This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of an Investigational Zoster Vaccine, in Subjects With a History of Herpes Zoster (V211-014) (NCT00322231), a randomized phase 3 study. The primary outcome is Vaccine-related Serious Adverse Experiences (SAEs) for 28 Days Postvaccination.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00322231 |
| Phase | Phase 3 |
| Condition | Herpes Zoster |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 101 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants with a history of herpes zoster who took part in this Phase III trial. The registry lists 101 participants enrolled and says all vaccinated participants were evaluated for safety. The posted safety denominators are 98 for ZOSTAVAX™ and 96 for placebo; why these denominators differ is not reported in the registry record.
Intervention
Zoster vaccine live (ZOSTAVAX™), given as one dose in the crossover sequence. In one sequence it was given on Day 1, followed by placebo at Week 4.
Comparator
Placebo, also given as one dose. In the other sequence it was given on Day 1, followed by ZOSTAVAX™ at Week 4. Each participant received both interventions.
Primary question
What vaccine-related serious adverse experiences were reported during the 28 days after vaccination with ZOSTAVAX™ or placebo? The posted serious-event measure lists 0 participants affected among 98 at risk for ZOSTAVAX™ and 0 among 96 at risk for placebo.
The question is about observed safety events, not whether the vaccine prevents herpes zoster or provides a particular level of immune response. The registry also lists antibody response outcomes, but their results are not reported in the registry record. The crossover arrangement means the intervention sequences differed: some participants received vaccine first and others placebo first. The registry’s safety summary presents outcomes by intervention, rather than a reported analysis that accounts for the paired observations from each participant. Details of any such analysis are not reported in the registry record.
3. Trial Design
This was a Phase III, randomized, double-blind crossover trial of zoster vaccine live in participants with a history of herpes zoster. The registry lists herpes zoster as the condition and 101 participants as enrolled. The study is marked completed. Its start is listed as 2006-05, and its primary completion as 2007-07.
Participants were assigned to one of two sequences. In the ZOSTAVAX™ / Placebo sequence, participants received zoster vaccine live on Day 1 in Period 1 and placebo on Week 4 in Period 2. In the Placebo / ZOSTAVAX™ sequence, participants received placebo on Day 1 and zoster vaccine live on Week 4. The registry says all participants received one dose each of ZOSTAVAX™ and placebo. A washout interval or other period-specific protocol details are not reported in the registry record.
Randomization determines the assigned sequence; it does not mean the two interventions were given to separate groups throughout the study. Because participants received both interventions, their observations under the two treatments are linked within each person. Double masking indicates that the study was described as double-blind, but who was masked and how masking was maintained are not reported in the registry record.
The stated purpose was to determine whether the investigational vaccine was generally well tolerated in people with a history of herpes zoster. The official title also identifies safety, tolerability and immunogenicity as study topics. The registry lists 3 outcome measures, including the primary serious adverse experience measure and secondary antibody response measures. It does not report the full protocol, a sample-size justification, or additional details of the conduct of the trial.
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.
Period 1
| Stage | ZOSTAVAX™ / Placebo | Placebo / ZOSTAVAX™ |
|---|---|---|
| STARTED | 51 | 50 |
| COMPLETED | 51 | 50 |
| NOT COMPLETED | 0 | 0 |
Period 2
| Stage | ZOSTAVAX™ / Placebo | Placebo / ZOSTAVAX™ |
|---|---|---|
| STARTED | 51 | 49 |
| COMPLETED | 51 | 49 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All vaccinated participants were evaluated for safety. This was a crossover study. All participants received one dose each of ZOSTAVAX™ and placebo. Data below reflect SAEs reported after receipt of ZOSTAVAX™ or placebo.
