Study to Assess the Immune Response and the Safety Profile of a High-Dose Quadrivalent Influenza Vaccine (QIV-HD) Compared to a Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD) in Taiwanese Adults 65 Years of Age and Older: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess the Immune Response and the Safety Profile of a High-Dose Quadrivalent Influenza Vaccine (QIV-HD) Compared to a Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD) in Taiwanese Adults 65 Years of Age and Older (NCT04537234), a randomized phase 3 study. The primary outcome is Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0.

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, quadruple-masked, parallel-group study. Participants were assigned to receive either high-dose quadrivalent influenza vaccine or standard-dose quadrivalent influenza vaccine. The record lists enrollment of 165 and indicates that the study is completed. The study began on 2020-11-10, with primary completion on 2021-02-09.

The two interventions were administered as single intramuscular injections at Day 0: 0.7 mL of QIV-HD or 0.5 mL of QIV-SD. The registry record describes the study population as Taiwanese adults 65 years of age and older and lists influenza in healthy volunteers as the condition. The specific eligibility criteria beyond this description are not reported in the registry record.

Randomization can reduce systematic differences between groups at assignment, while masking is intended to limit the influence of expectations on participant experience, care, and assessment. The record identifies the design as quadruple-masked but does not report which roles were masked or the procedures used to maintain masking. Details of the randomization sequence and allocation concealment are not reported in the registry record.

The stated objectives were descriptive: characterize immune response using HAI measurements and describe safety in the study groups. The record lists ten outcome measures, but no analysis results are reported in the registry record. It also lists zero analyses. The record therefore supports a description of the design and planned measurement, but does not provide the numerical primary outcome results needed to evaluate the observed immune response between groups.

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 165 participants were vaccinated in the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the full analysis set (FAS) that included randomized participants who received one of the study vaccine and had a post-vaccination blood sample. Participants were analyzed according to the vaccine group to which they were randomized.

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.

Population: Analysis was performed on all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0, measured over Day 0 (pre-vaccination).

The listed primary measure is geometric mean titers of antibodies against four influenza strains, measured by hemagglutination inhibition assay. The strains are A/H1N1, A/H3N2, B1 (B Victoria Lineage), and B2 (B Yamagata Lineage). Titers are expressed as 1/dilution. The specified timeframe is Day 0, before vaccination.

As a general statistical concept, an antibody titer is a dilution-based measure of the amount of antibody that inhibits hemagglutination in the assay. A GMT summarizes titers using a geometric rather than arithmetic average. This is often useful for titer data because values can vary multiplicatively and may be skewed; averaging on the logarithmic scale and transforming back gives a summary suited to that structure.

The record specifies a 95% confidence interval as the measure of dispersion. In general, a confidence interval conveys uncertainty around an estimated quantity; it is not a range that contains every participant’s measurement. However, numerical GMT estimates and confidence limits are not reported in the registry record. The baseline timing is also important: a Day 0 value characterizes antibody titers before the injections, not the post-vaccination response. The registry record’s stated analysis population requires a post-vaccination blood sample, but it does not explain how that criterion relates to the pre-vaccination primary measure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Randomization assigns participants to study groups by chance. As a general method, it is intended to make measured and unmeasured characteristics comparable between groups on average, although chance imbalances can still occur. This supports interpretation of a between-group comparison when outcomes are measured and analyzed as planned. The record identifies the study as randomized but does not report the sequence-generation method or allocation-concealment procedures. It also does not report baseline group characteristics, so the degree of observed comparability cannot be assessed from the information recorded.

What does quadruple masking mean for interpretation?

Masking is intended to reduce the influence of knowledge about treatment assignment on participant reporting, clinical care, outcome assessment, or analysis. The registry record labels this study quadruple-masked. The specific people included in that description and the practical masking procedures are not reported in the registry record. HAI antibody titers are laboratory measurements, but masking and standardized laboratory procedures can still matter for limiting bias in a clinical trial. The record does not describe laboratory blinding or assay quality-control procedures.

How should a GMT be understood?

As a general statistical concept, geometric means are appropriate summaries when measurements are positive and their variation is better understood multiplicatively than additively. A geometric mean is obtained by averaging logarithms of the values and transforming that average back to the original scale. It is not the same as an arithmetic average. A GMT provides a group-level summary; it does not describe the full distribution of individual titers or show how many participants had a particular value.

The primary outcome specifies GMTs with 95% confidence intervals. In general, a confidence interval communicates uncertainty in an estimated group summary. A narrower interval indicates greater precision under the assumptions of the analysis, while a wider interval indicates less precision. The confidence interval does not imply that individual participants’ titers fall within its limits. The methods used to calculate the GMTs and confidence intervals are not reported in the registry record, and numerical estimates are not reported there.

