A Dose-ranging Pediatric Study of an Adjuvanted Pandemic Influenza Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Dose-ranging Pediatric Study of an Adjuvanted Pandemic Influenza Vaccine (NCT04669691), a randomized phase 2 study. The primary outcome is Safety Endpoint 1: Percentages of Subjects With Solicited Local and Systemic Adverse Events (AEs).

2. Clinical Question

The study was designed as a pediatric dose-ranging evaluation of safety and immunogenicity across different MF59-adjuvanted H5N1 vaccine formulations. Its central comparison is across vaccine groups, rather than between a vaccine and an untreated group. The formulation labels distinguish dose level and adjuvant content, but the registry record does not give the actual antigen or MF59 quantities represented by those labels. It therefore does not support an interpretation about specific numerical dose levels.

The safety question is time-bounded: solicited local and systemic events were collected in the 7-day periods after each vaccination. The record specifies assessment by total population and age cohort. It also lists immunogenicity outcomes, but numerical results for those outcomes are not reported in the registry record. The primary endpoint is described as descriptive, without prespecified inferential analyses. Consequently, the clinical question can be framed, but the record does not establish a formal statistical test comparing the formulations.

3. Trial Design

This was a Phase 2, randomized, observer-blind, multicenter, parallel-group study. The registry record lists quadruple masking, but does not specify which participants or study personnel were masked. Enrollment was 420, and the study status is completed. The recorded start date is 2020-12-19 and the primary completion date is 2022-04-15.

The six groups received H5N1 antigen combined with MF59 adjuvant. Group descriptions distinguish lowest, low, and mid dose formulations, each represented with less adjuvant or as an adjuvanted formulation. All six descriptions specify two consecutive intramuscular administrations on Day 1 and Day 22. The actual antigen and adjuvant amounts are not reported in the registry record, so the group labels should not be treated as quantitative dose specifications.

Random allocation is intended to assign participants to groups by chance, supporting comparisons that are less dependent on participant or investigator choice. A parallel-group design means that the groups are compared as distinct treatment groups rather than through a crossover sequence. These are general design features; the registry record does not describe the allocation sequence, concealment procedures, or specific masking procedures. It also does not report the number of participating centers.

The primary endpoint concerns the percentages of subjects with solicited local and systemic adverse events in the specified post-vaccination windows. The registry description says that results are presented for the overall study population and by age cohort. The Solicited Safety Set includes subjects in the All Exposed Set with any solicited adverse-event information collected, including temperature measurements or use of analgesics or antipyretics. Secondary outcomes address HI and MN assay responses against the homologous H5N1 strain. Numerical findings for the primary solicited endpoint and the secondary immunogenicity endpoints are not reported in the registry record. The record also does not give details of the planned enrollment allocation across the six groups or the rationale for the chosen enrollment.

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: In total, 420 subjects were enrolled in the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Solicited Safety Set, defined as all subjects in the All Exposed Set with any solicited AE data collected, including temperature measurements or use of analgesics/antipyretics. Results are presented for the overall study population and for the 6 months to \<36 months and 3 years to \<9 years age cohorts.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety Endpoint 1: Percentages of Subjects With Solicited Local and Systemic Adverse Events (AEs), measured over Day 1 through Day 7 and Day 22 through Day 28.

The primary endpoint measures the percentages of subjects with solicited local and systemic adverse events. The registry defines the assessment periods as Day 1 through Day 7 and Day 22 through Day 28, covering the 7 days following each vaccination. It states that results are presented for the overall study population and by age cohort. The named safety population is the Solicited Safety Set: subjects in the All Exposed Set with any solicited adverse-event data collected, including temperature measurements or use of analgesics or antipyretics.

Solicited outcomes are events actively collected according to the study’s safety assessment, rather than only events that arise spontaneously in routine reporting. In general, reporting the percentage of participants with an event gives a direct description of how commonly the event was observed in the defined population and time window. That percentage depends on both the number of participants with recorded events and the population used as its denominator. The registry record does not provide the solicited local or systemic event counts or percentages, so their frequency cannot be described from this record.

