A Study to Evaluate the Immunogenicity and Safety of Seqirus Quadrivalent Influenza Vaccine (QIV) in a Pediatric Population 5 Through 17 Years of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Immunogenicity and Safety of Seqirus Quadrivalent Influenza Vaccine (QIV) in a Pediatric Population 5 Through 17 Years of Age (NCT02545543), a randomized phase 3 study. The primary outcome is The Geometric Mean Titer (GMT) Ratio of Each Virus Strain..

2. Clinical Question

The study asked whether the immune response to Seqirus Quadrivalent Inactivated Influenza Vaccine (Seqirus QIV) was noninferior to the response to a US-licensed 2015-2016 Quadrivalent Inactivated Influenza Vaccine (Comparator QIV) in a healthy pediatric population aged 5 through 17 years. It also assessed safety. The registry record describes eight co-primary endpoints: hemagglutination inhibition (HI) antibody geometric mean titer (GMT) and seroconversion rate (SCR) for each viral strain included in the vaccines.

3. Trial Design

The registry describes a Phase 3, randomized, multicenter, observer-blinded, parallel-group study. Its official title also describes the study as noninferiority. The recorded enrollment is 2278. Participants were in a healthy pediatric population 5 through 17 years of age and were assigned to Seqirus QIV or Comparator QIV. The registry lists quadruple masking; it does not give further detail about which people were masked or how masking was maintained.

The two interventions were biological products. Seqirus QIV was a split virion, inactivated vaccine; its description specifies 60 mcg total hemagglutinin antigen per 0.5 mL dose, 15 mcg for each of the four recommended strains for the Northern Hemisphere 2015/2016 season. Comparator QIV was a US-licensed quadrivalent inactivated influenza vaccine for that season. The registry record does not report additional details about administration or the randomization procedure.

The recorded study start is 2015-09, and primary completion is 2016-01. The study status is completed. Its primary assessment timeframe is 28 days after last vaccination. The registry lists 11 outcome measures, including the co-primary immunogenicity endpoints and safety outcomes; it records 0 analyses. Numerical results for the primary immunogenicity endpoints are not reported in the registry record, so the comparative immune response cannot be described from the posted outcome results.

These design features define a randomized comparison, but they do not by themselves establish what the results were. In particular, the record does not state a noninferiority margin or provide numerical GMT ratios, confidence intervals, or SCR comparisons. The reported enrollment also should not be treated as the count analyzed for every outcome; analysis-specific participant counts 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: Number of subjects screened: 2349. Number of subjects randomized: 2278

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Per Protocol Population was used for the primary and secondary analysis of immunogenicity data and included subjects in the Evaluable Population minus any subjects with deviations that were thought to potentially affect the immunogenicity results, following medical review prior to unblinding.

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: The Full Analysis Set (FAS) was used for analysis of subject characteristics and comprised all subjects who gave informed consent and who were randomized to treatment. Screening failures were not included in the FAS.

6. Primary Endpoint

The registry lists the primary outcome as The Geometric Mean Titer (GMT) Ratio of Each Virus Strain., measured over 28 days after last vaccination..

The primary endpoint is described as the GMT ratio for each virus strain, with a 95% confidence interval. HI antibody titers are laboratory measures of antibody response. A geometric mean summarizes titer values on a multiplicative scale, which is commonly useful when measurements are positively skewed. The study also names SCR as a co-primary endpoint for each included strain. The record does not provide numerical results for either endpoint.

The GMT ratio is defined as the comparator’s postvaccination HI GMT divided by the Seqirus QIV postvaccination HI GMT. In general, a ratio expresses the relative size of two quantities; its interpretation depends on which group is in the numerator and denominator. The ratio’s direction is specified in the registry, but no estimate or confidence interval is posted for the reader to assess.

These endpoints are used to compare immune responses rather than clinical influenza illness. The registry’s stated objective was noninferiority, which asks whether the response with one vaccine is not unacceptably lower than the comparator according to a prespecified margin. That margin is not reported in the registry record. Without both the numerical estimates and the margin, the posted record does not establish whether the noninferiority criterion was met. The stated assessment time was 28 days after last vaccination.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group comparison, with participants assigned to Seqirus QIV or Comparator QIV. Randomization is a general method for allocating participants by chance, intended to make groups comparable on average at the start of a study. It does not guarantee that every measured or unmeasured characteristic is balanced in a particular trial. The randomization sequence and allocation procedures are not reported in the registry record.

What does noninferiority mean?

General explanation: a noninferiority study evaluates whether the response to an intervention is not worse than that of a comparator by more than a prespecified acceptable margin. It is not the same question as whether two treatments are exactly equal. A noninferiority conclusion depends on the chosen margin, the endpoint, the direction of comparison, and the statistical interval or test used. The registry describes the study as noninferiority but does not report the margin or numerical primary results. The conclusion therefore cannot be independently evaluated from this record.

