Study in Children to Evaluate Non-Inferiority and Persistence up to 5 Years of GSK Bio Meningococcal Vaccine 134612: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study in Children to Evaluate Non-Inferiority and Persistence up to 5 Years of GSK Bio Meningococcal Vaccine 134612 (NCT00427908), a randomized phase 2 study. The primary outcome is Number of Subjects With Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitides Serogroups A, C, W-135, Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) Antibodies Vaccine Response.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group Phase 2 study with no masking. The registry lists an enrollment of 613 and a completed status. Its stated purpose was to evaluate immune response to meningococcal vaccine 134612 in children, using Mencevax ACWY or Meningitec as controls according to age. The study had a vaccination phase and a long-term follow-up phase. The latter was intended to assess protection up to 5 years after vaccination, with no additional subjects enrolled during follow-up.

Group A received vaccine 134612. Group B received Mencevax ACWY for subjects including and above two years of age and Meningitec for subjects below two years of age. Because the comparator depended on age, the overall study is not a simple comparison of the intervention with one identical control vaccine across every participant. Interpretation should retain that age-specific allocation context.

The study start date is 2007-02-07, and the primary completion date is 2007-12-03. Those dates describe the registry record's study milestones; they do not establish when every long-term assessment occurred. The record does not report the full randomization procedure, allocation ratio, recruitment details, or the timing and conduct of the later follow-up assessments. It also does not report the non-inferiority margin or a complete statistical analysis plan.

The primary immune-response population is described as subjects aged 2 years and above in the according-to-protocol cohort for immunogenicity. That is narrower than the overall age range in the study title. The cohort description refers to evaluable subjects with available assay results for at least one vaccine antigen component, but its full criteria are not reported in the registry record.

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: During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

Primary Phase

Reasons for not completing this period:

Persistence Phase Year 1

Persistence Phase Year 2

Persistence Phase Year 3

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on subjects of 2 years and above from the According-to-protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom assay results were available for antibodies against at least one study vaccine antigen component for the blood sample taken one month 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 With Serum Bactericidal Assay Using Rabbit Complement Against Neisseria Meningitides Serogroups A, C, W-135, Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY) Antibodies Vaccine Response, measured over One Month after vaccination.

The primary endpoint counts participants who met the study's definition of vaccine response for serum bactericidal assay using rabbit complement, abbreviated rSBA, against meningococcal serogroups A, C, W-135, and Y. The assessment was scheduled one month after vaccination. For participants who were initially seronegative, response meant a post-vaccination rSBA titer of at least 1:32. For participants who were initially seropositive, it meant at least a four-fold increase in rSBA titer from before to after vaccination.

This is a binary outcome at the participant level: each person either meets the stated response criterion or does not. Such a responder endpoint can make an immune-response criterion easier to interpret than a distribution of assay titers alone, because it expresses the proportion of participants crossing a prespecified threshold. That is a general explanation of this type of endpoint, not a claim about results in this trial.

The endpoint combines responses across four serogroups, but the registry title names the serogroup-specific antibody measures. The record does not report the numerical counts or proportions of responders, their uncertainty intervals, or a non-inferiority conclusion. It also does not state how any combined assessment across serogroups was handled in the primary analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the responder count represent?

The primary outcome is a participant count, and its statistical type is binary: participants are classified according to whether they satisfy the response definition. The definition differs according to initial serostatus. Initially seronegative participants must reach a post-vaccination rSBA titer of at least 1:32; initially seropositive participants must have at least a four-fold increase from pre- to post-vaccination titer. This approach converts assay measurements into a responder classification. In general, binary endpoints are often summarized using counts and proportions, and comparisons may be expressed as differences or ratios between groups. Those summaries are not reported for this primary outcome in the registry record.

Why does non-inferiority require a margin?

In general, a non-inferiority analysis is not established merely because a conventional test fails to find a statistically significant difference. The study needs a prespecified margin defining the largest difference that would still be considered compatible with non-inferiority. The estimated group contrast and its uncertainty are then assessed relative to that margin, with the direction of the contrast defined in the analysis plan. A confidence interval describes a range of values compatible with the data under the statistical model; its position in relation to the margin informs the non-inferiority decision. The margin, contrast, interval, and decision rule are not reported in the registry record, so the trial's non-inferiority method cannot be reconstructed.

How should precision be understood?

In general, an estimate is more informative when its uncertainty is also reported. A confidence interval communicates the range of effects that remain compatible with the observed data and analysis assumptions. A point estimate alone does not show whether the data are precise enough to distinguish a small difference from a potentially important one. No primary comparison estimate or confidence interval is reported in the registry record. The enrollment count cannot substitute for those results: enrollment alone does not reveal how many participants contributed to the primary analysis or how variable the endpoint was.

What does the analysis population mean?

