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 Study to Evaluate the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine (GSK2282512A) Compared to Fluzone® Quadrivalent in Children 6 to 35 Months of Age (NCT02242643), a randomized phase 3 study. The primary outcome is Haemagglutination Inhibition (HI) Antibody Titers Against Each of the 4 Vaccine Influenza Strains.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02242643 |
| Phase | Phase 3 |
| Condition | Influenza |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 2432 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Children 6 to 35 months of age with influenza listed as the condition of interest. The primary immunogenicity analysis was described for an According-to-Protocol cohort, with the cohort definition only partly available in the registry record.
Intervention
FluLaval™ Quadrivalent. Primed subjects received 1 dose at Day 0; unprimed subjects received 2 doses at Days 0 and 28.
Comparator
Fluzone® Quadrivalent, with the same stated schedule: 1 dose at Day 0 for primed subjects and 2 doses at Days 0 and 28 for unprimed subjects.
Primary question
What were the haemagglutination inhibition antibody seroconversion rates against each of the 4 vaccine influenza strains, and how did the rates compare between the vaccine groups?
The clinical question concerns an immune response measured after vaccination, rather than a reported comparison of influenza illness. The primary endpoint was assessed 28 days after the last vaccine dose: Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects. The registry defines seroconversion using both pre-vaccination and post-vaccination antibody titers.
The record identifies four vaccine strains: Flu A/California/7/2009 (H1N1), A/Texas/50/2012 (H3N2), B/Massachusetts/2/2012 (Yamagata) and B/Brisbane/60/2008 (Victoria). The endpoint was intended to describe antibody responses separately for these strains, with a reported seroconversion rate and a difference in rates as the stated measures. The primary results needed to answer the comparison are not reported in the registry record, so the relative immune responses cannot be assessed from the available results.
3. Trial Design
This was a Phase 3, randomized, triple-masked, parallel-group study sponsored by GlaxoSmithKline. The registry lists an enrollment of 2432 and describes a comparison of FluLaval™ Quadrivalent with Fluzone® Quadrivalent in children 6 to 35 months of age. The study status is completed. The start date was 2014-10-01, and the primary completion date was 2015-03-16.
Both groups had a schedule that depended on priming status. Primed subjects received 1 dose at Day 0, while unprimed subjects received 2 doses at Days 0 and 28. The primary antibody assessment was timed 28 days after the last dose, corresponding to Day 28 for primed subjects and Day 56 for unprimed subjects. Further details about the study procedures beyond the recorded descriptions are not reported in the registry record.
Random allocation is intended to create groups that are comparable, on average, with respect to factors that could affect outcomes. A parallel-group design assigns participants to a group and follows that group’s assigned intervention rather than switching participants between interventions. Triple masking indicates masking at three levels, but the identities of the masked parties are not reported in the registry record.
The record describes the primary immunogenicity analysis as using an According-to-Protocol cohort. It states that the cohort included evaluable subjects who received the assigned study vaccine and had antibody assay results for at least one study strain after vaccination. The remainder of the cohort definition is incomplete in the registry record. No additional details about allocation procedures, stratification, or the statistical plan are 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: Data has been analyzed in sub-groups by age: 6-17 months and 18-35 months and by priming status. 6 subjects were allocated subject numbers but did not receive the study vaccine dose and for 2 subjects the blood samples were withdrawn but they did not participate in the study due to screening failure.
Overall Study
| Stage | FluLaval™ Quadrivalent Group | Fluzone® Quadrivalent Group |
|---|---|---|
| STARTED | 1207 | 1217 |
| COMPLETED | 1132 | 1139 |
| NOT COMPLETED | 75 | 78 |
Reasons for not completing this period:
| Reason | FluLaval™ Quadrivalent Group | Fluzone® Quadrivalent Group |
|---|---|---|
| Protocol Violation | 1 | 2 |
| Withdrawal by Subject | 15 | 10 |
| Migrated/moved from study area | 1 | 3 |
| Lost to Follow-up | 54 | 61 |
| Child placed in foster care by family | 0 | 1 |
| Non-compliance | 1 | 0 |
| Consent withdrawal by parent | 1 | 0 |
| Protocol requirements not followed | 1 | 0 |
| Language barrier | 1 | 0 |
| Withdrawal by subject at Visit 2 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects, who received the study vaccine according to their treatment assignment and for whom the assay results for antibodies against at least one study vaccine strain after vaccination were available.
