Study of a Single Dose of Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine (SP284) in Japanese Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of a Single Dose of Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine (SP284) in Japanese Subjects (NCT01519713), a non-randomized phase 3 study. The primary outcome is Number of Participants With Serum Bovine Albumin Baby Rabbit (SBA-BR) Titers of >=1:128 Following Vaccination With One Dose of Menactra® Vaccine.

2. Clinical Question

The study is described as assessing safety and immunogenicity to support registration of the product in Japan. Its primary objective is to describe the seroprotection rate following vaccination in subjects 2 through 55 years of age. Secondary objectives concern safety and immune responses to the same four meningococcal serogroups.

This is a descriptive question about post-vaccination antibody measurements in a vaccinated group, not a randomized comparison of vaccination against an alternative. The record does not set out a causal comparison or provide a control group from which to estimate a difference between treatments. Consequently, the stated primary question concerns the observed immune response after a dose, rather than whether that response differs from a comparator.

The registry record gives the endpoint timing and threshold but no numerical result. The number of participants meeting the threshold, the denominator used for each serogroup, and any uncertainty interval are not reported in the registry record. Those omissions prevent an assessment of the observed seroprotection rate from the registry information alone.

3. Trial Design

This is a Phase 3, non-randomized, unmasked, parallel study. The registry record lists enrollment of 200 and describes adult, adolescent, and child study groups. Each group is described as receiving a single dose of the meningococcal polysaccharide diphtheria toxoid conjugate vaccine. No placebo, untreated group, or other active comparator is described, and the age-based groups are not presented as randomized treatment arms.

The recorded study start is 2012-01 and the primary completion is 2012-09. The status is completed. The registry record does not report the individual follow-up schedule beyond the primary endpoint timeframe of 28 days post-vaccination, nor does it state how long safety events were collected.

The title identifies the vaccine as SP284, and the brief description gives the intended Japanese registration context. The primary outcome title names Menactra®, whereas the intervention and study descriptions use generic vaccine wording and SP284. The record does not explain the terminology difference, so it should not be resolved by assuming a product relationship that is not stated there.

The safety listing reports adults, adolescents, and children as separate groups, with 194, 2, and 4 participants at risk, respectively, for the listed safety outcomes. These are the safety denominators in that listing; the number included in each endpoint-specific immunogenicity analysis is not reported in the registry record. The primary endpoint population is described as enrolled and vaccinated participants in the per-protocol population, but eligibility for that population and any exclusions are not specified.

Because there is no randomized comparator, the design is suited to describing measurements and events following vaccination, but it cannot by itself distinguish vaccine-related changes from other explanations such as background variation or differences in who was included in analysis. The registry record does not report the protocol rationale for the age groups, allocation process, or sample-size justification.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A total of 200 subjects who met the inclusion, but no exclusion criteria were enrolled and vaccinated.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Functional antibody activity against meningococcal serogroups A, C, Y and W-135 antigens were determined in all enrolled and vaccinated participants, 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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Serum Bovine Albumin Baby Rabbit (SBA-BR) Titers of >=1:128 Following Vaccination With One Dose of Menactra® Vaccine, measured over 28 Days post-vaccination.

The primary endpoint is the number of participants with SBA-BR titers of at least 1:128 following one dose of the vaccine, measured 28 days post-vaccination. The endpoint description identifies functional antibody activity against meningococcal serogroups A, C, Y, and W-135 and defines seroprotection as an SBA-BR titer of at least 1:128. The brief summary describes the primary objective in terms of the seroprotection rate; the outcome title expresses it as a participant count.

An antibody threshold turns a continuous laboratory measurement into a binary classification: each participant is counted as meeting or not meeting the stated threshold. Such a threshold can make a result easier to describe as a proportion of participants with a specified immune response. The threshold does not, by itself, describe the full distribution of antibody titers, and a count or rate does not show how far above or below the threshold individual measurements lie.

