Recombinant Influenza Vaccine Versus Standard Egg-Based Inactivated Influenza Vaccine in Adults 18-64 Years: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Recombinant Influenza Vaccine Versus Standard Egg-Based Inactivated Influenza Vaccine in Adults 18-64 Years (NCT05514002), a randomized phase 4 study. The primary outcome is RT-PCR-Confirmed Influenza Infection.

2. Clinical Question

The study also described a secondary hypothesis about humoral and cell-mediated immune responses after vaccination, assessed in a subset of participants. Its listed secondary outcome was time to return to usual health following influenza illness. These questions concern different outcomes: laboratory-confirmed infection, immune response markers, and recovery after illness should not be treated as interchangeable measures of vaccine effect.

3. Trial Design

This was a randomized, double-blind, parallel-group Phase 4 trial sponsored by the Centers for Disease Control and Prevention. It compared recombinant influenza vaccine with standard-dose egg-based inactivated influenza vaccine among adults aged 18–64 years in the United States. The registry lists enrollment of 3988 and a completed status.

The registered start date was 2022-09-13, and the primary completion date was 2023-12-31. Randomization means assignment to the comparison groups was intended to occur by chance. In general, random assignment can reduce systematic differences between groups at the start of a trial, though it does not guarantee that every measured or unmeasured characteristic will be balanced. Double blinding indicates that the registry identifies the trial as masked for participants and investigators; the official title explicitly describes it as participant- and investigator-blinded.

The recombinant arm is described as receiving Flublok Quadrivalent. The standard-dose egg-based arm description names Fluzone Quadrivalent or Fluarix Quadrivalent. The intervention list names Fluzone Quadrivalent and Flublok Quadrivalent. The registry does not provide further detail about how participants were assigned between the two named egg-based products.

The primary endpoint was RT-PCR-confirmed influenza infection during the influenza circulation period, assessed from at least 14 days after vaccination through the end of surveillance, up to 16 weeks. The primary analysis population was described as modified intention-to-treat rather than all enrolled participants: exclusions applied to participants with an influenza-positive test within 14 days after vaccination or without responses to surveillance contacts beyond 14 days after vaccination. The registry description identifies 1,963 participants in the recombinant arm; the corresponding complete population description is not reported in the registry record.

The record states a primary clinical-efficacy hypothesis and a secondary immunogenicity hypothesis. It does not report the detailed statistical plan, the sample-size justification, or the allocation sequence and concealment procedures.

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 randomized, participant- and investigator-blinded, active-comparator trial conducted during the 2022-2023 Northern Hemisphere influenza season at 7 geographic sites in the United States. Participants were randomized 1:1 to receive recombinant influenza vaccine (RIV) or standard-dose inactivated influenza vaccine (SD IIV).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analytic modified intention-to-treat population. Participants were excluded if they tested influenza-positive within 14 days after vaccination or did not respond to surveillance contacts beyond 14 days after vaccination. The resulting analysis population included 1,963 participants in the recombinant influenza vaccine group and 1,964 participants in the standard-dose inactivated influenza vaccine group.

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: Modified intention-to-treat population including randomized participants who received study vaccine and responded to at least one surveillance contact during the influenza circulation period.

6. Primary Endpoint

The registry lists the primary outcome as RT-PCR-Confirmed Influenza Infection, measured over From ≥14 days after vaccination through end of surveillance (up to 16 weeks).

The primary endpoint counts participants with RT-PCR-confirmed influenza infection during the influenza circulation period. The specified observation window began at least 14 days after vaccination and continued through the end of surveillance, up to 16 weeks. RT-PCR is a laboratory method used to detect influenza virus genetic material; using a laboratory-confirmed outcome distinguishes the endpoint from illness defined only by symptoms.

