Study to Evaluate the Immunogenicity and Safety of a Second Vaccination With the Adjuvanted Influenza Vaccine Candidate: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Immunogenicity and Safety of a Second Vaccination With the Adjuvanted Influenza Vaccine Candidate (NCT00385840), a randomized phase 2 study. The primary outcome is Number of Subjects With Any and Grade 3 Solicited Local Symptoms..

2. Clinical Question

3. Trial Design

The registry describes a randomized, triple-masked, parallel-group Phase 2 trial of a second vaccination with adjuvanted GSK1247446A compared with Fluarix™. The condition listed is influenza. Enrollment is recorded as 678. The study status is completed, with a start date of 2006-10-20 and a primary completion date of 2007-02-01.

The groups consisted of adults aged 60 years or older at re-vaccination who had received one dose of either Fluarix™ or GSK1247446A in study NCT00321763. Participants previously vaccinated with Fluarix™ received another dose of Fluarix™; those previously vaccinated with GSK1247446A received another dose of the adjuvanted GSK1247446A vaccine. Both vaccines were administered intramuscularly in the deltoid region of the non-dominant arm.

The registry identifies the study as randomized, but the method used to generate or conceal the allocation sequence is not reported in the registry record. The record also does not identify which people were masked under the triple-masking designation, or describe how masking was maintained. The group descriptions link the second vaccination to the vaccine received earlier, but the registry does not explain how that history relates to the randomization process. These details limit how specifically the design can be reconstructed from the record.

The study’s stated purpose was to evaluate immunogenicity and safety. Listed secondary outcomes include antibody titers, seroconversion, seroprotection, and a seroconversion factor for three influenza strains. The record lists eight outcome measures overall, but does not provide analysis results for those secondary measures.

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 analysis was performed on the Total Vaccinated cohort, on all vaccinated subjects with the vaccine administration documented and symptom sheet completed.

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 and Grade 3 Solicited Local Symptoms., measured over During the 7-day (Days 0-6) post-vaccination period.

The primary outcome is the number of subjects with any and Grade 3 solicited local symptoms during the 7-day (Days 0-6) post-vaccination period. The symptoms assessed were ecchymosis, pain, redness, and swelling. “Any” refers to the occurrence of a particular solicited local symptom regardless of intensity. Grade 3 pain means pain that prevented normal everyday activity; Grade 3 redness, swelling, or ecchymosis means a measurement greater than 50 millimeters.

This is a count-based endpoint: it concerns how many participants experienced each defined event, rather than a continuous measurement such as an antibody titer. Solicited symptoms are collected by asking about specified events, which makes the outcome definition more focused than an unrestricted report of any symptom. The intensity categories also distinguish occurrence from symptoms meeting the record’s Grade 3 criteria.

The registry identifies the analysis population as the Total Vaccinated cohort: vaccinated participants with vaccine administration documented and a completed symptom sheet. It does not report a single primary-outcome comparison, so the endpoint definition alone cannot establish the relative frequency of symptoms between the groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, triple-masked, parallel-group design, but detailed statistical methods for the trial are not reported in the registry record. In particular, the record does not report the allocation procedure, the identities of the masked parties, a prespecified statistical analysis plan, or an explanation of how outcome categories were to be combined. The methodological points below are general explanations of how such information would ordinarily help readers interpret clinical-trial results.

What does randomization contribute?

General: Randomization assigns participants to treatment groups by chance. When implemented and preserved appropriately, it can reduce systematic differences between groups at the time of assignment, supporting a fair comparison of outcomes. It does not guarantee that every characteristic will be identical between groups, and it does not remove problems caused by missing measurements or incomplete reporting. The registry calls this study randomized, but the sequence-generation and allocation-concealment methods are not reported in the registry record. The description of participants continuing with the vaccine they received in the earlier study also makes the relationship between earlier assignment and the present randomization important; that relationship is not explained in the record.

What does masking mean?

General: Masking is intended to reduce the influence of treatment knowledge on care, outcome reporting, or outcome assessment. A label such as triple-masked indicates a masking designation, but readers need to know which parties were masked and how masking was maintained to assess its practical meaning. Those details are not reported in the registry record. Solicited symptoms can depend on participant reporting, so the procedures for collecting symptom information are relevant to interpretation; the record identifies a completed symptom sheet as part of the primary analysis population but does not describe its administration.

How should a count endpoint be analyzed?

General: A count of participants with an event is often summarized as the number with the event and the number assessed in each group. A comparison can then be expressed using a measure such as a difference in event proportions or a relative measure. Each measure answers a slightly different question, and each should be accompanied by an uncertainty interval where possible. The registry record gives the primary endpoint definition but does not provide a single primary-outcome comparison or an uncertainty interval. No new comparison should be inferred from the endpoint definition.

