Evaluation of Persistence of Anti-meningococcal Bactericidal Antibodies Among Adolescents Who Previously Received MenACWY Conjugate Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Persistence of Anti-meningococcal Bactericidal Antibodies Among Adolescents Who Previously Received MenACWY Conjugate Vaccine (NCT00856297), a non-randomized phase 3 study. The primary outcome is Percentages of Subjects With Human Complement Serum Bactericidal Activity (hSBA) Titers≥ 1:8, After One Dose of Either MenACWY-CRM Conjugate or Licensed Comparator Vaccine.

2. Clinical Question

The central statistical issue is how to interpret antibody measurements collected at several follow-up times in groups formed by prior vaccination history. Because allocation was non-randomized, differences between groups cannot be attributed to vaccine assignment alone on the basis of this design. Participants in the previously vaccinated groups had different vaccination histories from the naïve group, and the registry does not report a randomized assignment process.

The study also describes booster groups, in which participants received MenACWY-CRM 3 years after primary vaccination. Those groups address a different history of exposure from follow-up after a primary dose alone. The registry record does not provide numerical endpoint results for either the primary-dose or booster groups, so the clinical question can be described but the observed antibody persistence cannot be quantified from the record.

3. Trial Design

This was a completed, Phase 3, open-label, multicenter study with non-randomized allocation and a parallel model. Enrollment was 389. The study began in 2009-02, and primary completion was recorded as 2012-11. The sponsor was Novartis Vaccines. The condition listed was meningococcal meningitis.

The primary objective was to evaluate persistence of bactericidal antibodies among adolescents who had previously received either Novartis MenACWY conjugate vaccine or a commercially available MenACWY conjugate vaccine in the parent study. Participants in those groups were followed after their primary vaccination. The licensed-comparator group was described as being followed at 5 years postvaccination. An age-matched naïve group, with no previous meningococcal vaccination, was included as an additional control.

The registry also describes two booster groups. Participants in one group had received primary MenACWY-CRM and a MenACWY-CRM booster 3 years after primary vaccination. Participants in the other had received a primary dose of quadrivalent meningococcal diphtheria toxoid conjugate vaccine and then a MenACWY-CRM booster 3 years after primary vaccination. These distinct vaccination histories matter when interpreting comparisons: the booster groups are not interchangeable with groups followed after a primary dose alone.

Open-label means masking was none, as recorded. Non-randomized allocation means that the registry does not describe random assignment to the vaccine groups. The posted results therefore should not be read as a randomized, like-for-like comparison; the registry explicitly flags this limitation. Details of recruitment, the reasons participants entered each group, and any adjustment for differences between groups are not reported in the registry record.

The registry lists 11 outcome measures, including the primary hSBA threshold outcome, geometric mean titers, outcomes among participants without prior vaccination, booster-response outcomes, and adverse events. It records 0 analyses. Numerical results for the primary endpoint are not reported in the registry record, so the design and intended comparisons can be described, but the magnitude of the antibody responses cannot be evaluated from the 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: All enrolled subjects were included in the trial.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was done on PP persistence population - subjects who provided one evaluable serum sample at baseline at any visit (21 months, 3 years and 5 years) and had no major protocol deviations.

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: Enrolled population

6. Primary Endpoint

The registry lists the primary outcome as Percentages of Subjects With Human Complement Serum Bactericidal Activity (hSBA) Titers≥ 1:8, After One Dose of Either MenACWY-CRM Conjugate or Licensed Comparator Vaccine, measured over 21 months, 3 years and 5 years postvaccination.

The primary endpoint was the percentage of participants with human complement serum bactericidal activity (hSBA) titers at or above 1:8. The endpoint was assessed against meningococcal serogroups A, C, W and Y at 21 months, 3 years and 5 years postvaccination. The stated comparison was between one dose of MenACWY-CRM and one dose of the licensed comparator vaccine.

hSBA is an antibody assay that measures bactericidal activity in the presence of human complement. A threshold-based endpoint converts each participant’s measured titer into whether it meets a specified level, then expresses the group result as a percentage. In general, such a threshold can make a biological response easier to summarize and compare than a list of individual titers. The registry also lists secondary outcomes using other hSBA thresholds and geometric mean titers, which describe antibody levels in a different way.