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 | FluLaval™ Quadrivalent Group | Fluzone® Quadrivalent Group | Total |
|---|---|---|---|---|
| Participants analysed | 1207 | 1217 | 2424 | |
| Age, Continuous | Months | 19.4 (SD 8.7) | 19.5 (SD 8.9) | 19.45 (SD 8.80) |
| Sex: Female, Male: Female | Participants | 547 | 582 | 1129 |
| Sex: Female, Male: Male | Participants | 660 | 635 | 1295 |
6. Primary Endpoint
The registry lists the primary outcome as Haemagglutination Inhibition (HI) Antibody Titers Against Each of the 4 Vaccine Influenza Strains, measured over 28 days after last vaccine dose (i.e. Day 28 for vaccine-primed subjects and Day 56 for vaccine-unprimed subjects).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Subjects |
| Endpoint classification | Binary Endpoint |
The primary endpoint was haemagglutination inhibition (HI) antibody titers against each of the 4 vaccine influenza strains. The registry describes these titers as seroconversion rate (SCR) and SCR difference, with the endpoint assessed 28 days after the last vaccine dose. SCR was defined as the proportion of vaccinees meeting either of two criteria: a pre-vaccination titer lower than 1:10 followed by a post-vaccination titer of at least 1:40, or a pre-vaccination titer of at least 1:10 followed by at least a four-fold increase in post-vaccination titer.
In general, an antibody response endpoint can provide evidence about the immune response generated after vaccination. Seroconversion combines the baseline titer with the later titer, so its definition distinguishes a rise from a low starting level from a substantial increase when the starting level is already higher. The SCR difference expresses the contrast in the proportions meeting that definition between groups.
These measures do not, by themselves, describe the occurrence of influenza illness. The registry record does not report the primary SCR results or the SCR differences for the vaccine strains. Therefore, the endpoint definition is available, but the comparative result and its precision are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the intended comparison and defines the main immunogenicity outcome, but it does not report the primary outcome values. Specifically, no seroconversion rates or between-group SCR differences are reported for the four vaccine strains. The posted results therefore do not establish the direction, size, or precision of the primary immunogenicity comparison. A conclusion about which group had a higher response, or how uncertain a difference might be, cannot be drawn from the record.
The record does include selected safety counts. Serious adverse events were recorded for 5 of 1207 subjects in the FluLaval™ Quadrivalent group and 4 of 1217 subjects in the Fluzone® Quadrivalent group. Other adverse events were recorded for 932 of 1207 and 895 of 1217, respectively. These are descriptive counts, not an adjusted comparison. The registry does not report uncertainty intervals or a statistical test for these comparisons, and the event definitions and ascertainment details are not fully described in the available record.
The listed serious-event terms include Febrile convulsion at 0.4%, Dehydration at 0.2%, Asthma at 0.2%, Respiratory syncytial virus bronchiolitis at 0.2%, Bronchiolitis at 0.2%, and Gastroenteritis at 0.2%. The record does not provide an arm-specific breakdown for these terms. The percentages should therefore be read as registry-listed summaries rather than as a basis for comparing the vaccine groups.
In general, a difference in observed counts is not enough to determine whether groups differ beyond the variation expected from sampling. A confidence interval would describe the range of values reasonably compatible with the data under the analysis assumptions; no such interval for these safety comparisons is reported in the registry record. Statistical significance, if reported, would also need to be interpreted alongside the size and precision of an effect, not as a measure of clinical importance.
The study was randomized and triple-masked, design features that can reduce certain sources of bias. They do not replace the need for complete outcome reporting. The registry lists 14 outcome measures and 8 analyses, but the available primary outcome results are not reported in the registry record. The absence of those results limits interpretation of the main comparison, regardless of the study design.
The safety counts should also be considered in context: they are counts observed within the recorded groups, and the registry does not supply a full account of adverse-event definitions, follow-up completeness, or the handling of missing safety information. The record lists no death counts. Consequently, the safety information supports a description of what was recorded, not a broad conclusion about comparative safety.
9. Statistical Methods Explained
The primary endpoint is binary at the participant level: each participant either meets the registry’s seroconversion definition or does not. The registry describes the endpoint as the number of subjects and specifies the seroconversion rate and rate difference. In general, a rate is the number of participants meeting the outcome divided by the number assessed for that outcome. A rate difference compares those proportions directly. Neither the primary counts nor the rates are reported in the registry record, so these quantities cannot be interpreted for the study’s vaccine comparison.
