A Study of Intradermal Administration of ZOSTAVAX™ (V211-051 AM2): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Intradermal Administration of ZOSTAVAX™ (V211-051 AM2) (NCT01385566), a randomized phase 1 study. The primary outcome is Geometric Mean Fold Change From Baseline in Varicella Zoster Virus (VZV)-Specific Antibodies.

2. Clinical Question

3. Trial Design

This was a randomized, single-masked, parallel-group phase 1 clinical trial sponsored by Merck Sharp & Dohme LLC. The registry record lists enrollment of 223, a start date of 2011-09, primary completion in 2013-05, and status as completed. The official title describes a partially blinded randomized clinical trial, while the masking field is recorded as single. Further details about who was masked or how masking was maintained are not reported in the registry record.

The intervention arms varied by vaccine dose and administration route. The primary endpoint results cover six vaccine groups: Full Dose Subcutaneous, 1/3 Dose Subcutaneous, Full Dose Intradermal, 1/3 Dose Intradermal, 1/10 Dose Intradermal, and 1/27 Dose Intradermal. The arm-specific primary analysis counts range from 34 to 52. These are analyzed participants, not a description of how many were randomized to every arm. The registry record does not report a full allocation schedule or the number assigned to each arm before analysis.

The record also includes a placebo group in the safety data and describes placebo injections in some arm descriptions. Those descriptions are truncated in the registry record, so the details of any later vaccination options are not reported in the registry record. The trial is listed as randomized and parallel, but the method used to generate or conceal the allocation sequence is not reported in the registry record. Eligibility criteria, site details, and the planned follow-up schedule beyond the primary endpoint timeframe are also not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The population analyzed included participants who received vaccination and did not have any protocol deviations that may have interfered with the immune response.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Geometric Mean Fold Change From Baseline in Varicella Zoster Virus (VZV)-Specific Antibodies, measured over Baseline and 6 weeks following vaccine administration.

The primary endpoint is the geometric mean fold change in Varicella Zoster Virus (VZV)-specific antibodies from baseline to 6 weeks following vaccine administration. Antibody titers were measured using a glycoprotein enzyme-linked immunosorbent assay at baseline and at 6 weeks. The fold change is defined as the 6-week value divided by the baseline value. The result is therefore a relative change in measured antibody titers, not an absolute antibody concentration.

A geometric mean is used when the endpoint is based on ratios or values that are naturally interpreted on a multiplicative scale. In general, geometric means summarize the central level after accounting for multiplicative rather than additive variation. The reported estimates are accompanied by 90% confidence intervals, which describe uncertainty around each arm-specific estimate under the analysis used. The registry record does not report the detailed computation of those intervals.

Antibody response is used as an immunogenicity outcome: it records a laboratory measure of the immune response after vaccination. It is distinct from a clinical outcome such as the occurrence of Herpes Zoster. The registry record does not report a clinical disease endpoint among the primary results. The analysis population excluded vaccinated participants with protocol deviations that may have interfered with immune response, according to the posted description.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is presented as a geometric mean fold change with a 90% confidence interval for each reported arm. These are descriptive arm-level estimates. The registry record does not report a model or a formal inferential procedure comparing the arms, so the estimates should not be read as evidence from a reported pairwise test.

Why use a geometric mean?

In general, a geometric mean is appropriate for positive measurements whose interpretation is multiplicative. Antibody fold change is a ratio: the 6-week titer divided by the baseline titer. A ratio of this kind can be more naturally summarized on a multiplicative scale than by an arithmetic average of raw differences. The geometric mean fold change gives a central summary of these ratios. An estimate above 1 represents a fold-change summary above the baseline reference on this scale; it does not give the absolute antibody concentration.

The assay, measurement times, and ratio definition are specified in the registry record. The record does not provide details such as the transformation used in estimation, the treatment of values below assay limits, or the exact method for constructing the confidence intervals. Those implementation details therefore cannot be assessed from the posted description.

What does the confidence interval communicate?

In general, a confidence interval expresses the precision of an estimate under the assumptions of the statistical procedure used. A narrower interval indicates greater precision than a wider interval for the same kind of estimate, while an interval still allows uncertainty about the underlying value. The intervals reported for this endpoint are 90% confidence intervals. They surround each arm’s fold-change estimate; they are not intervals for a difference between arms.

For example, the Full Dose Intradermal estimate is 3.24 and its 90% confidence interval is 2.66 to 3.94. This describes uncertainty around that group’s geometric mean fold change. It does not supply a direct estimate of how much that group differs from Full Dose Subcutaneous. A formal comparison would need to estimate a between-group contrast and its uncertainty using an analysis that accounts for the trial design and relevant assumptions. Such a contrast is not reported in the registry record.

