Assess Consistency of Immunogenicity of GlaxoSmithKline Biologicals' Pandemic Influenza Vaccine (GSK1562902A) in Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assess Consistency of Immunogenicity of GlaxoSmithKline Biologicals' Pandemic Influenza Vaccine (GSK1562902A) in Adults (NCT00449670), a randomized phase 3 study. The primary outcome is Titers for Serum Hemagglutination Inhibition (HI) Antibodies Against 2 Strains of Influenza Disease.

2. Clinical Question

The trial was designed to assess consistency of immunogenicity across lots of an adjuvanted pandemic influenza vaccine in adults aged between 18 and 60 years. Its stated primary measure was the geometric mean titer of serum hemagglutination-inhibition antibodies against two H5N1 strains, measured before vaccination. The intervention descriptions also include a non-adjuvanted regimen and booster vaccination with a heterologous strain. The registry record does not report numerical primary-outcome results, so the stated objective and the reported primary measure cannot be connected to a quantitative estimate of lot-to-lot consistency from this record.

3. Trial Design

This was a completed phase 3, randomized, parallel-group trial with no masking. The registry lists enrollment of 1206 participants. The trial started on 2007-03-24 and had a primary completion date of 2007-07-12. GlaxoSmithKline is listed as the sponsor. The listed conditions are influenza and influenza vaccines.

The principal intervention description concerns two doses of adjuvanted H5N1 split-virus vaccine containing the A/Vietnam/1194/2004 strain, administered at Day 0 and Day 21. Four lots are identified for this group. A subset, called the Boosted sub-cohort, received a heterologous adjuvanted H5N1 vaccine containing A/Indonesia/05; the remaining detail of that arm description is not reported in the registry record. The other arm received two doses of non-adjuvanted A/Vietnam/1194/2004 vaccine, followed by two heterologous adjuvanted A/Indonesia/05/2005 booster doses at Month 6 and Month 6 + 21 days.

Randomization can help balance participant characteristics across assigned groups, while a parallel design assigns participants to groups that proceed concurrently. These are general features of trial design; the registry record does not report the randomization procedure, allocation concealment, or the allocation ratio. No masking was used, so participants and trial personnel were not blinded according to the registry entry. Whether outcome assessors or laboratory staff were masked is not reported in the registry record.

The registry describes 41 outcome measures and 6 analyses. Secondary outcomes include HI and serum-neutralization antibody titers, as well as HI seroconversion counts; some are specified for participants who had not received the Month 6 booster. The registry record does not report the full schedule or results for every outcome. The stated primary endpoint is measured before vaccination, a time point that describes baseline antibody levels rather than the antibody response after vaccination. Accordingly, the primary measure as listed does not itself provide a post-vaccination assessment of lot consistency.

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.

Primary Phase (Study no.109630)

Reasons for not completing this period:

Booster Phase (Study no.109873)

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 vaccinated and eligible subjects for whom data concerning immunogenicity outcome measures were available.

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 2 Strains of Influenza Disease, measured over Before vaccination (Day 0).

The primary endpoint is serum hemagglutination-inhibition antibody titer against A/Vietnam/1194/2004 (H5N1) and A/Indonesia/5/2005 (H5N1), assessed before vaccination at Day 0. The registry presents this measure as a geometric mean titer, or GMT, with a 95% confidence interval. It also gives a reference seropositivity cut-off of at least 1:10.

General statistical explanation: antibody titers commonly have a right-skewed distribution, so geometric means can be a useful way to describe a typical level on a multiplicative scale. A confidence interval describes the uncertainty around an estimated quantity under the analysis assumptions; it is not a range containing every participant's value. The cut-off provides a reference for classifying antibody levels, but a GMT alone does not tell how many participants exceeded that threshold. The registry lists a separate secondary outcome for the number of subjects who seroconverted.

The endpoint's timing is important for interpretation. A Day 0 measure is obtained before the described vaccination schedule begins. It can characterize baseline antibody titers, but it cannot show the change after vaccination or compare post-vaccination responses among vaccine lots. The registry record does not report numerical GMT estimates or confidence intervals for the primary endpoint. It therefore does not provide a quantitative primary-endpoint result from which to assess baseline levels or infer post-vaccination lot consistency.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a geometric mean represent?

General statistical explanation: a geometric mean summarizes values using their logarithms and then returns the summary to the original measurement scale. It is often used for titers because the distribution may be asymmetric and differences can be more naturally expressed as multiplicative changes. The geometric mean is not the arithmetic average, and it does not reveal the spread of individual participant values by itself. In this trial, the primary outcome is identified as GMT for HI antibodies to the two named H5N1 strains.

How should the confidence interval be read?

The endpoint description specifies a 95% confidence interval. In general, a confidence interval conveys uncertainty in an estimate under the assumptions and method used to construct it. A narrower interval indicates greater precision than a wider interval for the same kind of estimate. It does not mean that most participant measurements fall inside the interval, and it does not remove uncertainty about how representative the analyzed participants are. Numerical confidence limits for the primary GMTs are not reported in the registry record, so their precision cannot be evaluated.

What does the baseline time point permit?