The registry describes the primary endpoint as a number of participants, while its stated relative vaccine effectiveness calculation is based on a hazard ratio comparing RIV with SD-IIV. A hazard ratio is a time-to-event comparison: in general, it relates the event rates over follow-up while accounting for when events occur, rather than simply comparing final event counts. The record defines relative vaccine effectiveness as (1 - hazard ratio) × 100%.

The endpoint is relevant to the stated clinical question because it focuses on influenza infection associated with the surveillance period, rather than immune markers alone. However, the registry record does not report the group-specific endpoint counts, hazard ratio, relative vaccine effectiveness estimate, or confidence interval. It therefore does not establish the direction, size, or precision of the comparative result. The outcome’s observation window and method are described, but the posted record does not include enough result information to quantify the comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, double-blind, parallel-group trial. In general, randomization assigns participants to groups by chance, helping limit systematic differences in expected baseline characteristics. It does not ensure exact balance in every feature, and randomization alone does not resolve issues such as missing outcome data or measurement error. A parallel design means participants are compared in assigned groups rather than crossing from one vaccine to the other during the trial. The record identifies participant and investigator blinding; it does not detail the masking procedures.

What does the primary analysis compare?

The primary outcome is the number of participants with RT-PCR-confirmed influenza infection during the surveillance period. The endpoint description gives a period beginning at least 14 days after vaccination and continuing until the end of surveillance, up to 16 weeks. The registry states that relative vaccine effectiveness was calculated from a hazard ratio comparing RIV with SD-IIV, using the formula (1 - hazard ratio) × 100%.

In general, a hazard ratio compares event rates over time among participants who remain under observation and have not yet experienced the event. It uses information about event timing, unlike a simple comparison of endpoint counts that ignores when events occurred. The registry does not provide the hazard ratio or the details needed to assess how it was estimated. Consequently, the relative vaccine effectiveness calculation cannot be reproduced from the posted record.

What does a confidence interval tell readers?

In general, a confidence interval expresses the uncertainty associated with an estimated effect under a statistical model and its assumptions. It helps show which effect sizes are reasonably compatible with the observed data. A point estimate alone does not describe precision, and a statistical significance result alone would not show the practical size of an effect. The primary estimate and its confidence interval are not reported in the registry record, so neither magnitude nor precision can be assessed.

Why does the analysis population matter?

The registry calls the primary population an analytic modified intention-to-treat population. It describes excluding participants who tested influenza-positive within 14 days after vaccination or who did not respond to surveillance contacts beyond 14 days after vaccination. In general, defining an analysis population clarifies which participants contribute to an estimate and how events occurring near the start of follow-up are handled. Excluding participants after randomization can affect comparability if the reasons for exclusion differ between groups or relate to outcome risk. The record does not report the full group-specific analysis population counts or enough detail to assess the consequences of these exclusions.

The registry description identifies 1,963 participants in the recombinant arm, but the remaining population description is incomplete in the registry record. The reported enrollment of 3988 is not interchangeable with the number included in a particular endpoint analysis. Enrollment describes recruitment into the trial; the analytic population can differ because of eligibility rules, follow-up, and endpoint-specific exclusions.

What do the planning assumptions mean?

The record describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. In general, such a calculation asks how many participants or events a future study might need under specified assumptions. It is not the number of participants actually analyzed, and it is not observed power. The record does not report numerical planning results in the registry record for this analysis, so no sample-size requirement can be stated.

The planning illustration is not the trial’s own design justification. The trial’s sample-size justification, assumptions used to plan enrollment, and any relationship between the planning illustration and the original protocol are not reported in the registry record. The record also does not specify an interim-analysis plan, stopping boundaries, or the detailed statistical model and covariates, so none should be presumed.

How should the stated hypotheses be read?