The primary endpoint description specifies subjects aged 2 years and above from the according-to-protocol cohort for immunogenicity. It describes that cohort as including evaluable subjects with assay results for antibodies against at least one study vaccine antigen component. In general, an according-to-protocol analysis focuses on participants who satisfy defined protocol and assessment criteria. This can be useful for an immunogenicity question, but interpretation depends on the exact inclusion and exclusion rules and on how participants omitted from the analysis differ from those included. The complete cohort definition and its participant flow are not reported in the registry record.

What can the design details tell us?

Randomization is intended, in general, to reduce systematic differences between treatment groups at assignment. A parallel-group design assigns participants to a group that receives its assigned intervention rather than switching between interventions within the study. The registry records randomization, a parallel model, and no masking. It does not report the allocation ratio, the method used to generate or conceal assignments, or whether outcome assessors were masked. These missing details limit evaluation of how randomization and masking were implemented; they do not by themselves show that the design was or was not properly conducted.

The comparator was age-specific: Mencevax ACWY was used for subjects including and above two years of age, and Meningitec for subjects below two years. This is important context for interpretation. In general, estimates from age groups using different control products should not be treated as if every participant shared one common comparator without checking the analysis structure. The registry record does not report the detailed statistical handling of these age-specific comparisons.

What do the planning assumptions mean?

The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes considering effects as stated fractions of the observed effect. In general, these are assumptions used to illustrate sample-size requirements under a particular statistical framework, not observed trial outcomes and not evidence that the study had a specified probability of success. The numerical planning estimates are not reported in the registry record. The record also does not report the trial's own sample-size justification, so the illustrations should not be treated as the original design calculation or as observed power.

For a binary endpoint, the number of responders and the number assessed in each group are central to interpreting the result. The uncertainty of a group comparison depends on those data and on the chosen measure and method. Since the primary responder counts and comparison statistics are not reported in the registry record, no trial-specific estimate, precision assessment, or recalculation can be described.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 81 outcome measures and 5 analyses. It includes several immune-response outcomes, such as rSBA antibody titers, counts above cut-off values, and anti-polysaccharide antibody concentrations. A large set of outcomes can raise multiplicity concerns because repeated statistical testing increases the chance of finding an apparently notable result by chance. In general, an analysis plan may address this through a prespecified hierarchy, adjustment, or a clearly defined distinction between confirmatory and exploratory outcomes. The registry record does not report whether or how multiplicity was handled.

The primary outcome description identifies a response assessment for four serogroups, but the record does not report how the multiple serogroup-specific measures relate to a single primary decision. The ordering of endpoints, testing sequence, alpha allocation, and any adjustment method are not reported in the registry record. No conclusion about statistical significance across the outcome set can be drawn from the endpoint list alone.

Missing-data handling is also not reported in the registry record. The primary population description refers to evaluable participants with available assay results, but it does not state how unavailable samples, unevaluable results, withdrawals, or protocol deviations were treated. The record does not provide participant flow by analysis population or a comparison of included and excluded participants. This matters because an analysis restricted to available or evaluable observations can be affected if missingness is related to response or group assignment.

The registry description of the according-to-protocol cohort is incomplete. The criteria for protocol adherence and the exact denominator for the primary analysis are not reported in the registry record. Without those details, it is not possible to assess how the analysis population was formed or whether other analysis populations were used to support the non-inferiority objective.

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: bronchitis chronic (2.7%), gastroenteritis rotavirus (2.7%), pneumonia (1.3%), bronchitis (1.3%), gastroenteritis (1.3%).

The serious adverse-event fields list, for the Nimenrix 1-2 Years of Age Group, 5 affected participants among 229 at risk; for the Nimenrix 2-11 Years of Age Group, 2 among 231; for the Meningitec 1-2 Years of Age Group, 7 among 75; and for the Mencevax 2-11 Years of Age Group, 1 among 78. The registry also records zero deaths in each of these groups. These are group-specific counts and denominators, not a direct comparison adjusted for age, follow-up, or other factors.

In general, a serious adverse-event count should be read as a safety summary within the stated group and observation period. It does not by itself describe event timing, duration, severity beyond the serious classification, relatedness to vaccination, or whether a participant had more than one event. The registry record does not report those details in the serious-event summary. It also does not provide a complete account of safety analyses or explain how the groups' observation periods compare.

The listed serious-event terms include bronchitis chronic, gastroenteritis rotavirus, pneumonia, bronchitis, gastroenteritis, and testicular torsion, with percentages recorded for those terms. The listed terms and percentages do not establish causation. No safety conclusion about comparative risk should be inferred from the counts alone.

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

The record establishes that a randomized Phase 2 study was designed to compare meningococcal vaccine 134612 with age-specific control vaccines in children and to assess immune response and longer-term persistence. It specifies a responder endpoint, the timing of its primary assessment, and the criteria used to define a response according to initial serostatus. Those details clarify what the intended primary measure represents.

