Study to Monitor the Safety and Reactogenicity of Fluarix™ in Korean Subjects Aged > 6 Months of Age.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Monitor the Safety and Reactogenicity of Fluarix™ in Korean Subjects Aged > 6 Months of Age. (NCT00750360), a non-randomized phase 4 study. The primary outcome is Number of Participants Reporting Severe Unsolicited Adverse Events.

2. Clinical Question

The study’s stated purpose was to collect safety and reactogenicity data in the local target population, in keeping with a Korean Food and Drugs Administration requirement. The primary outcome focuses on severe unsolicited events: the record defines severe events as those that prevent normal, everyday activities. It also lists outcomes covering solicited local and general adverse events, unsolicited adverse events, and serious adverse events.

This is a descriptive safety question rather than a comparative efficacy question. The record does not specify a treatment contrast against an unvaccinated group or another vaccine. Differences among the listed groups may reflect their age and prior-vaccination status, as well as other factors; the design does not establish that those groups are exchangeable. Accordingly, the main statistical reading is the event count reported within each group, not a causal comparison between groups.

3. Trial Design

The registry identifies this as a phase 4, non-randomized, parallel study with no masking. Fluarix™ is the listed biological intervention. The record gives enrollment as 883 and status as completed. The study start is listed as 2003-10-03, and primary completion as 2007-12-01.

Participants were organized into six groups according to age and prior influenza vaccination. The unprimed groups were subjects older than 6 months and younger than 72 months, and subjects aged 72 months or older and younger than 108 months. The primed groups were subjects older than 6 months and younger than 72 months; subjects aged 72 months or older and younger than 108 months; subjects aged 108 months or older and younger than 216 months; and subjects aged 216 months or older. The record defines unprimed as not previously vaccinated against influenza and primed as having previously received influenza vaccination.

Because allocation was non-randomized and the groups are defined by participant characteristics rather than assigned treatments, their outcomes should not be read as a controlled treatment comparison. The registry explicitly cautions that the arms are not a like-for-like control comparison. Masking is listed as none, so the record does not describe blinded outcome assessment.

The primary endpoint concerns severe unsolicited adverse events during the 21-day follow-up after vaccination. Other listed outcomes address solicited local and general adverse events by age category, unsolicited adverse events, and serious adverse events. The brief summary says the study collected local safety and reactogenicity data and identifies a target of 600 or more subjects in connection with the stated regulatory requirement. The registry record does not report further details of recruitment procedures, follow-up completeness, or the operational procedures used to collect events.

The record does not report a sample-size justification, randomization procedure, statistical analysis plan, interim analyses, or prespecified methods for adjusting comparisons. The study’s descriptive design and reporting of participant counts are therefore central to interpreting the posted results.

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

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 Number of Participants Reporting Severe Unsolicited Adverse Events, measured over During the 21-day follow-up period (Day 0 to Day 20) after vaccination.

The primary endpoint is the number of participants reporting severe unsolicited adverse events during the 21-day follow-up period, defined as Day 0 to Day 20 after vaccination. The registry’s general adverse-event definition is an untoward medical occurrence in a clinical investigation subject that is temporally associated with use of a medicinal product, whether or not considered related to that product. For this endpoint, severe events are defined as events that prevent normal, everyday activities.

An unsolicited-event endpoint captures events that are not being counted as solicited local or general reactions under the separately listed outcomes. The registry record does not give a more detailed definition of how an event was classified as solicited or unsolicited, or how severity was assessed beyond the stated definition. It also does not report an adjudication process or a measure of agreement between assessors.

Counting participants with an event is a binary-outcome approach: each participant is classified according to whether they reported the specified event during the defined observation period. This can make a safety summary straightforward to interpret, but a participant count does not convey the full clinical description, duration, recurrence, or consequences of every event. The endpoint is used to describe reported safety experience, not to establish a causal effect relative to an untreated or alternative-treatment group.

The posted primary results show one participant with a severe unsolicited adverse event in the unprimed group older than 6 months and younger than 72 months, and no such participants in the other listed groups. Those counts should be read with their group-specific denominators and the study’s non-randomized design in mind.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

For a binary outcome, each participant is classified into one of two categories for the outcome definition: the event was reported during the observation period, or it was not reported. The registry’s primary endpoint uses this framework by counting participants with severe unsolicited adverse events. The number at risk gives the group denominator associated with that count. Such a summary is direct, but it does not describe each event’s duration, recurrence, or clinical course. Those details are not reported in the registry record.