The endpoint is useful for characterizing short-term reactogenicity after vaccination. It is not, by itself, an inferential comparison between formulations: the registry explicitly says the analysis was descriptive and that no prespecified inferential analyses were specified for this endpoint. The record does not report event severity grades or a separate endpoint definition for each solicited symptom.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as percentages of subjects with solicited local and systemic adverse events. It specifies two observation periods, Day 1 through Day 7 and Day 22 through Day 28, and states that the analysis was descriptive. No inferential analyses were prespecified for this endpoint. In practical terms, a descriptive analysis reports the observed event counts or percentages in the relevant population; an inferential analysis would additionally quantify uncertainty or formally compare groups. The registry record does not report inferential results for the primary endpoint.

For a binary outcome such as whether a participant experienced an event, a percentage is based on an event count and a denominator. Interpretation therefore depends on knowing which participants were eligible for inclusion and which participants had outcome data. The Solicited Safety Set is defined as all subjects in the All Exposed Set with any solicited adverse-event data collected, including temperature measurements or use of analgesics or antipyretics. This definition tells readers how the safety population is characterized, but the record does not report how missing individual solicited assessments were handled or the actual endpoint denominators by group.

In general, randomization can support fair comparisons by assigning participants to groups independently of their characteristics, on average. It does not guarantee that every measured or unmeasured characteristic will be balanced in a particular trial. The record identifies the study as randomized, but does not report sequence generation, allocation concealment, or baseline balance information. Similarly, observer-blind and quadruple masking describe aspects of blinding, but the registry record does not identify who was masked or how masking was maintained.

The study is parallel-group, with participants assigned among six vaccine formulations. Its group labels distinguish lowest, low, and mid dose and less-adjuvant or adjuvanted content. No exact antigen or MF59 amounts are stated. The two administrations are specified as intramuscular and scheduled on Day 1 and Day 22. The registry does not report adherence to the schedule, deviations, or whether all participants completed both administrations.

In general, confidence intervals express the range of values compatible with the observed data under a statistical model and can communicate precision. A confidence interval around a difference between groups would help show how uncertain that estimated difference is. The registry record does not report confidence intervals for the primary endpoint. A p-value, in general, quantifies how incompatible data are with a specified null model under the assumptions of a test; it does not measure the size or clinical importance of an effect. No primary-endpoint p-value or specified inferential test is reported.

For outcomes with multiple groups, comparisons can be framed in different ways: each group might be compared with a reference group, or all groups might be assessed together. The choice affects the number and interpretation of tests. The record does not specify a reference group or a formal comparison strategy for the primary endpoint. It lists 11 outcome measures and 0 analyses in the registry analysis information, and states that the primary endpoint was descriptive. The multiplicity approach, if any, for secondary immunogenicity outcomes is not reported in the registry record.

The secondary endpoints include geometric mean titers and geometric mean ratios from HI and MN assays. In general, geometric means are used for measurements that are positive and can be strongly right-skewed; analyses often use a logarithmic scale and then express results on the original scale. A geometric mean ratio compares geometric means across specified conditions or time points. The record names these measures but does not provide their analysis model, transformation details, confidence intervals, or numerical results. Seroconversion is defined as moving from a non-detectable titer to at least 1:40, or having a 4-fold increase from a detectable Day 1 titer. A further endpoint is the percentage achieving seroconversion with a titer of at least 1:40. These are outcome definitions, not reported findings.

Over-dispersion is a general issue for count outcomes when variability exceeds what a simple probability model assumes; it can make standard errors too small if ignored. That concept is not a description of the primary endpoint analysis in this trial: the record does not report a count model, a dispersion estimate, or an inferential model. The primary endpoint is presented as percentages and was analyzed descriptively. No model-based adjustment, covariate adjustment, or interim analysis plan is reported in the registry record.

The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is specified as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not a result of the trial. The primary endpoint has several categories or time points and was not reduced to one comparison, so it does not yield a single primary-endpoint comparison for this illustration. No sample-size justification for the trial’s original design is reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures and 0 analyses. It identifies one primary safety endpoint and several secondary immunogenicity outcomes, including geometric mean titers, geometric mean ratios, and seroconversion outcomes measured by HI and MN assays. The primary endpoint description explicitly says that the analysis was descriptive and that no prespecified inferential analyses were specified. A multiplicity strategy for the secondary outcomes is not reported in the registry record.

