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 Immunogenicity and Safety of Meningococcal ACWY Conjugate Vaccine in Healthy Subjects From 2 to 18 Years in Taiwan (NCT01410474), a non-randomized phase 3 study. The primary outcome is Percentage of Overall Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01410474 |
| Phase | Phase 3 |
| Condition | Bacterial Meningitis |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 341 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis |
| Results posted | Yes |
2. Clinical Question
Population
Healthy subjects aged 2 to 18 years in Taiwan. The registry record reports enrollment of 341 participants. The primary outcome was analyzed in a modified intention-to-treat population, defined by exposure to vaccination and availability of evaluable serum assay results for at least one serogroup on day 1 and/or day 29.
Intervention
A single injection of Novartis meningococcal ACWY conjugate vaccine, MenACWY-CRM. The study evaluated immunogenicity and safety after vaccination.
Comparator
There was no randomized control group. The registry classifies the study as non-randomized and single-group, with no masking. The planned outcome description compares postvaccination antibody responses with prevaccination titers, not with outcomes in a separate control arm.
Primary question
What percentage of overall subjects had an hSBA seroresponse directed against meningococcal serogroups A, C, W and Y after vaccination? The endpoint description specifies evaluation on day 29, with day 1 and day 29 listed as the timeframe. The registry record does not report the observed percentages or confidence intervals.
The question concerns immune response measured by a serum bactericidal assay using human complement (hSBA). For participants with a prevaccination titer below 1:4, seroresponse was defined as a postvaccination titer of at least 1:8. For participants whose prevaccination titer was at least 1:4, it required an increase of at least four times the prevaccination titer. These definitions establish the endpoint rule; they do not give the number of participants meeting it.
The registry also describes secondary immunogenicity outcomes, including seroresponse by age group, geometric mean titers, geometric mean ratios, and the percentage with an hSBA titer of at least 1:8. Safety outcomes include solicited local and systemic events in age groups. Although these outcomes indicate the scope of the study, their results are not reported in the registry record. The central question is therefore clear, but the posted registry information does not establish the magnitude or precision of the observed immune response.
3. Trial Design
NCT01410474 is registered as a phase 3, multicenter, open-label study of MenACWY-CRM in healthy subjects from 2 to 18 years in Taiwan. It is classified as non-randomized, unmasked and single-group. The registry reports enrollment of 341 and a completed status. The study started in 2011-08, and primary completion was recorded as 2012-01.
All participants were assigned within a single-group design to the meningococcal ACWY conjugate vaccine intervention. The brief description specifies a single injection. There is no randomized comparison group, so the design does not provide a like-for-like control arm for separating changes associated with vaccination from changes that might occur over time or from other influences. The primary outcome instead describes seroresponse relative to participants’ own prevaccination titers.
The primary endpoint was the percentage of overall subjects with an hSBA seroresponse against serogroups A, C, W and Y. The endpoint description identifies day 29 as the postvaccination assessment, 28 days after one vaccination, and lists day 1 and day 29 as the timeframe. The primary analysis population is described as modified intention-to-treat: exposed participants with evaluable serum assay results available for at least one serogroup on day 1 and/or day 29.
The registry lists safety groups of 2-10 Years, 11-18 Years, and Overall (2 to 18 Years). The age-group descriptions attached to some secondary outcomes refer instead to 2 to 5 years and 6 to 18 years. These are the registry’s stated labels; the record does not explain the distinction. Safety denominators are reported separately from the enrollment count. Detailed procedures for allocation, follow-up, or other aspects of the protocol are not reported in the registry record. Neither a control group nor a masking procedure is reported.
The record describes a prospective assessment of immune-response and safety outcomes after vaccination, but does not post numerical results for the primary endpoint. It also reports no analyses in the statistical analysis listing. The study’s design and intended measurements can therefore be described, but its outcome estimates cannot be reconstructed from the registry information.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: All enrolled subjects were included in the trial.
Overall Study
| Stage | 2-10 Years | 11-18 Years |
|---|---|---|
| STARTED | 173 | 168 |
| COMPLETED | 173 | 167 |
| NOT COMPLETED | 0 | 1 |
Reasons for not completing this period:
| Reason | 2-10 Years | 11-18 Years |
|---|---|---|
| Withdrawal by Subject | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Analysis was done on modified intention-to-treat (MITT) population i.e subjects in the exposed population who provided evaluable serum samples whose assay results were available for at least one serogroup on day 1 and/or day 29.
