Immunogenicity of GSK Biologicals' Pandemic Influenza Vaccine (GSK1562902A) at Different Boosting Vaccination Schedules: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity of GSK Biologicals' Pandemic Influenza Vaccine (GSK1562902A) at Different Boosting Vaccination Schedules (NCT00652743), a randomized phase 3 study. The primary outcome is Number of Subjects Boosted at Month 12 With Haemagglutinin-inhibition (HI) Antibody Concentrations Above the Cut-off Value.

2. Clinical Question

The clinical question is about an immune response measured in blood, rather than a clinical influenza outcome. The registry record describes the study as an assessment of vaccine immunogenicity and lists antibody measures such as seropositivity, seroconversion, seroprotection, and geometric mean fold rise among its outcomes. It does not report whether participants developed influenza or whether the schedules differed on a clinical disease outcome.

The schedule groups had different intervals between the earlier primary vaccination and the booster. The record describes prior vaccination with two doses of adjuvanted investigational H5N1 vaccine using the A/Vietnam/1194/04 strain. It describes the Month 6 group as having received its booster in the earlier study, while the Month 12 and Month 36 groups received a dose in this booster study. The record does not provide the primary endpoint's observed count or a statistical comparison of schedules, so the clinical question can be stated but not answered from the posted outcome information.

3. Trial Design

This was a randomized, open-label, parallel-group Phase 3 study of pandemic influenza candidate vaccine GSK1562902A. The registry lists enrollment as 845 and the study status as completed. The listed condition is influenza, and the sponsor is GlaxoSmithKline. The recorded study dates run from 2008-03-23 to primary completion on 2011-06-08.

The groups were defined by the planned timing of a booster following primary vaccination: Month 6, Month 12, or Month 36. The arm descriptions characterize participants as healthy male or female adults who had previously received two doses of an adjuvanted investigational H5N1 vaccine in study 109630 (NCT00449670). The Month 6 group description says its booster was given in that earlier study; the Month 12 and Month 36 descriptions place the booster in this study. Each schedule used one dose of GSK1562902A.

Randomization means that assignment to study groups is intended to be determined by chance, which can reduce systematic differences between groups at enrollment. The registry does not report the allocation procedure or the allocation ratio. Open-label means masking is listed as none; the record does not describe blinding of participants or study personnel. A parallel design means the schedule groups are described as separate groups rather than as participants crossing through each schedule.

The registry summary says this posting concerns objectives and outcome measures of the secondary phase of a study, while objectives and outcome measures of the primary phase appear in a separate protocol posting. That context is important: the listed booster outcomes should not be treated as a complete account of the earlier phase. The registry record does not report further design details such as eligibility criteria beyond the arm descriptions, the randomization method, or the rationale for selecting the schedule intervals.

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 enrolled subject was not administered a booster vaccination and hence not considered to have started the study.

Months 12-18

Reasons for not completing this period:

Months 24-30

Reasons for not completing this period:

Months 36-42

Reasons for not completing this period:

Months 42-48

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 immunogenicity data were available. This included 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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects Boosted at Month 12 With Haemagglutinin-inhibition (HI) Antibody Concentrations Above the Cut-off Value, measured over At Month 12 + 21 days.

The primary endpoint is a count: the number of participants boosted at Month 12 whose haemagglutinin-inhibition (HI) antibody concentrations were above the stated cut-off at Month 12 + 21 days. In the registry description, seropositivity for participants who were seronegative before vaccination is defined as an HI concentration at least 1:10. The strain assessed was Flu A/Indonesia/05/2005.

HI is an antibody assay used to measure whether antibodies in a serum sample inhibit influenza virus haemagglutination. In general, an antibody concentration above a prespecified threshold is treated as evidence of a measurable response according to that assay definition. The endpoint therefore turns assay results into a participant count using a stated threshold and assessment time. It does not, by itself, measure prevention of influenza illness or the duration of protection.

Counts are useful for showing how many participants meet a defined response criterion, and they can be compared across groups if the study reports suitable denominators and an analysis. However, a count alone does not describe the uncertainty around the estimate or establish whether groups differ. The registry identifies the outcome and the analysis population but gives no observed count, denominator for this endpoint, confidence interval, or comparative estimate. Those results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint count?

