Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Meningococcal Vaccine With or Without Co-administration of Cervarix and Boostrix in Female Adolescents and Young Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Meningococcal Vaccine With or Without Co-administration of Cervarix and Boostrix in Female Adolescents and Young Adults (NCT01755689), a randomized phase 3 study. The primary outcome is Anti-Meningitis Antibody Titers by Serum Bactericidal Assay Using Rabbit Complement (rSBA).

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, parallel-group study with no masking listed in the registry. Its stated purpose was to evaluate safety and immunogenicity when the meningococcal vaccine was administered with Cervarix, with or without Boostrix, and to compare the listed combinations with vaccine regimens administered alone or together. The registry reports an enrollment of 1300 and a completed study status.

Five arm descriptions are recorded. One group received Nimenrix at Month 0 and Cervarix at Month 1, Month 2 and Month 7. A second received Nimenrix at Month 0 and Cervarix at Month 0, Month 1 and Month 6. A Cervarix-only group received doses at Month 0, Month 1 and Month 6. Another group received Nimenrix and Boostrix at Month 0, with Cervarix at Month 0, Month 1 and Month 6. The remaining group received Boostrix at Month 0 and Cervarix at Month 0, Month 1 and Month 6. The descriptions state that the vaccines were administered intramuscularly in the deltoid region.

The study start is listed as 2013-01-11, and primary completion as 2014-04-29. Although the record gives the overall enrollment, it does not report the number analyzed in each arm for the primary outcome in the registry record for this account. The registry record also does not report the allocation sequence method, concealment procedures, detailed visit schedule beyond the arm descriptions, or reasons for choosing the study size. These omissions limit what can be said about implementation and the precision planned before enrollment.

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:

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 from the ATP cohort for safety for whom assay results were available for antibodies against at least one study vaccine antigen component for the blood sample taken one month after vaccination with Nimenrix.

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 Anti-Meningitis Antibody Titers by Serum Bactericidal Assay Using Rabbit Complement (rSBA), measured over At one month after vaccination with Nimenrix (Month 1).

The primary outcome was anti-meningococcal antibody titer measured by serum bactericidal assay using rabbit complement, abbreviated rSBA. Results were to be summarized as geometric mean titers for serogroups MenA, MenC, MenW-135 and MenY. The stated assessment time was one month after vaccination with Nimenrix, and the primary analysis was limited to groups receiving Nimenrix.

A titer is an assay-based measure of antibody activity at a dilution level. A geometric mean is commonly used for antibody titers because such measurements tend to be skewed rather than distributed symmetrically on their original scale. In general, taking the geometric mean involves working on a logarithmic scale and then expressing the result on the original scale. This summary describes the central level of measured antibody titers; it is not itself a direct measure of clinical illness or individual protection.

The registry specifies a 95% confidence interval as the measure of dispersion for the GMTs. In general, a confidence interval conveys uncertainty around an estimated group-level quantity under the analysis assumptions. It does not show the range of individual participants’ titers. The numerical GMTs and confidence intervals for the primary outcome are not reported in the registry record, so the magnitude and precision of the observed antibody measurements cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes antibody outcomes as geometric mean titers and concentrations, with the primary outcome summarized using a 95% confidence interval. It does not report the full statistical analysis plan, the exact tests used for comparisons, or detailed procedures for handling every analysis issue. The explanations below describe the general statistical ideas behind the stated measures; they should not be read as a claim that a particular unreported method was used.

Why use a geometric mean for antibody titers?

Antibody measurements are often positive and may vary over a wide range. On the original scale, a few high values can make the distribution strongly skewed. A geometric mean is a standard way to summarize such measurements: values are transformed to a logarithmic scale, averaged there, and converted back. In general, this produces a summary that reflects multiplicative variation and is less dominated by extreme high values than an arithmetic mean could be.

The geometric mean remains a group-level summary. It does not describe every participant’s response, and a difference between group geometric means does not reveal how much individual measurements overlap. The registry identifies GMT as the primary parameter but does not report the numerical GMT estimates in the record described for this account.

What does a 95% confidence interval express?

In general, a confidence interval gives a range of estimates compatible with the observed data and the statistical procedure used, under its assumptions. It communicates sampling uncertainty around an estimate. A narrower interval indicates greater precision than a wider interval, but precision alone does not establish clinical importance. A confidence interval is not a range expected to contain a fixed proportion of individual participants’ measurements.

The primary outcome specifies 95% confidence intervals around GMTs. The registry record does not include their endpoints for the primary outcome, nor does it report a confidence interval for a clearly defined single contrast between arms. Therefore, the interval’s width and the precision of any comparison cannot be evaluated from the outcome description.

What role does the assay play?

The primary measurement used serum bactericidal assay with rabbit complement. This is an assay-based measure of bactericidal antibody activity against meningococcal serogroups. The registry lists results for MenA, MenC, MenW-135 and MenY. Assay results depend on the specified laboratory method and the samples available for analysis; the recorded method identifies the assay type, but further assay validation and laboratory details are not reported in the registry record.

