Post-licensure Safety Study of IMOJEV® in Thailand: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Post-licensure Safety Study of IMOJEV® in Thailand (NCT01981967), a non-randomized phase 4 study. The primary outcome is Number of Participants Experiencing a Grade 3 Immediate Systemic Adverse Events and Serious Adverse Events Following Any Vaccination With IMOJEV®.

2. Clinical Question

In statistical terms, the study is descriptive: it characterizes observed safety events in people who received the vaccine, rather than testing a randomized contrast against a concurrent control. The key quantities are counts of participants with events in each vaccination-history group. Such counts help describe what was observed in the study population, but they do not by themselves establish whether an event was caused by vaccination or whether event risk differs between groups.

The distinction between primary and booster vaccination is relevant to interpreting the results. The groups had different prior vaccination histories by definition, so they may also differ in other ways; the registry record does not give enough information to assess those differences. The intended question is therefore about the safety experience recorded after vaccination, not a causal comparison of the two histories.

3. Trial Design

This was a Phase IV, post-licensure safety study of IMOJEV® in Thailand. The registry lists the study as completed, with enrollment recorded as 10000. That registry enrollment figure should not automatically be treated as the number included in every analysis: the primary outcome description says safety outcomes were assessed in participants who received the study vaccine and were included in the Safety Analysis Set. The analyzed count for each endpoint is not separately reported in the registry record.

The design was parallel and non-randomized, with no masking. Participants were grouped according to vaccination history. The primary-vaccination group included people who had never received a Japanese encephalitis vaccine, those who had received a single dose of inactivated Japanese encephalitis vaccine, or those whose vaccination history was unknown or undocumented. The booster-vaccination group included people with specified prior inactivated or live vaccine histories at least one year earlier.

Both groups received IMOJEV®. Thus, the group labels represent different vaccination histories rather than different assigned treatments. The registry explicitly cautions that these arms are not a like-for-like control comparison. Without random allocation, differences in event counts between groups may reflect differences in participant history or other characteristics as well as chance; the record does not report an adjusted comparison that would address this.

The primary objective was to describe serious adverse events, including adverse events of special interest, through 60 days after one dose. The secondary objective was to describe Grade 3 severe systemic adverse events up to 30 minutes after one dose. The primary outcome title refers to both Grade 3 immediate systemic events and serious adverse events, while its stated timeframe extends from 30 minutes post-vaccination up to Day 60. The registry record does not provide further detail resolving that wording.

No randomization procedure, masking procedure, interim analysis plan, or detailed statistical analysis plan is reported in the registry record. The design supports descriptive safety reporting in the vaccinated groups; it does not provide the protection against confounding that a randomized controlled comparison is designed to offer.

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 10,000 participants who met all of the inclusion and none of the exclusion criteria were vaccinated in this study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety outcome were assessed in subjects who had received the study vaccine, the Safety Analysis Set

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 Experiencing a Grade 3 Immediate Systemic Adverse Events and Serious Adverse Events Following Any Vaccination With IMOJEV®, measured over 30 minutes post-vaccination up to Day 60 post-vaccination.

The primary outcome is expressed as a number of participants experiencing specified safety events after vaccination. Its title names Grade 3 immediate systemic adverse events and serious adverse events following any vaccination with IMOJEV®. The timeframe is described as 30 minutes post-vaccination up to Day 60 post-vaccination. Separately, the study objectives specify serious adverse events, including adverse events of special interest, up to 60 days, and Grade 3 systemic adverse events up to 30 minutes.

Counting participants with an event is a direct descriptive measure: it records how many people in the analyzed group met the stated event definition. It is useful in a safety study because serious or severe events warrant characterization even when they are uncommon, and a count can communicate the observed burden within the study population. The registry record does not report a formal hypothesis test or a confidence interval for the primary endpoint.

