Study of Live Attenuated ChimeriVax™-Japanese Encephalitis Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Live Attenuated ChimeriVax™-Japanese Encephalitis Vaccine (NCT00981630), a randomized phase 2 study. The primary outcome is Number of Participants Who Seroconverted to the Respective Homologous JE Vaccine Strain, 28 Days After Completion of the Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or A Placebo.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group Phase II study of live attenuated ChimeriVax™-JE vaccine and placebo. The official title describes it as double-blind and placebo-controlled, while the registry’s masking classification is quadruple. Those descriptions are recorded as stated; further details about which roles were masked or how masking was maintained are not reported in the registry record.

The study evaluated a lyophilised formulation at three dose levels. The dose groups received 3.0 log10 PFU, 4.0 log10 PFU, or 5.0 log10 PFU by single subcutaneous vaccination on Day 0. The placebo group received 0.5 mL of ChimeriVax™ diluent on Day 0. The registry gives an enrollment of 128 and marks the study completed. It lists the start as 2004-11 and primary completion as 2006-02.

The stated objectives covered safety and tolerability, antibody response, and durability of immune response up to 12 months after vaccination. The primary endpoint concerned seroconversion to the homologous vaccine strain. Secondary outcomes included geometric mean titers to homologous and wild-type Japanese encephalitis virus strains, and seropositivity to homologous virus over time.

The registry record does not report the randomization procedure, allocation concealment, visit schedule beyond the listed endpoint timeframe, or the rationale for selecting the dose levels. It also does not report the sample-size justification or a statistical analysis plan. The design therefore identifies the broad comparisons and objectives, but does not provide enough detail to reconstruct all operational or analytical decisions.

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 128 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled and vaccinated.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Seroconversion was assessed in all participants who were negative for homologous and all wild type JE antibodies at Day 0 and had no protocol violations that might have interfered with evaluation of primary criterion.

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 Who Seroconverted to the Respective Homologous JE Vaccine Strain, 28 Days After Completion of the Primary Immunization Schedule With One of 3 Doses of ChimeriVax™-JE Vaccine or A Placebo, measured over Day 11 and Day 30 post-vaccination.

The primary endpoint counted participants who seroconverted to the respective homologous Japanese encephalitis vaccine strain. Antibodies were measured with a 50% plaque reduction neutralization test, PRNT50, for neutralizing antibodies against homologous ChimeriVax™-JE and wild-type Japanese encephalitis virus strains.

For participants who were seronegative at baseline, seroconversion was defined as reaching a titer of at least 1:20 at a post-vaccination timepoint. For participants with a baseline titer, the definition also allowed a rise of at least 4-fold from baseline. This endpoint turns antibody measurements into a binary outcome for each eligible participant: the definition is either met or not met. The registry does not report the assay’s laboratory procedures beyond the named test and threshold.

Seroconversion is used to describe whether an immune response crossed a prespecified threshold, rather than the magnitude of every individual titer. It can therefore be interpreted alongside geometric mean titers, which are listed as secondary outcomes and retain information about antibody levels. Neither type of measure alone describes every aspect of immunity.

The endpoint title refers to assessment 28 days after completion of the primary immunization schedule, whereas its timeframe is listed as Day 11 and Day 30 post-vaccination. The relationship between these wordings is not clarified in the registry record. Most importantly, the registry record does not report the primary endpoint counts by group, so the observed seroconversion pattern and its uncertainty cannot be described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are the procedures used to summarize observed outcomes and compare groups. The registry identifies the trial as randomized and parallel, but a detailed statistical analysis plan is not reported in the registry record. The following concepts are general explanations of how the listed outcome types can be analyzed; they are not claims about procedures actually used in this study.

What does a binary endpoint represent?

Seroconversion is binary because each eligible participant either meets the stated criterion or does not. A group-level summary can report the number meeting the criterion and the number evaluated. A comparison can then express how the chance of meeting the criterion differs between groups, using a chosen effect measure. The registry lists the endpoint and its definition, but does not report the arm-level primary counts or the effect estimates. Without those results, there is no basis for describing the direction, magnitude, or precision of a vaccine-placebo contrast.

The eligible analysis population matters for this type of endpoint. The registry says the primary criterion was assessed among participants who were negative for homologous and all wild-type Japanese encephalitis antibodies at Day 0 and had no protocol violations that might interfere with evaluation. This is a stated endpoint population definition, not a complete account of how many participants met it or how missing measurements were handled. Those details are not reported in the registry record.

How should uncertainty be understood?

General explanation: a confidence interval gives a range of values compatible with the observed data under the statistical model and method used. It communicates precision as well as the point estimate. A narrow interval indicates greater precision than a wide interval, while neither interval width nor a point estimate by itself establishes clinical importance. The registry record does not report confidence intervals for the primary endpoint.

