Study of Influenza Vaccine Revaccination in Healthy Adults Previously Vaccinated With Fluzone ID or Fluzone IM: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Influenza Vaccine Revaccination in Healthy Adults Previously Vaccinated With Fluzone ID or Fluzone IM (NCT01011049), a randomized phase 2 study. The primary outcome is Number of Participants Reporting Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone Intradermal or Fluzone Intramuscular Vaccine.

2. Clinical Question

This is a question about describing reactions after vaccination, not a registry-reported test of whether one revaccination sequence is superior to another. The primary endpoint counts participants reporting solicited reactions. It covers injection-site reactions—erythema (redness), swelling, induration, pain, pruritus, and ecchymosis—and systemic reactions—headache, myalgia, malaise, shivering, and fever. The record does not give separate numerical results for these reaction categories in the material describing the primary outcome.

The four groups allow the vaccination sequence to be considered in the context of the previous formulation. That structure is relevant because the primary question concerns revaccination, while the secondary questions concern antibody titers, seroprotection, and seroconversion. The registry record states the objectives and outcome definitions, but does not report the results or analyses for those immunogenicity outcomes. The available safety counts should therefore be read as reported event summaries, not as a complete answer to every question raised by the objectives.

3. Trial Design

The registry describes NCT01011049 as a completed phase 2 study with randomized allocation, no masking, and a parallel-group model. Its title identifies healthy adults previously vaccinated with Fluzone ID or Fluzone IM; the official title specifies adults aged 18 to 64 years. The registry lists enrollment as 1250. The recorded study start is 2009-09, and primary completion is recorded as 2010-05.

Four groups varied both the prior formulation and the revaccination formulation. Group 1 received Fluzone ID after Fluzone ID in Study FID31. Group 2 received Fluzone IM after Fluzone ID. Group 3 received Fluzone IM after Fluzone IM. Group 4 received Fluzone ID after Fluzone IM. These are the sequence descriptions in the record; it does not provide further details about the allocation procedure or the method used to assign participants.

The primary objective was to evaluate and describe the safety profile of revaccination with Fluzone ID for all participants. The primary outcome was the number of participants reporting solicited injection-site and systemic reactions from Day 0 through Day 7 post-vaccination. Secondary objectives concerned immunogenicity after revaccination with either formulation. Listed secondary outcomes include geometric mean titers before and after vaccination, the percentage achieving seroprotection before and after vaccination, and the percentage achieving seroconversion after vaccination.

The registry record identifies the study as open label, so masking was not used. It does not report the randomization method, allocation concealment, detailed visit schedule, or a prespecified statistical plan. The enrollment entry is not itself a report of how many participants contributed to each endpoint. Group-specific counts are given for the adverse-event summaries, while the primary endpoint’s reaction categories are not reduced in the record to a single comparison. The record lists no statistical analyses for the outcome 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.

Before assignment: A total of 1248 participants who met the inclusion and exclusion criteria were enrolled and vaccinated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis was on all enrolled and vaccinated subjects with available reaction data, intent-to-treat population.

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 Participants Reporting Solicited Injection Site and Systemic Reactions After Vaccination With Fluzone Intradermal or Fluzone Intramuscular Vaccine, measured over Day 0 through Day 7 post-vaccination.

The primary endpoint counts participants reporting solicited injection-site or systemic reactions after vaccination. The observation window is Day 0 through Day 7 post-vaccination. The listed injection-site reactions are erythema (redness), swelling, induration, pain, pruritus, and ecchymosis; listed systemic reactions are headache, myalgia, malaise, shivering, and fever. The measure is a participant count, rather than a severity score or a measure of antibody response.

Solicited reactions are specified in advance for collection, which makes the outcome focused on particular symptoms during a defined period. This can support a structured description of short-term reactogenicity across the revaccination groups. It does not, by itself, establish whether a reaction was caused by vaccination, how severe it was, or whether the groups differ statistically. Those interpretations require details and analyses beyond a count alone.

The primary outcome description does not provide separate reported results for each reaction type or an overall comparison. The registry record also states that the primary outcome has several categories or time points and is not reduced to one comparison. The safety population is described as enrolled and vaccinated subjects with available reaction data, in the intent-to-treat population. The handling of participants without available reaction data is not reported in the registry record. The listed secondary immunogenicity outcomes address antibody measures, which are distinct from this primary reaction-count endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as randomized and parallel group. In general, randomization assigns participants to study groups using a chance-based process; its purpose is to reduce systematic differences between groups at the time of assignment. A parallel-group design means participants are assigned to a group that follows a particular vaccination sequence, rather than each participant receiving every sequence in turn. The registry record does not report the exact randomization procedure, allocation concealment, or any statistical adjustment used in analysis.

What does a participant count measure?

The primary outcome is a count of participants reporting solicited reactions within a stated period. A participant count is a binary-outcome summary at the level of each person: a participant either meets the outcome definition or does not, for the relevant summary. In general, such counts are most interpretable alongside the number of participants assessed and a clearly specified event definition. Here, the outcome description lists several reaction types and the registry record does not report a single combined comparison or category-specific outcome estimates.