The primary hypothesis anticipated superior clinical efficacy for RIV relative to SD-IIV. The secondary hypothesis concerned humoral and cell-mediated immune responses after vaccination in a subset. In general, a hypothesis states what a study is designed to evaluate; it does not establish the result. The registered endpoint definitions and hypotheses provide context, but without estimates and uncertainty measures they cannot answer whether the observed comparison was consistent with either hypothesis.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes a primary clinical-efficacy hypothesis and a secondary immunogenicity hypothesis. It lists time to return to usual health following influenza illness as a secondary outcome, and identifies 2 outcome measures and 1 analysis. The primary outcome is not reduced to one comparison in the available record because it has several categories or time points. The number of analyses alone does not establish which comparisons were prespecified or how multiple testing was handled.

Multiplicity arises when several outcomes, time points, groups, or statistical tests are considered. In general, testing many comparisons can increase the chance of a chance-positive finding if no adjustment or interpretive strategy is used. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a detailed analysis plan. It is therefore not possible to determine how the trial addressed multiplicity or which tests, if any, were designated confirmatory.

For missingness and analysis populations, the registry describes exclusions from the modified intention-to-treat population for an influenza-positive test within 14 days after vaccination or failure to respond to surveillance contacts beyond 14 days after vaccination. This makes clear that the primary analysis did not include every enrolled participant as described in the record. The group-specific number of exclusions, reasons for missing follow-up, and methods for handling missing outcome data beyond these exclusions are not reported in the registry record.

The record does not provide sensitivity analyses assessing the effects of missing data or alternative population definitions. The full analysis population description is also not reported in the registry record. These gaps limit assessment of how robust the primary comparison would be to different assumptions about follow-up and inclusion.

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.

The registry lists serious adverse event figures for both vaccine groups. For the quadrivalent recombinant influenza vaccine group, 1995 participants are listed as at risk for serious adverse events, with 0 affected; the other adverse event count is 0, and deaths are 0. For the quadrivalent standard-dose egg-based inactivated influenza vaccine group, 1993 participants are listed as at risk for serious adverse events, with 0 affected; the other adverse event count is 0, and deaths are 0.

These are the registry’s recorded figures for the listed categories. In general, a zero count means that no event was recorded in that category for the stated group and record; it does not prove that an event is impossible or establish the absence of all harms. The registry record does not provide additional detail about the safety observation period, event definitions, severity grading, or whether events were judged related to vaccination. The figures should not be interpreted as a complete account of every possible safety outcome.

The at-risk figures are category-specific registry counts and should not be confused with the primary modified intention-to-treat population. The record does not report comparative statistical estimates or uncertainty measures for these safety counts. Accordingly, the counts describe what was recorded, but do not by themselves quantify comparative safety or establish a causal difference between groups.

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

The trial’s stated purpose was to compare recombinant influenza vaccine with standard-dose egg-based inactivated influenza vaccine in adults aged 18–64 years. The primary endpoint focused on RT-PCR-confirmed influenza infection during surveillance that began at least 14 days after vaccination and continued through the end of surveillance, up to 16 weeks. The registry also described questions about immune responses and return to usual health following influenza illness.

The record establishes that the study was randomized, double-blind, parallel-group, and completed. It also gives the primary endpoint definition and the formula used for relative vaccine effectiveness. These details explain what the trial was designed to estimate. They do not establish the comparative result. Group-specific infection counts, the hazard ratio, relative vaccine effectiveness estimate, and confidence interval are not reported in the registry record.

For that reason, the posted information cannot support a conclusion about which group had fewer infections, the size of any comparative effect, or how precisely the effect was estimated. The absence of a reported effect estimate is not evidence that the groups were equivalent, nor does it show that the study found no difference. Those interpretations would require outcome results and an uncertainty assessment.

The record’s secondary immunogenicity hypothesis and recovery outcome address additional questions, but their comparative results are also not reported. Immune markers may inform biological response, while return to usual health concerns recovery after illness; neither should be substituted for the primary infection outcome. Likewise, the listed zero adverse-event counts describe the categories and groups recorded, but are not a complete characterization of safety or a comparative statistical analysis.