How should zero counts be read?

A zero observed count is an observation about the participants represented in the posted results. It is not evidence that the underlying event probability is exactly zero. In general, a confidence interval expresses uncertainty around an estimate and can show how much precision the data support. No confidence intervals for the primary group counts are reported in the registry record. Therefore, the reader should not treat the observed zeros as proof that severe unsolicited events cannot occur in those groups.

Why does the design matter for comparisons?

Random allocation is a design method for making treatment groups comparable, on average, with respect to measured and unmeasured participant characteristics. This study is listed as non-randomized. Its groups are also defined by age and prior influenza vaccination, and the record states that the arms are not a like-for-like control comparison. Consequently, a difference in counts between groups cannot be interpreted as a causal effect of the vaccine or as a clean comparison of treatment strategies. Descriptive comparisons can still show what was recorded in each group, but they do not remove confounding or selection differences.

What does no masking imply?

The registry lists masking as none. In general, masking can reduce the influence of expectations on event reporting, clinical assessment, or outcome classification. Without masking, participants and study personnel may know the treatment being given. The record does not describe specific measures used to limit reporting or assessment bias, so the extent to which such procedures were used is not reported in the registry record. This is a consideration when interpreting reported events, particularly outcomes that depend on symptom reporting or judgment about severity.

What are the other listed safety outcomes?

The registry lists outcomes for solicited local and general adverse events in subjects younger than 72 months and subjects aged 72 months and older, as well as unsolicited adverse events and serious adverse events. These categories describe different aspects of safety reporting. Solicited events are listed separately from unsolicited events, and serious events are a distinct outcome category from the primary endpoint’s severe events. The registry record does not give the full operational definitions for every category, so those distinctions should not be extended beyond the descriptions recorded.

What can be inferred from the analysis information?

The record lists zero analyses. This indicates that no statistical analyses are listed in the registry record; it should not be interpreted as proof that no analyses were performed. No inferential test, adjusted estimate, confidence interval, or model specification is reported for the primary endpoint. Without a reported model or analysis plan, there is no basis in the record for describing covariate adjustment, handling of clustering, or a prespecified hierarchy of hypotheses.

In general, over-dispersion matters when observed variability in count data exceeds what a model assumes. A model that fails to account for over-dispersion can give uncertainty estimates that are too small. That concept is relevant to some count-data analyses, but the primary outcome is reported as participants with a binary event, and the registry record does not describe a count model or a dispersion analysis. No conclusion about over-dispersion can be drawn from the posted information.

How should sample-size planning be separated from results?

The registry’s 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, a normal approximation, and target effects expressed as fractions of the observed effect. For non-time-to-event outcomes, the stated planning convention is participants per arm for a power target. Such calculations are planning illustrations, not observed power and not evidence that the study was designed with those assumptions. The registry record does not report the trial’s own sample-size justification. Nor does the available information establish that the study had a randomized two-arm comparison; its listed design is non-randomized and its groups are not like-for-like controls.

In general, power is a property of a planned statistical test under specified assumptions. It is not a retrospective measure of whether a result is reliable. A calculation using an observed effect can be especially sensitive to how that effect was estimated. Therefore, a planning illustration should not be used to claim that the completed study had adequate or inadequate observed power. The registry record does not report the design assumptions underlying the study’s enrollment target beyond the stated brief summary.

