Immunogenicity and Safety Study of a GlaxoSmithKline Biologicals' Candidate Influenza Vaccine in Healthy Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety Study of a GlaxoSmithKline Biologicals' Candidate Influenza Vaccine in Healthy Children (NCT00985790), a randomized phase 2 study. The primary outcome is Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the 3 Fluarix Vaccine Strains..

2. Clinical Question

3. Trial Design

This was a randomized, triple-masked, parallel-group Phase 2 study sponsored by GlaxoSmithKline. The registry record lists an enrollment of 599 and a completed study status. The study start date was 2009-10-08 and the primary completion date was 2010-05-21. These dates describe the record’s study timeline, not the timing or availability of each participant’s outcome data.

The two named interventions were influenza vaccine GSK2321138A and Fluarix. The recorded age range was 18 to 47 months. The arm descriptions distinguish subjects by whether they had previously received a 2-dose priming immunization with Fluarix in study NCT00764790. For previously primed subjects, each arm description specifies one dose of its assigned vaccine at Day 0. The text describing unprimed subjects is cut off, so their dose schedule and the details distinguishing the primed and unprimed groups cannot be fully established from the registry record.

Randomization and triple masking describe features of the study design, but the specific randomization procedure, who was masked, and how masking was maintained are not reported in the registry record. The record also does not report a primary-outcome comparison that could be interpreted as a direct estimate of the difference between the two vaccines. Because the primary outcome includes measurements before and after vaccination, and post-vaccination timing could be Day 28 or Day 56, a meaningful interpretation depends on the relevant measurement time and analysis population. The registry record identifies the post-vaccination measurements as primary, but does not provide a single numerical result for them.

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: For demography and safety, results are presented as per the main study groups. For some outcome measures and where relevant, subjects as in these 2 main groups are split according to their priming status at study entry.

Overall Study

Reasons for not completing this period:

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 for whom data concerning Immunogenicity outcomes variables were available and for whom assay results were available for antibodies against at least one study vaccine 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 Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against the 3 Fluarix Vaccine Strains., measured over At Day 0 [PRE] and at 28 days post last vaccination (Day 28 or Day 56) [POST].

The primary endpoint concerns serum hemagglutination inhibition, or HI, antibody titers against the 3 influenza strains included in Fluarix: FLU A/Brisbane/59/07 (H1N1), Flu A/Uruguay/716/07 (H3N2), and Flu B/Brisbane/60/08 Victoria (VICT). The registry describes titers as geometric mean titers, or GMTs. A geometric mean summarizes measurements on a multiplicative scale and is commonly used for antibody titers, which can vary over a wide range. It is not the same as an arithmetic average.

The record gives a reference cut-off value of 1:10. The endpoint was assessed at Day 0 before vaccination and 28 days after the last vaccination, with the post-vaccination visit recorded as Day 28 or Day 56. The post-vaccination results were designated as the primary outcome variables; the pre-vaccination measurements provide context for antibody levels before the study vaccination.

GMTs describe the central level of measured antibody titers in the analyzed population. The stated 95% confidence interval expresses uncertainty around an estimated GMT; it is not a range containing a fixed proportion of individual participants’ titers. Interpretation of a vaccine comparison would require the relevant post-vaccination GMTs and their uncertainty, ideally alongside a clearly specified contrast. Those numerical primary results and a single comparison are not reported in the registry record, so the endpoint’s direction, size, and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary antibody endpoint is expressed as a geometric mean titer. In general, titers are measured on a scale where changes are naturally interpreted multiplicatively rather than as fixed additive increments. A geometric mean is obtained by working on a logarithmic scale, averaging there, and returning to the original scale. This approach can be suitable for antibody measurements that are positively valued and widely spread. The registry record names GMT as the summary measure but does not give the exact calculation procedure, transformation, or handling of values below the assay cut-off.

The registry states a reference cut-off of 1:10. A cut-off is a threshold used to classify or contextualize measured antibody levels; it is not itself a treatment-effect estimate. The record does not describe how titers below that threshold were represented in the GMT calculation, whether the threshold was used in all analyses, or how assay results were handled when unavailable. Such details can affect summary statistics, so they should not be assumed.

The endpoint description includes a 95% confidence interval for GMTs. In general, a confidence interval conveys uncertainty due to sampling and analysis assumptions. A narrower interval indicates greater precision for the quantity being estimated, while a wider interval indicates more uncertainty. It is not a statement that a specified fraction of individual antibody measurements lies inside the interval. The registry record does not provide the numerical intervals, so precision cannot be evaluated for the primary endpoint.

The timing is also important. Measurements were specified at Day 0 before vaccination and 28 days after the last vaccination, with the post-vaccination visit identified as Day 28 or Day 56. The post-vaccination measurements are designated as primary. A pre-vaccination value can describe baseline antibody levels, while a post-vaccination value describes levels at the specified follow-up. A comparison could be framed using post-vaccination levels, change from baseline, or another prespecified quantity; these approaches need not give the same estimate. The registry record does not report the analysis contrast or how the two post-vaccination visit times were handled.