The endpoint is reported with a 95% confidence interval as its stated measure of dispersion. In general, a confidence interval conveys uncertainty around an estimated percentage; its width depends on the data and the method used to calculate it. The registry record does not report the endpoint percentages or their confidence intervals, nor does it report the calculation method. Consequently, neither the observed response levels nor their precision can be assessed from the registry record.

The primary endpoint population was the per-protocol persistence population: participants who provided an evaluable serum sample at one of the specified visits and had no major protocol deviations. The registry does not report how many participants contributed endpoint data at each follow-up visit or serogroup.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a threshold-based immune-response measure. For each participant, the hSBA titer is assessed against a specified level, and the endpoint summarizes the percentage meeting that threshold. The study specifies a threshold at or above 1:8 for serogroups A, C, W and Y. As a general statistical concept, a percentage is a proportion expressed on a 0-to-100 scale; the estimate depends on how many participants meet the criterion and how many contribute evaluable measurements. The registry record does not report those endpoint counts or percentages.

What does the confidence interval add?

The registry specifies a 95% confidence interval as the measure of dispersion for the primary endpoint. In general, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of its statistical method. A narrower interval indicates greater precision than a wider interval, but neither the interval width nor the underlying estimate is reported. The method used to calculate the intervals is not reported in the registry record. Without the estimates, intervals and contributing sample sizes, the precision of the endpoint cannot be evaluated.

Why report geometric mean titers as well?

Several secondary outcomes concern hSBA geometric mean titers (GMTs). In general, a geometric mean summarizes measurements on a multiplicative scale and is often used for quantities such as antibody titers that can span a broad range. It answers a different descriptive question from a threshold percentage: a threshold percentage reports how many participants meet a chosen level, while a GMT summarizes the distribution of measured titers. The registry lists GMT outcomes but does not report their numerical results or the calculation details, such as any handling of values below assay limits.

What does follow-up over time mean statistically?

Measurements at 21 months, 3 years and 5 years are intended to describe persistence at distinct follow-up times. In general, results at each time point should be interpreted with attention to the number of participants measured at that time and whether the same participants contributed repeatedly. The registry record does not report time-specific endpoint counts, the extent of repeated observations, or how incomplete follow-up was handled. The primary population definition requires an evaluable serum sample at one of the specified visits and no major protocol deviations; it does not, by itself, establish that every participant contributed a result at every visit.

The registry also includes outcomes among participants with no previous meningococcal vaccination and outcomes after a booster dose. These are related but distinct analyses because participants differ in vaccination history and exposure. The record does not report numerical results that would allow comparison of primary-dose and booster responses. Nor does it report whether comparisons were adjusted for baseline characteristics or other differences between the groups.

How does allocation affect interpretation?

Allocation was non-randomized, and masking was none. In general, randomization can help balance measured and unmeasured characteristics between comparison groups, while non-randomized groups may differ for reasons related to how participants entered each group. Open-label status means masking was not used, as recorded; the record does not describe whether or how this could have affected outcome measurement or other study processes. These design features do not erase the value of descriptive follow-up, but they constrain causal interpretation of between-group differences.

The registry explicitly flags the vaccine arms as not a like-for-like control comparison. This is particularly relevant because the groups reflect different earlier vaccination histories, and some received a booster. A numerical contrast, even if available, would need to be read in light of that design. The registry does not report a statistical model or adjustment strategy for these comparisons.

What analysis details are missing?

The registry lists the primary endpoint with a 95% confidence interval and lists 11 outcome measures, but records 0 analyses. The statistical analysis plan, methods for confidence intervals, handling of repeated measurements, subgroup methods, and any procedures for multiple comparisons are not reported in the registry record. The record also does not report a sample-size justification or the assumptions used to plan enrollment. These omissions prevent reconstruction of the intended inferential approach and make it important to distinguish the stated outcome definitions from numerical findings, which are not reported.

