The Long-term Antibody Persistence of GSK Biologicals' Meningococcal Vaccine GSK134612 in Healthy Toddlers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Long-term Antibody Persistence of GSK Biologicals' Meningococcal Vaccine GSK134612 in Healthy Toddlers (NCT00718666), a randomized phase 2 study. The primary outcome is Number of Subjects With Serum Bactericidal Assay (Using Human Complement) (hSBA) Titers ≥ the Cut-off.

2. Clinical Question

3. Trial Design

This is a randomized, open-label, parallel-group Phase 2 study with a registry enrollment of 387. It concerns healthy toddlers previously vaccinated in a separate primary study and a group of children aged 5-6 years who had not previously received a meningococcal vaccine. The registry record identifies three groups according to prior vaccination: one dose at 12 months, two doses at 9 and 12 months, or no previous meningococcal vaccination.

The study description sets out two related purposes. One is to evaluate antibody concentrations one, three, and five years after vaccination in participants vaccinated in the earlier study. Another is to evaluate safety and immune response after a dose administered five years after primary vaccination, as well as immune response after a dose in age-matched controls without prior vaccination. These aims should be distinguished from the primary endpoint specified in the outcome listing, which concerns the number of participants above the hSBA cut-off at Year 1.

The study began on 2008-10-20, had primary completion on 2013-11-13, and is marked completed. Random allocation is reported, but the allocation procedure and the details of how participants were assigned are not reported in the registry record. Masking is listed as none. The record does not report the protocol's rationale for its design, a sample-size justification, or a detailed schedule of assessments beyond the time points described in the study summary and endpoint listing.

Although the record gives an overall enrollment, it does not give the number randomized to each group or the number included in each endpoint analysis. The posted group-specific safety denominators are separate information and should not be treated as the primary endpoint analysis counts. No direct efficacy comparison or detailed statistical analysis plan is reported.

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: Out of 387 subjects originally enrolled in the study, only 248 subjects received vaccination.

Persistence Phase Year 1

Persistence Phase Year 3

Persistence Phase Year 5

Booster Phase Year 5

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 persistence Year 1, which included all evaluable subjects who were eligible in the primary study 109375, who complied with the protocol requirements and for whom assay results for at least 1 tested antigen were available at the considered time point.

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.

Population: Baseline Period for Nimenrix 1 Group and Nimenrix 2 Group is considered Year 1 and Baseline Period for Nimenrix Naive Group is considered Year 5.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects With Serum Bactericidal Assay (Using Human Complement) (hSBA) Titers ≥ the Cut-off, measured over At Year 1 (12 months post primary vaccination).

The primary endpoint counts participants whose serum bactericidal assay titers using human complement reached the stated cut-off at Year 1, described as 12 months after primary vaccination. Titers are assessed for four serogroups: MenA, MenC, MenW-135, and MenY. The specified threshold is ≥ 1:8. The registry record describes the analysis population as the According-To-Protocol cohort for Year 1 persistence, with eligible, evaluable participants from the primary study who complied with protocol requirements and had an assay result for at least one tested antigen. The remainder of that population description is not reported in the registry record.

As a general statistical concept, a threshold endpoint converts a measured antibody titer into a count of participants on either side of a predefined cut-off. This can make the result easier to interpret as a proportion or count meeting a stated criterion, but it discards information about how far a participant's titer lies above or below that threshold. It also does not, by itself, establish the clinical meaning of a titer or directly measure infection outcomes.

The endpoint is useful for describing antibody persistence against the listed serogroups at the specified time point. The registry record does not report the number meeting the cut-off, the number assessed for each serogroup, an effect estimate, or an uncertainty interval. It also does not give a primary endpoint result that would allow assessment of the observed degree of persistence.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a count of participants meeting an antibody-titer cut-off. This is a binary classification at the participant level: for each relevant serogroup, a participant either meets the stated threshold or does not. The registry record describes the assay as a serum bactericidal assay using human complement and gives the threshold as ≥ 1:8. The outcome title expresses the result as a number of participants, rather than as a continuous average titer.

What does a threshold count represent?

As a general statistical concept, converting titers into a threshold count simplifies a measurement by separating values into categories. It can support a direct description of how many participants meet a selected criterion. The trade-off is that values within each category are treated alike for this endpoint, even if their measured titers differ. The threshold count therefore answers a narrower question than a full description of the distribution of antibody titers. The registry record also lists secondary outcomes for antibody titers, but their results are not reported in the record.

The primary endpoint is tied to a stated follow-up time: Year 1, described as 12 months post-primary vaccination. Time matters because antibody levels can be assessed at different points after vaccination, and results at one time point do not automatically describe another. The study summary describes evaluation at one, three, and five years, while the primary endpoint listing identifies Year 1. The record does not provide a primary result for any of those time points in the material recorded for this outcome.

What is known about the analysis population?

The endpoint description identifies an According-To-Protocol cohort for Year 1 persistence. It states that this cohort included eligible and evaluable participants in the earlier primary study who complied with protocol requirements and had assay results for at least one tested antigen. Because the description ends before all eligibility details are given, the full definition is not reported in the registry record. The record does not state the number analyzed for each serogroup or explain how participants without a result for a particular assay were handled.