Multiplicity matters in general when several outcomes, time points, or group comparisons are assessed. Testing many hypotheses can increase the chance of obtaining at least one apparently notable result by chance. Prespecified control methods, such as prioritizing outcomes or adjusting inferential thresholds, can clarify how a collection of tests should be interpreted. No such method is reported for this study. Because numerical immunogenicity findings and inferential analyses are absent, the record does not allow assessment of how multiplicity may have affected interpretation.

The record defines the Solicited Safety Set and says that results are presented for the overall population and age cohorts. It does not report the number of participants with missing solicited measurements, the handling of missing diary or temperature information, or whether any imputation was used. It also does not report missing-data rules for the immunogenicity assessments. The All Exposed Set is named as the basis for the Solicited Safety Set, but a broader analysis-population strategy is not reported in the registry record.

The record does not describe interim analyses, stopping rules, or a statistical analysis plan. These details should not be inferred from the completed status or the listed endpoints. The available information supports recognition of the outcome families and safety population definition, but not a reconstruction of how missingness or multiplicity was handled in analyses that are not reported.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: animal bite (2.9%), pneumonia (1.4%), febrile convulsion (1.4%), thermal burn (1.4%), klebsiella infection (1.4%).

The posted safety counts distinguish serious adverse events, other adverse events, and deaths across six vaccine groups. For the lowest, low, and mid dose groups with less adjuvant, the serious-event counts were 0 of 69, 1 of 72, and 3 of 70, and the other-event counts were 37 of 69, 34 of 72, and 40 of 70. For the corresponding adjuvanted groups, the serious-event counts were 0 of 70, 1 of 69, and 3 of 70, and the other-event counts were 39 of 70, 37 of 69, and 33 of 70. The recorded death counts were 0, 1, 0, 0, 0, and 0 across the groups in the order listed in the registry.

These are counts of participants with events and their stated group denominators. They are not, by themselves, estimates of causal effects. The record does not report whether events were considered related to vaccination, their onset relative to each dose, their duration, or detailed case narratives. The serious-event terms listed include Animal bite at 2.9%, and Pneumonia, Febrile convulsion, Thermal burn, Klebsiella infection, and Septic shock at 1.4% each. The record does not provide enough context to interpret those terms as vaccine-related.

These serious-event figures are distinct from the primary solicited local and systemic adverse-event endpoint, whose numerical results are not reported in the registry record. They should not be substituted for that endpoint or treated as a complete account of short-term solicited reactions.

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

The record describes a completed randomized Phase 2 study comparing six H5N1 vaccine formulations in healthy pediatric subjects 6 months to < 9 years of age. It documents two intramuscular administrations on Day 1 and Day 22 and identifies a descriptive primary safety endpoint based on solicited local and systemic adverse events in the 7 days after each vaccination. Those features establish what the study set out to evaluate, but they do not provide the missing numerical results for the primary endpoint.

The posted serious adverse-event and other adverse-event counts allow a limited descriptive account of participants with reported events in each group. They do not establish that a formulation caused an event, nor do they establish that the groups differ. The registry record does not report event relatedness, a formal safety comparison, or uncertainty intervals for the counts. The listed serious-event terms and percentages also lack contextual details needed to attribute them to a vaccine formulation.

The secondary endpoint descriptions show that the study planned to evaluate immunogenicity through HI and MN assay measures, including geometric mean titers, geometric mean ratios, and seroconversion. However, the numerical immunogenicity results are not reported in the registry record. No conclusion about the size, precision, or comparative pattern of antibody responses can be drawn from endpoint names alone.

In general, a completed trial status indicates that the registry lists the study as completed; it does not mean all findings are available in the registry record or that every planned analysis can be assessed. Here, the primary endpoint is explicitly descriptive, and the record does not present prespecified inferential analyses for it. The available information therefore supports describing the design, endpoint definitions, and selected safety counts, but not claims that one formulation is safer, less safe, more immunogenic, or less immunogenic than another.