Overall, the methods information supports a restrained reading: observed participant counts can be described by group, but inferential conclusions require design and analysis details that are not reported in the registry record. A confidence interval, adjusted comparison, or causal estimate should not be inferred where none is reported.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Unprimed, > 6 to < 72 Months", "Unprimed, ≥ 72 to < 108 Months", "Primed, > 6 to < 72 Months", "Primed, ≥ 72 to < 108 Months", "Primed, ≥ 108 to < 216 Months", "Primed, ≥ 216 Months")
n      <- c(294, 1, 384, 79, 46, 71)
events <- c(0, 0, 0, 0, 0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Unprimed, > 6 to < 72 Months  294  0  0.0  0.0  1.2  0.0  1.3  0.0  1.2
ARM  Unprimed, ≥ 72 to < 108 Months  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Primed, > 6 to < 72 Months  384  0  0.0  0.0  1.0  0.0  1.0  0.0  1.0
ARM  Primed, ≥ 72 to < 108 Months  79  0  0.0  0.0  4.6  0.0  4.6  0.0  4.5
ARM  Primed, ≥ 108 to < 216 Months  46  0  0.0  0.0  7.7  0.0  7.7  0.1  7.5
ARM  Primed, ≥ 216 Months  71  0  0.0  0.0  5.1  0.0  5.1  0.0  5.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several safety outcomes: the primary count of participants reporting severe unsolicited adverse events, solicited local and general adverse events split by age category, unsolicited adverse events, and serious adverse events. When many outcomes are examined, the chance of at least one apparently unusual result can increase. Statistical methods sometimes address this multiplicity through prespecified outcome hierarchies or adjustments, but no multiplicity strategy is reported in the registry record.

The record lists zero analyses and does not provide a statistical analysis plan, hypothesis-testing procedure, or adjusted estimates. This does not establish that analyses were not done; it means they are not listed in the registry. The posted outcomes are therefore best read as descriptive summaries rather than as a collection of confirmed statistical tests.

Missing-data handling is not reported in the registry record. The record does not describe how participants with incomplete follow-up, missing event reports, or other unavailable outcome information were handled. It also does not report whether follow-up was complete for every participant in each group. Without those details, the listed counts cannot be used to assess the possible influence of missing observations.

Analysis populations are not reported in the registry record. No named intention-to-treat, per-protocol, or safety population is specified. The group-specific numbers at risk are available for the adverse-event summaries, but the record does not explain any exclusions or how those denominators were determined. These gaps limit assessment of the relationship between enrollment, follow-up, and the population included in each outcome summary.

12. 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: kawasaki's disease (0.3%).

Serious adverse events are a separate outcome from the primary endpoint of severe unsolicited adverse events. The posted serious-event counts show one participant in the unprimed group older than 6 months and younger than 72 months, and zero participants in each of the other listed groups. The corresponding numbers at risk are given by group. These are counts within the registry’s age and prior-vaccination categories, not comparisons against an untreated control.

The record names Kawasaki’s disease as the top serious-event term and reports 0.3% for that term. It does not provide further context for that percentage in the recorded details. The death fields are not populated, so deaths are not reported in the registry record; a blank or unavailable value should not be treated as confirmation that no deaths occurred.

Seriousness and severity should not be used as synonyms. The primary endpoint’s severe-event definition refers to events preventing normal, everyday activities, while the listed serious adverse event outcome is reported separately. The registry does not provide a detailed seriousness definition in the posted information. The counts summarize what was recorded over the study’s reporting and follow-up procedures, whose additional details are not reported in the registry record.

These small group counts do not establish that serious events cannot occur. They also do not establish a causal relationship to vaccination, since the registry’s general event definition includes events whether or not considered related to the medicinal product.

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

The posted results describe reported adverse events in a non-randomized study of Fluarix™ in Korean subjects, organized by age and prior influenza-vaccination status. For the primary endpoint, one participant in the unprimed group older than 6 months and younger than 72 months reported a severe unsolicited adverse event during the 21-day follow-up period. The other five groups have zero reported participants for that endpoint. This is a description of the recorded outcome, not a comparison with an unvaccinated group.

The results do not establish that the vaccine caused any particular reported event. The registry’s general event definition includes occurrences whether or not they are considered related to the medicinal product. The record does not provide a causal assessment for the primary event count. Likewise, a zero count in a group does not prove that the underlying event cannot occur, especially when no interval estimates are reported.

The study does not establish comparative safety against another vaccine, placebo, or no vaccination. It is non-randomized, has no masking, and groups participants by age and prior vaccination. Those characteristics prevent the group counts from functioning as a like-for-like treatment comparison. The posted information also does not report adjusted estimates or formal statistical tests.

The findings are specific to the outcomes as recorded: severe unsolicited events, other unsolicited events, solicited local and general events, and serious adverse events. They do not summarize every possible safety outcome or establish the frequency of events beyond the reported observation and collection procedures. Details of missing-data handling, analysis populations, and the statistical plan are not reported in the registry record.

