Safety and Immunogenicity Among Healthy Children Receiving Fluzone® Quadrivalent, Influenza Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity Among Healthy Children Receiving Fluzone® Quadrivalent, Influenza Vaccine (NCT02222870), a randomized phase 4 study. The primary outcome is Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination With the 2014-2015 Formulation of Fluzone® Quadrivalent Influenza Vaccine.

2. Clinical Question

3. Trial Design

This was a completed, randomized, open-label, parallel-group Phase 4 study sponsored by Sanofi Pasteur, a Sanofi Company. The registry lists enrollment of 60. The study began in 2014-08 and had primary completion in 2014-12. The registry does not report the date of final study completion in the registry record for this account.

The two groups were defined by age at enrollment: 6 months to < 36 months and 3 years to < 9 years. Both group descriptions identify Fluzone® Quadrivalent Influenza Vaccine, No Preservative. The study summary says the 2014-2015 formulation was administered in a 1- or 2-dose schedule in accordance with ACIP recommendations. The specific schedule within each age group, and how participants were assigned to a schedule, are not reported in the registry record.

Randomization indicates that assignment was randomized, while the open-label designation means masking was not used. The parallel model indicates that participants were assigned to a study group rather than following a crossover design. The record does not give further details about the randomization process, allocation concealment, or the rationale for the age-group structure. It also does not describe a comparator receiving another vaccine or no vaccine.

The stated objective was to describe safety. Observational objectives were to describe immunogenicity and to submit available sera for further analysis by CBER, WHO, CDC, and FDA to support recommendations for subsequent influenza vaccine formulations. The registry lists five outcome measures, including the primary solicited-reaction outcome and antibody-related outcomes. It reports no outcome analyses in the available 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: A total of 60 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled and vaccinated in the study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Solicited injection-site and systemic reactions were assessed in the Safety Analysis Set.

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Reporting Solicited Injection-site or Systemic Reactions Following Vaccination With the 2014-2015 Formulation of Fluzone® Quadrivalent Influenza Vaccine, measured over Day 0 up to Day 7 post-any injection.

The primary endpoint is the percentage of participants reporting solicited injection-site or systemic reactions from Day 0 up to Day 7 after any injection. “Solicited” means the assessment focused on a predefined list of reactions rather than collecting only events volunteered without prompting. As a general statistical principle, a predefined symptom list makes the measured outcome more consistent across participants, although it does not capture every possible adverse event.

The list differed by age group. For participants aged 6 to < 36 months, injection-site reactions were tenderness, erythema, and swelling; systemic reactions were fever, vomiting, abnormal crying, drowsiness, appetite lost, and irritability. For participants aged 3 to < 9 years, injection-site reactions were pain, erythema, and swelling; systemic reactions were fever, headache, malaise, and myalgia.

The registry also describes Grade 3 thresholds or definitions for these reactions. Examples include fever above 39.5˚C for the younger group and at least 39.0˚C for the older group, and symptom-specific definitions for severe vomiting, crying, drowsiness, appetite loss, irritability, headache, malaise, and myalgia. These criteria distinguish more substantial reactions from other reported levels. The registry record does not report the observed percentage for the primary endpoint, a confidence interval, or a statistical comparison. Thus, the outcome definition is available, but the analyzed result is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish the study’s design, outcome definitions, and reported findings. The registry identifies a randomized parallel-group study, a percentage-based primary endpoint, and descriptive safety counts. It does not report a statistical analysis plan or an analyzed primary endpoint. The distinctions below explain how these elements are usually interpreted without filling in unreported methods.

What does a percentage endpoint represent?

For a binary outcome, each participant is classified according to whether the event of interest was observed during the defined assessment period. The percentage is based on the number of participants meeting that definition relative to the relevant analysis population. Here, the event is at least one solicited injection-site or systemic reaction in the period from Day 0 up to Day 7 after any injection. The registry specifies the reaction lists and identifies the Safety Analysis Set as the population for assessment.

A percentage depends on both the event definition and the denominator. Different symptom lists apply to the two age groups, so the outcome is not a single identical symptom checklist across all ages. Also, the record does not report the primary endpoint’s actual numerator, denominator, or percentage. The group safety counts for serious and other adverse events are separate entries and should not be substituted for the solicited-reaction result.

Why does the reaction window matter?

An outcome is interpretable only in relation to its observation period. The primary endpoint covers Day 0 up to Day 7 post-any injection. That period defines which reports contribute to this particular outcome; it does not describe all possible follow-up or all adverse events during the study. The registry entries do not provide more detail about data collection procedures, how reports were solicited, or how events spanning the boundary of the window were handled.

Grade 3 criteria further define a severity category for specified reactions. Those criteria are symptom-specific: they include temperature thresholds and functional or frequency-based descriptions. As a general statistical principle, explicit thresholds make a category more reproducible, but estimates still depend on consistent measurement and complete reporting. The registry provides the definitions, not the number or percentage of participants in each severity category.

What can randomization tell the reader?

