Safety and Immunogenicity of Norovirus Bivalent Virus-Like Particle Vaccine in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of Norovirus Bivalent Virus-Like Particle Vaccine in Healthy Adults (NCT02142504), a randomized phase 2 study. The primary outcome is Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the First Injection.

2. Clinical Question

The primary endpoint concerns pain, erythema, induration, and swelling after injection. These events were solicited, meaning that the trial specifically assessed the listed local reactions rather than relying only on participants to report any event spontaneously. The registry record defines the assessment window as the seven days after the primary injection.

The trial also listed safety and immune-response outcomes, including solicited systemic events, fever, unsolicited events, and antibody responses. However, numerical results for the primary endpoint and those secondary outcomes are not reported in the registry record. The posted adverse-event counts offer some safety information, but they do not answer the primary endpoint question by themselves. The registry record also does not provide a numerical comparison of the vaccine groups for local reactions.

3. Trial Design

This was a Phase II, randomized, placebo-controlled, double-blind trial with a parallel-group design. The registry record describes masking as quadruple. It does not identify which specific roles were masked or give further details about how masking was maintained. Enrollment was 454, and the trial status is completed. The recorded start date is 2014-05-15, and the primary completion date is 2016-01-06.

Three groups are listed. One received saline placebo on Day 1 and a norovirus bivalent vaccine formulation without MPL on Day 365. The other two groups received vaccine formulations with MPL on Day 1, with listed GI.1/GII.4 antigen amounts of 15/50 μg and 50/50 μg, respectively. The descriptions indicate subsequent vaccination for these groups, but the full regimen details are not reported in the registry record. Each of the three group records also lists a subsequent GI.1/GII.4 15/15 μg vaccine formulation without MPL.

The primary endpoint was assessed in the Safety Analysis Set, defined as all participants who received at least one dose of trial vaccination. This population definition is relevant to interpreting safety results: it is based on vaccination received, rather than simply on randomization. The listed adverse-event group counts are 153, 145, and 154 participants at risk in the placebo-first, 15/50 μg, and 50/50 μg groups, respectively. The registry record does not explain any differences between the total enrollment and the group-specific safety denominators.

Randomization and a parallel-group structure support comparison between allocated groups, while masking is intended generally to reduce the influence of treatment knowledge on trial conduct and assessment. Those design features do not substitute for reported outcome data. Numerical primary-endpoint results, estimates of between-group differences, and uncertainty intervals 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.

Before assignment: Healthy volunteers were enrolled equally in 1 of 3 norovirus bivalent virus like particle (VLP) vaccine unique formulation treatment groups to receive: 2 formulation arms received 2 doses and 1 formulation arm received 1 dose.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set included all participants who received at least one dose of trial vaccination.

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: Randomized Set included all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the First Injection, measured over Days 1 through 7.

The primary endpoint is the percentage of participants with solicited local adverse events at the injection site after the first injection, over Days 1 through 7. The listed reactions are pain, erythema, induration, and swelling. The population is the Safety Analysis Set, which includes participants who received at least one dose of trial vaccination.

This kind of endpoint is used to describe the frequency of specifically anticipated local reactions during a defined period after injection. Soliciting the listed events can make assessment more systematic than relying only on spontaneous reports. A percentage expresses how common the endpoint was in the assessed group, but it does not convey severity, duration, or the experience of each individual participant unless those details are also reported.

The registry record does not report the primary endpoint percentages, participant counts for each reaction, or a comparison between groups. It also does not report a confidence interval or statistical test for this endpoint. Consequently, the endpoint definition is available, but its observed results and their precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods describe how trial data are converted into estimates and how uncertainty is assessed. The registry record gives the primary endpoint definition and safety population, but detailed statistical methods for the primary endpoint are not reported in the registry record. The registry lists zero analyses. That listing does not establish whether analyses were conducted outside the registry record; it means that no analyses are posted there.

What does a percentage describe?

In general, a percentage for a binary outcome describes the proportion of assessed participants who experienced the event. For this trial, the primary endpoint is framed as the percentage with one or more solicited local adverse events at the injection site during Days 1 through 7 after the first injection. The registry definition names pain, erythema, induration, and swelling. A percentage does not, by itself, show how many distinct event types each participant experienced, how severe an event was, or how long it lasted.

To interpret such a percentage, readers need both the event count and the relevant denominator, together with a clear rule for deciding which events count. The record specifies the Safety Analysis Set as participants who received at least one dose, but does not post primary-endpoint counts or percentages by group. The posted serious and other adverse-event counts concern different safety summaries and cannot be substituted for the primary endpoint result.

