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 Immunogenicity and Reactogenicity of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Split Virion Influenza Vaccine Fluarix Tetra (2015 Season Southern Hemisphere) in Adults 18 Years of Age and Above (NCT02369341), a non-randomized phase 3 study. The primary outcome is Humoral Immune Response for Each Vaccine Strain in Terms of Haemagglutination Inhibition (HI) Antibody Titers..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02369341 |
| Phase | Phase 3 |
| Condition | Influenza |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 121 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Adults aged 18-60 years and elderly participants aged >60 years with influenza were included. The study’s stated purpose was to evaluate safety and immunogenicity in these age groups. The primary analysis population is described as the According-to-Protocol (ATP) cohort for immunogenicity, consisting of evaluable participants with available immunogenicity outcome data and assay results for antibodies against at least one study vaccine antigen.
Intervention
Participants received Fluarix Tetra, the quadrivalent split virion influenza vaccine for the 2015 Southern Hemisphere season. The arm descriptions specify a dose at Day 0, administered intramuscularly in the deltoid of the non-dominant arm.
Comparator
There was no separate control intervention in the registry record. The adult and elderly groups were both assigned to receive the vaccine, and allocation was non-randomized. They therefore should not be read as a randomized vaccine-versus-control comparison or as groups designed to isolate an age-related treatment effect.
Primary question
The primary endpoint concerns haemagglutination inhibition (HI) antibody titers against each vaccine strain, expressed as geometric mean titers (GMTs), at Days 0 and 21. The question is whether the recorded antibody measurements describe the humoral response to the vaccine in each age group. Numerical primary endpoint results and a formal between-group comparison are not reported in the registry record.
3. Trial Design
The registry identifies NCT02369341 as a Phase III study sponsored by GlaxoSmithKline. It is listed as completed, with enrollment of 121, a start date of 2015-04-29 and primary completion on 2015-06-03. The study evaluated Fluarix Tetra for the 2015 Southern Hemisphere season in adults 18 years of age and above. The brief summary distinguishes adults aged 18 to 60 years from elderly participants over 60 years of age.
The design is parallel and non-randomized, with no masking. The two groups represent different age categories, not randomized treatment assignments. Both received the same vaccine, as a dose at Day 0 by intramuscular injection in the deltoid of the non-dominant arm. Since no control intervention is described, differences between the age groups would not by themselves establish that age caused any difference in antibody or safety outcomes. The groups may differ in ways not captured by the registry record, and the study was not a like-for-like randomized comparison.
The primary outcome is the humoral immune response for each vaccine strain in terms of HI antibody titers, summarized as GMTs with 95% confidence intervals at Days 0 and 21. The registry also lists secondary immune response and safety outcomes, including seropositivity, seroprotection, seroconversion, geometric mean increase, and solicited symptoms. Although the record lists 19 outcome measures, it lists no analyses. Numerical outcome results for the primary endpoint are not reported in the registry record.
The registry record does not report the rationale for the enrollment target, a sample-size justification, interim analyses, or a detailed statistical analysis plan. Any sample-size figures calculated from an observed effect are planning illustrations rather than the trial’s own design assumptions or evidence of observed power.
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: One subject was allocated the subject number but did not receive the study vaccination.
Overall Study
| Stage | Fluarix Tetra (Southern Hemisphere) Adult Group | Fluarix Tetra (Southern Hemisphere) Elderly Group |
|---|---|---|
| STARTED | 63 | 57 |
| COMPLETED | 62 | 57 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Fluarix Tetra (Southern Hemisphere) Adult Group | Fluarix Tetra (Southern Hemisphere) Elderly Group |
|---|---|---|
| Migrated/moved from study area | 1 | 0 |
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.
| Characteristic | Unit | Fluarix Tetra (Southern Hemisphere) Adult Group | Fluarix Tetra (Southern Hemisphere) Elderly Group | Total |
|---|---|---|---|---|
| Participants analysed | 63 | 57 | 120 | |
| Age, Continuous | Years | 40.8 (SD 12.2) | 67.2 (SD 6.0) | 53.3 (SD 16.4) |
| Sex: Female, Male: Female | Participants | 52 | 38 | 90 |
| Sex: Female, Male: Male | Participants | 11 | 19 | 30 |
6. Primary Endpoint
The registry lists the primary outcome as Humoral Immune Response for Each Vaccine Strain in Terms of Haemagglutination Inhibition (HI) Antibody Titers., measured over At Days 0 and 21..
