This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Immunogenicity of Novartis Meningococcal B Vaccine Formulated With OMV Manufactured at Two Different Sites, in Healthy Adolescents Aged 11-17 Years (NCT01423084), a randomized phase 3 study. The primary outcome is Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) Against 3 Neisseria.Meningitidis (N. Meningitidis) Serogroup B Reference Strains..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01423084 |
| Phase | Phase 3 |
| Condition | Meningococcal Disease, Meningococcal Meningitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 344 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis |
| Results posted | Yes |
2. Clinical Question
Population
Healthy adolescents aged 11–17 years. The registry record gives an enrollment of 344 and identifies the primary analysis population as the Per Protocol Set population.
Intervention
Serogroup B meningococcal vaccine, designated MenB Lot 1, administered as two doses one month apart.
Comparator
The same vaccine designated MenB Lot 2, also administered as two doses one month apart. The study compares lots, rather than comparing vaccination with no vaccination.
Primary question
Whether the immune responses following the two lots are equivalent, assessed mainly through hSBA geometric mean titers against three serogroup B reference strains. The record also describes comparison of ELISA geometric mean concentrations for vaccine antigen 287-953.
The trial addresses whether vaccine lots manufactured at two different sites produce sufficiently similar measured immune responses in adolescents. Its stated primary assessment is one month after the second vaccination, identified as day 61. The registry describes comparing the ratio of lot-specific hSBA geometric mean titers for H44/76, 5/99, and NZ98/254. The primary outcome title names the hSBA measures; the accompanying description also includes the ratio of ELISA geometric mean concentrations against antigen 287-953 in the equivalence assessment.
The registry specifies an equivalence interval of (0.5, 2.0). This defines the range used to judge whether the measured lot-to-lot ratios are compatible with the stated equivalence criterion. It does not, by itself, establish that the observed results met that criterion. Numerical primary outcome estimates and confidence intervals are not reported in the registry record, so the clinical question can be described but its answer cannot be determined from the available record.
3. Trial Design
This was a phase 3, randomized, comparative, multicenter study with a parallel-group design. The official title describes the study as observer-blind, while the registry’s masking classification is quadruple. The record does not clarify the relationship between these descriptions or specify which individuals were masked.
The study enrolled healthy adolescents aged 11–17 years and compared two lots of a serogroup B meningococcal vaccine. Each arm description specifies two doses administered one month apart. The registry lists an enrollment of 344; it does not state in the registry record how many participants were randomized, received each dose, or were included in each outcome analysis. Nor does it report the allocation method or the numbers assigned to each lot.
The primary assessment was planned one month after the second vaccination, at day 61. The primary analysis population is identified as the Per Protocol Set population. The study is marked completed, and the registry gives a start of 2011-08 and primary completion of 2011-12. These record dates do not supply further detail about follow-up or the timing of every safety assessment.
The comparison is between vaccine lots, not between the vaccine and a placebo or an untreated group. The record lists secondary immunogenicity outcomes including response percentages, geometric mean ratios, geometric mean titers, and geometric mean concentrations, with some assessments identified at day 45. The number of outcome measures is 13, and the record identifies 4 analyses. It does not report the specific analysis methods or results for those outcomes.
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 subjects were enrolled in the trial.
Overall Study
| Stage | 4CMenB_Rosia | 4CMenB_Siena |
|---|---|---|
| STARTED | 170 | 174 |
| COMPLETED | 168 | 170 |
| NOT COMPLETED | 2 | 4 |
Reasons for not completing this period:
| Reason | 4CMenB_Rosia | 4CMenB_Siena |
|---|---|---|
| Adverse Event | 0 | 1 |
| Withdrawal by Subject | 2 | 3 |
Analysis population for the primary outcome, as defined in the registry: Per Protocol Set population
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: adolescents aged 11-17 years
| Characteristic | Unit | 4CMenB_Rosia | 4CMenB_Siena | Total |
|---|---|---|---|---|
| Participants analysed | 170 | 174 | 344 | |
| Age, Continuous | years | 13.6 (SD 1.9) | 13.8 (SD 1.8) | 13.7 (SD 1.9) |
| Sex: Female, Male: Female | Participants | 72 | 82 | 154 |
| Sex: Female, Male: Male | Participants | 98 | 92 | 190 |
6. Primary Endpoint
The registry lists the primary outcome as Human Serum Bactericidal Activity (hSBA) Geometric Mean Titers (GMTs) Against 3 Neisseria.Meningitidis (N. Meningitidis) Serogroup B Reference Strains., measured over One month after the second vaccination (day 61).