Secondary outcomes also include antibody concentrations, threshold counts, seroconversion and booster responses for other antigens. These are different summaries of immune measurements. A threshold outcome counts participants meeting a stated measurement criterion; a concentration summary describes measured levels; seroconversion is a classification based on antibody measurements. Their definitions do not substitute for the missing numerical results.

What is the analysis population?

The primary analysis population is described as the According-to-Protocol cohort for immunogenicity. It included evaluable participants from the According-to-Protocol safety cohort for whom assay results were available for antibodies against at least one study-vaccine antigen component for the blood sample taken one month after vaccination. This description signals that the primary analysis was not simply every randomized participant: eligibility depended on protocol evaluability and available assay data.

In general, an according-to-protocol analysis can be useful for describing responses among participants meeting specified study requirements, but it may not preserve all the advantages of randomization if exclusions differ across groups. A full interpretation would need the number excluded, reasons for exclusion, group-specific analyzed counts and a comparison with an analysis of all randomized participants. Those details are not reported in the registry record details used.

What can be said about planning calculations?

The posted sample-size material is described as a planning illustration based on an observed effect, not as the trial’s original design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect specified as a fraction of the observed effect. Such calculations are hypothetical planning exercises: they show how a future study’s size could vary under stated assumptions. They are not observed power and do not establish that this trial was designed around those assumptions.

The registry record does not report a sample-size justification, the statistical plan used before enrollment, interim analyses, or a complete account of the analysis methods. The primary outcome also spans several serogroups and time or category dimensions and is not reduced to one comparison. Thus, the design information available does not support a single confirmatory test or an assessment of the trial’s planned error control.

10. Multiplicity, Missing Data and Analysis Populations

The study lists a broad set of immunogenicity outcomes: antibody titers and vaccine responses for four meningococcal serogroups; anti-T concentrations and threshold outcomes; anti-HPV-16 and anti-HPV-18 concentrations and seroconversion; and booster responses for anti-PT, anti-FHA and anti-PRN antibodies. The registry records 21 outcome measures and 17 analyses. Considering multiple outcomes, serogroups, thresholds, groups and assessment times raises a general multiplicity issue: the more results assessed, the greater the opportunity for chance findings if each is interpreted independently.

The registry record does not report a multiplicity adjustment, a hierarchy of outcomes, or which comparisons were intended to be confirmatory. It also does not report interim analyses or stopping rules. Without this information, the intended control of false-positive findings across the outcome set cannot be assessed. The absence of a reported adjustment does not establish that none was used; the relevant approach is not reported in the registry record.

For the primary outcome, the analysis population is the According-to-Protocol cohort for immunogenicity: evaluable participants from the safety cohort with available assay results for at least one vaccine antigen component at the one-month sample. The registry record does not give the detailed handling of missing assay values, protocol deviations, incomplete schedules, or missing follow-up. It does not report whether imputation was used, whether missingness was examined by group, or how sensitivity analyses were conducted.

These details matter because analysis-population exclusions and unavailable measurements can affect both the number of observations contributing to each estimate and the comparability of groups. The registry record also does not report a separate intention-to-treat analysis or the population definitions for every secondary analysis. As a result, the robustness of immunogenicity findings to alternative population and missing-data choices cannot be evaluated from the available 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: appendicitis (0.8%), dengue fever (0.8%), pharyngitis (0.4%), dermatitis atopic (0.4%), atrial septal defect (0.4%).

The registry reports serious adverse events and other adverse events separately for each listed group, with the number at risk and the number affected. Serious adverse events affected 3 participants in the Nimenrix+Cervarix (1,2,7-Month) Group, 2 in the Nimenrix+Cervarix (0,1,6-Month) Group, 5 in the Cervarix Group, 7 in the Nimenrix+Cervarix+Boostrix Group, and 6 in the Boostrix+Cervarix Group. The corresponding numbers at risk were 259, 259, 261, 260 and 261.

For other adverse events, the affected counts were 232, 228, 222, 236 and 243, respectively; the numbers at risk were 259, 259, 261, 260 and 261. The registry records 0 deaths in the first four groups and 1 in the Boostrix+Cervarix Group. These are descriptive counts. No statistical comparison or causal attribution is reported with them.

The registry also lists serious-event terms with percentages: Appendicitis and Dengue fever, 0.8% each; Pharyngitis, Dermatitis atopic, Atrial septal defect and Gastroenteritis, 0.4% each. These terms are not assigned to a particular group in the record details used. Counts and percentages do not indicate whether events were judged related to vaccination, and the record does not report that relationship. Comparisons should account for denominators, follow-up and event context; those details are not fully reported in the registry record.

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

The trial’s design addresses a practical statistical question: how measured immune responses and recorded safety events vary across regimens involving the meningococcal vaccine, Cervarix and Boostrix. Randomization can support fair comparisons when analyses preserve the randomized groups and follow the planned approach. The registry reports random allocation and a parallel design, but the primary immunogenicity population is an according-to-protocol cohort rather than all randomized participants.