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Titers |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint measures HI antibody titers against each of the vaccine’s influenza strains. HI assays assess whether antibodies in a sample inhibit haemagglutination, a laboratory process used to characterize an antibody response to influenza antigens. The registry describes titers as geometric mean titers and gives the measurement times as Days 0 and 21. The vaccine strains named in the record are Flu A/Christchurch/16/2010 (H1N1), Flu A/Switzerland/9715293/2013 (H3N2), Flu B/Phuket/3073/2013 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).
As a general statistical explanation, titers often have a skewed distribution, so a geometric rather than arithmetic mean can be a useful summary. The geometric mean is based on averaging on a logarithmic scale and then returning to the original scale. A 95% confidence interval communicates uncertainty around an estimated GMT: it describes the range of values compatible with the data and the analysis assumptions, rather than a range containing 95% of individual participants’ titers.
Measuring at baseline and a later time point can describe antibody levels over time. However, the registry record does not give numerical GMTs or confidence limits, so the magnitude or precision of the observed response cannot be described from the recorded primary outcome information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s question and design, but it does not report numerical results for the primary HI antibody endpoint. It identifies GMTs, 95% confidence intervals and measurements at Days 0 and 21, but gives no GMT estimates, interval limits, or statistical comparisons. Consequently, the size and precision of the antibody response cannot be evaluated from the primary outcome information in the registry record. The strain-specific response is also not numerically described.
The design context is important when interpreting any age-group values. Both the adult group and the elderly group received Fluarix Tetra; allocation was non-randomized, and there was no control group. A comparison between those groups would therefore be observational rather than a randomized contrast. Even if numerical differences were available, they would not isolate the effect of age or establish a causal treatment effect. The registry record does not describe adjustment for potential differences between groups.
The record lists several types of secondary immunogenicity outcomes: seropositive participants, seroprotected participants, geometric mean increase, seroconversion, and seroprotection power above a cut-off. It also lists solicited local and general symptoms. These outcomes answer different questions. A GMT summarizes the level of antibody titers across a group; a proportion meeting a threshold describes how many meet a specified classification; and a symptom count describes reported events. These measures are not interchangeable. Numerical results for the listed immune outcomes are not reported in the registry record.
For safety, the record reports serious adverse event counts of 0 in the adult group and 1 in the elderly group. It also lists Syncope at 1.8% among the top serious terms, without a group attribution in the recorded information. The record gives 63 and 57 participants at risk for serious adverse events, respectively. These counts are descriptive; without further details about event definitions, timing, relationship assessments, or follow-up, they do not establish whether the vaccine caused an event. The death fields are null, so deaths are not reported in the registry record.
Overall, the available record supports a description of the study’s intended measurements, its age-group structure and selected adverse-event counts. It does not provide enough outcome information to estimate the primary antibody response or to make a comparative effectiveness claim. The absence of numerical results in the registry record should not be interpreted as evidence that an outcome was absent or that an analysis found no effect.
9. Statistical Methods Explained
The registry describes the primary endpoint as a geometric mean of HI antibody titers, with a 95% confidence interval, measured at Days 0 and 21 for each vaccine strain. The record does not describe a complete statistical analysis plan or list analyses, so the explanations below are general interpretations of the methods named in the outcome description rather than claims about unreported procedures.
What does a geometric mean summarize?
As a general statistical explanation, a geometric mean is suited to measurements that vary multiplicatively or are strongly right-skewed. The calculation uses logarithms: values are transformed, averaged on that scale, and transformed back. This makes the summary less dominated by very high values than an arithmetic mean may be. It remains a group-level summary, not a description of the response of every participant. Its interpretation depends on how titers below an assay’s detection limit were handled, and that handling is not reported in the registry record.
What does the confidence interval tell the reader?
