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 Evaluation of the Safety and Tolerability of a Higher Potency Dose of an Investigational Vaccine Among Adults 50 Years of Age and Older (V211-009) (NCT00092417), a randomized phase 3 study. The primary outcome is Number of Participants With Vaccine-related Serious Clinical Adverse Experiences (SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00092417 |
| Phase | Phase 3 |
| Condition | Healthy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 695 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned adults 50 years of age or older. The registry lists the condition as Healthy. For the primary safety analysis, the population consisted of vaccinated participants with safety follow-up data. The record does not further describe eligibility criteria or the characteristics of participants who entered that analysis.
Intervention
Participants received the higher-potency dose of the investigational varicella zoster virus vaccine. The registry describes the trial as evaluating its safety and tolerability relative to the lower-potency dose. Details such as the vaccine dose amount, administration schedule, and route are not reported in the registry record.
Comparator
The comparator was the lower-potency dose of the investigational vaccine. This is an active comparison between two potency levels, not a comparison with placebo or no vaccination. The record does not state the dose amounts or describe any accompanying treatments.
Primary question
The primary question was whether the incidence of vaccine-related serious clinical adverse experiences differed between the higher- and lower-potency groups during Day 1-42 post vaccination. A qualified physician investigator determined whether an experience was vaccine-related. The registry description says the difference in risk was compared at the 2-sided 0.05 level, but it does not report a single comparative estimate or a test result for this endpoint.
3. Trial Design
This was a randomized, double-masked, parallel-group Phase 3 trial. Participants were assigned to receive either a higher-potency or a lower-potency dose of varicella zoster virus vaccine. A parallel design means participants remain in their assigned group for the comparison rather than crossing over between doses. Random allocation is intended to make the groups comparable on average, while masking is intended to limit the influence of knowledge about assigned treatment on participant experience or assessment. The registry does not describe the randomization procedure or which people were masked.
The registry records enrollment of 695. The primary safety population was defined as vaccinated participants with safety follow-up data. In the posted adverse-event figures, the higher-potency group has 459 participants at risk and the lower-potency group has 234 at risk. These outcome-specific denominators do not add to the enrollment figure; the registry record does not explain the relationship between them, such as how participants moved from enrollment into the safety analysis population. They should therefore be read as the denominators attached to the reported safety outcomes, not as a complete account of enrollment and disposition.
The study start is recorded as 2003-10 and primary completion as 2004-06, with status listed as completed. Its stated purpose was to compare the safety and tolerability profile of higher- and lower-potency investigational vaccine doses. The registry lists five outcome measures, but does not report a statistical analysis entry for the primary comparison. Further details about allocation concealment, follow-up procedures beyond the primary timeframe, protocol deviations, and the full analysis plan are 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
| Stage | Zoster Vaccine Higher Potency | Zoster Vaccine Lower Potency |
|---|---|---|
| STARTED | 464 | 234 |
| Vaccinated | 461 | 234 |
| COMPLETED | 459 | 233 |
| NOT COMPLETED | 5 | 1 |
Reasons for not completing this period:
| Reason | Zoster Vaccine Higher Potency | Zoster Vaccine Lower Potency |
|---|---|---|
| Lost to Follow-up | 2 | 0 |
| Withdrawal by Subject | 2 | 1 |
| Other | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The population for the primary safety analysis consisted of all vaccinated participants who had safety follow-up data.