Randomization is a method for assigning participants to groups. When implemented and analyzed appropriately, it can reduce systematic differences between groups at baseline. The record says the study was randomized, but it does not report the sequence-generation method, concealment procedure, or a statistical comparison between the age groups. Because both groups are described as receiving the same named vaccine and the groups are age-defined, the record does not establish a vaccine-versus-control contrast. Randomization alone does not create an interpretable treatment effect if the groups, intervention contrast, outcome analysis, and estimand are not specified.

The open-label designation indicates that masking was not used. In general, lack of masking can affect reporting or assessment, particularly for outcomes that rely on symptoms reported by participants or caregivers. This is a methodological consideration, not evidence that reporting was biased in this study. The registry does not describe safeguards or procedures that might address this possibility.

How should uncertainty be understood?

A confidence interval is a statistical range intended to describe uncertainty around an estimate under the assumptions of the analysis. A narrow interval usually indicates greater precision than a wide interval, while neither width nor location alone establishes clinical importance. No confidence interval for the primary endpoint is reported in the registry record. No p-value or inferential test result is reported either. Consequently, the primary endpoint cannot be assessed for precision or statistical compatibility with a specified comparison from this record.

Counts without an analysis plan do not reveal how missing observations were handled, whether participants were analyzed according to randomized assignment, or how repeated reactions were summarized. Those choices can affect both the estimate and its interpretation. The record identifies a Safety Analysis Set for the primary outcome but does not give its detailed definition or report its size by group.

What do the planning assumptions mean?

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes an effect to detect as a stated fraction of the observed effect. This is a design-planning framework, not a report of the trial’s observed effect. The numerical outputs and specific effect fractions are not reported in the registry record, so they cannot be interpreted as recommended enrollment targets or as evidence that the trial had a particular probability of detecting an effect.

In general, planning calculations depend on the outcome scale, assumed effect, variability or event frequency, significance level, allocation, and chosen power. A normal approximation simplifies the calculation and may be less appropriate when event counts are sparse or assumptions are not met. The record does not specify enough details to evaluate those assumptions for this study. Any sample-size figures associated with such an illustration are planning quantities, never observed power.

For percentage outcomes, variation can be substantial when event frequencies are low or the analyzed group is small. General methods may use a binomial model for participant-level events, but the registry does not state which model, variance estimator, or interval method was used. No such method should be attributed to the trial without an analysis report.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint includes several symptom categories and time points, and the registry indicates that it was not reduced to a single comparison. It does not report a multiplicity strategy, such as a hierarchy of tests, an adjustment to account for multiple comparisons, or a prespecified primary contrast. Without that information and without reported endpoint analyses, the false-positive risk across potential comparisons cannot be evaluated. This does not establish that a particular adjustment was required or omitted; the approach is not reported in the registry record.

The registry lists secondary outcomes for antibody geometric mean titers before and after vaccination, seroprotection, seroconversion, and geometric mean titer ratios. It also lists a serum-submission objective. Outcome definitions and analysis details beyond the listed descriptions are not reported in the available record. No secondary-outcome analysis results are included in the registry record for this account, so the listed outcomes should be read as intended measures, not findings.

The Safety Analysis Set is identified as the population used to assess solicited reactions. A detailed definition of that set, the number analyzed in each age group, and the reasons for any exclusions are not reported. The registry does not describe missing-data frequency, handling of missing symptom reports, imputation, sensitivity analyses, or whether participants were analyzed according to their randomized assignment. It is therefore not possible to assess the consequences of missing data or departures from the intended analysis population.

The record also does not report interim analyses, stopping rules, or a statistical analysis plan. These items should not be inferred from the study’s completion status or from the sample-size planning method. The absence of such information in the registry record limits assessment of how prespecified the analyses were and how multiplicity and incomplete observations were addressed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5.00% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abscess neck (3.3%).

The registry lists serious adverse event counts by age group: 1 among 30 participants in the 6 to < 36 months group and 0 among 30 in the 3 to < 9 years group. It separately lists other adverse events for 21 among 30 and 22 among 30 participants, respectively. These are descriptive entries and should not be read as the primary solicited-reaction outcome, which covers a defined set of symptoms during Day 0 up to Day 7 after any injection.

The record identifies “Abscess neck” as a top serious adverse event term, with a listed value of 3.3%. The available information does not include the denominator or event details associated with that value. It does not establish whether the event was considered related to vaccination. No causal attribution should be inferred from its appearance in the registry summary.

Deaths are not reported in the registry record. The counts alone do not describe timing, duration, severity beyond the serious-event classification, or clinical course. Nor do they provide an estimate of comparative risk: the record does not report an analysis comparing the groups. Small descriptive counts may be compatible with substantial uncertainty, and the record does not report uncertainty intervals for these safety figures.

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

The registry record establishes that a completed randomized, open-label, parallel-group Phase 4 study evaluated safety and immunogenicity of the 2014-2015 Fluzone Quadrivalent formulation in healthy children across two age-defined groups. It describes a primary outcome based on solicited injection-site and systemic reactions, alongside antibody-related secondary outcomes. It also records group-level counts for serious and other adverse events.

