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, Tolerability and Immunogenicity of Three Doses of Novartis Meningococcal B Vaccine When Administered to Healthy At-risk Adults (NCT00560313), a randomized phase 2 study. The primary outcome is Geometric Mean Titer of the Meningococcal B Vaccine Against the Different Strains at One Month After First, Second and Third Vaccination..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00560313 |
| Phase | Phase 2 |
| Condition | Meningococcal Disease |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 54 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Vaccines |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled healthy at-risk adults 18-50 years of age. The registry reports enrollment of 54. The primary endpoint analysis was described as using the per-protocol population; further eligibility details and the number included in that analysis are not reported in the registry record.
Intervention
The intervention of interest was Novartis 4CMenB, administered on a 0, 2, 6-month schedule. The endpoint focused on antibody titers against three meningococcal strains, measured one month after each vaccination.
Comparator
The study also included a single dose of Men ACWY-CRM. The registry identifies a randomized crossover design, but does not report the sequence or timing of the crossover, or how the vaccine periods were arranged for individual participants.
Primary question
The primary endpoint asks what geometric mean titers against the different meningococcal B strains were observed one month after the first, second and third 4CMenB vaccinations. The registry describes confidence intervals for these estimates, but the numerical titer results and confidence intervals are not reported in the registry record.
In practical statistical terms, the question is descriptive: how were antibody titers distributed on a geometric scale after successive vaccinations? It is not presented in the registry as a single comparison between randomized groups. The record identifies several strains and post-vaccination time points, so the primary outcome involves multiple estimates rather than one summary contrast. No numerical results are available to assess the magnitude or precision of those estimates.
3. Trial Design
This was a phase 2, multicenter, randomized, open-label crossover study sponsored by Novartis Vaccines. It enrolled healthy at-risk adults 18-50 years of age, with registry enrollment recorded as 54. The study status is completed. The registry lists a start in 2007-07 and primary completion in 2009-11.
The planned 4CMenB schedule was at 0, 2 and 6 months. Men ACWY-CRM was administered as a single dose. The primary endpoint was assessed one month after vaccinations. Although the registry identifies a crossover model, it does not describe the sequence of treatments, the transition between periods, or whether any washout interval was used. The allocation is recorded as randomized, but the randomization procedure and allocation ratio are not reported in the registry record.
Masking is recorded as none, so the study was open-label. The registry lists five outcome measures, but does not provide a numerical primary-endpoint result or report statistical analyses. It identifies the per-protocol population for the primary endpoint; the criteria for that population and the number of participants included are not reported in the registry record.
The posted design information identifies the vaccines, schedule, population and broad design features, but does not provide enough detail to reconstruct the treatment sequence or the analysis plan. In particular, the registry record does not report the protocol’s rationale for enrollment, the handling of repeated measurements within participants, or the methods used to account for the crossover structure.
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: Approximately 250 adults were planned to be enrolled in this study but only a total of 54 subjects were enrolled after the screening for the inclusion and exclusion criteria.
Overall Study
| Stage | 4CMenB |
|---|---|
| STARTED | 54 |
| COMPLETED | 48 |
| NOT COMPLETED | 6 |
Reasons for not completing this period:
| Reason | 4CMenB |
|---|---|
| Adverse Events or Death | 2 |
| Withdrawal by Subject | 2 |
| Lost to Follow-up | 1 |
| Protocol Violation | 1 |
Analysis population for the primary outcome, as defined in the registry: The analysis was done on the per protocol 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.
| Characteristic | Unit | 4CMenB |
|---|---|---|
| Participants analysed | 54 | |
| Age, Continuous | years | 31.8 (SD 6.1) |
| Sex: Female, Male: Female | Participants | 27 |
| Sex: Female, Male: Male | Participants | 27 |
6. Primary Endpoint
The registry lists the primary outcome as Geometric Mean Titer of the Meningococcal B Vaccine Against the Different Strains at One Month After First, Second and Third Vaccination., measured over One month after vaccinations.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | titer |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the geometric mean titer (GMT) of meningococcal B vaccine antibodies against three different strains, measured one month after the first, second and third vaccinations. A titer is a measure of antibody activity in a laboratory assay. The registry states that the GMT and its 95% confidence interval were measured after each vaccination. Numerical GMT estimates and confidence intervals are not reported in the registry record.
Geometric means are commonly used for antibody titers because titers can vary over a broad range and their distribution is often better represented on a logarithmic scale than by an arithmetic average. In general, the GMT is calculated by averaging log-transformed titers and converting that average back to the original scale. This makes the summary less dominated by unusually high values than an arithmetic mean may be. The registry does not report the calculation details or any data transformations used in this study.