For a binary outcome, uncertainty depends on the observed counts and the analysis method. Sparse event counts can make estimates unstable and intervals wide. That general issue is relevant to interpreting binary endpoints, but the primary seroconversion counts are absent from the registry record, so the degree of uncertainty for this endpoint cannot be assessed. The available safety counts should also be read descriptively because no comparative estimates or uncertainty intervals are reported for them.

What do the antibody-titer outcomes add?

General explanation: geometric means are often used for measurements such as antibody titers when values are right-skewed. The geometric mean is based on averaging on a logarithmic scale and then returning to the original scale. It summarizes the central level while treating multiplicative changes more naturally than an arithmetic mean. A geometric mean titer is not the same as the proportion meeting a seroconversion threshold. The registry lists geometric mean titers to homologous and wild-type virus strains as secondary outcomes, but does not report their values or analysis methods.

Repeated measurements over time can describe whether antibody levels or seropositivity persist, increase, or decline across recorded visits. General methods for repeated outcomes account for within-participant correlation because measurements from the same participant are not independent. The registry states an objective to assess durability up to 12 months and lists seropositivity over time, but does not report the visits, model, or results needed to characterize change over time.

What can planning calculations say?

General explanation: a sample-size calculation estimates the number of participants needed under specified assumptions to detect a chosen effect with a chosen statistical procedure. It is a planning exercise, not evidence that the trial achieved a particular probability of finding an effect. Any planning illustration based on an observed effect is still not observed power. The planning assumptions recorded for the illustrations include a two-sided significance level of 0.05, equal allocation between the compared arms, and a normal approximation. The registry does not report the trial’s own sample-size justification, so these assumptions should not be read as the study’s original design rationale.

When an analysis involves several dose groups, several endpoints, or repeated timepoints, the analyst must define which comparisons are primary and how multiplicity is handled. The registry does not report those choices. The absence of an analysis plan or posted inferential results means the statistical methods actually applied cannot be reconstructed from the record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 6 outcome measures and 0 statistical analyses. The primary endpoint concerns seroconversion to the homologous vaccine strain, while secondary outcomes include geometric mean titers to homologous and wild-type virus strains and seropositivity over time. The listed objectives and outcome measures involve multiple dose groups, outcome types, and timepoints. The registry record does not report how the investigators defined the primary comparison among these possibilities or whether they adjusted for multiple testing.

Multiplicity matters because examining multiple outcomes or comparisons can increase the chance of a seemingly unusual result arising by chance. General approaches include prespecifying a hierarchy of outcomes, adjusting significance thresholds, or treating secondary findings as exploratory. Which, if any, approach was used in this study is not reported in the registry record. Since primary endpoint results and inferential analyses are also absent, there are no posted p-values or confidence intervals to interpret in light of multiplicity.

The primary endpoint population is described as participants who were antibody-negative at Day 0 and had no protocol violations that might interfere with evaluation of the criterion. The number meeting this definition, the handling of missing antibody measurements, and the treatment of protocol deviations are not reported in the registry record. The record also does not explain whether participants were analyzed according to randomized group, received intervention, or another analysis population definition.

Missing outcome data can affect a binary response estimate if the probability of missingness differs across groups or is related to the response. General analyses may describe missingness, use assumptions about unobserved outcomes, or conduct sensitivity analyses. None of those procedures is reported for this study. Accordingly, the posted record does not establish how missing data or analysis populations may have influenced the reported endpoint counts.

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: gastroenteritis (3.1%), cellulitis (3.1%), peritonsillar abscess (3.1%), intervertebral disc protrusion (3.1%), pregnancy (3.1%).

The registry reports serious adverse event affected counts and counts at risk by group. For ChimeriVax™-JE 3 log10 PFU, the serious-event count is 2 among 32 at risk; for 4 log10 PFU, it is 1 among 32 at risk; for 5 log10 PFU, it is 0 among 32 at risk; and for placebo, it is 2 among 32 at risk. The registry also gives other-event counts of 16 among 32 at risk in each vaccine group and 17 among 32 at risk in the placebo group.

These figures describe participants recorded as affected, not the number of separate event episodes. The registry does not give event-level details that would show whether a participant had more than one event, when events occurred, or how long they lasted. The listed serious adverse event terms are Gastroenteritis, Cellulitis, Peritonsillar Abscess, Intervertebral Disc Protrusion, and Pregnancy, each reported at 3.1%. The listed summary does not identify the group associated with each term.

Serious-event counts are not a complete safety profile, and the registry record does not report a statistical comparison of groups. Death counts are not reported in the registry record. These data should therefore be read as descriptive safety information, not as a quantified estimate of comparative risk.

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

The registry record documents a randomized, placebo-controlled Phase II study designed to examine safety, tolerability, and immunogenicity of lyophilised ChimeriVax™-JE at three dose levels. It defines seroconversion using a neutralizing-antibody assay and gives a primary endpoint population. It also records group-level safety counts and a list of serious adverse event terms.

