Study of Japanese Encephalitis Chimeric Virus Vaccine Given With Measles-Mumps-Rubella Vaccine in Taiwanese Toddlers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Japanese Encephalitis Chimeric Virus Vaccine Given With Measles-Mumps-Rubella Vaccine in Taiwanese Toddlers (NCT01188343), a randomized phase 3 study. The primary outcome is Percentage of Participants With Seroconversion to Vaccine Antigens Following Concomitant Administration of Japanese Encephalitis Chimeric Virus Vaccine (JECV) and MMR or Single Administration of JE-CV and MMR Vaccine at 42 Days Following First Vaccination.

2. Clinical Question

The clinical question concerns immune responses to JE-CV and the MMR antigens, rather than a clinical disease outcome. The study also describes immune responses at other time points and solicited injection-site and systemic reactions. Those additional outcomes broaden the assessment, but they do not substitute for the primary comparison. Without the reported endpoint estimates and their uncertainty, the registry record cannot establish whether the prespecified non-inferiority objective was met.

3. Trial Design

This was a Phase 3, randomized, open-label, parallel-group study with a planned enrollment of 542. It enrolled toddlers aged 12 to 18 months in Taiwan and was marked completed in the registry. The recorded study start was 2010-08 and primary completion was 2012-07.

Participants were assigned to one of three vaccination schedules. Group 1 received JE-CV on Day 0 and MMR on Day 42. Group 2 received MMR on Day 0 and JE-CV on Day 42. Group 3 received both vaccines on Day 0. The separate schedules therefore differed in which vaccine was administered first, while the concomitant schedule administered both at the first visit.

Randomization can help balance participant characteristics across groups on average, while an open-label design means masking was not used. The registry record does not report further details about the randomization procedure, allocation concealment, or any steps to reduce bias in outcome assessment. It also does not report the rationale for choosing the planned enrollment or a detailed statistical analysis plan.

The primary objective was to demonstrate non-inferiority of antibody responses, measured by seroconversion, with concomitant vaccination compared with separate administration. Secondary objectives included describing immune responses and safety. Follow-up outcomes included assessments before vaccination, after vaccination, and at later time points. The registry record describes these outcome domains but does not report numerical results for the primary endpoint.

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 550 participants who met all of the inclusion and none of the exclusion criteria were randomized, 542 were vaccinated and reported.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Seroconversion was assessed in the Per Protocol Analysis Set with evaluable data.

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 Percentage of Participants With Seroconversion to Vaccine Antigens Following Concomitant Administration of Japanese Encephalitis Chimeric Virus Vaccine (JECV) and MMR or Single Administration of JE-CV and MMR Vaccine at 42 Days Following First Vaccination, measured over Day 0 (pre-vaccination) and Day 42 post-vaccination.

The primary endpoint is the percentage of participants with seroconversion to vaccine antigens, assessed at Day 42 after first vaccination. For JE-CV, antibodies were measured using a 50% plaque reduction neutralization test (PRNT50). For MMR antigens, antibodies were measured using enzyme linked immunosorbent assay (ELISA). The endpoint uses antigen-specific definitions rather than one identical threshold for every vaccine component.

For JE-CV, seroconversion required either a pre-vaccination titer <1/10 and a post-vaccination titer ≥1/10, or a pre-vaccination titer ≥1/10 and a 4-fold increase from pre- to post-vaccination. For measles, the definition was a post-vaccination titer ≥120 mIU/ml when the pre-vaccination titer was <120 mIU/ml. For mumps and rubella, it was a post-vaccination titer ≥1/10 U/ml when the pre-vaccination titer was <10 U/ml.

Seroconversion is a binary outcome: each evaluable participant is classified as meeting or not meeting the specified response definition for an antigen. Reporting the percentage gives a group-level description of how often that criterion was met. It is used to compare immune responses between vaccination schedules, not to measure disease incidence or clinical protection. The analysis population was the Per Protocol Analysis Set with evaluable data. Numerical endpoint results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary percentage represent?

In general, a binary outcome assigns each participant to one of two categories, such as meeting or not meeting a defined response criterion. The percentage of participants meeting that criterion describes the observed response frequency in the analyzed group. It does not show how much an individual antibody titer changed unless the underlying continuous measurements are also reported. For this trial, the endpoint is seroconversion to vaccine antigens, with a different operational definition for JE-CV, measles, mumps, and rubella.

The registry record identifies the Per Protocol Analysis Set with evaluable data as the population for the primary endpoint. That means the stated target population for this analysis is not simply everyone enrolled. The record does not describe the participant flow into that set, the number with evaluable results for each antigen, or the reasons participants may have been excluded from the analysis.

How is non-inferiority assessed?