A separate sample-size illustration, when presented, should be understood as a planning illustration rather than an observed property of this trial. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such illustrations are not the trial’s own design justification and are not observed power. The registry record does not report a sample-size justification for the study itself.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures spanning several kinds of immune-response summaries, follow-up settings and safety outcomes. The primary outcome itself covers four meningococcal serogroups and three follow-up times. Considering multiple outcomes or time points can raise a multiplicity question: when many comparisons are examined, the chance of at least one apparently unusual result may increase. In general, a prespecified analysis plan can clarify which comparisons are primary and whether any adjustment or hierarchy is used.

The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or whether any adjustment was planned. It also records 0 analyses, and numerical endpoint results are not reported. It is therefore not possible to determine which comparisons were actually performed or how any multiplicity was addressed. No claim that an adjustment was used or omitted can be made from the record.

The primary endpoint population was the per-protocol persistence population. It included participants with an evaluable serum sample at one of the specified follow-up visits and no major protocol deviations. The record does not report the numbers eligible for this population at each visit, the reasons for exclusion, or how missing measurements were handled. It does not say whether participants missing a visit were excluded from that time-specific analysis, whether any imputation was used, or whether a sensitivity analysis assessed the effect of missing data.

These gaps matter because follow-up measurements can be unavailable for reasons that may relate to participant characteristics or outcomes. In general, the interpretation of a complete-case estimate depends on the missingness pattern and analytic assumptions. The registry record does not report enough information to assess those assumptions. It also does not describe the analysis population or missing-data handling for each secondary outcome.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (1.3%), death (0.6%).

The registry reports serious adverse event counts by group. For MenACWY-CRM, 284 participants were at risk and 0 were reported as affected; for Licensed Comparator, 178 were at risk and 1 was affected; for Naive, 343 were at risk and 0 were affected. For MenACWY-CRM/MenACWY-CRM, 83 were at risk and 0 were affected; for Licensed Comparator /MenACWY-CRM, 77 were at risk and 1 was affected. These are counts of affected participants as recorded, not a basis for calculating a comparative risk from the posted information.

For other adverse events, the registry reports 284 at risk and 0 affected in MenACWY-CRM, 178 and 0 in Licensed Comparator, 343 and 0 in Naive, 83 and 55 in MenACWY-CRM/MenACWY-CRM, and 77 and 49 in Licensed Comparator /MenACWY-CRM. The registry lists Appendicitis (1.3%) and Death (0.6%) among the top serious-event terms. Group-specific death counts are not reported in the registry record.

These counts should be read descriptively. The groups had different vaccination histories and were not randomized, and the registry does not provide enough detail to establish comparability of exposure or follow-up. The counts alone do not show whether events were related to vaccination, and no causal safety conclusion can be drawn from them.

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

The record establishes that the study was designed to follow antibody responses after meningococcal conjugate vaccination, with a primary endpoint based on the percentage of participants reaching an hSBA titer at or above 1:8 against serogroups A, C, W and Y. It also establishes the specified follow-up times and identifies several groups with different vaccination histories, including a naïve group and booster groups.

It does not establish the observed antibody percentages, their confidence intervals, geometric mean titers, or the size of any difference between groups. Those numerical primary endpoint results are not reported in the registry record. The registry records 0 analyses. Accordingly, the listed endpoint should not be mistaken for a reported result, and the planned follow-up schedule should not be taken as evidence of a particular persistence pattern.

Even if numerical group results were available, the non-randomized allocation would limit causal interpretation. The arms are explicitly flagged as not a like-for-like control comparison, and participants entered with different prior vaccination histories. Descriptive differences could reflect those histories or other group differences; the record does not report an adjustment approach that would resolve this concern.

The safety counts similarly describe recorded affected participants, not whether a vaccine caused an event. The record gives selected counts and serious-event terms but does not provide the information needed for a balanced causal comparison. In general, statistical estimates describe the data under the assumptions of the study design and analysis; they do not independently establish causation.

