Study of a Live Attenuated Chikungunya Vaccine in a Previously Epidemic Area: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of a Live Attenuated Chikungunya Vaccine in a Previously Epidemic Area (NCT03101111), a randomized phase 2 study. The primary outcome is Number of Participants With AEs and Abnormal Lab Values, Vital Signs, and PE Findings.

2. Clinical Question

3. Trial Design

This was a randomized, quadruple-masked, parallel-group phase 2 study of MV-CHIK and MMR vaccine. The registry lists an enrollment of 34 and the status as completed. The study started on 2017-08-09, with primary completion on 2019-04-02. The setting was described as a previously epidemic area, and the participants as healthy volunteers.

The intervention descriptions include placebo injections alongside the assigned vaccine. For the MV-CHIK arm, subjects were scheduled to receive two injections on study day 0 and one injection on day 28; the vaccine dose is stated as 5E+05 (+/- 0.5 log) TCID50 intramuscularly in the deltoid muscle on both days. For the MMR arm, the description also specifies two injections on day 0 and one on day 28, with placebo injections and MMR vaccine administered by the routes described in the registry. The arm-description text for the MV-CHIK placebo injection is incomplete, so its full administration details are not reported in the registry record.

The brief summary describes an intended allocation of 80% to MV-CHIK and 20% to MMR vaccine. The adverse-event results are divided by vaccine group and serostatus. The registry does not report the randomization procedure, how masking was maintained, or whether the intended allocation was achieved. Those operational details should not be inferred from the group labels or counts alone.

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

Analysis population for the primary outcome, as defined in the registry: The intent-to-treat (ITT) population included all subjects who were randomized and received at least 1 dose of IVP. The ITT population was used for the safety analyses. Subjects were reported based on actual vaccine received.

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.

Population: MV-CHIK group: 12 seropositive, 14 seronegative subjects MMR-Placebo: 4 seropositive, 4 seronegative subjects

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With AEs and Abnormal Lab Values, Vital Signs, and PE Findings, measured over Throughout the whole study period (until day 392 after first dose).

The primary endpoint is the number of participants with adverse events and specified abnormal safety findings. The registry description includes solicited and unsolicited adverse events, grade 2 and higher events, and clinically significant abnormal safety laboratory results, vital signs, and physical examination findings. It describes these outcomes across the study period, through day 392 after the first dose, and frames the safety comparison in terms of previously exposed versus unexposed individuals.

Counting participants with an event is a way to describe how many people experienced at least one event within the defined outcome category. It differs from counting every event: a participant with multiple events may still contribute once to a participant count, depending on the endpoint’s coding. The record does not give enough detail to establish how repeated events were handled or how overlapping event categories were combined.

Safety is the primary focus in the brief study summary. The registry also identifies immunogenicity as a secondary outcome and says immune response and viremia will be assessed. The specific endpoint definitions, measurement schedules, and results for those secondary assessments are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the design as randomized, quadruple-masked, and parallel-group. These labels describe design features, not the statistical procedures used to analyze outcomes. The statistical analysis plan, including the model used for the primary outcome, is not reported in the registry record. No analysis estimates or hypothesis-test results are reported in the information available for this analysis.

What does a participant count measure?

A participant count records how many people meet an outcome definition. For a safety endpoint, the definition may combine events reported by participants with laboratory, vital-sign, or examination findings. Such a count is useful as a direct description of the number of participants affected, but it does not communicate how many events occurred in total, how long events lasted, or how severe each event was unless those features are separately reported. The registry describes several components but does not provide a breakdown of the posted group counts by component.

Participant counts can also conceal differences in follow-up. A count is most interpretable when the eligible population, observation period, and rules for event attribution are clear. The registry gives the overall safety period through day 392 after first dose and defines the safety population, but detailed handling of incomplete follow-up and recurrent events is not reported.

Why does randomization matter?

In general, randomization is intended to reduce systematic differences between groups at the time of assignment. It does not guarantee that small groups will have similar characteristics, and it does not remove uncertainty from sparse outcome counts. The registry states that assignment was randomized, but it does not report the randomization sequence, stratification factors, or allocation-concealment procedure. The record therefore supports identifying the study as randomized, but not reconstructing how assignment was implemented.