What the record does not provide is the primary endpoint result by group. There are no posted seroconversion counts, effect estimates, confidence intervals, or statistical tests in the information described. The endpoint definition cannot be used to infer how many participants responded, whether response differed by dose, or how precisely any difference was estimated. The listed secondary antibody outcomes likewise have no result values in the registry record.

The safety counts permit a limited descriptive account of affected participants, but they do not by themselves establish a comparative effect. Interpretation would require fuller information about event definitions, event timing, severity, exposure, and analysis methods. The serious adverse event terms and percentages do not identify which group experienced each term in the listed summary.

General explanation: an observed result, its statistical uncertainty, and its clinical relevance are related but distinct. A point estimate describes the observed contrast; an interval describes uncertainty under an analysis method; and clinical relevance requires context beyond statistical significance alone. Here, the primary estimates and uncertainty measures are not reported, so those dimensions cannot be assessed from the registry record.

The record therefore supports statements about the design, endpoint definition, stated objectives, and posted safety counts. It does not support a conclusion about whether the vaccine produced a particular level of seroconversion or whether one dose performed differently from another or placebo. Absence of reported primary results is not evidence that the groups were equivalent, nor does it indicate the direction of any unreported findings.

13. Why This Trial Matters Statistically

This trial illustrates why a clear endpoint definition is essential but not sufficient for statistical interpretation. The registry specifies a measurable antibody response, describes how seroconversion was defined, and identifies the population eligible for the primary endpoint. Those details make the intended outcome understandable. Without outcome counts and estimates, however, readers cannot evaluate the observed response or its precision.

The design also raises familiar questions for dose-ranging studies. Comparing multiple dose levels with placebo can inform how outcomes vary across groups, but the interpretation depends on the comparisons selected, the analysis plan, and how multiplicity is addressed. Those details are not reported in the registry record. The study’s stated objectives also span safety, immunogenicity, and response durability, which are different kinds of evidence and should not be collapsed into a single conclusion.

The distinction between threshold-based seroconversion and geometric mean titers is statistically important. A threshold can communicate how many participants reached a specified response criterion, while a titer summary describes the distribution’s central level. These measures answer related but distinct questions. The registry lists both types of outcome, but only describes their names and not their results.

Finally, posted safety counts are informative as descriptive observations but do not replace comparative estimates or detailed event reporting. This record shows how registry entries can offer useful design and outcome definitions while still leaving critical elements of interpretation unavailable. For clinical researchers, that distinction helps prevent an endpoint’s stated purpose from being mistaken for an observed treatment effect.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpretation is that primary seroconversion results by group are not reported in the registry record. The endpoint is defined, but there are no group-level response counts, estimates, confidence intervals, or inferential results to assess. The secondary antibody outcomes are listed without their numerical results.

The registry gives two different descriptions of primary endpoint timing: the endpoint title refers to 28 days after completion of the primary immunization schedule, while the timeframe is Day 11 and Day 30 post-vaccination. The record does not explain how those descriptions correspond. It also does not report the schedule details needed to clarify the wording.

Although the record describes the study as randomized and the official title calls it double-blind, the registry classification lists masking as quadruple. Details about masking roles, allocation concealment, randomization procedures, and maintenance of masking are not reported in the registry record. The sample-size justification, statistical analysis plan, and methods for handling multiple outcomes are also not reported.

The primary population definition refers to baseline antibody status and protocol violations, but the number meeting the definition and the handling of missing measurements are not reported. The record does not identify the analysis population used for posted outcomes. Safety reporting is limited to group counts and selected serious-event terms; event-level detail, group attribution for the listed terms, and death counts are not reported in the registry record.

These limitations prevent reconstruction of the trial’s primary statistical findings and constrain the safety interpretation to the descriptive counts recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Live Attenuated ChimeriVax™-Japanese Encephalitis Vaccine — NCT00981630.
• Registry record last updated 2012-12-05; status last verified 2012-11.
• Results first posted 2012-12-05.
• 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 describes NCT00981630, a completed randomized Phase II parallel-group study of lyophilised ChimeriVax™-JE in healthy adult volunteers aged 18-49 years. The study evaluated single subcutaneous doses of 3.0 log10 PFU, 4.0 log10 PFU, and 5.0 log10 PFU against ChimeriVax™ diluent placebo. Its objectives covered safety, tolerability, antibody response, and durability of immune response up to 12 months.

The primary endpoint was the number of participants who seroconverted to the homologous vaccine strain, assessed at the stated post-vaccination timepoints and defined by a neutralizing-antibody threshold or rise from baseline. The registry does not report primary endpoint results or statistical analyses. It does report serious and other adverse-event affected counts by group, along with selected serious adverse event terms. Those safety figures are descriptive and do not provide a comparative analysis.