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 Boosterability of Live Attenuated Japanese Encephalitis (JE) Vaccine in Children Who Have Previously Received Inactivated JE Vaccine (NCT00463476), a non-randomized phase 4 study. The primary outcome is Percentage of Participants With Demonstrated Seropositivity for Japanese Encephalitis (JE) Neutralizing Antibodies.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00463476 |
| Phase | Phase 4 |
| Condition | Japanese Encephalitis |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 305 |
| Arms in the primary outcome | n/a |
| Lead sponsor | PATH |
| Results posted | Yes |
2. Clinical Question
Population
Children in Sri Lanka aged 2 years or 5 years, each within ±3 months of the stated age, who had previously received inactivated mouse brain-derived Japanese encephalitis vaccine. The study description identifies healthy children and says they met age-specific eligibility criteria, but the full eligibility descriptions are not reported in the registry record.
Intervention
One dose of live attenuated Japanese encephalitis SA 14-14-2 vaccine (LJEV). The brief summary describes evaluation of co-administration with measles vaccine, but details of how co-administration was implemented are not reported in the registry record.
Comparator
There was no separate control group. The 2-year-old and 5-year-old cohorts are age groups within a single-group study, not randomized treatment arms or like-for-like controls.
Primary question
Among eligible children who received LJEV, what proportion had JE neutralizing antibodies meeting the registry's seropositivity definition 28 days after vaccination? The stated primary hypothesis was that this proportion would be greater than 80% in children of both ages who had already received at least two doses of inactivated JE vaccine.
The endpoint was also scheduled for assessment before vaccination and 1 year later. Those measurements can describe antibody status at different time points, but the primary question specified seropositivity at 28 days after vaccination. The registry record gives the question and measurement procedures, but does not report the observed proportions, confidence intervals, or a test of the hypothesis. Therefore, the study's posted record does not establish whether its primary hypothesis was met.
3. Trial Design
This was a completed Phase 4, non-randomized, single-group study sponsored by PATH. The registry lists enrollment of 305 participants. It began on 2007-07-09, and primary completion was 2007-11-01. The intervention was live attenuated Japanese encephalitis SA 14-14-2 vaccine. There was no masking.
Participants were described in two age cohorts: 2-year olds and 5-year olds. Each cohort had previously received inactivated JE vaccine; the descriptions specify vaccination according to the Sri Lankan childhood immunization schedule, although parts of the eligibility descriptions are truncated in the registry record. The study was intended to assess immunogenicity and safety in children in Sri Lanka. Its brief summary also describes co-administration of LJEV and measles vaccine, but further administration details are not reported in the registry record.
The design has no concurrent comparison group. The two age cohorts do not constitute a randomized comparison: age differs, and both groups received the same study vaccine. Their outcomes can be described separately, but a difference between them would not by itself isolate an effect of age or vaccination. The registry record does not report a control condition or a randomized allocation procedure.
The primary outcome was the percentage of participants with JE neutralizing antibodies meeting the seropositivity threshold. Blood was collected at Day 0, Day 28, and 1 year after vaccination. Secondary outcomes included geometric mean titer and several categories of reactions and adverse events. The registry record does not report a protocol, detailed analysis plan, or the results for these outcomes. It lists the study as completed, which is a status description rather than evidence that any particular endpoint met its target.
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.
Overall Study
| Stage | 2-year Olds | 5-year Olds |
|---|---|---|
| STARTED | 151 | 154 |
| COMPLETED | 149 | 151 |
| NOT COMPLETED | 2 | 3 |
Reasons for not completing this period:
| Reason | 2-year Olds | 5-year Olds |
|---|---|---|
| Withdrawal by Subject | 1 | 2 |
| Lost to Follow-up | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: The per-protocol analysis set included all participants of the appropriate age at study entry (2 years of age ±3 months and 5 years of age ±3 months for each group respectively) who received LJEV at Day 0 and with valid serology laboratory results 28 days post-vaccination. Five participants did not complete the 1-year post-vaccination visit.