What does masking contribute?

In general, masking can reduce the chance that knowledge of assignment influences participant reports, clinical assessments, or other study procedures. The registry labels the study quadruple-masked, but does not identify which roles were masked or describe the procedures used to preserve masking. The label is informative about the stated design, while the operational details are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval communicates a range of values compatible with an estimate under a specified statistical method. It helps readers assess precision rather than treating a point estimate as exact. No confidence intervals are reported for these safety counts. A zero observed serious-event count in a group is not the same as evidence that the true event risk is zero; the size of the group and the observation process affect how much can be learned from no recorded events.

In general, a significance test evaluates data against a specified null hypothesis and assumptions. A p-value, when reported, is not the probability that a treatment is safe or effective. The registry record does not report p-values or a testing procedure for the primary outcome. No adjusted comparisons should be inferred from the descriptive counts.

What can planning calculations tell readers?

In general, a sample-size calculation depends on the assumed effect, variability or event frequency, allocation, significance level, and analysis method. The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. These are illustration assumptions, not evidence that the trial was designed with those assumptions, and the record does not report a sample-size justification for the original study. Planning illustrations are not observed power and do not change the interpretation of the trial’s actual counts. No numerical planning results should be treated as observed trial outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy for handling the several safety categories, time points, or exposure-status comparisons described for the primary endpoint. When many outcomes or comparisons are considered, general statistical practice recognizes that the chance of at least one apparently notable result can increase. Whether and how that issue was addressed in this trial is not reported in the registry record. The posted data do not provide a set of inferential tests from which to assess such adjustments.

Missing-data procedures are also not reported in the registry record. The endpoint spans follow-up through day 392 after the first dose, but the information available does not describe how participants with incomplete follow-up, missing assessments, or unavailable laboratory measurements were handled. It does not state whether missing values were imputed, excluded from particular summaries, or treated in another way. No assumption about those procedures is warranted.

The registry defines the intent-to-treat population as all subjects who were randomized and received at least 1 dose of investigational vaccine product. It states that this population was used for safety analyses and that subjects were reported according to the vaccine actually received. This is the registry’s stated analysis population and classification rule. The record does not report the number of randomized participants who did not receive a dose, nor does it give further details about exclusions or deviations from assigned treatment.

The registry lists no analyses in the analysis field. That absence does not establish which analyses were performed outside the registry; it means that analysis details and inferential results are not reported in the registry record. Consequently, the safety entries should be treated as descriptive registry results, not as a substitute for an unreported statistical analysis plan.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event entries show 0 affected participants in each listed group. The associated numbers at risk are 12 for MV-CHIK/seronegative, 14 for MV-CHIK/seropositive, 4 for MMR/seropositive, and 4 for MMR/seronegative. The registry lists no serious-event terms. These observations describe what was recorded during the study; they do not rule out uncommon events or establish equal risk across groups.

The record also lists other affected-participant counts: 11 of 12, 13 of 14, 4 of 4, and 4 of 4 in the corresponding groups. These counts should be kept distinct from the serious-event counts. The registry does not provide the underlying event terms in the information, so the figures cannot be interpreted as a count of a particular symptom, diagnosis, or severity category.

In general, safety counts depend on the event definitions, collection methods, and follow-up completeness. The registry provides a broad primary-endpoint description and a study period through day 392 after first dose, but does not provide detail sufficient to reconstruct each participant’s event history. Comparisons should therefore remain descriptive.

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

The posted results establish that the registry records no serious adverse events among the participants in any of the reported vaccine-by-serostatus groups. They also show other affected-participant counts in every listed group. This is a description of the recorded experience in this study, not a definitive comparison of safety between MV-CHIK and MMR vaccine.

The counts do not show the nature, duration, or severity distribution of the other events, and the registry does not provide a component-by-component account of the broad primary endpoint. Nor does it report confidence intervals, adjusted comparisons, or a statistical test for the endpoint. The precision of any difference between groups therefore cannot be judged from the posted results. Small group counts make the descriptive evidence particularly limited.