As a general statistical concept, an analysis restricted to participants meeting protocol criteria can differ from an analysis that includes everyone randomized. Exclusions or missing measurements can change the participants represented in an estimate. A clear report normally identifies the analysis population, the number contributing to each outcome, and the handling of missing data. The registry record gives a partial population description but does not report the endpoint-specific denominators or missing-data methods.

What do the design labels establish?

Randomized allocation means group assignment was designated as random in the record. A parallel-group design means the study had distinct groups, and masking is listed as none. These labels describe important design features but do not specify the statistical model, the planned contrasts, or the adjustment strategy. The registry record does not report those analysis details. It also does not report the method used to generate the allocation sequence or the procedure for concealing assignment.

The record lists 36 outcome measures and zero analysis entries. These counts do not identify which comparisons, if any, were emphasized in a complete statistical analysis plan. No primary-outcome p-value, confidence interval, group contrast, or estimate is reported in the registry record. It is therefore not possible to attribute a particular inferential method to the study or to reconstruct its primary statistical analysis from the endpoint definition alone.

How should planning illustrations be read?

As a general concept, a sample-size calculation describes how many participants might be needed for a chosen statistical design and set of assumptions. The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; they describe the effect to detect as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm for a specified power. These are planning illustrations, not observed results or evidence of the trial's achieved power. They are not the trial's own design justification. The registry record does not report the original sample-size justification.

The distinction matters because an observed effect and a planning assumption serve different purposes. A planning illustration asks what sample size would correspond to an assumed effect under a set of assumptions. It does not establish that the trial was designed around that effect, that the effect was observed in the trial, or that the study had a particular chance of detecting it. No numerical effect estimate for the primary endpoint is reported in the registry record, so the endpoint's observed magnitude and precision remain unknown from this record.

For binary outcomes, statistical comparisons commonly depend on the number meeting the threshold and the number assessed in each group. As a general explanation, uncertainty tends to be greater when fewer observations contribute, while estimates also depend on the distribution of outcomes across groups. The registry record does not provide the relevant primary-outcome counts, denominators, or a comparative estimate. No new effect measure can be derived from the endpoint definition alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 36 outcome measures, including repeated descriptions of antibody-threshold counts and antibody titers for the four serogroups. It does not report a multiplicity strategy describing whether, or how, inference across outcomes, serogroups, groups, and time points was controlled. A statistical plan for prioritizing tests or adjusting interpretation for multiple comparisons is not reported in the registry record.

As a general statistical concept, examining many outcomes or comparisons can increase the chance that at least one result appears noteworthy by chance. A prespecified strategy can clarify which findings are primary and how secondary analyses should be interpreted. The endpoint listing identifies a primary outcome at Year 1, but the record does not state how the other measures were ordered or how multiplicity was addressed.

The primary endpoint population is described as an According-To-Protocol cohort, with eligibility and assay availability requirements. The full definition is not reported in the registry record, and endpoint-specific denominators are not given. The record does not explain how missing assay measurements, protocol deviations, or incomplete follow-up were handled. It also does not report whether missing data were excluded, imputed, or addressed through sensitivity analyses.

These omissions limit interpretation of both the endpoint and the set of secondary outcomes. Without participant counts and missing-data methods, it is not possible to assess how much data contributed to each outcome or whether exclusions could affect comparisons. The record lists zero analysis entries, so the statistical methods for handling multiple comparisons and incomplete outcome data are not reported in 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: humerus fracture (1.0%).

The registry safety figures list the Nimenrix 1 Group, Nimenrix 2 Group, and Nimenrix Naive Group. Serious events are reported as 0 of 38, 0 of 46, and 1 of 100, respectively. Deaths are reported as zero in each group. The registry also identifies Humerus fracture at 1.0% among the top serious terms. These figures describe the recorded counts and the listed term; they do not establish a causal relationship to vaccination.

Other adverse events are reported as 31 of 38, 43 of 46, and 67 of 100, respectively. Those counts are distinct from the serious-event counts and should not be read as counts of serious events. The registry record does not provide the event definitions, observation period, severity grading details, or causal assessments needed for a fuller comparison of safety between groups.

As a general statistical concept, event counts should be interpreted with their denominators and with attention to how events were collected. The denominators shown are the participants listed as at risk in each group, but the record does not state whether follow-up duration or ascertainment differed by group. The group labels are reproduced as recorded; the registry does not explain their relationship to every description of the intervention.

These safety figures are descriptive. They do not, by themselves, support a causal conclusion about whether the vaccine caused an event or a comparative safety conclusion beyond the observed counts.

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

The record establishes the trial's stated purpose and defines a primary immune-response endpoint: a count of participants with hSBA titers using human complement at or above ≥ 1:8 for MenA, MenC, MenW-135, and MenY at Year 1. It also describes aims involving antibody persistence at one, three, and five years and immune response after later dosing. These definitions clarify what investigators intended to assess, but they do not reveal the observed antibody results.