The primary measurement is specified before vaccination, at Day 0. General statistical explanation: a baseline measurement can describe participants' starting antibody levels and can be useful context for later response measurements. A baseline-only measure cannot estimate a change caused by vaccination, because it does not compare the same outcome after vaccination. It also cannot establish whether different lots produce similar post-vaccination responses. The registry lists additional antibody outcomes, but the relevant numerical post-vaccination estimates and their analyses are not reported in the registry record.

What does randomization contribute?

Random allocation is intended to make treatment groups comparable with respect to characteristics that could affect outcomes, including characteristics that were not measured. This is a general rationale, not a claim that balance was achieved in this trial. The registry identifies the study as randomized but does not describe sequence generation, allocation concealment, or the allocation ratio. The parallel design means participants were assigned to groups rather than crossing between regimens, according to the listed model. Since masking is listed as none, expectancy and behavior may differ by group in some settings; the registry does not describe whether any outcome assessment was masked.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variation is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors can be too small and confidence intervals can be too narrow. For immunogenicity measures, variation among participants and between measurement processes can influence precision. The registry information does not identify a model for the reported antibody outcomes or state whether over-dispersion was assessed, so no claim can be made about its handling in this trial.

What can be inferred from the analysis population?

The stated primary analysis used the According-to-Protocol cohort for Immunogenicity. It includes vaccinated and eligible subjects with available immunogenicity data. This definition describes who contributes to the primary analysis, but the registry record does not give the resulting analysis count, participant flow, or the reasons individuals may have been omitted. General statistical explanation: restricting analysis to participants who meet protocol and data-availability conditions can make the analyzed group different from everyone randomized. Interpretation then depends on whether exclusions are related to group assignment, outcome, or other characteristics; those details are not reported in the registry record.

What do the planning assumptions mean?

The registry includes a planning illustration based on the observed effect. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event illustrations, the quantity is total events using the Schoenfeld method; all other illustrations refer to participants per arm. These are planning assumptions, not trial outcomes. Sample-size illustrations are not observed power, and they do not establish that the trial was adequately powered for every endpoint. The registry record does not report a protocol sample-size justification or the numerical outputs for the planning illustration.

The actual statistical plan, including the methods for estimating GMTs, constructing confidence intervals, comparing lots, handling multiple outcomes, and addressing missing data, is not reported in the registry record. Without those details and the numerical results, the listed design and endpoint definitions cannot be used to reconstruct the sponsor's analyses or to make an independent quantitative assessment.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 41 outcome measures and 6 analyses, including several HI and serum-neutralization antibody outcomes, seroconversion, and outcomes for adults who had not received a Month 6 booster. With multiple outcomes and time points, a trial may need to distinguish primary confirmatory questions from supportive or exploratory analyses. General statistical explanation: testing many hypotheses can increase the chance of at least one apparently notable result when no adjustment or testing hierarchy is used. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or whether any adjustment was used.

The primary analysis population is the According-to-Protocol cohort for Immunogenicity, defined as vaccinated and eligible subjects with available immunogenicity data. This tells readers which broad population was intended for that analysis. The number actually analyzed, exclusions after randomization, and reasons for exclusion are not reported in the registry record. The record also does not report an intention-to-treat analysis or comparisons between analysis populations.

Missing-data methods are not reported in the registry record. In general, missing measurements can affect estimates when their occurrence is related to participant characteristics, treatment assignment, or the unobserved result. The registry description does not state how missing antibody measurements were handled, whether participants with partial data contributed to other outcomes, or whether sensitivity analyses were conducted.

These omissions matter because outcome multiplicity and analysis-population choices affect how strongly results can be interpreted. Since numerical results, a testing strategy, and missing-data procedures are not reported, neither the robustness of any finding nor the impact of these choices can be assessed from the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: ligament rupture (0.4%), benign ovarian tumour (0.4%), anxiety (0.4%), colonic polyp (0.4%), helicobacter gastritis (0.4%).

The registry lists serious adverse events for 961 participants at risk in the H5N1 Adjuvanted Group, with 25 affected, and for 245 participants at risk in the H5N1 Un-adjuvanted Group, with 5 affected. Deaths are listed separately: 1 in the adjuvanted group and 0 in the un-adjuvanted group. These are descriptive counts as recorded, not estimates of a causal treatment effect.

The registry also lists other adverse events for 961 participants at risk in the adjuvanted group, with 904 affected, and for 245 at risk in the un-adjuvanted group, with 159 affected. The record does not provide event timing, severity breakdowns for these other events, or a statistical comparison. It also does not report whether serious-event counts represent unique participants, how events were adjudicated, or whether investigators considered them related to vaccination. Those details should not be inferred from the counts.

Several serious-event terms are listed at 0.4%: ligament rupture, benign ovarian tumour, anxiety, colonic polyp, Helicobacter gastritis, and clavicle fracture. The registry does not assign these listed terms to a specific group in the information recorded. A listed event is not, by itself, evidence that the vaccine caused it. The figures should be read as registry safety reporting, alongside the missing context about definitions, timing, attribution, and comparative analyses.

