Immunogenicity of the Booster Dose of Two MenC Vaccines: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity of the Booster Dose of Two MenC Vaccines (NCT00392808), a randomized phase 4 study. The primary outcome is Serum Bactericidal Activity Against MenC.

2. Clinical Question

The key statistical feature is that this is not simply a comparison of two booster vaccines in a single, otherwise identical group. The registry separates children according to both their priming history and the booster received. Thus, the descriptive results apply to four different vaccine sequences. They can help readers see the reported immune-response measurements in each sequence, but they do not by themselves isolate the booster-vaccine effect from differences in priming history.

3. Trial Design

The registry describes a randomized, open-label, active-control, parallel-assignment clinical trial, listed as phase 4. The study status is completed, and the stated enrollment is 389. The sponsor is Centro Superior de Investigación en Salud Publica. The registry lists a start date of 2007-01 and a primary completion date of 2008-05.

Four groups are described by the sequence of priming and booster vaccines. Children primed with MenC-TT received either MenC-TT or MenC-CRM as the booster. Children primed with MenC-CRM likewise received either MenC-TT or MenC-CRM as the booster. The registry describes the MenC-TT-primed group as having received two MenC-TT priming doses, and the MenC-CRM-primed group as having received three MenC-CRM priming doses. The booster was given in the second year of life; the official title specifies 14–18 months of life.

Open-label means the registry does not describe masking of the treatment assignment. Randomization is reported, but the sequence-generation procedure, allocation concealment, and randomization details are not reported in the registry record. The record also does not explain how the four sequences were allocated or whether randomization was stratified by prior vaccine history.

The primary outcome is serum bactericidal activity against MenC, expressed as geometric mean titres, with a stated timeframe of one month after booster dose. The posted outcome results include group-specific sample sizes, estimates, and 95% confidence intervals. The registry lists two outcome measures but reports no secondary outcome results. It lists zero analyses, so the record does not provide a formal hypothesis test or adjusted comparison for the primary outcome.

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.

Overall Study

Reasons for not completing this period:

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 Serum Bactericidal Activity Against MenC, measured over One month after booster dose.

The primary endpoint is serum bactericidal activity against MenC, reported as geometric mean titres (GMTs) one month after the booster dose. A bactericidal assay measures whether serum can support killing of the meningococcal target under laboratory conditions. In this context, the result is an immune-response measure; it is not itself a record of clinical meningococcal disease.

A geometric mean is commonly used when measurements are positive and vary across a multiplicative scale. General statistical explanation: taking logarithms makes multiplicative differences easier to model, and transforming an average on the log scale back to the original scale gives a geometric mean. A geometric mean therefore describes a group’s central response differently from an arithmetic mean. The registry does not state the assay procedure, laboratory methods, handling of values below or above assay limits, or the precise calculation used for the GMT.

The posted GMT for each group is accompanied by a 95% confidence interval. General statistical explanation: a confidence interval conveys the uncertainty around an estimated group value under the assumptions of the method used. It is not a range containing every participant’s response, and it does not directly test whether two groups differ. A comparative inference would require a specified contrast and its uncertainty, neither of which is posted as a primary analysis.

The single stated measurement time is one month after boosting. The registry does not report later immune-response measurements in the posted primary outcome, so these GMTs describe the response at that stated time rather than its persistence.

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 is appropriate for measurements whose variation is better understood proportionally than additively. For example, equal multiplicative changes are treated symmetrically on the logarithmic scale. This differs from an arithmetic mean, which summarizes additive distances. The registry identifies the endpoint as a geometric mean and reports confidence intervals, but it does not describe whether values were transformed for analysis or how the intervals were calculated.

The posted result for each vaccine sequence is a single group-level estimate. It summarizes the distribution of serum bactericidal activity within that group; it does not show individual responses or the full shape of the distribution. The registry provides no standard deviations, medians, quartiles, or participant-level values for this endpoint. As a result, variability among individuals cannot be reconstructed from the posted GMT and confidence interval alone.

How should a 95% confidence interval be read?

