Study in Adolescents/Adults to Evaluate Non-inferiority&Persistence up to 5 Years of GSK Bio MenACWY Conjugate Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study in Adolescents/Adults to Evaluate Non-inferiority&Persistence up to 5 Years of GSK Bio MenACWY Conjugate Vaccine (NCT00356369), a randomized phase 2 study. The primary outcome is Vaccine Response to Meningococcal Antigens for Serum Bactericidal Assay Using Rabbit Complement (rSBA).

2. Clinical Question

3. Trial Design

This was a Phase IIb primary vaccination study, listed as Phase 2 in the registry, comparing GSK Biologicals’ meningococcal ACWY conjugate vaccine with Mencevax ACWY. It enrolled 500 healthy subjects aged 11–55 years. The registry describes the study as randomized, unmasked, and parallel-group. The official title specifies intramuscular administration for the GSK vaccine and subcutaneous administration for Mencevax ACWY. The registry record does not report how the random sequence was generated, whether allocation was concealed, or whether any safeguards were used to limit bias in outcome assessment.

The registry lists a start date of 2006-12-23, a primary completion date of 2007-09-07, and a completed status. The sponsor was GlaxoSmithKline. The brief summary describes a vaccination phase and a long-term follow-up phase intended to assess persistence up to five years after vaccination. The primary endpoint timeframe is one month post vaccination. The registry record does not report follow-up completion, retention, or endpoint results for the extension phase, so the planned duration should not be mistaken for documented follow-up in the posted results.

The primary immunogenicity analysis population was the According-to-Protocol cohort for immunogenicity. It included evaluable subjects for whom immunogenicity data were available. This population definition is important: the primary analysis was not described as including every enrolled subject. The registry record does not report the cohort size, the reasons subjects might have been excluded, or how exclusions were distributed between groups. It also does not report whether any additional analysis populations were used for the primary endpoint.

The primary objective concerned the immune response to vaccine antigens measured using serum bactericidal assay with rabbit complement. The registry lists 32 outcome measures and 5 analyses, including antibody response and persistence-related measures. However, the posted record does not provide the group-level primary outcome results or a single primary comparison that can be interpreted as a complete non-inferiority analysis. It therefore describes the study’s design and endpoint but does not establish the outcome of the planned comparison.

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.

Active Phase

Reasons for not completing this period:

Year 1

Year 2

Year 3

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.

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 Vaccine Response to Meningococcal Antigens for Serum Bactericidal Assay Using Rabbit Complement (rSBA), measured over One month post vaccination.

The primary endpoint was the percentage of subjects with a vaccine response to meningococcal antigens measured by serum bactericidal assay using rabbit complement, or rSBA, one month post vaccination. The response definition depended on the subject’s starting antibody status. For initially seronegative subjects, defined as having an rSBA titer < 1:8, response required a post-vaccination titer ≥ 1:32. For initially seropositive subjects, with a baseline titer ≥ 1:8, response required at least a 4-fold increase from before to after vaccination.

Using a percentage makes the endpoint a binary outcome at the subject level: each evaluable subject either meets the specified response definition or does not. The endpoint is therefore a summary of the proportion meeting the criterion, rather than a direct measure of the size of each subject’s antibody change. Reporting the two baseline-status rules matters because the same response criterion does not apply to every subject.

rSBA is an assay-based measure of serum bactericidal activity against the listed meningococcal serogroups. It provides a defined way to assess antibody response, while the endpoint’s threshold rules specify what counts as a response for this study. The registry record identifies a 95% confidence interval as the dispersion measure. A confidence interval communicates uncertainty around an estimated response percentage; its width depends on the data and analysis. The primary response percentages and confidence intervals are not reported in the registry record, so neither the magnitude nor precision of the observed response can be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is sufficient to identify the outcome’s form and the intended analysis population, but it is not a full statistical analysis plan. The primary outcome is a percentage of subjects meeting a binary response criterion, and the stated dispersion measure is a 95% confidence interval. The registry record does not report the model, test, contrast, non-inferiority margin, or decision rule used for the primary comparison.

What does a percentage endpoint represent?