The primary outcome is an assay-based immune measurement, not a count of meningococcal infections. GMTs and their confidence intervals would describe antibody titers and uncertainty in group estimates. They do not, by themselves, establish a clinical effect or individual-level protection. The numerical primary results and confidence intervals are not reported in the registry record, so the record cannot show the magnitude or precision of those measurements.

The secondary outcomes broaden the assessment to other antibody measures and vaccine responses. Their presence does not demonstrate that any particular threshold was met or that groups differed. Numerical secondary results are not reported in the registry record details used for this account. Likewise, the safety counts describe recorded events but do not establish whether a vaccine caused them or whether an apparent difference is more than chance variation.

Statistical interpretation would require outcome estimates, uncertainty intervals or appropriate comparison results, plus details of the analysis populations and handling of missing measurements. For a study with several outcomes and serogroups, interpretation also depends on which comparisons were planned and how multiplicity was addressed. Those results and analysis details are not reported in the registry record.

Accordingly, the record supports an account of the study question, randomized design, scheduled regimens, outcome definitions and reported safety counts. It does not support a conclusion about the direction or size of antibody differences, statistical significance, equivalence, non-inferiority, or clinical benefit. The absence of numerical results in the record is an information limitation, not evidence that an outcome was positive or negative.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of a multi-arm immunogenicity design. Its groups varied in whether the meningococcal vaccine was given with Cervarix, whether Boostrix was included, and when Cervarix doses were scheduled. Such designs can address more than one practical comparison, but they also make the analysis question important: each contrast, outcome, serogroup and time point needs a clear role in interpretation.

The primary outcome uses GMTs, a familiar summary for antibody titers, and confidence intervals to express estimate uncertainty. It also specifies an assay and a one-month assessment after Nimenrix vaccination. These features define what is being measured and when, helping distinguish an immune-response outcome from a clinical infection outcome. The record’s explicit analysis-population definition further shows that the primary analysis depended on evaluability and assay availability.

The design also illustrates why numerical results and analysis details matter alongside outcome definitions. Without the GMT estimates, intervals and planned comparisons, readers cannot judge the size or precision of the immunogenicity findings. Without multiplicity and missing-data information, they cannot determine how a broad outcome set was handled or how sensitive results might be to exclusions and unavailable measurements. Safety counts are useful descriptive information, but they are not substitutes for comparative estimates or event-attribution details.

The registry record therefore offers a clear outline of a complex randomized study while leaving key inferential elements unreported. That distinction is important when interpreting trial records: a detailed question and design do not alone establish what the observed data show.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important limitation for statistical interpretation is that numerical results for the primary GMT outcome are not reported in the registry record details used. There are no group-specific GMTs or confidence intervals to assess, and the primary outcome is not reduced to one comparison. Numerical results for the listed secondary immunogenicity outcomes are likewise not reported in the record.

The primary analysis used an according-to-protocol immunogenicity cohort, defined by evaluability and assay availability. The registry record does not provide group-specific analysis counts, exclusions and reasons, or a comparison with all randomized participants. It also does not report the detailed missing-data approach, sensitivity analyses, or whether any imputation was used. These omissions prevent evaluation of how participant exclusions or unavailable samples could affect estimates.

The record does not report a full statistical analysis plan, multiplicity procedures, interim analyses, or the original sample-size justification. The study’s several arms and broad outcome set make those details relevant to understanding which comparisons were intended to carry confirmatory weight. The planning illustration described in the record is based on an observed effect and is not the trial’s original design justification.

Safety reporting is also limited for causal interpretation. Event counts and at-risk denominators are listed, but comparative statistical analyses and event relatedness are not reported in the registry entries used. Serious-event terms and percentages are listed without group attribution. The available safety information therefore supports descriptive reporting, not conclusions about causation or comparative risk.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Meningococcal Vaccine With or Without Co-administration of Cervarix and Boostrix in Female Adolescents and Young Adults — NCT01755689.
• Registry record last updated 2018-07-03; status last verified 2017-11.
• Results first posted 2018-07-03.
• 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

The registry describes a completed, randomized, unmasked, parallel Phase 3 study of meningococcal vaccine regimens with Cervarix, with or without Boostrix, in female adolescents and young adults aged 9-25 years. Enrollment was 1300. The listed schedules included two Nimenrix-plus-Cervarix timing regimens, Cervarix alone, Nimenrix with Cervarix and Boostrix, and Boostrix with Cervarix.

The primary outcome was rSBA geometric mean titers for MenA, MenC, MenW-135 and MenY one month after Nimenrix vaccination, analyzed in the According-to-Protocol cohort for immunogenicity. Numerical primary and secondary immunogenicity results are not reported in the registry record details used. Safety counts include serious adverse events, other adverse events and deaths by group. The record does not report the full statistical plan, multiplicity handling, or detailed missing-data methods.