The study was conducted in healthy volunteers in a previously epidemic area, with results grouped by serostatus as well as vaccine. The findings should be interpreted within that population and design. The registry record does not provide enough information to determine how these results apply to other populations or settings. No conclusion about immune response or viremia can be drawn from the safety counts; although the brief summary says those measures would be assessed, their results are not reported in the registry record.

More broadly, an absence of observed serious events is not proof that a risk cannot occur. Conversely, counts of participants with other events do not identify whether the vaccine caused those events. Interpreting causation requires event details, appropriate comparisons, and analysis procedures, which are not fully. The appropriate reading is therefore limited: the record provides descriptive safety counts, but not a complete inferential assessment or a basis for a treatment recommendation.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a safety question and a fully reported safety analysis. The primary endpoint combines participant-reported adverse events with specified clinical and laboratory findings, and it spans a long follow-up period through day 392 after the first dose. Such breadth can be useful for surveillance, but it also makes clear definitions, component-specific reporting, and transparent analysis procedures important for interpretation.

The study is randomized and quadruple-masked according to the registry, features that are relevant to reducing bias in general. Yet the posted information does not describe how randomization or masking was implemented, and the reported groups are small, particularly for MMR. Design labels alone do not resolve uncertainty in the observed counts or supply the missing comparative analysis.

The record also illustrates why zero serious-event counts need careful wording. They communicate that no serious events were recorded in the listed groups, while the limited group sizes and absence of interval estimates prevent a strong conclusion about the range of possible underlying risks. Reporting the count and its denominator is more informative than stating only that no events occurred, but event details and precision estimates would add important context.

Finally, the registry distinguishes safety as the primary purpose from immunogenicity as a secondary outcome, and the brief summary mentions viremia. Without reported results for those secondary measures or an analysis plan for the primary endpoint, readers should separate the study’s stated aims from the conclusions supported by the posted data. This distinction is central to sound interpretation of clinical-trial results.

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 registry record does not report a formal sample-size justification for the original study. It describes a planning illustration based on an observed effect and specified statistical assumptions, but that illustration should not be mistaken for the trial’s design rationale or for evidence of adequate precision. The group counts themselves remain limited, especially in the MMR groups.

The primary outcome is described as covering multiple event types and time points, including adverse events and clinically significant abnormalities in laboratory results, vital signs, and physical examinations. The posted group counts do not separate these components, and the registry indicates that the outcome was not reduced to one comparison. This makes it difficult to identify which observations drive the overall safety picture.

The registry does not report confidence intervals, hypothesis tests, adjusted estimates, event-level details, or a statistical analysis plan. It also does not describe procedures for missing data, incomplete follow-up, repeated events, or multiplicity. These omissions limit assessment of precision, robustness, and the intended interpretation of the comparisons.

The record describes a healthy-volunteer population in a previously epidemic area and reports groups by serostatus. It does not provide detailed participant characteristics or enough information to assess how well the groups were balanced. The randomization and masking procedures are not described beyond their design labels. The MV-CHIK arm-description text is incomplete, limiting reconstruction of all administration details. Finally, although immunogenicity is listed as a secondary outcome and the brief summary mentions viremia, their results are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of a Live Attenuated Chikungunya Vaccine in a Previously Epidemic Area — NCT03101111.
• Registry record last updated 2021-07-19; status last verified 2018-09.
• Results first posted 2021-07-19.
• 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

NCT03101111 is a completed randomized, quadruple-masked, parallel-group phase 2 study of MV-CHIK compared with MMR vaccine in healthy volunteers in a previously epidemic area. The registry lists enrollment of 34, a study start date of 2017-08-09, and primary completion on 2019-04-02. The primary outcome concerns participants with adverse events and specified abnormal safety findings through day 392 after first dose. Immunogenicity is listed as a secondary outcome.

The posted serious-event counts are 0 in each reported vaccine-by-serostatus group. Other affected-participant counts are also recorded, but detailed event terms and inferential comparisons are not reported. The registry defines an intent-to-treat safety population based on randomization and receipt of at least 1 dose, with reporting according to vaccine received. Statistical analysis, missing-data, and multiplicity procedures are not reported in the registry record, so the results support descriptive rather than definitive comparative conclusions.