General statistical explanation: a confidence interval expresses the precision of an estimate under a statistical procedure and its assumptions. A narrower interval indicates greater precision for that particular estimate than a wider interval would, but precision is not the same as clinical importance. A 95% confidence interval is not a statement that 95% of individual observations fall inside its limits. Nor does an interval for one group directly provide a test of the difference between two groups.

For this outcome, the record reports 95% confidence intervals for all four group GMTs. It does not specify the confidence-interval method, whether the interval is based on a log-scale calculation, or any adjustments. No formal comparative estimate or uncertainty interval for a between-group contrast is posted. Therefore the group intervals support descriptive reading of the reported estimates, not a definitive inference about which booster sequence differs from another.

Why does the four-group structure matter?

General statistical explanation: when an experiment includes multiple treatment sequences, the question being estimated needs to be stated precisely. A comparison of boosters among children with the same priming history differs from a comparison across groups with different priming histories. This trial’s groups vary on both factors: prior vaccine and booster vaccine. The four group summaries retain that structure, but the record does not report a factorial model, a pairwise comparison plan, or a combined estimate of the booster effect.

That distinction matters because a numerical contrast between two sequence groups could reflect more than the booster difference if their priming histories also differ. Comparisons within the same priming history would hold that listed factor constant descriptively, but a formal estimate and its uncertainty would still be needed for an inferential claim. The registry does not report such an analysis.

What does randomization contribute?

General statistical explanation: random assignment is intended to make treatment groups comparable on average with respect to factors known and unknown at assignment, subject to the conduct of the trial and chance variation. Here, randomization is reported, but the registry does not describe how it was implemented, the allocation concealment, or whether assignment occurred separately within prior-vaccine strata. The record therefore supports stating that the study was randomized, but not describing details of its randomization procedure.

Open-label assignment means masking is listed as none. The registry does not explain whether laboratory personnel assessing the endpoint were masked. Because the endpoint is a laboratory immune-response measure, the absence of that detail is relevant to understanding how measurement procedures were controlled, but it does not establish that measurements were biased.

What can be concluded from the posted analyses?

The record lists zero analyses. It supplies endpoint summaries but no p-values, no model results, no adjusted estimates, and no stated primary contrast. The study summary says the purpose includes evaluating immune response and assessing interchangeability of the vaccines. However, the registry does not post an equivalence or non-inferiority margin, a hypothesis-testing framework, or a formal assessment of interchangeability. General statistical explanation: evidence of similarity or interchangeability ordinarily depends on a prespecified margin and an analysis designed to evaluate that margin; simply observing group estimates that are near one another is not enough to establish equivalence.

The registry record does not report a sample-size justification or the assumptions used by the trial designers. Any planning illustrations associated with the posted results are distinct from the trial’s original design calculations: they are based on the observed effect under stated assumptions and are not observed power. They should be read as hypothetical planning quantities, not evidence that the trial had a particular probability of detecting an effect.

Why is over-dispersion sometimes relevant?

General statistical explanation: over-dispersion occurs when the observed variability in data is greater than a statistical model assumes. It can make standard errors too small if ignored, leading to confidence intervals that are too narrow and tests that are too optimistic. The registry does not report a model for this endpoint or any assessment of over-dispersion. This concept is therefore a general consideration, not a reported feature of this trial’s analysis.

In summary, the methods that can be identified are the randomized, open-label, parallel-group design and the reporting of group GMTs with 95% confidence intervals. The detailed analysis methods needed to interpret formal comparisons are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures but posts results for the primary endpoint described as serum bactericidal activity against MenC. It reports zero analyses and zero posted secondary outcomes. A statistical analysis plan, a hierarchy of outcomes, and any multiplicity adjustment are not reported in the registry record.

General statistical explanation: multiplicity arises when several outcomes, time points, treatment comparisons, or subgroup analyses are tested. If many hypotheses are tested without accounting for that, the chance of at least one apparently unusual result can increase. A prespecified testing strategy can define which comparisons are confirmatory and how error rates are controlled. Since no formal analyses or analysis plan are posted, the registry does not show whether multiplicity was considered.

