Revaccination With Influenza Vaccine GSK1247446A: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Revaccination With Influenza Vaccine GSK1247446A (NCT00545025), a non-randomized phase 2 study. The primary outcome is Number of Subjects With Any, Grade 3 and Related Solicited Local Symptoms.

2. Clinical Question

3. Trial Design

This completed phase 2 study used a parallel-group, non-randomized design with no masking. Its stated focus was safety after revaccination. The registry record lists GlaxoSmithKline as sponsor and enrollment of 243. The study began on 2007-10-15, and primary completion was recorded on 2007-12-12.

The groups were defined by vaccination received in the earlier study, NCT00374842. Subjects aged 18-60 years who had previously received AS03-adjuvanted GSK1247446A received a further GSK1247446A dose with a half dose of AS03. Those previously vaccinated with Fluarix™ received another dose of Fluarix™. Thus, the current comparison also distinguishes participants by their prior vaccine history. The registry record does not describe randomized assignment, and it explicitly identifies the comparison as non-randomized rather than like-for-like.

The study lists GSK1247446A and Fluarix™ as biological interventions. The primary outcome is a count of subjects with solicited local symptoms during the post-vaccination follow-up period. Listed secondary outcomes concern hemagglutination inhibition antibody titers, seroconversion, seroprotection, and seroconversion factor against three influenza strains. These measures address immunogenicity, while the stated protocol purpose emphasizes safety.

The registry record does not report a sample-size justification, detailed statistical analysis plan, or allocation mechanism beyond non-randomized assignment. Such omissions limit what can be concluded about the intended precision or comparability of the groups. Completion status means the study is recorded as completed; it does not by itself establish that every outcome is reported or that a treatment effect has been demonstrated.

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: Subjects were allocated to study groups based on their vaccination course in the NCT00374842 primary study, so as to receive a re-vaccination dose of the vaccine previously administered.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects.

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 Subjects With Any, Grade 3 and Related Solicited Local Symptoms, measured over During a 7-day (Days 0-6) follow-up period after re-vaccination.

The primary endpoint counts subjects with solicited local symptoms during a 7-day (Days 0-6) follow-up period after revaccination. The assessed symptoms were ecchymosis, pain, redness, and swelling at the injection site. The endpoint distinguishes symptoms of any intensity from Grade 3 symptoms. Grade 3 pain means pain that prevented normal everyday activity; Grade 3 redness, swelling, or ecchymosis means a symptom spreading beyond 50 millimeters from the injection site. The description states that all assessed solicited local symptoms were considered by the investigator to be related to study vaccination.

Counting affected subjects is a binary-outcome approach: each subject is classified according to whether the specified symptom criterion occurred, rather than the count reflecting how many episodes an individual experienced. A symptom can also be described by severity, so an any-intensity count and a Grade 3 count answer different questions. The any-intensity measure captures occurrence, while the Grade 3 definition focuses on symptoms meeting the stated severity threshold. The record’s primary endpoint title also refers to related symptoms, reflecting the investigator’s attribution.

Solicited symptoms are useful for structured safety monitoring because the symptoms are specified in advance and assessed over a defined interval. That structure does not, by itself, show how often symptoms occurred in this study. The registry record does not report the primary endpoint counts, so the frequency of any, Grade 3, or related symptoms cannot be described from the posted results summarized in the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what the registry can and cannot establish. The primary endpoint is a count of subjects meeting symptom criteria. For analysis, such an outcome is commonly represented as a binary indicator for each subject: the criterion was met or it was not. Group summaries may report the number meeting the criterion and the number assessed. Those quantities describe the observed sample, while estimates of an underlying event probability require statistical uncertainty to be considered. The registry record does not report the primary symptom counts or an analysis of them.

What does a confidence interval add?

A confidence interval expresses uncertainty around an estimated quantity under a specified statistical procedure. A narrow interval indicates greater precision than a wide interval, while a wide interval indicates that the data are compatible with a broader range of values. It is not a guarantee that the true value lies within the interval, nor is it a measure of clinical importance. Because no confidence interval for the primary endpoint is reported in the registry record, its precision cannot be assessed from this information.

For event counts, precision depends in part on the amount of information available and on how frequently events occur. Rare events are especially difficult to characterize: observing few events does not establish that the underlying risk is absent. This is relevant to the serious-event figures, which are descriptive counts. Without an interval estimate, prespecified comparison, and details of event ascertainment, they should not be treated as a precise estimate of comparative risk.

Why does allocation matter?