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 | Zoster Vaccine Higher Potency | Zoster Vaccine Lower Potency | Total |
|---|---|---|---|---|
| Participants analysed | 461 | 234 | 695 | |
| Age, Continuous | years | 65.2 (SD 9.16) | 65.6 (SD 9.69) | 65.4 (SD 9.34) |
| Sex: Female, Male: Female | Participants | 282 | 134 | 416 |
| Sex: Female, Male: Male | Participants | 179 | 100 | 279 |
| Race/Ethnicity, Customized: Asian | participants | 10 | 6 | 16 |
| Race/Ethnicity, Customized: Black | participants | 6 | 4 | 10 |
| Race/Ethnicity, Customized: Hispanic American | participants | 10 | 8 | 18 |
| Race/Ethnicity, Customized: Multi-Racial | participants | 1 | 2 | 3 |
| Race/Ethnicity, Customized: Native American | participants | 2 | 0 | 2 |
| Race/Ethnicity, Customized: White | participants | 432 | 214 | 646 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Vaccine-related Serious Clinical Adverse Experiences (SAEs), measured over Day 1-42 post vaccination.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with vaccine-related serious clinical adverse experiences during Day 1-42 post vaccination. It is a binary participant-level outcome: for the endpoint, each participant either had at least one event meeting the definition or did not. It does not count the total number of episodes per participant. The registry says that a qualified physician investigator determined whether a serious clinical adverse experience in the timeframe was vaccine-related.
Serious adverse experiences are important safety outcomes because they capture events considered serious under the trial’s adverse-experience framework. Attribution to vaccination narrows the endpoint further: the measure concerns events judged by the investigator to be related to the vaccine, rather than every serious event occurring during follow-up. This makes the endpoint relevant to a comparison of vaccine safety, while also making the result dependent on how seriousness and relationship to vaccination were assessed. The registry record does not provide the detailed criteria used for those judgments.
The endpoint is expressed as a number of participants, but interpreting a group count requires its at-risk denominator. The posted figures report both counts and denominators for the two potency groups. The registry description says the difference in risk between groups was compared at the 2-sided 0.05 level. It does not report a comparative risk estimate, confidence interval, or test result for the primary endpoint, so the observed counts alone do not establish the precision or statistical significance of a between-group difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted serious-event figures are 4 participants with vaccine-related serious clinical adverse experiences among 459 at risk in the higher-potency group and 1 among 234 at risk in the lower-potency group. These are small event counts. They describe what was recorded in the safety population and timeframe; they do not, by themselves, show whether a difference between doses is compatible with chance or how precisely the underlying risks are estimated.
The trial’s endpoint description identifies a planned comparison of risk at the 2-sided 0.05 level. However, the registry lists 0 analyses, and no primary comparative result is reported in the record. In particular, there is no reported effect estimate, confidence interval, or p value for the primary endpoint. It is therefore not possible from the registry record to assess the result against the stated significance level or to quantify uncertainty around a difference. The posted counts should not be turned into a claim that one dose has more or less risk than the other.
Other adverse-experience counts are also recorded: 296 participants among 459 at risk in the higher-potency group and 141 among 234 at risk in the lower-potency group. The record does not supply a comparative analysis for this outcome, and its precise category definition is not described in the registry record recorded for this trial. These counts should be treated as a separate reported outcome, not as a substitute for the primary serious-event endpoint.
The listed serious-event terms include small cell lung cancer stage unspecified at 0.4%, and angina pectoris, coronary artery disease, enteritis, and depression at 0.2% each. These labels do not establish whether a term was considered vaccine-related, how often it occurred in each group, or whether the groups differed. The registry does not report group-specific comparisons for these terms. Nor does it explain the relationship between the terms and the participant-level primary endpoint.
Overall, the posted information supports a descriptive reading of the safety counts, but not a definitive comparative conclusion. Sparse event counts make uncertainty especially important: the observed count can change substantially with only a few events, and the registry does not provide the interval or model-based results needed to assess that uncertainty. No treatment recommendation or conclusion about vaccine effects follows from these counts alone.
9. Statistical Methods Explained
The registry describes the primary outcome as the number of participants with vaccine-related serious clinical adverse experiences. In statistical terms, this is a binary outcome at the participant level. A participant is counted as having the outcome if at least one qualifying event occurs during the stated timeframe; the measure does not distinguish participants with one event from those with multiple events. The registry gives the measure in participants and identifies Day 1-42 post vaccination as the timeframe.
What does a risk comparison mean?
For a binary endpoint, risk is the proportion of participants in a group who experience the outcome, using the relevant at-risk participants as the denominator. A risk difference compares those group risks by subtraction. This is a general explanation of the statistic, not a reported result for this trial. The registry says that the difference in risk was compared at the 2-sided 0.05 level, but does not publish the comparative estimate or the test result. No recalculated effect estimate is available in the registry record.