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | Titers |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is human serum bactericidal activity (hSBA) geometric mean titers against three Neisseria meningitidis serogroup B reference strains: H44/76, 5/99, and NZ98/254. The measurement is scheduled one month after the second vaccination, identified as day 61, and the stated analysis population is the Per Protocol Set population.
hSBA is an assay-based measure of serum bactericidal activity. A geometric mean summarizes titers on a multiplicative scale, which is useful when measurements vary across a wide range and are naturally compared as ratios. In this trial, the intended comparison is the ratio of the lot-specific geometric mean titers for each strain. The registry’s equivalence interval is (0.5, 2.0); interpretation would depend on whether the relevant confidence intervals fall within that range, according to the trial’s stated criterion.
The registry’s primary outcome title names hSBA titers. Its description of the equivalence assessment also includes ratios of ELISA geometric mean concentrations for vaccine antigen 287-953. The record therefore identifies both assay-based immune measures in its primary objective description, but does not report their numerical estimates or confidence intervals. The endpoint’s purpose is to assess similarity of measured immune responses between vaccine lots; it is not, on its own, a direct measure of clinical protection.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a planned equivalence comparison, not a test of whether one vaccine lot is superior to the other. For each of the three reference strains, the stated approach compares the lots through a ratio of hSBA geometric mean titers. The description also includes a ratio of ELISA geometric mean concentrations against antigen 287-953. The equivalence interval is (0.5, 2.0), and the primary outcome specifies 95% confidence intervals as the dispersion measure.
To interpret an equivalence result, the estimated lot-to-lot ratio and its confidence interval must be considered together against the prespecified interval. A point estimate within the interval is not enough if the confidence interval extends beyond its limits. Conversely, a confidence interval fully within the interval would support equivalence under the stated criterion for that measure. These are general interpretive principles; the registry record does not report the actual estimates or confidence intervals needed to apply them.
The study is marked completed, but that status is not evidence that the equivalence criterion was met. Numerical primary results are not reported in the registry record. The record also does not state whether the results differed by strain, whether the ELISA assessment met its criterion, or how the four listed analyses relate to the several immune outcomes. The trial’s primary question therefore remains unanswered by the information available in the record.
Several secondary outcomes are listed, including the percentage of participants with hSBA at or above 1:5, geometric mean ratios, and measurements at day 45. Listing an outcome does not establish its result. No numerical values for these secondary outcomes are reported in the registry record, so neither response rates nor differences between lots can be described.
Safety information includes zero serious adverse events among 169 participants at risk in the 4CMenB Rosia group and zero among 173 at risk in the 4CMenB Siena group. This is a summary count, not proof that serious events could not occur or that the lots have identical safety profiles. The registry does not report deaths as a numeric result; the death entries are null. Other adverse events are listed separately, and those counts should not be confused with serious events.
The sample-size illustrations use a stated significance level of 0.05, equal allocation, a normal approximation, and fractions of the observed effect. Such calculations describe hypothetical planning under those assumptions. They are not the trial’s original sample-size justification and are not observed power. Numerical illustration results are not included in the registry record described in the registry record.
9. Statistical Methods Explained
What does a geometric mean represent?
A geometric mean summarizes measurements that are positive and are more naturally compared multiplicatively than additively. This is common for assay titers and concentrations, where values may span a broad range. Conceptually, the geometric mean is obtained by averaging values on a logarithmic scale and then returning to the original scale. It is therefore suited to questions about relative levels, such as whether one lot’s typical measured response is similar to the other lot’s.