A count alone does not convey the precision of an estimate or whether a difference between groups could plausibly reflect sampling variation. A confidence interval is a statistical range describing uncertainty around an estimate under a specified method. The registry record does not report confidence intervals for the primary endpoint. It also does not report p-values or a model-based estimate for that endpoint, so there is no inferential result to interpret for the solicited reactions.

Why distinguish descriptive summaries from comparisons?

Descriptive summaries report what was observed in a group. A comparative analysis estimates how outcomes differ between groups and quantifies uncertainty using a specified statistical method. The serious adverse-event entries are group-level counts with numbers at risk, but the record does not include a comparative estimate or analysis. It would therefore be inappropriate to describe those counts as evidence of a statistically established difference or no difference.

For an event count, one possible general approach is to compare the proportion of participants with an event across groups. Other approaches may be used depending on the endpoint definition, design, and analysis plan. The registry record does not identify a method for the serious-event summaries, nor does it provide a prespecified statistical plan for the primary endpoint. No particular model, adjustment, or test should be inferred.

What is over-dispersion, in general?

Over-dispersion is a general statistical issue that can arise when the observed variation in counts is greater than a model assumes. If a count model assumes less variation than the data contain, uncertainty may be understated. This concept is not a reported finding from this trial: the primary endpoint is expressed as participants with reactions, and the registry record does not describe an over-dispersion assessment or a count-model analysis.

How should planning illustrations be understood?

In general, a sample-size illustration based on an observed effect asks how many participants might be needed under stated assumptions to detect an effect of a specified size. Such a calculation is not an observed result and does not show the probability that this completed study detected an effect. The planning assumptions described for this record use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. For non-time-to-event calculations, the stated convention is participants per arm for a specified power. These are planning illustrations, not the trial’s own design justification or observed power. The registry record does not report the study’s sample-size justification.

More generally, power depends on the assumed effect, variability or event frequency, allocation, analysis method, and significance threshold. An illustration cannot replace a prespecified protocol calculation or an analysis of observed outcomes. The record does not report the protocol assumptions behind trial enrollment or whether any interim analyses occurred.

What can be concluded from absent analyses?

The record lists no analyses for its outcome measures. It therefore provides no documented statistical method for the primary solicited-reaction endpoint or the named immunogenicity outcomes. General statistical concepts can explain how such outcomes might be analyzed, but they cannot be used to fill in methods or results that the registry record does not report. The estimates, uncertainty intervals, model choices, and multiplicity procedures are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The study includes a primary safety objective and several secondary immunogenicity outcomes. The primary outcome itself encompasses multiple solicited injection-site and systemic reaction categories, and the registry record notes that the primary outcome has several categories or time points and is not reduced to one comparison. When several outcomes or comparisons are examined, multiplicity is a general statistical concern: repeated testing can increase the chance of at least one apparently unusual result even when no true difference exists. The registry record does not report whether a multiplicity adjustment, hierarchy, or other strategy was planned.

The record lists no analyses for the outcome measures. No statistical plan is reported for the primary or secondary outcomes, and no interim-analysis plan is reported in the registry record. It is also not reported in the registry record whether the secondary outcomes were intended for formal hypothesis testing or descriptive reporting.

The safety population is described as all enrolled and vaccinated subjects with available reaction data, within the intent-to-treat population. This identifies the stated basis for the safety analysis, but does not explain how unavailable reaction data were handled. The record does not report the number of participants with missing reaction data, the reasons for missingness, or any method used to address missing values.

For immunogenicity, the listed outcomes include measurements before and after vaccination, but the analysis population and missing-data procedures are not reported in the registry record. The registry record also does not report whether any participants were excluded from those analyses or how the before-and-after measurements were paired or summarized. These omissions limit interpretation of any conclusion about the planned outcomes. They should not be filled by assuming standard practice: the handling of multiplicity and missing data is not reported in the registry record.

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 5.0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: uterine leiomyoma (0.4%), psychiatric decompensation (0.4%), knee arthroplasty (0.4%), pneumonia (0.4%), incisional hernia (0.4%).

The registry record presents serious adverse-event summaries by vaccination sequence. Group 1 has 507 participants at risk and 9 affected; Group 2 has 252 at risk and 2 affected; Group 3 has 243 at risk and 3 affected; Group 4 has 246 at risk and 5 affected. These figures describe the entries in the registry and should be read as counts, not as results of a statistical comparison.

The listed serious-event terms are uterine leiomyoma, psychiatric decompensation, knee arthroplasty, pneumonia, incisional hernia, and post procedural complication; each is reported as 0.4%. The record does not provide event-specific group breakdowns or comparative estimates for these terms. It also does not report a statistical analysis of the serious adverse-event summaries.