A confidence interval is a range of values produced by a statistical procedure that conveys the precision of an estimated effect. A relatively wide interval indicates less precision; a narrow interval indicates greater precision, subject to the assumptions of the method. The interval is also useful because it shows which effect sizes remain compatible with the data under that procedure. The registry record does not report a confidence interval for the primary comparison. Without one, readers cannot assess the range of plausible between-group differences using the posted analysis.
What does the stated significance level tell readers?
The 2-sided 0.05 level describes a threshold for a statistical test as stated in the endpoint description. In general, a two-sided test considers departures in either direction rather than only a prespecified increase or decrease. The significance level is a rule for interpreting a test result; it is not itself evidence that a difference exists, and it does not measure the size or clinical importance of an effect. Because the registry does not report the primary test result, the stated level cannot be used to infer whether the comparison met that threshold.
A p value, when reported, describes how unusual the observed data or more extreme data would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, nor a measure of how likely the result is to be reproduced. No p value for the primary comparison is reported in the registry record. The planned significance level should therefore be distinguished from an observed test result.
Why do the counts need their denominators?
A count alone does not describe the frequency of an outcome unless the population at risk is known. The registry reports 4 affected participants among 459 at risk in the higher-potency group and 1 among 234 at risk in the lower-potency group. Those figures are descriptive inputs to a risk comparison, but a formal comparison also depends on a chosen estimation and testing procedure. The record does not specify that procedure beyond its statement about comparing risk at the 2-sided 0.05 level.
With binary data, uncertainty is influenced by the number of events as well as the number of participants. When event counts are small, estimated risks and group differences can be imprecise. A confidence interval or an appropriate test can help describe that uncertainty, but neither is reported for the primary endpoint. The counts should not be treated as though they were a complete inferential analysis.
What is not documented about the statistical plan?
The registry does not report the detailed statistical analysis method, an adjustment strategy, handling of missing follow-up, or a prespecified estimand. An estimand is the precise treatment effect a trial aims to estimate, including the population, outcome, comparison, and handling of events that occur after treatment assignment. The registry does identify the primary safety population as vaccinated participants with safety follow-up data, but does not provide further details about how that population was assembled or how incomplete records were handled.
General statistical practice distinguishes a protocol-planned analysis from calculations reconstructed from summary counts. A simple unadjusted re-calculation, if available, would not necessarily match a sponsor’s analysis because the sponsor may use a different analysis population, model, or handling of data. The registry record does not report a sponsor analysis of the primary endpoint to compare with any reconstructed estimate. No sample-size justification or interim-analysis plan is reported. Any sample-size planning illustration based on an observed effect is not the original trial design and is not observed power.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures, while the primary endpoint is vaccine-related serious clinical adverse experiences during Day 1-42 post vaccination. When a study considers multiple outcomes or repeated comparisons, the chance of at least one apparently notable result can increase. Statistical methods for addressing multiplicity may be prespecified, but the registry record does not report whether a multiplicity adjustment or hierarchy was used. The existence of multiple listed outcomes alone does not establish that a particular adjustment was required or performed.
The record lists 0 analyses. It therefore does not supply a reported inferential analysis for the primary endpoint, nor enough information to identify how the different outcome measures were analyzed relative to one another. It also does not report interim analyses, stopping rules, or a detailed statistical analysis plan. These omissions mean readers cannot determine from the registry record whether any planned analyses were adjusted for multiple looks or multiple endpoints.
The primary safety population is described as vaccinated participants with safety follow-up data. That is the population specified for the primary analysis, but the registry does not report the number excluded for missing follow-up, the reasons for missingness, or any method used to handle incomplete observations. It does not state whether all participants were analyzed according to randomized assignment for this endpoint. The at-risk denominators in the posted safety figures are 459 for the higher-potency group and 234 for the lower-potency group; the record does not explain how these denominators relate to the enrollment figure of 695.
