Study of a Quadrivalent Meningococcal Conjugate Vaccine in Subjects Aged 56 and Older: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of a Quadrivalent Meningococcal Conjugate Vaccine in Subjects Aged 56 and Older (NCT01732627), a randomized phase 2 study. The primary outcome is Percentage of Participants With Antibody Titers ≥1:4 and ≥1:8 Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W 135 Before Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine.

2. Clinical Question

The study’s stated objectives were to describe antibody responses measured using serum bactericidal assays with human complement and baby rabbit complement, and to describe safety after a single dose of either vaccine. Those objectives frame a descriptive comparison of immune measurements and safety, rather than a question about clinical cases of meningitis or invasive meningococcal disease.

A central interpretive distinction is the timing of the listed primary endpoint. Its timeframe is Day 0, before vaccination. A baseline measurement can characterize participants’ antibody titers at study entry, but cannot measure an antibody response induced by the dose that is given afterward. The registry record does not report comparative post-vaccination antibody results or a treatment-effect estimate for them. Thus, the recorded primary endpoint and the broader stated objective of describing induced responses should not be treated as interchangeable.

3. Trial Design

This was a Phase 2, randomized, open-label, parallel-group study. Participants were assigned to receive one of two meningococcal vaccines: MenACYW conjugate vaccine or Menomune. The registry record lists 301 participants enrolled and a completed study. The study started on 2012-11-12, with primary completion on 2013-01-17.

Both groups consisted of adults aged 56 years and older, and both received a single dose on Day 0. The intervention was a conjugate vaccine containing meningococcal polysaccharides from serogroups A, C, Y, and W 135 linked to tetanus protein. The comparator was the combined meningococcal polysaccharide vaccine covering the same four serogroups. The registry record describes the groups and intervention but does not report the randomization sequence or allocation procedure.

Randomization is a design feature intended, in general, to make baseline differences less systematically related to assigned treatment. It does not ensure that the groups will be identical, particularly in a study of this size, and it does not replace examination of the outcome data. Parallel-group design means participants were assigned to one group rather than receiving both study vaccines in sequence. Masking was listed as none, so the study was open label; the registry record does not describe additional steps to limit the influence of knowledge of treatment assignment on outcome assessment.

The primary outcome is described as a percentage with specified baseline antibody titers measured by hSBA. The registry record also states that the study objectives included hSBA and rSBA antibody responses and safety. It does not report a complete statistical analysis plan, a sample-size justification for the trial, or details of interim analyses. The sample-size illustrations associated with the posted results are planning calculations based on an observed effect, not the documented basis for the study’s enrollment and not observed power.

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: A total of 301 participants were enrolled and vaccinated in the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on Per-Protocol Analysis Set (PPAS) population which included participants who received at least one dose of the study vaccine, had any valid serology result, and no 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: Analysis was performed on all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Antibody Titers ≥1:4 and ≥1:8 Measured by Serum Bactericidal Assay Using Human Complement (hSBA) Against Meningococcal Serogroups A, C, Y, and W 135 Before Vaccination With MenACYW Conjugate Vaccine or Menomune® Vaccine, measured over Day 0 (pre-vaccination).

The listed primary endpoint is the percentage of participants with hSBA antibody titers of at least 1:4 and 1:8 against meningococcal serogroups A, C, Y, and W 135 before vaccination. hSBA is a serum bactericidal assay using human complement. In general, an assay-based titer is a laboratory measurement of antibody activity under specified test conditions; it is not itself a count of meningitis cases or other clinical infections.

Reporting percentages at antibody thresholds describes how many participants meet each specified laboratory cutoff. Multiple thresholds and serogroups allow the baseline antibody profile to be characterized from more than one angle. Such measurements can be useful in immunogenicity research because they quantify an immune response using a defined laboratory assay. The registry record’s primary endpoint timeframe is Day 0, however, so these measurements describe antibody status before the study dose. They do not establish the amount of change after vaccination.

The endpoint specifies a per-protocol analysis set: participants who received at least one dose, had any valid serology result, and had no protocol deviations. This definition identifies the population intended for the endpoint as described in the registry. The record does not report the baseline percentages or confidence intervals, nor does it provide a post-vaccination estimate under this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins by matching the analysis to the endpoint. Here, the primary endpoint is a percentage of participants crossing specified antibody-titer thresholds, measured before vaccination. A percentage is a summary of a binary classification: each participant either meets a stated threshold or does not. General explanation: for such outcomes, the observed percentage depends on both the number meeting the criterion and the number assessed. The registry record gives the outcome definition, but does not post the counts or percentages for this primary endpoint.

What does a confidence interval communicate?

The endpoint lists a 95% confidence interval as its dispersion measure. General explanation: a confidence interval expresses uncertainty around an estimate under the statistical procedure used to construct it. A narrower interval indicates greater precision under that procedure; a wider interval indicates less precision. It is not a range containing a known proportion of individual participants’ values, and it does not by itself establish whether a difference is clinically important. No endpoint confidence intervals are reported in the registry record, so their width and implications cannot be assessed.

