Immune Responses Induced by Different Licensed Influenza Vaccines: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immune Responses Induced by Different Licensed Influenza Vaccines (NCT00902278), a randomized na study. The primary outcome is T Cell Responses Following Immunization.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, parallel-group study of immune responses induced by different manufacturers of influenza vaccines. The listed products are Flulaval, Fluvirin, Fluzone, Fluarix, and Afluria. In a parallel design, participants are assigned to a group and outcomes are compared between groups, rather than comparing each participant across different assigned treatments. The record does not give the allocation ratio, the method used to generate assignments, or details of the assignment process.

Masking is listed as none. This indicates that the registry classifies the study as unmasked; details about who knew the assigned vaccine, and whether laboratory staff were masked when assessing samples, are not reported in the registry record. These details can matter when outcomes involve judgment or decisions during measurement. They do not establish whether any particular measurement was affected.

The listed enrollment is 193. The record gives a study start of 2008-10 and a primary completion date of 2016-04, and its status is completed. The phase is listed as NA. The reason for the study duration, any changes in recruitment, and the dates of follow-up for individual participants are not reported in the registry record.

The primary outcome is a continuous measure, described as mean fold change with standard deviation as its dispersion measure. The primary-outcome description specifies a comparison of mean peak fold increases in ELISPOT H1N1, H3N2, and B responses between vaccine groups. Data for that outcome were collected only for participants from the 2008-2009 influenza season; the description also says data were not collected for the Flulaval group and that only participants with evaluable data were included. The reasons for these restrictions are not reported in the registry record.

The study aim, as described in the record, is to examine how the body's immune system responds to different manufacturers' influenza vaccines. A secondary outcome is listed as antibody responses following immunization. Numerical results for the primary outcome, and statistical analyses for the comparisons, 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: Data was collected only for participants from the 2008-2009 influenza season. Data was not collected for Flulaval group.Only participants with evaluable data were included in the analysis.

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 T Cell Responses Following Immunization, measured over Prevaccination and approximately 7 days,14 days ,1month and up to 3-5 months post vaccination.

The primary endpoint is the mean peak fold increase in ELISPOT responses to H1N1, H3N2, and B, compared between vaccine groups. A fold change expresses a measurement relative to a reference measurement; in this record, the specified reference is prevaccination. The endpoint description identifies the observations as ELISPOT responses and names the immune-response categories being compared. It does not provide the actual group means, standard deviations, or the magnitude of any fold increase.

In general, a cellular immune-response measure can provide information different from an antibody measure. The registry lists antibody responses as a secondary outcome, while the primary endpoint is based on T-cell responses. These are distinct outcome types, and results for one should not be treated as a substitute for results for the other. The registry record does not give detailed assay procedures or explain why this endpoint was selected over other possible measures.

The scheduled measurement description includes prevaccination and approximately 7 days,14 days ,1month and up to 3-5 months post vaccination. The primary-outcome text refers to peak fold increases, but the exact rule for identifying a peak across these times is not reported in the registry record. Nor does the record state whether each listed response category and time point was treated as a separate hypothesis or how those comparisons were combined. That matters because a collection of endpoint comparisons can be harder to interpret than one prespecified contrast.

The endpoint is useful for describing the immune responses measured in this study, but it is not itself a clinical outcome. The registry record does not report whether any measured response was linked to a clinical benefit or other patient outcome. Without posted numerical results and analysis details, the endpoint definition alone cannot establish the size, precision, or comparative direction of the observed responses.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a continuous measure summarized by a mean and standard deviation. The mean represents the average observed value in a group. The standard deviation describes the spread of individual observations around that average; it is not the same as the uncertainty in the estimated mean. The record identifies the measure as fold change, but does not report group-specific values for either summary statistic.

What does a mean comparison tell the reader?

A difference between group means describes how far apart the group averages are on the endpoint scale. For a fold-change outcome, interpretation depends on the precise definition of the fold calculation and on which observations are included. The registry record identifies prevaccination and postvaccination measurement times and refers to mean peak fold increases, but does not specify the exact calculation or peak-selection rule. No new mean comparison can be reconstructed without the underlying numerical summaries.

In general, a confidence interval gives a range of values compatible with the data and the statistical method used, reflecting uncertainty in an estimate. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. A confidence interval is not a guarantee that the true value lies within its endpoints. The registry record does not report confidence intervals for the primary endpoint.

How should a significance test be read?

In general, a significance test evaluates how compatible the observed data are with a specified null hypothesis, under the assumptions of the test. A p-value does not measure the size or practical importance of an effect, and it does not give the probability that the null hypothesis is true. It should be read alongside an effect estimate and a measure of uncertainty. The registry record lists no analyses, so it does not report a test statistic or p-value for the primary outcome.