The registry record also lists secondary measures involving a lower titer threshold, a 4-fold rise from Day 0 to Day 28, geometric mean titers, geometric mean of individual titer ratios, and solicited injection-site or systemic reactions. These provide different summaries of immune response and safety. They do not replace the primary endpoint, and the record does not report their numerical findings.

No primary endpoint count, rate, serogroup-specific denominator, confidence interval, or statistical test result is reported in the registry record. The endpoint definition is therefore available, but the magnitude and precision of the observed response cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Outcome type. The primary measure is a binary classification based on whether an SBA-BR titer reaches the stated threshold. The registry outcome title reports a number of participants, while the brief summary describes the objective as a seroprotection rate. A count tells how many participants met the criterion; a rate additionally requires a denominator. The registry record does not report either the observed count or the denominator for the primary endpoint.

What does the threshold capture?

Converting a laboratory titer into a threshold outcome simplifies interpretation: a participant is classified as meeting or not meeting the criterion. This approach can be useful when the scientific question is framed around attaining a specified level of measured antibody activity. It also discards information about the exact titer values within each classification. Two participants on the same side of the threshold can have different measurements, and a binary summary does not show that variation.

The primary endpoint description associates SBA-BR testing with functional antibody activity against serogroups A, C, Y, and W-135. The threshold is stated as at least 1:128. The record does not report the laboratory values, the number meeting the criterion by serogroup, or how results were handled if one or more measurements were unavailable.

How should counts and rates be distinguished?

A count is the number of participants who satisfy an outcome definition. A rate or proportion relates that count to a specified analysis population. The denominator must be clear to interpret the proportion, particularly when some participants may lack measurements or be excluded from an analysis population. Here, the primary outcome is worded as a count, while the primary objective refers to a rate. The exact analysis denominator and resulting rate are not reported in the registry record.

The primary population is described as all enrolled and vaccinated participants, per-protocol population. The criteria for that population are not reported. A per-protocol analysis generally refers to participants meeting study-defined requirements, but the specific requirements and any exclusions in this study are not reported in the registry record. The enrollment figure should not be treated as the endpoint denominator without a reported analysis count.

What can statistical uncertainty tell a reader?

In general, a confidence interval presents a range of values compatible with an estimate under a particular statistical method and its assumptions. It helps communicate how much uncertainty remains around a measured response. An interval does not correct for selection, lack of a comparator, or unreported missing data. No confidence interval is reported for the primary endpoint in the registry record, so its precision cannot be evaluated.

A p-value, in general, measures how compatible data are with a specified null hypothesis under a statistical model. It does not measure the probability that a hypothesis is true or the practical importance of a finding. The registry record lists no analyses and reports no p-value. No inferential conclusion should be attributed to the study on the basis of the endpoint definition alone.

What does the study design permit?

Randomization can help make groups comparable at baseline when comparing interventions. This study is explicitly non-randomized, and all described study groups receive the same vaccine. The age groups are useful categories for descriptive reporting, but they are not a randomized treatment-versus-control contrast. Differences between groups, if reported, could reflect age or other differences rather than a treatment contrast. No such outcome comparisons are reported in the registry record.

Masking is listed as none. The record does not describe additional procedures to reduce observer or participant knowledge of treatment, and no comparative treatment allocation is described. The endpoint is laboratory-based, but the registry record does not state whether laboratory personnel were masked to participant group or measurement timing. That detail is not reported in the registry record.

How should planning illustrations be read?

General sample-size calculations can illustrate how many participants per arm might be needed to detect a specified effect under stated assumptions. The registry record’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect framed as a stated fraction of the observed effect. Those are planning illustrations, not evidence that the original study used those design assumptions. The record does not report its own sample-size justification, and any illustrated sample size should not be interpreted as observed power or as an analysis result.