General explanation: a non-inferiority analysis asks whether a new or alternative approach is not worse than a comparator by more than a prespecified acceptable margin. The analysis requires a defined contrast, a direction for that contrast, and a margin chosen before examining the results. The estimate and its uncertainty are then assessed against the margin. A result that fails to show a meaningful difference is not, by itself, evidence of non-inferiority; the uncertainty and decision boundary matter.

For this study, the objective is to compare seroconversion after concomitant vaccination with responses after separate administration. The registry record does not report the margin, the exact primary contrast, the statistical test, or the confidence interval. It therefore does not permit readers to reproduce or verify a non-inferiority assessment. The analysis method should not be inferred from the objective alone.

Why does the analysis population matter?

General explanation: per-protocol analyses focus on participants who meet specified criteria for following the study procedures and having usable outcome data. Such an analysis can be relevant to a non-inferiority question, because departures from the assigned schedule may affect the observed comparison. However, excluding participants can also change the composition of the groups. A clear interpretation therefore depends on knowing the population rules and how many participants contributed to each endpoint.

The registry record names a per-protocol population with evaluable data but does not give its detailed criteria or group-specific denominators for the primary endpoint. It also does not report a complementary analysis population or a comparison of results across analysis populations. The robustness of any primary conclusion cannot be assessed without those details and the endpoint results.

How should multiple antigen outcomes be understood?

General explanation: when a study evaluates several outcomes or several related measures, the chance of an apparently notable finding across the collection can differ from the chance for one prespecified comparison. A statistical plan may define a testing sequence, adjust for multiplicity, or treat results as descriptive. The appropriate interpretation depends on that plan and on which outcomes are primary or secondary.

The primary outcome description covers seroconversion to multiple vaccine antigens. The secondary outcomes include seroconversion, seroprotection at later visits, geometric mean titers, and solicited reactions. The registry record does not report a multiplicity strategy or explain how conclusions across the antigens were combined. It also records no analysis entries. This does not establish that no analyses were performed; it means the analysis details and results are not reported in the registry record.

What does a confidence interval add?

General explanation: an estimate gives a central summary of an observed contrast, while a confidence interval expresses its statistical uncertainty under the model and analysis assumptions. A narrow interval indicates greater precision than a wide interval, but neither width nor location can be judged without the actual interval and the scale of the comparison. For a non-inferiority question, the interval must be considered relative to the prespecified margin.

No primary effect estimate or confidence interval is reported in the registry record. As a result, readers cannot assess precision, whether the data are compatible with a range of clinically relevant differences, or whether the non-inferiority boundary was crossed.

What can planning illustrations tell readers?

General explanation: sample-size planning illustrations show how a hypothetical study might be designed under stated assumptions. They are not observed results, and they are not observed power. The registry record’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions are described as an illustration rather than the trial’s own design justification. The registry record does not report the trial’s sample-size justification.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint covers seroconversion to several vaccine antigens, each with its own measurement method and response definition. Secondary outcomes add seroprotection, geometric mean titers, and solicited reactions. Considering several endpoints can raise multiplicity questions: a statistical plan may specify which comparisons are confirmatory, how multiple tests are handled, and which results are descriptive. A multiplicity strategy is not reported in the registry record.

The registry record identifies the Per Protocol Analysis Set with evaluable data for the primary endpoint. It does not report detailed inclusion criteria, the number of participants analyzed for each antigen, or how missing or unevaluable results were handled. The missing-data approach, including any assumptions or sensitivity analyses, is not reported in the registry record. Without these details, it is difficult to judge whether participants with unavailable measurements could affect the comparison.

The record lists zero analysis entries. This indicates that analysis details are not included in the registry record; it does not show whether analyses were or were not conducted. The primary endpoint estimates, confidence intervals, p-values, and non-inferiority margin are not reported in the registry record. Nor does the record explain how the two separate-vaccination groups were incorporated into the primary comparison.

These reporting gaps limit verification of the stated objective. They do not establish that the analysis was inappropriate, but they prevent readers from assessing its prespecification, multiplicity control, handling of missing data, and consistency across analysis populations.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: herpangina (2.3%), gastroenteritis (2.0%), pneumonia (2.0%), bronchiolitis (1.4%), bronchopneumonia (1.4%).

The registry record reports serious adverse-event counts by group: 10 participants among 102 in Group 1, 21 among 219 in Group 2, and 13 among 220 in Group 3. It also reports other adverse-event counts: 30 among 102 in Group 1, 80 among 219 in Group 2, and 79 among 220 in Group 3. These are descriptive counts of participants affected, not estimates adjusted for differences or evidence that an event was caused by a vaccine.

The listed serious adverse-event terms include Herpangina at 2.3%, Gastroenteritis at 2.0%, Pneumonia at 2.0%, Bronchiolitis at 1.4%, Bronchopneumonia at 1.4%, and Diarrhea infectious at 1.0%. The registry record does not provide enough detail in these entries to determine how terms were counted across groups or how they relate to the participant-level counts. Death counts are not reported in the registry record.