Interpretation is also limited by the absence of detailed dose quantities, group allocation procedures, missing-data handling, and a statistical analysis plan. These omissions do not negate the recorded design, but they constrain what can be independently evaluated. The appropriate conclusion is narrow: the registry provides a framework for understanding the trial and selected safety reporting, while important outcome results and analysis details are not reported.

13. Why This Trial Matters Statistically

This trial illustrates why the definition and reporting of an endpoint matter as much as its label. The primary outcome is not a single symptom or a single time point; it covers solicited local and systemic adverse events in two post-vaccination windows, with results intended for the overall population and age cohorts. The registry explicitly says that the analysis was descriptive. That distinction prevents readers from treating reported percentages, if available, as though they were prespecified inferential comparisons.

The study also has multiple formulation groups and multiple immunogenicity outcomes. In general, a collection of group, assay, and outcome comparisons requires a clear plan for specifying which comparisons answer the main question and how uncertainty is handled. The registry record names the outcomes but does not report a multiplicity strategy or inferential analysis plan. That absence makes it especially important to distinguish endpoint definitions from evidence about comparative effects.

Safety reporting contains more than one kind of information. Solicited events in defined follow-up windows address short-term symptoms gathered by active assessment, while serious adverse-event counts summarize a different safety category. The posted serious-event counts cannot stand in for the primary solicited endpoint, and neither set of counts alone establishes causality. Clear denominators, time windows, and population definitions are essential to interpreting each outcome.

Finally, this record shows the difference between a trial’s planned design and the information available for statistical interpretation. Randomization, masking, and parallel groups describe the study structure, while outcome counts, uncertainty estimates, missing-data rules, and analysis specifications determine how strongly comparisons can be assessed. When those results or methods are not reported, statistical conclusions should remain limited to the information actually documented.

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 numerical results for the primary solicited local and systemic adverse-event endpoint. Although the endpoint’s time windows, target population, and descriptive nature are stated, the counts and percentages by group and age cohort are absent. Numerical findings for the secondary immunogenicity endpoints are also not reported, limiting interpretation of antibody response patterns.

Group labels identify lowest, low, and mid dose formulations and distinguish less-adjuvant from adjuvanted formulations, but actual antigen and adjuvant quantities are not reported in the registry record. This prevents quantitative assessment of the dose levels. The record identifies the study as randomized, observer-blind, multicenter, parallel, and quadruple-masked, but does not explain allocation concealment, who was masked, the number of centers, or how masking was maintained.

For safety, the record lists serious and other adverse-event counts, deaths, and selected serious-event terms. It does not report event relatedness, timing, severity grading, case descriptions, or a formal comparison across groups. The event-term percentages are listed without a fuller explanation of their denominators in the record. Those details constrain interpretation and do not permit causal attribution.

The registry does not describe the original sample-size justification, interim analyses, missing-data handling, or a statistical analysis plan. It defines the Solicited Safety Set, but does not give the number of missing observations or rules for incomplete safety or immunogenicity assessments. It also does not report a multiplicity strategy for the secondary outcomes. These omissions limit reproducibility and prevent independent evaluation of planned versus completed analyses. The record states that the primary endpoint was descriptive, so inferential conclusions about group differences are not available from that endpoint description.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Dose-ranging Pediatric Study of an Adjuvanted Pandemic Influenza Vaccine — NCT04669691.
• Registry record last updated 2024-03-13; status last verified 2024-02.
• Results first posted 2024-01-16.
• 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

NCT04669691 is a completed randomized Phase 2, observer-blind, multicenter, parallel study sponsored by Seqirus. It enrolled 420 healthy pediatric subjects 6 months to < 9 years of age and evaluated six MF59-adjuvanted H5N1 vaccine formulations. Each group received two intramuscular administrations on Day 1 and Day 22.

The primary endpoint was the percentage of subjects with solicited local and systemic adverse events in the 7 days following each vaccination, assessed during Day 1 through Day 7 and Day 22 through Day 28. The registry describes the analysis as descriptive, with no prespecified inferential analyses. Secondary outcomes address HI and MN assay immunogenicity measures, including geometric mean titers, geometric mean ratios, and seroconversion.

The record includes selected serious and other adverse-event counts and death counts by group. Numerical results for the primary solicited endpoint and secondary immunogenicity outcomes, along with several analysis details, are not reported in the registry record.