In this study, the primary hSBA outcomes are geometric mean titers for three reference strains. The registry describes comparing the two lots through ratios of those geometric means. The description also includes ELISA geometric mean concentrations against antigen 287-953. A ratio near one would indicate similar measured levels in general terms, but a conclusion about equivalence requires the confidence interval and the stated criterion, not merely a point estimate. No numerical estimates are reported in the registry record.
How does an equivalence interval work?
Equivalence testing asks whether the uncertainty around a treatment or group comparison is sufficiently narrow to rule out differences considered too large under a prespecified margin. The registry gives an interval of (0.5, 2.0). Under the stated approach, the relevant ratio and its confidence interval would be assessed relative to both boundaries. If the interval crosses either boundary, the evidence would not satisfy that equivalence criterion, even if the point estimate itself lies within the range. This explanation is general; the actual trial estimates and confidence intervals are not reported in the registry record.
Equivalence is distinct from showing that two groups have exactly the same response. Statistical estimates have uncertainty, and the margins define the degree of difference that the study’s criterion treats as compatible with equivalence. A margin is meaningful only in relation to the scientific rationale and the analysis plan. That rationale and the detailed plan are not reported in the registry record.
What does a confidence interval communicate?
A confidence interval gives a range of values compatible with the observed data under the statistical procedure used. Its width conveys precision: a narrower interval indicates greater precision than a wider interval, all else being equal. It does not mean that there is a specified probability that the fixed true value lies within this particular calculated interval. For an equivalence question, the interval’s location relative to the equivalence boundaries matters as well as its width.
The primary outcome names 95% confidence intervals. The registry does not provide the intervals, standard errors, or enough numerical result information to assess their precision. The confidence interval designation alone does not show whether the estimates were close to one another or whether an equivalence criterion was met.
Why compare three reference strains?
The hSBA endpoint covers three named serogroup B reference strains: H44/76, 5/99, and NZ98/254. Separate strain-specific measurements can describe assay responses across more than one reference strain rather than relying on a single measure. The registry lists each as part of the primary immune-response objective. It does not report strain-specific findings, so no conclusion about consistency across strains can be drawn from the record.
The registry also lists secondary hSBA outcomes based on the percentage of participants reaching an assay threshold of at least 1:5, as well as geometric mean ratios. Threshold-based outcomes and geometric means answer different descriptive questions: the former concerns the proportion meeting a specified level, while the latter summarizes the distribution of measurements on a multiplicative scale. This is a general distinction; the record does not report numerical results for either type of outcome.
What can the sample-size illustrations tell a reader?
The record describes sample-size illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The illustrations consider detecting a stated fraction of that effect. These are planning calculations under assumptions, not observed power and not evidence about the precision achieved in this completed trial. They also should not be mistaken for the original design justification; the trial’s own sample-size justification is not reported in the registry record.
Sample-size planning depends on the target effect, variability, analysis method, allocation, and chosen error rates. Changing an assumption changes the resulting planning requirement. A planning estimate does not establish that a trial was adequately powered for every outcome, especially when multiple outcomes or a specific equivalence criterion are involved. The numerical results of the illustrations are not reported in the registry entries.
How should multiple outcomes be understood?
The record lists 13 outcome measures and identifies 4 analyses. The secondary outcomes include immune-response measures at different assessment times and several forms of summary, including titers, concentrations, ratios, and threshold response percentages. When many outcomes are evaluated, the chance of observing at least one apparently notable result by chance can increase if no adjustment or hierarchy is used. This is a general statistical consideration, not a claim about the trial’s actual analysis. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a complete statistical analysis plan.
The primary outcome’s description includes several strains and an additional ELISA measure in the stated equivalence objective. Because no numerical results or detailed analysis plan are reported, it is not possible to determine how those measures were combined, whether each was tested separately, or how the overall conclusion was defined. A reader should distinguish the registry’s statement of intended comparisons from evidence that those comparisons met their criteria.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 13 outcome measures and identifies 4 analyses. The primary immune-response assessment involves hSBA geometric mean titers for three reference strains, and its description also includes ELISA geometric mean concentrations for antigen 287-953. Secondary outcomes include geometric mean ratios, threshold response percentages, and assessments identified at day 45. This collection of outcomes creates multiple opportunities for statistical comparisons.
