Safety Study of CSL Limited's Influenza Virus Vaccine in the Paediatric Population Aged >= 6 Months to < 18 Years: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety Study of CSL Limited's Influenza Virus Vaccine in the Paediatric Population Aged >= 6 Months to < 18 Years (NCT00825162), a non-randomized phase 4 study. The primary outcome is Frequency and Intensity of Local and Systemic Solicited Adverse Events, Cohort A (6 Months to Less Than 3 Years).

2. Clinical Question

This is a safety and tolerability question, not a comparison of vaccine against an untreated or alternative-treatment group. The registry also lists secondary outcomes concerning unsolicited adverse events, serious adverse events, and new onsets of chronic illness. Those outcomes extend the safety description beyond the solicited events in the primary outcome, but the record does not provide a comparative treatment-effect question. Because the study is open label and has no separate control group, the observed event counts describe events recorded in the study population; they do not by themselves establish how those events compare with what would have occurred without vaccination.

3. Trial Design

The registry identifies this as a Phase IV, open-label, multi-centre study of CSL Limited Influenza Virus Vaccine in a paediatric population aged 6 months to less than 18 years. The recorded enrollment is 1992. The study began in 2009-03, had primary completion in 2010-02, and is listed as completed. Seqirus is named as the sponsor.

The design is non-randomized and single-group, with no masking. Participants are described in three age-based cohorts: Cohort A includes those aged 6 months to less than 3 years; Cohort B includes those aged 3 years to less than 9 years; and Cohort C includes those aged 9 years to less than 18 years. The registry lists CSL Limited Influenza Virus Vaccine as the intervention for each cohort. These cohort labels do not create randomized treatment groups or an untreated comparison group.

The primary outcome is titled as the frequency and intensity of local and systemic solicited adverse events for Cohort A, with a timeframe of 7 days post-vaccination. The registry also lists secondary outcomes for unsolicited adverse events, serious adverse events, and new onsets of chronic illness. It records 9 outcome measures and 0 analyses. The record does not report a statistical analysis plan, a sample-size justification for the study, or details of any interim analyses. Any planning illustration based on an observed effect should be read as a hypothetical design calculation, not as observed power or as evidence from a randomized comparison.

The Safety Population is described as participants who received CSL's IVV and provided at least one safety assessment after vaccination. The description adds a condition for safety analyses of solicited events after the second vaccination, but the registry text ends before completing that condition. Further details about the analysis population and handling of follow-up are not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Safety Population comprised all participants who received CSL's IVV and provided at least one safety assessment after vaccination. For the safety analysis of solicited AEs after the second vaccination, only those participants who received a second vaccination and provided safety follow-up after the second vaccination were included.

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 Frequency and Intensity of Local and Systemic Solicited Adverse Events, Cohort A (6 Months to Less Than 3 Years), measured over 7 days post-vaccination.

The primary endpoint concerns the frequency and intensity of solicited local and systemic adverse events in Cohort A, whose age range is 6 months to less than 3 years. The listed local events are pain, redness, and swelling/induration. The listed systemic events are fever, headache, myalgia, nausea/vomiting, diarrhea, loss of appetite, and irritability. The observation timeframe is 7 days post-vaccination.

Solicited events are specified in advance for active monitoring. This approach can make recording more consistent than relying only on spontaneous reports, because participants or caregivers can be asked about particular symptoms within a defined observation window. As a general statistical point, a short, defined window can help describe events temporally close to vaccination, while it cannot characterize events outside that window. The registry does not state the exact questioning schedule, event-grading criteria, or method used to collect these reports.

The endpoint is presented in terms of frequency and intensity, but the listed primary result information identifies the measure as a number of participants. The registry record does not provide the primary endpoint’s numerical results or an analysis estimate. It therefore does not permit a reader to determine from this record how often each solicited event occurred or how intensity was distributed. The secondary safety outcomes address different event categories and should not be treated as substitutes for the specified primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies the study as non-randomized, open label, and single-group. These features determine what statistical conclusions are available. A randomized comparison can balance measured and unmeasured characteristics on average, subject to the design and conduct of the trial. This study does not have that structure. Its safety results are therefore best read as event descriptions within the enrolled cohorts, rather than as estimates of differences caused by treatment relative to a control.