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 | 2-year Olds | 5-year Olds | Total |
|---|---|---|---|---|
| Participants analysed | 151 | 154 | 305 | |
| Age, Continuous | months | 24.5 (SD 1.4) | 60.4 (SD 1.6) | 42.6 (SD 18) |
| Sex: Female, Male: Female | Participants | 72 | 78 | 150 |
| Sex: Female, Male: Male | Participants | 79 | 76 | 155 |
| Region of Enrollment: Sri Lanka | participants | 151 | 154 | 305 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Demonstrated Seropositivity for Japanese Encephalitis (JE) Neutralizing Antibodies, measured over Day 0 (pre-vaccination) and 28 days and 1 year post-vaccination.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants with demonstrated seropositivity for JE neutralizing antibodies. Serum neutralizing antibodies to the Beijing-1 JE strain were measured using a plaque reduction neutralization test. In that assay, the neutralizing titer was the inverse dilution at which plaque counts were reduced by 50%. Seropositivity was defined as a titer of ≥ 1:10.
Antibody measurement is used as an immunogenicity endpoint: it records whether participants reached the specified laboratory threshold, rather than whether they experienced a clinical disease outcome. A percentage expresses how common the defined antibody status was in the analysis population. Its interpretation depends on the population included, timing of blood collection, assay procedure, and threshold definition.
The primary timeframe was 28 days after vaccination, with measurements also scheduled before vaccination and 1 year later. The registry record's stated hypothesis concerns the Day 28 seropositivity rate and sets a benchmark of greater than 80%. The endpoint definition and hypothesis are reported, but the observed endpoint values and their confidence intervals are not reported in the registry record. Consequently, the record does not show the measured rate or its precision at any of the stated time points.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record specifies a clear primary immunogenicity question: whether the Day 28 seropositivity rate in previously vaccinated children was greater than 80%. It also defines seropositivity using a neutralizing antibody titer of ≥ 1:10. However, the posted record does not report the observed seropositivity rate, its 95% confidence interval, or a statistical test against the stated benchmark. The primary result therefore cannot be interpreted from the registry information available.
A confidence interval would describe the uncertainty around an estimated seropositivity rate. General interpretation: a narrower interval indicates greater precision, while a wider interval indicates more uncertainty about the underlying rate. Without the reported estimate and interval, it is not possible to assess either the direction of the observed result relative to 80% or how precisely the rate was estimated. No conclusion about whether the stated hypothesis was supported can be drawn from the endpoint definition alone.
The study includes 2-year-old and 5-year-old cohorts, but it is not a randomized comparison. Any difference between the age groups would be descriptive unless supported by an appropriate analysis and design; the registry record reports no such analysis. It also does not report a comparison with children who did not receive LJEV, or with a different vaccine regimen. Thus, the design described cannot attribute an observed change in antibody status to LJEV by comparison with a concurrent untreated or alternative-treatment group.
Measurements were planned before vaccination, at Day 28, and 1 year later. These time points could describe antibody status over time, but their values are not reported in the registry record. It is not possible to determine from this record whether seropositivity changed between measurements, how many participants contributed at each time point, or how missing measurements were handled.
The listed safety figures describe participants affected by serious adverse events in the age cohorts, along with deaths and selected serious-event terms. They should be read as descriptive registry entries, not as a randomized safety comparison. The record does not establish that an event was caused by vaccination, and the listed event terms do not replace the full safety results. Overall, the registry information describes the study question and some safety counts, but does not provide the primary efficacy-style endpoint result needed to answer its stated immunogenicity question.
9. Statistical Methods Explained
What does seropositivity represent?
Seropositivity is a binary classification based on a laboratory threshold. In this study, a participant was classified as seropositive when the JE neutralizing antibody titer met the definition of ≥ 1:10. The endpoint then expresses the number of participants meeting that definition as a percentage of the relevant analysis population. This is distinct from the geometric mean titer, which is a separate secondary outcome that summarizes antibody levels rather than the share meeting a cutoff.
The classification depends on the stated laboratory method and threshold. The registry describes use of a plaque reduction neutralization test against the Beijing-1 JE strain, with the neutralizing titer measured as the inverse dilution at which plaque counts were reduced by 50%. The record does not report additional assay validation details or laboratory quality-control results.
