Study to Evaluate Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine GSK2282512A When Administered to Children From 6 to 35 Months of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine GSK2282512A When Administered to Children From 6 to 35 Months of Age (NCT01974895), a randomized phase 2 study. The primary outcome is Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of FluLaval® Quadrivalent Vaccine..

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, triple-masked, parallel-group study. The registry record lists GlaxoSmithKline as the sponsor and reports 316 enrolled participants. The study status is completed. The listed start date is 2013-10-23, and the primary completion date is 2014-02-27. The registry record does not specify who was masked or describe the randomization procedure.

Participants were children 6 to 35 months of age. One group received FluLaval Quadrivalent, and the other received Fluzone®. In each group, participants received 1 or 2 doses at Day 0 or Days 0 and 28, according to age and vaccine priming status. The registry defines primed subjects as those who had received a total of 2 or more doses of seasonal influenza vaccine since 01 July 2010. Unprimed subjects had never received seasonal influenza vaccine or had received only one dose since that date.

The study assessed immunogenicity and safety. The primary outcome was the number of FluLaval Quadrivalent recipients who seroconverted for HI antibodies against each of four vaccine strains. Secondary outcomes included antibody titers, seroprotection, mean geometric increase, solicited symptoms, fever, and symptom duration. The record lists 13 outcome measures, but does not report analysis records. It does not describe the allocation ratio, group-specific enrollment at randomization, sample-size justification, or detailed statistical plan.

The two groups allow the study to collect information on both vaccines under a randomized parallel design. However, the listed primary outcome is limited to the FluLaval Quadrivalent group. The registry record therefore does not define the primary outcome as a between-group contrast, even though the study summary describes comparing vaccine activity.

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: 2 subjects were allocated subject numbers but study vaccine was not administered, thus were excluded from the study prior to group assignment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available and subjects for whom assay results were available for antibodies against at least one study vaccine antigen component after 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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Seroconverted Subjects for Haemagglutination Inhibition (HI) Antibodies Against Each of the Four Vaccine Influenza Strains of FluLaval® Quadrivalent Vaccine., measured over 28 days after the last vaccine dose (at Day 28 for primed subjects and at Day 56 for unprimed subjects).

The primary endpoint is a count of FluLaval Quadrivalent recipients who met the registry definition of seroconversion for HI antibodies against each of four vaccine influenza strains. A participant qualified through either of two patterns: a pre-vaccination titer less than 1:10 followed by a post-vaccination titer greater than or equal to 1:40, or a pre-vaccination titer of at least 1:10 followed by at least a 4-fold increase in post-vaccination titer. The registry uses the endpoint to describe an antibody response after vaccination.

The four strains were Flu A/California/7/2009 (H1N1), Flu A/Texas/50/2012 (H3N2), Flu B/Massachusetts/2/2012 (Yamagata), and Flu B/Brisbane/60/2008 (Victoria). Measurement was scheduled 28 days after the last vaccine dose: at Day 28 for primed subjects and at Day 56 for unprimed subjects. The endpoint is based on antibody measurements rather than a count of influenza illness episodes.

In general, a seroconversion measure summarizes whether antibody titers crossed a specified threshold or rose by a specified amount. It can make immunogenicity results easier to interpret as counts of participants meeting a defined response criterion. It does not, by itself, establish how well a vaccine prevents illness. The primary outcome results and strain-specific counts are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a randomized, triple-masked, parallel-group design. In general, random allocation is intended to reduce systematic differences between groups at study entry. Masking is intended to limit the influence of knowledge about assignment on study conduct, assessment, or reporting. The record does not say which people were masked, how the random sequence was generated, how assignments were concealed, or how departures from the assigned groups were handled. These details are not reported in the registry record.

What does the endpoint count?

The primary outcome is a number of subjects meeting the seroconversion definition for each of four strains. It is a binary participant-level classification for each strain: a subject either meets the stated response criterion or does not. The criteria use baseline and post-vaccination HI titers. One criterion requires a baseline titer less than 1:10 and a post-vaccination titer greater than or equal to 1:40; the other requires a baseline titer of at least 1:10 and at least a 4-fold increase.

In general, binary outcomes can be summarized as counts and proportions, while comparisons between groups may use differences, ratios, or model-based estimates. The registry record gives the endpoint unit as subjects and parameter as number. It does not report the strain-specific outcome counts, group comparisons, confidence intervals, p-values, or the statistical test or model used. No numerical inferential result can therefore be interpreted from the registered primary outcome description.

How should the timing be understood?

Outcome measurement was scheduled 28 days after the last dose. The calendar study visit differed by priming status: Day 28 for primed subjects and Day 56 for unprimed subjects. This means the endpoint is tied to time since the last dose, while the named visit day depends on the dosing schedule. In general, a measurement window helps define the period to which an outcome applies. The record does not report whether assessments outside the stated visit timing were permitted or how timing deviations were handled.

What does the analysis population indicate?

