A Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Seasonal Influenza Vaccine in Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Seasonal Influenza Vaccine in Adults (NCT01144299), a non-randomized phase 3 study. The primary outcome is Hemagglutination Inhibition (HI) Antibody Titer.

2. Clinical Question

3. Trial Design

This was a Phase III, parallel, non-randomized study with no masking. The registry record gives enrollment as 114. It lists two age-defined groups: the Fluarix Adult Group, whose participants were aged 18 to 60 years, and the Fluarix Elderly Group, whose participants were aged > 60 years. Each group description says participants received one dose of Fluarix™. The record does not describe a placebo or another vaccine as a control.

The study was designed to assess immunogenicity and reactogenicity of the seasonal vaccine containing strains recommended for the 2010-2011 season. The recorded start date is 2010-06-17, the primary completion date is 2010-07-10, and status is completed. These registry dates describe the study record; they do not by themselves establish when each participant was vaccinated or assessed.

The primary endpoint was HI antibody titer, summarized as a geometric mean titer for all three vaccine influenza virus strains at Day 0 and Day 21. The primary analysis population was the ATP cohort for immunogenicity, consisting of subjects with available data. The registry record lists secondary outcomes for solicited local symptoms, solicited general symptoms, unsolicited adverse events, and serious adverse events.

Because allocation was non-randomized and the groups were defined by age, the design does not support treating one age group as a control for the other. The registry record does not report the allocation process, eligibility criteria beyond the age descriptions, masking procedures beyond none, or details of the statistical plan. No randomized treatment comparison should be inferred from the parallel-group label.

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 Hemagglutination Inhibition (HI) Antibody Titer, measured over Day 0 and Day 21.

The primary endpoint is hemagglutination inhibition antibody titer. HI assays measure the ability of antibodies in a sample to inhibit a virus’s ability to agglutinate red blood cells. In general, antibody titers are used as an indicator of the immune response elicited by vaccination. They are not, on their own, a direct measure of whether an individual will avoid influenza or experience a particular clinical outcome.

The registry record says titers were summarized as geometric mean titers (GMTs) for all three vaccine influenza virus strains at Day 0 and Day 21. A geometric mean is a way to summarize measurements that are positive and may be skewed; it works on a multiplicative rather than an additive scale. In general, this can make it more suitable than an arithmetic mean for antibody titer data. The record specifies 95% confidence intervals as the dispersion measure.

Comparing measurements at the stated time points can describe antibody levels over the study assessment period. However, numerical GMTs, confidence limits, and a reported statistical comparison are not present in the registry record. The direction, magnitude, and precision of the primary endpoint findings therefore cannot be assessed from the record. The endpoint is a laboratory measure of immunogenicity, not a direct clinical efficacy endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a geometric mean titer (GMT) as the primary summary for HI antibody titers, with a 95% confidence interval. The following explains these statistical ideas generally; it does not fill in analyses or results that are not reported in the registry record.

Why summarize titers with a geometric mean?

Antibody titers are positive measurements that can vary over a broad range. For data of this kind, values often behave more naturally on a multiplicative scale: a change from one level to another may be better understood as a relative change than as a fixed additive increment. A geometric mean is calculated by transforming measurements to a logarithmic scale, taking an average there, and transforming back. In general, this gives a summary that is less dominated by very large observations than an arithmetic mean can be.

A GMT remains a group summary. It does not indicate that every participant had a titer equal to the GMT, nor does it describe the full distribution of individual measurements. The registry record identifies the GMT as the summary but does not report individual-level data, the transformation details, or checks of the distributional assumptions.

What does the confidence interval describe?

In general, a confidence interval expresses uncertainty in an estimate arising from sampling variability under the analysis method. It gives a range of values compatible with the observed data and the method’s assumptions. It is not a range containing a specified proportion of individual participant measurements, and it does not account automatically for bias, missing data, or limitations in the study design. A 95% confidence interval is the dispersion measure named for the primary endpoint in the registry record.

Since the numerical GMTs and confidence intervals are not reported in the registry record, no judgment about their width or the precision of the estimates is possible. The stated confidence level alone is not evidence that an estimate is precise.

Why do the assessment times matter?

The primary endpoint is specified at Day 0 and Day 21. Measurements at different time points describe antibody levels at those assessment times, but a comparison requires knowing whether the summaries are paired within participants, calculated separately, or analyzed with another model. The registry record does not report those analysis details. It also does not report the numerical results by time point. Thus, the time points identify the intended measurement schedule but do not establish the size of a change.