Random assignment can support causal comparisons by reducing systematic differences between groups at the point of assignment. In general, it does not prevent later differences in follow-up, missing observations, measurement, or analysis. The registry record identifies the study as randomized and parallel, but the assignment procedure, allocation ratio, and analysis approach are not reported. Masking is listed as none. The record does not state whether laboratory personnel assessing ELISPOT responses were masked to group assignment.

Why do multiple responses and times matter?

The primary-outcome description includes H1N1, H3N2, and B responses and several scheduled times. When several outcomes, time points, or group comparisons are examined, the chance of finding at least one apparently notable result can increase if each is tested separately without an appropriate plan. Statistical methods for multiplicity can address this issue, but the registry record does not report a multiplicity strategy or clarify which comparisons were treated as primary. It also does not report an analysis model for repeated measurements or for selecting the peak value.

The registry lists standard deviation as the dispersion measure. In general, that summary describes variability but does not explain its shape. If observations are unusually spread out or concentrated, or if their distribution differs from the assumptions of a chosen model, the mean and standard deviation may not fully describe the data. Over-dispersion is a concern when variability exceeds what a model assumes; accounting for it can affect standard errors and confidence intervals. The registry record does not report distributional checks or a method for addressing over-dispersion, so it is not possible to say whether either issue arose in this study.

What do the planning assumptions mean?

The record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed using those assumptions or that the trial achieved a particular level of power. The record does not report a sample-size justification from the trial's own design. Because the primary outcome contains several categories or time points and is not reduced to one comparison, a single observed effect is not identified in the registry record for interpreting the illustration.

In general, a planning calculation estimates the sample size needed under specified assumptions; it does not describe what happened in the observed study. Its result depends on the selected effect size, variability, significance level, allocation, and statistical method. A calculation based on an observed effect is especially dependent on how that effect was estimated. The registry record does not report a numeric planning estimate alongside an identifiable primary comparison. Any sample-size illustration should therefore be read as planning information rather than observed power or a finding about the study's results.

10. Multiplicity, Missing Data and Analysis Populations

The primary-outcome description covers ELISPOT responses to H1N1, H3N2, and B, with measurements at prevaccination and approximately 7 days,14 days ,1month and up to 3-5 months post vaccination. It refers to mean peak fold increases but does not state exactly how the peak was defined or which comparisons were designated as the principal test. When more than one response category, time point, or vaccine-group contrast is examined, multiplicity can affect how statistical evidence should be interpreted. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a statistical analysis plan.

The record says primary-outcome data were collected only for participants from the 2008-2009 influenza season, were not collected for the Flulaval group, and included only participants with evaluable data. It does not define evaluability or report why data were unavailable for that group. The numbers contributing to each endpoint comparison, the amount and pattern of missing measurements, and the methods used to handle missingness are not reported in the registry record.

In general, missing observations can affect both precision and the comparability of groups, especially when the reason data are missing is related to participants' characteristics or outcomes. Restricting analysis to participants with evaluable data can also change which participants contribute to a result. These are general considerations, not claims about what occurred in this study. Without details of the missing-data process or analysis population, the potential impact cannot be assessed.

The record lists antibody responses following immunization as a secondary outcome, but does not provide its analysis details or results. It lists two outcome measures and zero analyses. The registry record does not report whether secondary outcomes were adjusted for multiplicity or how primary and secondary results were prioritized.

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 non-serious adverse event terms

The registry lists serious adverse events by group. For Flulaval, 0 serious adverse events are listed among 52 at risk; for Fluvirin, 0 among 34; for Fluzone, 0 among 53; for Fluarix, 0 among 11; and for Afluria, 0 among 36. The record also lists 0 deaths in each vaccine group. These are the counts recorded in the registry, not estimates of the probability of an event.

The record separately lists other adverse events: 30 among 52 at risk for Flulaval, 24 among 34 for Fluvirin, 32 among 53 for Fluzone, 6 among 11 for Fluarix, and 25 among 36 for Afluria. The registry does not provide event descriptions in the listed serious-event terms, and the serious-event terms list is empty. Details such as event definitions, collection procedures, severity grading, and the observation period are not reported in the registry record.

A zero recorded count does not establish that an event is impossible or that the true risk is zero; the observed count is limited by the participants and follow-up captured in the record. Group counts also should not be treated as a formal comparison without an analysis that accounts for the study design and uncertainty. These safety counts do not describe the primary T-cell endpoint and cannot be used to infer its results.

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

The registry record establishes that the study was designed to compare immune responses among five influenza-vaccine groups in a randomized, parallel design. It identifies a primary T-cell endpoint based on mean peak fold increases in ELISPOT H1N1, H3N2, and B responses, as well as a secondary outcome concerning antibody responses. It also records the scheduled measurement periods and notes that the primary-outcome data were restricted to participants from the 2008-2009 influenza season, did not include Flulaval, and were limited to participants with evaluable data.

Those details describe the study question and some features of the available outcome population. They do not show whether one vaccine group had a higher or lower immune response than another. Numerical endpoint estimates, their variability, confidence intervals, and tests are not reported in the registry record. Consequently, neither the magnitude nor the precision of any group comparison can be judged from this record.

