compatible with the observed data under the model and assumptions used. A point estimate without an interval gives less information about precision; a p-value alone, if reported, would not communicate the size of an effect or its precision. The registry lists zero analyses and does not report a primary endpoint estimate, confidence interval, or p-value. No precision judgment about the immune-response question can be made from the posted results.

What do the adverse-event counts convey?

The adverse-event record distinguishes participants at risk from participants affected. These are descriptive quantities, not an adjusted comparison. For serious related adverse events, the record reports zero affected participants in each arm. For other related adverse events, it reports 3 affected participants in the vaccine group and 0 in the natural-immunity group. The record does not report an inferential analysis for these figures.

In general, zero observed events do not prove that an event is impossible or that two groups have identical risks. The interpretation of a zero count depends on the amount and type of observation, the event definition, and the completeness of reporting. Nor does a difference in raw counts by itself establish a treatment effect. In this study, the groups are not randomized and are different in age and intervention, so direct causal interpretation is especially limited.

Are planning calculations trial results?

General planning calculations use assumptions about an effect to be detected, the statistical error threshold, allocation, and the analysis method. The registry describes its sample-size assumptions as a planning illustration computed from an observed effect, rather than as the trial’s own design. Such calculations are not observed power and should not be read as evidence that the study was designed around a particular effect. The registry record does not report a sample-size justification from the investigators or a prospective statistical plan. Any planning illustration does not replace missing outcome estimates or analyses.

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("Zostavax™ Vaccine Group", "Naturally-acquired VZV Immunity")
n      <- c(45, 9)
events <- c(45, 9)
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  Zostavax™ Vaccine Group  45  45  100.0  92.1  100.0  92.1  100.0  92.3  99.9
ARM  Naturally-acquired VZV Immunity  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and zero analyses. It does not report a multiplicity strategy, such as a prespecified hierarchy of outcomes or an adjustment for testing multiple hypotheses. Without the analysis details and results, it is not possible to determine whether multiple outcome questions were tested, how they were prioritized, or how any testing affected interpretation. The study aim of identifying immune signatures does not itself establish a formal hypothesis-testing plan.

Missing-data handling is not reported in the registry record. The record does not describe how unavailable measurements, withdrawals, or incomplete follow-up were handled, nor does it provide the amount or pattern of missing outcome data. No assumption about complete follow-up or imputation can be made.

Analysis populations are also not described. The record does not say whether primary analyses included all enrolled participants, only participants who received the intervention, or a different defined group. The arm descriptions identify who was intended for each group, while the adverse-event entry lists participants at risk; these details do not establish the population used for any primary analysis.

The record does not provide an analysis plan, endpoint-specific results, or a report of protocol deviations. Consequently, it is not possible to assess whether analyses followed a prespecified plan or whether outcome reporting was selective. These absences limit interpretation independently of the non-randomized design.

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 non-serious adverse event terms

The registry reports zero related serious adverse events among 45 participants at risk in the Zostavax™ vaccine group, and zero among 9 participants at risk in the naturally acquired VZV immunity group. The record separately lists other related adverse events: 3 affected participants in the vaccine group and 0 in the natural-immunity group. These figures are counts of affected participants, not a statistical comparison.

The groups were not randomized and differ in age range and intervention status, so their raw adverse-event counts should not be treated as a like-for-like estimate of vaccine-associated risk. The registry does not report inferential analyses, confidence intervals, or further event details that would establish the precision or comparability of these counts. A zero recorded count means no affected participants were listed for that category in the record; it does not prove that the event cannot occur.

Death figures are not reported in the registry record. The posted safety information should therefore be read as limited descriptive reporting, rather than as a complete assessment of comparative safety.

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

The posted record documents a Phase 4 study intended to examine VZV-specific immune responses in a vaccinated group and a group with naturally acquired VZV immunity. It gives the intervention, age descriptions, primary endpoint title and timeframe, and selected adverse-event counts. It does not report immune-response findings or primary endpoint results. Thus, it does not establish which immune signatures were associated with better or poorer responses.