Missing outcome information can affect a safety comparison if the chance of observation differs across groups or is related to an event. This is a general statistical concern, not evidence that missingness biased this trial. Without a description of missing-data handling and participant flow, the extent to which the posted outcome data represent the intended population cannot be fully assessed.
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 |
|---|---|---|---|
| Zoster Vaccine Higher Potency | 4 | 459 | 0.9% |
| Zoster Vaccine Lower Potency | 1 | 234 | 0.4% |
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 |
|---|---|
| Zoster Vaccine Higher Potency | 296 of 459 |
| Zoster Vaccine Lower Potency | 141 of 234 |
Most frequent serious adverse event terms
| Event term | Organ system | Zoster Vaccine Higher Potency | Zoster Vaccine Lower Potency |
|---|---|---|---|
| Angina pectoris | Cardiac disorders | 1 of 459 | 0 of 234 |
| Coronary artery disease | Cardiac disorders | 1 of 459 | 0 of 234 |
| Enteritis | Gastrointestinal disorders | 1 of 459 | 0 of 234 |
| Small cell lung cancer stage unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 459 | 1 of 234 |
| Depression | Psychiatric disorders | 1 of 459 | 0 of 234 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Zoster Vaccine Higher Potency | Zoster Vaccine Lower Potency |
|---|---|---|---|
| Injection Site Erythema | General disorders | 227 of 459 | 111 of 234 |
| Injection Site Pain | General disorders | 217 of 459 | 91 of 234 |
| Injection Site Swelling | General disorders | 189 of 459 | 77 of 234 |
| Injection Site Pruritus | General disorders | 58 of 459 | 21 of 234 |
| Headache | Nervous system disorders | 43 of 459 | 16 of 234 |
Serious events with the highest arm-level rate: small cell lung cancer stage unspecified (0.4%), angina pectoris (0.2%), coronary artery disease (0.2%), enteritis (0.2%), depression (0.2%).
The registry reports 4 participants with vaccine-related serious clinical adverse experiences among 459 at risk in the higher-potency group, and 1 among 234 at risk in the lower-potency group. The endpoint timeframe is Day 1-42 post vaccination. The investigator, described as a qualified physician, determined whether a serious clinical adverse experience in that timeframe was vaccine-related. These figures are counts of participants, not a count of every event episode.
There are also counts for other adverse experiences: 296 participants among 459 at risk in the higher-potency group and 141 among 234 at risk in the lower-potency group. The registry entries do not define this category in enough detail to establish its relationship to the serious-event category. The figures should therefore be read as separate reported counts rather than combined or treated as mutually exclusive.
The record lists serious-event terms with percentages: small cell lung cancer stage unspecified at 0.4%, and angina pectoris, coronary artery disease, enteritis, and depression at 0.2% each. These percentages are not accompanied by group-specific counts or a comparative analysis. The registry does not clarify from these entries alone how each term maps to the primary attribution judgment. Neither the term list nor the participant counts provide a complete description of the events’ timing, clinical course, or causal assessment.
12. What the Result Does, and Does Not, Mean
The result can be read as a registry description of safety outcomes after vaccination with higher- and lower-potency doses. For the primary endpoint, the posted counts are 4 participants in the higher-potency group and 1 in the lower-potency group, with their respective at-risk denominators reported. These are observations in the analyzed safety data, not a complete estimate of the difference in underlying risk. The registry does not report a confidence interval or a test result for the primary comparison.
Accordingly, the counts do not establish that the doses differ, and they do not establish that the doses are equivalent. A failure to report a statistical test is not evidence that the test was negative. Likewise, a small number of observed events is not proof that an outcome cannot occur or that a difference is absent. The record’s statement that risk was compared at the 2-sided 0.05 level describes the intended threshold, not the result of that comparison.
The available information also does not establish the full safety profile of either dose. The endpoint concerns vaccine-related serious clinical adverse experiences within a specified follow-up period, as judged by an investigator. It does not encompass every possible adverse outcome, longer-term outcome, or question about vaccine benefit. Other adverse-experience counts and the listed serious-event terms add descriptive information, but without definitions and group-specific analyses they do not support broader conclusions about comparative safety.