Random assignment, when used and properly implemented, helps make treatment groups comparable on average with respect to both measured and unmeasured characteristics. This study is recorded as non-randomized. Participants entered the groups according to the vaccine received in the earlier study, and then received the corresponding revaccination. The groups may therefore differ in ways related to their earlier vaccination or other characteristics. Statistical adjustment can address measured differences only when the relevant data and an appropriate analysis are available; it cannot automatically remove all confounding. The registry record does not report an adjusted analysis.

The parallel structure means the study describes groups receiving their respective regimens during the same follow-up study, rather than a within-person crossover comparison. No masking is recorded. These design features matter when interpreting outcomes that involve symptom assessment or investigator attribution. The record does not describe procedures intended to reduce assessment bias, so such procedures should not be assumed.

What do the planning assumptions mean?

The registry record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The illustration considers detecting a stated fraction of the observed effect. These are planning assumptions, not evidence that the original study was designed with those assumptions, and not observed power. The record does not report the trial’s own sample-size justification. No numerical planning result can be interpreted from the available registry information alone.

In general, a planning calculation estimates the sample size needed under stated assumptions about the target effect, variability or event probability, significance level, and desired power. If the target effect is a fraction of an observed effect, the illustration depends on that observed effect and should not be confused with a new result from the trial. Sample-size illustrations are conditional calculations; they do not change the precision of the data already collected.

Why distinguish the endpoint from other outcomes?

The primary endpoint is defined in terms of solicited local symptoms. The listed secondary outcomes concern antibody titers and immune-response classifications against three influenza strains. These endpoints measure different features of the study. A difference in an antibody measure would not, by itself, answer the local-symptom safety question; likewise, symptom counts do not establish an antibody response. The registry record lists eight outcome measures but reports no analyses. It does not give the statistical methods, uncertainty estimates, or numerical results for the primary endpoint in this record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists eight outcome measures, including the primary local-symptom endpoint and secondary antibody outcomes against three influenza strains. When a study evaluates several outcomes or several comparisons, the chance of at least one apparently unusual result can rise if each is tested separately without accounting for multiplicity. A prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory analyses can help readers understand how results should be interpreted. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how the analyses accounted for multiple outcomes.

The record lists zero analyses. That entry indicates that analysis details are not listed in the registry record; it does not establish that analyses were not conducted. Statistical methods for estimating event frequencies, comparing groups, handling covariates, or producing uncertainty intervals are not reported. The registry record also does not report interim analyses or a detailed statistical analysis plan.

The primary endpoint population is the Total Vaccinated cohort, described as including all vaccinated subjects. This defines the stated analysis population, but does not explain how missing symptom assessments were handled. The registry record does not report the amount or pattern of missing data, reasons for missing observations, imputation procedures, or sensitivity analyses. Those details matter because incomplete follow-up can affect the estimated frequency of symptoms if missingness is related to symptoms or group membership. Without the relevant reporting, the potential effect of missing data cannot be assessed.

The record’s stated follow-up interval is a 7-day period after revaccination. It does not describe adherence to symptom collection or whether all participants completed that interval. The absence of those details should be treated as uncertainty in the reporting, not proof that data were missing or that follow-up was incomplete.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cerebrovascular accident (1.2%).

The serious adverse-event figures are counts within the groups, not evidence of a causal relationship. The registry records 0 serious adverse events among 160 at risk in the GSK1247446A group and 1 among 83 at risk in the Fluarix group. Deaths are recorded as 0 for both groups. Cerebrovascular accident is listed among the top serious terms at 1.2%. The record does not give further context for that term in the information available, so it should not be used to infer a comparative rate or cause.

These serious-event counts should not be conflated with the primary endpoint. The primary endpoint concerns solicited local symptoms assessed during a 7-day (Days 0-6) follow-up period. The serious-event figures describe a separate safety category, and the registry information does not state that they share the same observation window. Nor do the serious-event figures provide the missing counts for local symptoms.

Other adverse-event counts are recorded as 143 among 160 at risk in the GSK1247446A group and 57 among 83 at risk in the Fluarix group. These figures are not a substitute for the primary solicited-symptom results, and the available record does not provide enough detail to infer which specific events they include. Because allocation was non-randomized, simple group contrasts are descriptive rather than causal. No confidence intervals or statistical comparison for these figures are reported in the registry record.

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

The registry record establishes that this was a completed phase 2 study focused on safety after revaccination, with a defined local-symptom endpoint and secondary immunogenicity outcomes. It also records the vaccination histories that determined group membership, the post-vaccination symptom follow-up interval, and selected adverse-event counts. These details help readers understand what the study set out to observe.