Those details do not provide an analyzed estimate for the primary endpoint. The registry does not report the percentage of participants with solicited reactions, an uncertainty interval, or a statistical test. It also does not report analyses of the listed immunogenicity outcomes. Thus, the record cannot establish the frequency of the primary endpoint in each group, quantify a contrast, or characterize the precision of an effect estimate.

The listed serious and other adverse event counts are descriptive. They do not by themselves show whether an event was caused by vaccination, how groups compare statistically, or what would have occurred without vaccination. The serious-event term and its listed percentage likewise lack the context needed for causal interpretation in the registry entries. The absence of a reported death count should not be converted into a claim about deaths; deaths are not reported in the registry record.

More broadly, study design labels are not outcome findings. Randomization does not supply a treatment-effect estimate when no relevant analysis is reported, and open-label status is a design feature rather than a result. The registry also does not provide enough information to judge missing-data handling, multiplicity, or the details of the statistical plan.

The most defensible reading is therefore descriptive: the study’s stated questions, outcome definitions, design features, and selected safety counts are recorded, while the key analyzed results and their uncertainty are not. The information does not support conclusions that the vaccine does or does not produce a particular level of reaction, antibody response, or comparative safety.

13. Why This Trial Matters Statistically

This study is statistically instructive because it separates outcome definition from outcome reporting. The primary endpoint is described in detail, including the observation window, age-specific reaction lists, and Grade 3 criteria. Yet those definitions do not substitute for an estimate. Without the analyzed percentage and its uncertainty, readers cannot tell how common the endpoint was in the study population or how precisely it was measured.

The age-specific measurement lists also matter. Participants in the two age groups were assessed for overlapping but not identical symptoms. This makes clear why endpoint wording and population definitions are essential when comparing results: a percentage has meaning only in relation to a consistent event definition, assessment period, and denominator. The registry does not report a single comparison that resolves those elements into one estimate.

The record illustrates why safety summaries require careful separation of outcomes. Counts for serious adverse events and other adverse events are not interchangeable with solicited reactions. They refer to different categories of information, and the registry entries do not supply the details needed to merge them or make causal claims. Descriptive counts can be informative about what the registry records while remaining insufficient for comparative inference.

Finally, the study’s planning illustration is distinct from evidence about observed performance. Assumptions such as equal allocation and a normal approximation describe a calculation framework, not an empirical result. Likewise, randomized assignment and completed status do not tell readers which analysis was conducted or whether it was precise. The registry record is therefore useful for identifying the research question and the limits of available evidence, while demonstrating why estimates, uncertainty, analysis populations, and missing-data methods are needed for a complete statistical interpretation.

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 central limitation of the available record is that it does not report the analyzed primary outcome. It gives the outcome definition and assessment window, but no reaction percentage, confidence interval, or test result. The record also indicates that the endpoint involves several categories or time points and was not reduced to a single comparison. This prevents a quantitative assessment of the primary safety question from the information available.

The groups are described by age, and both are associated with the same named vaccine. The record does not explain the allocation of the 1- or 2-dose schedules or provide a comparator receiving a different intervention. It therefore does not present a clearly specified vaccine-versus-control contrast in the registry record. Randomized status alone does not resolve that limitation.

Detailed methods are also absent. The registry record does not report the randomization procedure, allocation concealment, a statistical analysis plan, or a detailed definition of the Safety Analysis Set. It does not describe missing observations, exclusions, imputation, or sensitivity analyses. The handling of multiple outcome categories and time points is not reported. These omissions limit assessment of potential bias and reproducibility.

The safety summary contains counts, but not enough context to determine event timing, relatedness, or the denominator behind the listed serious-event term percentage. It does not report deaths. The listed immunogenicity outcomes have no corresponding analyses in the registry entries. Finally, planning calculations are described in general terms without numerical outputs or the specific effect fractions, so their practical implications cannot be evaluated. These are limitations of what the registry record reports; they do not establish that the underlying study lacked methods or analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity Among Healthy Children Receiving Fluzone® Quadrivalent, Influenza Vaccine — NCT02222870.
• Registry record last updated 2015-10-19; status last verified 2015-09.
• Results first posted 2015-10-19.
• 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

NCT02222870 is a completed randomized, open-label, parallel-group Phase 4 study sponsored by Sanofi Pasteur, a Sanofi Company. It enrolled 60 healthy children and evaluated the 2014-2015 formulation of Fluzone® Quadrivalent Influenza Vaccine in age-defined groups: 6 months to < 36 months and 3 years to < 9 years.

The primary outcome was the percentage reporting solicited injection-site or systemic reactions from Day 0 up to Day 7 after any injection. The stated secondary outcomes concerned antibody titers, seroprotection, seroconversion, and titer ratios. The registry lists serious and other adverse event counts by age group, but does not report a primary endpoint analysis or immunogenicity results in the available record. The statistical plan, missing-data methods, and approach to multiplicity are not reported in the registry record.