Interpretation is further limited by the absence of a reported analysis population flow, missing-data methods, and detailed statistical plan. These omissions do not show that the trial was conducted improperly; they limit what can be concluded from the registry record. The defensible reading is restricted to the design features and counts recorded, with uncertainty about the comparative effect remaining unquantified.
13. Why This Trial Matters Statistically
This trial illustrates why safety results need to be read together with their endpoint definition, denominators, and analysis. A count of participants with a serious event is not interchangeable with a count of all event episodes, and the primary endpoint specifically concerns events judged both serious and vaccine-related. The registry also distinguishes the primary outcome from other adverse-experience counts, which should not be merged without a clear definition.
The comparison is randomized and double-masked, features intended in general to reduce bias in treatment assignment and outcome assessment. Yet design labels do not replace reporting of the analysis itself. The registry states that the risk difference was compared at the 2-sided 0.05 level, while listing 0 analyses and no comparative estimate or uncertainty interval. This makes the distinction between a planned statistical approach and a reported result particularly important.
The safety denominators are outcome-specific and are not explained in relation to the enrollment figure. Recognizing this prevents an unsupported assumption about participant flow or the reason for the difference in those figures. It also highlights the value of reporting analysis populations and missing follow-up clearly.
More broadly, rare or infrequent safety outcomes require careful communication of precision. General statistical reasoning indicates that a small number of events can leave substantial uncertainty, even when group counts are reported. Without an interval or a test result, readers should avoid converting a descriptive contrast into a firm comparative claim. The record is therefore useful as an example of how registry results can offer concrete event counts while leaving key inferential details unreported.
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 main limitation for interpreting this trial’s primary safety result is that the registry reports the participant counts and at-risk denominators but not a comparative estimate, confidence interval, or test result. Although the endpoint description says the groups’ risks were compared at the 2-sided 0.05 level, no result of that comparison is listed. The precision and statistical compatibility of the observed group difference therefore cannot be assessed from the record.
The primary safety population is described as vaccinated participants with safety follow-up data, but no participant-flow account explains how that population relates to enrollment of 695 or to the outcome-specific denominators of 459 and 234. The record does not report the reasons for absent follow-up, the extent of missing outcome data, or how missingness was handled. This prevents a full assessment of the population represented by the posted counts.
The registry does not provide detailed definitions for seriousness, vaccine-related attribution, or the other adverse-experience category. It states that a qualified physician investigator determined vaccine relationship, but does not describe adjudication procedures or whether assessments were independently reviewed. The listed serious-event terms are not accompanied by group-specific comparisons, and their relationship to the primary endpoint is not fully explained.
Other limitations include the absence of a detailed statistical analysis plan, multiplicity procedures, interim-analysis information, and sample-size justification. These details are not reported in the registry record. Their absence should be understood as a limit on what can be evaluated from this record, not as evidence about how the trial was conducted. The registry describes a defined post-vaccination period, so the posted primary outcome does not by itself address events beyond that timeframe.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluation of the Safety and Tolerability of a Higher Potency Dose of an Investigational Vaccine Among Adults 50 Years of Age and Older (V211-009) — NCT00092417.
- Registry record last updated 2015-10-07; status last verified 2015-10.
- Results first posted 2010-06-10.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed, randomized, double-masked, parallel Phase 3 trial comparing higher- and lower-potency varicella zoster virus vaccine doses in adults aged 50 years or older. Enrollment is recorded as 695, with study start at 2003-10 and primary completion at 2004-06.
The primary safety endpoint was the number of participants with vaccine-related serious clinical adverse experiences during Day 1-42 post vaccination. The reported counts are 4 among 459 at risk in the higher-potency group and 1 among 234 at risk in the lower-potency group. The registry lists 0 analyses and does not report a comparative estimate, confidence interval, or test result for this endpoint. The counts are descriptive; the comparative effect and its precision are not reported in the registry record.