Why does the analysis population matter?

The primary endpoint is assigned to the Per-Protocol Analysis Set. The record defines this set as participants who received at least one dose, had any valid serology result, and had no protocol deviations. In general, restricting an analysis to a per-protocol population can make the estimate describe participants meeting those conditions rather than everyone randomized. The number of participants in this endpoint population, the reasons for any exclusions, and the impact of exclusions are not reported in the registry record. The record also does not specify whether another population was used for a sensitivity analysis.

What can randomization and open-label status tell the reader?

General explanation: random assignment is used to reduce systematic differences between treatment groups at the start of a study. It does not guarantee balance on every characteristic. This study is listed as randomized and parallel, with no masking. Open-label status means treatment assignment was not masked; for laboratory outcomes, the potential consequences depend on how samples were handled, assays were run, and results were assessed. Those procedures are not reported in the registry record. The method used to generate and implement the random assignment is also not reported in the registry record.

How should multiple measurements be considered?

The study objectives name four serogroups and two assay methods, while the primary outcome title names two titer cutoffs and four serogroups. These are multiple related measurements, not one isolated comparison. General explanation: when many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity adjustment or a hierarchy for interpreting these measurements. It also does not provide enough posted analysis results to evaluate the pattern across assays, serogroups, or thresholds.

What do the planning calculations mean?

The record describes sample-size illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says the target effect is a stated fraction of the observed effect, and that non-time-to-event illustrations are expressed as participants per arm. These are planning illustrations, not evidence that the study was designed with those assumptions. They are not observed power. The trial’s own sample-size justification and the assumptions used to set enrollment are not reported in the registry record. No planning result should be read as a clinical outcome or as a substitute for the estimate and its uncertainty.

In general, over-dispersion occurs when observed variability is greater than a statistical model assumes. Accounting for it can affect standard errors and confidence intervals. The registry record does not identify an over-dispersion model or provide enough statistical detail to determine whether it was relevant to the primary endpoint. More broadly, the primary endpoint analysis method beyond its stated population and confidence-interval measure is not reported in the registry record. That limits reproducibility and makes it inappropriate to infer an unreported model or testing procedure.

10. Multiplicity, Missing Data and Analysis Populations

The study’s measurements span multiple serogroups, antibody cutoffs, and assay types. The primary outcome title specifies hSBA titers of at least 1:4 and 1:8 for serogroups A, C, Y, and W 135; the objectives also name rSBA. Considering several related outcomes can be scientifically useful, but it creates a multiplicity question: how should evidence across the set be interpreted, and was any adjustment or ordering specified? The registry record does not report a multiplicity strategy or identify a single post-vaccination comparison for interpretation. The posted results do not contain analysis records.

Missing-data handling is also important for a laboratory endpoint. The per-protocol population requires a valid serology result and no protocol deviations, but the record does not report how many participants lacked a valid result, why results might be missing, or how missing measurements were handled. It does not report whether participants excluded from the per-protocol set were included in another analysis population. Consequently, the possible influence of exclusions or unavailable measurements cannot be assessed.

The endpoint is measured at Day 0, before vaccination. The registry record does not report a corresponding post-vaccination comparative estimate in the posted outcome analyses. It also does not report interim analyses, a prespecified statistical analysis plan, or the trial’s sample-size justification. These omissions do not show that such plans or procedures did not exist; they mean their details are not reported in the registry record. Without them, the analysis choices, multiplicity control, and sensitivity of conclusions to missing data cannot be independently evaluated from the 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 non-serious adverse event terms

The safety record lists 199 participants at risk in the MenACYW conjugate vaccine group and 100 in the Menomune group. It records 0 serious adverse events in the first group and 0 in the second, and 0 deaths in each group. It also records other adverse events in 114 participants in the MenACYW group and 54 in the Menomune group.

These counts should be read as registry-reported event summaries. The record does not provide the specific terms for serious adverse events, and the list of top serious terms is empty. The description of other adverse events does not give event types, severity, timing, duration, or attribution. It also does not state in the posted summary whether the counts refer to participants with at least one event or to event episodes; therefore, that detail should not be inferred.

Zero recorded serious events or deaths in a study does not establish that the underlying risk is zero. General explanation: observed counts are limited by the number of participants, follow-up, and event ascertainment. The record does not report enough detail about follow-up or safety definitions to judge those aspects. These figures are descriptive and do not, on their own, establish a causal difference between vaccines.

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

The registry record describes a randomized, open-label Phase 2 comparison of one dose of MenACYW conjugate vaccine with one dose of Menomune in adults aged 56 years and older. Its stated aims concerned antibody responses to four meningococcal serogroups and safety. The listed primary endpoint, however, is the percentage meeting hSBA thresholds before vaccination. That endpoint characterizes baseline antibody status, not the response induced by the study dose.