For a direct comparison between groups, the statistical question should be made explicit. A difference on the original scale, a ratio of GMTs, or a comparison of changes can answer different questions. A confidence interval for the contrast is generally more informative than considering whether separate group intervals overlap. The registry record does not report a contrast, a test statistic, a p-value, or a model used for the primary outcome. No adjusted analysis is reported in the registry record.

The record defines the primary immunogenicity population as an According-To-Protocol cohort. It describes this as including evaluable subjects for whom immunogenicity outcome data were available and assay results were available for antibodies against at least one study vaccine component. In general, an according-to-protocol analysis focuses on participants meeting specified evaluation criteria and with usable measurements. It can differ from an analysis based on all randomized participants. The full cohort definition, exclusions, participant flow, and group-specific analysis counts are not reported in the registry record.

Several strains and time points create multiple opportunities for results to be examined. In general, multiplicity matters because interpreting many tests as if each were the sole test can increase the chance of a misleading positive finding. A statistical plan may address this by defining a primary contrast, a testing order, or an adjustment procedure. The registry record does not report a multiplicity strategy, a hierarchy among strains and visits, or an adjustment for multiple testing. It is therefore not possible to determine how any underlying analyses accounted for the collection of endpoints.

Over-dispersion is a general issue when the observed variation in data exceeds what a chosen statistical model assumes. In that setting, uncertainty estimates from a model that ignores the extra variation can be too small. For antibody titers, the choice of scale and distribution is relevant to how variation is represented. The record does not identify a fitted model or provide diagnostics, so there is no basis to assess whether over-dispersion was evaluated or whether a particular model was used.

Sample-size calculations are planning tools, not evidence about the observed trial result. The registry record describes a planning illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such an illustration estimates the participants per arm that might be needed under its assumptions to detect a specified effect with a stated power. It is not the trial’s own design justification and is not observed power. Because the primary result is not reduced to one comparison in the record, the planning illustration cannot be interpreted as a definitive assessment of the study’s ability to detect a single primary effect. The record does not report the original sample-size justification or a statistical analysis plan.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint spans antibody titers against 3 strains and includes pre-vaccination and post-vaccination measurements, with the post-vaccination visit identified as Day 28 or Day 56. The secondary outcomes add titers, seropositivity, seroconversion, and seroconversion factors against 4 strains. This breadth raises a general multiplicity issue: when many outcomes, visits, or contrasts are examined, interpretation depends on which comparisons were prespecified and whether any adjustment or testing hierarchy was used. The multiplicity strategy is not reported in the registry record.

The registry does not report an analysis population flow or group-specific counts for the primary endpoint. It describes the immunogenicity analysis population as an According-To-Protocol cohort of evaluable subjects with available immunogenicity data and assay results for antibodies against at least one study vaccine component. The remaining cohort wording is incomplete in the registry record. The record does not explain which participants were excluded, how protocol deviations were handled, or whether results were also analyzed in a population including all randomized participants.

Missing-data handling is not reported in the registry record. In general, missing antibody measurements can affect estimates if the probability of having an observed result is related to antibody levels or other characteristics. Complete-case or according-to-protocol analyses describe those with usable data but do not, by themselves, establish that missingness has no effect. The record does not state whether values were imputed, whether sensitivity analyses were conducted, or how unavailable assay results were treated.

The number of analyses is listed as 0, and the record does not report a statistical analysis plan, outcome-level estimates, or inferential tests. Thus the available information does not permit an assessment of multiplicity control, missing-data assumptions, or the robustness of the primary result.

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: bronchopneumonia (0.3%), urticaria (0.3%).

The registry record reports serious adverse events for the GSK2321138A group as 0 among 298 at risk, and for the Fluarix group as 2 among 301 at risk. These are descriptive counts over the safety reporting period represented in the record. No deaths value is reported in the registry record, so the missing value should not be read as confirmation that no deaths occurred.

The record lists bronchopneumonia and urticaria as top serious event terms, each with a reported value of 0.3%. It does not specify in this summary which group or groups those terms correspond to, or whether the percentages refer to participants, events, or another denominator. Their context therefore cannot be resolved from the registry record alone.

Other adverse events are reported as affecting 230 of 298 at risk in the GSK2321138A group and 221 of 301 at risk in the Fluarix group. These counts are not the serious adverse event counts. The record does not provide event-level detail, severity distributions, exposure-adjusted rates, or a statistical comparison. Differences in raw counts should not be interpreted as evidence of a causal safety difference. The registry record does not report the detailed definitions, ascertainment procedures, or complete follow-up context needed for a more extensive safety analysis.