What does a single-group design estimate?

In general, a single-group safety study can count participants who experience specified events and describe when those events were monitored. Those counts can characterize the observed study experience. To estimate a contrast between treatments, researchers need suitable data for both treatment conditions and a defined comparison. That comparison is not reported in the registry record. No control event rate, relative effect, or treatment contrast is available to interpret.

The three age cohorts are not interchangeable comparison arms. They cover different age ranges, and the registry does not report a randomized allocation process between them. Differences in counts across cohorts can reflect differences in the number of participants under observation, age composition, follow-up, or event recording, among other possibilities. Without a prespecified comparative analysis and relevant supporting information, a raw difference in counts cannot isolate an age effect or a vaccine effect.

What do event counts and denominators convey?

A count reports how many participants were recorded with an event; its denominator indicates the group at risk as listed in the record. Reporting both is more informative than reporting a count alone, because the number observed depends in part on how many participants were followed. However, counts and denominators do not, by themselves, show how precise an estimated frequency is. A confidence interval could describe sampling uncertainty around an estimate under a stated method. No such intervals are reported in the registry record for these adverse-event figures.

For a participant-level binary outcome, a participant is classified as having or not having the event within the applicable definition and observation period. This is different from counting every occurrence if one participant can experience repeated events. The record describes the primary measure in terms of participants, but does not report enough detail to determine how repeated episodes, event severity categories, or multiple events within one participant were handled in the results.

Why does the observation window matter?

The primary outcome uses a defined period of 7 days post-vaccination. As a general principle, an observation window specifies which events are counted for that endpoint. Events outside it do not contribute to that particular window-based endpoint, even if they may be relevant to other safety outcomes. The registry also lists outcomes for unsolicited adverse events, serious adverse events, and new onsets of chronic illness, but their detailed timeframes and operational definitions are not reported in the registry record. The primary window should not be assumed to apply to every secondary outcome.

Solicited symptoms are named in advance: local events include pain, redness, and swelling/induration, and systemic events include fever, headache, myalgia, nausea/vomiting, diarrhea, loss of appetite, and irritability. In general, soliciting named symptoms can reduce reliance on a participant spontaneously deciding what to report. It does not remove the possibility of incomplete reporting, differences in interpretation, or variation in assessment. The registry does not describe the instruments, reporting frequency, or grading thresholds used for these symptoms.

What can be said about statistical testing?

The registry lists 0 analyses. The statistical analysis plan, any hypothesis tests, confidence-interval methods, and adjustment procedures are not reported in the registry record. A p-value, when available, measures how compatible data are with a specified null model under the assumptions of a test; it does not measure clinical importance or prove causation. No p-values are available, and the design does not supply a randomized control comparison to which a conventional treatment-effect test could be applied.

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such calculations are general planning exercises: they ask what size a hypothetical study might need under stated assumptions. They are not the observed power of this single-group safety study, do not represent its actual enrollment rationale, and do not create a valid control contrast where none is reported. The trial's own sample-size justification is not reported in the registry record.

Why can over-dispersion matter?

As a general statistical concept, over-dispersion occurs when the variability in data is greater than a chosen model assumes. It can make standard errors too small if a model fails to account for that extra variability, leading to confidence intervals that are too narrow or tests that appear more decisive than warranted. The primary measure in this record is a count of participants with events, not a reported event-rate model, and the registry does not describe a model for over-dispersion. It would therefore be inappropriate to infer that such a model was used or needed for the reported analyses.

Overall, the methods information supports a careful descriptive reading: event counts are recorded by cohort, the primary solicited-event window is stated, and the study design is clear. The inferential methods, detailed endpoint definitions, and precision estimates needed for a more complete statistical assessment are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures, including a primary solicited adverse-event outcome for Cohort A and secondary outcomes for unsolicited adverse events, serious adverse events, and new onsets of chronic illness. When many outcomes or event categories are examined, the chance of at least one apparently unusual finding can increase. As a general statistical matter, multiplicity procedures can address this issue by adjusting inference or by specifying which outcomes are primary. The registry record does not report a multiplicity strategy, an adjustment method, or a detailed hierarchy among the outcome measures.