Over-dispersion is a general concern when observed variation is greater than a statistical model expects; ignoring it can make uncertainty appear too small. It is relevant to some count outcomes, but this primary endpoint is a participant count based on a binary criterion. The registry record does not describe a model for the endpoint, report an over-dispersion assessment, or provide enough results to assess model fit. No particular statistical method should be attributed to the study beyond what the record states.

Overall, the registry record supplies an endpoint definition and broad design descriptors, but not a statistical analysis plan or analysis results. The method used to estimate the primary response, account for missing laboratory results, or handle multiple outcomes is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and several secondary outcomes, including SBA-BR titers of at least 1:8, a 4-fold rise from Day 0 to Day 28, geometric mean titers, geometric mean of individual titer ratios, and solicited injection-site or systemic reactions. The brief summary also frames immune responses across four meningococcal serogroups. Examining multiple outcomes or serogroups can raise multiplicity questions: when many statistical tests are performed, the chance of at least one apparently notable result can increase. The record does not report a multiplicity adjustment, testing hierarchy, or other strategy for addressing this issue.

The number of analyses is listed as 0. No analysis estimates, tests, or uncertainty intervals are reported in the registry record. It is therefore not possible to determine whether a particular multiplicity procedure was applied or how any result would have been interpreted across outcomes and serogroups.

The endpoint population is described as enrolled and vaccinated participants in the per-protocol population. The criteria for that population, the number analyzed, and the handling of participants without a Day 28 measurement are not reported in the registry record. Missing-data methods, including any imputation or sensitivity analysis, are also not reported. The record does not state whether analysis populations differed between the primary and secondary outcomes.

These gaps limit reproducibility and interpretation. A reader cannot establish the denominator for the primary response, evaluate the effect of missing measurements, or determine whether analyses were restricted according to prespecified rules. The protocol’s statistical plan and sample-size justification are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5.00% reporting threshold.

Most frequent non-serious adverse event terms

The registry safety listing reports serious adverse events affecting 0 participants in the adult group, 0 in the adolescent group, and 0 in the child group. The corresponding numbers at risk are 194, 2, and 4. These figures describe the counts entered in the registry for the listed groups; they are not a comparison against an unvaccinated or alternative-treatment group.

For other adverse events, the listing reports 63 affected participants among 194 at risk in the adult group, 2 among 2 in the adolescent group, and 4 among 4 in the child group. The registry record does not provide event terms, severity details, timing, or a breakdown by event type for these counts. It also does not report how events were attributed to the vaccine.

Death counts are not reported in the registry record. A recorded zero for serious adverse events means that the registry lists no affected participants in these groups; it does not establish that no serious event could occur, particularly when the group sizes differ. Counts alone do not describe the range of possible event rates or their precision, and the non-randomized design offers no direct safety comparison.

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

The registry record is informative about the question the investigators intended to address: antibody response and safety after a single dose in Japanese subjects 2 through 55 years of age. It specifies the primary antibody threshold, the measurement timing, and the serogroups of interest. It also identifies adult, adolescent, and child study groups and gives a completed status.

It does not report the primary endpoint result. There is no count of participants meeting the seroprotection threshold, no rate by serogroup, and no confidence interval. As a result, the registry information cannot establish how common the specified response was among analyzed participants or how precisely it was estimated. The secondary immune-response outcomes are listed, but their findings are not reported either.

The safety listing records no serious adverse events in the three groups and reports counts for other adverse events. These descriptive entries do not establish a comparative safety profile. With no control group, non-randomized allocation, and no event-level detail, the counts cannot isolate an effect of vaccination or describe whether events were mild, severe, related, or unrelated.

The study is not a randomized comparison, so its design does not support a causal estimate of what would have happened to the same participants under another intervention. The record also does not describe the statistical methods, missing-data handling, analysis denominators, or multiplicity approach. Those omissions restrict interpretation beyond the basic design and endpoint definitions.

Accordingly, the record documents a completed study and its planned descriptive objectives, but the registry information does not permit an assessment of the magnitude or precision of the immunogenicity findings. It also does not establish that the intervention does or does not produce a particular clinical effect. The endpoint is a laboratory measure of antibody activity, not a report of clinical meningitis outcomes.