Overall, the registry record supports a description of the design, endpoints, and some safety counts. It does not provide the efficacy results needed to judge the observed clinical comparison. Conclusions about effect direction, magnitude, precision, or broader implications are therefore not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for framing its primary clinical comparison around a time-to-event measure. The registry describes RT-PCR-confirmed influenza infection and calculates relative vaccine effectiveness from a hazard ratio. In general, analyzing event timing can retain information that a simple final count does not use. It also makes clear why the hazard ratio and its uncertainty are central to interpretation: the endpoint count alone would not reproduce the stated relative-effect calculation.

The analysis population is another important statistical feature. The registry describes a modified intention-to-treat population with exclusions tied to early positive tests and later nonresponse to surveillance contacts. Such rules define the population represented by the primary estimate. In general, readers need both the rule and group-specific numbers to judge how exclusions may affect the randomized comparison. The complete population detail is not reported in the registry record.

The trial also illustrates the distinction between clinical efficacy and immunogenicity. Its primary question concerned confirmed infection, while the secondary hypothesis concerned humoral and cell-mediated immune responses in a subset. These outcomes require different interpretation and do not automatically answer the same question. The registry additionally lists time to return to usual health following influenza illness, a recovery outcome rather than an infection endpoint.

Finally, the stated superiority hypothesis must be separated from evidence of superiority. A completed trial and a prespecified question do not reveal the observed effect without an estimate and uncertainty interval. Because those primary results are not reported in the registry record, the statistical importance of the study design can be described, but the comparative clinical result cannot be characterized from this 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 main limitation for interpreting the primary comparison is that the registry record does not report the group-specific RT-PCR-confirmed infection counts, hazard ratio, relative vaccine effectiveness estimate, or confidence interval. Without these results, the effect’s direction, magnitude, and precision cannot be assessed. The completed trial status does not resolve this absence.

The registry identifies a modified intention-to-treat population and describes exclusions for positive influenza tests within 14 days after vaccination and nonresponse to surveillance contacts beyond 14 days after vaccination. However, the full analysis population description is not reported in the registry record. Group-specific exclusions, the extent and pattern of missing surveillance data, and sensitivity analyses are also not reported, limiting evaluation of possible selection effects.

The outcome description specifies surveillance through the end of the influenza circulation period, up to 16 weeks, but the posted information does not provide more detail about follow-up completeness or how event timing and censoring were handled. The statistical model, covariate adjustment, and diagnostic checks are not reported in the registry record.

The registry describes both clinical and immunogenicity hypotheses, but does not report a detailed multiplicity strategy or comparative results for the secondary questions. It also does not report the trial’s sample-size justification, interim-analysis plan, or detailed statistical analysis plan. The safety figures list zero events in the stated categories, but the record does not provide additional detail on their observation period or event definitions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Recombinant Influenza Vaccine Versus Standard Egg-Based Inactivated Influenza Vaccine in Adults 18-64 Years — NCT05514002.
• Registry record last updated 2026-07-30; status last verified 2026-06.
• Results first posted 2026-07-30.
• 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

NCT05514002 is a completed, randomized, double-blind, parallel-group Phase 4 trial sponsored by the Centers for Disease Control and Prevention. It compared Flublok Quadrivalent recombinant influenza vaccine with standard-dose egg-based inactivated influenza vaccine among adults aged 18–64 years in the United States. The registry lists enrollment of 3988, a start date of 2022-09-13, and a primary completion date of 2023-12-31.

The primary outcome was the number of participants with RT-PCR-confirmed influenza infection from at least 14 days after vaccination through the end of surveillance, up to 16 weeks. Relative vaccine effectiveness was defined using a hazard ratio comparing the groups. The record also describes an immunogenicity hypothesis and lists time to return to usual health following influenza illness.

Primary comparative outcome estimates and their precision are not reported in the registry record. The record lists zero serious adverse events, other adverse events, and deaths in each vaccine group.