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.
| Characteristic | Unit | ZOSTAVAX™ / Placebo | Placebo / ZOSTAVAX™ | Total |
|---|---|---|---|---|
| Participants analysed | 51 | 50 | 101 | |
| Age, Customized: 50 to 59 Years of age | participants | 10 | 10 | 20 |
| Age, Customized: ≥ 60 Years of age | participants | 41 | 40 | 81 |
| Sex: Female, Male: Female | Participants | 36 | 24 | 60 |
| Sex: Female, Male: Male | Participants | 15 | 26 | 41 |
| Race/Ethnicity, Customized: Asian | participants | 1 | 3 | 4 |
| Race/Ethnicity, Customized: Black | participants | 3 | 3 | 6 |
| Race/Ethnicity, Customized: Hispanic American | participants | 0 | 2 | 2 |
| Race/Ethnicity, Customized: White | participants | 47 | 42 | 89 |
6. Primary Endpoint
The registry lists the primary outcome as Vaccine-related Serious Adverse Experiences (SAEs) for 28 Days Postvaccination, measured over To Day 28 postvaccination.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled “Vaccine-related Serious Adverse Experiences (SAEs) for 28 Days Postvaccination.” It counts participants with a serious adverse experience during the stated period after vaccination. The registry describes a serious adverse experience as an adverse experience at any dose that meets one or more specified criteria, including death, persistent or significant disability or incapacity, prolongation of an existing inpatient hospitalization, a life-threatening event, a congenital anomaly or birth defect, cancer, overdose, or another important medical event.
A serious-event endpoint is used to summarize events that meet serious criteria, rather than every symptom or adverse experience. It is therefore distinct from a measure of all adverse experiences. The registry reports the serious-event measure separately for ZOSTAVAX™ and placebo, with 0 affected participants in each group. The relevant denominators are 98 and 96, respectively.
The endpoint title specifies vaccine-related serious events, but the record does not describe how relatedness was assessed or give a detailed adjudication process. The registry’s posted outcome measure is therefore best read as a reported count under its serious-event definition, not as a complete account of all safety observations. The time window is to Day 28 postvaccination; the record does not provide a more detailed schedule for event collection.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted serious adverse experience counts are 0 among 98 participants at risk after ZOSTAVAX™ and 0 among 96 participants at risk after placebo. These are counts of participants with an event, not event rates expressed as percentages and not counts of every adverse experience. The registry’s primary endpoint concerns vaccine-related serious adverse experiences through Day 28 postvaccination. The record gives no further breakdown of the serious-event results.
Both reported counts are zero, so this particular summary does not show a difference in the number of participants with a recorded serious event between the intervention entries. That observation should not be read as evidence that the interventions have identical safety profiles. A zero count in a trial of this size cannot rule out uncommon events, and the registry does not provide confidence intervals or a statistical comparison for these results. It also does not report a test of equivalence or non-inferiority.
The safety table separately lists other adverse experiences: 45 participants among 98 at risk for ZOSTAVAX™ and 4 among 96 at risk for placebo. Those figures refer to the “other” adverse-experience category, not to the primary serious-event endpoint. The registry does not provide enough detail to describe the types, severity, timing, or relatedness of those other experiences. They should not be combined with the serious-event counts or interpreted as a causal comparison without further analysis.
The study used a crossover design: participants received both interventions in different periods. In general, outcomes from the same participant are not independent in the way outcomes from two unrelated groups would be. A comparison should account for that pairing and for the sequence and period structure. The registry record does not report an inferential analysis of the primary endpoint, and the posted counts alone do not show how any within-participant comparison would have been handled.
The registry lists two secondary antibody outcomes: geometric mean titer of varicella-zoster virus antibody responses at 4 weeks postvaccination, and geometric mean fold rise from prevaccination to 4 weeks postvaccination. Their results are not reported in the registry record. Thus, the safety counts can be described, but the listed immune-response outcomes cannot be interpreted from this record.
Precision is also important. A confidence interval, when reported, describes the range of values compatible with the data under the analysis assumptions; it helps show uncertainty around an estimate. No such interval is reported. The counts are therefore descriptive evidence for this trial, not a precise estimate of the frequency of rare serious experiences in a broader population.