What does the analysis population mean?

The primary analysis was performed in the ATP cohort for immunogenicity, among subjects with available data. In general, an according-to-protocol population focuses on participants meeting specified protocol requirements, while an analysis restricted to available data uses observations that can be analyzed for the endpoint. The precise ATP criteria, the number excluded, and the handling of participants with missing measurements are not reported in the registry record. These details matter because exclusions or missing observations can affect how representative the analyzed group is of all enrolled participants.

How should non-randomized groups be understood?

Random allocation, in general, helps balance measured and unmeasured participant characteristics across treatment groups. This study is recorded as non-randomized, and its groups are distinguished by age. They are not exchangeable treatment arms: the age-based grouping itself means that participant characteristics may differ. A simple contrast between group summaries would therefore be descriptive, not a randomized estimate of a treatment effect. The registry record does not report an adjusted model or a causal comparison.

The parallel model means the groups are followed as separate groups rather than described as a crossover design. The absence of masking is also recorded. Neither fact reveals whether outcome measurement or laboratory assessment was standardized; those details are not reported in the registry record.

What can be said about planning calculations?

Any sample-size illustrations associated with these results are planning examples based on an observed effect, not the trial’s original design justification and not observed power. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. In general, such calculations ask how much information a hypothetical future design might need under stated assumptions. They do not demonstrate the probability that this completed study found an effect, and they do not establish that the assumptions match a future study.

The registry record does not report the original sample-size justification, an interim-analysis plan, or a full statistical analysis plan. It also does not report a primary endpoint test result. Consequently, planning assumptions should not be confused with the methods actually used for the immunogenicity analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists nine outcome measures, including the primary HI antibody titer endpoint and secondary adverse-event outcomes. It does not describe a multiplicity strategy, such as how inference was to account for multiple strains, time points, or outcomes. The adjustment approach, if any, is not reported in the registry record. Without this information, any significance testing across multiple measures would need cautious interpretation; no such test results are reported.

The primary analysis population is described as the ATP cohort for immunogenicity, using subjects with available data. The criteria for ATP membership, counts excluded from that cohort, and reasons for exclusion are not reported in the registry record. The record does not specify whether missing measurements were imputed, handled through a model, or omitted from the relevant summaries. The extent and pattern of missing primary endpoint data are also not reported. Because missingness and exclusion can influence estimates, the available-data description is not enough to judge potential bias.

The registry record lists zero analyses. Numerical primary endpoint estimates, confidence intervals, p-values, and analysis details are not reported in the registry record. It is also not clear from the record whether all planned analyses were posted. These absences limit assessment of multiplicity, analysis-population choices, and the relationship between planned and reported outcomes. They should be treated as reporting limitations rather than evidence that a particular analysis or adjustment was or was not performed.

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 non-serious adverse event terms

The serious adverse-event figures are reported separately for the Fluarix Adult Group and the Fluarix Elderly Group. The record lists zero affected among 60 at risk in the adult group and zero affected among 54 at risk in the elderly group. These are descriptive registry counts. They indicate that no serious adverse events were recorded as affecting participants in these group summaries; they do not prove that the risk is absent.

The record does not report a comparison with an untreated or alternative-vaccine group, nor does it specify follow-up duration, ascertainment procedures, or a detailed serious-event listing. The serious-event terms are not reported in the registry record. Death counts are also not reported in the registry record.

For other adverse events, the record lists 50 affected in the adult group and 30 affected in the elderly group, with 60 and 54 at risk, respectively. These are not serious adverse-event counts, and the record does not provide enough detail to interpret the event types, severity, or timing. Adverse-event counts should be read as reported observations, not as a comparative estimate of vaccine-attributable risk.

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

The registry record documents a Phase III study designed to assess the immunogenicity and reactogenicity of a seasonal influenza vaccine in adults. It identifies HI antibody titer as the primary endpoint, specifies GMT summaries and 95% confidence intervals, and names the ATP immunogenicity cohort with available data as the analysis population. It also provides group-level adverse-event counts.

However, the numerical primary endpoint results are not reported in the registry record. Without GMT estimates or confidence intervals, the antibody measurements cannot be described in terms of observed level, change, or precision. The endpoint description is not itself a result. The record also lists zero analyses, and does not report a statistical test or adjusted comparison.