For a binary endpoint, each subject is classified according to whether the prespecified criterion is met. The percentage summarizes the share of analyzed subjects classified as responders. It does not preserve all information about the antibody titer: subjects with different titers can both count as responders, while a subject just below the threshold and a subject with a much lower titer can both count as nonresponders. That is why the registry also lists titer-based secondary outcomes, although their results are not reported in the registry record.

The study’s response rule uses baseline serostatus to define the criterion. Initially seronegative subjects were required to reach a post-vaccination rSBA titer ≥ 1:32 after a baseline titer < 1:8. Initially seropositive subjects were required to have at least a 4-fold increase from pre-vaccination to post-vaccination. These rules are part of the endpoint definition, not results. The record does not report the proportions initially seronegative or seropositive, or how those categories contributed to the overall response estimate.

What does a confidence interval add?

A confidence interval presents a range of values compatible with the data under the method used to calculate it. It helps readers distinguish a point estimate from the uncertainty around that estimate. It does not mean that the true value has a specified probability of falling within that particular calculated interval. The width reflects both the amount of information and the variability of the outcome, along with the statistical method. Although the primary endpoint lists a 95% confidence interval, neither the interval endpoints nor the response estimates are reported in the registry record.

For a comparison between groups, uncertainty around the contrast is central. Looking only at whether separate group intervals overlap is not a substitute for a confidence interval or test for the between-group contrast. The registry record does not give a primary contrast estimate, its confidence interval, or a p-value. Consequently, no direction or precision of a group difference can be inferred from the endpoint description alone.

Why does the non-inferiority framing need more information?

A non-inferiority analysis asks whether the intervention’s outcome is not unacceptably worse than the comparator according to a prespecified margin. The margin must be interpreted alongside the contrast and its uncertainty; the study title or objective is not a substitute for those quantities. The registry record does not report the margin or the analysis rule, and the primary response results are not reported. It is therefore not possible to assess whether the planned non-inferiority criterion was met. The record also does not state whether other analyses, such as a per-protocol and an intention-to-treat analysis, were required or how their findings would be reconciled.

What can be learned from the sample-size assumptions?

The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. This is a planning calculation, not a description of the trial’s original design justification. It is not observed power and does not establish the probability that the study detected an effect. The registry record does not report the trial’s own sample-size justification. The primary outcome was not reduced to a single comparison because it has several categories or time points, so a single primary comparison should not be inferred from an illustration for another specification.

In general, sample-size planning depends on assumptions about the effect to detect, variability or event frequency, the chosen error rate, allocation, and analysis method. If an effect estimate from a completed study is used to illustrate future planning, the result describes a hypothetical design under those assumptions. It does not retroactively describe the study’s design, and it does not tell whether an observed result is reliable. The posted record does not report a numerical sample-size illustration for the primary endpoint that can be interpreted as the trial’s planned enrollment rationale.

How should the analysis population be interpreted?

The primary analysis population is described as the According-to-Protocol cohort for immunogenicity, including evaluable subjects for whom immunogenicity data were available. In general, an analysis population defined this way can differ from the enrolled group if some subjects lack evaluable data or do not meet the protocol’s analysis criteria. The registry record does not describe those criteria in detail, list exclusions, report missing primary endpoint data, or give group-specific analysis denominators. The possible effect of exclusions on the estimated response therefore cannot be assessed.

Randomization can support a fair comparison when allocation is preserved and outcomes are analyzed appropriately. However, the registry record does not provide enough detail to assess sequence generation, concealment, or the handling of post-randomization exclusions. The unmasked design is reported, but the record does not explain whether knowledge of assignment could have influenced outcome assessment or how that risk was addressed. These are limitations in what can be evaluated from the registry record, not proof that a specific bias occurred.

The registry lists 32 outcome measures and 5 analyses. In general, testing or interpreting many outcomes can raise multiplicity concerns: the chance of a false-positive finding can increase when many hypotheses are examined without an appropriate strategy. The registry record does not report a multiplicity adjustment, hierarchy among outcomes, or a strategy distinguishing confirmatory from exploratory analyses. The number of listed outcomes alone does not establish that any particular result is false or biased; it means the inferential strategy cannot be fully assessed from the record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 32 outcome measures and 5 analyses, including primary and secondary immunogenicity measures. It does not report a multiplicity strategy, such as an ordering of confirmatory outcomes, an adjustment to control the family of comparisons, or a distinction between confirmatory and exploratory testing. When many outcomes or comparisons are considered, multiplicity can make isolated findings harder to interpret because the chance of a false-positive result may increase. This is a general statistical concern; the registry record does not establish that any reported result was affected by it.