The study design also limits causal interpretation. The comparison was non-randomized, and the arms differ in age range as well as exposure to vaccination. A contrast between the groups would not isolate the effect of vaccination from other differences. The record does not report an adjusted analysis that would resolve this limitation.

The adverse-event figures describe what the registry lists for the stated categories and at-risk groups. They do not establish equivalence between the arms or quantify comparative risk with reported uncertainty. The lack of reported analyses and missing-data information further limits the strength of conclusions that can be drawn from the registry record.

In general, a study’s stated objective, design, endpoint, and posted results answer different questions. An objective describes what investigators sought to learn; an endpoint defines a measurement; and an analysis estimates a result from data. Here, the record states an immune-signature objective and names a participant-count endpoint, but does not report analyses addressing the main immune-response question. The results should not be extended beyond the descriptive information that is actually reported.

14. Why This Trial Matters Statistically

This study illustrates why a control group must be evaluated in light of how it was formed. The natural-immunity arm is not a randomized control for the vaccine arm: it represents participants aged 40–49 with prior chicken pox, while the vaccine group comprises participants over 50 years who received Zostavax™. The design may be relevant for examining age and inherited factors in VZV-specific immune response, as stated in the arm description, but a simple between-arm contrast would not isolate vaccination.

It also illustrates the difference between an interesting research objective and a reported statistical result. The study aimed to identify immune signatures associated with effective or poor responses. The primary endpoint title, however, describes a count of participants who received immunization or had natural VZV exposure during Day 0 to Day 35. The registry does not report immune measurements or analyses that connect a signature with response quality. Readers need endpoint definitions and results, not only a broad objective, to evaluate the evidence.

Finally, adverse-event counts are informative as descriptive registry entries but cannot substitute for a comparative analysis. The record reports at-risk and affected counts, while leaving the analysis methods and uncertainty unreported. This makes the study a useful example of how design, endpoint choice, and reporting completeness jointly determine what can be concluded from clinical data.

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 primary endpoint results, immune-response measurements, or analyses. The stated aim concerns immune signatures, but the posted information does not show how such signatures were defined, measured, or related to response. The primary endpoint is described as a participant count over Day 0 to Day 35, without a fuller operational definition or group-specific result.

The non-randomized design and dissimilar arms limit direct comparison. The vaccine group included participants over 50 years who received Zostavax™, whereas the natural-immunity group included participants aged 40–49 who received no intervention. Age, prior exposure status, and intervention therefore vary together. The record does not report statistical adjustment or another approach to account for these differences.

Masking was none. The registry does not report further detail about outcome assessment, missing data, analysis populations, protocol deviations, or a prespecified statistical analysis plan. It lists three outcome measures and zero analyses, and does not provide estimates or precision measures for the primary question. The safety information is limited to the listed related adverse-event counts; death figures are not reported in the registry record.

These limitations concern the information available in the registry record. They do not establish what may have been measured or analyzed outside that record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: T Cell Responses to Varicella Zoster Virus (VZV) Vaccine SLVP020 — NCT01911065.
• Registry record last updated 2023-12-18; status last verified 2023-11.
• Results first posted 2017-03-03.
• 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

NCT01911065 is a completed, non-randomized, parallel Phase 4 study sponsored by Stanford University. The record lists enrollment of 54, a start of 2010-09, and primary completion in 2011-12. Participants over 50 years were assigned to receive Zostavax™; participants aged 40–49 with naturally acquired VZV immunity received no intervention.

The primary endpoint is titled as the number of participants who received Zostavax immunization or had natural exposure to VZV from Day 0 to Day 35. The record lists three outcome measures and zero analyses, but does not report primary endpoint results or immune-response findings. Related serious adverse events were listed for zero participants among 45 at risk in the vaccine group and zero among 9 at risk in the natural-immunity group. Other related adverse events were listed for 3 participants in the vaccine group and 0 in the natural-immunity group. The design does not support a like-for-like randomized comparison.