What does the seroconversion definition capture?
The definition uses the pre-vaccination and post-vaccination HI titers together. For a pre-vaccination titer lower than 1:10, the stated criterion is a post-vaccination titer of at least 1:40. For a pre-vaccination titer of at least 1:10, the criterion is at least a four-fold increase after vaccination. In general, this type of definition makes the response threshold depend on the baseline value: a participant starting below the stated threshold is assessed using an absolute post-vaccination level, while a participant starting at or above it is assessed by the size of the increase.
What would a confidence interval add?
In general, a confidence interval communicates the uncertainty around an estimated effect. A narrow interval indicates greater precision under the analysis assumptions; a wide interval indicates that a range of effect sizes remains compatible with the data. For a difference in rates, the interval would help distinguish a precise estimate from one that is too uncertain to support a clear interpretation. The registry record does not report confidence intervals for the primary comparisons, and it does not report the primary SCR estimates themselves.
What does randomization contribute?
In general, random assignment helps balance both measured and unmeasured participant characteristics across groups on average. Masking can limit the influence of knowledge about treatment assignment on behavior, assessment, or reporting, depending on who is masked and how the study is conducted. The registry describes the study as randomized and triple-masked, but does not report the allocation procedure or identify the masked parties. These design labels alone do not show that all potential sources of bias were eliminated.
What can the adverse-event counts tell a reader?
The reported safety figures are counts of subjects with events and the corresponding group denominators. In general, counts should be interpreted with their denominators because group sizes may differ. A direct statistical comparison would also need to account for uncertainty and specify the event definitions and analysis approach. No adjusted safety comparison, confidence interval, or test result is reported in the registry record. The counts should therefore be treated as descriptive rather than as proof of a difference or equivalence.
What is the role of the planning illustrations?
In general, a sample-size calculation describes the number of participants a future or planned study might require under specified assumptions about the effect to detect, the significance level, allocation, and statistical approximation. The planning illustrations associated with this study are based on the observed effect and state assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. Such illustrations are planning scenarios, not observed power and not evidence that the study was designed using those assumptions. The registry record does not report the trial’s own sample-size justification or design calculation.
In general, observed power is not a substitute for an effect estimate and its uncertainty. A study’s observed result is best understood through the estimated group contrast, its confidence interval, and the outcome definition. For this record, the primary contrast and its uncertainty are not reported. The planning assumptions cannot fill that reporting gap or establish whether the primary comparison was conclusive.
The record identifies an According-to-Protocol cohort for the immunogenicity analysis. Such a population is generally intended to include participants who meet specified requirements for receiving the assigned intervention and having outcome data. The record’s cohort description is incomplete, so the full eligibility rules and exclusions cannot be assessed. Details of the statistical model, covariate adjustment, missing-data methods, and sensitivity analyses are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint covers antibody responses to each of the 4 vaccine influenza strains, and the registry also lists secondary outcomes across age groups, priming-status groups, antibody measures, and solicited symptoms. The record lists 14 outcome measures and 8 analyses. These multiple outcomes and subgroup views create more than one possible statistical comparison. In general, when many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan addresses multiplicity.
The registry record does not report whether a multiplicity adjustment was planned, whether outcomes were ordered hierarchically, or whether a particular strain or comparison was designated as controlling the overall error rate. The stated primary outcome has several categories or time points and is not reduced to one comparison in the posted results. Without the relevant analysis plan and complete results, a reader cannot determine how any multiple-testing issue was handled.
The record describes the immunogenicity population as an According-to-Protocol cohort and gives part of its definition, but the description is truncated. It does not report the full analysis-population criteria, the number analyzed for each outcome, or reasons participants may have been excluded from an analysis. Missing-data handling, including any imputation or sensitivity analysis, is not reported in the registry record.
These omissions matter because analysis populations and missing outcomes can affect the interpretation of a treatment-group contrast. In general, excluding participants after randomization may alter the balance created by random assignment, while missing outcome data can introduce uncertainty if the missingness relates to participant characteristics or outcomes. The record does not provide enough information to evaluate these possibilities for the primary immunogenicity analysis.