A confidence interval expresses uncertainty around an estimated quantity under the statistical model and assumptions used. The 95% confidence interval named for the primary endpoint concerns uncertainty in the estimated GMT, not the spread of individual titers. A narrower interval generally indicates greater precision in the estimate, while a wider interval indicates less precision. Because the registry record does not report GMT values or interval limits, the precision of the primary estimates cannot be assessed.
A confidence interval should also be interpreted in relation to the question being asked. An interval around a group GMT is not automatically a test of a difference between groups or time points. To assess a contrast, the analysis would need to define and estimate that contrast, with uncertainty calculated for it. The registry record does not report such a comparison or its results.
Why use HI antibody measurements?
As a general explanation, HI titers are laboratory measures of antibodies that inhibit haemagglutination. They provide an immunogenicity measure: a way to characterize antibody levels following vaccination. They are not direct counts of clinical influenza cases. The registry lists four vaccine strains and describes antibody titers against each, allowing the intended outcome to be strain-specific. The record does not provide numerical strain-specific outcomes, so no conclusion about relative responses to the strains can be drawn from the recorded results.
How should measurements at two times be understood?
Measurements at Days 0 and 21 describe antibody levels at those scheduled times. A baseline measurement can contextualize a later measurement, but a change or ratio between time points must be defined and estimated by an analysis. The registry lists a secondary outcome for geometric mean increase, but does not report its numerical result or the exact calculation used. The time points alone do not establish the size of any increase.
In general, paired measurements from the same participants can be analyzed in a way that accounts for their within-person relationship. The registry record does not explain whether or how pairing was incorporated into the analysis. It also does not report the handling of participants without measurements at both scheduled times.
What do threshold-based immune outcomes add?
The listed secondary outcomes include seropositivity, seroprotection, seroconversion, and seroprotection power above a cut-off. These are categorical or threshold-based summaries rather than continuous GMT summaries. In general, such measures classify participants according to criteria defined for the assay or outcome. They can make a response easier to describe against a threshold, but the result depends on the threshold and classification rules. The registry lists the outcome concepts but does not report all detailed criteria or numerical results in the recorded information.
Counts and proportions for threshold outcomes can be affected by the denominator used. The registry’s primary population description refers to the ATP cohort for immunogenicity, but detailed outcome-specific denominators are not reported in the registry record. They should not be inferred from the enrollment count or the adverse-event at-risk counts.
What do planning sample sizes mean?
As a general statistical explanation, power calculations estimate the sample size needed to detect a specified effect under chosen assumptions. The record’s stated planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm for 80% or 90% power; time-to-event illustrations use a total number of events. These are planning illustrations based on an observed effect, not the trial’s own design rationale and not observed power. The registry record does not report a sample-size justification for this trial or the actual numerical planning estimates.
Power is not a measure of whether a result is true, nor does a calculated planning sample size establish that a study was adequately designed for every listed outcome. A planning calculation depends on the effect size and assumptions used. Those assumptions may not reflect the trial’s actual design, particularly in a non-randomized, parallel study with age-defined groups.
Why can over-dispersion matter?
As a general statistical explanation, over-dispersion occurs when the variability in count data exceeds what a chosen model assumes. If a model underestimates variability, confidence intervals may be too narrow and tests may appear more decisive than warranted. This concern can arise in some count or event analyses, but the registry record does not report a count-model specification or indicate whether over-dispersion was assessed. It would therefore be inappropriate to claim that a particular adjustment was made.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary immune outcome for each vaccine strain and multiple secondary outcomes, including seropositivity, seroprotection, geometric mean increase, seroconversion, seroprotection power and solicited symptoms. Examining several strains and outcome types creates multiple opportunities to observe results that appear notable by chance. As a general statistical principle, a prespecified approach to multiplicity can help control the interpretation of a family of comparisons. The multiplicity strategy, including whether any adjustment or hierarchical testing was planned, is not reported in the registry record.
The registry lists 19 outcome measures but no analyses. It does not report numerical results for the primary immunogenicity endpoint, so the actual number of tests performed or their results cannot be determined from the record. It would not be appropriate to infer that an adjustment was or was not applied solely from the listed outcome measures.