A confidence interval describes uncertainty around an estimate under the assumptions of the statistical method. A narrower interval indicates greater precision, while a wider interval indicates less precision. The 95% confidence intervals named in the endpoint description would help readers judge precision for each strain and vaccination time point, but their values are not reported. Without the estimates and intervals, the primary endpoint cannot be quantitatively interpreted from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a repeated, descriptive antibody-titer endpoint: geometric mean titers against three strains after each of three 4CMenB vaccinations, with measurement one month after vaccination. It also specifies that confidence intervals were intended to accompany the estimates. However, no numerical primary endpoint results are reported in the registry record. There is therefore no posted estimate from which to describe the observed titers, compare time points, or assess the precision of the endpoint measurements.
The design is randomized and crossover, but the primary endpoint is not reduced in the record to a single between-treatment comparison. The registry explicitly describes several strains and time points. Consequently, a single effect estimate or one significance test cannot represent all of the listed endpoint information. The sequence of treatment periods, the correspondence between the crossover design and the primary endpoint, and the statistical handling of within-person measurements are not reported in the registry record.
Safety counts are posted separately by vaccination group. The registry lists zero participants affected by serious adverse events in each group, alongside the numbers at risk for those entries. These counts describe what was recorded in the listed groups; they do not provide a comparison adjusted for the crossover design or establish the frequency of events beyond the participants and observations recorded. The registry does not report serious adverse-event terms, and death entries are not reported in the registry record.
The posted record also gives counts for “other” adverse events. Those entries should not be conflated with the serious adverse-event counts. The categories and denominators are recorded by vaccination group, and the groups include different numbers at risk. Because this is a crossover study, group entries need not represent separate sets of people. The registry does not explain the relationship between repeated vaccination periods and these adverse-event counts.
These gaps limit the statistical conclusions that can be drawn. The record supports describing the planned endpoint, design and posted safety counts, but not a numerical assessment of antibody response, a treatment contrast, statistical significance, or precision for the primary endpoint. No statistical analysis results are reported in the registry record. A completed status indicates that the study is recorded as completed, not that its primary results are available in this record.
9. Statistical Methods Explained
What does a geometric mean titer represent?
Antibody titers are measurements of activity in a laboratory assay. A geometric mean summarizes a set of titers after taking their logarithms, averaging on that transformed scale, and converting the result back to the original scale. In general, this approach is useful when measurements are positive and spread across a wide range, because multiplicative differences are often more meaningful than equal additive differences. It also reduces the influence that very high observations can have on an arithmetic mean.
The endpoint description specifies GMTs against three strains, measured one month after first, second and third vaccinations. Those are separate strain-by-time summaries, not a single overall result. The registry does not report the actual GMT values, the assay details, how values below assay limits were handled, or the exact computation used. Those details matter when reproducing or comparing antibody summaries.
How should the confidence intervals be read?
A confidence interval represents uncertainty around an estimated quantity under a statistical model. In general, a 95% confidence interval is constructed by a method designed to cover the underlying quantity in 95% of repeated samples when the model assumptions hold. It is not a statement that a particular interval has a 95% probability of containing the fixed underlying value. Its width conveys precision: narrower intervals indicate more precise estimates, and wider intervals indicate less precise estimates.
The registry says 95% confidence intervals were to be reported with the GMTs. It does not post their limits. Therefore, readers cannot judge the precision of the titers or determine whether estimates for different strains or vaccination times are compatible with a range of values. No inferential comparison or p-value for these endpoint measurements is reported in the registry record.
What does the crossover design imply?
In general, a crossover design exposes participants to more than one intervention in different periods, so measurements can be related within the same participant. This can make within-person comparisons informative, but statistical analysis must account for the repeated observations and the order in which interventions occur. Period effects, sequence effects and carryover can also matter, depending on the intervention and design. These are general considerations, not a description of methods confirmed for this study.
The registry labels the study randomized and crossover, but does not give the treatment sequences, period structure, washout details, or the statistical model used to handle repeated observations. It is therefore not possible to determine from the record how the crossover design informed the primary GMT summaries or any comparison. The per-protocol designation is reported, but eligibility rules for that population and the handling of participants with incomplete measurements are not described.
What can be inferred from the planning assumptions?
The record includes assumptions for a planning illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is described as planning rather than as the trial’s own design calculation. Its sample-size values, if presented elsewhere, should be understood as hypothetical planning quantities, not as observed power or as a report of how this study was originally sized. The record does not report the trial’s sample-size justification.
