Immunogenicity and Safety of GSK Biologicals' Influenza Vaccine Versus a Licensed Comparator in Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety of GSK Biologicals' Influenza Vaccine Versus a Licensed Comparator in Children (NCT00764790), a randomized phase 3 study. The primary outcome is Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains.

2. Clinical Question

3. Trial Design

This was a Phase 3 randomized, double-blind, parallel-group trial comparing Fluarix with Fluzone in children aged 6 to 35 months. The registry lists 3317 participants enrolled and identifies GlaxoSmithKline as the sponsor. The study status is completed. Its recorded start date is 2008-10-01, and its primary completion date is 2009-03-05.

The trial had three groups: Fluarix Dose A, Fluarix Dose B, and Fluzone. Dose B used half the volume of Dose A. The registry describes 1 or 2 intramuscular doses, given at Day 0 or at Days 0 and 28. It notes that the schedule depended on prior influenza vaccination, but the available arm descriptions are truncated and do not set out the complete criteria for assigning the schedule. The record also describes different injection sites depending on age.

Randomization is intended to make treatment groups comparable on average, while masking is intended to reduce the influence of treatment knowledge on care and assessment. These are general explanations of the design features; the registry does not report the randomization sequence, concealment procedures, or which people were masked. A parallel design assigns participants to a group for comparison rather than describing a crossover between treatments. The record does not give further detail about follow-up procedures or the statistical plan.

The study assessed immunogenicity and safety. The primary outcome was antibody geometric mean titre against each vaccine strain. Secondary outcomes included seroprotection, seroconversion factor, solicited symptoms, unsolicited adverse events, serious adverse events, new onset of chronic diseases, and rare serious events. The registry does not report numerical results for the primary outcome or a single combined estimate comparing the treatment groups.

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.

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 analysis of immunogenicity, on subjects with available data.

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 Geometric Mean Titer (GMT) of Serum Anti-hemagglutinin (HA) Antibodies Against Each of the Influenza Vaccine Strains, measured over Day 0 (PRE), Day 28 or Day 56 (POST).

The primary endpoint was the geometric mean titre (GMT) of serum anti-hemagglutinin antibodies against each of the three influenza strains in the vaccine. The registry lists measurements at Day 0, before vaccination, and after vaccination at Day 28 or Day 56. The post-vaccination timing depended on whether subjects were primed or unprimed. The analysis population was described as the According-to-Protocol cohort for immunogenicity, among subjects with available data.

Antibody titre is a measure of the concentration of antibodies detected by the specified assay. A geometric mean summarizes titre values on a multiplicative scale and can be useful when measurements are right-skewed or vary across orders of magnitude. This is a general explanation of the statistic; the registry record does not describe the assay’s detailed procedures or the distribution of observed titres.

The endpoint was used to evaluate immunogenicity, meaning the antibody response associated with vaccination. The registry says GMT estimates were to be presented with 95% confidence intervals for all three strains. A confidence interval conveys uncertainty around an estimated group mean under the analysis method; it is not a range that contains a stated proportion of individual participants’ titres. The record does not include the GMT estimates, their confidence intervals, or a reported test of differences between groups. Therefore, the direction and precision of the observed antibody responses cannot be described from the registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean titre describe?

Geometric mean titre is a summary of antibody titre measurements calculated on a multiplicative scale. In general, researchers often use a geometric mean when values are positive and their distribution is skewed, because taking logarithms makes multiplicative differences easier to summarize with methods based on means. The estimate can be transformed back to the original titre scale for interpretation. This is a general description; the registry record does not specify the transformation, the assay details, or the exact calculation procedure used for this trial.

The primary outcome concerned serum anti-hemagglutinin antibodies against each influenza vaccine strain. A GMT is a group-level summary, not a count of people who reached a particular antibody threshold. The registry lists seroprotection as a separate secondary outcome, reinforcing that the GMT and the proportion meeting a threshold are different kinds of summaries. No numerical GMT estimates or seroprotection results are reported in the available record.