How should the arm estimates be compared?

The arm summaries can be read descriptively: the point estimates differ across the listed doses and routes. But descriptive differences are not the same as established statistical differences. The registry record reports no analyses, and no pairwise effect estimates or corresponding tests are posted for the primary endpoint. It therefore does not establish whether the apparent ordering of the point estimates is distinguishable from sampling variation. The record does not report an adjusted comparison, a prespecified primary contrast, or an analysis plan for comparing all dose and route groups.

There are several groups and possible contrasts in this design. In general, when many comparisons are considered, the chance of at least one apparently unusual result can increase unless the analysis addresses multiplicity. The registry record does not report whether any multiplicity adjustment was planned or used. Without that information and without reported contrast estimates, the arm-specific confidence intervals should not be treated as a complete set of confirmatory comparisons.

What do the planning illustrations represent?

Planning illustrations based on an observed effect are distinct from observed trial results. The registry record describes a planning framework using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. For outcomes other than time-to-event outcomes, the planning quantity is participants per arm. These assumptions describe an illustration, not the design justification for this trial and not a measure of observed power. The registry record does not report the trial’s own sample-size justification or a protocol-based power calculation.

In general, a planning calculation estimates the sample size needed to detect a specified effect under chosen assumptions. It does not show that the trial actually had that probability of detecting an effect, nor does it change the uncertainty in the observed estimates. The record does not report the numerical planning outputs in the registry record for this analysis, so no particular planned sample size should be inferred from the assumptions alone.

What can be inferred from the posted analysis record?

The record gives an analysis population definition and arm-specific estimates, but it does not report the detailed statistical analysis plan. The method for handling missing data, protocol deviations beyond the stated exclusion, or multiplicity is not reported in the registry record. No interim analyses are reported in the registry record. These omissions limit assessment of how the estimates were produced and whether the reported analysis matched a prespecified plan. They do not change what the posted estimates describe: geometric mean antibody fold changes in the analyzed participants at the specified follow-up.

10. Multiplicity, Missing Data and Analysis Populations

The primary results include six vaccine groups spanning different doses and routes. The registry record does not identify a single reported pairwise contrast as the primary comparison, and it does not report inferential analyses comparing the arms. A multiplicity procedure, such as an adjustment for examining multiple contrasts, is not reported in the registry record. The planned hierarchy of comparisons, if any, is not reported in the registry record. Accordingly, the arm-level estimates should be interpreted descriptively rather than as a family of confirmed comparative findings.

The primary analysis population is described as participants who received vaccination and did not have protocol deviations that may have interfered with the immune response. The record does not report how many vaccinated participants had such deviations, how participants with missing baseline or follow-up measurements were handled, or whether any imputation method was used. The handling of incomplete safety follow-up is also not reported in the registry record. The arm-level analysis counts are posted, but they do not by themselves explain why participants may be absent from an analysis.

The registry record reports 0 secondary results and 0 analyses. It does post numerical primary endpoint summaries by arm, but it does not report a formal statistical analysis for those results. Interim analyses are not reported in the registry record. The record also does not report whether analysis decisions or exclusions were prespecified in a protocol or statistical analysis plan. These gaps make it difficult to assess the intended multiplicity control and the relationship between the planned and reported analysis populations.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse event counts are 0 in every listed group. The corresponding numbers at risk are 52 for Full Dose Subcutaneous, 34 for 1/3 Dose Subcutaneous, 34 for Full Dose Intradermal, 35 for 1/3 Dose Intradermal, 34 for 1/10 Dose Intradermal, 34 for 1/27 Dose Intradermal, and 39 for Placebo. The serious adverse event terms list is empty. This means the registry record posts no serious adverse events for these groups; it does not establish that the risk is zero or that no event could occur.

The registry record also posts counts for other adverse events: 30, 10, 27, 23, 21, 19, and 5, respectively, for those same groups. The definitions and event details for this category are not reported in the registry record, so these counts should not be interpreted as a comparison of event severity or type. Death counts are not reported in the registry record. Follow-up duration for these safety counts, and whether each count represents participants with at least one event or another counting convention, are not reported in the registry record.

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

The posted results show that the analyzed participants in each vaccine group had a geometric mean VZV-specific antibody fold-change estimate above the baseline reference at 6 weeks. The estimates range from 1.64 to 3.24 across the six reported regimens, with group-specific 90% confidence intervals. This is a description of the laboratory endpoint at that timepoint, not a direct comparison of the regimens.

The results do not establish that one dose or route is statistically superior to another. The record does not report between-group contrasts, p-values, or confidence intervals for differences between arms. A larger arm-specific point estimate is not, by itself, proof of a larger underlying response than in another group. The record also does not report clinical outcomes demonstrating whether antibody changes correspond to protection against Herpes Zoster.