13. Why This Trial Matters Statistically

This trial is statistically useful to examine because its primary objective and primary outcome are not phrased identically. The objective describes a seroprotection rate, while the outcome title describes a number of participants meeting the threshold. A rate requires a clear denominator, so reporting both the count and analysis population would be important for interpretation. The registry record does not provide those results.

It also illustrates the distinction between a study’s descriptive aim and a comparative treatment question. The record describes a non-randomized, unmasked study in which each age-based group receives a single dose. The design can organize observations by age group, but those categories do not constitute a randomized control comparison. Interpretation should therefore stay within the descriptive question the record states.

The endpoint uses a specified laboratory threshold, which supports a direct count of participants who meet a defined criterion. At the same time, thresholding does not show the full range of antibody titers. Secondary outcomes listed in the record include measures that could describe responses differently, such as geometric mean titers and 4-fold rises, but their results are not reported.

The record also highlights how important analysis details are for a binary endpoint. The endpoint population is identified as per-protocol, yet the criteria, denominator, missing-data handling, and statistical methods are not described. These details affect how a count or rate should be read and how another analyst could reproduce the result.

Finally, the separate safety counts are descriptive and have very different group sizes. Presenting counts without event details or a comparator leaves important questions unanswered. The record is therefore useful for identifying the study’s design and intended measurements, while also showing why results and analysis documentation are essential for judging precision and scope.

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 primary limitation for interpretation is that the registry record does not report the primary immunogenicity result or any statistical analyses. The endpoint definition and timing are available, but the observed counts, rates, denominators, and precision estimates are not. The secondary outcome results are also not reported, so the record cannot support a quantitative description of the immune responses.

The non-randomized design has no described comparator, and all age-based groups receive the same single dose. It cannot provide a randomized estimate of a difference between vaccination and another treatment or no treatment. Any comparisons among the age groups would also need to account for differences between those groups; the registry record does not report such analyses.

The analysis population is described as enrolled and vaccinated participants in the per-protocol population, but the criteria and endpoint-specific sample sizes are not stated. Missing-data handling and the number with evaluable Day 28 measurements are not reported in the registry record. Thus, the relationship between enrollment and the primary analysis denominator cannot be assessed.

The record does not report the protocol’s sample-size justification, statistical analysis plan, multiplicity strategy, or details of any interim analyses. It also does not give laboratory masking information. The listing uses SP284 in the study title and Menactra® in the primary outcome title, without explaining the difference in terminology.

For safety, the registry provides group-level counts but no event terms, event timing, severity detail for other events, attribution, or reported death counts. The differing group sizes and absence of a comparator limit what can be inferred from those counts. These are limitations of what the registry record reports; they do not establish what may have been documented elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of a Single Dose of Meningococcal Polysaccharide Diphtheria Toxoid Conjugate Vaccine (SP284) in Japanese Subjects — NCT01519713.
• Registry record last updated 2013-05-28; status last verified 2013-05.
• Results first posted 2013-05-28.
• 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 record describes a completed Phase 3, non-randomized, unmasked, parallel study of a single dose of a meningococcal groups A, C, Y, and W-135 polysaccharide diphtheria toxoid conjugate vaccine in Japanese subjects 2 through 55 years of age. It lists enrollment of 200, a start of 2012-01, and primary completion in 2012-09.

The primary endpoint is the number of participants with SBA-BR titers of at least 1:128 at 28 days post-vaccination, described as seroprotection. The outcome title refers to Menactra®, while the study title names SP284. Numerical primary and secondary results, statistical analyses, and uncertainty estimates are not reported in the registry record.

The safety listing reports serious adverse events affecting 0 participants in each age group, and other adverse events affecting 63 adults, 2 adolescents, and 4 children. The corresponding at-risk counts are 194, 2, and 4. Death counts are not reported in the registry record.