The assumptions also state that the effect to detect is a stated fraction of the observed effect. This kind of illustration explores how a hypothetical future design might be sized under specified assumptions. It does not establish that the observed effect is unbiased, clinically important, or reproducible. The registry does not report an analysis result from which to assess such an effect for this endpoint.
Why does over-dispersion matter in general?
Over-dispersion occurs when observed variability exceeds what a statistical model assumes. In general, ignoring it can make standard errors too small and confidence intervals too narrow, giving an overly confident impression of precision. It is a consideration in count or rate models and other settings where the data show more variability than a basic model allows. The registry does not report an over-dispersion assessment or identify a model for the primary endpoint, so this is general statistical context rather than a claim about the study’s analysis.
Overall, the statistical methods that can be identified from the record are limited to the planned GMT summaries, 95% confidence intervals, per-protocol analysis population, and the stated assumptions for a separate planning illustration. Detailed methods for the primary analysis, missing observations, multiplicity, and crossover structure are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint spans three meningococcal strains and measurements after the first, second and third 4CMenB vaccinations. This creates multiple estimates and potential comparisons. In general, making many statistical comparisons can increase the chance of at least one false-positive finding if each is evaluated without adjustment. Researchers may address this through prespecified hierarchies, adjusted significance thresholds, or by treating analyses as descriptive. The registry record does not report a multiplicity strategy, identify a hierarchy among strains or time points, or provide the statistical analyses needed to see how multiplicity was handled.
Missing-data handling is also not reported in the registry record. The primary endpoint is described for the per-protocol population, but the criteria for inclusion, reasons for exclusion, and handling of missing titers are not given. The record does not state whether incomplete measurements were omitted, imputed, or handled using another approach. Those choices can affect both the population represented and the precision of estimated GMTs.
The registry identifies the per-protocol population, but does not report whether other analysis populations were used or how they were defined. The relationship between that population and the randomized crossover design is not described. The statistical analysis plan, interim analyses and sample-size justification are not reported in the registry record. Without those details, it is not possible to assess whether the endpoint analysis followed a prespecified plan or how deviations and incomplete data were treated.
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 (1st Vaccination) | 0 | 53 | 0.0% |
| 4CMenB (2nd Vaccination) | 0 | 52 | 0.0% |
| 4CMenB (3rd Vaccination) | 0 | 50 | 0.0% |
| Men ACWY-CRM | 0 | 41 | 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 (1st Vaccination) | 52 of 53 |
| 4CMenB (2nd Vaccination) | 51 of 52 |
| 4CMenB (3rd Vaccination) | 50 of 50 |
| Men ACWY-CRM | 19 of 41 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 4CMenB (1st Vaccination) | 4CMenB (2nd Vaccination) | 4CMenB (3rd Vaccination) | Men ACWY-CRM |
|---|---|---|---|---|---|
| Injection site pain | General disorders | 52 of 53 | 50 of 52 | 50 of 50 | 10 of 41 |
| Injection site erythema | General disorders | 22 of 53 | 23 of 52 | 28 of 50 | 9 of 41 |
| Injection site induration | General disorders | 23 of 53 | 24 of 52 | 29 of 50 | 5 of 41 |
| Malaise | General disorders | 16 of 53 | 17 of 52 | 26 of 50 | 11 of 41 |
| Myalgia | Musculoskeletal and connective tissue disorders | 15 of 53 | 19 of 52 | 24 of 50 | 5 of 41 |
| Headache | Nervous system disorders | 16 of 53 | 13 of 52 | 21 of 50 | 9 of 41 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 10 of 53 | 12 of 52 | 20 of 50 | 6 of 41 |
| Nausea | Gastrointestinal disorders | 7 of 53 | 5 of 52 | 9 of 50 | 4 of 41 |
| Nasopharyngitis | Infections and infestations | 0 of 53 | 3 of 52 | 3 of 50 | 1 of 41 |
| Pyrexia | General disorders | 3 of 53 | 1 of 52 | 0 of 50 | 2 of 41 |
The registry lists serious adverse-event counts separately for 4CMenB at the first, second and third vaccination, and for Men ACWY-CRM. In each listed group, zero participants are recorded as affected by serious adverse events. The corresponding numbers at risk are 53, 52, 50 and 41, respectively. These are group-specific entries; in a crossover study, they should not be read as counts of separate, non-overlapping sets of people.
Zero recorded serious adverse events in these entries means that the registry reports none among the participants at risk for those group entries. It does not establish that an event could not occur, nor does it determine risk outside the study observations. No serious adverse-event terms are listed. The death fields are not reported in the registry record, so they should not be interpreted as zero deaths.