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 done on all the enrolled subjects.
| Characteristic | Unit | 2-10 Years | 11-18 Years | Total |
|---|---|---|---|---|
| Participants analysed | 173 | 168 | 341 | |
| Age, Continuous | Years | 6.3 (SD 2.6) | 14.0 (SD 2.2) | 10.1 (SD 4.5) |
| Sex: Female, Male: Female | Participants | 92 | 88 | 180 |
| Sex: Female, Male: Male | Participants | 81 | 80 | 161 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Overall Subjects With Seroresponse, Directed Against Neisseria Meningitidis Serogroups A, C, W and Y After MenACWY-CRM Vaccination, measured over Day 1 and Day 29.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentages of Subjects |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the percentage of overall subjects with an hSBA seroresponse to meningococcal serogroups A, C, W and Y after MenACWY-CRM vaccination. The assay uses human complement. The registry defines seroresponse using both the prevaccination titer and the postvaccination titer: a participant with a prevaccination hSBA titer below 1:4 had to reach at least 1:8 after vaccination, while a participant whose prevaccination titer was at least 1:4 had to show an increase of at least four times the baseline titer.
This threshold-based endpoint converts assay measurements into a proportion of participants meeting a prespecified response definition. In general, a proportion can be easier to interpret as a count-based summary of how many participants met a criterion than a list of individual titers. The registry also specifies an associated 95% Clopper-Pearson confidence interval. In general, a confidence interval expresses uncertainty around an estimated proportion; its width depends on the amount of information available and the observed response pattern.
The timeframe lists day 1 and day 29, and the description states that the assessment was made 28 days after one vaccination, on day 29. The endpoint’s definition and analysis population are reported, but the observed percentage, confidence interval, and serogroup-specific primary values are not reported in the registry record. Therefore, the endpoint’s intended meaning is identifiable, but the size and precision of the recorded response cannot be described from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question and design, but does not provide the numerical primary outcome results. It names the primary outcome as the percentage of overall subjects with seroresponse to serogroups A, C, W and Y and specifies a 95% Clopper-Pearson confidence interval. It does not report the observed percentage, the confidence interval limits, or the number of participants meeting the response definition. No conclusion about the magnitude or precision of the primary immune-response estimate can be drawn from this record alone.
The study has a single group and is not randomized or masked. Thus, its primary endpoint is a within-participant comparison of postvaccination response with prevaccination titer, rather than a comparison of randomized groups. General statistical interpretation: a before-and-after response measure can describe changes relative to baseline, but without a separate control group it cannot by itself distinguish the effect of the intervention from other possible influences on the measured outcome. This is a design limitation, not a statement about the observed response.
The registry lists several secondary immunogenicity outcomes: seroresponse by age group, geometric mean titers, geometric mean ratios, and the percentage with hSBA titer at least 1:8 for the four serogroups. It also lists solicited local and systemic adverse events by age group. The record does not post numerical results for these outcomes. The presence of an outcome in the registration is not evidence of its result, and no direction or size of an effect should be inferred from the outcome title.
For safety, the registry reports serious adverse events in the safety groups as one among 173 in the 2-10 Years group, zero among 167 in the 11-18 Years group, and one among 340 overall. It lists pneumonia at 0.6% among the top serious terms. Separately, other adverse events are reported for 110 among 173, 98 among 167, and 208 among 340, respectively. These entries are counts, not assessments of causation. The registry does not provide event-level context or the full details needed to determine how individual events were classified or related to vaccination.
The record reports enrollment of 341, while the overall safety denominator is 340. The primary analysis population has its own eligibility definition based on exposure and evaluable assay results, but its size is not reported. These population counts should not be treated as interchangeable. The registry also reports zero analyses in its analysis listing, so it does not supply an inferential analysis beyond the planned endpoint description. Overall, the record supports a description of the study’s design, definitions and selected safety counts, but not a quantitative interpretation of the primary immunogenicity findings.
9. Statistical Methods Explained
The registry’s statistical information consists mainly of endpoint definitions and the confidence-interval method named for the primary outcome. It does not provide a full statistical analysis plan or numerical results. The concepts below explain what the named methods and measures generally mean; they do not fill in any unreported trial procedures or findings.