These figures should be read as registry safety descriptions, not as a randomized comparison with a stated statistical test. The record does not report event-level timing, attribution, or comparative uncertainty. It also does not establish that an adverse event was caused by vaccination.

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

The study addresses a practical statistical question: whether antibody responses after giving JE-CV and MMR together are non-inferior to responses after giving the vaccines separately. It is randomized and includes both possible orders of separate administration as well as a concomitant schedule. The registry record also defines seroconversion using laboratory measurements and antigen-specific thresholds.

What the posted information does show is the study structure, planned enrollment, endpoint definitions, stated analysis population, secondary outcome domains, and adverse-event counts. The study is marked completed. These details help describe what was intended to be compared and how the primary outcome was defined.

What it does not show is the primary endpoint result. The registry record does not report the group-specific seroconversion percentages, the contrast between schedules, its confidence interval, the non-inferiority margin, or a p-value. Consequently, it does not establish whether the stated non-inferiority objective was met, how precise the comparison was, or whether responses differed across antigens.

General statistical interpretation: an objective is a question to be answered by data, not a finding. A non-inferiority conclusion requires the observed estimate to be interpreted against a prespecified margin, with uncertainty taken into account. Without those elements, neither a positive nor a negative conclusion about the primary comparison is justified from the registry record.

The safety counts provide descriptive information but do not establish causation or comparative safety. The listed events and affected-participant counts should not be converted into claims about treatment effects. Overall, the record describes a randomized comparison and its intended outcomes, but the missing primary results prevent a conclusion about the central immunogenicity question.

13. Why This Trial Matters Statistically

This study illustrates why a clearly stated endpoint is not enough to interpret a trial’s main statistical question. The registry specifies seroconversion as the primary outcome and defines the response thresholds for JE-CV, measles, mumps, and rubella. Those definitions make clear what counts as a response, while also showing that the endpoint includes distinct antigen-specific criteria.

The non-inferiority objective makes the analysis details especially important. Interpretation requires the comparison to be defined, the non-inferiority margin to be known, and the estimate to be considered with its uncertainty. Because those results and details are not reported in the registry record, readers cannot determine whether the trial’s stated objective was achieved. A completed study status does not supply the missing statistical evidence.

The three-arm structure also matters for interpretation. Separate administration occurred in two orders, whereas concomitant administration occurred at the first visit. A primary comparison should make clear how the separate schedules contribute to the comparator. That comparison detail is not reported in the registry record.

Finally, the record distinguishes the primary immunogenicity question from secondary immune-response and safety outcomes. That distinction helps prevent descriptive safety counts or secondary measures from being mistaken for evidence about the primary non-inferiority objective. This is a useful example of how registry completeness affects the extent to which readers can independently evaluate trial conclusions.

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 of the registry information is that the primary endpoint results are not reported. Without group-specific seroconversion results and a comparative estimate with uncertainty, the main objective cannot be assessed. The non-inferiority margin and the exact statistical comparison are also not reported in the registry record.

The primary analysis population is described as the Per Protocol Analysis Set with evaluable data, but detailed criteria, group-specific analysis denominators, and participant disposition are not reported. The handling of missing or unevaluable outcome data is not reported in the registry record. These omissions prevent assessment of how exclusions or unavailable measurements may have influenced the analysis.

Several antigens and secondary outcomes are described, but the record does not report a multiplicity strategy or explain how results across the antigens were interpreted. It also does not clarify how the two separate-vaccination schedules were combined or selected for the primary comparison. Further details of the randomization procedure, allocation concealment, and outcome-assessment procedures are not reported in the registry record.

Safety entries are descriptive and do not include comparative uncertainty or sufficient detail to establish causation. Death counts are not reported in the registry record. The sample-size assumptions are described as a planning illustration based on the observed effect, not as the trial’s design justification. The record does not report the justification for the planned enrollment of 542.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Japanese Encephalitis Chimeric Virus Vaccine Given With Measles-Mumps-Rubella Vaccine in Taiwanese Toddlers — NCT01188343.
• Registry record last updated 2014-08-15; status last verified 2014-07.
• Results first posted 2014-08-15.
• 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

NCT01188343 is a completed, randomized, open-label, parallel-group Phase 3 study of JE-CV and MMR vaccination in Taiwanese toddlers aged 12 to 18 months. Planned enrollment was 542. The study compared concomitant administration with two schedules that gave the vaccines separately, in opposite orders, at Day 0 and Day 42.

The primary objective was non-inferiority of seroconversion responses 42 days after first vaccination. The endpoint used PRNT50 for JE-CV and ELISA for MMR antigens, with antigen-specific definitions. The primary analysis population was the Per Protocol Analysis Set with evaluable data.

The registry describes secondary immune-response and safety outcomes and lists adverse-event counts. Primary endpoint results, the non-inferiority margin, and detailed analysis methods are not reported in the registry record, so the main comparison cannot be evaluated from the posted information.