Evaluation of Immunogenicity and Safety of VARIVAX™ New Seed Process (NSP) in Children (V210-063): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Immunogenicity and Safety of VARIVAX™ New Seed Process (NSP) in Children (V210-063) (NCT02062502), a randomized phase 3 study. The primary outcome is Percentage of Participants With Varicella Zoster Virus (VZV) Antibody Levels >=5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL.

2. Clinical Question

3. Trial Design

This was a Phase III, randomized, parallel-group, controlled study. The official title describes it as double blind, while the registry classification lists triple masking. The registry record does not explain the difference between those descriptions or identify which study roles were masked.

The study evaluated VARIVAX™ manufactured with a New Seed Process against VARIVAX™ manufactured with the 2007 process. M-M-R II™ was administered with either varicella vaccine, so the comparison concerns the two varicella vaccine processes within a shared co-administration schedule. Each vaccine was given by subcutaneous injection on Day 1 and Day 91. The New Seed Process and 2007 process vaccines were administered in the left arm, and M-M-R II™ in the right arm.

The registry reports enrollment of 611 and a completed study. The recorded study start was 2014-03-07, and primary completion was 2015-02-24. These enrollment and study-level figures should not be conflated with the analysis denominators for a particular outcome: the primary endpoint results use 254 participants in each group, while the adverse-event figures use different denominators.

The primary endpoint was assessed 6 weeks (43 days) after the first vaccination, in participants meeting the stated per-protocol serology criteria. The registry record lists five secondary outcomes concerning fever, rash or systemic symptoms, and solicited injection-site reactions after vaccination 1 or vaccination 2. Details about sequence generation, allocation concealment, masking procedures, and the rationale for the chosen enrollment 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

Analysis population for the primary outcome, as defined in the registry: The analysis population is participants with a seronegative antibody titer at baseline and postvaccination serology contributing to the per-protocol analysis.

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.

Population: All randomized participants

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Varicella Zoster Virus (VZV) Antibody Levels >=5 Glycoprotein Enzyme-linked Immunosorbent Assay (gpELISA) Units/mL, measured over 6 weeks (43 days) after vaccination 1.

The primary endpoint is the percentage of participants with VZV antibody levels >=5 gpELISA Units/mL at 6 weeks (43 days) after vaccination 1. It is a binary response measure: each participant either meets the stated antibody threshold or does not, and the group result is expressed as a percentage. The analysis population consists of participants who were seronegative at baseline and had postvaccination serology contributing to the per-protocol analysis.

As a general statistical point, a threshold-based antibody endpoint turns a laboratory measurement into an interpretable response proportion. It describes how often a specified antibody level was reached, rather than the average antibody level across participants. That makes the percentage suitable for comparing response rates between the two vaccine-process groups at the stated time point. The registry summary also refers to a hypothesis about mean antibody titer, but the posted primary endpoint result is the percentage above the threshold.

The endpoint therefore addresses an immunogenicity question, not a direct count of varicella illness. The registry record does not report the clinical meaning assigned to the threshold, nor does it provide the non-inferiority margin or the acceptable-response criterion. Those details are needed to assess the prespecified decision rules in full.

7. Results Posted in the Registry

• VARIVAX™ 2007 Process + M-M-R II™: 97.2% (247/254) versus 97.2% (247/254) on control; risk difference 0.0 percentage points (95% CI -2.8 to 2.8), risk ratio 1.00 (0.97–1.03); unadjusted two-proportion z-test p = 1.000.

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish the response percentages, the recalculated comparison, and the sponsor-reported analysis. The endpoint is binary, the comparison is expressed as a risk difference, and the sponsor identifies its method as Miettinen and Nurminen. The registry also classifies the sponsor analysis as non-inferiority or equivalence. Those labels describe different parts of the analysis and should not be treated as interchangeable.

What does a response percentage describe?

The primary outcome counts participants who met the antibody threshold and expresses that count as a percentage of the relevant analysis group. In this study, the reported endpoint is the percentage with VZV antibody levels >=5 gpELISA Units/mL at 6 weeks (43 days) after vaccination 1. A percentage summarizes the observed response frequency in the analysis population; it does not give the antibody level of every participant or describe how far above the threshold an individual result was.

The endpoint is reported for a per-protocol population defined by baseline seronegativity and available postvaccination serology contributing to that analysis. The primary result lists 254 participants in each group and 247 threshold responses in each group. The adverse-event denominators differ, so denominators should always be interpreted in relation to the specific outcome rather than assumed to represent one common analysis population.