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

The available record establishes that this was a randomized, triple-masked, parallel-group Phase 2 study in healthy children and identifies GSK2321138A and Fluarix as the interventions. It also describes a primary immunogenicity endpoint based on GMTs against the 3 Fluarix vaccine strains, with pre-vaccination and post-vaccination assessment. These design details clarify the question the study was intended to address.

However, the record does not include numerical results for the primary GMT endpoint, confidence intervals, a group contrast, or a test of the primary outcome. It does not reduce the multiple strains and time points to one comparison. Thus it is not possible to judge from the registry record how large or precise any antibody-titer difference was, or whether the data support a particular statistical interpretation. Missing results do not show that the groups were equivalent, nor do they demonstrate that one group had a greater response.

The safety counts describe serious and other adverse events in the recorded groups, but are not a substitute for an analysis of the primary immunogenicity question. They also do not, by themselves, establish a safety difference or equivalence. The record’s serious event terms lack enough contextual detail to connect each listed term to a particular group or denominator.

These limits concern what can be concluded from the registry record, not necessarily what investigators may have analyzed elsewhere. Additional numerical results and analysis details are not reported in the registry record. Without those details, interpretation should remain descriptive: the study’s design and endpoint are identifiable, while the primary effect estimate, its uncertainty, and the handling of several analysis choices are not available. No conclusion about treatment benefit or lack of benefit follows from the information recorded.

13. Why This Trial Matters Statistically

This study is statistically relevant because it illustrates the distinction between a clearly named endpoint and a result that can be interpreted quantitatively. The registry specifies GMTs for antibody titers, a 95% confidence interval, the strains of interest, and the measurement schedule. Those details identify what the investigators intended to measure. A numerical estimate and a defined comparison are still needed to understand the observed response and its precision.

It also highlights the importance of defining the analysis target when an endpoint spans several strains and visits. A result for one strain or time point may not stand for the full set of outcomes. Prespecifying a primary contrast and explaining how additional tests are handled helps readers distinguish the central question from supporting analyses. Those details are not reported in the registry record.

The stated According-To-Protocol population illustrates another important statistical distinction. An analysis limited to evaluable participants with available assay results can differ from an analysis of all randomized participants. Transparent reporting of exclusions, missing observations, and sensitivity analyses helps readers assess how well the analyzed population represents the randomized groups. That information is not available in the record.

Finally, the safety counts show why raw event numbers need context. Denominators and event definitions matter, and a count alone does not quantify comparative risk or establish causality. In this case, the record permits a basic descriptive reading of the reported counts but not a complete comparative safety analysis. The trial is therefore useful as an example of how design and measurement details can be present while the information needed for statistical interpretation remains incomplete.

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 consequential limitation for interpreting the trial is the absence of numerical primary outcome results. Although the record identifies GMTs and 95% confidence intervals, it does not report the estimates, their intervals, or a direct group comparison. It also does not provide a single primary comparison across the several strains and post-vaccination time points. This prevents assessment of effect size and precision.

The primary analysis population is only partly described. The record defines an According-To-Protocol cohort using evaluability and assay availability, but the description is incomplete. Group-specific analysis counts, participant flow, exclusions, and protocol-deviation rules are not reported in the registry record. Missing-data methods and sensitivity analyses are also not reported.

The endpoint description leaves analysis details unresolved. The registry does not state how measurements at Day 28 or Day 56 were handled together, how pre-vaccination values entered the analysis, or how titers below the reference cut-off of 1:10 were treated. The statistical model, contrast scale, and multiplicity approach are not reported. These omissions limit assessment of whether estimates would be comparable across strains, visits, and analysis choices.

The arm descriptions distinguish primed and unprimed subjects, but the text for unprimed subjects is incomplete. The record therefore does not fully establish the dosing details for those subjects or how prior priming status related to randomization and analysis. The safety summary also lacks detailed event context, and the deaths value is not reported. These limitations restrict interpretation of both immunogenicity and safety from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity and Safety Study of a GlaxoSmithKline Biologicals' Candidate Influenza Vaccine in Healthy Children — NCT00985790.
• Registry record last updated 2018-09-21; status last verified 2016-09.
• Results first posted 2013-03-12.
• 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.

18. Record Summary

This completed, randomized, triple-masked, parallel-group Phase 2 study compared influenza vaccine GSK2321138A with Fluarix in healthy children aged 18 to 47 months. The registry lists enrollment of 599, a start date of 2009-10-08, and a primary completion date of 2010-05-21.

The primary endpoint was serum HI antibody GMTs against 3 Fluarix strains, measured at Day 0 and 28 days after the last vaccination, recorded as Day 28 or Day 56. Post-vaccination results were identified as primary. The numerical primary results and a single comparison are not reported in the registry record.

Safety counts are reported by group, but detailed context and a comparative statistical analysis are not reported. The record also does not report the statistical analysis plan, multiplicity handling, missing-data methods, or full analysis-population details.