Study of Safety and Immunogenicity of Fluzone® in Healthy Children: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Safety and Immunogenicity of Fluzone® in Healthy Children (NCT00831675), a non-randomized phase 4 study. The primary outcome is Number of Participants With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation.

2. Clinical Question

The study question is descriptive: what safety reactions and immune responses were observed among healthy children receiving the specified two-dose schedule? It is not a randomized treatment-effect question. Age groups can be described separately, but a difference between them would not by itself establish that age caused a difference in reactions or immune response. The registry record gives the primary outcome definition and the population used for the safety analysis, but does not give the primary outcome counts or numerical immunogenicity results. Consequently, the clinical question is clear while its posted numerical answers are incomplete.

3. Trial Design

NCT00831675 is a completed Phase 4, parallel-group study sponsored by Sanofi Pasteur, a Sanofi Company. The recorded study start is 2004-09, and primary completion is 2006-04. Enrollment was 30. The registry describes the study as non-randomized and unmasked, with two age-defined groups rather than randomized treatment arms.

Infants younger than 12 months were aged at least 6 months and younger than 12 months at enrollment. Toddlers were aged at least 12 months and younger than 36 months. Participants in each group received two doses of the 2004-2005 pediatric formulation of Fluzone®. Thus, age is the basis for grouping, while the vaccine schedule is shared. The registry record does not describe a placebo group, an untreated group, or another vaccine comparator.

The study’s stated aims were to describe safety and immunogenicity following the two-dose schedule. The primary safety outcome counted participants with solicited local and systemic reactions during Days 0-3 after vaccination. The safety population is described as all enrolled and vaccinated subjects with available reaction data, identified in the registry as the intent-to-treat population. That wording makes availability of reaction data part of the stated analysis population; the registry does not explain how unavailable reaction data were handled.

Non-randomized allocation and the absence of masking are important context for interpretation. This design can document observed outcomes in the enrolled children, but it does not provide a randomized contrast that isolates a treatment effect. The age-group descriptions are not equivalent to a control comparison. The registry record does not report a detailed statistical analysis plan, a sample-size justification, or interim analyses. Those design details should therefore not be inferred from the study’s Phase 4 designation or from its stated aims.

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 30 participants who met the inclusion and exclusion criteria were enrolled and vaccinated.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety analysis was on all enrolled and vaccinated subjects with available reaction data, intent-to-treat population

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 With Solicited Local and Systemic Reactions After Vaccination With Fluzone® 2004-2005 Pediatric Formulation, measured over Days 0-3 Post-dose.

The primary endpoint is the number of participants with solicited local or systemic reactions after vaccination with the 2004-2005 pediatric formulation of Fluzone®. The specified observation window is Days 0-3 post-dose. The listed local reactions are erythema, bruising, induration, and pain at the injection site. The listed systemic reactions are fever, irritability, crying, lethargy, decreased appetite, diarrhea, vomiting, and rash. The registry describes these reactions as collected daily for four days after each injection.

This endpoint is a participant count: it concerns whether a participant had a solicited reaction, rather than the total number of reaction episodes or a continuous measurement. In general, such a safety endpoint is useful for describing how commonly prespecified symptoms were recorded in a study population over a defined observation period. Specifying the symptoms and collection window helps make the outcome interpretable and provides a consistent framework for recording reactions.

The posted registry information defines the endpoint but does not report its numerical results. It therefore does not establish how many participants experienced each reaction, how many experienced any solicited reaction, or the severity or duration of reactions. The endpoint definition alone is not a result. The registry’s separate adverse-event counts should not be assumed to be the primary endpoint counts, because the record does not state that they use the same definitions or observation window.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study uses a parallel structure, but its groups are defined by age rather than by randomized allocation to different treatments. Both groups received the same vaccine schedule. This distinction matters: a parallel design can organize observations into groups, but it does not by itself make those groups comparable for causal inference. Because allocation was non-randomized, the age groups should not be interpreted as a vaccine group and a control group.

What does a participant count represent?

The primary outcome is expressed as a number of participants with solicited reactions. This is a binary outcome at the participant level: a participant either meets the outcome definition or does not, according to the recorded reaction data and the analysis rules. In general, a count is interpretable only alongside its denominator and a clear definition of what qualifies as an event. Here the registry defines the reaction categories and the post-dose observation window, but it does not report the primary outcome counts or their denominators in the outcome results described for this analysis.

Counting participants is different from counting episodes. A participant with more than one listed symptom may still contribute only once to an endpoint defined as the number of participants with any qualifying reaction. Whether that is how the registry’s endpoint was operationalized is not reported in the registry record. The record also does not give separate counts for each listed symptom, so symptom-specific frequencies cannot be inferred.

Why does the age-group structure limit comparisons?

Random assignment is one way to reduce systematic differences between groups, on average. This study is recorded as non-randomized, and its two groups differ by age definition. Even if group-specific outcome counts were available, a difference in those counts would not alone identify a causal effect of age, vaccination, or any other factor. General statistical methods can adjust for measured characteristics, but no adjusted analysis is reported in the registry record. Nor does the record describe a control condition.