The primary endpoint is expressed as a percentage with a 95% confidence interval, but no endpoint estimates or intervals are reported. The endpoint description also refers to several serogroups and a response definition based on initial serostatus. The registry notes that the primary outcome has several categories or time points and was not reduced to one comparison. Accordingly, a single primary contrast should not be assumed from the record. The method for selecting or combining categories and time points is not reported in the registry record.

The stated primary population was the According-to-Protocol cohort for immunogenicity, comprising evaluable subjects with available data. This definition indicates that the analysis depends on both evaluability and data availability. The registry record does not report how much primary endpoint data were missing, why data might be unavailable, how missing values were handled, or whether any sensitivity analyses were performed. It also does not report the size of this analysis cohort or its group-specific denominators.

The record does not describe how protocol deviations, withdrawals, or incomplete follow-up were handled. It does not report whether the extension phase used the same analysis population as the primary vaccination phase. These omissions limit assessment of potential selection effects and the robustness of findings, especially for persistence outcomes. They do not show that missing data or multiplicity invalidated the study; they mean the relevant methods and results 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: mental disorder (0.3%), costochondritis (0.3%).

The registry reports safety figures for the Nimenrix Group and the Mencevax Group. The listed denominators at risk for serious events are 374 and 126, respectively. The serious-event counts are 1 and 0, and the death counts are 0 and 0. These are descriptive counts in the registry record. They do not by themselves establish whether an event was caused by vaccination, and the record does not report a causal assessment.

The top serious-event terms are Mental disorder and Costochondritis, each listed as 0.3%. The registry record does not clarify the relationship between these terms and the serious-event counts, whether terms refer to subjects or events, or how the percentages were calculated. The percentages should therefore be read as reported, not converted into counts or combined with other safety categories.

Other adverse events are listed for 186 subjects in the Nimenrix Group and 53 in the Mencevax Group. These are not the serious-event counts. The registry does not provide a fuller breakdown of event types, duration, severity, timing, or relatedness in the registry record recorded for this summary. The group denominators and counts are descriptive; they should not be treated as a comparative risk estimate without a specified analysis and context. No safety comparison or causal conclusion is reported in the registry record.

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

The posted results identify a randomized, unmasked, parallel-group study and define the primary immunogenicity endpoint. They also describe the planned long-term assessment and list selected safety figures. The registry record does not report the primary response percentages, confidence intervals, or comparative estimate. It therefore does not show whether the GSK vaccine’s measured response was higher, lower, or similar to that of Mencevax ACWY, nor whether a non-inferiority criterion was met.

The endpoint is an assay-based response classification one month post vaccination. Meeting that definition means a subject reached the specified titer threshold or fold increase according to baseline serostatus. It does not, on its own, establish the duration of a response, clinical protection, or the outcome of meningococcal disease. The registry’s description of a persistence follow-up up to five years is a study objective, not a reported persistence result. Long-term outcomes are not reported in the registry record.

The 500 enrolled subjects provide the study’s overall enrollment figure, but the primary analysis was defined using an evaluable According-to-Protocol immunogenicity cohort with available data. Its size and group-specific denominators are not reported. Enrollment should not be interpreted as the number contributing to each endpoint. Without the analysis denominators and outcome data, the precision and representativeness of the primary estimate cannot be judged.

The serious-event counts, death counts, and other adverse-event counts are descriptive safety information. They do not establish causation or a treatment effect, and the record does not report a comparative safety analysis. Similarly, listing secondary antibody measures does not convey their results. A complete interpretation would require the actual outcome estimates, their uncertainty, and the relevant analysis methods.