The posted record does not report numerical primary endpoint results, post-vaccination antibody comparisons, confidence intervals, or analysis records. As a result, it cannot support a quantitative conclusion about relative antibody responses from the registry results available. The safety summary reports zero serious adverse events and zero deaths in each group, alongside other adverse-event counts. Those observations describe the recorded counts; they do not establish that there is no risk, nor do they determine whether reported events were caused by a vaccine.

General explanation: laboratory antibody measurements and clinical outcomes answer different questions. An assay can measure antibody activity under laboratory conditions, while clinical outcomes concern events such as illness. A laboratory endpoint may be relevant to immunogenicity research, but its interpretation depends on the assay, threshold, timing, and evidence linking the measurement to clinical outcomes. The registry record does not report clinical disease comparisons in this study.

Accordingly, the study’s design and stated aims are informative about what investigators set out to describe, while the posted results are insufficient to establish comparative post-vaccination immunogenicity or clinical effectiveness. The record also does not provide the analysis detail needed to evaluate multiplicity, missing measurements, or the precision of endpoint estimates. These limits concern what can be concluded from the registry record, not whether unreported analyses or information existed elsewhere.

13. Why This Trial Matters Statistically

This trial illustrates why the endpoint’s timing must be read alongside its name. The broader study objectives concern antibody responses induced by vaccination, but the listed primary measure is explicitly at Day 0, before vaccination. A baseline percentage and a post-dose response are different quantities. Keeping that distinction clear prevents a pre-vaccination measurement from being interpreted as a vaccine effect.

It also illustrates the difference between a study objective and a posted result. The registry describes intended measurements using hSBA and rSBA and names safety as an objective. But the posted results do not include analysis records or numerical comparative antibody estimates. The presence of a detailed endpoint definition does not itself provide the endpoint’s result, its precision, or evidence of a between-group difference.

Several outcomes are relevant to the stated aims: four serogroups, specified antibody thresholds, two assay methods, and safety. General statistical practice requires attention to how multiple outcomes are analyzed and interpreted. The record does not report a multiplicity plan, so the reader cannot determine how the investigators intended to distinguish primary from secondary evidence across those measures.

Finally, the registry’s safety counts show why descriptive event summaries need context. Counts can be reported without enough information about event definitions, follow-up, or attribution to support causal interpretation. The study therefore serves as a useful example of reading design features, endpoint timing, analysis-population definitions, and result availability together. Statistical conclusions depend not only on a trial’s stated purpose, but also on the measurements actually reported and the uncertainty and analysis details attached to them.

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 registry record does not report numerical results for the listed primary endpoint. It gives no baseline percentages or confidence intervals and lists no analysis records. The stated objectives include antibody responses induced by vaccination, but comparative post-vaccination antibody results are not reported in the registry record. This prevents assessment of the magnitude or precision of an immunogenicity comparison from these posted results.

The endpoint’s timing is a specific concern: the primary measure is at Day 0, before vaccination. It therefore does not directly measure a response after the assigned dose. The record does not explain the relationship between this baseline endpoint and any post-vaccination analyses beyond the general study objectives.

The analysis population is defined as per protocol, but its size and the numbers excluded are not reported in the registry record. Reasons for missing or invalid serology, handling of missing data, and any analyses in alternative populations are also not reported in the registry record. The statistical analysis method, multiplicity strategy, randomization procedure, and sample-size justification are not reported in the registry record.

The safety summary is limited to counts. Event terms, severity, timing, duration, attribution, and additional follow-up details are not reported in the registry record. Masking is listed as none, but the record does not describe procedures for blinded laboratory measurement or outcome assessment. These limitations restrict interpretation of the posted information; they do not establish that unreported procedures or analyses were absent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of a Quadrivalent Meningococcal Conjugate Vaccine in Subjects Aged 56 and Older — NCT01732627.
• Registry record last updated 2022-04-04; status last verified 2022-03.
• Results first posted 2020-06-09.
• 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

NCT01732627 is a completed randomized, open-label, parallel-group Phase 2 study with 301 participants enrolled. Adults aged 56 years and older received a single dose of either MenACYW conjugate vaccine or Menomune. The study started on 2012-11-12, and primary completion was on 2013-01-17.

The stated objectives were to describe antibody responses to meningococcal serogroups A, C, Y, and W 135 using hSBA and rSBA, and to describe safety. The listed primary endpoint measures baseline hSBA titers before vaccination. The registry record does not report numerical primary outcome results or comparative post-vaccination antibody analyses.

The safety summary reports 0 serious adverse events and 0 deaths in each group, with other adverse events recorded among participants in both groups. The record does not report a multiplicity plan, missing-data methods, sample-size justification, or detailed statistical analysis plan.