What does a 95% confidence interval mean?

In general, a confidence interval expresses the sampling uncertainty around an estimated quantity under the assumptions of the statistical method. It gives a range of values compatible with the data and method at the stated confidence level. It does not mean that most individual measurements fall within the interval, nor does it by itself establish that treatment groups are meaningfully different. To interpret a comparison, the estimate, interval, and the specific contrast being evaluated are needed. The registry says GMTs and their 95% confidence intervals were presented, but provides no such values in the available record.

When an interval is narrow, the estimate is more precise than when an interval is wide, all else equal. Precision depends on factors such as variability and the number of observations contributing to an estimate. The registry does not report outcome-specific analysis counts or the observed variability, so the precision of the trial’s GMT estimates cannot be evaluated from the information available.

Why are there separate assessment times?

The record lists Day 0 as the pre-vaccination assessment and Day 28 or Day 56 as post-vaccination assessments. It says the post-vaccination time depended on priming status: Day 28 for primed subjects and Day 56 for unprimed subjects. This means that the timing is part of the interpretation, rather than a detail that can be ignored when comparing reported summaries. A post-vaccination titre at one time point should not automatically be treated as directly interchangeable with one measured at another. The record does not provide the observed results by time point or further information about how those results were modeled.

What does randomization contribute?

In general, random assignment is intended to balance measured and unmeasured participant characteristics across study groups on average. That can support a causal comparison when assignment, follow-up, and analysis are conducted appropriately. It does not guarantee that every group will have the same characteristics, and it does not remove the need to assess missing data, protocol deviations, and analysis choices. The registry identifies the trial as randomized but does not describe its sequence generation, allocation concealment, or the statistical method used for the primary endpoint.

Double masking is intended to limit bias that could arise if participants or study personnel know which intervention was assigned. The record identifies the trial as double-blind but does not say which parties were masked or how masking was maintained. The description is therefore a design label, not enough detail to assess implementation.

How should safety counts be read?

The registry lists counts of participants with serious adverse events alongside the number at risk for each group. These are descriptive summaries. In general, comparing event counts requires attention to group size, event definitions, observation time, and the possibility of chance variation. A raw count is not itself a risk estimate or a test of a treatment difference. The registry record does not provide a comparative effect estimate, confidence interval, hypothesis test, or detailed exposure time for serious events.

The serious adverse event counts are 35 in Fluarix Dose A, 29 in Fluarix Dose B, and 31 in Fluzone. The corresponding at-risk counts are 1107, 1106, and 1104. These figures should be read as separate group-level counts and denominators, not as evidence on their own that one group is safer. The record lists deaths as null, which means deaths are not reported in the registry record.

What do planning calculations represent?

General sample-size illustrations estimate how many participants might be needed under stated assumptions to detect a chosen effect with a chosen statistical power. They are planning aids, not observed outcomes and not a measure of the trial’s achieved power. The stated assumptions for the illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a fraction of the observed effect. The registry does not report a trial-specific sample-size justification or the sample-size planning rationale. Any planning figures should therefore not be presented as the design basis for this trial or as evidence of the strength of its results.

The record does not reduce the primary outcome, which has multiple strains and time points, to one comparison. Without a specified contrast and reported numerical results, a single effect estimate or a single inferential conclusion cannot be reconstructed from the endpoint description. The registry also does not report interim analyses, a statistical analysis plan, or adjustments for multiple testing. These absences limit what can be said about how inferential decisions were made.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint covers each of three influenza vaccine strains and includes pre-vaccination and post-vaccination assessments. Post-vaccination timing differs according to priming status, with Day 28 for primed subjects and Day 56 for unprimed subjects. Multiple strains, time points, and treatment-group contrasts can create multiple opportunities to evaluate results. In general, testing many outcomes can increase the chance of at least one apparently unusual result if no multiplicity strategy is used. The registry record does not report a multiplicity adjustment, a hierarchy of hypotheses, or which comparisons were designated for formal testing.