The primary outcome description refers to an According-to-Protocol cohort for immunogenicity. It says the cohort included evaluable subjects with available immunogenicity outcome data and subjects with assay results for antibodies against at least one study vaccine antigen. In general, an according-to-protocol analysis focuses on participants who meet specified study requirements and have usable measurements. The exact eligibility rules, exclusions, numbers analyzed, and reasons for exclusion are not reported in the registry record. The description of the cohort is incomplete in the record.

Analysis-population choice can affect interpretation. A restricted cohort may not include everyone randomized, and the result may differ from an analysis that retains all randomized participants according to assigned group. The registry record does not report an intention-to-treat analysis or explain whether the immunogenicity analysis followed randomized assignment. It also does not report how missing antibody measurements were handled, whether missingness was assessed by group, or whether any imputation was used.

Why does uncertainty matter?

In general, a confidence interval describes a range of values reasonably compatible with an estimate under the statistical method used. Its width reflects precision: wider intervals indicate more uncertainty. A p-value, when reported, describes how incompatible the data are with a specified null hypothesis under a model; it does not measure the size or clinical importance of an effect. Neither type of result is reported for the primary endpoint in the registry record.

For counts and proportions, precision depends in part on the number of observations and the frequency of the outcome. Analyses for four separate strains also raise the question of how multiple outcomes are interpreted. The registry record does not report an adjustment or other multiplicity strategy. General methods for handling multiple comparisons vary according to whether analyses are confirmatory or exploratory and how outcomes are prioritized; no particular method can be attributed to this study from the record.

What is the role of planning assumptions?

In general, sample-size planning uses assumptions about the expected effect, variability, significance level, allocation, and desired power. A planning calculation is not an observed result, and it does not establish that a study had a particular probability of detecting an effect after the data are known. The record does not report the trial's own sample-size justification. It also does not provide the primary outcome estimate needed to interpret an illustration based on an observed effect. The listed planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect; they do not establish the study's original design rationale.

Because the registry record has no analysis records and does not give primary outcome results, the statistical methods actually used for the primary endpoint are not reported in the registry record. Any interpretation should distinguish the registered definitions and design from analyses that are not documented.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 13 outcome measures. The primary outcome concerns seroconversion for each of four vaccine strains, while the secondary outcomes include seroconversion counts, HI antibody titers, seroprotection, mean geometric increase, solicited local and general symptoms, fever, and symptom duration. Considering multiple outcomes can increase the chance of finding at least one apparently notable result by chance if many tests are conducted. In general, a prespecified testing hierarchy or multiplicity adjustment can address that issue. The record does not report a multiplicity strategy, testing hierarchy, or which outcomes were intended to support confirmatory conclusions.

The record lists no analysis records. It does not report primary outcome counts, estimates, confidence intervals, or p-values. Thus, the absence of an analysis record should not be read as evidence that there was no analysis; it means that analyses are not reported in the registry record.

For immunogenicity, the record identifies an According-to-Protocol cohort and describes inclusion in terms of evaluability and available assay data. It does not give the number in that cohort, the number excluded, reasons for exclusion, or the number with missing measurements. The record also does not report whether participants were analyzed according to randomized group or how missing data were treated. In general, missingness can affect estimates when the availability of outcome measurements is related to group assignment or participant characteristics. Without counts and handling details, the direction and extent of any such effect cannot be assessed.

The registry record does not report whether a separate safety population was defined, although it gives participants at risk for the adverse-event summaries. It also does not describe follow-up completeness or missing safety information. These reporting gaps limit assessment of how well the analyzed groups represent all enrolled or randomized participants.

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% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: respiratory syncytial virus infection (1.3%), abscess neck (0.6%), convulsion (0.6%), failure to thrive (0.6%), respiratory syncytial virus bronchiolitis (0.6%).

The registry record reports serious adverse events for 158 participants at risk in the FluLaval Quadrivalent group and 156 in the Fluzone group. Serious events affected 5 participants in the FluLaval Quadrivalent group and 4 in the Fluzone group. For other adverse events, the record reports 115 participants affected among 158 at risk in the FluLaval Quadrivalent group and 103 among 156 at risk in the Fluzone group. These figures describe the recorded counts; the registry record does not provide confidence intervals or a comparative statistical analysis.

The listed serious-event terms are respiratory syncytial virus infection at 1.3%, abscess neck at 0.6%, convulsion at 0.6%, failure to thrive at 0.6%, respiratory syncytial virus bronchiolitis at 0.6%, and dehydration at 0.6%. The registry record does not state the group for each term in this list, so the terms and percentages should not be assigned to a particular group based on this record alone. Death counts are not reported in the registry record.

In general, adverse-event counts are descriptive and depend on event definitions, observation time, and completeness of reporting. The record does not provide event-level timing, duration, relatedness for the serious events, or detail on whether participants could contribute more than one event. Counts alone do not establish whether an event was caused by a vaccine or whether groups differ beyond chance variation.