The endpoint counts participants whose HI antibody concentration meets a prespecified threshold at a specified visit. This is a binary classification at the participant level: a person either meets the threshold or does not, according to the assay result and the endpoint definition. The count is then the number meeting the criterion in the analysis population. General statistical principle: a count is easiest to interpret alongside its denominator, because the same count can represent different response rates in groups of different sizes. The registry record does not report the Month 12 primary endpoint count or denominator.

Why use an antibody threshold?

The endpoint uses seropositivity defined as at least 1:10 for participants seronegative before vaccination. A prespecified threshold gives a consistent rule for classifying assay results and can make a response measure easier to communicate than a set of individual laboratory values. It also discards information: participants just below and just above a cut-off are categorized differently despite potentially similar measurements, while different values above the threshold are treated alike for this count. General statistical principle: continuous antibody measurements and threshold-based response counts answer related but not identical questions. Both can be useful, and one cannot be substituted for the other without changing the interpretation.

What does the analysis population mean?

The primary outcome description names the According-to-Protocol cohort for immunogenicity. It defines this cohort as evaluable participants for whom immunogenicity data were available, including participants with assay results for antibodies against at least one study vaccine antigen component. An analysis population is the set of participants whose data are included in a particular analysis. Such populations may differ from everyone enrolled, for example when eligibility for an analysis depends on evaluability or availability of measurements. The registry does not give the number included in the primary endpoint analysis or a fuller account of exclusions from that cohort.

General statistical principle: restricting analysis to participants with usable measurements can make the observed data more complete for the assay, but it can also affect interpretation if the availability of measurements is related to participant characteristics or response. Whether that concern applies depends on the missingness and exclusion patterns. The registry record does not report those patterns, reasons for missing assays, or a comparison of included and excluded participants.

What would a schedule comparison require?

To compare booster timing, an analysis would ordinarily specify the outcome in each relevant group and an estimate of the between-group contrast, with uncertainty. For a threshold-based endpoint, the analysis could use counts and denominators or a model for binary outcomes. General statistical principle: randomization supports causal comparisons when assignment and follow-up are handled appropriately, but it does not remove the need to report the analysis population, missing data, outcome estimates, and uncertainty. The registry lists randomized allocation and parallel design, but it provides no primary-outcome analyses, comparative estimates, or interval estimates.

The primary endpoint is focused on the Month 12 group rather than being described as a direct contrast between all schedule groups. The record does not explain how this single-group endpoint relates to planned comparisons among schedules. The statistical plan, including the intended contrasts and any adjustment for baseline antibody status beyond the endpoint's stated seronegative criterion, is not reported in the registry record.

How should the planning illustration be read?

General statistical principle: sample-size calculations depend on assumptions about the target effect, variability or event rate, significance level, allocation, and analysis method. A planning illustration is not the number of participants actually analyzed and is not a measure of the trial's observed power. The stated illustration method uses 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 fraction of the observed effect. Those are planning assumptions, not evidence that the trial was designed using them.

The registry-derived information indicates that planning illustrations are skipped when the primary outcome has fewer than two arms. No planning figures are available for this primary outcome in the posted record. The trial's own sample-size justification is not reported in the registry record. No assumptions about the protocol's intended power, effect size, or recruitment target should be inferred from the illustration method.

What can be said about inference?

General statistical principle: an estimate describes the observed data, while a confidence interval communicates uncertainty around that estimate under a model and procedure. A hypothesis test addresses compatibility with a specified null hypothesis, but a p-value alone does not quantify the size or practical importance of an effect. For an antibody count, the underlying estimate is more informative when paired with a denominator and a clear group contrast. None of these primary-result quantities or tests is reported in the registry record, and the analysis count is recorded as zero.