What does a percentage with a confidence interval represent?
The primary outcome is a percentage: the share of the analysis population meeting the seroresponse definition. In general, an estimated proportion summarizes a binary outcome, in which each participant either meets the criterion or does not. A confidence interval communicates uncertainty around that estimate. It is not a range of individual participant responses, nor does it indicate that the true value is known with certainty to lie within its limits.
The registry specifies a 95% Clopper-Pearson confidence interval. In general, the Clopper-Pearson method is an exact binomial interval for a proportion. The interval is calculated from the number meeting the outcome and the number assessed. Its width reflects sampling uncertainty, with the available sample information and observed proportion both relevant. The registry record names this method but does not report the resulting interval or the number of participants contributing to the primary estimate.
How is seroresponse defined?
The response criterion depends on prevaccination hSBA titer. A baseline titer below 1:4 requires a postvaccination titer of at least 1:8. A baseline titer of at least 1:4 requires a postvaccination increase of at least four times the baseline titer. This rule recognizes that participants can begin at different titers and defines response in relation to that starting point. The registered primary endpoint applies the definition to serogroups A, C, W and Y.
The endpoint is measured using an hSBA assay with human complement. The registry names the measurement and timing, but does not report assay validation details, laboratory procedures, or how results were handled when an assay measurement was unavailable. Such details are not reported in the registry record and should not be assumed.
What do geometric mean titers and ratios describe?
Geometric mean titers (GMTs) are listed among the secondary outcomes. In general, a geometric mean summarizes measurements that are positive and often have a skewed distribution by averaging on a logarithmic scale and expressing the result back on the original scale. A geometric mean ratio (GMR) generally expresses a ratio between geometric means, often to describe a change or contrast between measurements. These summaries can describe antibody levels differently from the binary seroresponse percentage: the percentage focuses on meeting a defined threshold, while a geometric mean summarizes the distribution of titer values.
The registry lists GMT and GMR outcomes for serogroups A, C, W and Y, but does not report their values, confidence intervals, transformation details, or exact comparison definitions. The statistical interpretation of these outcomes therefore cannot go beyond their general purpose and registered labels.
Why can over-dispersion matter?
General explanation: over-dispersion occurs when the variability in observed data is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors can be too small and confidence intervals can be too narrow. The registry record does not report a count model, an over-dispersion assessment, or any related adjustment for this study. This concept is not identified as part of the primary binary seroresponse method; it is relevant only when a chosen model for other data requires assumptions about variability.
What can the study design support?
The study is single-group, non-randomized and open-label. Its primary measure summarizes response after vaccination against a baseline-based criterion. General explanation: a randomized comparator can help separate treatment-group differences from other influences, while a single-group design does not offer that same concurrent contrast. The registered design can describe measured responses and safety observations in the enrolled population, but the registry information does not support a randomized between-group treatment-effect estimate.
The registry describes a sample-size illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the illustrated effect is a stated fraction of the observed effect. Those assumptions describe a planning illustration, not the trial’s own design or observed power. The actual study is registered as a single-group, non-randomized study, and the registry does not report a sample-size justification or protocol power calculation. No planning illustration should be interpreted as evidence that the study had a particular probability of detecting an effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary immunogenicity endpoint and several secondary outcomes covering seroresponse, geometric mean titers, geometric mean ratios, hSBA titer thresholds, and solicited adverse events. Multiple outcomes can create a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase. General statistical approaches may control that risk by specifying a testing hierarchy or adjusting significance thresholds, but the registry record does not report whether any such strategy was used. It also does not report a statistical analysis plan or inferential results for the listed secondary outcomes.
The endpoint description specifies a 95% Clopper-Pearson confidence interval for the primary seroresponse measure. It does not state how confidence intervals or tests across the four serogroups were handled, or whether any multiplicity adjustment was planned. The registry does not report analyses in its analysis listing. It is therefore not possible to determine whether results were adjusted across outcomes or to assess the statistical significance of any result.
The modified intention-to-treat population is defined as exposed participants with evaluable serum samples whose assay results were available for at least one serogroup on day 1 and/or day 29. This definition identifies eligibility for the primary analysis, but the number included and the handling of missing results are not reported. The record does not describe imputation, exclusions beyond the stated population definition, or sensitivity analyses for missing data. The safety denominators are reported separately, and the primary analysis denominator should not be inferred from them.