The Safety Analysis Set is described as participants who received the study vaccine. The record does not provide a fuller endpoint definition, such as detailed criteria for event attribution, adjudication, or handling of multiple events in one participant. Accordingly, the posted counts should be read as the registry’s reported participant counts, not as evidence about causation or as a complete measure of all possible safety outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

A participant count records how many people in an analysis group experienced an event that met the stated definition. It is distinct from a count of all event episodes: one person may experience more than one event, while a participant-based outcome generally counts that person as an affected participant. The registry identifies the outcome unit as participants and describes the safety population as people who received the study vaccine. Its serious-event summary reports 204 affected participants in the primary-vaccination group and 59 in the booster-vaccination group.

A count is easiest to interpret alongside the number at risk or analyzed in the same group. The registry lists 6851 at risk for the primary-vaccination group and 3149 for the booster-vaccination group. Those denominators provide context for the counts, but no rate or percentage should be inferred from them unless it is explicitly reported. In particular, the numerical counts alone do not establish a difference in risk.

Why does the study design matter for comparison?

Randomization is a design method that aims to make comparison groups similar, on average, with respect to both measured and unmeasured characteristics. This study was non-randomized. Its groups were formed according to prior vaccination history, and both received the study vaccine. Thus, a comparison between their observed counts is not equivalent to a randomized treatment comparison.

In general, confounding occurs when characteristics associated with group membership also relate to the outcome. The registry’s group definitions establish that vaccination histories differ, but the record does not report enough participant characteristics or an adjusted analysis to evaluate the influence of other differences. Consequently, a contrast between the groups would be descriptive, not a causal estimate of the effect of vaccination history or vaccine exposure.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a specified model and sampling framework. A narrower interval indicates greater precision under those assumptions; a wider interval indicates less precision. For safety counts, intervals may be useful when converting counts to an estimate such as a proportion, but their interpretation depends on the analysis population, event definition, and method used.

The registry record does not report confidence intervals for the serious-event counts. It also does not report p-values or a formal test comparing the vaccination-history groups. Without those inferential quantities, the results support a description of observed counts, not a conclusion about statistical significance or the precision of a group difference.

Why are uncommon safety events challenging to characterize?

In general, rare events can be difficult to estimate precisely because relatively few observations contribute information about them. A study may document events that occur during follow-up while still leaving substantial uncertainty about how frequently they would occur in a broader population. The size of an observed count alone does not establish whether an event was caused by vaccination; attribution requires an appropriate clinical and analytical framework, which is not detailed in the registry record.

Serious adverse events and Grade 3 severe events are not interchangeable labels. Seriousness refers to a regulatory or clinical classification of an event, while severity describes the intensity of an event. The study objectives refer to serious adverse events through Day 60 and Grade 3 systemic adverse events through 30 minutes. The primary outcome title brings both terms together, but the record does not supply detailed definitions or separate endpoint results for all components. Interpretation should preserve that distinction rather than treating every serious event as Grade 3 or every severe event as serious.

What do the planning calculations mean?

In general, a sample-size calculation describes the amount of information a future study might need under specified assumptions. It is not a result observed in the current study. The registry’s planning illustration is described as using the observed effect, two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. Such planning calculations depend on those assumptions and are not evidence that the study had a particular probability of detecting an effect.

Any displayed planning values should therefore be read as illustrations for hypothetical future studies, not as observed power for this completed study. The registry record does not report a study-specific sample-size justification or show that the trial was designed to detect a particular safety difference. A sample-size illustration based on an observed effect also does not resolve confounding in a non-randomized comparison.

What is not available for reproducing an analysis?

The registry record reports no analyses for the outcomes in the analysis summary. It does not report a detailed statistical plan, handling of missing observations, adjustment for covariates, interim analyses, or methods for accounting for repeated events. Those details matter because they can affect which participants and events contribute to a result and how uncertainty is quantified.