The posted information does not include the primary endpoint counts. It therefore cannot show how many subjects experienced any solicited local symptom, how many met the Grade 3 definitions, or whether observed symptom frequencies differed between groups. The listed secondary outcomes do not include numerical antibody results in the registry information. A study objective, outcome definition, or completed status is not itself a result.

The serious-event figures are limited descriptive observations. A recorded count of zero does not prove that an event cannot occur, while a recorded event does not by itself show that a vaccine caused it. The non-randomized design further limits causal interpretation of differences between groups. Since group assignment followed prior vaccination history, the groups cannot be assumed comparable in all relevant respects.

Accordingly, this record does not establish that one regimen is safer, less safe, more immunogenic, or less immunogenic than the other. Such conclusions would require outcome results, appropriate uncertainty estimates, and analysis details, along with careful consideration of the non-randomized design. The record supports a precise description of the study’s intent and selected safety data, but the missing endpoint results and analysis information prevent a full statistical assessment of its principal question.

13. Why This Trial Matters Statistically

This study illustrates why a trial’s question, design, and reported results need to be read together. Its primary endpoint is a structured count of solicited local symptoms, with definitions for any-intensity and Grade 3 symptoms and a stated follow-up interval. Those definitions make the intended measurement understandable, but without the corresponding counts they do not answer how frequently symptoms occurred.

The non-randomized group structure is also central to statistical interpretation. Participants were grouped according to the vaccine received in the earlier study and then received a further dose in the corresponding group. Consequently, a comparison is not simply a contrast of two randomly assigned current treatments. Prior treatment history and other group differences may complicate attribution of any observed difference to the current revaccination.

The record also demonstrates the distinction between safety counts and evidence of comparative safety. A small number of serious events can be important to report, but counts alone do not establish a treatment effect or its precision. The absence of a reported analysis, uncertainty interval, or primary symptom result leaves important questions unresolved. A completed study record can still be statistically incomplete for readers seeking to assess a particular endpoint.

Finally, the listed immunogenicity outcomes and the safety endpoint represent different domains. Antibody measures and solicited symptoms should not be treated as interchangeable evidence. Clear reporting of outcome-specific estimates, uncertainty, analysis populations, missing-data handling, and multiplicity methods is needed to connect the study design to defensible conclusions. The registry information makes several design features visible while also showing where those interpretive details are not reported.

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 consequential limitation for interpreting the primary question is that the registry record does not report the primary local-symptom counts. Without those results, the endpoint cannot be summarized or compared between groups. The record also does not report confidence intervals or a statistical comparison for that endpoint, so its precision and the uncertainty around any potential contrast cannot be evaluated.

Non-randomized allocation limits causal interpretation. The groups were formed according to prior vaccination in NCT00374842, and the current vaccine received differed by group. This creates the possibility that group differences reflect prior vaccination or other characteristics rather than the current regimen alone. The registry information does not describe an adjusted analysis that might address measured differences.

The registry record lists eight outcome measures but does not report analyses or a multiplicity plan. It also does not report a detailed statistical analysis plan, sample-size justification, interim analyses, missing-data methods, or the extent of missing symptom assessments. These omissions prevent assessment of whether the reported outcomes were analyzed as intended and whether incomplete follow-up could affect estimates.

The adverse-event information is limited to group counts and a listed serious-event term. Further detail about event definitions, observation periods, severity, relatedness, and statistical uncertainty is not reported in the available registry information. Those limitations are distinct from the symptom endpoint’s specified assessment period and prevent a fuller safety comparison. The stated completion status does not resolve these reporting gaps.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Revaccination With Influenza Vaccine GSK1247446A — NCT00545025.
• Registry record last updated 2019-06-26; status last verified 2019-06.
• Results first posted 2013-05-07.
• 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

The registry record describes a completed phase 2, parallel, non-randomized, unmasked study of revaccination with GSK1247446A or Fluarix™ among adults aged 18-60 years previously vaccinated in NCT00374842. Enrollment was 243, and GlaxoSmithKline is listed as sponsor. The primary endpoint concerns solicited local symptoms during a 7-day (Days 0-6) follow-up after revaccination.

The primary symptom counts and numerical results for the listed antibody outcomes are not reported in the registry record. Serious adverse-event counts are 0 among 160 at risk in the GSK1247446A group and 1 among 83 at risk in the Fluarix group; deaths are recorded as 0 in each group. The non-randomized design, absent primary endpoint results, and unreported analysis details limit comparative and causal interpretation.