Why do confidence intervals matter?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a stated method and assumptions. It helps distinguish a relatively precise estimate from one that is compatible with a broad range of underlying values. For a comparison between groups, an interval for the difference or another contrast can show both the estimated direction and the range of values consistent with the data and method.

No confidence interval for the primary endpoint or for a between-group contrast is reported in the registry record. Nor is a primary-endpoint test statistic or p-value reported. Without these results, the precision of the endpoint estimate cannot be evaluated. The record also does not report the statistical procedure used to construct any interval or test for the endpoint.

What does randomization contribute?

In general, random allocation is intended to make treatment groups comparable in expectation at the start of a trial, including with respect to factors that are measured and those that are not. In a parallel-group trial, participants are assigned to groups and outcome data are compared between those groups. Randomization alone does not guarantee identical group composition, establish that every analysis preserves the benefits of allocation, or resolve missing outcome data.

This trial is recorded as randomized, parallel, and quadruple-masked. The registry does not report details of the randomization sequence, allocation concealment, masking roles, or the statistical analysis plan. Accordingly, the design labels can be described, but procedural details and their implementation cannot be assessed from the registry record.

How should event counts be understood?

The posted safety summary reports numbers at risk and numbers affected for serious and other adverse events. These are descriptive counts. In general, counts help show how many participants were represented in a safety category, while denominators make the size of the assessed group clear. A count does not indicate whether events were related to vaccination, and comparisons of counts alone do not account for uncertainty or potential differences in follow-up and event ascertainment.

The registry does not report the analysis rules for the serious and other adverse-event summaries, such as how repeat events in one participant were handled, how event timing was defined, or how relatedness was assessed. Those details are important when interpreting whether the unit is participants with an event or the total number of events. The available group fields describe participants at risk and affected, but fuller definitions are not reported in the registry record.

What can sample-size planning show?

In general, sample-size planning uses assumptions about an outcome, a target effect, significance level, allocation, and a statistical method to illustrate the number of participants that might be needed for a planned analysis. Such planning is not a measure of the probability that a completed trial detected an effect. It also does not replace observed results or uncertainty intervals.

The registry record does not report the trial’s own sample-size justification, planned power, or the assumptions used to choose enrollment. It also does not report a statistical analysis plan specifying a primary comparison or approach to missing data. Therefore, no conclusion about the adequacy of trial planning or the power of the completed trial can be drawn from the posted record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 27 outcome measures, including safety outcomes and antibody-response outcomes. Multiple outcomes create a general statistical issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan addresses multiplicity. In general, possible approaches include defining a hierarchy of outcomes or adjusting inference across a specified family of tests. The registry record does not report whether any such approach was planned or used.

The primary endpoint is stated, but no numerical result or inferential analysis for it is posted. The registry also lists secondary safety and immunogenicity outcomes, including outcomes after the second injection and seroresponse measures. Results for those measures are not reported in the registry record. The record does not specify which outcomes were intended for confirmatory inference, whether analyses were exploratory, or how any multiplicity would be handled.

The primary population is described as the Safety Analysis Set: all participants who received at least one dose. The record does not report a separate intention-to-treat population, per-protocol population, or immunogenicity analysis population. It does not provide participant flow by analysis population, reasons for exclusions, or the number of participants with missing measurements for the primary endpoint.

Missing-data methods are not reported in the registry record. In general, missing outcome data can affect estimates if participants with missing measurements differ in relevant ways from participants with observed measurements. Interpretation therefore depends on knowing the amount and pattern of missingness and the assumptions used to address it. Those details cannot be assessed for the primary or secondary outcomes from the posted record.

The registry gives enrollment and group-specific safety denominators, but does not explain the relationship between them or report endpoint-specific denominators. Thus, completeness of outcome assessment and the handling of participants without evaluable data remain unclear.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac arrest (0.7%), kidney infection (0.7%), sepsis (0.7%), urinary tract infection (0.7%), intentional overdose (0.7%).

The registry reports serious adverse-event counts of 4 among 153 participants in the saline-placebo-first group, 4 among 145 in the 15/50 μg vaccine group, and 6 among 154 in the 50/50 μg vaccine group. It also reports other adverse-event counts of 33 among 153, 24 among 145, and 25 among 154, respectively. These figures are descriptive summaries, not the primary solicited local-reaction outcome.

In general, a serious adverse event is a defined safety category, but the registry record does not give the event-by-event criteria or assessment details for these counts. The listed serious-event terms are Cardiac arrest, Kidney infection, Sepsis, Urinary tract infection, Intentional overdose, and Migraine; each is reported as 0.7%. The record does not specify in this summary whether terms refer to participants or events, whether categories overlap, or how relatedness to vaccination was judged.