The record identifies the primary outcome and its 7 days post-vaccination timeframe, but does not provide its numerical results or analysis details. It lists 0 analyses. The hypothesis-testing plan, confidence-interval approach, and any planned subgroup analyses are not reported in the registry record. The absence of these details does not show that a particular procedure was or was not used; it means that the procedure cannot be assessed from the record.

The Safety Population is described as participants who received CSL's IVV and provided at least one safety assessment after vaccination. The text also specifies that safety analysis of solicited events after the second vaccination includes only those who received a second vaccination and provided safety follow-up, but the description is incomplete. The exact eligibility condition, handling of participants without follow-up, and analysis populations for the other outcomes are not reported in the registry record.

Missing-data amounts, reasons for missing assessments, and methods for handling missing information are not reported in the registry record. In general, missing safety assessments can affect an observed frequency if participants with and without assessments differ in event experience or reporting. Without these details, the degree and direction of any such effect cannot be evaluated. The record also does not describe whether participants were analyzed according to a prespecified approach beyond the stated Safety Population definition.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: asthma (0.7%), pneumonia (0.3%), pharyngitis (0.3%), soft tissue infection (0.3%), bronchiolitis (0.1%).

The registry lists serious adverse events by cohort. Cohort A has 19 participants with a serious adverse event among 703 at risk; Cohort B has 5 among 875; and Cohort C has 2 among 398. These are counts of participants with an event as recorded, not a comparison with an unvaccinated group. The registry lists Asthma (0.7%), Pneumonia (0.3%), Pharyngitis (0.3%), Soft tissue infection (0.3%), Bronchiolitis (0.1%), and Croup infectious (0.1%) among the most frequent serious-event terms.

These data describe recorded events; they do not establish that vaccination caused an event, nor do they show what the event frequency would have been without vaccination. The record does not report a comparator group, event-attribution method, or uncertainty intervals for these figures. The listed percentages should be read as the registry's reported values, not as estimates recalculated from the cohort counts.

Additional adverse-event counts are listed as 531 among 703 in Cohort A, 467 among 875 in Cohort B, and 97 among 398 in Cohort C. The category definition and details of event-level handling are not reported in the registry record. Deaths are not reported in the registry record; this should not be interpreted as a reported count of zero.

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

The record shows that the study was designed to describe the safety and tolerability profile of CSL Limited Influenza Virus Vaccine in a paediatric population across three age cohorts. Its primary outcome focused on solicited local and systemic events in Cohort A during 7 days post-vaccination. The registry also records serious adverse events and additional adverse-event counts by cohort. These elements provide descriptive information about what the study monitored and the event counts it recorded.

The design does not establish a randomized treatment contrast. Because the trial is single-group and non-randomized, its event counts cannot show whether vaccination increased or decreased event frequency compared with no vaccination or another intervention. The counts also cannot, without suitable comparative data, distinguish events caused by vaccination from events that would have occurred for other reasons. This limitation is fundamental to the design, not a conclusion about the direction or magnitude of any treatment effect.

The registry record does not report numerical results for the primary endpoint’s frequency and intensity, despite describing its event list and observation timeframe. It also does not report confidence intervals, p-values, or a detailed analysis plan. Therefore, the precision of the primary outcome findings cannot be assessed from the record, and no inferential conclusion should be attributed to it. The serious-event counts and listed event terms are not substitutes for the primary outcome results.

Age-based cohort counts should not be interpreted as a comparison of risk across ages. The cohorts differ in age range and in their listed denominators, and no comparative analysis is reported. The registry also does not supply enough detail to evaluate missing safety assessments, event ascertainment, event grading, or the complete analysis population for follow-up after a second vaccination.