The registry separately lists “other” adverse events, with affected counts of 52, 51, 50 and 19 in the respective groups. These are a different category from the serious adverse-event counts and do not replace them. The record does not provide further detail in the listed information about event types, severity within this category, or how repeated periods were handled in summarizing safety.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase 2, randomized, open-label crossover study was conducted in healthy at-risk adults 18-50 years of age. It describes a 4CMenB schedule at 0, 2 and 6 months, a single dose of Men ACWY-CRM, and a primary endpoint based on GMTs against three meningococcal strains one month after vaccination. It also records group-level adverse-event counts and identifies the primary analysis population as per protocol.
Those details describe what the study was designed to examine; they do not provide the numerical primary endpoint results. Since the GMT estimates and their 95% confidence intervals are not reported in the registry record, the size and precision of the antibody measurements cannot be assessed from this record. It also does not report a single primary comparison, an inferential test, or a numerical treatment effect.
The safety entries show zero serious adverse events recorded in each listed group, while the “other” adverse-event counts are reported separately. The registry does not list serious-event terms, and death information is not reported in the registry record. These entries should be read as descriptions of the posted observations rather than as proof of absence of risk or as a comparison of safety between treatments.
Accordingly, the posted information supports an account of the study design, its planned endpoint and selected safety counts. It does not establish a quantitative antibody response, the comparative effect of the vaccines, statistical significance, or the clinical importance of any result. Those judgments require results and analysis details that are not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates why an endpoint definition is not the same as an endpoint result. The record specifies GMTs, strains, post-vaccination timing and confidence intervals, enough to identify the intended statistical summaries. Without the numerical estimates and intervals, however, readers cannot evaluate either the observed titers or their precision. A clear outcome definition alone cannot support conclusions about the size of an effect.
The crossover label also highlights the importance of analysis details. In general, crossover data may include repeated observations from the same participant, so treatment periods and within-person correlation can matter. The registry does not explain how these features were handled. Without the sequence and analysis method, a reader cannot reconstruct a treatment contrast or determine how the design was reflected in uncertainty estimates.
The endpoint includes several strains and post-vaccination time points, making multiplicity relevant to interpretation. The record does not state how these multiple estimates were prioritized or whether any formal comparisons were adjusted. This matters because a collection of results should not automatically be treated as a single confirmatory test.
Finally, the safety record distinguishes serious adverse events from “other” adverse events and lists denominators by vaccination group. That distinction is important for reading counts accurately, particularly in a crossover study where group entries may relate to different periods for the same participants. The registry’s missing primary results and limited analytic detail show how record completeness affects the conclusions that can responsibly be drawn from posted trial information.
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 is that numerical results for the primary endpoint are not reported in the registry record. Although GMTs and 95% confidence intervals are specified, their values are absent. No primary statistical analyses are reported, so the magnitude, precision and statistical interpretation of the antibody measurements cannot be evaluated.
Important details about the crossover design are also missing. The registry does not report treatment sequences, period timing, washout procedures, or the statistical approach to repeated measurements. The allocation procedure and ratio are not described. These omissions prevent reconstruction of how randomization and crossover affected the intended comparisons.
The record identifies the per-protocol population but does not state its criteria, the number analyzed, or how incomplete measurements and exclusions were handled. The protocol, statistical analysis plan, multiplicity approach, interim analyses and sample-size justification are not reported in the registry record. Consequently, it is not possible to assess prespecification or evaluate the effect of missing data and analysis choices.
Safety information is limited to group-level counts. Serious-event terms are not listed, death fields are not reported in the registry record, and details of event timing or repeated-period handling are absent. The “other” adverse-event category is not described further in the posted information. These limitations constrain interpretation of both the primary endpoint and the safety entries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability and Immunogenicity of Three Doses of Novartis Meningococcal B Vaccine When Administered to Healthy At-risk Adults — NCT00560313.
- Registry record last updated 2016-04-01; status last verified 2016-03.
- Results first posted 2011-07-08.
- 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.
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18. Record Summary
The registry records a completed phase 2, multicenter, randomized, open-label crossover study sponsored by Novartis Vaccines. It enrolled 54 healthy at-risk adults 18-50 years of age. The study examined 4CMenB on a 0, 2, 6-month schedule and a single dose of Men ACWY-CRM.
The primary endpoint was the geometric mean titer against three meningococcal B strains, measured one month after vaccinations, with 95% confidence intervals and a per-protocol analysis population specified. Numerical endpoint results and statistical analyses are not reported in the registry record. Serious adverse-event counts are recorded as zero affected in each listed vaccination group; death information is not reported in the registry record.