In general, missing outcome data can affect both the estimated proportion and its uncertainty, particularly if the availability of measurements is related to participants’ response or follow-up. Without the number and pattern of missing assay results, the direction or extent of any such effect cannot be assessed. The registry’s available information defines the intended analysis population but leaves the actual analysis population size and missing-data procedures unreported.
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 |
|---|---|---|---|
| 2-10 Years | 1 | 173 | 0.6% |
| 11-18 Years | 0 | 167 | 0.0% |
| Overall (2 to 18 Years) | 1 | 340 | 0.3% |
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 |
|---|---|
| 2-10 Years | 110 of 173 |
| 11-18 Years | 98 of 167 |
| Overall (2 to 18 Years) | 208 of 340 |
Most frequent serious adverse event terms
| Event term | Organ system | 2-10 Years | 11-18 Years | Overall (2 to 18 Years) |
|---|---|---|---|---|
| Pneumonia | Infections and infestations | 1 of 173 | 0 of 167 | 1 of 340 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 2-10 Years | 11-18 Years | Overall (2 to 18 Years) |
|---|---|---|---|---|
| Injection site pain | General disorders | 64 of 173 | 62 of 167 | 126 of 340 |
| Injection site erythema | General disorders | 58 of 173 | 43 of 167 | 101 of 340 |
| Injection site induration | General disorders | 49 of 173 | 36 of 167 | 85 of 340 |
| Myalgia | Musculoskeletal and connective tissue disorders | 20 of 173 | 49 of 167 | 69 of 340 |
| Malaise | General disorders | 13 of 173 | 35 of 167 | 48 of 340 |
| Headache | Nervous system disorders | 13 of 173 | 29 of 167 | 42 of 340 |
| Upper respiratory tract infection | Infections and infestations | 16 of 173 | 6 of 167 | 22 of 340 |
| Nausea | Gastrointestinal disorders | 10 of 173 | 10 of 167 | 20 of 340 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 3 of 173 | 13 of 167 | 16 of 340 |
| Rash | Skin and subcutaneous tissue disorders | 11 of 173 | 4 of 167 | 15 of 340 |
Serious events with the highest arm-level rate: pneumonia (0.6%).
The registry reports serious adverse event counts for three safety groups: one among 173 participants aged 2-10 Years, zero among 167 aged 11-18 Years, and one among 340 overall. These are the posted counts and denominators; they are not estimates of whether the vaccine caused an event. The record also lists pneumonia at 0.6% among the top serious terms. It does not provide enough detail in this entry to link that term to a particular group or to describe individual event circumstances.
Other adverse events are reported separately: 110 among 173 in the 2-10 Years group, 98 among 167 in the 11-18 Years group, and 208 among 340 overall. These counts should not be conflated with serious adverse events. The registry also names solicited local and systemic events as secondary outcomes, but does not report their detailed results in the record.
The safety denominators differ from the enrollment count, and the overall safety group contains 340 participants while enrollment is 341. The registry does not explain this difference. Deaths are not reported in the registry record. These safety entries describe recorded counts, not comparative risks, and the single-group open-label design has no randomized control group for a direct safety comparison.
12. What the Result Does, and Does Not, Mean
The registry record identifies a study of MenACWY-CRM in healthy subjects aged 2 to 18 years in Taiwan, with a primary endpoint based on hSBA seroresponse. It reports the response definition, the assay, the assessment timing, and the intended modified intention-to-treat population. It also reports selected safety counts. These details make clear what the investigators intended to measure and how the primary response criterion was defined.
The record does not report the observed primary seroresponse percentage, its 95% confidence interval, or the number of participants meeting the response definition. It also does not post numerical results for the listed secondary immunogenicity outcomes. As a result, the magnitude and precision of the immune response cannot be assessed from the registry record. A registered endpoint is a plan for measurement, not a result.
The safety entries show the recorded serious and other adverse event counts for the stated groups. They do not establish whether events were caused by vaccination, and the record does not provide event-level descriptions or a randomized comparator. The listed pneumonia term at 0.6% is reported among the top serious terms, but the registry information does not establish its relation to the group counts or provide enough context to interpret it further.