Accordingly, the most defensible interpretation is that the registry documents a small number of reported events for the specified outcomes and groups, with the primary result concentrated in one listed group. The design and reporting support descriptive safety monitoring in the study population. They do not by themselves establish that Fluarix™ does or does not cause an adverse event, nor do they establish the absence of rare or unrecorded events.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of a safety-monitoring question that is primarily descriptive. Rather than estimating a treatment effect against a randomized control, the registry records adverse-event counts in age and prior-vaccination groups. That distinction matters because the same numerical contrast can have very different meaning depending on how the groups were formed. Non-randomized groups defined by participant characteristics do not supply the exchangeability that a randomized comparison is designed to support.

The endpoint also illustrates why safety summaries need precise definitions. The primary outcome counts participants with severe unsolicited events, and severity is described in terms of interference with normal, everyday activities. Separate outcomes address solicited reactions and serious adverse events. Keeping those categories distinct prevents a count from being misread as an estimate of all safety concerns or as a count of only medically serious events.

Rare or infrequent outcomes are difficult to characterize precisely from simple event counts. A zero count is useful descriptive information, but it is not proof of zero underlying risk. Confidence intervals or other uncertainty estimates can help readers understand the range of values compatible with observed data; none are reported for the primary endpoint in the registry record. The absence of such estimates makes it especially important not to overstate what group-level counts establish.

The registry also illustrates the importance of transparent analysis reporting. Statistical methods, analysis populations, missing-data procedures, and multiplicity handling are not reported. Those omissions do not negate the value of collecting local safety data, but they constrain what can be inferred from the posted results and how reproducible an inferential analysis would be. The record’s stated purpose is local safety and reactogenicity monitoring; its design and reporting are best understood within that descriptive purpose.

15. 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.

Several features specific to this study constrain interpretation. Allocation is non-randomized, masking is listed as none, and the arms are organized by age and prior influenza-vaccination status. The registry expressly cautions that they are not a like-for-like control comparison. Consequently, between-group differences cannot be attributed to the vaccine or interpreted as controlled treatment effects.

The primary outcome is reported as participant counts, without confidence intervals, formal tests, or adjusted estimates in the registry record. The primary endpoint covers severe unsolicited adverse events during the 21-day follow-up period; it does not describe all possible safety outcomes or event experience beyond that period. Detailed event-collection procedures and definitions for all secondary safety categories are not reported.

The record does not report missing-data handling, follow-up completeness, analysis populations, a statistical analysis plan, or multiplicity procedures. It lists zero analyses, but that does not establish that no analyses occurred outside the registry. The study’s own sample-size justification is not reported in the registry record; the brief summary states a target of 600 or more subjects in relation to the stated local requirement, but this does not explain a statistical design calculation.

Finally, the serious-event listing includes a reported top term and percentage, while death values are not populated. The registry does not supply further detail to clarify those fields. These limitations mean that the posted figures are most appropriately treated as reported descriptive safety information, not as a complete or causal assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Monitor the Safety and Reactogenicity of Fluarix™ in Korean Subjects Aged > 6 Months of Age. — NCT00750360.
• Registry record last updated 2018-11-06; status last verified 2016-11.
• Results first posted 2009-06-02.
• 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.

19. Record Summary

NCT00750360 is a completed phase 4, non-randomized, parallel study of GlaxoSmithKline’s Fluarix™ in Korean subjects. Masking is listed as none, and enrollment is recorded as 883. The study start is 2003-10-03, with primary completion on 2007-12-01.

The study’s stated purpose was to collect local safety and reactogenicity data in the target population in connection with a Korean Food and Drugs Administration requirement. Participants were grouped by age and prior influenza-vaccination status. The primary endpoint was the number reporting severe unsolicited adverse events during the 21-day period from Day 0 to Day 20 after vaccination.

The posted primary counts show one participant in the unprimed group older than 6 months and younger than 72 months, and zero in each of the other listed groups. The registry also lists solicited local and general adverse events, unsolicited adverse events, and serious adverse events. Because the study was non-randomized and its groups are not like-for-like controls, the results are descriptive rather than a controlled treatment comparison. Statistical analysis, missing-data, and analysis-population details are not reported in the registry record.