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

The registry record establishes that a randomized, triple-masked, parallel-group Phase 2 study compared FluLaval Quadrivalent and Fluzone in children 6 to 35 months of age. It specifies a primary immunogenicity outcome based on seroconversion against four influenza strains, measured 28 days after the last dose. It also documents the dosing schedule, the broad outcome categories, and adverse-event counts.

The primary endpoint results are not reported in the registry record. The record therefore cannot show the number of participants who met the seroconversion criteria, the precision of those counts, or whether response differed between vaccine groups. Although the study summary describes comparison of vaccine activity, the stated primary outcome is for FluLaval Quadrivalent recipients only. A comparative conclusion would require a documented analysis that the record does not include.

The available adverse-event figures describe how many participants were affected in each group, but do not provide a statistical comparison or uncertainty estimates. The serious-event terms are listed with percentages, without group attribution in the list. The record also does not report deaths. These limitations mean that the posted safety information is descriptive rather than a complete comparative safety analysis.

In general, immunogenicity outcomes measure immune responses, not clinical illness prevention. A seroconversion result can indicate that a participant met the study's antibody-response rule, but it does not alone establish how often influenza occurred or whether a vaccine prevented infection or complications. The registry record lists influenza as the condition and antibody outcomes as measures; it does not report clinical efficacy results.

These data do not establish that either vaccine is more effective or safer. They also do not establish that the vaccines are equivalent. Such conclusions would require outcome estimates, suitable comparisons, and their uncertainty, none of which are reported for the primary outcome in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a comparative study design and a comparative primary endpoint. The study is described as randomized and as comparing two vaccines, but the registered primary outcome counts seroconversion only in the FluLaval Quadrivalent group. A randomized design can support between-group inference, yet the outcome definition alone does not supply that contrast. Readers need to know what was compared and how, not only that groups were randomized.

The endpoint also illustrates how a biological measurement becomes a statistical outcome. HI titers are converted into a binary response using defined baseline and post-vaccination criteria. That makes the result interpretable as the number of subjects meeting a response rule, while also discarding information about the exact titers among participants who fall on either side of the rule. The record does not report the measured counts or additional analyses that might describe the full titer distribution.

Timing depends on priming status and the number of doses: assessment was 28 days after the last dose, at Day 28 for primed subjects and Day 56 for unprimed subjects. This makes clear why endpoint timing should be read alongside the dosing schedule and participant definitions. It also raises analysis questions about how priming groups were represented, which the registry record does not answer.

Finally, the record demonstrates why statistical interpretation depends on reporting of estimates, uncertainty, analysis populations, and missing-data handling. A completed study with enrollment and outcome definitions does not, by itself, provide enough evidence to assess the size or precision of an effect. The absence of reported primary results is a substantive limitation on what can be concluded from this registry record.

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 of the registry record is that it does not report the primary outcome results. It provides no strain-specific seroconversion counts, comparative estimates, confidence intervals, or p-values. It also lists no analysis records. As a result, the primary immunogenicity question cannot be evaluated from the record.

The primary outcome is stated for the FluLaval Quadrivalent group alone, even though the study summary describes comparing vaccine activity with Fluzone. The record does not explain whether comparative immunogenicity analyses were performed or how they were defined. This limits interpretation of the trial as a direct comparison based on its named primary endpoint.

Details needed to assess the immunogenicity analysis are limited. The record refers to an According-to-Protocol cohort, but does not give its size, exclusions, or complete eligibility criteria. It does not report missing-data amounts or methods, analysis by randomized assignment, or the number of participants assessed at each visit. The cohort description itself is incomplete in the registry record.

The record lists 13 outcome measures but does not describe a multiplicity plan or distinguish confirmatory from exploratory analyses. It does not report the trial's sample-size justification, statistical analysis plan, interim analyses, allocation ratio, or methods for random sequence generation and concealment. These items are not reported in the registry record.

Safety reporting is also limited. Serious and other adverse-event counts are available, but the record does not provide uncertainty estimates or a comparative analysis. The serious-event term list does not identify the group for each term. Event definitions, timing, relatedness, and follow-up completeness are not reported in the registry record. Death counts are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate Immunogenicity and Safety of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Influenza Vaccine GSK2282512A When Administered to Children From 6 to 35 Months of Age — NCT01974895.
• Registry record last updated 2018-09-07; status last verified 2016-08.
• Results first posted 2015-04-13.
• 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

This completed Phase 2 study was randomized, triple-masked, and parallel-group. It enrolled 316 children 6 to 35 months of age and compared FluLaval Quadrivalent with Fluzone®. Dosing was 1 or 2 doses at Day 0 or Days 0 and 28, depending on age and vaccine priming status.

The primary outcome was the number of FluLaval Quadrivalent recipients who seroconverted for HI antibodies against four vaccine strains, measured 28 days after the last dose. Secondary outcomes covered antibody responses and safety. The registry record lists 13 outcome measures and no analysis records.

Primary outcome results, comparative immunogenicity estimates, and uncertainty measures are not reported in the registry record. Adverse-event counts are reported for both groups, but the record does not provide a comparative statistical analysis or enough detail to assign each listed serious-event term to a group.