The primary result has a stated timeframe of one month after the booster dose. Other time points, if collected, and their analysis are not reported in the registry record. The record also does not report a prespecified primary contrast among the four vaccine sequences.

The posted outcome sample sizes are 81.0, 86.0, 107.0, and 100.0 across the four groups, while overall enrollment is 389. The registry does not explain why the outcome counts differ from one another or from enrollment, whether measurements were missing, or how missing values were handled. It does not state whether the analyses used an intention-to-treat, per-protocol, or other analysis population. These matters are not reported in the registry record.

Without the missing-data method and analysis-population definition, readers cannot determine from the registry alone how exclusions, incomplete measurements, or protocol deviations may have affected the endpoint summaries. This limits interpretation of the estimates and any attempt to reproduce a formal analysis.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: asthma (2.2%), fever (1.9%), febrile seizures (1.1%), cutaneous abscess (1.1%), ataxia (1.1%).

The registry posts serious adverse event counts by vaccine-sequence group. The numbers at risk and numbers affected are: MenC-TT/MenC-TT, 87 at risk and 3 affected; MenC-TT/MenC-CRM, 89 at risk and 5 affected; MenC-CRM/MenC-TT, 109 at risk and 2 affected; and MenC-CRM/MenC-CRM, 104 at risk and 2 affected. These are counts as recorded, not comparative estimates adjusted for differences among groups.

The registry also lists the most frequent serious adverse event terms as asthma (2.2%), fever (1.9%), and febrile seizures, cutaneous abscess, ataxia, and pneumonia (each 1.1%). The record does not provide further event-level detail, such as timing, duration, severity grading, or attribution to vaccination. It does not report deaths in the posted safety data; death counts are not reported in the registry record.

Other adverse events are also posted as counts affected: zero in the MenC-TT/MenC-TT group, 1 in the MenC-TT/MenC-CRM group, 6 in the MenC-CRM/MenC-TT group, and 5 in the MenC-CRM/MenC-CRM group. The registry does not provide definitions or a detailed breakdown of these events in the record.

General statistical explanation: adverse-event counts are descriptive unless a comparative safety analysis, with methods suited to the event data, is reported. Small counts can be imprecise, and raw counts alone do not establish whether groups differ. The registry lists no formal safety analyses, so these figures should be read as the posted event counts rather than as evidence of a comparative safety effect.

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

The posted primary results describe serum bactericidal activity one month after boosting in four groups with different priming and booster vaccine sequences. Each group has a GMT and a 95% confidence interval. Those values characterize the reported immune-response measurements in the participants contributing to each group summary.

The results do not establish a formal difference between booster vaccines. Although the group estimates can be compared descriptively, the registry reports no direct statistical contrast, p-value, adjusted estimate, or analysis model. The groups also differ by their priming vaccine and number of priming doses, so the group summaries do not isolate the effect of booster choice.

The record states that interchangeability was an objective, but it does not report a prespecified equivalence or non-inferiority margin, or an analysis testing interchangeability. General statistical explanation: a failure to report a significant difference would not establish equivalence; equivalence requires an appropriate design and inference tied to a defined margin. In this record, no such inference is posted.

The endpoint is an immune-response measure, not a clinical disease outcome. The registry does not report whether participants later developed meningococcal infection, nor does it state an assay threshold for interpreting a GMT as protective. The results therefore cannot, from the registry record alone, establish clinical protection or its duration.

The safety figures are counts of serious and other adverse events by group. The registry does not provide a comparative safety analysis or detailed event attribution. These counts should not be taken as proof that one vaccine sequence has more or fewer adverse effects than another.

Overall, the record supports a descriptive account of the four group-level immune-response estimates and the posted safety counts. It leaves the formal comparative question, the analysis populations, and the clinical meaning of the assay results unresolved. These limitations are about what the registry reports and do not imply that additional analyses or information do not exist elsewhere.