9. Statistical Methods Explained
The registry identifies the trial as randomized, double-blind and crossover, but it does not report a statistical analysis for the primary endpoint. The posted record lists 3 outcome measures and 0 analyses. The discussion below separates general statistical context from what can be established about this particular trial.
What does randomization contribute?
General statistical context: Random assignment can reduce systematic differences in baseline characteristics between assigned sequences, on average. In this trial, assignment was to a sequence of interventions, rather than to receive only vaccine or only placebo. Randomization does not ensure that every characteristic is balanced in a particular trial, and it does not remove uncertainty from a result. The record does not give the method used to generate the allocation sequence, whether allocation was concealed, or the number of participants assigned to each sequence.
Why does the crossover structure matter?
General statistical context: In a crossover study, each participant receives multiple interventions over time. Measurements from one participant can be more alike than measurements from different participants. An analysis that compares the two intervention periods can use this within-participant pairing, which may improve precision when its assumptions are appropriate. It must also consider the order of treatment and the possibility that period-related changes influence the observed outcomes. These are general design and analysis considerations; the analysis used for this endpoint is not reported in the registry record.
The registry describes Day 1 as Period 1 and Week 4 as Period 2, and says each participant received one dose of each intervention. It does not report the interval between the first and second administration in more detail, a washout plan, or how possible carryover was assessed. No conclusion about these protocol features or their handling in an analysis can be drawn from the posted information.
What does the event count represent?
The primary outcome is a participant count for serious adverse experiences within the stated postvaccination window. The registry gives the number at risk and the number affected for each intervention. It reports 0 affected among 98 at risk for ZOSTAVAX™ and 0 affected among 96 at risk for placebo. The counts are descriptive. A model or test would require additional assumptions and a defined way to account for the crossover structure; the registry does not report either for this outcome.
General statistical context: A confidence interval communicates uncertainty around an estimate, while a hypothesis test evaluates compatibility with a specified null hypothesis under stated assumptions. Neither can be reconstructed as a reported analysis because the record gives no confidence interval, p-value, or test result. Even when a participant count is zero, the underlying risk is not known to be zero; the amount of uncertainty depends on the sample and analysis. No interval estimate for that uncertainty is reported in the registry record.
How should the adverse-experience categories be kept separate?
The safety results distinguish serious adverse experiences from other adverse experiences. The serious-event entry has 0 participants affected in each intervention group. The other adverse-experience entries list 45 participants for ZOSTAVAX™ and 4 for placebo. These are different outcome categories and should not be added together or treated as interchangeable measures. The record does not give the individual event terms in the serious category, and the list of top serious terms is empty. Detailed event descriptions and a breakdown of the other experiences are not reported in the registry record.
General statistical context: In analyses of counts, over-dispersion means that variability is greater than a chosen model expects. It can make model-based uncertainty too small if ignored. This endpoint is presented as participants with an event, rather than as a count of recurrent events per person, and the record does not report a count model or any assessment of over-dispersion. This concept therefore does not establish how the trial was analyzed; it illustrates why the analysis scale and model need to be stated.
What do the planning illustrations mean?
The sample-size illustrations accompanying the page are not the trial’s observed power and are not the trial’s design justification. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated share of the observed effect. They are planning illustrations based on the observed effect, not evidence that the trial was designed with those assumptions. The record does not report its own sample-size justification or power calculation.
For this primary endpoint, the posted material does not reduce the outcome’s categories or time points to one comparison. As a result, a single planning comparison should not be mistaken for the registry’s analysis. Any participant counts shown for planning should be interpreted only under their stated assumptions and never as observed participants or as proof that the trial had adequate power.
General statistical context: A valid analysis also depends on the population included, how missing observations are handled, the endpoint definition, and the treatment of the crossover sequence. Those choices affect what an estimate means. The record identifies all vaccinated participants as evaluated for safety, but does not report a detailed analysis population or missing-data method. That absence limits what can be said about the analysis beyond the posted counts.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures: the primary vaccine-related serious adverse experience outcome and two secondary antibody outcomes. The secondary measures concern geometric mean titer at 4 weeks postvaccination and geometric mean fold rise from prevaccination to 4 weeks postvaccination. The antibody results are not reported in the registry record, and the record lists 0 analyses.