The record names secondary outcomes that reflect several aspects of HI antibody response, including geometric mean fold rise (GMFR). General statistical principle: antibody measurements are often analyzed on a logarithmic scale because their distributions can be skewed and changes are naturally multiplicative; back-transformed summaries can then be expressed as geometric means or fold changes. The registry does not describe the precise transformations or statistical models used for these outcomes. It lists outcome names, not enough detail to reconstruct an analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("GSK1562902A M12 Group")
n      <- c(186)
events <- c(178)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  GSK1562902A M12 Group  186  178  95.7  91.7  98.1  91.7  97.8  91.7  97.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 32 outcome measures, including multiple measures of H5N1 HI antibody response. Several labels recur in the outcome list, including seropositivity and geometric mean fold rise. Having several outcomes or time points can create multiplicity: if many statistical tests are conducted, the chance of at least one apparently unusual result can increase. General statistical principle: a prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory analyses can help readers understand how multiple results are interpreted.

The registry record does not report a multiplicity strategy, a hierarchy of secondary endpoints, or whether any analyses were adjusted for multiple testing. It also reports no outcome analyses. The absence of a reported plan does not establish that no plan existed; the details are not reported in the registry record.

The primary analysis population is described as the According-to-Protocol cohort for immunogenicity, comprising evaluable participants with immunogenicity data available for at least one study vaccine antigen component. The record does not provide the number in that cohort for the primary endpoint, the amount or pattern of missing assay data, reasons for exclusions, or methods for handling missing measurements. Imputation, sensitivity analyses, and rules for deviations from protocol are not reported in the registry record.

General statistical principle: missing outcome data can affect an estimate if participants without measurements differ systematically from those with measurements. The direction and size of any effect depend on why data are missing and how missingness relates to the response. Without counts and reasons for missingness, the extent of this issue cannot be assessed from the posted record.

12. 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: meniscus lesion (0.9%), appendicitis (0.7%), ligament rupture (0.7%), chest pain (0.5%), cholecystitis chronic (0.5%).

The registry reports serious-event entries by schedule group. For the GSK1562902A M6 Group, 14 of 219 participants are listed as affected for the serious-event measure. For the M12 Group, the corresponding entries are 13 of 188, and for the M36 Group they are 28 of 437. The record lists zero deaths in each group.

The other-event entries list 169 affected among 188 at risk in the M12 Group and 336 affected among 437 at risk in the M36 Group. For the M6 Group, the record lists zero at risk and zero affected for this measure. Because its at-risk count is zero, that entry does not establish that no other events occurred in that group; it indicates that no participants are represented as at risk in that record field.

The serious-event terms listed include Meniscus lesion (0.9%), Appendicitis (0.7%), Ligament rupture (0.7%), Chest pain (0.5%), Cholecystitis chronic (0.5%), and Arthralgia (0.5%). The record does not give a denominator or explain whether participants could contribute to more than one term. These entries describe recorded safety information, not a causal comparison between schedules. The registry record does not report a comparative safety analysis or enough detail to interpret differences in exposure or follow-up across groups.

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

The record establishes that a randomized, open-label, parallel Phase 3 study assessed immune responses after GSK1562902A boosting at different intervals following earlier H5N1 vaccination. It identifies a primary threshold-based HI antibody endpoint for participants boosted at Month 12 and specifies its assessment time, strain, seropositivity cut-off, and analysis population. These details define what the primary measure was intended to capture.

The record does not report the primary endpoint result, a denominator for that analysis, a confidence interval, a statistical test, or a comparison between boosting schedules. It therefore cannot show from the posted results how many participants met the antibody threshold or whether immune responses differed by booster timing. The outcome descriptions alone are not evidence that a schedule is superior, equivalent, or inferior.

The endpoint is an immunogenicity measure, not a direct measure of influenza cases, severe illness, duration of immunity, or population-level protection. General statistical principle: an antibody response may be relevant to vaccine evaluation, but an antibody threshold should not be interpreted as a clinical outcome unless the study provides evidence linking the assay measure to that outcome. That linkage is not reported in the registry record.

The safety entries offer some descriptive information, including serious-event counts and deaths by group, but the registry does not report a comparative safety analysis. Event counts need context such as follow-up, exposure, event definitions, and the analysis method to support a fair comparison. The entries should not be treated as proof of causation or as a complete account of safety.