The registry lists several secondary outcomes, including seroprotection, seroconversion factor, solicited local and general symptoms, unsolicited adverse events, serious adverse events, new onset of chronic diseases, and rare serious events. Their listing does not establish that every outcome was formally tested or that the analyses were adjusted for multiple comparisons. A statistical plan for these analyses is not reported in the registry record.

The primary immunogenicity population is described as the According-to-Protocol cohort, among subjects with available data. The record does not report the number analyzed, the criteria for protocol adherence, or how missing antibody measurements were handled. It also does not give outcome-specific denominators or describe any imputation or sensitivity analysis. Consequently, the impact of missing data and exclusions from the primary analysis cannot be evaluated.

These limitations do not show that a particular analysis choice was inappropriate; they identify details needed to assess the reported evidence. The record does not include the numerical primary outcome results, a statistical analysis plan, or the methods used to address multiplicity and missing observations.

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: upper respiratory tract infection (0.6%), gastroenteritis (0.5%), gastroenteritis rotavirus (0.4%), pneumonia (0.4%), bronchiolitis (0.4%).

The registry lists serious adverse event counts and the corresponding numbers at risk. In the Fluarix Dose A group, 35 serious adverse events were reported among 1107 at risk; in the Fluarix Dose B group, 29 were reported among 1106 at risk; and in the Fluzone group, 31 were reported among 1104 at risk. The registry also lists upper respiratory tract infection at 0.6%, gastroenteritis at 0.5%, gastroenteritis rotavirus at 0.4%, pneumonia at 0.4%, bronchiolitis at 0.4%, and asthma at 0.2% among the top serious terms.

These entries are descriptive registry summaries. A serious adverse event count is not, on its own, a comparative estimate of harm. General statistical interpretation requires considering how events were defined and collected, the time over which participants were observed, and uncertainty around any group comparison. Those details and a comparative statistical analysis are not reported in the registry record. The record lists deaths as null, so deaths are not reported in the registry record; null should not be read as a confirmed count of zero.

The registry separately lists other adverse-event counts: 805 among 1107 at risk in Fluarix Dose A, 791 among 1106 at risk in Fluarix Dose B, and 808 among 1104 at risk in Fluzone. These are not interchangeable with the serious adverse event counts. The available record does not provide enough detail to interpret their event definitions, timing, or statistical comparison.

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

The trial record establishes that a Phase 3 randomized, double-blind, parallel-group study compared Fluarix regimens with Fluzone in children aged 6 to 35 months. It identifies antibody geometric mean titre against each of the vaccine’s three strains as the primary outcome and describes the planned assessment timing. It also records safety outcomes and group-level serious adverse event counts.

That information does not establish the direction or size of any difference in antibody response. Numerical GMT estimates and their confidence intervals are not reported in the registry record. Without those results, the precision of the estimates, the degree of overlap between groups, and whether any comparison met a statistical criterion cannot be assessed. The registry record also does not report a single primary comparison that combines the multiple strains and assessment times.

The serious adverse event counts can be described as recorded, but they do not establish a causal difference in safety between groups. The registry does not provide a comparative effect estimate or uncertainty interval for those counts. Nor does the available record report the complete numerical results for the other listed safety outcomes.

General statistical interpretation distinguishes a study’s design from its findings. Randomization and masking describe how a trial was intended to limit bias; they are not evidence of a particular treatment effect. Similarly, a defined endpoint and planned confidence intervals indicate how an outcome was framed, but do not replace its observed estimates. The record’s enrollment figure describes the study as registered, while the primary analysis population is an According-to-Protocol cohort with available data; the analyzed number is not reported.

Accordingly, the registry information supports a description of the comparison, outcome, and selected safety counts, but not a conclusion about comparative immunogenicity or safety. The absence of numerical results in the registry record does not imply that results were null or that no difference existed. It means the reported information is insufficient to characterize the result.