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 |
|---|---|---|---|
| FluLaval™ Quadrivalent Group | 5 | 1207 | 0.4% |
| Fluzone® Quadrivalent Group | 4 | 1217 | 0.3% |
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 |
|---|---|
| FluLaval™ Quadrivalent Group | 932 of 1207 |
| Fluzone® Quadrivalent Group | 895 of 1217 |
Most frequent serious adverse event terms
| Event term | Organ system | FluLaval™ Quadrivalent Group | Fluzone® Quadrivalent Group |
|---|---|---|---|
| Febrile convulsion | Nervous system disorders | 5 of 1207 | 4 of 1217 |
| Dehydration | Metabolism and nutrition disorders | 2 of 1207 | 3 of 1217 |
| Asthma | Respiratory, thoracic and mediastinal disorders | 2 of 1207 | 1 of 1217 |
| Bronchiolitis | Infections and infestations | 1 of 1207 | 2 of 1217 |
| Gastroenteritis | Infections and infestations | 1 of 1207 | 2 of 1217 |
| Cellulitis | Infections and infestations | 1 of 1207 | 1 of 1217 |
| Respiratory syncytial virus bronchiolitis | Infections and infestations | 2 of 1207 | 0 of 1217 |
| Urinary tract infection | Infections and infestations | 1 of 1207 | 1 of 1217 |
| Abscess | Infections and infestations | 0 of 1207 | 1 of 1217 |
| Accidental exposure to product | Injury, poisoning and procedural complications | 1 of 1207 | 0 of 1217 |
Most frequent non-serious adverse event terms
| Event term | Organ system | FluLaval™ Quadrivalent Group | Fluzone® Quadrivalent Group |
|---|---|---|---|
| Irritability/Fussiness | General disorders | 630 of 1159 | 582 of 1152 |
| Pain | General disorders | 509 of 1156 | 462 of 1151 |
| Drowsiness | General disorders | 471 of 1159 | 471 of 1152 |
| Loss of Appetite | General disorders | 391 of 1159 | 385 of 1152 |
| Fever | General disorders | 183 of 1159 | 178 of 1152 |
| Upper respiratory tract infection | Infections and infestations | 111 of 1207 | 102 of 1217 |
| Fever | General disorders | 82 of 1159 | 93 of 1152 |
| Cough | Respiratory, thoracic and mediastinal disorders | 70 of 1207 | 77 of 1217 |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 59 of 1207 | 76 of 1217 |
| Nasopharyngitis | Infections and infestations | 66 of 1207 | 54 of 1217 |
Serious events with the highest arm-level rate: febrile convulsion (0.4%), dehydration (0.2%), asthma (0.2%), respiratory syncytial virus bronchiolitis (0.2%), bronchiolitis (0.2%).
The registry reports serious adverse events for 5 of 1207 subjects in the FluLaval™ Quadrivalent group and 4 of 1217 subjects in the Fluzone® Quadrivalent group. It also reports other adverse events for 932 of 1207 and 895 of 1217, respectively. These figures are counts with their recorded group denominators; they are not adjusted comparisons and do not by themselves establish that the groups differ.
The record lists Febrile convulsion at 0.4%, Dehydration at 0.2%, Asthma at 0.2%, Respiratory syncytial virus bronchiolitis at 0.2%, Bronchiolitis at 0.2%, and Gastroenteritis at 0.2% among the top serious adverse-event terms. It does not report which group contributed each listed term or provide the underlying term-specific counts. Death counts are not reported in the registry record.
In general, safety comparisons are easier to interpret when event definitions, observation periods, group-specific counts, and uncertainty estimates are available. The registry record does not report a statistical test or confidence interval for the figures above. They should be read as descriptive reports of recorded events, not as evidence of equivalence or a definitive difference in safety.
12. What the Result Does, and Does Not, Mean
The trial record describes a randomized, triple-masked comparison of two quadrivalent influenza vaccines in children 6 to 35 months of age. Its primary outcome was an antibody-response measure, defined through seroconversion against each of the 4 vaccine strains. The registry provides the endpoint definition and assessment timing, but not the primary response rates or the differences between groups.
That distinction is central to interpretation. Without the primary estimates, there is no basis in the registry record for describing the magnitude or direction of the immunogenicity comparison, or the precision of any difference. A study design can make a comparison more credible, but it cannot substitute for the results needed to evaluate the comparison.