These serious-event summaries are distinct from the primary endpoint, which concerns solicited reactions during Day 0 through Day 7. They should not be substituted for the primary endpoint’s reaction counts. The record does not report death counts. More broadly, the serious-event entries alone do not establish whether an event was caused by vaccination, whether groups differ, or how precisely any between-group difference is estimated.

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

This trial’s registry entry describes a randomized, open-label comparison of four revaccination sequences in healthy adults aged 18 to 64 years previously vaccinated with Fluzone ID or Fluzone IM. Its primary objective was to describe the safety profile of revaccination with Fluzone ID, using solicited reactions reported from Day 0 through Day 7. Secondary objectives concerned immunogenicity after revaccination with either formulation.

The registry record does not report statistical analyses for the outcomes. In particular, it does not provide a numerical result or comparative estimate for the primary solicited-reaction endpoint, or results for the named immunogenicity outcomes. The serious adverse-event counts and terms are descriptive entries, not an analysis of whether one vaccination sequence had a different risk from another. They do not establish equivalence or a difference.

In general, a confidence interval helps show how precisely an estimated effect is known, while a p-value addresses compatibility between observed data and a specified statistical null model. Neither is reported for the primary endpoint in the registry record. Without an effect estimate and its uncertainty, readers cannot assess the precision of a primary comparison from this record. Likewise, the absence of reported immunogenicity results means that the secondary objectives cannot be evaluated from the registry entry.

The record does establish what the investigators set out to study, which groups were described, what reaction categories were specified, and which serious adverse-event summaries were entered. It does not establish a clinical benefit, a causal explanation for any event, or a treatment recommendation. It also does not provide the missing analyses or details of the statistical plan. Any interpretation should stay within those limits and distinguish the planned questions from reported results.

13. Why This Trial Matters Statistically

This study is statistically notable for its four-group sequence structure. Participants had previously received either Fluzone ID or Fluzone IM, and the registry describes revaccination with either formulation. That arrangement raises questions about both the formulation used for revaccination and the prior vaccination history. A clear analysis would need to state which group contrasts address which question; the registry record does not report a single primary pairwise comparison or an analysis plan defining such contrasts.

The primary endpoint is also broader than one event label: it lists several injection-site and systemic reactions across a defined observation window. Such an endpoint can be useful for structured safety description, but its interpretation depends on how individual reaction categories are reported and whether any combined summary is defined. The registry record notes multiple categories or time points and does not reduce the outcome to one comparison. This makes it especially important not to imply a singular result where none is reported.

Finally, the difference between a study objective and a reported analysis matters. The record names safety and immunogenicity aims, but lists no analyses for its outcomes. It gives serious-event counts, yet no comparative estimate or uncertainty measure. These features make the entry useful for understanding the design and intended questions while limiting what can be concluded statistically. They also illustrate why endpoint definitions, analysis populations, missing-data procedures, and prespecified comparisons are essential to interpreting a clinical study.

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 the randomization procedure, allocation concealment, or a statistical analysis plan. It identifies the study as open label, but does not describe any procedures used to reduce bias in outcome collection or assessment. The record also does not specify the intended comparisons among the four vaccination sequences.

The primary endpoint has multiple reaction categories and a defined observation period, but no category-specific numerical results or single comparison are reported. Although the safety population is described as enrolled and vaccinated subjects with available reaction data, the handling and extent of missing reaction data are not reported in the registry record. The record lists no statistical analyses, so it supplies no estimate or uncertainty interval for the primary endpoint.

The listed secondary outcomes involve antibody titers, seroprotection, and seroconversion. Their results, analysis population, statistical methods, and missing-data handling are not reported in the registry record. The record also does not report multiplicity procedures or whether interim analyses occurred.

The serious adverse-event entries provide group counts and a list of terms, but not comparative analyses, event-specific group results, or causal assessments. Death counts are not reported in the registry record. Enrollment is listed as 1250, but that entry does not establish the number assessed for each outcome or explain the composition of the analysis populations. These gaps limit interpretation of both the primary safety question and the immunogenicity objectives.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Influenza Vaccine Revaccination in Healthy Adults Previously Vaccinated With Fluzone ID or Fluzone IM — NCT01011049.
• Registry record last updated 2016-04-14; status last verified 2016-04.
• Results first posted 2011-08-11.
• 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

NCT01011049 is recorded as a completed phase 2, randomized, open-label, parallel-group study of revaccination in healthy adults aged 18 to 64 years previously vaccinated with Fluzone ID or Fluzone IM. Enrollment is listed as 1250. The study start is recorded as 2009-09 and primary completion as 2010-05.

Four groups represented ID-to-ID, ID-to-IM, IM-to-IM, and IM-to-ID vaccination sequences. The primary outcome counted participants with solicited injection-site and systemic reactions from Day 0 through Day 7. Secondary outcomes concerned geometric mean titers, seroprotection, and seroconversion.

The registry record lists group-specific serious adverse-event counts and terms, but no statistical analyses for the outcomes. Numerical primary reaction results, immunogenicity results, comparative estimates, and uncertainty measures are not reported in the registry record.