The endpoint is limited to antibody measurements at 6 weeks following vaccination. It does not answer how long the measured response persists, whether the same pattern occurs at later follow-up, or whether the response is associated with clinical benefit. Those outcomes are not reported in the registry record. The analysis population excludes participants with protocol deviations considered capable of interfering with immune response, and the record does not provide enough detail to assess how that exclusion affects representativeness.

The safety counts likewise need cautious interpretation. The registry record posts 0 serious adverse events in each listed group, but it does not report the follow-up duration or death counts. It posts other adverse event counts without event descriptions in the registry record for this analysis. Neither the zero serious-event counts nor the other-event counts alone provide a complete account of safety, or a formal comparison between regimens.

Overall, the posted record offers arm-level immunogenicity summaries and safety counts from a completed randomized phase 1 trial. It leaves comparative statistical inference, longer-term outcomes, and several analysis details unreported. The findings therefore describe what was measured in the analyzed groups without establishing a clinical effect or a definitive difference among doses and routes.

13. Why This Trial Matters Statistically

This trial is statistically informative because it places several dose and route regimens side by side and reports an antibody response on a fold-change scale. That structure raises distinct questions: how each group changed from baseline, how precisely each change was estimated, and whether differences between groups are supported by comparative analyses. The record answers the first questions with arm-specific estimates and 90% confidence intervals, but does not report the last as a formal test.

The distinction matters in early-phase research. A laboratory response can be useful for describing immunogenicity, but arm-level results do not automatically establish comparative effects or clinical outcomes. A reader can identify the posted estimates and their uncertainty while recognizing that a comparison requires its own estimate and analysis. This prevents descriptive rankings from being mistaken for demonstrated differences.

The range of routes and doses also makes multiplicity relevant as a general statistical concern. When investigators consider multiple possible contrasts, the analysis plan determines how those comparisons are interpreted. The registry record does not report a multiplicity strategy or a prespecified contrast hierarchy. That absence is important context when reading several estimates together.

Finally, the record makes clear why study completion, enrollment, and analyzed sample size are not interchangeable concepts. It reports enrollment of 223 and provides separate analysis counts for the primary endpoint groups. The record does not explain all differences between enrollment and those analysis counts, so conclusions should remain tied to the stated analysis population. Careful attention to population, endpoint, uncertainty, and unreported methods is essential for interpreting this trial’s statistical evidence.

14. 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 a formal comparison among the vaccine arms, despite the study’s focus on different doses and administration routes. The arm-specific fold-change estimates therefore cannot establish whether differences between regimens exceed chance variation. There are no posted between-group confidence intervals or p-values for the primary endpoint.

The primary endpoint is a laboratory antibody measure at 6 weeks following vaccination. Results for later antibody measurements, clinical Herpes Zoster outcomes, and duration of response are not reported in the registry record. The endpoint is therefore limited in time and scope, and should not be treated as a clinical outcome.

The primary analysis excludes vaccinated participants with protocol deviations that may have interfered with immune response. The record does not report the number excluded, the reasons for deviations, or how missing measurements were handled. It also does not report the detailed statistical model, the confidence-interval construction method, or any sensitivity analyses. The impact of exclusions and missingness cannot be assessed from the posted information.

Although the record identifies the trial as randomized and single-masked, allocation generation and concealment methods, and the identity of masked parties, are not reported in the registry record. The sample-size justification and any protocol-based power calculation are also not reported. Multiplicity handling and interim analyses are not reported. Safety follow-up duration and death counts are not reported in the registry record, and the posted other adverse event counts lack event descriptions in the registry record for this analysis. These limitations constrain evaluation of both the comparative evidence and the completeness of safety interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Intradermal Administration of ZOSTAVAX™ (V211-051 AM2) — NCT01385566.
• Registry record last updated 2016-06-23; status last verified 2016-05.
• Results first posted 2013-02-21.
• 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.

18. Record Summary

NCT01385566 is a completed, randomized, single-masked, parallel-group phase 1 trial sponsored by Merck Sharp & Dohme LLC. The registry record reports enrollment of 223 and evaluates ZOSTAVAX™ administered subcutaneously or intradermally at different doses.

The primary endpoint is geometric mean fold change in VZV-specific antibodies from baseline to 6 weeks following vaccination, measured by glycoprotein enzyme-linked immunosorbent assay. Results are posted for six vaccine groups, with arm-specific analysis counts and 90% confidence intervals. The registry record does not report inferential comparisons between those groups.

Safety data include serious and other adverse event counts for the vaccine groups and a placebo group. Serious event counts are 0 in all listed groups. The record does not report death counts, safety follow-up duration, detailed analysis methods, multiplicity handling, or missing-data procedures.