Safety and Immunogenicity of an Adjuvanted Trivalent Influenza Vaccine in Children 6 to <72 Months of Age in Mexico.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of an Adjuvanted Trivalent Influenza Vaccine in Children 6 to <72 Months of Age in Mexico. (NCT02255279), a randomized phase 3 study. The primary outcome is Number of Naive Subjects 6 to < 36 Months Old Reporting Solicited Local and Systemic Adverse Events (AEs) From Day 1 to Day 7 Following Each Vaccination..

2. Clinical Question

The study therefore addresses a safety question about solicited events following vaccination, while also examining immune-response outcomes. The listed secondary outcomes include seroconversion, geometric mean ratios of hemagglutination-inhibition titers, and the percentages of subjects reaching specified HI-titer thresholds. These outcomes are described for naive and non-naive subjects at day 1 and 21 days after the last vaccination.

Random allocation makes the vaccine-group comparison a randomized comparison, but the registry information available does not establish how all outcomes were analyzed or whether the analysis preserved the randomized groups. The record does not report a numerical primary-outcome estimate, a confidence interval, or a test result. As a result, the central safety question can be described from the outcome definition, but the size and precision of the primary comparison cannot be judged from the registry record.

3. Trial Design

This was a phase 3, randomized, parallel-group, multi-center study in Mexico. The registry describes triple masking and calls the study observed-blind. Enrollment was 287. The record lists influenza as the condition and identifies Novartis Vaccines as the sponsor. The study began in 2014-10, reached primary completion in 2015-05, and is marked completed.

Participants were assigned to receive either aTIV or TIV. The intervention descriptions distinguish participants by prior influenza-vaccination status: non-naive subjects were scheduled to receive one dose on day 1, while naive subjects were scheduled to receive a dose on day 1 and another on day 29. The registry's group descriptions also separate naive and non-naive subjects for safety reporting. The primary endpoint is narrower still, referring to naive subjects 6 to <36 months old.

Randomization is intended, in general, to reduce systematic differences between groups at the start of a trial. A parallel-group design assigns participants to a group that receives one of the interventions rather than comparing both interventions within each participant. Masking can reduce the influence of expectations on care, reporting, or assessment, although the registry record does not describe which roles were masked or how masking was implemented. The term observed-blind is included in the official study title, while the registry's design field states triple masking.

The record describes both safety and immunogenicity objectives. The primary outcome is a count of participants reporting solicited local and systemic adverse events over specified post-vaccination windows. Secondary outcomes concern HI antibody responses, including seroconversion, geometric mean ratios, and proportions meeting stated titer thresholds. The registry record does not report the full protocol, the allocation procedure, the centers involved, eligibility details beyond the age and population descriptions, or the operational definitions used for every immunogenicity outcome.

Enrollment is a trial-level figure, not a substitute for the denominator in each analysis. The listed safety groups have their own at-risk counts, and those counts differ by group. The registry record does not provide a complete participant flow or explain whether every randomized participant contributed data to every outcome. Group-specific counts should therefore be read in the context of the particular outcome and analysis population, rather than treated as a complete accounting of trial participation.

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: All enrolled subjects were included in study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis performed on the Solicited Safety 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 Naive Subjects 6 to < 36 Months Old Reporting Solicited Local and Systemic Adverse Events (AEs) From Day 1 to Day 7 Following Each Vaccination., measured over From Day 1 to Day 7 by vaccination.

The primary endpoint is the number of naive subjects 6 to <36 months old who reported solicited local or systemic adverse events. The registry defines the observation periods as day 1 to day 7 following each vaccination, and describes the second-dose period as day 29 to day 35. The outcome is expressed as a number of participants, not as an average symptom score or a measure of antibody response.

Solicited events are events specifically sought during a defined observation period. In general, collecting them systematically can make groups easier to compare than relying only on events volunteered without prompting. The period matters because an event count tied to a specified window answers a more focused question than a count covering an unspecified duration. However, the registry record does not provide the event checklist, severity grading rules, or the detailed method used to collect reports.

Participant counts are useful for describing how many people experienced an event, but a count alone does not show the full distribution of event types, intensity, duration, or recurrence. Nor does it identify whether the same participant reported more than one kind of event. The record's wording indicates that the primary outcome encompasses local and systemic events, but does not report the results separated by category in the primary outcome description.