How should the confidence interval be understood?
The primary endpoint lists a 95% confidence interval as its dispersion measure. General explanation: a confidence interval communicates the uncertainty associated with an estimated rate, taking account of the finite analysis sample. It is not a guarantee that the true rate lies within the particular interval, and it does not describe the spread of individual antibody titers. For a percentage endpoint, the estimate and interval are both important: the estimate gives the observed proportion, while the interval indicates how uncertain that estimate is.
The actual rate and interval are not reported in the registry record. It is therefore not possible to assess their width or determine whether the interval is compatible with the stated benchmark of greater than 80%. The presence of a planned confidence-interval measure does not itself provide a result.
Why do the age cohorts not make a treatment comparison?
The study is described as non-randomized and single-group, with cohorts of 2-year olds and 5-year olds. Both cohorts received LJEV. A comparison of their outcomes would contrast age-defined groups, not LJEV against a control intervention. General explanation: randomization can help balance measured and unmeasured participant characteristics across treatment groups. Without randomized allocation or a concurrent control group, group differences may reflect underlying differences between participants as well as any treatment-related factors. The registry record does not describe an adjusted comparative analysis.
What can the time points contribute?
Serum collection was scheduled at Day 0, Day 28, and 1 year after vaccination. General explanation: repeated measurements can describe baseline status, an early post-vaccination response, and later antibody status. To interpret changes, readers need the results at each time point and clarity about which participants contributed to each measurement. The registry record does not report those values or the number with valid results at every time point.
What is over-dispersion, and is it relevant to this endpoint?
General explanation: over-dispersion arises when observed variation exceeds what a statistical model assumes. It can matter for outcomes such as counts when a simple model understates variability, potentially making uncertainty look too small. This primary endpoint is a participant-level binary classification summarized as a percentage, not a count outcome modeled with a reported count distribution. The registry record does not report a model for the endpoint, so no claim about over-dispersion handling can be made.
What can be said about planning calculations?
General explanation: sample-size planning estimates describe how many participants might be needed under specified assumptions to detect a chosen effect with a chosen statistical procedure. They are not observed results and are not a measure of the probability that the study's finding is true. The record describes an illustrative planning approach based on an observed effect, two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect, but no specific fraction or sample-size result is reported in the registry record. The trial itself is described as single-group, so the illustration's equal-allocation assumption should not be mistaken for the study's actual design. No sample-size justification for the original trial is reported in the registry record.
The record lists no analyses. It does not report a hypothesis-test result, model specification, handling of multiple endpoints, or any recalculated estimate. Without posted endpoint results, there is no numerical estimate to assess for consistency or precision. The sponsor's own analysis cannot be described because it is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary seropositivity outcome and secondary outcomes covering geometric mean titer, immediate reactions, local and systemic reactions, unsolicited adverse events, and solicited reactions over specified observation periods. Examining several outcomes can raise a multiplicity question: when many statistical tests are performed, the chance of at least one apparently notable result can increase. General explanation: an analysis plan may address this through prespecified outcome hierarchy or adjustment procedures. Such procedures are not reported in the registry record, and the record lists no analyses.
The primary endpoint is specified at Day 28, while seropositivity was also scheduled for measurement at Day 0 and 1 year after vaccination. The record does not explain how inferential claims across these time points were to be handled. It does not report p-values or confidence intervals for the primary or secondary outcomes.
The primary analysis population is described as per protocol: participants of the appropriate age at study entry who received LJEV at Day 0 and had valid serology laboratory results 28 days after vaccination. The population description is truncated after the words “Five participants did not”; what those participants did not do is not reported in the registry record. The record does not report the number included in the primary analysis or the handling of participants without valid results. It also does not describe an intention-to-treat analysis or imputation method.
Missing data can affect a percentage endpoint if the participants with measured outcomes differ from those without them. General explanation: excluding participants with unavailable results may change the composition of the analysis population, while imputation requires assumptions about unobserved values. Because the missing-data approach and complete analysis counts are not reported, the extent and direction of any such effect cannot be assessed.