Why does the endpoint timing matter?

The recorded timeframe is Day 0, before vaccination. This makes the specified primary measure a baseline antibody summary. A post-vaccination measure, a change from baseline, or a comparison of post-vaccination values could address a different question about immune response. Those results are not reported in the registry record. The brief summary describes an objective to characterize immune response, but the listed primary measure is explicitly pre-vaccination. The record does not explain this difference between the objective wording and the endpoint timing.

The stated full analysis set comprises randomized participants who received a study vaccine and had a post-vaccination blood sample, analyzed according to randomized group. In general, analysis by randomized assignment preserves the intended randomized comparison, while requiring a post-vaccination sample may exclude participants without that measurement. The registry record does not report how many participants contributed to the primary endpoint, whether all required measurements were available, or how missing values were handled. It also does not clarify how a post-vaccination sample requirement was applied to a Day 0 endpoint.

What do the safety counts describe?

Safety counts are descriptive unless accompanied by a defined analysis and uncertainty estimates. The record lists serious adverse event counts, other adverse event counts, deaths, and numbers at risk by group. A count is not the same as a rate: interpreting a rate requires a defined denominator and, for some safety outcomes, a defined observation period. The serious-event entries show zero recorded events in each group, but the registry record does not report confidence intervals or a formal comparison. The other adverse event entries are counts, with no event-level detail or comparative analysis reported.

What is the status of the statistical plan?

The registry record lists ten outcome measures and zero analyses. A detailed statistical analysis plan, methods for comparing groups, treatment of multiplicity, and any prespecified subgroup analyses are not reported in the registry record. Thus, it is not possible to determine from the record whether a specific inferential procedure was prespecified or how it would handle the four strain-specific measurements.

The record also describes sample-size planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the target effect is expressed as a fraction of the observed effect. These are planning assumptions, not evidence about the design rationale used by the trial. The trial’s own sample-size justification is not reported in the registry record. A planning calculation based on an observed effect is not observed power and does not provide evidence that an effect was detected. The registry record does not include the numerical planning illustrations.

10. Multiplicity, Missing Data and Analysis Populations

The primary measure includes four influenza strains, and the registry record states that the primary outcome has several categories or time points and was not reduced to one comparison. It lists ten outcome measures overall. When several outcomes or strain-specific comparisons are examined, the chance of at least one apparently unusual result can increase if each is assessed separately. As a general statistical principle, multiplicity procedures can address this issue, but they may affect the interpretation and precision of individual comparisons.

The registry record does not report a multiplicity adjustment, a testing hierarchy, or which comparisons would be treated as confirmatory. It also lists zero analyses, and numerical outcome results are not reported in the registry record. Therefore, no conclusion about statistical significance across strains or outcomes can be drawn from the available record. The record does not report interim analyses or stopping rules.

The stated full analysis set includes randomized participants who received a study vaccine and had a post-vaccination blood sample, with participants analyzed according to their randomized group. This is the analysis-population description recorded for the primary measure, although that measure is specified at Day 0 before vaccination. The record does not report endpoint-specific participant counts, missing-data amounts, reasons for missingness, imputation methods, or sensitivity analyses. It also does not state whether any other analysis population was used. These omissions make it difficult to judge how missing observations might affect the endpoint estimates.

The statistical analysis plan is not reported in the registry record. In particular, the record does not explain the method for calculating the GMT confidence intervals or the planned approach to comparing groups. Without those details and the numerical results, the precision and inferential status of any group contrast cannot be evaluated.

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 serious adverse event entries report zero events for the QIV-HD group and zero for the QIV-SD group. The corresponding numbers at risk are 82 and 83. Deaths are also recorded as zero in each group. These are event counts as recorded in the registry, not proof that serious events or deaths could not occur.

Zero observed events leave uncertainty about the underlying event risk. In general, when no events are observed, a study still cannot rule out events that might occur in a broader population or over a different observation period. The registry record does not report confidence intervals for these safety counts, a formal group comparison, or detailed follow-up duration for safety outcomes.

The record also lists 46 other adverse events in the QIV-HD group and 35 in the QIV-SD group. These are distinct from the serious-event counts. Event terms, severity, timing, and participant-level detail are not reported in the registry record. The counts should therefore be read descriptively, without treating them as rates or as evidence of a comparative safety difference.

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

This trial record identifies a randomized, quadruple-masked comparison of high-dose and standard-dose quadrivalent influenza vaccines in Taiwanese adults 65 years of age and older. It states objectives covering immune response and safety and identifies HAI antibody GMTs for four influenza strains as the primary measure. The listed GMT timeframe is Day 0, before vaccination. This timing describes baseline antibody levels, not the change or response after vaccination.