The registry record does not report the primary endpoint's numerical results, a vaccine-group effect estimate, or a confidence interval. It also does not report a single primary comparison in a form that can be interpreted as one estimate. The endpoint definition is therefore clear enough to describe what was intended to be counted, but the recorded information does not establish the observed primary result or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

In general, randomization assigns participants to study groups using a chance-based process. Its purpose is to make pre-existing characteristics less likely to differ systematically between groups, so that later outcome differences can be interpreted more plausibly as related to the assigned interventions. Randomization does not guarantee that groups will be identical, and it does not by itself address missing outcomes, departures from assigned treatment, or errors in measurement.

The registry identifies this study as randomized and parallel-group. It does not report the sequence-generation method, allocation concealment procedures, stratification factors, or whether the reported outcome analyses followed the original randomized assignment. Those details are not reported in the registry record. The description of triple masking indicates that masking was part of the design, but the record does not identify which participants, investigators, assessors, or other roles were masked. In general, masking can reduce the possibility that knowledge of assignment influences participant reports or outcome assessment, but its practical effect depends on how it is implemented.

What does the primary outcome count?

The primary outcome is a participant count for solicited local and systemic adverse events among naive subjects 6 to <36 months old. The specified observation periods are linked to vaccination days: day 1 to day 7 following each vaccination, with the second period described as day 29 to day 35. This is a count-based endpoint. The registry's statistical classification also identifies the outcome type as binary, with the interpretation that it concerns participants with an event. In general, an event outcome can be represented for each participant as whether the event occurred, then summarized as the number of participants with an event within a group.

A group count is not, on its own, a comparative effect estimate. To interpret a difference between groups, readers would ordinarily need the relevant group results and an analysis that specifies the comparison measure and uncertainty. The registry record does not report a single primary comparison, its confidence interval, or a test result. It also does not report enough detail to establish how repeated observations across the vaccination windows were combined or whether local and systemic events were analyzed separately.

How should uncertainty be understood?

In general, an estimate is subject to sampling variability because the participants enrolled are only one realization of the population a study aims to inform. A confidence interval describes uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies in the interval, and it does not resolve possible bias from missing data, measurement, or study conduct. A p-value, when reported, describes how compatible the observed data are with a specified null model; it does not measure clinical importance or the probability that a hypothesis is true.

Neither a primary-outcome confidence interval nor a primary-outcome p-value is reported in the registry record. The absence of these reported quantities means the precision and statistical evidence for the primary comparison cannot be assessed from the registry information. It does not imply that a particular result was non-significant, nor does it establish that no analysis was conducted.

What do the planning assumptions mean?

The registry describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. Such a calculation is a planning exercise: in general, it asks how many participants per arm might be needed under specified assumptions to detect a chosen effect with a chosen power. It is not observed power, and it does not establish the trial's original design rationale.

The registry record does not report the trial's own sample-size justification, nor does it report a complete statistical plan. The calculated planning outputs are not included among the registry entries available for interpretation. As a result, no participant-per-arm planning figure or power value can be stated. Even when a planning illustration is available, its assumptions should be treated as hypothetical rather than as proof that a completed study was adequately powered for every endpoint.

In general, planning calculations depend on the anticipated event rate or effect, variability, allocation, significance level, desired power, and the selected analysis method. If an observed effect is used as the planning basis, the illustration can be sensitive to random fluctuation in that estimate. Planning for a smaller fraction of an effect generally requires more information than planning for the full effect, all else equal. This general principle does not supply a trial-specific sample size or justify a conclusion about this study's design.

Why do outcome definitions and analysis populations matter?

The primary endpoint is restricted to naive subjects in a particular age range, while the safety listings distinguish naive and non-naive subjects in groups described as 6 to <72 months. These populations should not be treated as interchangeable. In general, a result applies most directly to the population and observation window used to produce it. Differences in age range, prior vaccination status, event definition, and follow-up can change what a count represents.