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

The record supports a description of a randomized, parallel-group phase 3 trial enrolling 1206 adults, with adjuvanted and non-adjuvanted H5N1 vaccine regimens and a stated interest in lot-to-lot immunogenicity consistency. It specifies a primary endpoint based on HI antibody GMTs against two H5N1 strains before vaccination, and identifies the analysis population as an According-to-Protocol immunogenicity cohort.

It does not provide the numerical primary endpoint estimates, confidence limits, or post-vaccination lot-specific comparisons. Therefore, the record cannot show the size or precision of the antibody response, whether responses were similar across lots, or how the regimens compared on immunogenicity. The baseline timing is especially limiting for that question: measurements made before vaccination describe starting levels, not responses after the vaccine schedule.

General statistical explanation: a conclusion about consistency ordinarily depends on estimates of differences among groups and a prespecified way to judge whether those differences are acceptably small. The registry record does not report the lot-comparison estimates, uncertainty intervals, or a decision criterion. It is not possible to infer those quantities from enrollment or from the intervention descriptions alone.

The safety counts describe reported events among participants at risk, but do not establish causation or comparative risk. The registry record does not provide event attribution, timing, or a statistical safety analysis. The trial's completed status confirms that the study is recorded as completed; it does not supply missing outcome estimates.

Thus, the information establishes what the study set out to evaluate and how the listed groups were described, but it is insufficient to determine the immunogenicity result. No conclusion that the vaccine lots were consistent or inconsistent, or that one regimen was superior or inferior, is supported by the numerical results recorded because those results are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable because its stated objective is lot-to-lot consistency, a question that differs from simply asking whether antibody titers change after vaccination. Assessing consistency requires estimates that distinguish variation among lots from variation among participants, together with uncertainty around the relevant comparisons. The registry identifies four adjuvanted-vaccine lots, but does not report lot-specific post-vaccination estimates or the criteria used to judge consistency.

The primary endpoint as registered is a GMT measure at Day 0, before vaccination. This highlights why timing and estimand matter: an endpoint can be well-defined yet not directly address the trial's stated comparison if it is measured before the intervention. The record also lists many secondary antibody outcomes, making the prespecification and interpretation of multiple analyses relevant. Neither an analysis hierarchy nor a multiplicity approach is reported.

The analysis population is also consequential. An According-to-Protocol cohort can support an analysis among eligible vaccinated participants with available measurements, but it is not automatically equivalent to the full randomized population. Participant counts for that cohort and the handling of missing measurements are not reported.

These features make the registry useful for understanding the design question and the limits of the available evidence. It does not provide enough numerical outcome information to evaluate lot consistency, compare regimens, or assess precision. The distinction between a planned objective, a defined endpoint, and a reported result is central to interpreting this record.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The clearest limitation is the mismatch between the stated objective and the registered primary endpoint timing. The objective concerns consistency of vaccine immunogenicity, while the primary measure is listed before vaccination at Day 0. A baseline GMT cannot directly quantify post-vaccination responses across the four adjuvanted-vaccine lots. Post-vaccination antibody outcomes are listed among the secondary outcomes, but their estimates are not reported in the registry record.

The registry record does not report numerical primary GMTs or their 95% confidence intervals. It also does not provide lot-specific results, comparisons between lots, or a threshold for what would count as acceptable consistency. Without those details, the principal scientific question cannot be quantitatively evaluated.

Important design and analysis details are absent, including the randomization procedure, allocation ratio, protocol sample-size justification, statistical analysis methods, multiplicity strategy, and missing-data procedures. The primary analysis population is described, but its analyzed size and participant exclusions are not reported. Masking is listed as none; whether laboratory staff or outcome assessors were masked is not reported in the registry record.

The arm description for the boosted adjuvanted subgroup is incomplete, and the intervention schedules differ across the described groups, including later boosters in the non-adjuvanted group. The record does not provide enough information to characterize all subgroup details or compare like-for-like schedules. Safety information is limited to event counts and listed terms, without timing, attribution, or comparative analysis. These limitations constrain interpretation of both immunogenicity and safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Assess Consistency of Immunogenicity of GlaxoSmithKline Biologicals' Pandemic Influenza Vaccine (GSK1562902A) in Adults — NCT00449670.
• Registry record last updated 2020-04-09; status last verified 2020-03.
• Results first posted 2020-04-09.
• 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 is a completed phase 3 randomized parallel-group trial sponsored by GlaxoSmithKline, with no masking listed and enrollment of 1206. It enrolled adults aged between 18 and 60 years and evaluated H5N1 vaccine regimens, including an adjuvanted vaccine described as four lots and a non-adjuvanted regimen.

The stated primary outcome is HI antibody GMT against A/Vietnam/1194/2004 and A/Indonesia/5/2005 before vaccination at Day 0, with a 95% confidence interval. The primary analysis population is the According-to-Protocol cohort for Immunogenicity. The record lists 41 outcome measures and 6 analyses, including additional HI, neutralization, and seroconversion outcomes.

Numerical primary immunogenicity results, post-vaccination lot comparisons, the statistical analysis plan, and missing-data procedures are not reported in the registry record. Serious adverse events and deaths are listed descriptively, without details needed to assess attribution or comparative effects.