When a study assesses multiple outcomes or multiple comparisons, the chance of at least one apparently unusual result can change. General statistical context: A multiplicity plan can specify which outcomes are primary, how comparisons are ordered, or how error rates are controlled. The registry record does not report a multiplicity procedure, whether secondary outcomes were adjusted, or how the primary and secondary outcomes were handled together. No inference about such a plan should be made from the outcome list alone.
The safety population is described as all vaccinated participants. The adverse-experience denominators are 98 for ZOSTAVAX™ and 96 for placebo, while enrollment is listed as 101. The record does not explain the differences between these counts, identify missing observations, or state how participants with incomplete safety information were treated. It also does not report a missing-data method for the antibody outcomes.
The registry does not give a detailed analysis population for each endpoint, describe exclusions from analysis, or state whether all randomized participants were included. Those details are not reported in the registry record. This matters because the population analyzed and the handling of incomplete observations define the scope of any statistical result. Here, interpretation should remain with the stated safety counts and should not assume unreported analysis choices.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| ZOSTAVAX™ | 0 | 98 | 0.0% |
| Placebo | 0 | 96 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| ZOSTAVAX™ | 45 of 98 |
| Placebo | 4 of 96 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ZOSTAVAX™ | Placebo |
|---|---|---|---|
| Injection Site Pain | General disorders | 36 of 98 | 1 of 96 |
| Injection Site Erythema | General disorders | 33 of 98 | 3 of 96 |
| Injection Site Swelling | General disorders | 26 of 98 | 2 of 96 |
| Injection Site Pruritus | General disorders | 5 of 98 | 0 of 96 |
Read the serious-event figures as participant counts with their corresponding numbers at risk. The registry lists 0 participants affected among 98 at risk for ZOSTAVAX™ and 0 among 96 at risk for placebo. These are the posted figures for the serious adverse experience measure, whose title specifies vaccine-related events during the 28 days after vaccination. The record does not provide a more detailed breakdown of serious events.
The separate “other” adverse-experience figures are 45 participants among 98 at risk for ZOSTAVAX™ and 4 among 96 at risk for placebo. They do not represent the serious-event endpoint. The registry does not report detailed terms, severity, timing, or relatedness for these other experiences in the material. The counts should therefore be read as a descriptive safety summary, not as a complete account of each participant’s experience or a causal estimate of intervention effects.
Because this was a crossover trial, participants received both interventions, but the posted denominators differ. The reason for the difference is not reported in the registry record. No confidence intervals or statistical comparison accompany these counts. They describe the results recorded for this trial, but do not establish that serious events cannot occur or that the interventions have the same safety profile.
12. What the Result Does, and Does Not, Mean
The clearest result in the registry’s primary safety measure is that no participants are listed as having a serious adverse experience in either intervention group: 0 among 98 at risk after ZOSTAVAX™ and 0 among 96 at risk after placebo. This is a description of the posted observations during the specified window. It is not an estimate that the underlying risk is exactly zero, and it does not rule out uncommon events.
The registry also reports other adverse experiences in 45 participants among 98 at risk for ZOSTAVAX™ and 4 among 96 at risk for placebo. These counts are separate from the primary serious-event endpoint. Without details about event terms, severity, timing, relatedness, and analysis, the difference in the posted counts cannot by itself establish why those experiences occurred or how the interventions compare in overall safety.
The trial’s crossover design means participants received both vaccine and placebo at different times. A formal comparison would need to account for the within-participant structure and the sequence or period, as appropriate. The record does not report an inferential analysis for the primary outcome. It therefore does not provide a statistical estimate of a treatment contrast, a confidence interval, or a hypothesis-test result for the serious-event comparison.