In practical statistical terms, the record supports a bounded reading: it identifies the safety questions, describes the population and design, and lists selected event counts. It does not establish causality, comparative safety, the absence of an event, or the precision of the primary endpoint estimate. These boundaries matter when interpreting any observed count as evidence about a vaccine.

13. Why This Trial Matters Statistically

This study is statistically notable as a large, open-label safety study in a broad paediatric age range, with outcomes organized into age-based cohorts. Its design illustrates how safety monitoring can be structured around specified symptoms and a defined period after vaccination. The primary endpoint names both local and systemic solicited events, while the registry also lists broader outcomes such as unsolicited adverse events, serious adverse events, and new onsets of chronic illness.

The record also illustrates an important distinction between descriptive surveillance and comparative inference. A single-group study can document events observed in participants, but it lacks the concurrent contrast needed to estimate how event frequencies differ under another treatment condition. Recording a denominator alongside event counts helps describe the data, yet it cannot replace a control group or determine causation.

The age cohorts make the population coverage easier to describe, but they should not be mistaken for comparison arms. Their age ranges differ, and no randomized allocation is reported. Statistical comparisons across such groups would require careful definitions and methods, and those analyses are not reported in the registry record.

Finally, the study highlights why registry transparency matters for interpreting safety findings. The record reports selected serious-event counts, but does not provide numerical results for the primary solicited-event endpoint, uncertainty estimates, detailed missing-data procedures, or a complete statistical analysis plan. Clear reporting of these elements would help readers judge both the event frequencies and their precision. In their absence, the appropriate interpretation remains descriptive and limited to the information recorded.

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 principal limitation is the non-randomized, single-group design. There is no separate comparator group, so the study cannot provide a controlled estimate of differences in adverse-event frequency. The open-label design also means that participants and study staff were not masked, although the registry does not describe how this may have affected safety reporting or assessment.

The primary outcome is specified for Cohort A and covers solicited events during 7 days post-vaccination. Numerical frequency and intensity results for that endpoint are not reported in the registry record. The registry also does not provide a detailed definition of intensity, a collection schedule, or the method used to determine whether an event was present. The results therefore cannot be fully interpreted against the endpoint description alone.

The Safety Population definition is incomplete regarding safety assessments after a second vaccination. The registry does not report the full rule for inclusion in that analysis, the handling of participants lacking follow-up, or missing-data methods. It also does not provide detailed outcome timeframes for all secondary measures. These omissions limit assessment of who contributed data to each safety outcome and how complete observation was.

Although 9 outcome measures are listed, the record states 0 analyses and does not report a statistical analysis plan, multiplicity approach, confidence intervals, or p-values. The serious adverse-event counts and selected event terms are descriptive; the record does not provide a comparative analysis or detailed attribution methods. Deaths are not reported in the registry record, which is not the same as reporting no deaths.

The record does not report the study's sample-size justification or interim-analysis plan. Further information about event ascertainment, follow-up beyond the primary timeframe, and handling of repeated events is also not reported in the registry record. These limitations restrict both causal interpretation and assessment of statistical precision.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety Study of CSL Limited's Influenza Virus Vaccine in the Paediatric Population Aged >= 6 Months to < 18 Years — NCT00825162.
• Registry record last updated 2018-05-23; status last verified 2018-04.
• Results first posted 2011-07-29.
• 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

NCT00825162 is a completed Phase IV, open-label, multi-centre, non-randomized, single-group study sponsored by Seqirus. It evaluated CSL Limited Influenza Virus Vaccine in a paediatric population aged 6 months to less than 18 years. Recorded enrollment was 1992; the study began in 2009-03 and primary completion was in 2010-02.

Participants were grouped into Cohort A (6 months to less than 3 years), Cohort B (3 years to less than 9 years), and Cohort C (9 years to less than 18 years). The primary outcome concerned the frequency and intensity of solicited local and systemic adverse events in Cohort A during 7 days post-vaccination. The registry lists 9 outcome measures and 0 analyses. Serious adverse-event counts and selected event terms are recorded by cohort, but the primary endpoint’s numerical results, inferential estimates, and detailed statistical methods are not reported in the registry record.