In general, a measured immune response is an outcome on a biological scale; it is not automatically evidence of a difference in a clinical outcome. The record does not report a link between the primary endpoint and illness, protection, or another patient-centered outcome. No conclusion about clinical benefit should be drawn from the endpoint description alone. This is a distinction about what the recorded outcome measures, not a claim that such a relationship cannot exist.

The registry does report safety counts, including no serious adverse events recorded in any listed vaccine group. Counts of recorded events are informative as descriptions of what was reported, but do not establish that the event risk is zero. Nor do these counts answer the primary question about cellular immune responses. The record does not provide enough detail about event definitions or follow-up to interpret safety comparisons beyond the reported counts.

Overall, the posted information supports a description of the study's design, intended immune-response comparison, and selected safety counts. It does not support a quantitative conclusion about relative immune responses, statistical significance, or clinical effects. Those conclusions would require outcome estimates and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically notable for the gap between a clear comparative question and the limited outcome analysis information in the registry record. The design is described as randomized and parallel, and the primary endpoint is defined as a mean peak fold increase in several ELISPOT response categories. However, no numerical results or statistical analyses are listed. Without group estimates and uncertainty measures, readers cannot distinguish a small, precisely estimated difference from a larger but imprecise one.

The endpoint spans multiple response categories and scheduled measurement times, and the record refers to peak fold increases. That creates questions about how peaks were selected, how comparisons across categories and time points were organized, and how multiplicity was handled. These choices can affect the interpretation of estimates and tests. The registry record does not report the methods used to address them, so the analysis cannot be reconstructed from the outcome description alone.

The stated analysis population also matters: primary-outcome data are described for participants from the 2008-2009 influenza season, with no Flulaval data and inclusion only of participants with evaluable data. These restrictions mean that enrollment is not a substitute for the number contributing to each comparison. Information about evaluability, missingness, and group-specific analysis counts is not reported in the registry record.

Finally, the record's sample-size assumptions are described as a planning illustration based on an observed effect, not as the study's own design justification. This distinction is important: planning calculations are conditional on assumptions and do not establish the precision actually achieved. The record gives no numerical primary outcome analyses against which to assess precision. The statistical importance of the study therefore lies in the questions it raises about analysis specification and reporting, rather than in a comparative result that can be quantified from the registry record.

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 registry record does not report numerical primary-outcome results or analyses. It therefore does not provide group means, standard deviations, uncertainty intervals, or tests for the stated T-cell comparison. The primary question cannot be answered quantitatively from the registry record.

The primary-outcome population is restricted in the description to participants from the 2008-2009 influenza season, excludes primary-outcome data for Flulaval, and includes only participants with evaluable data. The reasons for the missing Flulaval data, the criteria for evaluability, the number of participants analyzed in each group, and the handling of missing observations are not reported in the registry record. This prevents assessment of how closely the analyzed population represents the enrolled groups.

The endpoint includes H1N1, H3N2, and B responses and several measurement times, while the record refers to peak fold increases. The precise peak definition, the selected comparisons, and any adjustment for multiple testing are not reported. Neither the ELISPOT assay details nor the model used to compare groups is specified in the registry record. These omissions limit reproducibility and make it difficult to assess whether the analysis matched the outcome structure.

Masking is listed as none, but the record does not say whether laboratory personnel were masked during response measurement. The allocation ratio, randomization procedure, baseline group characteristics, and any protocol or analysis-plan changes are also not reported in the registry record. These details would help readers assess the conduct and interpretation of the comparisons.

The safety information is limited to listed event counts and at-risk group sizes. Event definitions, follow-up duration for safety, and event-level descriptions are not reported. The record's completed status and primary completion date do not fill these gaps or substitute for a detailed account of outcome ascertainment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immune Responses Induced by Different Licensed Influenza Vaccines — NCT00902278.
• Registry record last updated 2017-11-20; status last verified 2017-06.
• Results first posted 2017-11-20.
• 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 identifies a completed randomized, parallel-group study titled “Immune Responses Induced by Different Licensed Influenza Vaccines.” It lists enrollment of 193, a study start of 2008-10, primary completion in 2016-04, no masking, and phase NA. The listed products are Flulaval, Fluvirin, Fluzone, Fluarix, and Afluria.

The primary outcome is a mean peak fold increase in ELISPOT H1N1, H3N2, and B responses. Its description specifies prevaccination and approximately 7 days,14 days ,1month and up to 3-5 months post vaccination, but limits data to the 2008-2009 influenza season, excludes Flulaval data, and includes only participants with evaluable data. Antibody responses following immunization are listed as a secondary outcome.

The registry record lists safety counts, but no primary outcome analyses. Numerical immune-response results, analysis methods, missing-data methods, and multiplicity procedures are not reported in the registry record. The record supports a description of the study question and design, but not a quantitative comparison of the immune responses.