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-year Olds | 22 | 151 | 14.6% |
| 5-year Olds | 8 | 154 | 5.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 2-year Olds | 0 of 151 |
| 5-year Olds | 0 of 154 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 2-year Olds | 54 of 151 |
| 5-year Olds | 54 of 154 |
Most frequent serious adverse event terms
| Event term | Organ system | 2-year Olds | 5-year Olds |
|---|---|---|---|
| Viral infection | Infections and infestations | 7 of 151 | 1 of 154 |
| Lower respiratory tract infection | Infections and infestations | 5 of 151 | 1 of 154 |
| Upper respiratory tract infection | Infections and infestations | 2 of 151 | 1 of 154 |
| Urticaria | Skin and subcutaneous tissue disorders | 2 of 151 | 1 of 154 |
| Tonsillitis | Infections and infestations | 1 of 151 | 1 of 154 |
| Febrile convulsion | Nervous system disorders | 2 of 151 | 0 of 154 |
| Abdominal Pain | Gastrointestinal disorders | 0 of 151 | 1 of 154 |
| Vomiting | Gastrointestinal disorders | 1 of 151 | 0 of 154 |
| Pyrexia | General disorders | 1 of 151 | 0 of 154 |
| Bacterial infection | Infections and infestations | 1 of 151 | 0 of 154 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 2-year Olds | 5-year Olds |
|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | 20 of 151 | 20 of 154 |
| Pyrexia | General disorders | 16 of 151 | 17 of 154 |
| Nasopharyngitis | Infections and infestations | 17 of 151 | 11 of 154 |
| Lower respiratory tract infection | Infections and infestations | 5 of 151 | 3 of 154 |
| Viral infection | Infections and infestations | 7 of 151 | 1 of 154 |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | 2 of 151 | 4 of 154 |
| Wheezing | Respiratory, thoracic and mediastinal disorders | 4 of 151 | 2 of 154 |
| Diarrhoea | Gastrointestinal disorders | 3 of 151 | 2 of 154 |
| Rash pustular | Infections and infestations | 0 of 151 | 4 of 154 |
| Vomiting | Gastrointestinal disorders | 2 of 151 | 1 of 154 |
Serious events with the highest arm-level rate: viral infection (4.6%), lower respiratory tract infection (3.3%), upper respiratory tract infection (1.3%), febrile convulsion (1.3%), urticaria (1.3%).
The registry lists serious adverse event figures separately for the 2-year-old and 5-year-old cohorts. In the 2-year-old cohort, 151 participants were at risk and 22 were listed as affected; in the 5-year-old cohort, 154 were at risk and 8 were listed as affected. Deaths are listed as 0 in each cohort. These are registry counts; no rates are calculated.
The record also lists serious-event terms and percentages: Viral infection, 4.6%; Lower respiratory tract infection, 3.3%; Upper respiratory tract infection, 1.3%; Febrile convulsion, 1.3%; Urticaria, 1.3%; and Vomiting, 0.7%. The denominator and detailed event-count context for these percentages are not reported in the registry record. The entries do not establish that events were caused by vaccination.
These figures are descriptive and do not provide a controlled comparison of safety. The cohorts differ by age, and the study is non-randomized and single-group. The registry record also lists outcomes for immediate reactions, solicited local and systemic reactions, and unsolicited adverse events, but their results are not reported in the registry record. The serious-event entries should not be treated as a complete account of all safety findings.
12. What the Result Does, and Does Not, Mean
The study was designed to assess immunogenicity and safety after LJEV in children who had previously received inactivated JE vaccine. Its primary question was whether the Day 28 seropositivity rate exceeded 80%, using a laboratory threshold of ≥ 1:10. The posted record supplies the endpoint definition, planned measurement times, and the stated hypothesis, but not the observed primary result. It therefore does not show whether the benchmark was met or how precisely the rate was estimated.
Even if a post-vaccination seropositivity estimate were available, that endpoint would describe antibody status according to the specified assay and cutoff. General explanation: a laboratory marker can be useful for studying immune response, but it is not itself a direct measure of clinical illness or protection in an individual. The registry record does not report clinical disease outcomes as the primary endpoint, nor does it give results that would connect the antibody classification to such outcomes.