13. Why This Trial Matters Statistically

This trial illustrates why a clinical study’s outcome definition and its numerical results need to be read together. The registry specifies antibody GMTs for each of three vaccine strains, confidence intervals, and post-vaccination timing that depends on priming status. Those details define the intended evidence, but the endpoint description alone cannot show the size or precision of an observed response. Without the estimates and intervals, a statistical interpretation of comparative immunogenicity is not possible.

The design also illustrates the difference between a registered enrollment and an analysis population. The record reports 3317 enrolled but describes the primary immunogenicity analysis as using an According-to-Protocol cohort among subjects with available data. The number analyzed and the rules for inclusion are not reported. These details matter because the participants contributing to an outcome can differ from those enrolled, and readers need denominators to understand the scope of an estimate.

Safety interpretation presents a related lesson. Serious adverse event counts are useful descriptive information, but counts alone are not comparative effect estimates. Study duration, definitions, denominators, and statistical uncertainty all affect interpretation. The record provides some counts and at-risk figures, but does not report a comparative analysis or detailed event observation time.

Finally, multiple strains, time points, and secondary outcomes make it important to know how comparisons were prioritized and whether multiplicity was addressed. The registry does not report that statistical plan. This trial therefore serves as a practical example of how a well-defined randomized design can coexist with limits in what can be concluded from the registry information alone. Transparent outcome values, analysis populations, and methods are necessary to assess the evidence, not merely to identify the study 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 registry record does not report numerical results for the primary GMT outcome, including estimates and 95% confidence intervals. It therefore does not permit assessment of the size or precision of antibody responses or direct numerical comparison between Fluarix and Fluzone. The outcome involves three strains and post-vaccination assessment at Day 28 or Day 56 according to priming status, but results by strain, time, and group are not reported.

The primary analysis population is described as the According-to-Protocol cohort among subjects with available data. The number analyzed, criteria for protocol adherence, and handling of missing measurements are not reported in the registry record. This limits assessment of who contributed to the primary outcome and whether exclusions or unavailable data could affect the findings.

The available arm descriptions are truncated. Although the registry states that participants received 1 or 2 doses at Day 0 or at Days 0 and 28, it does not provide a complete account of the schedule-selection criteria. The record also does not describe the randomization sequence, allocation concealment, which parties were masked, or how masking was maintained.

The registry lists several secondary outcomes but does not provide their numerical results or a statistical analysis plan. Multiplicity procedures, interim analyses, sample-size justification, and methods for missing data are not reported in the registry record. Safety information includes selected counts and terms, but comparative estimates, uncertainty intervals, and detailed event follow-up are not reported. These gaps restrict interpretation of both efficacy-related immunogenicity and safety; they do not establish that an unreported result was absent or null.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity and Safety of GSK Biologicals' Influenza Vaccine Versus a Licensed Comparator in Children — NCT00764790.
• Registry record last updated 2018-07-31; status last verified 2016-10.
• Results first posted 2010-07-27.
• 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 NCT00764790, a completed Phase 3 randomized, double-blind, parallel-group study sponsored by GlaxoSmithKline. It compared Fluarix Dose A and Dose B with Fluzone in children aged 6 to 35 months and lists 3317 participants enrolled.

The primary outcome was geometric mean titre of serum anti-hemagglutinin antibodies against each of the three vaccine strains. The record specifies Day 0 and post-vaccination assessment at Day 28 or Day 56, depending on priming status, and describes an According-to-Protocol immunogenicity analysis among subjects with available data. Numerical primary outcome estimates are not reported in the registry record.

Secondary outcomes included immune-response measures and safety events. The registry lists serious adverse event counts by group but does not report a comparative statistical analysis. Details about multiplicity, missing-data handling, and the statistical analysis plan are not reported in the registry record.