Masking is recorded as none. In general, awareness of treatment or study participation can affect reporting or assessment of outcomes, particularly for symptoms that depend on observation or participant and caregiver reports. The record does not describe additional procedures for limiting such influence. This is a design consideration, not evidence that reported reactions were biased.

How should uncertainty be understood?

In general, a confidence interval gives a range of values compatible with the observed data under the statistical method used. Wider intervals indicate less precision, while narrower intervals indicate greater precision. An interval is not a guarantee that the true value lies within its limits, and its interpretation depends on the method and assumptions. No confidence intervals for the primary endpoint or adverse-event counts are reported in the registry record. Precision therefore cannot be assessed from the listed counts alone.

In general, a p-value measures how incompatible data are with a specified statistical model or null hypothesis, assuming that model and hypothesis. It does not measure the probability that a treatment works, nor does it describe the size or practical importance of an effect. No p-values or inferential analyses are reported in the registry record. A significance threshold mentioned as an assumption for a planning illustration is not evidence that a trial result met that threshold.

What can planning calculations show?

Sample-size calculations are planning tools that relate a target effect, a statistical method, and assumptions such as allocation and significance level to a prospective enrollment requirement. They are not a measure of what a completed study observed. The stated planning illustration is based on the observed effect, assumes equal allocation between two arms, a two-sided significance level of 0.05, and a normal approximation; it describes target effects as fractions of the observed effect. The registry record does not give a sample-size justification from the study’s original design. Any planning illustration should therefore be understood as a hypothetical calculation, not as proof that the original enrollment was adequate or as observed power.

For time-to-event outcomes, one general planning approach relates event totals to the ability to detect a difference over time. The primary outcome in this study is a participant count, not a time-to-event measure. The registry record does not describe a time-to-event analysis for this outcome. More generally, planning results depend on their assumptions and should not be treated as observed study findings.

What is not documented?

The registry record contains no analyses. It does not report the statistical test or model used for the primary endpoint, any adjustment for participant characteristics, any confidence intervals, or any missing-data method. It does not report interim analyses or a detailed statistical analysis plan. In general, a statistical plan identifies the intended population, endpoint definitions, analysis methods, and handling of incomplete observations before results are interpreted. Without those details, readers should not infer a method from the outcome’s binary format or from the study’s design label.

The registry’s description of the safety population includes all enrolled and vaccinated subjects with available reaction data and calls it an intent-to-treat population. In general, analysis-population labels can have different operational definitions across studies. The wording does not clarify how participants with incomplete reaction records were handled, whether all enrolled participants received both doses, or whether the immunogenicity population was the same as the safety population. Those matters are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, while the analysis information records zero analyses. A list of outcomes does not by itself show which outcomes were tested, how they were prioritized beyond the stated primary outcome, or whether formal hypothesis tests were planned. The registry record does not report a multiplicity adjustment or a strategy for controlling false-positive findings across outcomes or reaction categories.

In general, when many outcomes or comparisons are examined, the chance of obtaining at least one apparently unusual result can increase. Methods for addressing multiplicity depend on the questions and analysis plan; none is documented in the registry record. Because no inferential results are recorded, there are no posted p-values to interpret as a family of tests.

For safety, the analysis population is described as all enrolled and vaccinated subjects with available reaction data, identified as intent-to-treat. The record does not state how unavailable reaction data were handled, how many observations were missing, or whether missingness differed by age group or reaction. It also does not give the number of participants with complete data for the primary endpoint. These details are relevant because the endpoint depends on recorded symptoms during a defined period.

The registry record does not describe imputation, sensitivity analyses, or other methods for incomplete observations. It also does not clarify the analysis population for immunogenicity. These are not grounds to assume that a particular method was or was not used outside the registry; they are simply limitations of the documented record. The posted information supports a description of the stated analysis population, but not an evaluation of missing-data handling or multiplicity control.

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 serious adverse-event listings show 0 affected participants among 12 at risk in the infants group and 0 among 18 at risk in the toddlers group. These are counts for the recorded groups, not estimates of risk with reported uncertainty. The registry lists no top serious adverse-event terms. Death counts are not reported in the registry record.

The other adverse-event listings show 11 affected participants among 12 at risk in the infants group and 14 among 18 at risk in the toddlers group. The record does not provide the event terms or further details needed to interpret these counts, such as event severity, timing, duration, or whether events were considered related to vaccination. They should not be equated with the solicited local and systemic reactions in the primary endpoint, whose defined observation period is Days 0-3 post-dose.

In general, a zero count in a study group means no affected participants were recorded in that group; it does not establish that the underlying event is impossible or that risk is exactly zero. The size of the group and the absence of a comparison condition also limit what can be concluded. These safety figures are descriptive registry entries, not a randomized comparison or a complete account of all safety outcomes.