The design also limits comparative interpretation. Both age cohorts received LJEV, with no randomized control group. The record therefore cannot support a direct estimate of how outcomes would differ under another intervention or no vaccination. Age-group differences, if any, would not by themselves establish a vaccine effect.
The safety entries include affected-participant counts, deaths, and selected serious-event terms, but do not report a full analysis or establish causality. The absence of a reported death in the listed cohorts is not a substitute for the complete safety assessment. The outcome results for the other listed reaction categories are not reported in the registry record.
In short, the registry describes what investigators intended to measure and how the primary laboratory endpoint was defined. It does not report enough outcome information to determine the observed immune response, its precision, or whether the stated primary hypothesis was supported. No clinical recommendation follows from the registry entries alone.
13. Why This Trial Matters Statistically
This trial raises a common statistical distinction between a well-defined research question and a reportable result. The primary question is explicit: estimate Day 28 seropositivity after LJEV in previously vaccinated children and assess it against a benchmark of greater than 80%. The registry also defines the assay threshold and identifies the analysis population in general terms. Yet without the observed percentage and its confidence interval, readers cannot evaluate the magnitude or precision of the primary finding.
The single-group design also makes the interpretation of immune-response outcomes especially important. A post-vaccination percentage can describe the participants measured, but without a concurrent control group it cannot show how that percentage compares with an alternative regimen. The separate age cohorts may be informative descriptively, but they are not substitutes for randomized treatment groups.
The record illustrates why analysis-population details matter. The stated primary population requires vaccination and a valid Day 28 laboratory result. The registry's description is incomplete, and the number included is not reported. Clear reporting of exclusions, missing measurements, and the analysis denominator is necessary to understand what a percentage represents.
Finally, the safety record contains selected serious-event counts and terms, while results for other listed safety outcomes are absent. A careful statistical reading distinguishes the presence of outcome definitions from the availability of results. Here, the registry record documents a study question and some safety information, but not the primary numerical evidence needed to judge the stated immunogenicity target.
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 statistical interpretation is that the registry record does not report the primary seropositivity results. No observed percentage, confidence interval, or hypothesis-test result is available in the record. The same absence applies to the scheduled measurements at Day 0 and 1 year after vaccination, so the trajectory of antibody status cannot be described.
The study is non-randomized and single-group, with no concurrent control condition. The two age cohorts received the same intervention and cannot serve as like-for-like controls. The record therefore does not support causal comparisons of LJEV with another intervention or with no vaccination.
The per-protocol population description is truncated, and the number included in the primary analysis is not reported in the registry record. The handling of missing serology, exclusions, and participants who did not contribute valid results is also not reported. These omissions prevent assessment of the analysis denominator and potential selection effects.
Further limitations include the absence of a reported detailed statistical analysis plan, multiplicity procedure, model specification, and outcome results for the listed secondary endpoints. The safety entries provide selected counts and terms, but do not report the full results or establish causality. Parts of the age-specific eligibility descriptions are incomplete in the registry record, and details of measles-vaccine co-administration are not reported. The original sample-size justification is not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Boosterability of Live Attenuated Japanese Encephalitis (JE) Vaccine in Children Who Have Previously Received Inactivated JE Vaccine — NCT00463476.
- Registry record last updated 2020-03-31; status last verified 2018-09.
- Results first posted 2020-03-31.
- 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
NCT00463476 is a completed Phase 4, non-randomized, single-group study sponsored by PATH, with enrollment of 305. It assessed live attenuated Japanese encephalitis SA 14-14-2 vaccine in 2-year-old and 5-year-old children who had previously received inactivated JE vaccine.
The primary outcome was the percentage with JE neutralizing antibodies meeting the seropositivity definition of ≥ 1:10, assessed before vaccination, at Day 28, and 1 year after vaccination. The stated primary hypothesis concerned a Day 28 rate greater than 80%. The primary outcome values and confidence intervals are not reported in the registry record.
The registry lists secondary immunogenicity and safety outcomes, and reports serious adverse event counts and selected terms. It does not report the results for the primary endpoint, the detailed analysis plan, or the handling of missing data.