The primary population is described as the ATP cohort for immunogenicity, including evaluable participants with available immunogenicity outcome data and assay results for antibodies against at least one study vaccine antigen. The detailed rules for evaluability, exclusions, missing assays, missing scheduled measurements, or imputation are not reported in the registry record. The record also does not describe whether additional analysis populations were used or how outcome-specific denominators were established.
As a general matter, excluding participants without evaluable measurements can change the composition of an analysis population if missingness is related to participant characteristics or outcomes. Results from an ATP cohort therefore describe the analyzed participants under the stated eligibility rules; they do not automatically represent every enrolled participant. The record does not provide enough detail to assess the possible influence of missing data.
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 |
|---|---|---|---|
| Fluarix Tetra (Southern Hemisphere) Adult Group | 0 | 63 | 0.0% |
| Fluarix Tetra (Southern Hemisphere) Elderly Group | 1 | 57 | 1.8% |
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 |
|---|---|
| Fluarix Tetra (Southern Hemisphere) Adult Group | 27 of 63 |
| Fluarix Tetra (Southern Hemisphere) Elderly Group | 13 of 57 |
Most frequent serious adverse event terms
| Event term | Organ system | Fluarix Tetra (Southern Hemisphere) Adult Group | Fluarix Tetra (Southern Hemisphere) Elderly Group |
|---|---|---|---|
| Syncope | Nervous system disorders | 0 of 63 | 1 of 57 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Fluarix Tetra (Southern Hemisphere) Adult Group | Fluarix Tetra (Southern Hemisphere) Elderly Group |
|---|---|---|---|
| Pain | General disorders | 27 of 63 | 13 of 57 |
| Erythema (redness) | Skin and subcutaneous tissue disorders | 9 of 63 | 7 of 57 |
| Swelling | General disorders | 7 of 63 | 6 of 57 |
| Myalgia | Musculoskeletal and connective tissue disorders | 9 of 63 | 3 of 57 |
| Headache | Nervous system disorders | 8 of 63 | 1 of 57 |
| Fatigue | General disorders | 6 of 63 | 2 of 57 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 6 of 63 | 2 of 57 |
| Upper respiratory tract infection | Infections and infestations | 1 of 63 | 3 of 57 |
Serious events with the highest arm-level rate: syncope (1.8%).
The registry reports serious adverse events among participants at risk in each vaccine group. In the adult group, 63 participants were listed at risk and 0 were reported as affected. In the elderly group, 57 participants were listed at risk and 1 was reported as affected. These are descriptive counts in the registry record, not estimates of a causal vaccine effect. The non-randomized design and absence of a control group limit comparisons with an untreated or alternative-treatment group.
The record lists Syncope at 1.8% among the top serious terms, but the recorded information does not attribute that term to a specific group. It should not be assigned to either age group based on the available details. The registry does not report the timing, clinical course, assessment of relatedness, or full context for the serious event. Deaths are not reported in the registry record.
Serious adverse events are distinct from the solicited local and general symptoms listed as secondary outcomes. Counts in one category should not be read as counts in another. The registry also reports 27 participants affected by other adverse events in the adult group and 13 in the elderly group, but these figures do not substitute for detailed event descriptions or establish causation. Without fuller reporting and a suitable control comparison, the counts describe what was recorded rather than the risk attributable to vaccination.
12. What the Result Does, and Does Not, Mean
The trial record describes a Phase III evaluation of the immunogenicity and reactogenicity of Fluarix Tetra in adult and elderly groups. It specifies a primary antibody endpoint based on HI titers, summarized as GMTs with 95% confidence intervals at Days 0 and 21. This defines what the study intended to measure; it does not, on its own, reveal the observed antibody response. Numerical primary endpoint results are not reported in the registry record.
The record also identifies secondary immune outcomes and solicited symptoms, but does not provide their numerical results. As a result, the available information does not establish the magnitude, precision, or distribution of the antibody response, nor does it show how many participants met the listed immune-response classifications. The lack of results in the registry record is not evidence that an outcome was absent or that a statistical test was negative.
The study has no randomized control group. Both age groups received the vaccine, and allocation was non-randomized. The design can describe the groups and their recorded outcomes, but an age-group comparison would not be equivalent to a randomized comparison. Differences could reflect factors other than age, and the record does not report adjustments that would address such differences.