Death counts are not reported in the registry record. The posted counts should not be interpreted as demonstrating causation or as a complete account of safety. Timing, duration, severity details, and adjudication methods are not reported in the registry record.

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

The record establishes that a Phase II randomized trial evaluated a norovirus bivalent VLP vaccine in healthy adults, with a saline-placebo-first group and two vaccine-first groups. It defines a primary safety endpoint based on solicited local reactions during Days 1 through 7 after the first injection. It also posts group-level counts for serious and other adverse events.

Those details do not establish the frequency of the primary local-reaction outcome, because its numerical results are not reported in the registry record. The serious and other adverse-event counts do not answer that question: they are different safety summaries. The record also does not report numerical results for the listed immune-response outcomes, so no conclusion about antibody responses can be drawn from the posted results.

In general, an observed event in a clinical trial does not by itself establish that the intervention caused it. Causal interpretation requires attention to timing, comparison groups, event definitions, randomization, missingness, and the analysis method. The registry’s brief adverse-event summaries do not provide all of those details. Likewise, differences between group counts should not be treated as evidence of a real group effect without an appropriate estimate and assessment of uncertainty.

The trial’s status is completed, but completion does not mean that all planned outcomes or analyses are available in the registry record. The record lists 27 outcome measures and zero analyses. It does not report the statistical analysis plan, multiplicity strategy, missing-data approach, or sample-size justification. These omissions limit what can be learned about the planned and completed statistical comparisons.

The appropriate interpretation is therefore narrow: the registry record documents the study design, endpoint definitions, and selected adverse-event counts, while leaving the primary endpoint result and much of the statistical analysis unreported. These posted data alone do not support a conclusion about the vaccine’s safety profile as a whole, efficacy, or immune response.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between an outcome definition and an outcome result. The registry precisely names solicited local reactions and the assessment window, but does not post the primary-endpoint counts or percentages. A well-specified endpoint is necessary for interpretation; it is not a substitute for reporting what was observed.

The three-group, randomized, parallel design also illustrates why group-specific denominators matter. The safety summaries identify participants at risk in each group, while the overall enrollment is 454. Because endpoint-specific results and a participant-flow explanation are not posted, readers cannot determine how completely the primary endpoint was assessed or reconcile the group safety populations with total enrollment.

Multiplicity is relevant because the registry lists 27 outcome measures spanning safety and immunogenicity. In general, a prespecified hierarchy or other inferential strategy helps readers understand how multiple outcomes were considered. The registry record does not report such a strategy, so readers cannot determine how the listed outcomes relate to any confirmatory analysis.

Finally, the available adverse-event counts show why descriptive safety data need context. Counts are useful for documenting reported events, but they do not alone establish causation, precision, or between-group differences. The record’s missing primary results and analysis details place a clear boundary on what statistical conclusions can be drawn.

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 principal limitation is that numerical results for the primary endpoint are not reported in the registry record. Although the endpoint and its assessment period are defined, there are no posted group-specific percentages, event counts, confidence intervals, or statistical comparisons for solicited local reactions after the first injection.

The registry lists 27 outcome measures but does not report results for the listed immunogenicity outcomes or most of the described secondary outcomes. It lists zero analyses. This restricts assessment of both the trial’s stated safety aims and its immune-response questions.

The adverse-event information is limited to group-level counts and selected serious-event terms. The registry record does not report detailed event timing, participant-level event histories, relatedness assessments, or methods for handling repeated events. Death counts are not reported. The listed serious-event terms, each at 0.7%, cannot be interpreted as evidence of causation from these data alone.

The record does not report a statistical analysis plan, the trial’s own sample-size justification, multiplicity handling, or missing-data methods. It also does not explain the relationship between enrollment of 454 and the group-specific safety denominators. The full regimen descriptions for the two vaccine-first groups are not reported in the registry record. These limitations prevent a complete appraisal of outcome completeness, statistical precision, and the exact treatment schedules.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of Norovirus Bivalent Virus-Like Particle Vaccine in Healthy Adults — NCT02142504.
• Registry record last updated 2017-08-21; status last verified 2017-08.
• Results first posted 2017-02-23.
• 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

NCT02142504 is a completed Phase II randomized, placebo-controlled, parallel-group trial of a norovirus bivalent VLP vaccine in healthy adults. The record lists enrollment of 454 and masking as quadruple. The primary endpoint is solicited local adverse events at the injection site during Days 1 through 7 after the first injection, in participants who received at least one dose.

Three groups are listed, including a saline-placebo-first group and two vaccine-first groups. The record posts serious and other adverse-event counts by group, but does not report numerical results for the primary endpoint or the listed immunogenicity outcomes. The statistical analysis plan, missing-data methods, and sample-size justification are not reported in the registry record.