In general, over-dispersion is relevant when count data vary more than a chosen statistical model expects; it can make standard errors too small if the model does not account for that extra variation. The registry record does not report a count model or a model-based comparison, so over-dispersion is not an established feature of the posted analysis. It is a general consideration for analyses of event counts, not a finding from this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple safety outcomes, including serious adverse events, adverse events of special interest, and Grade 3 systemic adverse events. When several outcomes are tested, the chance of at least one apparently unusual result can increase if each is assessed separately. Statistical methods can address this issue when confirmatory testing is planned, but the registry record does not report a multiplicity adjustment or a hierarchy of inferential tests.

The analysis summary reports no analyses. No p-values, confidence intervals, or formal group comparisons are reported in the record. It is therefore not possible to determine whether multiplicity was relevant to any inferential conclusions or how it might have been handled. The event counts remain descriptive rather than results from a reported family of hypothesis tests.

The stated analysis population is the Safety Analysis Set, defined as participants who received the study vaccine. The registry does not describe how missing safety information was handled, whether every participant had complete follow-up through the full stated period, or whether the number at risk changed during follow-up. It also does not report an imputation method or a sensitivity analysis for missing data. These details are important because incomplete follow-up can affect the opportunity to observe events.

The record’s enrollment entry is 10000, but the primary outcome description defines the assessed population by receipt of vaccine and inclusion in the Safety Analysis Set. The registry does not provide a separate endpoint-specific analysis count beyond the at-risk counts in the serious-event summary. The distinction between enrollment and an outcome-specific analysis population should be retained when interpreting 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

Serious events with the highest arm-level rate: gastroenteritis (0.4%), febrile convulsion (0.4%), pneumonia (0.4%), bronchitis (0.3%), influenza (0.2%).

The serious adverse-event summary lists 6851 participants at risk and 204 affected participants in the primary-vaccination group, and 3149 at risk and 59 affected participants in the booster-vaccination group. These counts describe the registry’s reported serious-event experience in the two groups. They are not a randomized comparison and should not be read as evidence that one vaccination-history group has a higher or lower causal risk.

The registry also lists serious-event terms and percentages: gastroenteritis, febrile convulsion, and pneumonia at 0.4% each; bronchitis at 0.3%; influenza at 0.2%; and pharyngitis at 0.1%. These are the percentages attached to the terms in the registry record. The record does not explain the denominator or whether the list is exhaustive, so the figures should be interpreted in that limited descriptive context.

In general, safety-event counts depend on event definitions, follow-up, and how events are collected and classified. The record describes follow-up through Day 60 for serious adverse events but does not give further detail on adjudication or attribution. The counts establish what the registry reports, not whether an event was caused by IMOJEV®.

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

The results provide a descriptive account of serious adverse events reported among people who received IMOJEV® in a post-licensure study. They distinguish participants by prior vaccination history and report the number at risk and the number affected in each group. This information contributes to characterization of safety events observed in the study setting.

The results do not establish that vaccination caused a reported event. Events occurring after vaccination are not necessarily caused by vaccination, and the registry record does not report an attribution analysis that would answer that question. Nor do the counts establish that an event could not occur outside the observation period or in a different population.

The two groups are not randomized treatment arms. Both received the vaccine, and membership was defined by vaccination history. The registry specifically cautions that the arms are not a like-for-like control comparison. Differences in their counts should not be presented as an estimate of a treatment effect, a booster effect, or a causal effect of prior vaccination.

The record does not report confidence intervals, p-values, or adjusted comparisons for these safety outcomes. It therefore does not quantify the precision of a group contrast or provide a basis for declaring that a difference is statistically significant. The available results are event counts and listed terms, not a complete comparative analysis.

The study’s objectives cover more than one safety concept and timeframe: serious adverse events, including adverse events of special interest, through Day 60, and Grade 3 systemic adverse events up to 30 minutes. The reported serious-event counts should not be treated as a complete result for every endpoint named in the registry. The record does not provide enough detail to resolve every element of the primary outcome title or to determine how all outcome components were analyzed.