The serious adverse event counts are limited descriptive information: 0 in the adult group and 1 in the elderly group. The listed Syncope term at 1.8% lacks group attribution in the recorded details. Those figures do not establish causation, comparative safety, or the absence of unreported or less common events. Further event-level context and complete outcome reporting would be needed for a fuller statistical assessment.
In short, the registry record supports understanding the design, endpoints, analysis population description and selected safety counts. It does not support a conclusion about the numerical primary immunogenicity result, a causal treatment effect, or a randomized safety comparison.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why study design and outcome reporting matter alongside the name of an endpoint. The primary measure, GMT of HI antibody titers, is a continuous summary that addresses antibody level, while the listed secondary outcomes classify responses using seropositivity, seroprotection or seroconversion criteria. Those measures provide different kinds of information and should not be treated as interchangeable.
The parallel age-group structure also matters. Because the study was non-randomized and both groups received the vaccine, the groups do not form a randomized treatment contrast. This limits what a comparison between them can establish, even if outcome estimates are available. Design features determine the scope of interpretation; statistical methods cannot make an uncontrolled age-group comparison equivalent to a randomized comparison.
The registry describes a 95% confidence interval for the primary GMT endpoint, which is important because an estimate without uncertainty can be difficult to assess. Yet the numerical GMTs and intervals are not reported in the registry record. This illustrates the distinction between a clearly specified measurement and an interpretable result: endpoint definitions explain what was intended, while estimates and uncertainty are needed to judge the observed data.
The record also lists many outcome measures but no analyses. That gap matters for multiplicity, missing-data assessment and understanding which outcomes were actually evaluated. A detailed statistical plan and complete results would be needed to determine how the listed outcomes were analyzed and how uncertainty was handled. The available record is therefore useful for identifying the questions and design, but limited for quantitative inference.
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 direct limitation for statistical interpretation is that numerical results for the primary HI antibody endpoint are not reported in the registry record. The record names GMTs, 95% confidence intervals, vaccine strains and time points, but supplies no estimates or interval limits. Numerical findings for the secondary immunogenicity outcomes are also not reported. This prevents assessment of effect magnitude, precision and consistency across the listed strains.
The study is non-randomized, has no masking and does not include a control intervention in the recorded design. The adult and elderly groups are different age categories receiving the same vaccine, not randomized comparison arms. Any apparent group differences would be vulnerable to confounding, and the registry record does not describe adjustment methods.
The record describes an ATP immunogenicity cohort but does not provide detailed eligibility, exclusion, missing-measurement or imputation rules. Outcome-specific denominators and the handling of incomplete assay data are not reported in the registry record. The detailed multiplicity strategy and statistical analysis plan are also not reported, despite the listed immune and safety outcomes.
Safety information is limited in the recorded summary. It includes serious adverse event counts and a serious term, but not event-level timing, relatedness, clinical detail or group attribution for Syncope. Deaths are not reported in the registry record. These limitations constrain interpretation of both the safety counts and any comparison between age groups.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Immunogenicity and Reactogenicity of GlaxoSmithKline (GSK) Biologicals' Quadrivalent Split Virion Influenza Vaccine Fluarix Tetra (2015 Season Southern Hemisphere) in Adults 18 Years of Age and Above — NCT02369341.
- Registry record last updated 2017-10-09; status last verified 2017-09.
- Results first posted 2016-08-29.
- 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
NCT02369341 is a completed Phase III, parallel, non-randomized study sponsored by GlaxoSmithKline, with enrollment of 121. It evaluated Fluarix Tetra for the 2015 Southern Hemisphere season in adults aged 18-60 years and elderly participants aged >60 years. Both groups received a dose at Day 0 by intramuscular injection.
The primary endpoint was HI antibody titers against each vaccine strain, expressed as GMTs with 95% confidence intervals at Days 0 and 21. The registry lists 19 outcome measures and no analyses. Numerical primary immunogenicity results are not reported in the registry record. Serious adverse event counts were 0 in the adult group and 1 in the elderly group; deaths are not reported in the registry record.