The appropriate reading is therefore narrow: the registry defines a persistence question, records a non-randomized study design, and includes selected safety counts, but it does not report the numerical primary immune-response findings. It cannot support a conclusion about the magnitude or precision of antibody persistence, nor a causal conclusion comparing the vaccine groups.

13. Why This Trial Matters Statistically

This study raises several useful statistical issues for clinical researchers. First, antibody persistence is inherently a longitudinal question: a response is measured at distinct times after vaccination, and interpretation depends on which participants contribute data at each time. The registry specifies 21 months, 3 years and 5 years, but does not report time-specific sample sizes or numerical results. That distinction illustrates why a follow-up schedule is not a substitute for complete outcome reporting.

Second, the study has several groups defined by prior vaccination and booster history. These groups can address different descriptive questions, but they are not automatically exchangeable. The registry identifies the allocation as non-randomized and warns that the arms are not a like-for-like control comparison. This is a reminder that comparison-group structure affects what an estimate can mean, even when the outcome is measured consistently.

Third, the primary endpoint is threshold-based, while secondary outcomes include geometric mean titers. These summaries address complementary aspects of an antibody response: whether titers reach a criterion, and the overall level of titers on a geometric scale. A well-interpreted report needs clear outcome definitions, estimates, uncertainty measures and analysis populations. The registry states a 95% confidence interval for the primary endpoint but does not report the interval results or calculation method.

Finally, the record lists multiple outcomes but no analyses. Without numerical findings, multiplicity methods, missing-data handling and analysis details, readers cannot evaluate statistical precision or robustness. The study is a useful example of why registry descriptions of objectives and endpoints must be distinguished from the reported evidence needed to assess those objectives.

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 direct limitation for interpreting this record is that numerical primary endpoint results are not reported in the registry record. There are no posted percentages or confidence intervals for the hSBA threshold outcome, and no reported GMT results. The registry records 0 analyses. As a result, the central persistence question cannot be answered quantitatively from the record.

The design is non-randomized, and the registry cautions that the arms are not a like-for-like control comparison. Participants had different prior vaccination histories, and some groups received a booster. This structure limits causal comparison and makes it difficult to separate group differences from differences in prior exposure or other characteristics. The registry record does not report statistical adjustment methods that might account for such differences.

The primary population definition is restricted to participants in the per-protocol persistence population who had an evaluable sample at one of the specified visits and no major protocol deviations. The record does not report how many participants met this definition at each visit, how many were excluded, or the reasons for missing measurements. Missing-data procedures and sensitivity analyses are not reported in the registry record.

Other analysis details are also absent: the statistical analysis plan, confidence-interval method, multiplicity approach, and the study’s sample-size justification are not reported in the registry record. The registry lists safety counts, but detailed event definitions, exposure duration, and group-specific death counts are not reported. These limitations restrict assessment of both the immune-response comparisons and the safety summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluation of Persistence of Anti-meningococcal Bactericidal Antibodies Among Adolescents Who Previously Received MenACWY Conjugate Vaccine — NCT00856297.
• Registry record last updated 2017-06-14; status last verified 2017-05.
• Results first posted 2014-01-22.
• 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

This completed, Phase 3, open-label, multicenter study had non-randomized allocation and a parallel model, with enrollment of 389. It evaluated persistence of hSBA responses among adolescents previously vaccinated with MenACWY-CRM or a licensed MenACWY conjugate vaccine, and included age-matched participants without previous meningococcal vaccination. The primary endpoint was the percentage with hSBA titers at or above 1:8 against serogroups A, C, W and Y at 21 months, 3 years and 5 years.

The registry lists 11 outcome measures and records 0 analyses. Numerical primary endpoint results and their confidence intervals are not reported in the registry record. The design is non-randomized, and the registry flags the arms as not a like-for-like control comparison. Safety counts are listed by group, but they do not establish causation or a comparative safety profile.