The registry record does not report the primary endpoint counts, a comparison between groups, a confidence interval, or a p-value. It therefore does not show how many participants met the cut-off or how precisely an effect was estimated. A missing result in the record should not be interpreted as evidence that there was no difference, nor as proof that an effect was present. The result is simply not reported in the registry record.

As a general concept, an antibody threshold is a laboratory outcome, not a direct count of infections or a direct demonstration of clinical protection. Reaching a predefined cut-off describes the assay result according to the endpoint definition. Its clinical significance depends on evidence beyond the threshold count itself, and the registry record does not provide infection outcomes or a stated link between the threshold and clinical outcomes.

The randomized, open-label, parallel-group design provides context for understanding how the study was organized. It does not overcome the lack of posted outcome estimates. The safety counts likewise describe recorded events but do not establish that vaccination caused them. A complete interpretation would require results, denominators, methods, and uncertainty estimates that are not reported in the registry record.

The planning illustrations should be kept separate from the trial findings. They represent hypothetical sample-size requirements under stated assumptions, not the number of participants observed with an outcome and not observed power. They cannot supply the missing primary endpoint result or establish what the study demonstrated.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining a persistence question with assessments of immune response after later dosing. The study description spans antibody evaluation one, three, and five years after earlier vaccination, while the listed primary endpoint focuses on the number meeting an hSBA threshold at Year 1. Keeping the overall aims distinct from the endpoint's specified time point is important when interpreting what a particular outcome can answer.

The primary outcome is a threshold count across four serogroups. As a general statistical matter, this type of endpoint is straightforward to describe, but it does not retain the full variation in antibody titers. The record also lists antibody titers as secondary outcomes, which represent a different way of describing immune response. Without posted results, the relative information from those outcome types cannot be assessed.

The study record illustrates why design information and results must be read separately. Randomization, parallel groups, and the absence of masking are recorded, but there are no reported primary estimates or analysis entries. Design labels alone do not establish the size or precision of a group difference. Similarly, an enrollment figure does not state how many participants contributed to each endpoint analysis.

The registry record also leaves important analysis details unreported, including a full analysis-population definition, missing-data handling, multiplicity strategy, and the original sample-size justification. These gaps limit reproducibility and the scope of interpretation. The planning illustrations have a separate role: they show hypothetical requirements under stated assumptions rather than providing evidence about observed outcomes.

For clinical researchers and statisticians, the central lesson is to distinguish the question an endpoint was designed to answer from the results available to answer it. Here, the endpoint definition is specific, but the registry record does not report the primary result or its uncertainty. That distinction prevents an endpoint description from being mistaken for evidence of an observed effect.

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 primary limitation for interpreting the trial is that the registry record does not report the primary endpoint result. There are no group-specific threshold counts, denominators for the primary analysis, comparative estimates, confidence intervals, or p-values. Without these, neither the magnitude nor the precision of any difference can be assessed.

The primary analysis population is described only in part. The record identifies an According-To-Protocol cohort for Year 1 persistence and gives some eligibility and assay requirements, but the complete definition is not reported in the registry record. The number analyzed for each serogroup and the handling of missing assays are also not reported. These omissions prevent assessment of how the analyzed participants relate to the randomized groups.

The trial has multiple outcome measures, including serogroup-specific threshold counts, antibody titers, several assessment times, and safety measures. A plan for multiplicity and a full statistical analysis plan are not reported in the registry record. Consequently, the status and interpretation of secondary comparisons cannot be determined from the outcome list alone.

The record states that the study was randomized, open-label, and parallel-group, but details of the allocation procedure and planned statistical contrasts are not reported. The registry enrollment is not a substitute for endpoint-specific sample counts. The record also does not provide an original sample-size justification, so the rationale for the enrollment target is not established.

Finally, the safety figures are descriptive and lack details about ascertainment periods, event definitions, and causal assessment. They should not be treated as evidence of a treatment effect. The available record supports description of study aims, selected design features, endpoint definitions, and recorded safety counts, but not conclusions about primary immune-response outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Long-term Antibody Persistence of GSK Biologicals' Meningococcal Vaccine GSK134612 in Healthy Toddlers — NCT00718666.
• Registry record last updated 2019-06-26; status last verified 2019-06.
• Results first posted 2018-08-23.
• 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

NCT00718666 is a completed Phase 2 randomized, open-label, parallel-group study sponsored by GlaxoSmithKline, with enrollment of 387. It concerns antibody persistence after earlier meningococcal vaccination in healthy toddlers and immune response after a later dose, including assessment in children without prior meningococcal vaccination. The record describes groups with one prior dose, two prior doses, or no prior meningococcal vaccination.

The primary endpoint is the number of participants with hSBA titers using human complement at or above ≥ 1:8 for MenA, MenC, MenW-135, and MenY at Year 1. The primary analysis population is described as an According-To-Protocol persistence cohort. The record lists 36 outcome measures and zero analysis entries.

Primary endpoint results and detailed statistical methods are not reported in the registry record. The posted safety figures include serious-event and other-event counts by listed group, but do not establish causation. Planning illustrations are hypothetical and should not be read as observed results or observed power.