Multiplicity matters because repeated testing can increase the chance of at least one result appearing statistically notable by chance. Common approaches include prespecifying a hierarchy, adjusting significance thresholds, or treating outcomes as descriptive. These are general methods, not claims about the study. Whether any such approach was used is not reported in the registry record. The detailed analysis plan, including the handling of multiple strains and endpoints, is also not reported.
The primary population is identified as the Per Protocol Set population. The registry entries do not describe the criteria for membership in that set, the number analyzed, or whether other analysis populations were used. They also do not report how missing outcome measurements, withdrawals, protocol deviations, or incomplete vaccination courses were handled. Without these details, the effect of missing data or analysis-population choices on the results cannot be assessed.
The record gives enrollment but does not report participant flow by arm or outcome. It is therefore not possible to compare the enrolled, randomized, treated, and analyzed populations or to assess whether exclusions were balanced. These omissions limit interpretation independently of the missing numerical endpoint results.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 4CMenB_Rosia | 0 | 169 | 0.0% |
| 4CMenB_Siena | 0 | 173 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 4CMenB_Rosia | 165 of 169 |
| 4CMenB_Siena | 171 of 173 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 4CMenB_Rosia | 4CMenB_Siena |
|---|---|---|---|
| injection site pain | General disorders | 162 of 169 | 170 of 173 |
| injection site erythema | General disorders | 111 of 169 | 111 of 173 |
| myalgia | Musculoskeletal and connective tissue disorders | 99 of 169 | 118 of 173 |
| Headache | Nervous system disorders | 75 of 169 | 89 of 173 |
| Fatigue | General disorders | 75 of 169 | 85 of 173 |
| injection site swelling | Investigations | 80 of 169 | 74 of 173 |
| injection site induration | General disorders | 65 of 169 | 75 of 173 |
| nausea | Gastrointestinal disorders | 49 of 169 | 56 of 173 |
| arthralgia | Musculoskeletal and connective tissue disorders | 28 of 169 | 45 of 173 |
| rash | Skin and subcutaneous tissue disorders | 11 of 169 | 16 of 173 |
The registry lists zero serious adverse events among 169 participants at risk in the 4CMenB Rosia group and zero among 173 participants at risk in the 4CMenB Siena group. These are the serious-event counts recorded for the groups. They should be read as observed counts in the stated at-risk groups, not as proof that serious events were impossible or that the lots have identical safety profiles.
The record does not give a numeric death count: the death entries are null. A null entry should not be interpreted as a recorded count of zero. The record also does not report the safety observation period, event definitions beyond the serious-event category, or details about severity, relatedness, or adjudication. These omissions restrict interpretation of the serious-event summary.
Other adverse events are listed separately: 165 affected among 169 at risk in 4CMenB Rosia, and 171 affected among 173 at risk in 4CMenB Siena. Those are not serious-adverse-event counts and should not be treated as such. The registry lists no top serious-event terms. Because the record does not provide detailed event narratives or comparative statistical analyses, these counts alone do not establish whether safety differed between groups.
12. What the Result Does, and Does Not, Mean
The study was designed to compare immune responses after two vaccine lots in healthy adolescents. Its stated equivalence interval and choice of geometric mean measures describe a framework for assessing whether responses were sufficiently similar under the study’s criterion. The completed status and randomized design describe the trial, but neither tells whether the primary objective was achieved.
The registry record does not report numerical primary outcome estimates or confidence intervals for hSBA titers against H44/76, 5/99, or NZ98/254. It also does not report numerical ELISA results for antigen 287-953. Consequently, the available information does not establish whether the lot-to-lot comparisons met the stated equivalence interval. It also does not establish that the responses were different. Both conclusions require the missing outcome estimates and their uncertainty.
Even if equivalence were demonstrated for the specified immune measurements, that finding would concern those endpoints, population, and assessment timing. It would not by itself establish clinical effectiveness or answer questions beyond the outcomes measured. Conversely, the absence of numerical results in the registry record is not evidence that the study failed to find equivalence.