The registry names the Solicited Safety Set as the population for the primary outcome. It does not define the membership rules for that set or report the number analyzed for the primary endpoint. The record also does not report how missing diaries, incomplete follow-up, or participants with partial observations were handled. These details affect denominators and can affect interpretation, especially when the outcome depends on participant reporting over a specified period.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary immunogenicity outcomes: seroconversion percentages, geometric mean ratios of HI titers, and the percentages of subjects reaching HI-titer thresholds of ≥ 40, ≥110, and ≥330. The listed assessments distinguish naive from non-naive subjects and include day 1 and 21 days after the last vaccination. These multiple outcomes and subgroup/time assessments create a multiplicity issue in general: the more statistical comparisons made, the greater the chance that at least one result may appear notable by chance if every comparison is judged separately.

The registry record does not report a multiplicity adjustment, a hierarchy of hypotheses, a prespecified testing sequence, or which secondary comparisons were confirmatory versus exploratory. It therefore does not establish how to interpret any collection of nominal test results. Numerical results and test statistics for the listed secondary outcomes are not reported in the registry record, so there is no basis for evaluating the pattern or consistency of those comparisons.

Missing-data handling is also not reported in the registry record. The record does not describe how unavailable event reports, missed visits, incomplete vaccination schedules, or missing laboratory measurements were handled. In general, missingness can affect both the number of participants contributing to an analysis and the comparability of groups. Its impact depends on why information is missing and on the analysis method; the direction and size of any effect cannot be assumed without data.

The primary outcome names the Solicited Safety Set, but the registry record does not define that set or provide its analysis denominator. It also does not report a full analysis-population description for the secondary outcomes. Consequently, the relationship between randomized assignment, vaccination received, and inclusion in each analysis cannot be assessed. These reporting gaps limit evaluation of multiplicity control, missing-data assumptions, and the population to which each outcome result would apply.

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% reporting threshold.

Most frequent non-serious adverse event terms

The safety listing reports zero serious adverse events in each of the four groups: naive aTIV, naive TIV, non-naive aTIV, and non-naive TIV. The corresponding at-risk counts are 77, 78, 67, and 64, respectively. These are descriptive counts in the registry record. The record does not report a comparative effect estimate or confidence interval for serious adverse events, so the counts should not be treated as a formal test of differences between groups.

The record lists other adverse events for the same groups: 58, 52, 35, and 31, respectively. These figures are separate from the serious-event counts and do not represent the primary solicited-event endpoint by definition. The registry record does not explain the full event categories, observation period, severity criteria, or how multiple events in one participant were counted in this listing. The serious adverse event follow-up duration is also not reported in the registry record.

In general, observing zero serious events does not prove that an event is impossible or that two groups have identical risk. The interpretation depends on the observation period, event definitions, number of participants at risk, completeness of follow-up, and statistical uncertainty. Those details are not fully reported for this listing. Death counts are not reported in the registry record.

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

The registry record establishes that the study randomized children in Mexico to adjuvanted or non-adjuvanted trivalent influenza vaccine and planned to assess safety and immunogenicity. It defines a primary safety outcome in naive subjects 6 to <36 months old and lists immunogenicity outcomes based on HI titers. It also reports descriptive serious and other adverse-event counts by naive or non-naive status and vaccine group.

What the record does not establish is the numerical result for the primary endpoint. It does not report a single primary vaccine-group estimate, a confidence interval, or a test result. Therefore, the registry information does not support a quantified statement about the size or precision of a primary safety difference. The listed serious-event counts are not a substitute for that endpoint, because they describe a different adverse-event category and are not accompanied by comparative uncertainty estimates.

The immunogenicity outcomes also cannot be interpreted comparatively from the available record because their numerical results are not reported. Naming seroconversion, geometric mean ratios, and HI-titer thresholds identifies what the study intended to evaluate, but does not itself establish the observed antibody responses or differences between vaccines. The study's objectives and outcome definitions should be distinguished from results.

In general, a randomized trial can provide evidence about comparative effects when outcomes are reported with clear definitions, analysis populations, estimates, and uncertainty. Interpretation also depends on completeness of follow-up, prespecified analyses, and the handling of multiple comparisons. The registry record does not report enough information to evaluate all of these elements. This does not show that the study failed to conduct analyses; it describes the limits of what the registry record reports.