The registry record does not report numerical primary endpoint estimates, confidence intervals, or comparative analyses. As a result, it does not show which group had higher baseline GMTs, how large any difference was, or how precisely a difference was estimated. It also does not provide post-vaccination immunogenicity results that could quantify antibody response after the injections.

For safety, the record reports zero serious adverse events and zero deaths in each group, alongside other adverse event counts. These figures describe the recorded events; they do not establish that the risks are absent or equivalent between groups. No comparative safety estimate or uncertainty interval is reported in the registry record.

The design can support a randomized comparison when outcomes and analyses are available, but it does not by itself establish an outcome. The enrollment figure and study completion status describe trial conduct, not evidence of a vaccine effect. The registry record therefore allows readers to understand the comparison and the reported safety counts, but not to determine comparative immunogenicity or make a precise comparative safety assessment.

13. Why This Trial Matters Statistically

This trial is statistically notable because the stated objective is to describe immune response, while the recorded primary antibody measure is explicitly taken before vaccination. Baseline measurements can characterize the groups at the start of a study, but they do not show a response induced by the study injections. Clear alignment between an objective, endpoint definition, and measurement time is essential for interpreting what a result can answer.

The record also describes four strain-specific antibody measures and indicates that the primary outcome has multiple categories or time points rather than one reduced comparison. Multiple outcomes require a clear analysis strategy so readers can distinguish planned confirmatory comparisons from descriptive ones. The registry record does not report a multiplicity approach or numerical results for the strain-specific measures.

The study is described as randomized and quadruple-masked, features intended to support a fair comparison and reduce bias. Yet interpretation depends on more than design labels: endpoint data, analysis methods, and uncertainty estimates are needed to evaluate the comparison. The record lists zero analyses and does not report numerical GMT estimates or confidence intervals.

The safety entries illustrate another statistical distinction: observed counts are not the same as estimated risks. Zero serious events in the recorded groups is informative as a description of what was reported, but does not establish that the true risk is zero or that the groups are equivalent. Together, these features make the record useful for assessing the scope and limits of the available evidence, while leaving the principal comparative questions unresolved.

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 main limitation for interpretation is that numerical primary outcome results are not reported in the registry record. Although the primary measure is described as GMTs with 95% confidence intervals for four strains, no estimates, confidence limits, or group comparisons are included. The record therefore does not permit assessment of the magnitude or precision of baseline antibody differences.

The primary measure is specified at Day 0, before vaccination, while the study objective refers to immune response induced by vaccination. A pre-vaccination measure cannot by itself describe the response after the injection. The record does not explain this difference, and it does not report post-vaccination GMTs or changes from baseline. It also defines the full analysis set using receipt of a vaccine and availability of a post-vaccination blood sample, without explaining how that criterion applies to the Day 0 endpoint.

The registry record does not report the statistical analysis plan, the method used to calculate confidence intervals, a multiplicity strategy, endpoint-specific analysis counts, or missing-data methods. It lists ten outcome measures and zero analyses. These gaps restrict assessment of how the outcomes were analyzed and how robust any estimates would be.

For safety, the record gives serious adverse event and death counts but does not report confidence intervals, event-level details, or a formal comparison. Other adverse event counts are listed without terms, severity, or timing. Follow-up duration for safety outcomes is not reported in the registry record. The trial’s own sample-size justification is also not reported in the registry record; the stated planning assumptions are illustrations rather than a documented design rationale.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Assess the Immune Response and the Safety Profile of a High-Dose Quadrivalent Influenza Vaccine (QIV-HD) Compared to a Standard-Dose Quadrivalent Influenza Vaccine (QIV-SD) in Taiwanese Adults 65 Years of Age and Older — NCT04537234.
• Registry record last updated 2025-09-24; status last verified 2025-09.
• Results first posted 2021-11-08.
• 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, randomized, quadruple-masked, parallel-group Phase 3 study of high-dose versus standard-dose quadrivalent influenza vaccine in Taiwanese adults 65 years of age and older. Participants received a single intramuscular injection at Day 0. Enrollment was 165; the study start was 2020-11-10 and primary completion was 2021-02-09.

The stated objectives cover HAI-measured immune response and safety. The listed primary measure is GMTs for antibodies against A/H1N1, A/H3N2, B1 (B Victoria Lineage), and B2 (B Yamagata Lineage) at Day 0 before vaccination. Numerical GMT results and comparative analyses are not reported in the registry record.

The record reports zero serious adverse events and zero deaths in each group, with other adverse event counts of 46 and 35. These are descriptive entries; comparative safety estimates and uncertainty intervals are not reported in the registry record.