13. Why This Trial Matters Statistically

This trial is statistically notable because it reports four vaccine sequences rather than a single two-group contrast. Each sequence combines a priming history and a booster choice. That structure makes the scientific question important to define: a comparison of boosters among children with a common priming history is not the same as a comparison across different priming histories.

The posted GMTs and confidence intervals let readers inspect the scale and precision of the immune-response summaries for each sequence. They also illustrate why descriptive group estimates and inferential comparisons are different statistical products. A collection of group estimates is useful for description, but it does not replace a specified contrast with an uncertainty estimate when the objective is to compare vaccine sequences.

The trial summary names interchangeability as a purpose, making the absence of a posted equivalence or non-inferiority analysis particularly relevant. General statistical explanation: the conclusion that two interventions are sufficiently similar requires a definition of how much difference would still count as acceptable, together with an analysis designed to evaluate that criterion. The registry does not provide those elements, so the posted results cannot be read as a formal interchangeability finding.

The record also shows the importance of interpreting immunogenicity endpoints within their scope. Serum bactericidal activity is a laboratory measure of immune response. It is distinct from clinical disease outcomes, and the registry does not provide a threshold or later follow-up that would connect these specific GMT summaries to clinical protection or persistence.

Finally, reporting the endpoint sample sizes alongside the overall enrollment raises a practical interpretation issue: the record does not explain the contributing analysis populations or missing data. Clear reporting of those details would help readers assess how the group summaries relate to the randomized participants. In this record, the most defensible reading is descriptive and bounded by the information posted.

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 registry does not report eligibility criteria, participant baseline characteristics, or further details of the population contributing to the primary endpoint. Although the official title specifies booster administration at 14–18 months of life, the record does not provide additional age distributions or a detailed account of the children enrolled.

The trial is described as randomized and open-label, but the randomization method, allocation concealment, and masking of endpoint assessors are not reported in the registry record. The number of participants originally assigned to each group and their movement through the study are also not provided. Consequently, the relationship between the overall enrollment of 389 and the endpoint sample sizes cannot be fully assessed.

The primary endpoint is reported as GMTs with 95% confidence intervals, but assay methods, data transformations, confidence-interval calculations, and handling of assay limits are not reported. The registry provides no participant-level distribution or supplementary summary measures of variability. The endpoint is measured one month after the booster; later measurements and durability are not reported in the posted results.

The four arms have differing priming histories, including different numbers of priming doses. No formal comparison, adjusted analysis, or prespecified contrast is posted. The stated interest in interchangeability is not accompanied by a posted margin or equivalence/non-inferiority analysis. The statistical analysis plan, sample-size justification, and any interim analyses are not reported in the registry record.

For safety, event counts are posted, but definitions, timing, attribution, and a comparative analysis are not reported. Death counts are not reported in the registry record. Secondary outcome results are also not posted. These limits mean that the registry supports a narrow descriptive interpretation of the immune-response estimates and event counts, rather than a complete account of the trial’s design, conduct, or inferential findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity of the Booster Dose of Two MenC Vaccines — NCT00392808.
• Registry record last updated 2013-10-11; status last verified 2013-08.
• Results first posted 2013-10-11.
• 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

NCT00392808 is a completed phase 4 randomized, open-label, active-control, parallel-assignment trial of MenC vaccine booster sequences. The registry lists enrollment of 389 and a primary completion date of 2008-05. Its stated purpose was to evaluate the immune response to a booster in the second year of life and assess interchangeability of two MenC vaccines.

The primary outcome is serum bactericidal activity against MenC, expressed as GMTs with 95% confidence intervals one month after the booster. Four groups are reported, reflecting MenC-TT or MenC-CRM priming followed by either booster. The record posts group estimates and safety counts, but lists zero analyses and no posted secondary outcome results.

The registry does not report a formal comparative analysis, detailed statistical plan, analysis populations, missing-data methods, or an equivalence assessment. The results therefore support description of the posted group summaries, not a formal conclusion about comparative efficacy, interchangeability, or clinical protection.