What is a risk difference?

A risk difference subtracts one group's event proportion from the other group's event proportion. It is an absolute measure on the proportion scale; a value of 0.0 indicates no observed difference at the displayed precision. The simple recalculation from the posted summary statistics is unadjusted. Its reported interval is -0.029 to 0.029, and its unadjusted p-value is 1.0.

The sponsor reports a risk difference of 0.0 percentage points, with a 95% confidence interval from -3.2 to 3.2 percentage points. The interval is expressed on a percentage-point scale, while the recalculated interval is expressed on the proportion scale. The sponsor's method is identified as Miettinen and Nurminen. The methods text and margin used for the sponsor's hypothesis test are not reported in the registry record.

How does non-inferiority differ from a conventional difference test?

As a general explanation, a conventional difference test asks whether the data are inconsistent with a specified no-difference null hypothesis. A non-inferiority test instead evaluates whether the data rule out a loss larger than a prespecified margin in the chosen direction. An equivalence test evaluates whether the data are sufficiently compatible with differences inside prespecified bounds. The hypotheses and decision rules depend on the margin and, for non-inferiority, on the direction of the comparison.

The registry classifies the sponsor's result as a non-inferiority/equivalence analysis and reports p < 0.001. That p-value should be understood within the sponsor's stated analysis type, not as evidence of a conventional difference between groups. Because the registry record does not report the margin or detailed hypothesis, the decision rule cannot be independently reconstructed from the listed result. The sponsor's own analysis takes precedence over the simple recalculation when describing the trial's reported inferential result.

What does a confidence interval contribute?

As a general explanation, a confidence interval gives a range of values compatible with the observed data and the method's assumptions at a stated confidence level. It conveys uncertainty about the estimated effect. It is not a range containing a fixed proportion of individual participant outcomes, nor does it by itself decide non-inferiority or equivalence. For those conclusions, the interval must be assessed against the prespecified margin or bounds. The sponsor reports a 95% interval, but the registry does not state the margin against which it was judged.

Widths and endpoints also depend on the analysis method and the scale used. The simple unadjusted recalculation and the sponsor's Miettinen and Nurminen result should not be treated as identical calculations merely because both report a risk difference. The recalculation is not a substitute for the sponsor's analysis.

What do the planning illustrations mean?

The sample-size material is described as a planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation. Such illustrations describe hypothetical planning under stated assumptions; they are not observed power and do not establish the design rationale for this trial. The registry record does not report the trial's own sample-size justification. No planning illustration can resolve the unreported margin, missing-data approach, or analysis-population details.

10. Confidence Intervals and Precision

The sponsor-reported estimate is a risk difference of 0.0 percentage points, with a 95% confidence interval from -3.2 to 3.2 percentage points. The interval spans differences on either side of the estimate. Its interpretation is conditional on the sponsor's method and the data used in the analysis; the registry identifies the method as Miettinen and Nurminen.

As a general statistical explanation, an interval expresses uncertainty in an estimated group contrast. It is not evidence that the true difference is exactly 0.0, even when the point estimate is 0.0. The observed percentages are both 97.2%, but equal displayed values do not remove sampling uncertainty. The interval's endpoints indicate the range of differences compatible with the analysis at the stated confidence level, under the method's assumptions.

The unadjusted recalculation reports a risk-difference interval from -0.029 to 0.029 and a point estimate of 0.0. This is a simple recalculation from posted summary statistics, not the sponsor's analysis. The sponsor-reported interval and p-value are the relevant results for describing the trial's own non-inferiority/equivalence analysis; the discrepancy means the sponsor's own analysis takes precedence.

Precision alone does not establish non-inferiority or equivalence. That assessment requires comparing the interval with a prespecified margin or equivalence bounds. Those limits are not reported in the registry record, so the reported interval cannot be evaluated against them from the registry information. The interval also pertains to the specified per-protocol endpoint, not automatically to other populations, outcomes, or follow-up times.

11. Analyses Reported by the Sponsor

The sponsor-reported analysis compares the two groups using the Miettinen and Nurminen method and reports a risk difference of 0.0 percentage points, a 95% confidence interval from -3.2 to 3.2 percentage points, and p < 0.001. The registry classifies this as a non-inferiority/equivalence analysis. Its p-value belongs to that reported analysis and should not be read as a conventional test showing a difference between the groups.