For this outcome, the rules for “any” and Grade 3 symptoms are not identical. Combining symptom types or severity levels may answer a broader question, but it can conceal differences among the individual symptoms. The registry does not report a single reduced comparison for the primary endpoint, and the rationale or planned hierarchy for presenting the categories is not reported in the registry record. The number of outcome measures is listed as eight, while the number of analyses is listed as zero; the record does not explain how analyses were specified or conducted.

What do confidence intervals and p-values tell readers?

General: A confidence interval describes the range of estimates compatible with the data under a particular statistical procedure and its assumptions. Its width reflects precision: wider intervals generally indicate less precise estimates, while narrower intervals indicate greater precision. A p-value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. Neither quantity, on its own, describes clinical importance or proves a treatment effect. The registry does not report a primary-outcome estimate, confidence interval, or p-value for the comparison under discussion.

What is the status of the planning assumptions?

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, and a normal approximation. The record explicitly distinguishes this illustration from the trial’s own design. Such planning values are not observed outcomes and are not “observed power.” The registry does not report the trial’s own sample-size justification, so the planning assumptions should not be presented as its original design rationale.

General: Sample-size calculations depend on the outcome, the effect chosen for detection, the expected variability or event frequency, and the analysis method. A calculation based on an observed effect is a retrospective illustration and can be unstable when the estimate itself is imprecise. It does not substitute for a prospective design justification. The specific assumptions used for the trial’s original planning are not reported in the registry record.

The primary outcome is binary at the participant level: a person either meets a specified event definition during the observation window or does not. General: Binary outcomes can be affected by how events are solicited, how missing symptom records are handled, and whether the denominator includes every randomized participant or only those with usable follow-up. Here, the record names the Total Vaccinated cohort and its documentation requirements, but it does not report the number excluded from that cohort, the amount of missing symptom information, or a method for handling missing data.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome contains multiple local-symptom categories and distinguishes any occurrence from Grade 3 symptoms. The registry record states that these categories or time points were not reduced to a single comparison. This matters statistically because examining multiple outcomes or categories can increase the chance of finding an apparently notable result by chance if each is tested separately. General: A prespecified hierarchy or multiplicity adjustment can help control that risk, while a clearly defined primary comparison can make the main inference easier to interpret. The registry does not report a multiplicity strategy, a hierarchy among the symptom outcomes, or the statistical plan used for testing them.

The record lists eight outcome measures and zero analyses. It describes secondary immunogenicity outcomes involving antibody titers, seroconversion, seroprotection, and a seroconversion factor against three influenza strains. Results and analysis details for those outcomes are not reported in the registry record. The record also does not explain whether the outcome list changed over time or how any outcome-selection decisions were made.

For the primary analysis, the stated population is the Total Vaccinated cohort, defined as participants with documented vaccine administration and a completed symptom sheet. The number included in that cohort, the number with incomplete or missing symptom data, and the handling of such data are not reported in the registry record. The analysis population and missing-data rules for the secondary outcomes are also not reported.

General: Restricting an analysis to participants with complete measurements can affect comparability if missingness is related to treatment or outcome. An intention-to-treat analysis, a vaccinated-population analysis, and a complete-case analysis can target different populations or rely on different assumptions. The registry’s named cohort should therefore be distinguished from other possible analysis populations rather than assumed to represent them. Without the analysis plan and missing-data details, the possible influence of exclusions or incomplete follow-up cannot be assessed.

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: pneumonia (0.8%), pulmonary embolism (0.8%), cholelithiasis (0.2%), pancreatitis (0.2%), sudden death (0.2%).

The registry reports serious adverse events for the Fluarix Group as 1 affected participant among 133 at risk, and for the GSK1247446A Group as 2 affected participants among 545 at risk. It also records 66 affected participants among 133 at risk and 434 among 545 at risk in an “other” adverse-event category. The precise definition of that other category is not reported in the registry record, so it should not be assumed to mean a particular severity class.

These counts describe recorded events in the listed groups; they do not provide a full comparison of risk or establish that an event was caused by vaccination. General: Rare-event counts are especially sensitive to small changes in the observed number of events, and estimates based on few events can be imprecise. A comparative interpretation would normally consider the event definitions, observation period, denominators, uncertainty, and whether the groups were analyzed in the same way. The record does not report uncertainty intervals for these counts.

The listed serious-event terms include Pneumonia and Pulmonary embolism at 0.8%, and Cholelithiasis, Pancreatitis, and Sudden death at 0.2%. The record does not connect these term percentages to a specific group in the information available. Death counts are not reported in the registry record. The term list should therefore not be read as an arm-specific comparison or as a complete account of all safety outcomes.

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

The registry record describes a trial designed to evaluate immunogenicity and safety after a second vaccination in adults aged 60 years and above. It specifies the two vaccines, the previous vaccination history described for each group, the route and injection site, and the primary local-symptom outcome. Those details establish the clinical and measurement context, but they are not themselves evidence of a difference between the groups.

For the primary outcome, the registry defines the symptoms, the Grade 3 criteria, the observation window, and the Total Vaccinated analysis population. It does not report a single primary-outcome comparison. As a result, the record does not establish the frequency of the defined symptoms by arm in a form that supports a comparative estimate, nor does it report the precision of such an estimate.