In general, a trial’s objective, endpoint definition, and observed results are distinct pieces of evidence. The registry record describes the objective and measurement rules, but the primary outcome results needed to evaluate the central comparison are absent. The defensible interpretation is therefore limited to what was planned and what descriptive safety figures were posted; no conclusion about comparative immune response, non-inferiority, or persistence follows from the available results.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a reported result are both necessary for statistical interpretation. The primary endpoint uses an explicit rSBA response criterion and reports the intended summary as a percentage with a 95% confidence interval. Defining response by baseline serostatus makes the classification rule transparent. At the same time, a reader needs the resulting response estimates and their uncertainty to understand what the study observed. Those primary results are not reported in the registry record.

The study’s non-inferiority framing also highlights the role of a prespecified margin and a direct comparison. A non-inferiority objective cannot be evaluated from a study title or from the existence of a response endpoint alone. The margin, analysis rule, group estimates, and uncertainty must be available to assess the question. Their absence in the registry record leaves the central inferential claim unresolved.

The design and analysis populations matter as well. Randomization is reported, but the procedure is not. The primary analysis is defined as an According-to-Protocol cohort of evaluable subjects with available data, but its size and exclusions are not reported. These details affect how readers judge the relation between the randomized groups and the analyzed groups. The registry’s unmasked designation is another feature to consider, while the record does not describe any steps to address potential assessment bias.

The registry lists multiple outcome measures and analyses, but does not state how multiplicity was handled. This shows why a count of outcomes is not itself a statistical conclusion: readers need to know which comparisons were primary, how uncertainty was controlled, and whether analyses were exploratory or confirmatory. The record also distinguishes a planned long-term persistence phase from actual reported follow-up results. Together, these features make the trial useful as an example of how registry entries can describe design and measurement without providing enough evidence to resolve the study’s principal statistical question.

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 main limitation for interpretation is that the primary endpoint results are not reported in the registry record. The record supplies the response definition and confidence-interval measure but no group-specific response percentages, intervals, or direct comparison. It also does not report the non-inferiority margin or decision rule. Thus, the central comparative objective cannot be evaluated from the posted results.

The primary analysis population is described as the According-to-Protocol cohort for immunogenicity, including evaluable subjects with available data. The record does not give the size of that cohort, group-specific denominators, exclusions, or missing-data handling. This prevents assessment of how much outcome information was available or whether analysis-population exclusions may have affected comparability.

Although the study is reported as randomized, the randomization procedure and allocation concealment are not described. The study was unmasked, but the record does not explain how outcome assessment was conducted or whether any procedures addressed possible bias. The registry record also does not provide the statistical model, analysis details, or multiplicity strategy for the listed outcomes and analyses.

The brief summary describes long-term follow-up intended to assess persistence up to five years, but the record does not report the persistence results, follow-up completion, or analysis denominators at later time points. The safety information is limited to the listed counts and top serious-event terms; fuller detail on timing, severity, relatedness, and comparative analysis is not reported in the registry record. These gaps limit interpretation of efficacy-related and safety-related questions without establishing that any particular result is biased or unreliable.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study in Adolescents/Adults to Evaluate Non-inferiority&Persistence up to 5 Years of GSK Bio MenACWY Conjugate Vaccine — NCT00356369.
• Registry record last updated 2018-07-03; 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

NCT00356369 is a completed, randomized, unmasked, parallel-group Phase 2 study sponsored by GlaxoSmithKline. It enrolled 500 healthy subjects aged 11–55 years and compared a GSK meningococcal ACWY conjugate vaccine with Mencevax ACWY. The official title describes intramuscular administration of the GSK vaccine and subcutaneous administration of Mencevax ACWY. The registry lists a start date of 2006-12-23 and a primary completion date of 2007-09-07.

The primary endpoint was the percentage of subjects meeting a serostatus-dependent rSBA response definition one month post vaccination, with a 95% confidence interval as the stated dispersion measure. The primary immunogenicity analysis population was the According-to-Protocol cohort of evaluable subjects with available data. The registry record does not report primary endpoint estimates, their confidence intervals, or the non-inferiority margin. It describes intended persistence follow-up up to five years but does not report persistence results. Safety figures include serious-event counts of 1 and 0, death counts of 0 and 0, and other adverse-event counts of 186 and 53 for the Nimenrix and Mencevax groups, respectively.