The two groups are defined by age and were not randomly allocated. Both group descriptions specify Fluarix™; neither is described as an untreated or alternative-vaccine control. The study therefore does not provide a randomized comparison of vaccination against another condition. Differences between the age groups, if observed in some posted measure, would not automatically establish an effect caused by age or by the vaccine.

HI antibody titers are laboratory measures of immune response. In general, such measures can help characterize immunogenicity, but they are not direct evidence of clinical protection. The registry record does not report clinical influenza outcomes that would support a conclusion about prevention of illness.

The adverse-event counts are descriptive and lack a control comparison in the registry record. Zero recorded serious adverse events in the group summaries should not be interpreted as proof of zero risk. Overall, the record supports a description of study design, endpoint definitions, analysis-population wording, and reported safety counts. It does not support a conclusion about the magnitude or precision of the primary immune response, comparative safety, or clinical efficacy.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a defined endpoint and a reported result. The record clearly names HI antibody titer, specifies a GMT summary and 95% confidence intervals, and identifies the ATP immunogenicity cohort. Yet it does not report the numerical endpoint estimates. A method description can explain what investigators intended to measure, but it cannot substitute for the observations needed to evaluate magnitude or precision.

The design also illustrates why group labels matter. The adult and elderly groups are defined by age, and allocation is non-randomized. They are not randomized treatment arms or a control comparison. Statistical interpretation depends not only on which summaries are calculated, but also on how groups were formed and whether the design supports the comparison being contemplated.

The registry record further distinguishes immunogenicity from clinical outcomes. Antibody titers are laboratory measures; they do not, without relevant clinical data, quantify protection against influenza. This distinction is important when interpreting a vaccine study whose primary endpoint is immunological rather than a clinical illness outcome.

Finally, the record demonstrates the importance of transparent reporting about analysis populations, missing observations, multiplicity, and safety ascertainment. The ATP cohort is named, but its criteria and missing-data handling are not described. Adverse-event counts are posted, but detailed definitions and follow-up information are not. These gaps do not erase the reported design details, but they restrict the conclusions that statistical readers can draw.

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 GMT results or confidence intervals for the primary endpoint. Consequently, the antibody response cannot be assessed for magnitude or precision. It also lists zero analyses, so no inferential result is available in the record.

The study is non-randomized, unmasked, and organized into age-defined groups. The record does not describe a control group receiving no vaccine or a different vaccine. The age groups therefore do not provide a like-for-like comparison, and the record does not report an adjusted analysis that could address group differences.

The ATP immunogenicity population is described as subjects with available data, but ATP criteria, participant exclusions, missingness patterns, and missing-data methods are not reported in the registry record. These omissions make it difficult to judge the representativeness of the endpoint analysis. The record also does not report a multiplicity strategy, detailed statistical analysis plan, original sample-size justification, or interim-analysis plan.

For safety, the record gives counts but not detailed event definitions, severity information, ascertainment methods, or follow-up duration. Serious adverse-event terms are not reported in the registry record, and death counts are not reported. The posted counts are not a comparison against an untreated or alternative-vaccine group.

Finally, the primary endpoint is an antibody measure rather than a direct clinical outcome. The registry record does not report clinical influenza results. These design and reporting limitations restrict conclusions about clinical protection and comparative effects.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Seasonal Influenza Vaccine in Adults — NCT01144299.
• Registry record last updated 2018-09-24; status last verified 2016-09.
• Results first posted 2010-10-27.
• 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

NCT01144299 is a completed Phase III, parallel, non-randomized, unmasked study of Fluarix™/Influsplit SSW® in adults. The registry record gives enrollment as 114 and describes an adult group aged 18 to 60 years and an elderly group aged > 60 years; each group received one dose of Fluarix™. The study assessed immunogenicity and reactogenicity of vaccine strains recommended for the 2010-2011 season.

The primary endpoint was HI antibody titer, summarized as a GMT with a 95% confidence interval at Day 0 and Day 21 for all three vaccine strains. The primary analysis population was the ATP immunogenicity cohort with available data. Numerical primary endpoint findings are not reported in the registry record.

The record lists zero serious adverse events affecting participants in either group, and lists other adverse events affecting 50 participants in the adult group and 30 in the elderly group. The study has no randomized control comparison described in the record, and the age-defined groups should not be interpreted as like-for-like treatment arms.