How should the GMT ratio be read?

The registry defines the ratio as the postvaccination HI GMT for Comparator QIV divided by the postvaccination HI GMT for Seqirus QIV. General explanation: a ratio compares the scale of two group summaries, and its meaning follows from the stated numerator and denominator. The GMT is a geometric mean, a summary suited to data analyzed on a multiplicative scale. The registry specifies a 95% confidence interval for the ratio, but does not post the ratio estimate or interval. HI titer results are immunogenicity measures and are not, by themselves, observed counts of influenza illness.

What does a confidence interval convey?

General explanation: a confidence interval represents uncertainty around an estimate under a particular statistical procedure and its assumptions. A narrower interval indicates greater precision than a wider interval on the same scale. For noninferiority, the interval must be judged relative to the specified margin and the correct direction of effect. Neither the interval nor the margin is reported in the registry record, so precision and noninferiority cannot be assessed from the posted primary outcome information.

Why include seroconversion?

The study names SCR as a co-primary immunogenicity endpoint for each included viral strain. A rate summarizes the proportion of participants meeting a defined response criterion. The registry record does not provide the operational definition used for seroconversion or the numerical rates. It also does not provide the specific statistical method used to compare those rates. The endpoint name alone is not enough to recreate that analysis.

How should the safety counts be understood?

General explanation: counts of participants with events are descriptive unless accompanied by a defined analysis that accounts for the relevant population and observation period. A comparison may require information about follow-up, event definitions, and the analysis method. The registry gives group denominators and counts for serious and other adverse events, but does not report a formal comparative estimate or the follow-up details needed to interpret the counts as rates over time. A missing death count is not evidence of zero deaths.

The registry identifies the Per Protocol Population for primary and secondary immunogenicity analyses. It defines this population as the Evaluable Population minus participants whose deviations were judged potentially to affect immunogenicity, following medical review before unblinding. General explanation: per-protocol analyses exclude some participants according to adherence or protocol-deviation criteria, so their results can depend on those criteria. The record does not report the number excluded or the participant counts analyzed for each endpoint.

The sample-size material is described as a planning illustration computed from the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. Its scenarios concern detecting a stated fraction of the observed effect. These are planning illustrations, not observed power and not a substitute for the trial’s own design justification. The registry record does not report the trial’s sample-size justification or enough numerical primary results to assess those illustrations independently.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes eight co-primary endpoints: GMT and SCR for each viral strain included in the vaccines. Evaluating multiple endpoints raises a general multiplicity question: when several hypotheses are tested, the overall chance of at least one false-positive result can differ from the chance associated with a single test. Noninferiority also requires interpreting each relevant result against the prespecified margin. The registry record does not report a multiplicity adjustment, testing hierarchy, or other strategy for handling the co-primary endpoints. It does not provide numerical results for the endpoints or the noninferiority margin.

The primary and secondary immunogenicity analyses used the Per Protocol Population. The record defines this as the Evaluable Population minus participants with deviations thought potentially to affect immunogenicity, following medical review before unblinding. The number included in that population and endpoint-specific analysis counts are not reported in the registry record. The population or analysis set used for the safety counts is also not described in detail.

Missing-data handling is not reported in the registry record. The record does not state how missing titers or incomplete assessments were treated, whether any imputation was used, or whether sensitivity analyses were conducted. These details matter because the available observations may differ from all randomized participants, and conclusions can depend on how incomplete data are addressed. The registry records 0 analyses and does not report interim analyses or a statistical analysis plan. No specific procedure should be inferred from the study’s design label or endpoint descriptions.

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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: suicide attempt (0.2%), abortion spontaneous (0.2%), gasteritis viral (0.1%), influenza (0.1%), depression (0.1%).

The registry’s safety listing reports 8 participants with serious adverse events among 1692 at risk in the Seqirus QIV group, and 2 among 560 at risk in the Comparator QIV group. It also lists other adverse events for 1019 participants at risk in the Seqirus QIV group and 319 at risk in the Comparator QIV group. These are the posted counts; the record does not give a formal statistical comparison or confidence intervals for the groups.

General explanation: adverse-event counts should be interpreted in light of who was observed, how long follow-up lasted, and how events were defined and collected. Those details are not reported in the registry record for these entries. The group denominators also do not match the total recorded enrollment, and the record does not explain that relationship. The counts therefore should not be treated as a complete account of all randomized participants or as directly comparable rates.

The registry lists several serious-event terms with percentages, including suicide attempt and spontaneous abortion, but does not provide further context in that listing about the events or their attribution. The death entries are null; deaths are therefore not reported in the registry record, rather than established as absent.