The design is non-randomized, unmasked and single-group. General interpretation: without a separate randomized comparison group, observed changes from baseline cannot by themselves establish how outcomes would have differed in the absence of vaccination. This does not negate the descriptive role of the study; it defines the scope of conclusions its design can support.
The registry record also does not provide a sample-size justification, detailed statistical analysis plan, multiplicity strategy, or missing-data procedures. The sample-size assumptions described for a planning illustration are not evidence of the trial’s own design calculation or observed power. The posted information therefore supports a careful account of design, endpoint definitions and recorded safety counts, but not a conclusion about the size of an immune response or a causal treatment effect.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how an immunogenicity endpoint can be defined in a single-group vaccine study. Its primary outcome is not simply an antibody titer: it classifies response using both the prevaccination level and a specified postvaccination criterion. The registry also names an exact confidence-interval method for the response proportion. Those choices matter because the definition and uncertainty measure determine what a reported percentage would mean.
The design makes the distinction between descriptive evidence and comparative evidence especially important. The study is classified as non-randomized, open-label and single-group. Its primary question concerns the proportion meeting a response definition after vaccination, not a contrast with an unvaccinated or alternative-treatment group. Statistical interpretation must respect that structure rather than reading a within-participant response as a randomized treatment effect.
The record also illustrates why registration details and posted results are not interchangeable. It contains extensive outcome descriptions, including multiple immune measures and safety outcomes, but does not report the numerical primary results or analyses. A reader can identify the planned estimand and the population definition, yet cannot evaluate the observed response or its precision without the result values.
Finally, the safety counts demonstrate why denominators and outcome categories need to be read carefully. Enrollment, the primary modified intention-to-treat population, and the safety populations are distinct concepts. The registry reports separate safety denominators and does not report the primary analysis population size. Preserving those distinctions avoids implying that every registered count represents the same set of participants or the same outcome. The statistical value of the record is in clarifying these design and interpretation boundaries.
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 trial-specific limitation for interpreting results from the registry is that numerical primary endpoint findings are not reported. The primary outcome has a defined response rule and a named confidence-interval method, but the observed percentage, confidence interval and contributing sample size are absent. Secondary immunogenicity results are also not reported. This prevents assessment of response magnitude and precision.
The non-randomized, single-group design has no concurrent control arm. The primary endpoint compares postvaccination titers with prevaccination criteria, but that design does not provide a randomized between-group comparison. The study is also open-label, and the registry does not describe masking. The extent to which these design features could affect outcome measurement is not reported.
The registry’s population counts are not interchangeable: enrollment is 341, the overall safety denominator is 340, and the size of the modified intention-to-treat population is not reported. The record does not explain the difference between enrollment and the overall safety denominator. It also does not detail missing assay data, exclusions, or sensitivity analyses. Consequently, the completeness of the primary analysis cannot be evaluated from the registry information.
The record does not report the statistical analysis plan, multiplicity handling, sample-size justification, or protocol-level power calculation. The sample-size assumptions attached to a planning illustration are not the trial’s design rationale. The registry’s safety entries give counts and one listed serious term, but not event-level context, causality assessments, or a randomized comparison. These gaps limit both outcome interpretation and evaluation of the analysis methods.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Immunogenicity and Safety of Meningococcal ACWY Conjugate Vaccine in Healthy Subjects From 2 to 18 Years in Taiwan — NCT01410474.
- Registry record last updated 2014-09-22; status last verified 2014-09.
- Results first posted 2014-09-22.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT01410474 is a completed phase 3, multicenter, open-label, non-randomized, single-group study of MenACWY-CRM in healthy subjects aged 2 to 18 years in Taiwan. Enrollment was 341. The study started in 2011-08, with primary completion in 2012-01.
The primary outcome was the percentage of overall subjects with hSBA seroresponse to serogroups A, C, W and Y, with a 95% Clopper-Pearson confidence interval specified. The registry defines seroresponse using prevaccination and postvaccination titers and describes a modified intention-to-treat analysis population. The numerical primary results and analyses are not reported in the registry record.
Safety counts are reported for age groups 2-10 Years and 11-18 Years and overall. The record lists one serious adverse event in the younger group, zero in the older group, and one overall; deaths are not reported in the registry record. It also lists other adverse event counts and pneumonia at 0.6% among the top serious terms. These are descriptive entries, not comparative or causal estimates.