In short, the findings are useful as descriptive safety information from the vaccinated study population. They do not answer every question about causation, comparative risk, or safety in populations not represented in the record. Those distinctions are essential when moving from observed counts to broader conclusions.

13. Why This Trial Matters Statistically

Post-licensure safety studies address a different statistical purpose from randomized efficacy trials. They can describe safety events after a product is used in a defined setting and can help characterize the types of events recorded during follow-up. This study’s focus on serious adverse events and severe immediate systemic events reflects that descriptive safety role.

The study also illustrates why the design behind a comparison matters as much as the counts. Its primary-vaccination and booster-vaccination groups were defined by prior vaccination history, not randomly assigned. That means the group labels carry differences in prior exposure by design, and a simple contrast cannot be interpreted as if the groups differed only in one assigned intervention. The registry’s explicit caution against treating the arms as like-for-like is therefore central to statistical interpretation.

Another useful lesson is the distinction between a reported count and an inferential result. A count documents observed participants with events, while a comparative estimate with an uncertainty interval would address a different question. The record reports serious-event counts but no inferential group analysis, confidence intervals, or p-values. Readers should not supply those missing inferential conclusions themselves.

The study’s outcome wording also highlights the importance of precise endpoint definitions. Seriousness and severity describe different properties, and the registry objectives assign them different follow-up windows. A clear interpretation must keep those concepts and windows separate rather than treating all safety events as one interchangeable outcome.

Finally, planning illustrations are not evidence of observed power and do not repair design limitations. In this record, any sample-size planning values are described as hypothetical calculations under specified assumptions. They cannot turn a non-randomized descriptive study into a controlled comparison or establish the precision of unreported analyses.

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 comparative interpretation is the non-randomized design. The groups were formed by prior vaccination history, and both received IMOJEV®. The registry cautions that the arms are not a like-for-like control comparison. As a result, their observed counts cannot isolate a causal effect of vaccination or of vaccination history.

The registry record does not report a detailed statistical analysis plan, adjusted comparisons, confidence intervals, p-values, or analyses for the listed outcomes. It also does not report how missing safety observations were handled, whether follow-up was complete for all participants, or whether event counts were adjusted for differences in observation time. These omissions limit assessment of precision and potential bias.

Endpoint detail is limited. The primary outcome title refers to Grade 3 immediate systemic adverse events and serious adverse events, while the objectives describe separate event categories and time windows. The record does not provide detailed definitions, attribution procedures, or separate numerical results for every component. The serious-event counts therefore should not be assumed to represent all components of the outcome title.

The registry lists enrollment as 10000, while the safety analysis population is described as participants who received the vaccine. The record does not report the endpoint-specific analyzed population in a way that fully explains the relationship between enrollment and each outcome. The serious-event summary does give at-risk counts by group, but it does not provide further detail on the flow of participants or missing follow-up.

Finally, the serious-event terms are accompanied by percentages without a full explanation of their denominator or reporting method in the record. Those values are best treated as descriptive registry entries rather than as fully documented comparative incidence estimates.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Post-licensure Safety Study of IMOJEV® in Thailand — NCT01981967.
• Registry record last updated 2016-05-04; status last verified 2016-03.
• Results first posted 2016-05-04.
• 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

NCT01981967 is a completed, non-randomized, unmasked, parallel Phase IV post-licensure safety study of IMOJEV® in Thailand. The registry records enrollment as 10000 and identifies primary-vaccination and booster-vaccination groups defined by prior Japanese encephalitis vaccination history.

The study aimed to describe serious adverse events, including adverse events of special interest, through Day 60 after one dose, and Grade 3 systemic adverse events up to 30 minutes after vaccination. The Safety Analysis Set is described as participants who received the study vaccine.

The serious-event summary reports 204 affected participants among 6851 at risk in the primary-vaccination group and 59 among 3149 at risk in the booster-vaccination group. The registry cautions that these non-randomized arms are not a like-for-like control comparison. No inferential analyses are reported in the registry record, so the counts are descriptive and do not establish causation or a comparative treatment effect.