The separate serious adverse-event counts are descriptive entries. Their interpretation is constrained by the small event counts, the absence of reported uncertainty intervals, and the lack of an arm attribution for the listed serious-event term percentages. The other adverse-event category is not precisely defined in the record, and death counts are not reported. These limitations do not prove that a safety difference exists or that none exists; they mean the available registry information is insufficient to assess those possibilities reliably.

The listed secondary outcomes concern antibody responses, seroconversion, seroprotection, and seroconversion factors. Without reported results, they cannot be used to draw conclusions about the measured immune responses. Likewise, the registry’s randomized and triple-masked design labels describe intended design features, but the allocation and masking procedures are not detailed enough to assess their implementation.

In short, the record supports a description of the trial question, outcome definitions, and selected safety counts. It does not support a conclusion that either vaccine had more or fewer local symptoms, or that one had a better or worse safety profile. Such conclusions require comparative outcome results and enough information to judge their precision and analysis.

13. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported comparative estimate are both necessary for statistical interpretation. The primary outcome specifies which local symptoms were assessed, distinguishes any symptom from Grade 3 symptoms, and fixes an observation window of 7 days (Days 0-6). Those details make the intended measurement understandable. But multiple symptom categories do not automatically produce one interpretable primary comparison, and the registry record explicitly does not reduce them to one.

The design also highlights the importance of explaining how trial phases relate when participants have a prior vaccination history. The record states that participants had received a dose in study NCT00321763 and then received the corresponding vaccine again. Although the trial is identified as randomized, the process linking prior vaccination, present assignment, and analysis is not described. For readers assessing comparability, that missing detail is relevant to understanding what treatment contrast the study estimates.

Safety reporting offers another statistical lesson. The registry gives serious-event counts with denominators, but the numbers are small and no uncertainty intervals are reported. A count alone is not a precise estimate of comparative risk. In addition, event-term percentages without a stated arm attribution cannot be used to compare groups. Clear definitions, denominators, time windows, and group-specific estimates are essential for an interpretable safety account.

Finally, the record lists outcomes but does not provide analyses for them. A trial’s design and outcome definitions explain what investigators intended to measure; they do not replace the results needed to estimate effects. Readers should distinguish the existence of a randomized study from the availability of an analyzed comparison. This distinction is central to evidence appraisal and to avoiding conclusions that go beyond the reported data.

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 for statistical interpretation is that the registry record does not report a single primary-outcome comparison, despite defining the local symptoms and the observation window. It therefore does not provide an arm-level estimate or its precision for the main question. The record also lists zero analyses, and does not give results for the listed secondary immunogenicity outcomes.

The primary outcome includes several symptom categories and separates any occurrence from Grade 3 events. The registry says these categories or time points were not reduced to one comparison, but does not report a prespecified hierarchy or explain how multiplicity was addressed. Without those details, readers cannot determine which comparisons were considered primary for inference or how to interpret multiple possible findings.

The analysis population is described as vaccinated participants with documented administration and a completed symptom sheet. The number included in that population, the number with missing symptom information, and the methods for handling missing data are not reported in the registry record. It is also unclear from the record how the named analysis population relates to any other analyses.

Although randomization and triple masking are registered, the allocation method, masking procedures, and the relationship between the earlier vaccination and present allocation are not explained. These omissions make it difficult to assess how the intended design features were implemented. The trial’s own sample-size justification and statistical analysis plan are also not reported.

Safety interpretation is limited by the absence of uncertainty intervals, the small serious-event counts, and the lack of a precise definition for the other adverse-event category. The listed serious-event term percentages are not attributed to an arm in the information available, and death counts are not reported in the registry record. These are limits of what can be interpreted from the record, not evidence that unreported outcomes did or did not occur.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate the Immunogenicity and Safety of a Second Vaccination With the Adjuvanted Influenza Vaccine Candidate — NCT00385840.
• Registry record last updated 2018-06-08; status last verified 2016-10.
• Results first posted 2013-04-29.
• 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

The registry describes a completed randomized, triple-masked, parallel-group Phase 2 study of a second vaccination with adjuvanted GSK1247446A compared with Fluarix™ in adults aged 60 years and above. Participants had previously received the corresponding vaccine in study NCT00321763. The primary outcome concerns solicited local symptoms during the 7-day (Days 0-6) post-vaccination period, including symptoms meeting Grade 3 criteria.

The primary analysis population is defined as vaccinated participants with documented vaccine administration and a completed symptom sheet. The registry does not report a single primary-outcome comparison, and it lists zero analyses. Serious adverse-event counts are reported as 1 of 133 in the Fluarix Group and 2 of 545 in the GSK1247446A Group. The record does not report uncertainty intervals, the trial’s statistical analysis plan, or a comparative primary-outcome estimate. The listed secondary immunogenicity outcomes have no reported results in the registry record.