The safety summary records no serious adverse events in either listed group, while deaths are not numerically reported. This is limited information about recorded events in the groups, not a comprehensive characterization of safety. Other adverse events are listed separately, and the registry does not provide sufficient detail to assess their nature or clinical importance.
The most defensible reading is therefore that the registry documents a randomized lot-comparison study and its intended immune-response framework, but does not report the numerical evidence needed to resolve the main statistical question. The record’s outcome labels and planned criteria should not be substituted for observed results.
13. Why This Trial Matters Statistically
Comparisons between manufacturing lots can be framed as equivalence questions rather than conventional superiority questions. That distinction matters statistically: failure to find a difference is not, by itself, evidence that two lots are sufficiently similar. An equivalence claim depends on a prespecified margin and estimates precise enough for the confidence interval to remain within that margin. This study’s registry description gives an interval of (0.5, 2.0), making the intended framework explicit.
The design also illustrates the use of several related immune measures. hSBA geometric mean titers are specified for three reference strains, while the equivalence objective description includes ELISA geometric mean concentrations for a vaccine antigen. Considering multiple assay measures can provide a broader description of measured immune response, but it also makes the analysis plan and handling of multiple comparisons important. Those details are not reported in the registry record.
The study is identified as randomized, parallel-group, phase 3, and multicenter, with two vaccine lots administered on the same two-dose schedule. These features clarify the planned comparison, while the Per Protocol Set identifies the stated primary population. The record does not give participant flow or the exact analysis methods, so readers cannot assess how these design features translated into the reported analysis.
The registry’s missing numerical outcome results are especially important for an equivalence study. Without the estimates and confidence intervals, neither similarity nor meaningful difference can be established from the record. This makes the distinction between a stated objective and an observed result central to interpreting the trial.
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 principal limitation for statistical interpretation is that the registry record does not report numerical primary outcome results. No hSBA geometric mean titers, lot-to-lot ratios, or confidence intervals are given for the three reference strains. Numerical ELISA geometric mean concentrations and their ratios are also not reported. As a result, the stated equivalence interval cannot be applied to the observed data.
The record does not provide detailed participant flow, arm-specific enrollment or analysis counts, or the number included in the Per Protocol Set. Although enrollment is listed, the relationship between that figure and the analyzed populations is not described. Criteria for the Per Protocol Set and handling of missing measurements, withdrawals, or protocol deviations are not reported.
The statistical analysis plan is not reported in sufficient detail to establish how multiple strains, assays, time points, and secondary outcomes were handled. The record identifies 13 outcome measures and 4 analyses, but does not describe any hierarchy or multiplicity adjustment. The rationale for the equivalence interval and the study’s own sample-size justification are also not reported.
The masking descriptions differ in level of detail: the official title calls the study observer-blind, while the registry classification is quadruple. The record does not clarify who was masked or how masking was implemented. The safety summary lacks a stated observation period and detailed event definitions, and death entries are null rather than numeric. These limitations prevent a complete assessment of safety and of the precision and robustness of the immune-response comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Immunogenicity of Novartis Meningococcal B Vaccine Formulated With OMV Manufactured at Two Different Sites, in Healthy Adolescents Aged 11-17 Years — NCT01423084.
- Registry record last updated 2015-02-20; status last verified 2015-02.
- Results first posted 2015-02-20.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a completed, randomized, parallel-group phase 3 comparison of two serogroup B meningococcal vaccine lots in healthy adolescents aged 11–17 years. The official title describes a multicenter observer-blind study; the masking classification is quadruple. Both groups were scheduled to receive two doses one month apart.
The primary immune-response assessment was planned one month after the second vaccination, at day 61, in the Per Protocol Set population. It focuses on hSBA geometric mean titers against three reference strains and describes an equivalence interval of (0.5, 2.0); the objective description also includes ELISA concentrations against antigen 287-953.
Numerical primary outcome results and confidence intervals are not reported in the registry record, so whether the equivalence criterion was met cannot be determined. Serious adverse-event counts are zero in both listed groups; death entries are null. The record does not report the detailed analysis plan, participant flow, or handling of missing data.