The safety record supplies counts for serious and other adverse events in each group and lists selected serious-event terms with percentages. Those figures provide descriptive information about recorded events. They do not establish that the groups had the same safety profile, nor do they establish a difference. The registry does not report uncertainty intervals or a statistical comparison for these safety counts, and it does not provide an arm-specific breakdown for the listed serious-event terms.
In general, an immune-response endpoint and a clinical disease outcome answer different questions. An antibody measure characterizes the response defined by the study; it does not, by itself, report how often participants experienced influenza. The registry lists influenza as the condition but does not report a clinical influenza outcome in the primary endpoint description.
The record therefore supports a careful account of the study design, the prespecified response definition, and selected safety counts. It does not support a conclusion about the comparative primary immunogenicity result or a broad conclusion about comparative safety. The missing primary results and limited detail about analysis populations and missing data should remain part of any interpretation.
13. Why This Trial Matters Statistically
This study illustrates why a clinical trial record needs both a clear outcome definition and complete result reporting. The primary endpoint is described in enough detail to understand what counted as seroconversion and when the response was assessed. Those details make the intended estimand more interpretable: the study sought to compare the proportions meeting the response definition after vaccination, across four vaccine strains.
At the same time, the record does not report the primary rates or their differences. This creates a direct gap between knowing what the trial planned to measure and knowing what its data showed. In statistical interpretation, the estimated contrast and its uncertainty are essential; a design description alone cannot answer the comparison.
The study also shows why denominators and analysis populations matter. The safety counts are paired with group denominators, while the immunogenicity analysis is described for an According-to-Protocol cohort whose full definition is unavailable. These are different contexts for interpreting results. A reader needs to know who contributed outcome data and how exclusions or missing measurements were handled to assess the reach of an estimate.
Finally, the multiple strains, outcomes, age groups, and priming-status categories create a setting in which multiplicity and analysis choices may matter. The registry lists many outcomes and analyses but does not report how multiplicity was handled. This does not establish that the analysis was inappropriate; it means the available record does not allow that aspect to be evaluated. The example underscores that precision, outcome reporting, population definitions, and transparent analysis plans all contribute to a sound statistical reading.
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 most important limitation for interpreting this registry record is that the primary immunogenicity results are not reported. The record does not give the seroconversion rates or the between-group differences for the four strains, so the main comparison cannot be quantified or evaluated for precision.
The immunogenicity population description is incomplete. It identifies an According-to-Protocol cohort and begins to state eligibility conditions, but the full definition is not reported in the registry record. The number analyzed for each strain, the exclusions from the cohort, and the handling of missing assay results are also not reported. These details are needed to understand which participants contributed to the primary analysis.
Although the record lists 14 outcome measures and 8 analyses, it does not describe a multiplicity strategy or provide a complete statistical analysis plan. It also does not report the primary comparison’s uncertainty estimates, statistical tests, or any adjusted analyses. The trial’s own sample-size justification is not reported in the registry record; the planning illustrations are not a substitute for that justification or for observed estimates.
The safety information is limited to group-level counts for serious and other adverse events and selected serious-event terms with percentages. The listed terms are not broken down by group, and death counts are not reported in the registry record. Definitions, follow-up details, and statistical comparisons for these safety outcomes are not available in the record. These limitations restrict interpretation of both the primary comparison and the scope of the safety findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate the Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine (GSK2282512A) Compared to Fluzone® Quadrivalent in Children 6 to 35 Months of Age — NCT02242643.
- Registry record last updated 2018-09-07; status last verified 2017-10.
- Results first posted 2016-04-12.
- 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.
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18. Record Summary
The registry describes a completed Phase 3, randomized, triple-masked, parallel-group study sponsored by GlaxoSmithKline. It compared FluLaval™ Quadrivalent with Fluzone® Quadrivalent in children 6 to 35 months of age, with an enrollment of 2432. The primary endpoint was HI antibody seroconversion against each of the 4 vaccine strains, assessed 28 days after the last dose.
The registry defines seroconversion and describes an According-to-Protocol immunogenicity cohort, but the cohort description is incomplete. Primary seroconversion rates and between-group differences are not reported in the registry record. Safety counts are reported for serious and other adverse events in both groups, alongside selected serious-event terms. The record does not report uncertainty estimates or statistical comparisons for those safety counts. Multiplicity handling, missing-data methods, and the trial’s own sample-size justification are not reported in the registry record.