The registry identifies immune-response outcomes, but their results are not reported in the registry record. These safety findings cannot answer what antibody responses were observed. Nor do the posted figures establish whether the vaccine prevents herpes zoster, because prevention is not the endpoint.
In short, the record documents zero participants with a reported serious adverse experience in each intervention entry and gives separate counts for other experiences. The scope is limited to the posted safety measures and their stated denominators. The absence of reported serious events in these entries is not proof of no risk, and it is not evidence of equivalence between vaccine and placebo.
13. Why This Trial Matters Statistically
This trial is statistically notable because its crossover design changes how the intervention comparison should be understood. Participants received both zoster vaccine live and placebo, in randomized sequences. Their observations are therefore linked within participants, unlike a design in which one group receives only vaccine and a separate group receives only placebo. A sound comparative analysis would need to respect that structure. The registry record does not report such an analysis for the primary safety outcome.
The posted results also illustrate the distinction between a serious-event endpoint and a broader adverse-experience summary. The serious-event count is 0 in both intervention entries, whereas the separate counts for other adverse experiences are 45 for ZOSTAVAX™ and 4 for placebo. Keeping these categories separate prevents a broad safety count from being mistaken for the primary endpoint. The registry’s serious-event definition includes specified criteria, while detailed terms and classifications are not given.
Another statistical lesson is that a zero count is informative but not definitive. It describes what was observed in the trial, but without an uncertainty interval it does not quantify the range of plausible underlying event frequencies. The posted record also gives no inferential comparison, making it important not to turn a descriptive result into a claim of equivalence.
Finally, the trial’s registry record lists immune-response outcomes as well as the safety measure, but does not report those results. This emphasizes the value of distinguishing outcomes that were listed from outcomes with interpretable results. The record supports a focused description of the posted safety counts, while leaving broader comparative and immunogenicity questions unanswered.
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 is limited in the detail it reports about both the design and the results. Although it identifies a randomized, double-blind crossover study, it does not report the allocation method, masking procedures, washout details, or how possible period or carryover effects were addressed. These omissions matter to interpretation of any within-participant comparison, but they do not establish that a particular design feature was absent.
The primary serious-event result is presented as counts and denominators, without a confidence interval, p-value, or reported statistical analysis. The record lists 0 analyses. It does not explain why the safety denominators differ from each other or from the enrollment count of 101. It identifies all vaccinated participants as evaluated for safety, but does not provide a detailed account of exclusions, missing observations, or endpoint-specific analysis populations.
There is little detail about event characterization. The record gives a serious-event definition and the counts, but no serious-event terms are listed in the top serious terms entry. For other adverse experiences, the posted counts are 45 among 98 at risk for ZOSTAVAX™ and 4 among 96 at risk for placebo; detailed terms and relatedness are not reported. The record also does not describe how relatedness to vaccination was assessed.
The two secondary antibody outcomes are listed, but their results are not reported in the registry record. The record does not report a multiplicity procedure, a sample-size justification, or an analysis plan. These limitations prevent a fuller assessment of precision, comparative safety, and immunogenicity based on the posted registry information alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of an Investigational Zoster Vaccine, in Subjects With a History of Herpes Zoster (V211-014) — NCT00322231.
- Registry record last updated 2015-01-26; status last verified 2015-01.
- Results first posted 2010-12-15.
- 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.
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18. Record Summary
This completed Phase III study examined zoster vaccine live in participants with a history of herpes zoster. It was randomized, double-blind and crossover, with participants receiving one dose each of ZOSTAVAX™ and placebo in one of two sequences. The registry lists 101 enrolled participants.
The primary endpoint was vaccine-related serious adverse experiences through Day 28 postvaccination. The posted serious-event count was 0 among 98 at risk for ZOSTAVAX™ and 0 among 96 at risk for placebo. Separate other adverse-experience counts were 45 and 4, respectively. The registry lists two secondary antibody outcomes, but their results are not reported in the registry record.
No inferential analysis, confidence interval, or p-value is reported for the primary safety outcome. The results are therefore best understood as descriptive counts, with limits on comparative interpretation and precision.