In short, the registry record documents the study design, schedule groups, endpoint definition, and selected safety data. It does not include enough posted outcome information to draw a statistical conclusion about the immune response or the relative performance of the boosting schedules.

14. Why This Trial Matters Statistically

This trial is statistically interesting because it asks about the timing of a booster after earlier vaccination, rather than comparing the vaccine with an unrelated treatment. The schedule groups are defined by different intervals after the primary vaccination, and the study uses antibody measures to characterize the response. That design makes clear why the estimand and comparison matter: a result for the Month 12 group alone is not automatically a contrast among all booster schedules.

The primary endpoint also illustrates the trade-off between a measurable laboratory response and a clinical outcome. A count above a stated HI threshold is straightforward to define and communicate. At the same time, it compresses a range of assay values into a yes-or-no classification and cannot, without further evidence, answer a question about influenza illness. The record's additional named outcomes, such as geometric mean fold rise and seroprotection, represent different summaries of immune response rather than interchangeable versions of the same result.

Randomization is a meaningful design feature because, in general, assignment by chance can help balance measured and unmeasured characteristics across groups. But the value of that design for interpretation depends on reporting the analyses and participant flow. Here, the registry record states the allocation and endpoint framework but reports no analyses for the primary outcome. The missing estimates and uncertainty are therefore central to what a reader can conclude from the record.

The posting also shows why registry descriptions and numerical results serve different purposes. The outcome definition tells readers what investigators planned to measure; it does not reveal the observed response. Statistical interpretation requires the actual counts or estimates, denominators, comparison method, and uncertainty. Those are not reported for the primary endpoint in the registry record.

15. 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 principal trial-specific limitation in the registry record is that the primary endpoint is described without its observed result. No Month 12 count, denominator, comparative estimate, uncertainty interval, or analysis is reported. Although the title and group descriptions concern different booster schedules, the record does not report a primary analysis comparing those schedules.

The endpoint population is described as an According-to-Protocol immunogenicity cohort, but the record does not state how many participants contributed to the primary analysis or detail exclusions and missing assays. The available description says that the cohort included evaluable participants with immunogenicity data for at least one study vaccine antigen component; it does not establish how many had data for the specific H5N1 endpoint.

The study is open-label, with masking listed as none. This fact is relevant to the design description, although the endpoint is based on a laboratory antibody assay. The registry record does not describe laboratory blinding, assay procedures beyond the stated cut-off and strain, or measures used to limit potential assessment bias.

The record describes prior vaccination in an earlier study and places the Month 6 booster in that study, while the later booster groups received a dose in this booster study. It does not report further details about follow-up comparability, baseline antibody distributions, or the handling of differences related to schedule timing. It also does not report the protocol's sample-size justification, statistical analysis plan, multiplicity procedure, interim analyses, or missing-data methods. Those omissions limit assessment of both precision and the intended inferential framework; they should not be filled by assumption.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Immunogenicity of GSK Biologicals' Pandemic Influenza Vaccine (GSK1562902A) at Different Boosting Vaccination Schedules — NCT00652743.
• Registry record last updated 2018-08-02; status last verified 2018-06.
• Results first posted 2018-08-02.
• 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.

19. Record Summary

NCT00652743 is a completed randomized, open-label, parallel Phase 3 study sponsored by GlaxoSmithKline, with enrollment listed as 845. It assessed the immunogenicity of pandemic influenza candidate vaccine GSK1562902A given as a booster at Month 6, Month 12, or Month 36 after earlier H5N1 vaccination.

The primary outcome is the count of Month 12 booster recipients with HI antibody concentrations meeting the stated seropositivity cut-off at Month 12 + 21 days for Flu A/Indonesia/05/2005. The primary analysis population is described as the According-to-Protocol cohort for immunogenicity. The registry record does not report the primary result or any analysis.

Other listed outcomes include antibody seropositivity, booster response, seroconversion, geometric mean fold rise, and seroprotection. Safety entries include serious events, other events, and deaths by group. The record gives no reported multiplicity plan, detailed missing-data methods, or trial-specific sample-size justification.