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

This record establishes that a Phase 3 randomized study compared Seqirus QIV with a US-licensed Comparator QIV in a healthy pediatric population 5 through 17 years of age. Its stated purpose was to assess immune response and safety, with noninferiority evaluated through GMT and SCR endpoints for each included strain. It also records selected safety counts and identifies the Per Protocol Population for immunogenicity analyses.

It does not provide numerical primary results. There are no posted GMT ratio estimates, 95% confidence intervals, or SCR comparisons in the registry record, and the noninferiority margin is not reported. Consequently, the record cannot show whether the trial met its noninferiority objective, how large any observed difference was, or how precisely the immune-response comparison was estimated. The designation of an endpoint as primary or the completion status does not supply the missing result.

The safety entries can be read as descriptive group counts, but they are not a complete comparative safety analysis. The registry does not give the formal between-group analysis, detailed follow-up context, or death counts. An absent death count must not be interpreted as zero deaths. The posted counts alone cannot establish a causal relationship between a vaccine and an event.

General explanation: trial findings are specific to the population, interventions, endpoints, and analysis used. The study concerns immunogenicity and safety in the described pediatric population; it does not report clinical influenza illness outcomes as the primary endpoint. No conclusion about protection from influenza or about treatment benefit can be drawn from the information recorded. The appropriate statistical reading is limited to the study design and the outcomes actually reported, while recognizing that key efficacy results are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between a study’s objective and its reported evidence. The record clearly identifies a randomized Phase 3 comparison and a noninferiority question, but it does not report the numerical results needed to assess that question. Statistical interpretation requires the estimate, its uncertainty, and the noninferiority margin; an endpoint label alone cannot establish a conclusion.

The design also uses multiple co-primary immunogenicity endpoints: GMT and SCR for each included strain. General statistical practice treats multiplicity as an important consideration when several outcomes contribute to a study’s conclusions. The registry record does not report how multiplicity was handled, so readers cannot determine whether or how the endpoint family was controlled in the analysis.

Another important feature is the stated Per Protocol Population for immunogenicity analyses. The registry defines how protocol deviations were considered, including medical review before unblinding, but does not report how many participants were analyzed or excluded. This makes the population definition visible while leaving the resulting analysis counts and their relationship to enrollment unclear.

Finally, safety counts are posted separately from the primary immunogenicity outcomes. They offer some descriptive information but do not replace a comparative analysis with clear follow-up and uncertainty. Together, these features show why registry interpretation depends not only on design labels and endpoint names, but also on complete results, analysis populations, and statistical methods. In this record, those elements are incomplete for evaluating the main noninferiority question.

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 statistical interpretation is that numerical primary outcome results are not reported in the registry record. The GMT ratios, 95% confidence intervals, and SCR results are unavailable, as is the noninferiority margin. Without these items, the stated objective cannot be evaluated from the posted record.

The registry lists eight co-primary endpoints but does not report a multiplicity strategy, the statistical method for comparing SCR, or a statistical analysis plan. Missing-data methods and interim analyses are also not reported in the registry record. Although the Per Protocol Population is defined for immunogenicity analyses, the record does not give its size or endpoint-specific participant counts. The safety analysis population is not fully described.

The safety listings provide group denominators and counts, but do not give a formal between-group estimate, confidence interval, observation-period detail, or explanation of how the denominators relate to recorded enrollment. Death counts are not reported in the registry record. The event-term listing does not by itself establish attribution or comparative risk.

The registry reports an enrollment of 2278, but enrollment should not be substituted for the number analyzed for a particular endpoint. It records 0 analyses, limiting the available quantitative interpretation. The study’s own sample-size justification is not reported in the registry record; the described sample-size material is a planning illustration based on the observed effect, not observed power. These omissions mean the record supports a design-level account and a limited description of safety counts, but not a full assessment of the principal statistical question.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Immunogenicity and Safety of Seqirus Quadrivalent Influenza Vaccine (QIV) in a Pediatric Population 5 Through 17 Years of Age — NCT02545543.
• Registry record last updated 2018-05-23; status last verified 2018-04.
• Results first posted 2017-04-18.
• 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

The registry record describes a completed Phase 3, randomized, multicenter, observer-blinded, parallel-group study of Seqirus QIV versus a US-licensed Comparator QIV in a healthy pediatric population 5 through 17 years of age. Recorded enrollment was 2278. The study start is listed as 2015-09 and primary completion as 2016-01.

The primary objective was noninferiority on GMT and SCR for each included strain, assessed 28 days after last vaccination. The GMT ratio is defined as Comparator QIV divided by Seqirus QIV, with a 95% confidence interval. Numerical primary results and the noninferiority margin are not reported in the registry record. The record identifies the Per Protocol Population for immunogenicity analyses and lists selected safety counts, but does not provide a formal safety comparison. It records 0 analyses.