The simple unadjusted recalculation from the posted summary statistics reports a risk difference of 0.0, an interval from -0.029 to 0.029, and an unadjusted p-value of 1.0. The recalculated result is not the sponsor's analysis, and the registry indicates a discrepancy. Accordingly, the sponsor's own analysis takes precedence when reporting the trial's inferential result; the recalculation is best treated as a separate descriptive check.

The registry record does not report the non-inferiority margin, detailed hypothesis specification, or further analytical explanation that would allow the sponsor's decision rule to be independently reconstructed. The result can be described as the sponsor's reported non-inferiority/equivalence analysis, but the margin-dependent interpretation cannot be fully verified from the record alone.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists five secondary outcomes: fever at the stated temperature threshold; systemic measles-like, rubella-like, varicella-like or mumps-like symptoms and injection-site rash after vaccination 1; the corresponding symptom and rash outcome after vaccination 2; and solicited injection-site erythema, swelling, and pain or tenderness after each vaccination. These outcomes address safety and tolerability in addition to the primary antibody response endpoint.

When a study assesses multiple outcomes, time points, or comparisons, the chance of at least one apparently unusual result can increase if each is interpreted separately. As a general statistical point, multiplicity procedures can control the interpretation of a family of tests, but their choice depends on the prespecified analysis plan. The registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or how secondary analyses were intended to support conclusions. It also lists three analyses, while detailed information about the analyses beyond the reported non-inferiority/equivalence result is not reported in the registry record.

The primary population is described as participants who were seronegative at baseline and had postvaccination serology contributing to the per-protocol analysis. That definition identifies the population contributing to the posted endpoint, but it does not explain how missing measurements, protocol deviations, or exclusions were handled. The registry record does not report the number of participants with missing primary endpoint data or the reasons for any exclusions.

The adverse-event denominators are 291 for the New Seed Process group and 293 for the 2007 process group, unlike the primary endpoint denominators. This indicates that outcome-specific denominators are being reported; the registry record does not explain the difference between the analysis sets. Randomization alone does not resolve questions about missing outcome data or the consequences of restricting an analysis to a per-protocol population. The posted results therefore need to be read in light of the stated population for each outcome, without assuming that every analysis includes the same participants.

13. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchiolitis (1.0%), gastroenteritis (0.7%), respiratory syncytial virus bronchiolitis (0.7%), lobar pneumonia (0.3%), pneumonia (0.3%).

The registry reports serious adverse events for 6 participants among 291 at risk in the VARIVAX™ New Seed Process + M-M-R II™ group, and for 9 participants among 293 at risk in the VARIVAX™ 2007 Process + M-M-R II™ group. These are the serious-event figures recorded for the stated adverse-event groups. They should be interpreted using those denominators, not the primary endpoint denominators.

The most frequently listed serious-event terms are bronchiolitis (1.0%), gastroenteritis (0.7%), respiratory syncytial virus bronchiolitis (0.7%), lobar pneumonia (0.3%), pneumonia (0.3%), and dehydration (0.3%). The registry record does not provide further detail in the information about event timing, severity beyond the serious-event classification, or whether events were considered related to vaccination. The listed term percentages should not be treated as a complete description of all safety findings.

Other adverse events are recorded for 225 participants in the New Seed Process group and 224 in the 2007 process group, using the same group-specific denominators stated for adverse events. Death results are not reported in the registry record. These data describe recorded events; they do not, on their own, establish a causal relationship or resolve differences in safety between groups.

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

The primary results describe antibody responses in a defined per-protocol population at a specific time after the first vaccination. The observed percentage reaching VZV antibody levels >=5 gpELISA Units/mL is 97.2% in each group. The sponsor's reported risk difference is 0.0 percentage points, with a 95% confidence interval from -3.2 to 3.2 percentage points. These statistics describe the posted immunogenicity comparison and its uncertainty.

They do not show that every participant had the same antibody level, that the two vaccine processes are identical, or that the true response rates are exactly equal. A group percentage reduces individual laboratory results to whether a threshold was reached; it does not describe the distribution of antibody levels above or below that threshold. The registry summary mentions a mean-antibody-titer hypothesis, but the primary result described in the registry is a threshold response percentage.