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

The record describes a study of safety and immunogenicity in healthy children aged 6 months to less than 36 months who received two doses of the 2004-2005 pediatric formulation of Fluzone®. It defines a primary safety outcome based on solicited local and systemic reactions during Days 0-3 post-dose. It also records serious and other adverse-event counts for the two age groups. These details identify what the study set out to observe and provide a limited descriptive safety account.

The record does not report numerical results for the defined primary endpoint or immunogenicity. It therefore does not show how frequently the solicited reactions occurred, what immune responses were measured, or how precise any estimates were. The adverse-event counts do not fill that gap because the record does not establish that they use the primary endpoint’s definitions or collection window.

The study cannot provide a randomized comparison of vaccine versus no vaccine: both age groups received the vaccine, and allocation was non-randomized. Any observed difference between the age groups would not, by itself, demonstrate that age caused the difference. The record reports no adjusted analyses or inferential results that might address group differences.

In general, a completed study can contribute descriptive information even when the registry record does not contain all outcome results. But study completion, Phase 4 status, and a stated objective are not substitutes for numerical findings. The appropriate conclusion is bounded by what is actually recorded: the design and outcome definitions are available, selected adverse-event counts are posted, and important primary and immunogenicity results are not reported in the registry record. No claim about benefit, lack of benefit, or comparative effect follows from these entries alone.

13. Why This Trial Matters Statistically

This study illustrates why the design structure matters as much as the outcome label. It has two parallel age groups, but both receive the same vaccine schedule and allocation is non-randomized. Those groups can organize descriptive reporting, yet they do not create a randomized treatment contrast. Recognizing that distinction prevents age-group counts from being misread as evidence for or against a treatment effect.

It also illustrates the difference between an endpoint definition and an endpoint result. The registry carefully identifies solicited reactions and the post-dose collection window, but the numerical results for that primary outcome are not reported in the registry record. A clear definition improves interpretability, but it cannot supply the missing event counts or their precision.

Safety counts require context. The serious adverse-event listings include zero affected participants in each group, alongside nonzero counts for other adverse events. Without uncertainty estimates, fuller event descriptions, and details of completeness, these values are descriptive rather than definitive. The record’s unavailable-data wording also makes it important to distinguish the stated analysis population from a fully documented account of who contributed data to each endpoint.

Finally, the record demonstrates the limits of drawing conclusions from study status or stated aims. A completed Phase 4 study can still have incomplete outcome reporting in its registry record. Statistical interpretation depends on the documented estimates, analysis methods, and uncertainty—not simply on the trial label, enrollment, or whether the study is marked completed. This is a useful example of reading registry entries conservatively and separating what was planned, what was recorded, and what can actually be inferred.

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 numerical results for the primary solicited-reaction endpoint and for immunogenicity are not reported in the registry record. The primary outcome is defined, but its participant counts are absent from the information available for this analysis. The record therefore does not permit assessment of the frequency or precision of the primary safety outcome or the magnitude of immune responses.

The study is non-randomized, unmasked, and organized by age. Both groups received the same two-dose vaccine schedule, so there is no randomized comparator. Age-group differences, if calculated, would be descriptive and could reflect differences other than age. No adjusted analysis is recorded.

The registry describes the safety population as enrolled and vaccinated subjects with available reaction data, but does not report completeness by outcome or explain the handling of missing observations. It does not report whether the immunogenicity analysis used the same population. No statistical tests, confidence intervals, or analysis models are recorded, and the registry includes zero analyses. Multiplicity handling, interim analyses, and a detailed statistical analysis plan are not reported in the registry record.

The serious and other adverse-event counts are limited by the detail recorded. The registry does not report deaths, event timing, severity, duration, attribution, or a list of serious event terms. The other-event counts cannot be assumed to represent the solicited-reaction endpoint. The study’s enrollment was 30, but the record does not give a study-specific sample-size justification. The planning illustration is not the original design justification and should not be interpreted as observed power. Taken together, these limitations constrain the record to design description and selected descriptive safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Safety and Immunogenicity of Fluzone® in Healthy Children — NCT00831675.
• Registry record last updated 2016-04-14; status last verified 2016-04.
• Results first posted 2009-08-27.
• 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

NCT00831675 is a completed Phase 4, non-randomized, unmasked, parallel study of the 2004-2005 pediatric formulation of Fluzone® in healthy children aged 6 months to less than 36 months. Enrollment was 30. Infants younger than 12 months and toddlers aged at least 12 months but younger than 36 months each received two doses.

The primary outcome was the number of participants with solicited local and systemic reactions during Days 0-3 post-dose. Numerical results for that endpoint and for immunogenicity are not reported in the registry record. The adverse-event listings record 0 serious-event-affected participants among 12 infants and 0 among 18 toddlers; other adverse events affected 11 infants and 14 toddlers. Death counts are not reported. The non-randomized age groups do not constitute a treatment-control comparison, and the registry records no analyses.