The registry record does not report the numerical primary-endpoint results. It therefore does not show the observed number of responders, the size or direction of the group contrast, or the precision of that contrast. The non-inferiority margin and decision procedure are also not reported in the registry record. Without those elements, the record cannot establish whether the stated non-inferiority objective was met.

The planned follow-up up to 5 years is not the same as reported evidence of persistence. Numerical long-term results are not reported in the registry record, so the duration of the intended follow-up should not be interpreted as a finding about how long immune responses persisted. Likewise, the study's enrollment count does not disclose how many participants contributed results at each assessment.

The safety summary records serious-event counts and no deaths in the listed groups. These figures provide a limited description of events recorded for those groups; they do not by themselves establish whether events were caused by a vaccine or whether risks differed between groups. The available summary does not provide the timing, relatedness assessments, or full analysis context needed for broader safety interpretation.

In general, a trial result is interpreted by considering the endpoint definition, analysis population, estimate, uncertainty, design, and prespecified decision criteria together. Here, the record gives some design and endpoint information but not the central numerical efficacy or persistence findings. The appropriate conclusion is therefore about what was planned and recorded, not about comparative immune response or long-term protection.

13. Why This Trial Matters Statistically

This study illustrates why a well-defined endpoint and a reported statistical result are both necessary for interpretation. The registry gives a detailed responder definition for the primary immune-response measure, including different criteria for participants who were initially seronegative and seropositive. That makes the intended classification understandable. However, without the responder counts, group comparison, uncertainty interval, and non-inferiority margin, the definition cannot answer whether the groups met the study's intended comparison objective.

The age-specific comparator is another important statistical feature. Participants below two years of age received Meningitec, while subjects including and above two years received Mencevax ACWY. Thus, interpretation needs to retain the distinction between the control products and age groups rather than treating all control participants as an interchangeable single comparator. The registry record does not report the detailed approach used to analyze these comparisons.

The study also distinguishes an early immune-response assessment from planned long-term follow-up. These address different questions: the one-month endpoint concerns response after vaccination, while persistence requires outcomes collected over later follow-up. The record's stated intention to assess persistence up to 5 years does not provide the later outcome data needed to evaluate it.

Finally, the record lists many outcomes and analyses but does not describe multiplicity procedures, missing-data handling, or a complete analysis plan. This highlights a general principle: design labels, endpoint definitions, and outcome inventories describe the framework of a trial, while effect estimates and their uncertainty are needed to assess the evidence. In this case, the statistical record identifies the framework but leaves the primary numerical conclusion unreported.

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 important limitation for interpretation is that numerical primary immune-response results are not reported in the registry record. The record does not give group responder counts, the estimated comparison, an uncertainty interval, or the non-inferiority margin. It therefore does not support a determination of whether the primary objective was met or how precise the comparison was.

The primary analysis description is incomplete. It identifies subjects aged 2 years and above in an according-to-protocol immunogenicity cohort and mentions available assay results, but the full cohort criteria are not reported in the registry record. Participant flow, denominators for the endpoint, protocol deviations, and the handling of missing or unevaluable samples are also not reported.

The comparator differs by age group, and the registry does not report the detailed analysis used to account for those age-specific control vaccines. It also does not report the randomization method, allocation ratio, concealment procedures, or assessor masking. The study is recorded as unmasked, but the roles of participants, investigators, and outcome assessors in that designation are not detailed.

The record describes long-term follow-up as intended to assess protection up to 5 years, but numerical persistence results and details of later assessments are not reported in the registry record. The reported dates identify study milestones but do not establish the availability or completeness of long-term data.

Finally, the record lists 81 outcome measures and 5 analyses without reporting how multiplicity was addressed or distinguishing confirmatory from exploratory analyses. The trial's own sample-size justification is not reported. These omissions limit assessment of the statistical plan, precision, missing-data risks, and the strength of any comparative conclusion.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study in Children to Evaluate Non-Inferiority and Persistence up to 5 Years of GSK Bio Meningococcal Vaccine 134612 — NCT00427908.
• Registry record last updated 2018-06-04; status last verified 2018-05.
• Results first posted 2018-06-04.
• 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

NCT00427908 is a completed randomized, unmasked, parallel-group Phase 2 study with an enrollment of 613. It evaluated GSK Biologicals' meningococcal vaccine 134612 in healthy children and used Mencevax ACWY or Meningitec as age-specific controls. The study began on 2007-02-07, and its primary completion date was 2007-12-03.

The primary endpoint counted participants meeting an rSBA vaccine-response definition for serogroups A, C, W-135, and Y one month after vaccination. The registry describes planned long-term follow-up up to 5 years. Numerical primary and long-term immune-response results, the non-inferiority margin, and key details of the statistical analysis plan are not reported in the registry record. Serious adverse-event counts and group-specific zero deaths are recorded, but the summary does not establish event causation or comparative safety.