The safety listings provide observed counts within the listed groups, not a complete account of every possible safety outcome or a full benefit-risk analysis. They do not establish that an intervention is effective or ineffective, and they do not provide medical guidance. The most defensible reading is limited to the study design, outcome definitions, and descriptive figures explicitly recorded, while recognizing that the primary comparative result and its precision are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable for the way its stated primary endpoint and its available safety listings address different questions. The primary endpoint concerns solicited local and systemic events in naive subjects 6 to <36 months old during specified windows after vaccination. The serious adverse event listing is a separate descriptive safety summary for naive and non-naive groups described across the broader age range. Keeping those endpoints distinct avoids treating a serious-event count as though it answered the primary solicited-event question.

The study also separates participants by prior vaccination status. That distinction is relevant to the planned dose schedule: naive subjects were scheduled for two doses, while non-naive subjects were scheduled for one. In general, subgroup-specific reporting can clarify whether results differ across populations, but it also creates additional comparisons and makes clear definitions of subgroup membership and analysis methods important. The registry record does not report a complete statistical plan for those comparisons.

Immunogenicity assessment adds another kind of endpoint to the safety objectives. Seroconversion, geometric mean ratios, and proportions meeting HI-titer thresholds capture different aspects of an antibody response. They are not interchangeable measures, and their interpretation depends on specified definitions and analysis methods. The record identifies these outcomes but does not report their numerical results.

For statistical readers, the central lesson is that design details and outcome definitions are not enough to evaluate comparative evidence. Effect estimates, uncertainty intervals, analysis populations, missing-data methods, and multiplicity decisions are also important. Those results and methods are not reported in the registry record for the primary comparison. The descriptive counts that are recorded can still be read accurately, but they should not be made to carry conclusions beyond their scope.

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 most direct limitation is that the registry record does not report a single numerical result for the primary endpoint, a vaccine-group effect estimate, a confidence interval, or a test result. Without those details, the primary comparison's direction, magnitude, and precision cannot be assessed. The endpoint itself includes specified event windows, but its numerical group results are not available in the registry record.

The primary outcome is defined for naive subjects 6 to <36 months old, while the safety group descriptions cover naive and non-naive subjects 6 to <72 months of age. The registry record does not report the number analyzed for the narrower primary population or a full participant-flow account. The at-risk counts in the adverse-event listing should not be assumed to be the primary endpoint denominators.

Important methods are not reported in the registry record: details of randomization and allocation concealment, the roles included in triple masking, the statistical analysis plan, multiplicity procedures, missing-data handling, and the complete rules for the analysis populations. The record also does not provide the solicited-event checklist, severity grading, or detailed methods for collecting the primary safety reports. These omissions limit assessment of how consistently outcomes were measured and how the analyses relate to randomized assignment.

The serious adverse event counts are descriptive, with no reported comparative uncertainty estimate or stated follow-up duration. The record lists other adverse-event counts but does not fully specify their categories or observation period. Death counts are not reported in the registry record. Numerical results for the named immunogenicity outcomes are also not reported. These reporting limitations restrict interpretation to the design and figures recorded and do not demonstrate what analyses may have been conducted outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of an Adjuvanted Trivalent Influenza Vaccine in Children 6 to <72 Months of Age in Mexico. — NCT02255279.
• Registry record last updated 2017-01-27; status last verified 2016-01.
• Results first posted 2016-02-03.
• 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

This completed phase 3 randomized, parallel-group study compared adjuvanted trivalent influenza vaccine with non-adjuvanted trivalent influenza vaccine in children in Mexico. Enrollment was 287. The registry describes triple masking, one dose for non-naive subjects, and two doses on day 1 and day 29 for naive subjects.

The primary outcome counts solicited local and systemic adverse events among naive subjects 6 to <36 months old during specified post-vaccination periods. Secondary outcomes concern HI seroconversion, geometric mean ratios, and titer thresholds. The registry lists serious adverse-event counts of zero in each group and provides counts for other adverse events.

A single numerical primary-outcome comparison, its uncertainty, and numerical results for the listed immunogenicity outcomes are not reported in the registry record. The record also does not report the full statistical plan or key details of missing-data and multiplicity handling.