The endpoint is an antibody measure, not a direct measure of varicella disease. The record does not report a clinical disease outcome as the primary endpoint, the non-inferiority margin, or the acceptable-response criterion. Consequently, the sponsor's p-value and confidence interval cannot be used alone to verify the margin-based conclusion from the registry information.

Safety figures likewise describe recorded event counts and listed terms, rather than proving whether an event was caused by a vaccine. The registry record does not report the details needed to assess attribution or to infer from these figures alone that one process has a different safety profile.

Overall, the posted data support a precise description of the measured response and reported safety events in their stated analysis groups. Broader conclusions about clinical outcomes, all randomized participants, or unreported analysis rules go beyond what the registry record reports.

15. Why This Trial Matters Statistically

This trial illustrates why the estimand and analysis population matter as much as the headline percentage. The primary result concerns participants who were seronegative at baseline and contributed postvaccination serology to the per-protocol analysis. It is not automatically an estimate for every participant enrolled or for every population that might be of interest.

It also illustrates the distinction between a threshold response rate and an average antibody titer. The percentage above a stated threshold gives one useful summary of immunogenicity, while not conveying the full distribution of antibody measurements. The registry summary refers to both response rate and mean titer hypotheses, but the posted primary outcome result is the threshold-based percentage.

The comparison demonstrates why a non-inferiority/equivalence result cannot be interpreted as though it were a routine test for any difference. The sponsor reports a risk difference, a confidence interval, and p < 0.001 under an analysis classified as non-inferiority/equivalence. Without the margin and detailed hypothesis in the registry record, readers cannot independently assess the margin-based decision rule. The simple unadjusted recalculation is a distinct analysis and does not supersede the sponsor's result.

Finally, different denominators across endpoint and adverse-event summaries are a reminder to read each result with its own analysis population. Clear reporting of margins, missing-data handling, multiplicity, and analysis populations is essential for interpreting a clinical trial, particularly when a conclusion depends on a prespecified decision boundary.

16. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record does not report the non-inferiority margin or the criterion used to define an acceptable antibody response. Those omissions limit independent assessment of the sponsor's non-inferiority/equivalence result, even though the record reports its point estimate, confidence interval, method, and p-value.

The primary endpoint uses a per-protocol population defined by baseline seronegativity and postvaccination serology. The number excluded from that analysis, reasons for exclusion, missing-data handling, and results for other analysis populations are not reported in the registry record. The primary endpoint denominators are also different from the adverse-event denominators, and the reason for that difference is not reported.

The registry lists five secondary outcomes, but the multiplicity approach, outcome hierarchy, and detailed analysis plan are not reported. Although the study summary mentions a mean antibody titer hypothesis, the posted primary result is the percentage above the antibody threshold; detailed mean-titer results are not reported in the registry information used for this summary.

The registry record does not report further details about randomization procedures, masking implementation, or the discrepancy between the official title's double-blind description and the triple-masking classification. It also does not report the trial's sample-size justification. The sample-size illustrations are planning exercises based on the observed effect, not a record of the original design rationale or observed power.

Safety results list serious-event counts and selected terms, but further event-level context, attribution, and death results are not reported in the registry record. These limitations do not negate the posted figures; they define what can and cannot be concluded from them.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Evaluation of Immunogenicity and Safety of VARIVAX™ New Seed Process (NSP) in Children (V210-063) — NCT02062502.
• Registry record last updated 2018-10-30; status last verified 2018-10.
• Results first posted 2016-03-01.
• 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.

20. Record Summary

NCT02062502 is a completed Phase III randomized, parallel-group study of VARIVAX™ New Seed Process compared with VARIVAX™ 2007 Process, with M-M-R II™ given alongside each. The registry reports enrollment of 611, a study start of 2014-03-07, and primary completion on 2015-02-24.

The primary endpoint was the percentage with VZV antibody levels >=5 gpELISA Units/mL at 6 weeks (43 days) after vaccination 1, in the stated per-protocol serology population. The posted percentage was 97.2% in each group. The sponsor reported a Miettinen and Nurminen risk difference of 0.0 percentage points, a 95% confidence interval from -3.2 to 3.2 percentage points, and p < 0.001 for an analysis classified as non-inferiority/equivalence.

The registry record does not report the margin, missing-data approach, or multiplicity plan. The simple unadjusted recalculation is distinct from the sponsor analysis; because a discrepancy is recorded, the sponsor's own analysis takes precedence.